<i>Objective</i>. To investigate plasma cytokines (interferon gamma, interleukin-4, and interleukin-17) in patients with viral myocarditis (VMC) and evaluate their predictive value in the progression from VMC to dilated cardiomyopathy (DCM). <i>Methods</i>. A prospective, multicenter, observational study included 536 patients with newly diagnosed VMC admitted in cardiology departments of 24 tertiary super specialised university-affiliated hospitals in the China registry from January 2012 to June 2016. Demographics and clinical characteristics at baseline and after three months were collected, including laboratory blood tests, ECG, echocardiography, and drug treatment in each participating site. The plasma anti-viral antibodies (Abs), anti-heart autoimmune Abs, and cytokines were detected by ELISA. <i>Results</i>. Of the 536 patients, 534 were included for analysis after two patients died in less than a month. The plasma levels of IFN-<i>γ</i>, IL-4, and IL-17 were continually higher in patients with incident DCM than in those without incident DCM at baseline, from the 1st month and the 3rd month; all had a <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.0498209pt" id="M1" height="8.68572pt" version="1.1" viewBox="-0.0498162 -8.6359 8.15071 8.68572" width="8.15071pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g></svg> value of &lt;0.0001. There was a positive correlation between IL-4 and LVEDd (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="16.751pt" style="vertical-align:-0.2063904pt" id="M2" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 16.751 8.55521"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-115" d="M393 379C402 394 400 411 393 422C384 437 365 448 348 448C301 448 237 372 186 285H182L193 335C210 408 205 448 178 448C150 448 80 402 29 344L45 321C80 355 114 373 122 373C128 373 130 365 124 330C106 228 76 98 50 -5L57 -12C82 -5 112 3 132 6L172 203C196 256 234 304 254 329C275 355 293 367 306 367C318 367 330 360 342 348C347 343 355 343 365 350S386 367 393 379Z"/></g><g transform="matrix(.013,0,0,-0.013,9.12,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.912pt" style="vertical-align:-0.2063904pt" height="8.55521pt" version="1.1" viewBox="20.3331838 -8.34882 21.912 8.55521"><g transform="matrix(.013,0,0,-0.013,20.383,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,26.623,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,29.587,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,35.827,0)"><use xlink:href="#g113-49"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M3" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="34.445pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 34.445 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.845,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>)</span></span> and between IL-17 and LVEDd (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="16.751pt" style="vertical-align:-0.2063904pt" id="M4" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 16.751 8.55521"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-115"/></g><g transform="matrix(.013,0,0,-0.013,9.12,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.912pt" style="vertical-align:-0.2063904pt" height="8.55521pt" version="1.1" viewBox="20.3331838 -8.34882 21.912 8.55521"><g transform="matrix(.013,0,0,-0.013,20.383,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,26.623,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,29.587,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,35.827,0)"><use xlink:href="#g113-50"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M5" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g></svg>).</span></span> When all these covariates have entered the model simultaneously, elevated IL-4 and IL-17 were still significantly associated with DCM incidence. The RR (95% CI) of DCM incidence were 1.04 (1.02-1.06) for IL-4 and 5.24 (2.81-9.79) for IL-17. <i>Conclusion</i>. The continued elevation of plasma IL-4 and IL-17 in VMC patients were associated with a high incidence of DCM at three months, and these two cytokines were independent predictors for the progression from VMC to DCM.

Z. H. Wang

Y. H. Liao

J. Yuan

X. J. Jin

M. Yu

R. Z. Chen

D. J. Xu

J. Wei

J. Wan

D. C. Zhao

H. Y. Han

B. Li

G. Tian

G. Hu

J. Xu

Continued Elevation of Plasma IL-4 and IL-17 Predicts the Progression from VMC to DCM

<i>Background</i>. Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor with a high tumor recurrence rate and poor postoperative survival. Recent studies suggest that CD276- (B7-H3) targeted therapy represents a promising therapeutic option for solid tumors. However, little is known about the expression status of CD276 or its association with progression and prognosis of ACC. <i>Methods</i>. Clinical data were retrospectively analyzed from patients who underwent resection of ACC at our institution (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="17.789pt" style="vertical-align:-0.2063904pt" id="M1" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 17.789 8.55521"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-111" d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="12.679pt" style="vertical-align:-0.2063904pt" height="8.55521pt" version="1.1" viewBox="21.3711838 -8.34882 12.679 8.55521"><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,27.661,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g></svg>).</span></span> Archived, formalin-fixed, and paraffin-embedded samples were collected for immunohistochemical analysis, and the correlation between CD276 expression and clinicopathological parameters was evaluated. Kaplan–Meier and univariate/multivariate Cox regression methods were implemented to identify any prognostic effects. Data from The Cancer Genome Atlas (TCGA) ACC cohort (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="17.789pt" style="vertical-align:-0.2063999pt" id="M2" height="8.32035pt" version="1.1" viewBox="-0.0498162 -8.11395 17.789 8.32035"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-111"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="12.679pt" style="vertical-align:-0.2063999pt" height="8.32035pt" version="1.1" viewBox="21.3711838 -8.11395 12.679 8.32035"><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g><g transform="matrix(.013,0,0,-0.013,27.663,0)"><use xlink:href="#g113-56"/></g></svg>)</span></span> were retrieved for quantitative validation analysis. <i>Results</i>. Positive expression of CD276 was detected on the cell membrane and in the cytoplasm of cancer cells or tumor-associated vascular cells in 91.67% (44/48) of ACCs. Vascular expression of CD276 was associated with local aggression (higher T stage, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M3" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g></svg>)</span></span> and advanced ENSAT stage (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M4" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-51"/></g></svg>).</span></span> Specifically, patients with a higher CD276-positive cancer cell density exhibited significantly worse overall survival and recurrence-free survival in our cohort (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M5" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-73" d="M729 650H468V622C546 615 554 610 554 527V365H213V527C213 610 221 616 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style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 15.63 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,39.233,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.197,0)"><use xlink:href="#g113-57"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M6" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>,</span></span> and <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M7" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-73"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><use xlink:href="#g190-83"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.894pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 21.894 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,39.236,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.2,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g><g transform="matrix(.013,0,0,-0.013,48.44,0)"><use xlink:href="#g113-51"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M8" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-50"/></g></svg>,</span></span> respectively) and in the validation cohort (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M9" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-73"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><use xlink:href="#g190-83"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="15.63pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 15.63 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,39.233,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.197,0)"><use xlink:href="#g113-53"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M10" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-52"/></g></svg>,</span></span> and <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M11" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-73"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><use xlink:href="#g190-83"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="15.63pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 15.63 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,39.234,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.198,0)"><use xlink:href="#g113-56"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M12" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-50"/></g></svg>,</span></span> respectively). The prognostic association remained significant in multivariate Cox regression analysis. Further analysis indicated that CD276 participates in regulating the immune response as well as in the malignant biological behaviors of ACC. <i>Conclusion</i>. These findings highlight the immune checkpoint factor CD276 as an independent prognostic factor and a potential therapeutic target in ACC.

Jiayu Liang

Zhihong Liu

Tianjiao Pei

Yingming Xiao

Liang Zhou

Yongquan Tang

Chuan Zhou

Kan Wu

Fuxun Zhang

Fan Zhang

Xiaoxue Yin

Ni Chen

Xin Wei

Yiping Lu

Yuchun Zhu

Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma

<i>Background</i>. Previous studies have demonstrated that <i>P21</i> (WAF1/CIP1) is a valuable prognostic factor in several malignant tumors. However, it is not known whether <i>P21</i> can predict the prognosis in patients with esophageal cancer (EC). The aim of this research was to investigate the contribution of <i>P21</i> expression to the clinicopathological characteristics and of EC. <i>Methods</i>. A systematic review and meta-analysis of study focusing on <i>P21</i> expression, clinicopathological characteristics, and clinical outcomes in patients with EC was performed using seven databases (PubMed, Embase, Web of Science, and four Chinese databases). Pooled hazard ratios and odds ratios were used to explore the association between <i>P21</i> expression, clinicopathological characteristics, and outcomes in patients with EC. The heterogeneity of the studies was classified by the <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04979992pt" id="M1" height="11.6412pt" version="1.1" viewBox="-0.0498162 -11.5914 10.6309 11.6412" width="10.6309pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-74" d="M405 650H141L135 622C222 616 230 610 215 535L133 116C118 41 113 33 29 28L23 0H289L295 28C209 33 205 40 219 116L298 535C312 609 317 616 399 622L405 650Z"/></g><g transform="matrix(.0091,0,0,-0.0091,5.567,-5.741)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g></svg> statistic. The sensitivity analysis was then utilized to assess the robustness of the results. Finally, the funnel plot and Begg’s test were used to evaluate the publication bias. <i>Results</i>. Forty-five studies with 3098 patients were eligible for inclusion in the meta-analysis. Thirty of these studies reported on clinicopathological characteristics and 15 on clinical outcomes. The pooled hazard ratio of 1.456 (95% confidence intervals 1.033–2.053, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M2" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g></svg>)</span></span> for overall survival indicated that a low <i>P21</i> expression level was an unfavorable prognostic factor for a clinical outcome in patients with EC. Furthermore, the pooled odds ratio confirmed an association between decreased <i>P21</i> expression and poor clinicopathological characteristics, including differentiation, lymph node metastasis, invasion, and higher grade and clinical stage. Notably, high <i>P21</i> expression was a significant predictor of a favorable response to chemotherapy. There was no evidence of publication bias. <i>Conclusion</i>. Reduced <i>P21</i> expression is associated with a poor outcome in patients with EC.

Junbo Wu

Liang Liu

Feng Wu

Li Qiu

Ming Luo

Qing Ke

Xinzhou Deng

Zhiguo Luo

Clinical and Prognostic Implications of <i>P21</i> (WAF1/CIP1) Expression in Patients with Esophageal Cancer: A Systematic Review and Meta-Analysis

<i>Backgrounds</i>. Both pretreatment serum CRP (C-reactive protein) level and ALB (albumin) level have been found to be predictive of survival for multiple malignancies including sarcoma. Since both of the GPS (Glasgow prognostic score) and CAR (C-reactive protein to albumin ratio) are based on the combination of CRP and ALB, we conducted a meta-analysis to evaluate the prognostic role of these two parameters for sarcoma patients. <i>Methods</i>. A detailed literature search was conducted in MEDLINE, Embase, and Cochrane Library for relevant research publications written in English. Patients’ clinical characteristics, outcomes of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were extracted. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were combined to evaluate the prognostic role of GPS or CAR. <i>Results</i>. Twelve articles containing 2695 patients were identified as eligible studies. The results showed that an elevated GPS was significantly correlated with poor OS (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M1" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-73" d="M729 650H468V622C546 615 554 610 554 527V365H213V527C213 610 221 616 297 622V650H38V622C120 616 128 611 128 527V123C128 39 120 34 40 28V0H303V28C221 34 213 40 213 123V322H554V123C554 39 546 34 460 28V0H728V28C647 34 639 39 639 123V527C639 610 647 615 729 622V650Z"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><path id="g190-83" d="M631 18C609 24 585 35 559 65C534 91 514 117 478 169C448 214 406 281 389 313C462 346 516 399 516 485C516 545 490 590 449 616C412 641 363 650 290 650H42V622C120 615 128 612 128 527V125C128 40 120 34 38 28V0H300V28C221 34 212 40 212 125V284H244C295 284 312 272 329 244C359 195 395 133 430 84C475 19 516 -3 592 -7C603 -8 615 -8 627 -8L631 18ZM212 316V563C212 591 215 602 223 607C231 613 248 617 277 617C352 617 423 577 423 469C423 415 407 375 368 345C343 324 310 316 260 316H212Z"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.894pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 21.894 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,39.233,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,42.197,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,48.438,0)"><use xlink:href="#g113-51"/></g></svg>;</span></span> 95% CI: 1.98-2.94; <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M2" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>;</span></span> fixed-effects model), DSS (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M3" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-73"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><use xlink:href="#g190-83"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.894pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 21.894 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,39.233,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.197,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,48.437,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g></svg>;</span></span> 95% CI: 1.75-2.97; <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>;</span></span> fixed-effects model), and DFS (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M5" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-73"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><use xlink:href="#g190-83"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.894pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 21.894 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,39.233,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.197,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,48.437,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>;</span></span> 95% CI: 1.62-2.60; <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M6" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>;</span></span> fixed-effects model). A higher CAR also was shown to be significantly correlated with poor OS (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M7" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-73"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><use xlink:href="#g190-83"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.894pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 21.894 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,39.233,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.197,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,48.437,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g></svg>;</span></span> 95% CI: 1.70-2.92; <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M8" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>;</span></span> fixed-effects model) and DFS (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="29.361pt" style="vertical-align:-0.2063904pt" id="M9" height="8.73137pt" version="1.1" viewBox="-0.0498162 -8.52498 29.361 8.73137"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-73"/></g><g transform="matrix(.013,0,0,-0.013,9.958,0)"><use xlink:href="#g190-83"/></g><g transform="matrix(.013,0,0,-0.013,21.73,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.894pt" style="vertical-align:-0.2063904pt" height="8.73137pt" version="1.1" viewBox="32.9431838 -8.52498 21.894 8.73137"><g transform="matrix(.013,0,0,-0.013,32.993,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,39.233,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,42.197,0)"><use xlink:href="#g113-57"/></g><g transform="matrix(.013,0,0,-0.013,48.437,0)"><use xlink:href="#g113-50"/></g></svg>;</span></span> 95% CI: 1.7-2.58; <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M10" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>;</span></span> fixed-effects model). <i>Conclusion</i>. An elevated GPS is predictive of poor survival in patients with sarcomas and is promising to be used as a factor for risk stratification. A higher CAR value is also predictive of poor survival; however, the optimal CAR cut-off value is still to be determined.

Erhu Fang

Xiaolin Wang

Jiexiong Feng

Xiang Zhao

The Prognostic Role of Glasgow Prognostic Score and C-reactive Protein to Albumin Ratio for Sarcoma: A System Review and Meta-Analysis

<i>Background.</i> The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. <i>Methods.</i> Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T<sub>-13910</sub> polymorphism genotyping and fructose H<sub>2</sub>/CH<sub>4</sub> breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire. <i>Results.</i> The median TMAO and zonulin serum concentrations were 2.66 (1.93–4.14) <i>μ</i>mol/L and 40.83 (34.73–47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M1" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-50"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.273pt" style="vertical-align:-3.42938pt" id="M2" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.273 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-239" d="M516 277C516 378 460 448 376 448C335 448 288 434 240 401C158 345 127 277 107 159C53 -161 38 -221 23 -247L28 -261C43 -260 95 -250 114 -226C122 -216 129 -199 146 -75C152 -29 157 0 164 31C182 9 206 -12 237 -12C267 -12 325 8 376 46C451 102 516 179 516 277ZM432 259C432 134 366 40 259 40C236 40 204 48 171 76L195 203C219 327 253 400 326 400C398 400 432 336 432 259Z"/></g><g transform="matrix(.013,0,0,-0.013,10.642,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.18pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="21.855183800000002 -8.34882 28.18 11.7782"><g transform="matrix(.013,0,0,-0.013,21.905,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.145,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.109,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,37.349,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.013,0,0,-0.013,43.589,0)"><use xlink:href="#g113-49"/></g></svg>).</span></span> The strongest correlations were observed in 87 females (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M3" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-49"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.273pt" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.273 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-239"/></g><g transform="matrix(.013,0,0,-0.013,10.642,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.18pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="21.855183800000002 -8.34882 28.18 11.7782"><g transform="matrix(.013,0,0,-0.013,21.905,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.145,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.109,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,37.349,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g><g transform="matrix(.013,0,0,-0.013,43.591,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g></svg>)</span></span> and 49 males (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M5" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-56"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.273pt" style="vertical-align:-3.42938pt" id="M6" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.273 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-239"/></g><g transform="matrix(.013,0,0,-0.013,10.642,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.18pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="21.855183800000002 -8.34882 28.18 11.7782"><g transform="matrix(.013,0,0,-0.013,21.905,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.145,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.109,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,37.349,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,43.589,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>)</span></span> without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M7" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-51"/></g></svg>,</span></span> <span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M8" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 57.7445 11.7782" width="57.7445pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-239"/></g><g transform="matrix(.013,0,0,-0.013,10.642,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,21.905,0)"><path id="g117-33" d="M535 230V280H52V230H535Z"/></g><g transform="matrix(.013,0,0,-0.013,29.536,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,35.776,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,38.74,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,44.98,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.013,0,0,-0.013,51.22,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g></svg>).</span> <i>Conclusion.</i> This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.

Sophie Meinitzer

Andreas Baranyi

Sandra Holasek

Wolfgang J. Schnedl

Sieglinde Zelzer

Harald Mangge

Markus Herrmann

Andreas Meinitzer

Dietmar Enko

Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers

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<p><em>Disease Markers</em> publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.</p>


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<p>Chief Editor Paola Gazzaniga is an Associate Professor in the Department of Molecular Medicine at Sapienza University of Rome, Italy. Her core research focuses on liquid biopsies in patients with solid tumors.</p>


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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

Disease Markers