<i>Aims.</i> The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation.<i> Methods.</i> 51 lung transplant patients at Shanghai Pulmonary Hospital were included.<i> IL-18</i> polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and<i> CYP3A5 </i>rs776746 were genotyped. Dose-adjusted trough blood concentrations (<i>C/D</i> ratio, mg/kg body weight) in lung transplant patients during the first 4 postoperative weeks were calculated.<i> Results</i>. IL-18 rs5744247 allele C and rs1946518 allele A were associated with fast tacrolimus metabolism. Combined analysis showed that the numbers of low IL-18 mRNA expression alleles had positive correlation with tacrolimus<i> C/D</i> ratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimus<i> C/D</i> ratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimus<i> C/D</i> ratios difference of IL-10 polymorphisms was found in our data.<i> Conclusions. IL-18</i> polymorphisms may influence tacrolimus elimination in lung transplantation patients.

Xiaoqing Zhang

Jiandong Xu

Junwei Fan

Tao Zhang

Yuping Li

Boxiong Xie

Wei Zhang

Shengtao Lin

Ling Ye

Yuan Liu

Gening Jiang

Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients

Our previous studies using the mass spectrum analysis provided evidence that fibrinopeptide A (FPA) could be a potential biomarker for schizophrenia diagnosis. We sought further to demonstrate that variants in the fibrinogen alpha chain gene<i> (FGA)</i> coded FPA might confer vulnerability to schizophrenia. 1,145 patients with schizophrenia and 1,016 healthy volunteers from the Han population in Northeast China were recruited. The association of three tag single nucleotide polymorphisms (SNPs) (rs2070011 in the <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M1" height="11.6425pt" version="1.1" viewBox="-0.0498162 -11.4361 10.1586 11.6425" width="10.1586pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><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(.0091,0,0,-0.0091,6.24,-5.741)"><path id="g50-31" d="M310 541L304 571C290 586 211 619 185 610L80 76L131 52L310 541Z"/></g></svg>UTR, rs2070016 in intron 4, and rs2070022 in the <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M2" height="11.6425pt" version="1.1" viewBox="-0.0498162 -11.4361 10.1586 11.6425" width="10.1586pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><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(.0091,0,0,-0.0091,6.24,-5.741)"><use xlink:href="#g50-31"/></g></svg>UTR) in<i> FGA</i> and schizophrenia was examined using a case-control study design. Genotypic distributions of these three SNPs were not found to be significantly different between cases and controls (rs2070011: <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.6382pt" id="M3" height="15.2296pt" version="1.1" viewBox="-0.0498162 -11.5914 49.329 15.2296" width="49.329pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-244" d="M565 434L556 448L482 423L322 189L287 373C280 410 261 448 236 448C207 448 161 415 110 338L131 317C160 355 181 374 193 374C204 374 208 366 217 330C230 279 247 185 259 116L50 -175C18 -223 29 -260 41 -278H51C97 -198 207 -33 270 57L313 -165C328 -235 349 -261 376 -261S445 -244 510 -150L487 -127C444 -178 423 -186 411 -186C402 -186 398 -177 387 -130C371 -62 349 39 332 135C390 217 524 392 565 434Z"/></g><g transform="matrix(.0091,0,0,-0.0091,7.568,-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><g transform="matrix(.013,0,0,-0.013,16.146,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.013,0,0,-0.013,27.409,0)"><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,-0.013,33.649,0)"><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,-0.013,36.613,0)"><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,-0.013,42.853,0)"><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>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M4" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 51.1027 8.8423" width="51.1027pt"><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><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)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-54"/></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="#g113-57"/></g></svg>; rs2070016: <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.6382pt" id="M5" height="15.2296pt" version="1.1" viewBox="-0.0498162 -11.5914 49.329 15.2296" width="49.329pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-244"/></g><g transform="matrix(.0091,0,0,-0.0091,7.568,-5.741)"><use xlink:href="#g50-51"/></g><g transform="matrix(.013,0,0,-0.013,16.146,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,27.409,0)"><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,-0.013,33.65,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,36.614,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,42.854,0)"><use xlink:href="#g113-50"/></g></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M6" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 51.1027 8.8423" width="51.1027pt"><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><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="#g113-50"/></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="#g113-57"/></g></svg>; rs2070022: <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.6382pt" id="M7" height="15.2296pt" version="1.1" viewBox="-0.0498162 -11.5914 49.329 15.2296" width="49.329pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-244"/></g><g transform="matrix(.0091,0,0,-0.0091,7.568,-5.741)"><use xlink:href="#g50-51"/></g><g transform="matrix(.013,0,0,-0.013,16.146,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,27.409,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,33.649,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,36.613,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,42.853,0)"><use xlink:href="#g113-52"/></g></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M8" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 51.1027 8.8423" width="51.1027pt"><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><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="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-53"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-50"/></g></svg>). There were also no significant differences in SNP allelic frequencies between cases and controls (all <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6370001pt" id="M9" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 9.2729" width="44.8393pt"><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="g117-92" d="M512 230V281L75 514V456L453 256V254L75 55V-3L512 230Z"/></g><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="#g113-54"/></g></svg>). Additionally, the frequency of haplotypes consisting of alleles of these three SNPs was not significantly different between cases and healthy control subjects (global <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.6382pt" id="M10" height="15.2296pt" version="1.1" viewBox="-0.0498162 -11.5914 49.329 15.2296" width="49.329pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-244"/></g><g transform="matrix(.0091,0,0,-0.0091,7.568,-5.741)"><use xlink:href="#g50-51"/></g><g transform="matrix(.013,0,0,-0.013,16.146,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.013,0,0,-0.013,27.409,0)"><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><g transform="matrix(.013,0,0,-0.013,33.651,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,36.615,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,42.855,0)"><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></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M11" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 51.1027 8.8423" width="51.1027pt"><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><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="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-58"/></g></svg>). Our study did not show a significant association of<i> FGA</i> SNPs with schizophrenia. Future studies may need to test more<i> FGA</i> SNPs in a larger sample to identify those SNPs with a minor or moderate effect on schizophrenia.

Wenwang Rao

Na Zhou

Huiping Zhang

Rui Liu

Shangchao Zhang

Yingying Su

Guang Yang

Yue Ma

Jieping Shi

Yaqin Yu

Qiong Yu

A Case-Control Study of the Association between Polymorphisms in the Fibrinogen Alpha Chain Gene and Schizophrenia

<i>Purpose</i>. To determine if the MMP-9 genotype has an influence on development of pituitary adenoma (PA).<i> Methodology</i>. The study enrolled <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M1" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 34.1002 8.55521" width="34.1002pt"><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><g transform="matrix(.013,0,0,-0.013,21.421,0)"><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><g transform="matrix(.013,0,0,-0.013,27.661,0)"><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></svg> patients with PA and <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063904pt" id="M2" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 40.3636 8.55521" width="40.3636pt"><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><g transform="matrix(.013,0,0,-0.013,21.421,0)"><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,-0.013,27.661,0)"><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,-0.013,33.901,0)"><use xlink:href="#g113-55"/></g></svg> healthy controls (reference group). The genotyping of MMP-9 was carried out using the real-time polymerase chain reaction method.<i> Results</i>. Our data demonstrated that the MMP-9 (–1562) C/C genotype was more frequent in PA group than in healthy controls (81.4% versus 64.6%, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M3" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><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)"><use xlink:href="#g117-34"/></g><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)"><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,-0.013,31.809,0)"><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="#g113-51"/></g></svg>); C/C genotype was more frequently present in PA females compared to healthy control females, 81.5% versus 64.6%, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><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><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)"><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,-0.013,44.289,0)"><use xlink:href="#g113-57"/></g></svg>, as well. MMP-9 (–1562) C/C genotype was frequently observed for all subgroups: noninvasive and invasive, nonrecurrence, and inactive PA compared to healthy controls: 81.8% versus 64.6%, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M5" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><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><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="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>; 81.0% versus 64.6%, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M6" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><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><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)"><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,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>; 81.8% versus 64.6%, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M7" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><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><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="#g113-54"/></g></svg>; 100.0% versus 64.6%, <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 50.7895 11.7782" width="50.7895pt"><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)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><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>, respectively. MMP-9 (–1562) C/C genotype was more frequent in inactive PA compared to active PA: 100.0% versus 71.4%; <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.42938pt" id="M9" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 50.7895 11.7782" width="50.7895pt"><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><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>.<i> Conclusion</i>. MMP-9 (–1562) C/C genotype plays a role in nonrecurrence, inactive, and invasive as well as in nonivasive PA development. 

Brigita Glebauskiene

Rasa Liutkeviciene

Alvita Vilkeviciute

Loresa Kriauciuniene

Silvija Jakstiene

Egle Zlatkute

Abdonas Tamosiunas

Reda Zemaitiene

Paulina Vaitkiene

Dalia Zaliuniene

Does MMP-9 Gene Polymorphism Play a Role in Pituitary Adenoma Development?

<i>Objective</i>. We assess the behavior of serum concentrations of HE4 marker in female carriers of BRCA1 and assess the diagnostic usefulness of HE4 in ovarian and endometrial cancer.<i> Methods</i>. A total of 619 women with BRCA1 gene mutation, ovarian, endometrial, metastatic, other gynecological cancers, or benign gynecological diseases were included. Intergroup comparative analyses were carried out, the BRCA1 gene carriers subgroup was subjected to detailed analysis, and ROC curves were determined for the assessment of diagnostic usefulness of HE4 in ovarian and endometrial cancer.<i> Results</i>. Statistically lower serum HE4 and CA 125 levels were observed in BRCA1 gene mutation premenopausal carriers. Occult ovarian/fallopian tube cancer was found 3.6&#x25;. Each of those patients was characterized by slightly elevated levels of either CA 125 (63.9 and 39.4 U/mL) or HE4 (79&#x2009;pmol/L). The ROC-AUC curves were 0.892 and 0.894 for diagnostic usefulness of ovarian cancer and 0.865 for differentiation of endometrial cancer from endometrial polyps.<i> Conclusions</i>. Patients with BRCA1 gene mutations have relatively low serum HE4 levels. Even the slightest elevation in HE4 or CA 125 levels in female BRCA1 carriers undergoing prophylactic surgery should significantly increase oncological alertness. The HE4 marker is valuable in ovarian and uterine cancer diagnosis.

Anita Chudecka-G&#x142;az

Aneta Cymbaluk-P&#x142;oska

Aleksandra Strojna

Janusz Menkiszak

HE4 Serum Levels in Patients with BRCA1 Gene Mutation Undergoing Prophylactic Surgery as well as in Other Benign and Malignant Gynecological Diseases

Arterial stiffness is associated with cardiovascular risk, morbidity, and mortality. The present paper reviews the main vitamins related to arterial stiffness and enabling destiffening, their mechanisms of action, providing a brief description of the latest studies in the area, and their implications for primary cardiovascular prevention, clinical practice, and therapy. Despite inconsistent evidence for destiffening induced by vitamin supplementation in several randomized clinical trials, positive results were obtained in specific populations. The main mechanisms are related to antiatherogenic effects, improvement of endothelial function (vitamins A, C, D, and E) and metabolic profile (vitamins A, B12, C, D, and K), inhibition of the renin-angiotensin-aldosterone system (vitamin D), anti-inflammatory (vitamins A, D, E, and K) and antioxidant effects (vitamins A, C, and E), decrease of homocysteine level (vitamin B12), and reversing calcification of arteries (vitamin K). Vitamins A, B12, C, D, E, and K status is important in evaluating cardiovascular risk, and vitamin supplementation may be an effective, individualized, and inexpensive destiffening therapy.

Ioana Mozos

Dana Stoian

Constantin Tudor Luca

Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness

<i>Introduction</i>. Intra-amniotic infection (IAI) is a major cause of preterm labor and adverse neonatal outcome. We evaluated amniotic fluid (AF) proteolytic cascade forming biomarkers in relation to microbial invasion of the amniotic cavity (MIAC) and IAI in preterm pregnancies with intact membranes.<i> Material and Methods</i>. Amniocentesis was made to 73 women with singleton pregnancies; 27 with suspected IAI; and 46 controls. AF biomarkers were divided into three cascades: Cascade 1: matrix metalloproteinase-8 (MMP-8), MMP-9, myeloperoxidase (MPO), and interleukin-6; Cascade 2: neutrophil elastase (HNE), elafin, and MMP-9; Cascade 3: MMP-2, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), MMP-8/TIMP-1 molar ratio, and C-reactive protein (CRP). MMP-8 was measured by an immunoenzymometric assay and the others were measured by ELISA. Standard biochemical methods, molecular microbiology, and culture techniques were used.<i> Results</i>. MMP-8, MMP-9, MPO, elafin, and TIMP-1 concentrations were higher in IAI suspected cases compared to controls and also in IAI suspected cases with MIAC compared to those without MIAC when adjusted by gestational age at amniocentesis. All biomarkers except elafin and MMP-2 had the sensitivity of 100&#x25; with thresholds based on ROC-curve. Odd ratios of biomarkers for MIAC were 1.2-38 and 95&#x25; confidential intervals 1.0-353.6.<i> Conclusions</i>. Neutrophil based AF biomarkers were associated with IAI and MIAC.

Tarja Myntti

Leena Rahkonen

Irmeli Nupponen

Anu P&#xe4;t&#xe4;ri-Sampo

Minna Tikkanen

Timo Sorsa

Juuso Juhila

Sture Andersson

Jorma Paavonen

Vedran Stefanovic

Amniotic Fluid Infection in Preterm Pregnancies with Intact Membranes

<i>Background</i>. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear.<i> Materials and Methods</i>. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients.<i> Results</i>. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6370001pt" id="M1" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 9.2729" width="44.8393pt"><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="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><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></svg>). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6370001pt" id="M2" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 44.8393 9.2729" width="44.8393pt"><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><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></svg>). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2064009pt" id="M3" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 51.1027 8.8423" width="51.1027pt"><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="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><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)"><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>).<i> Conclusion</i>. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC.

Wen-han Li

Yong-chun Song

Hao Zhang

Zhang-jian Zhou

Xin Xie

Qing-nuo Zeng

Kun Guo

Ting Wang

Peng Xia

Dong-min Chang

Decreased Expression of Hsa&#x5f;circ&#x5f;00001649 in Gastric Cancer and Its Clinical Significance

CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M1" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g121-65" d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><path id="g121-95" d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><path id="g58-116" d="M487 439H304V409C361 402 367 391 351 344C328 280 297 190 262 110C235 178 192 284 168 353C152 396 153 403 208 409V439H-1V409C54 401 61 394 85 338C133 221 179 111 224 -10H255C312 139 363 260 398 336C426 394 432 401 487 409V439Z"/></g></svg>2.2) encodes an N-type voltage-gated calcium channel (VGCC) ubiquitously expressed in brain and peripheral nervous system that is important for regulating neuropathic pain. Because intracellular calcium concentration is a key player in cell proliferation and apoptosis, VGCCs are implicated in tumorigenesis. Recent studies have identified CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M2" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g121-65"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><use xlink:href="#g121-95"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><use xlink:href="#g58-116"/></g></svg>2.2) being overexpressed in prostate and breast cancer tissues when compared to adjacent normal tissues; however, its role in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we determined the mRNA and protein expression of CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M3" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g121-65"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><use xlink:href="#g121-95"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><use xlink:href="#g58-116"/></g></svg>2.2) in NSCLC tumorous and adjacent nontumorous tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC), respectively. CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M4" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g121-65"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><use xlink:href="#g121-95"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><use xlink:href="#g58-116"/></g></svg>2.2) protein expressions in tumorous tissues were correlated with NSCLC patients’ clinical characteristics and overall survival. CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M5" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g121-65"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><use xlink:href="#g121-95"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><use xlink:href="#g58-116"/></g></svg>2.2) mRNA and protein expression levels were higher in NSCLC tumorous tissues than in nontumorous tissues. High CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M6" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g121-65"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><use xlink:href="#g121-95"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><use xlink:href="#g58-116"/></g></svg>2.2) protein expression was associated with higher TNM stages, and CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M7" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g121-65"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><use xlink:href="#g121-95"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><use xlink:href="#g58-116"/></g></svg>2.2) protein expression is an independent prognostic marker in NSCLC. Based on our results, we conclude that CACNA1B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M8" height="12.0621pt" version="1.1" viewBox="-0.0498162 -8.7664 19.5693 12.0621" width="19.5693pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g121-65"/></g><g transform="matrix(.013,0,0,-0.013,8.762,0)"><use xlink:href="#g121-95"/></g><g transform="matrix(.0091,0,0,-0.0091,14.523,3.132)"><use xlink:href="#g58-116"/></g></svg>2.2) plays a role in NSCLC development and progression. Elucidating the underlying mechanism may help design novel treatment by specifically targeting the calcium regulation pathway for NSCLC, a devastating disease with increasing incidence and mortality in China.

Xiaoyu Zhou

Wei Wang

Shu Zhang

Xudong Wang

Zhiyuan Tang

Jun Gu

Jun Li

Jianan Huang

CACNA1B (Ca<sub>v</sub>2.2) Overexpression and Its Association with Clinicopathologic Characteristics and Unfavorable Prognosis in Non-Small Cell Lung Cancer

<i>Objective</i>. It was examined whether PTH and 25-dihydroxyvitamin D (25(OH)D) levels, together or separately, are indicators of the risk of stroke.<i> Materials and Methods</i>. This prospective study was performed at two centers. In the study, 100 patients diagnosed with acute ischemic stroke and 100 control individuals in the same age range were examined. In addition to neurological examination, cranial imaging, extensive routine blood chemistry, PTH, and 25(OH)D levels were evaluated in all cases. Stroke risk factors were determined. Logistic regression was used for statistical analysis.<i> Results</i>. A total of 60 patients and 79 control individuals were included in the study. Different estimation models were designed in order to examine the relationship between PTH and 25(OH)D levels with stroke. According to modeling results, it was determined that the most effective predictor for risk of stroke was 25(OH)D levels, followed by hypertension and PTH levels, respectively.<i> Conclusion</i>. PTH and 25(OH)D levels together can make important contributions to determination of stroke risk, and further investigations are needed to understand this relationship more fully.

G&#xfc;ner &#xc7;elik

Ali Do&#x11f;an

&#x15e;efik Dener

&#x15e;erefnur &#xd6;zt&#xfc;rk

Sevsen Kulaks&#x131;zo&#x11f;lu

Hakan Ekmek&#xe7;i

Parathyroid Hormone Levels in the Prediction of Ischemic Stroke Risk

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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