Mei-Ying Wang

Chao-Hung Wang

Wei-Siang Chen

Chien-Ming Chu

Huang-Ping Wu

Min-Hui Liu

Yi-Tsen Lin

Kuo-Chin Kao

Chung-Yu Liang

Wen-Hsin Chen

Huei-Jen Wang

Shu-Chiu Lee

U-Shape Relationship between Plasma Leucine Level and Mortality in the Intensive Care Unit

<i>Background</i>. Since the beginning of the pandemic, clinicians and researchers have been searching for alternative tests to improve the screening and diagnosis of the SARS-CoV-2 infection. Currently, the gold standard for virus identification is the nasopharyngeal (NP) swab. Saliva samples, however, offer clear, practical, and logistical advantages but due to a lack of collection, transport, and storage solutions, high-throughput saliva-based laboratory tests are difficult to scale up as a screening or diagnostic tool. With this study, we aimed to validate an intralaboratory molecular detection method for SARS-CoV-2 on saliva samples collected in a new storage saline solution, comparing the results to NP swabs to determine the difference in sensitivity between the two tests. <i>Methods</i>. In this study, 156 patients (cases) and 1005 asymptomatic subjects (controls) were enrolled and tested simultaneously for the detection of the SARS-CoV-2 viral genome by RT-PCR on both NP swab and saliva samples. Saliva samples were collected in a preservative and inhibiting saline solution (Biofarma Srl). Internal method validation was performed to standardize the entire workflow for saliva samples. <i>Results</i>. The identification of SARS-CoV-2 conducted on saliva samples showed a clinical sensitivity of 95.1% and specificity of 97.8% compared to NP swabs. The positive predictive value (PPV) was 81% while the negative predictive value (NPV) was 99.5%. Test concordance was 97.6% (Cohen’s <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="44.694pt" style="vertical-align:-3.168421pt" id="M1" height="11.6934pt" version="1.1" viewBox="-0.0498162 -8.52498 44.694 11.6934"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-76" d="M667 0V28C619 34 599 43 546 100C496 154 386 277 311 372C378 440 449 512 488 547C551 605 575 615 650 622V650H410V622L433 619C478 614 479 604 449 568C404 513 337 443 282 390C254 364 234 350 212 345V520C212 609 222 616 299 622V650H41V622C120 616 128 611 128 520V128C128 41 120 34 44 28V0H304V28C221 34 212 41 212 128V318C229 321 242 318 266 291C355 185 436 87 514 0H667Z"/></g><g transform="matrix(.013,0,0,-0.013,8.592,0)"><path id="g190-98" 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(.013,0,0,-0.013,14.052,0)"><path id="g190-113" d="M169 380V459C122 440 66 423 24 416V392C86 384 90 382 90 317V-135C90 -201 81 -207 17 -213V-240H253V-213C176 -207 169 -201 169 -125V6C182 -1 208 -11 238 -12C368 12 487 109 487 260C487 358 421 449 310 449C298 449 279 444 261 433L169 380ZM169 346C196 367 237 389 269 389C341 389 403 329 403 221C403 109 347 37 263 37C228 37 191 53 169 76V346Z"/></g><g transform="matrix(.013,0,0,-0.013,20.72,0)"><use xlink:href="#g190-113"/></g><g transform="matrix(.013,0,0,-0.013,27.597,0)"><use xlink:href="#g190-98"/></g><g transform="matrix(.013,0,0,-0.013,37.063,0)"><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="21.893pt" style="vertical-align:-3.168421pt" height="11.6934pt" version="1.1" viewBox="48.2761838 -8.52498 21.893 11.6934"><g transform="matrix(.013,0,0,-0.013,48.326,0)"><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,-0.013,54.566,0)"><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,-0.013,57.53,0)"><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,-0.013,63.77,0)"><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>;</span></span> 95% CI 0.81-0.91). The LoD of the test was 5 viral copies for both samples. <i>Conclusions</i>. RT-PCR assays conducted on a stored saliva sample achieved similar performance to those on NP swabs, and this may provide a very effective tool for population screening and diagnosis. Collection of saliva in a stabilizing solution makes the test more convenient and widely available; furthermore, the denaturing properties of the solution reduce the infective risks belonging to sample manipulation.

Michela Bulfoni

Emanuela Sozio

Barbara Marcon

Maria De Martino

Daniela Cesselli

Chiara De Carlo

Romina Martinella

Angelica Migotti

Eleonora Vania

Agnese Zanus-Fortes

Jessica De Piero

Emanuele Nencioni

Carlo Tascini

Miriam Isola

Francesco Curcio

Validation of a Saliva-Based Test for the Molecular Diagnosis of SARS-CoV-2 Infection

<i>Background</i>. Acute kidney injury (AKI) is an important complication in critically ill patients, especially in sepsis and septic shock patients. Early prediction of AKI in septic shock can provide clinicians with sufficient information for timely intervention so that improve the patients&#x2019; survival rate and quality of life. The aim of this study was to establish a nomogram that predicts the risk of AKI in patients with septic shock in the intensive care unit (ICU). <i>Methods</i>. The data were collected from the Medical Information Mart for Intensive Care III (MIMIC-III) database between 2001 and 2012. The primary outcome was AKI in the 48&#x2009;h following ICU admission. Univariate and multivariate logistic regression analyses were used to screen the independent risk factors of AKI. The performance of the nomogram was evaluated according to the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis, and clinical impact curve. <i>Results</i>. A total of 2415 patients with septic shock were included in this study. In the training and validation cohort, 1091 (64.48&#x0025;) of 1690 patients and 475 (65.52&#x0025;) of 725 patients developed AKI, respectively. The predictive factors for nomogram construction were gender, ethnicity, congestive heart failure, diabetes, obesity, Simplified Acute Physiology Score II (SAPS II), angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs), bilirubin, creatinine, blood urea nitrogen (BUN), and mechanical ventilation. The model had a good discrimination with the area under the ROC curve of 0.756 and 0.760 in the training and validation cohorts, respectively. The calibration curve for probability of AKI in septic shock showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. <i>Conclusion</i>. The proposed nomogram can quickly and effectively predict the risk of AKI at an early stage in patients with septic shock in ICU, which can provide information for timely and efficient intervention in patients with septic shock in the ICU setting.

Suru Yue

Shasha Li

Xueying Huang

Jie Liu

Xuefei Hou

Yufeng Wang

Jiayuan Wu

Construction and Validation of a Risk Prediction Model for Acute Kidney Injury in Patients Suffering from Septic Shock

<i>Objective.</i> This study is aimed at determining the expression and function of the GASL1 and PI3K/AKT pathways in isoproterenol- (ISO-) induced heart failure (HF). To determine the moderating effect of valsartan (VAL) on the progression of ISO-induced HF and to elucidate the related mechanism. <i>Materials and Methods.</i> First, in <i>in vivo</i> experiment, we examined the effect of VAL on cardiac function in rats with ISO-induced HF. Similarly, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of VAL on ISO-treated rat primary cardiomyocytes. Then, si-GASL1-transfected primary cardiomyocytes were constructed and Ad-si-GASL1 was injected through rat tail vein to achieve the effect of lowering GASL1 expression, so as to investigate the role of GASL1 in VAL&#x2019;s treatment of ISO-induced HF. <i>Results.</i> In ISO-induced HF rat models, the GASL1 decreased while PI3K and p-AKT expressions were abnormally elevated and cardiac function deteriorated, and VAL was able to reverse these changes. In primary cardiomyocytes, ISO induces apoptosis of cardiomyocytes, and expression of GASL1 decreased while PI3K and p-AKT were abnormally elevated, which can be reversed by VAL. The transfection of primary cardiomyocytes with si-GASL1 confirmed that GASL1 affected the expression of PI3K, p-AKT, and the apoptosis of primary cardiomyocytes. Rat myocardium injected with Ad-si-GASL1 was found to aggravate the cardiac function improved by VAL. <i>Conclusions.</i> This study was the first to confirm that VAL improves ISO-induced HF by regulating the PI3K/AKT pathway through GASL1. And this study demonstrated a significant correlation between HF, VAL, GASL1, and the PI3K/AKT pathway.

Jian Zhou

Xiujuan Duan

Jibing Wang

Yunhong Feng

Jiangyong Yuan

Valsartan Regulates PI3K/AKT Pathways through lncRNA GASL1 to Improve Isoproterenol-Induced Heart Failure

<i>Objectives.</i> Recent resting-state functional magnetic resonance imaging (fMRI) studies have focused on glaucoma-related neuronal degeneration in structural and spontaneous functional brain activity. However, there are limited studies regarding the differences in the topological organization of the functional brain network in patients with glaucoma. In this study, we aimed to assess both potential alterations and the network efficiency in the functional brain networks of patients with primary angle-closure glaucoma (PACG). <i>Methods</i>. We applied resting-state fMRI data to construct the functional connectivity network of 33 patients with PACG (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="38.461pt" style="vertical-align:-3.40338pt" id="M1" height="11.7522pt" version="1.1" viewBox="-0.0498162 -8.34882 38.461 11.7522"><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(.013,0,0,-0.013,6.24,0)"><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,-0.013,12.48,0)"><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,-0.013,15.444,0)"><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,-0.013,21.684,0)"><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,-0.013,30.83,0)"><path id="g117-37" d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"/></g></svg><span class="ibiop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="50.845pt" style="vertical-align:-3.40338pt" height="11.7522pt" version="1.1" viewBox="41.3161838 -8.34882 50.845 11.7522"><g transform="matrix(.013,0,0,-0.013,41.366,0)"><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,-0.013,47.609,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,50.573,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,56.813,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,65.228,0)"><path id="g190-122" d="M478 437H297V411C355 404 361 392 349 355C329 292 285 174 257 106L167 356C153 394 158 404 205 411L204 437H2V411C57 404 66 391 88 336C117 265 162 144 202 30C208 13 209 0 204 -15C199 -28 191 -49 173 -84C149 -128 130 -153 98 -172C81 -184 73 -193 73 -209C73 -233 101 -257 129 -257C143 -257 156 -252 161 -232C175 -179 197 -122 264 38C333 203 364 286 390 339C417 395 425 403 478 411V437Z"/></g><g transform="matrix(.013,0,0,-0.013,71.09,0)"><path id="g190-102" d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z"/></g><g transform="matrix(.013,0,0,-0.013,76.694,0)"><path id="g190-98" 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(.013,0,0,-0.013,82.283,0)"><path id="g190-115" d="M181 342V451C133 431 89 419 40 411V388C98 381 102 377 102 311V104C102 38 95 32 33 26V0H263V26C186 32 181 38 181 104V287C203 343 235 372 261 372C277 372 289 366 304 352C310 346 318 345 330 350C349 359 362 379 362 399C362 422 338 449 304 449C256 449 213 393 183 342H181Z"/></g><g transform="matrix(.013,0,0,-0.013,87.028,0)"><path id="g190-116" d="M319 325C317 349 306 409 297 431C277 440 250 449 209 449C117 449 57 389 57 319C57 243 122 209 182 182C232 159 261 135 261 91C261 48 227 21 190 21C130 21 85 79 68 145L41 140C41 104 51 36 58 22C75 7 121 -12 172 -12C252 -12 337 35 337 126C337 195 286 231 210 262C166 281 126 304 126 348C126 388 152 417 191 417C240 417 274 378 294 318L319 325Z"/></g></svg>)</span></span> and 33 gender- and age-matched healthy controls (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="38.461pt" style="vertical-align:-3.40338pt" id="M2" height="11.7522pt" version="1.1" viewBox="-0.0498162 -8.34882 38.461 11.7522"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><use xlink:href="#g113-53"/></g><g transform="matrix(.013,0,0,-0.013,21.684,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,30.83,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="50.845pt" style="vertical-align:-3.40338pt" height="11.7522pt" version="1.1" viewBox="41.3161838 -8.34882 50.845 11.7522"><g transform="matrix(.013,0,0,-0.013,41.366,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,47.609,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,50.573,0)"><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,-0.013,56.813,0)"><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,-0.013,65.228,0)"><use xlink:href="#g190-122"/></g><g transform="matrix(.013,0,0,-0.013,71.09,0)"><use xlink:href="#g190-102"/></g><g transform="matrix(.013,0,0,-0.013,76.694,0)"><use xlink:href="#g190-98"/></g><g transform="matrix(.013,0,0,-0.013,82.283,0)"><use xlink:href="#g190-115"/></g><g transform="matrix(.013,0,0,-0.013,87.028,0)"><use xlink:href="#g190-116"/></g></svg>).</span></span> The differences in the global and regional topological brain network properties between the two groups were assessed using graph theoretical analysis. Partial correlations between the altered regional values and clinical parameters were computed for patients with PACG. <i>Results.</i> No significant differences in global topological measures were identified between the two groups. However, significant regional alterations were identified in the patients with PACG, including differences within visual and nonvisual (somatomotor and cognition-emotion) regions. The normalized clustering coefficient and normalized local efficiency of the right superior parietal gyrus were significantly correlated with the retinal fiber layer thickness (RNFLT) and the vertical cup to disk ratio (V C/D). In addition, the normalized node betweenness of the left middle frontal gyrus (orbital portion) was significantly correlated with the V C/D in the patients with PACG. <i>Conclusions</i>. Our results suggest that regional inefficiency with decrease and compensatory increase in local functional properties of visual and nonvisual nodes preserved the brain network of the PACG at the global level.

Dan Liu

Junwei Gao

Tao You

Shenghong Li

Fengqin Cai

Chonggang Pei

Xianjun Zeng

Brain Functional Network Analysis of Patients with Primary Angle-Closure Glaucoma

<i>Objectives</i>. The epithelial-to-mesenchymal transition (EMT) is one key step for the invasion and metastasis of colorectal cancer (CRC). Up until now, the underlying mechanism of EMT in CRC is still unpromising. Thus, it is essential to have a better understanding of its carcinogenesis. The transfer RNA-derived small fragments (tsRNAs) are a new group of small noncoding RNAs (sncRNAs), including tRNA-derived stress-induced RNAs (tiRNAs) and tRNA-derived fragments (tRFs), which have been observed to play an important role in many cancers. However, the relationship between tRFs and EMT in CRC is still unknown. Herein, we aimed to investigate the involvement of tRFs in EMT and its contribution to CRC development. <i>Methods</i>. We identified the differentially expressed tsRNAs in colorectal cancer cell line HT29 treated with TGF-<i>β</i> compared with control cells by using high-throughput sequencing and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). QRT-PCR was conducted to validate the differentially expressed fragments in 68 CRC tumor samples (22 women and 46 men) and adjacent nontumor samples. The association of the expression of tRFs with CRC metastasis and clinical stage was analyzed. Meanwhile, the correlation between tRF expression and overall survival (OS) was also analyzed. TargetScan and miRanda and multiple bioinformatic approaches were used to predict the possible target genes of tsRNAs and analyze possible functions of the tRFs. <i>Results.</i> A series of differentially expressed tsRNAs were identified in TGF-<i>β</i>-treated HT29 cells compared with control cells. tRF-phe-GAA-031 and tRF-VAL-TCA-002 were found to be significantly upregulated in CRC tissues compared to adjacent nontumor tissues. They were significantly correlated with distant metastasis and clinical stage. We compared the differences between tumor samples and nontumor tissues from the ROC curves. The area under the ROC curve (AUC) was up to 0.7554 (95% confidence interval: 0.6739 to 0.8369, <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="M1" 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="34.448pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 34.448 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)"><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="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><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> for tRF-Phe-GAA-031 and up to 0.7313 (95% confidence interval: 0.6474 to 0.8151, <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)"><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="34.448pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 34.448 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="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.529,0)"><use xlink:href="#g113-50"/></g></svg>)</span></span> for tRF-VAL-TCA-002. For OS analysis, higher tRF-phe-GAA-031 and tRF-VAL-TCA-002 expressions were associated with shorter survival for CRC patients. <i>Conclusion.</i> A series of differentially expressed tsRNAs are identified in the EMT process of CRC. And tRF-phe-GAA-031 and tRF-VAL-TCA-002 are higher expressed in CRC tissues, and they might play an important role in the metastasis of CRC. Meanwhile, they may be potential biomarkers and intervention targets in the clinical treatment of CRC.

Hui Chen

Zhiying Xu

Hua Cai

Ya Peng

Li Yang

Zhen Wang

Identifying Differentially Expressed tRNA-Derived Small Fragments as a Biomarker for the Progression and Metastasis of Colorectal Cancer

Fasting is a prevalent approach to weight loss and is a feasible method for treating some diseases, such as type 2 diabetes. Meanwhile, the effects of intermittent fasting on health, aging, and disease process are hot issues and are of concern by researchers of multiple areas, even the public. This article introduces the effects of fasting on human lipid metabolism, glucose metabolism, protein metabolism, and neuroendocrine metabolism; demonstrates the metabolic conversion caused by fasting; and describes the effects of fasting on human psychological health, the relationship between mood regulation and glucose, and the emotional enhancing effect induced by fasting.

Yiren Wang

Ruilin Wu

The Effect of Fasting on Human Metabolism and Psychological Health

Zhiyuan Li

Haiyan Wang

Mo Liang

Zhenghua Li

Yvliang Li

Xiaoping Zhou

Guoping Kuang

Hypochlorous Acid Can Be the Novel Option for the Meibomian Gland Dysfunction Dry Eye through Ultrasonic Atomization

<i>Objective</i>. To elucidate the role of metformin in influencing VSMCs via the involvement of lncRNA-ATB. <i>Methods</i>. qRT-PCR was conducted to detect serum levels of lncRNA-ATB and p53 in CHD patients (<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="g113-54" 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="g113-49" 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></svg>)</span></span> and healthy subjects (<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="M2" 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)"><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:-0.2063904pt" 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)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,27.661,0)"><use xlink:href="#g113-49"/></g></svg>).</span></span> Correlation in serum levels of lncRNA-ATB and p53 in CHD patients was assessed by Pearson correlation test. ROC curves were depicted for analyzing the predictive potential of lncRNA-ATB in the occurrence of CHD. After metformin induction in VSMCs overexpressing lncRNA-ATB, relative levels of lncRNA-ATB and p53 were detected. Meanwhile, proliferative, migratory, and invasive abilities in VSMCs were, respectively, examined by CCK-8 and transwell assay. The interaction between lncRNA-ATB and p53 was tested by RIP. In addition, the coregulation of lncRNA-ATB and p53 in cell functions of VSMCs was finally determined. <i>Results</i>. Increased serum level of lncRNA-ATB and decreased p53 level were detected in CHD patients than those of healthy subjects. LncRNA-ATB could interact with p53 and negatively regulate its level. In addition, lncRNA-ATB could serve as a potential biomarker for predicting the occurrence of CHD. The overexpression of lncRNA-ATB triggered viability, migratory, and invasive abilities in VSMCs, and the above trends were abolished by metformin induction. The overexpression of p53 partially abolished the promotive effects of lncRNA-ATB on proliferative, migratory, and invasive abilities in VSMCs. <i>Conclusions</i>. Metformin induction inhibits proliferative, migratory, and invasive abilities in VSMCs by downregulating lncRNA-ATB, which may be related to p53 activation.

Wei Jia

Yue Zhou

Lina Sun

Jianlong Liu

Zhiyuan Cheng

Shuofang Zhao

Potential Effects of Metformin on the Vitality, Invasion, and Migration of Human Vascular Smooth Muscle Cells via Downregulating lncRNA-ATB

<i>Objective</i>. Adriamycin is a clinically important chemotherapeutic drug, but its use is restricted due to its myocardial toxicity. Therefore, it is especially important to explore the toxicity mechanism of Adriamycin (ADR) to cardiomyocytes. <i>Methods</i>. The myocardial toxicity model of ADR was constructed in vitro, and the effect of miR-218 inhibitor and sh-Serp1 on the activity of H9C2 cells induced by ADR was detected by MTT method. Also, flow cytometry, real-time polymerase chain reaction (RT-PCR), and TUNEL staining were used to detect the cell apoptosis. The activity of LDH was detected by colorimetry, and the interaction of miR-218 with Serp1 was detected by double-luciferase reporter gene assay. Western blotting technique was used to detect the expression level of caspase3 and p38 MAPK signal pathway. <i>Results</i>. miR-218 inhibitor can obviously inhibit ADR-induced decrease in cell activity of H9C2 cells, inhibit cell apoptosis, and inhibit p38 MAPK signaling pathway activation. Conversely, sh-Serp1 aggravated the decrease in H9C2 cell activity and promoted cell apoptosis. <i>Conclusion</i>. Upregulation of miR-218 expression will promote ADR-induced apoptosis of H9C2 cells. At the same time, we confirmed that the mechanism by which miR-218 promotes myocardial apoptosis was through the Serp1/p38 MAPK/caspase-3 signaling pathway.

Qinghua Chen

Gang Chen

MiR-218 Promotes Adriamycin-Induced H9C2 Apoptosis by Inhibiting Stress-Associated Endoplasmic Reticulum Protein 1

About this journal

<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>


Journal profile

Meet the editorial board

<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>


Editor spotlight

Submit your proposal

Do you think there is an emerging area of research that really needs to be highlighted? Or an existing research area that has been overlooked or would benefit from deeper investigation? Raise the profile of a research area by leading a Special Issue.

Special Issues

Author guidelines

Editorial board

Databases and indexing

title

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