bluuebunny/crossref_metadata_2025 huggingface dataset:
The horizontal and vertical components of nystagmus evoked by the supine roll test in horizontal semicircular canal canalolithiasis
Authors: Zhang Xueqing , Deng Qiaomei , Liu Qiang , Wen Chao , Wang Wei , Chen Taisheng
Published: August 2022

Objective

The characteristics of horizontal and vertical components of nystagmus evoked by the supine roll test in patients with horizontal semicircular canal canalolithiasis (HSC-Can) were analyzed, according to Ewald’s first law. It provided a basis for the study of human horizontal semicircular canal function and structure, objective diagnosis, and treatment of benign paroxysmal positional vertigo (BPPV).

Materials and methods

The records of patients that had been tested with 2-dimensional videonystagmography (2D-VNG) were reviewed between June 2019 and June 2021. The intensity and direction of horizontal and vertical nystagmus elicited by the supine roll test were analyzed in 189 patients with idiopathic HSC-Can.

Results

All the 189 patients with HSC-Can were induced horizontal nystagmus with the same direction as head-turning (geotropic) in the supine roll test, of which 119 patients (63.96%) had a weak vertical upward component of nystagmus on the affected and unaffected sides, 57 patients (30.16%) had a vertical downward component of nystagmus on the affected side and/or the unaffected side, and 13 patients (6.88%) had no vertical component of nystagmus on both the sides. The intensity values of the horizontal component on the affected and unaffected sides were 42.14 ± 24.78 (range: 6.26–138.00°/s) and 17.48 ± 10.91°/s (range: 2.40–53.83°/s), with a ratio of 2.96 ± 2.17:1, representing a significant difference (p < 0.001). We analyzed the characteristics of horizontal and vertical components in 119 patients with HSC-Can (57 L-HSC-Can and 62 R-HSC-Can) on the supine roll test. The intensity values of the horizontal component on the affected and unaffected sides were 43.17 ± 23.76 (range: 8.60–124.51°/s) and 17.98 ± 10.99°/s (range: 2.40–53.83°/s), and the intensity values of the vertical component on the affected and unaffected sides were 10.65 ± 8.46 (range: 1.90–50.83°/s) and 4.81 ± 3.45°/s (range: 0.30–20.43°/s), representing a significant difference between groups (p < 0.001). Among 119 patients with HSC-Can who had a vertical upward component on both the affected and unaffected sides in the supine roll test, unilateral weakness (UW) was normal in 53 cases and abnormal in 51 cases, and 15 cases did not undergo the caloric test. We compared the horizontal and vertical components of nystagmus induced on the affected and unaffected sides in the supine roll test in 53 patients with normal UW and 51 patients with abnormal UW, and the difference was not statistically significant.

Conclusion

There is mostly a vertical upward component based on the horizontal component in HSC-Can, and the direction and intensity characteristics of nystagmus accord with Ewald’s first law, which can provide a basis for the study of human HSC function and structure, objective diagnosis, and treatment of BPPV.
Case report: Candidiasis of gastrojejunostomosis after pancreaticoduodenectomy: Preliminary experience from two cases
Authors: Nguyen Thanh Khiem , Nguyen Ham Hoi , Nguyen Cong Long , Luong Tuan Hiep , Dinh Long Doan , Le Van Duy , Dang Kim Khue , Tran Thi Lan
Published: August 2022

Introduction

Invasive Candida infection, or candidiasis, especially in gastrointestinal tract (GIT) is an infrequent but aggressive disease caused by Candida species. Candidiasis of gastrojejunostomosis after extensive gastrointestinal surgery may cause serious complications such as perforative peritonitis and anastomotic stenosis, which requires surgical interventions.

Case presentation

Our two patients had undergone pancreaticoduodenectomy (PD), respectively, due to pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasms of the pancreatic head. Both the patients were malnutritioned and debilitated before the surgery, and they required reoperation for postoperative Candidiasis-relevant complication.In the first case, the patient was readmitted to the hospital with symptoms of perforative peritonitis, for which he underwent surgery and had Candida found in both gastrojejunostomosis ulcer and peritoneal fluid. In our second case, the patient was admitted to the hospital twice after the first operation and diagnosed with Candida-induced gastrojejunostomosis stenosis by esophagogastroduodenoscopy (EGD) and endoscopic biopsy. Fluconazole was indicated for a 2-week regimen. Blood sample withdrawn afterward showed no evidence of fungal agents, and the anastomotic stenosis responded well to treatment. However, after 3 weeks, he came back with cachexia and symptoms of gastrojejunostomotic stenosis. EGD showed no image of fungal agents but anastomotic stenosis due to chronic inflammatory process. The patient was then reoperated to redo his gastrojejunostomosis.

Conclusion

Candidiasis of gastrojejunostomosis after extensive gastrointestinal surgery such as PD is a very aggressive condition that may cause perforative peritonitis and anastomotic stenosis. However, there have been no publications on this disorder, and the strategic treatment remains unknown. We hereby present a report of two cases with postoperative gastrojejunostomosis candidiasis presenting with non-specific but aggressive and early clinical symptoms.
Pulmonary mucoepidermoid carcinoma in the Chinese population: A clinical characteristic and prognostic analysis
Authors: Li Qiuyu , Wei Xuejing , Wang Yanfei , Liu Chang , Fan Boshi , Lv Cheng , Si Wenzhe , Li Min
Published: August 2022

Background

Mucoepidermoid carcinoma is dominant in salivary glands and rarely occurs in the lung. Primary pulmonary mucoepidermoid carcinoma is a type of non-small-cell lung cancer, but the prognostic factors in Chinese patients remain controversial. This investigation aimed to review cases of pulmonary mucoepidermoid carcinoma, analyse the prognosis of this disease.

Methods

Patients with pathologically proven pulmonary mucoepidermoid carcinoma were screened at the Department of Respiratory and Critical Care Medicine at the Peking University Third Hospital, Beijing Friendship Hospital Affiliated to Capital Medical University, and Peking University Cancer Hospital for inclusion in this retrospective study. Demographic data, including age, sex, clinical symptoms, smoking, alcohol consumption, allergies, family history, imaging findings, fibrobronchoscopy findings, surgical procedures, tumour location and pathologic stage, were collected. Telephone follow-up was conducted for all patients not lost to follow-up. The associations of sex, age, smoking, tumour differentiation, tumour size, lymph node metastasis, pathologic stage, and patient survival were retrospectively analysed. Kaplan–Meier, univariate and multivariate analysis curves were used to analyse patient prognosis and prognostic factors.

Results

Thirty-one patients, comprising 23 males and 8 females, were enrolled in the analysis. The mean age was 60.77 ± 11.44 years. The first symptom was nonspecific, with cough being the most common (21/31, 67.77%); smokers accounted for 16 of the 31 patients, and ten patients had a history of alcohol consumption. Overall, the tumours could occur in either lobe of the lungs; tumours occurred in the right lung in 19/31 patients, and tumours occurred in the left lung in 12/31 patients. Regarding TNM stage, 10 patients had stage I (5 with stage 1a, 5 with stage 1b), 5 had stage II (1 with stage 2a, 4 with stage 2b), 3 had stage III (1 with stage 3a, 2 with stage 3b), and 13 had stage IV (10 with stage 4a, 3 with stage 4b). In our Cox univariate survival analysis of patients with pulmonary mucoepidermoid carcinoma, we found that TNM stage IV, degree of differentiation and lymph node metastasis were risk factors for pulmonary mucoepidermoid carcinoma and that degree of differentiation was an independent risk factor.

Conclusion

The clinical, radiographical and pathological features of pulmonary mucoepidermoid carcinoma were systemically analysed and summarized, and the degree of differentiation and lymph node metastasis, as well as prognostic factors in addition to clinical stage, were confirmed.
Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma
Authors: Xin Rui , Shen Biao , Jiang Ying-Jie , Liu Ji-Bin , Li Sha , Hou Li-Kun , Wu Wei , Jia Cheng-You , Wu Chun-Yan , Fu Da , Ma Yu-Shui , Jiang Geng-Xi
Published: August 2022

Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTENhigh) and low- (PTENlow) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Ptenflox/+). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.
POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin–paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma
Authors: Rao Sheela , Jones Mark , Bowman Jill , Tian Chuan , Spano Jean-Philippe
Published: August 2022

Background

Squamous carcinoma of the anal canal (SCAC) is a human papillomavirus (HPV)-driven cancer with poor prognosis in locally advanced or recurrent settings. Carboplatin–paclitaxel is the preferred first-line regimen for unresectable locally advanced or metastatic SCAC, with the reported median progression-free survival (PFS) and overall survival (OS) of 8.1 and 20.0 months, respectively. Immune checkpoint blockade (ICB) demonstrates improved survival in HPV-driven cervical and head and neck cancers. Retifanlimab (INCMGA00012) is an investigational humanized, hinge-stabilized, immunoglobulin G4κ monoclonal antibody targeting programmed cell death-1 (PD-1), with characteristics common to the ICB class. In POD1UM-202, retifanlimab showed substantial clinical activity and an expected safety profile in patients with advanced SCAC who progressed on platinum-based chemotherapy. Based on these encouraging results, POD1UM-303/InterAACT 2 (NCT04472429), a phase III, double-blind, randomized, multiregional study, investigates the addition of retifanlimab to the standard of care (SOC) carboplatin–paclitaxel in patients with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy.

Methods and analysis

Patients ≥18 years with inoperable locally recurrent or metastatic SCAC, measurable disease per RECIST v1.1, and no prior systemic chemotherapy or PD-(L)1-directed therapy will be enrolled and stratified by PD-L1 expression, region, and extent of disease. Patients with well-controlled human immunodeficiency virus infection are eligible. Planned enrollment is approximately 300 patients worldwide, with a 1:1 randomization to retifanlimab or placebo. Patients will receive up to six induction cycles (24 weeks) of carboplatin (area-under-the-curve 5 on day 1) and paclitaxel (80 mg/m2 on days 1, 8, and 15) every 28 days per SOC. Concurrently, retifanlimab 500 mg or placebo will be administered intravenously in a blinded fashion on day 1 of each 28-day cycle for up to 13 cycles (1 year) in the absence of unacceptable toxicity, disease progression, withdrawal of consent, loss to follow-up, or premature discontinuation. Crossover to open-label retifanlimab will be allowed for patients assigned to placebo upon verification of progression by blinded independent central radiographic review (BICR). The primary study endpoint is PFS per RECIST v1.1 by BICR. Secondary endpoints are OS, objective response rate, duration of response, disease control rate, safety, and retifanlimab pharmacokinetics. The study is currently recruiting.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT04472429; https://clinicaltrialsregister.eu/ctr-search/search?query=2020-000826-24
Targeting the key cholesterol biosynthesis enzyme squalene monooxygenasefor cancer therapy
Authors: Zou Yuheng , Zhang Hongying , Bi Feng , Tang Qiulin , Xu Huanji
Published: August 2022

Cholesterol metabolism is often dysregulated in cancer. Squalene monooxygenase (SQLE) is the second rate-limiting enzyme involved in cholesterol synthesis. Since the discovery of SQLE dysregulation in cancer, compelling evidence has indicated that SQLE plays a vital role in cancer initiation and progression and is a promising therapeutic target for cancer treatment. In this review, we provide an overview of the role and regulation of SQLE in cancer and summarize the updates of antitumor therapy targeting SQLE.
Clinical applications of circulating tumor cells in hepatocellular carcinoma
Authors: Hua Yinggang , Dong Jingqing , Hong Jinsong , Wang Bailin , Yan Yong , Li Zhiming
Published: August 2022

Hepatocellular carcinoma (HCC) is a highly malignant tumor and ranked as the fourth cause of cancer-related mortality. The poor clinical prognosis is due to an advanced stage and resistance to systemic treatment. There are no obvious clinical symptoms in the early stage and the early diagnosis rate remains low. Novel effective biomarkers are important for early diagnosis and tumor surveillance to improve the survival of HCC patients. Circulating tumor cells (CTCs) are cancer cells shed from primary or metastatic tumor and extravasate into the blood system. The number of CTCs is closely related to the metastasis of various solid tumors. CTCs escape from blood vessels and settle in target organs, then form micro-metastasis. Epithelial-mesenchymal transformation (EMT) plays a crucial role in distant metastasis, which confers strong invasiveness to CTCs. The fact that CTCs can provide complete cellular biological information, which allows CTCs to be one of the most promising liquid biopsy targets. Recent studies have shown that CTCs are good candidates for early diagnosis, prognosis evaluation of metastasis or recurrence, and even a potential therapeutic target in patients with HCC. It is a new indicator for clinical application in the future. In this review, we introduce the enrichment methods and mechanisms of CTCs, and focus on clinical application in patients with HCC.
Bile-derived exosome noncoding RNAs as potential diagnostic and prognostic biomarkers for cholangiocarcinoma
Authors: Pan Yan , Shao Shijie , Sun Hang , Zhu Huafeng , Fang Haixing
Published: August 2022

Background

Cholangiocarcinoma (CCA) is one of the most aggressive malignancies, lacking novel diagnostic and prognostic biomarkers. Exosome noncoding RNAs (ncRNA) were previously proposed as a potential source of biomarkers in several cancers. This study aimed to interpret the value of specific bile-derived ncRNA as predictors for early diagnosis and prognosis of CCA.

Methods

We recruited 100 patients who received endoscopic retrograde cholangiopancreatography at our hospital for bile duct obstruction due to CCA (n = 50) and biliary stone (n = 50). They were further divided into training set and validation set (3:2). A panel of CCA-specific ncRNAs including 5 miRNAs (PMID: 30165035) and 2 lncRNAs (PMID: 29050258) were detected in both serum and bile exosomes. The diagnostic accuracy was assessed using the area under the receiver operating characteristic curve. Logistic analysis was used to classify the potential predictors of CCA and further establish the diagnostic model. And the prognostic value of the ncRNAs was also assessed.

Results

Exosomes were successfully collected from bile and serum. Exosomal miR-141-3p, miR-200a-3p, miR-200c-3p in serum and bile, as well as miR-200b-3p and ENST00000588480.1 in bile showed AUCs of >0.70 in the diagnosis of CCA. Bile exosomal miR-200c-3p displayed the best diagnostic value with the AUC of 0.87. The combination of serum CA19-9 into the model could increase the AUC to 0.906. Bile exosomal miR-200a-3p and miR-200c-3p were found to be independent predictors of CCA. Among exosomal ncRNAs in human bile and blood, 3 (serum and bile exosomal miR-200c-3p, bile exosomal miR-200a-3p) showed significant value in predicting cancer recurrence and 1 (serum exosomal miR-200c-3p) had great predictive ability of cancer death. High levels of serum exosomal miR-200c-3p showed unfavorable tumor-free survival and overall survival.

Conclusion

The bile exosomal miR-200 family, particularly miR-200c-3p, was verified to be a potential biomarker for the early detection of CCA. The diagnostic ability of exosomal ncRNAs in human bile is better than that in blood. Moreover, high levels of bile exosomal miR-200a-3p, miR-200c-3p, and serum exosomal miR-200c-3p represented adverse clinical outcomes.
Precision oncology for RET-related tumors
Authors: Verrienti Antonella , Grani Giorgio , Sponziello Marialuisa , Pecce Valeria , Damante Giuseppe , Durante Cosimo , Russo Diego , Filetti Sebastiano
Published: August 2022

Aberrant activation of the RET proto-oncogene is implicated in a plethora of cancers. RET gain-of-function point mutations are driver events in multiple endocrine neoplasia 2 (MEN2) syndrome and in sporadic medullary thyroid cancer, while RET rearrangements are driver events in several non-medullary thyroid cancers. Drugs able to inhibit RET have been used to treat RET-mutated cancers. Multikinase inhibitors were initially used, though they showed modest efficacy and significant toxicity. However, new RET selective inhibitors, such as selpercatinib and pralsetinib, have recently been tested and have shown good efficacy and tolerability, even if no direct comparison is yet available between multikinase and selective inhibitors. The advent of high-throughput technology has identified cancers with rare RET alterations beyond point mutations and fusions, including RET deletions, raising questions about whether these alterations have a functional effect and can be targeted by RET inhibitors. In this mini review, we focus on tumors with RET deletions, including deletions/insertions (indels), and their response to RET inhibitors.
Comparative analysis of cystic biliary atresia and choledochal cysts
Authors: Chen Yu-tong , Gao Ming-juan , Zheng Ze-bing , Huang Lu , Du Qing , Zhu Dai-wei , Liu Yuan-mei , Jin Zhu
Published: August 2022

Objective

Cystic biliary atresia (CBA) is a rare and peculiar type of biliary atresia (BA) that is easily confused with infantile choledochal cysts (CCs). This study explored information for early CBA diagnosis and treatment.

Method

The authors retrospectively analyzed the clinical data of 32 children with hilar cysts from January 2013 to May 2021. According to the diagnosis, they were divided into the CBA (n = 12) and CC (n = 20) groups. Patient features, biochemical indexes, preoperative ultrasound characteristics, cholangiography features, and intraoperative findings were analyzed and compared between the two groups.

Results

The alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels in the CBA group were higher than in the CCs group (P < 0.05). Additionally, B-mode ultrasound showed a cystic mass in front of the hepatic hilum, and the cyst size was much smaller in the CBA group compared with the CC group (2.2 ± 1.3 cm vs. 6.0 ± 2.2 cm, P < 0.001). Among all of the parameters, cyst width was the most accurate for identifying CBA and CCs. A cutoff value of 2.5 cm (area under the curve, 0.98, P < 0.001) showed 90.9% sensitivity and 95% specificity for cyst size.

Conclusion

For children with early-onset severe jaundice, and if the width of the cystic mass was ≤2.5 cm, a diagnosis of CBA was highly likely. Early cholangiography and surgical treatment are necessary for the effective treatment of these infants.
Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Tsai I-Chen , Hsu Chih-Wei , Chang Chun-Hung , Tseng Ping-Tao , Chang Ke-Vin
Published: August 2022

Coenzyme Q10 (CoQ10) is a popular nutritional supplement, an antioxidant and an essential component of the mitochondrial electron transport chain. Several clinical studies have suggested that fatigue can be reduced by antioxidant supplementation. However, the data on this topic has been sparse to date. Hence, we conducted this meta-analysis with the aim of investigating the effectiveness of fatigue reduction via CoQ10 supplementation. More specifically, we searched electronic databases for randomized controlled trials (RCTs) published from the database inception to January 2022. A random effects model was implemented to conduct the meta-analysis among 13 RCTs (with a total of 1,126 participants). As compared with the placebo groups evaluated in each RCT, the CoQ10 group showed a statistically significant reduction in fatigue scores (Hedges’ g = −0.398, 95% confidence interval = −0.641 to −0.155, p = 0.001). The directions of the treatment effects were consistent between the healthy and diseased participants. Compared with the placebo group, the effect of reducing fatigue was statistically significant in the subgroup using the CoQ10-only formulation but not in the subgroup using CoQ10 compounds. The results of our meta-regression demonstrate that increases in the daily dose (coefficient = −0.0017 per mg, p < 0.001) and treatment duration (coefficient = −0.0042 per day, p = 0.007) of CoQ10 supplementation were correlated with greater fatigue reduction. There was only one adverse (gastrointestinal) event in the 602 participants who underwent the CoQ10 intervention. Based on the results of this meta-analysis, we conclude that CoQ10 is an effective and safe supplement for reducing fatigue symptoms.

Systematic Review Registration:https://inplasy.com/inplasy-2022-1-0113/, identifier INPLASY202210113
Pharmacokinetic assessment of vancomycin in critically ill patients and nephrotoxicity prediction using individualized pharmacokinetic parameters
Authors: Ghasemiyeh Parisa , Vazin Afsaneh , Zand Farid , Haem Elham , Karimzadeh Iman , Azadi Amir , Masjedi Mansoor , Sabetian Golnar , Nikandish Reza , Mohammadi-Samani Soliman
Published: August 2022

Introduction: Therapeutic drug monitoring (TDM) and pharmacokinetic assessments of vancomycin would be essential to avoid vancomycin-associated nephrotoxicity and obtain optimal therapeutic and clinical responses. Different pharmacokinetic parameters, including trough concentration and area under the curve (AUC), have been proposed to assess the safety and efficacy of vancomycin administration.

Methods: Critically ill patients receiving vancomycin at Nemazee Hospital were included in this prospective study. Four blood samples at various time intervals were taken from each participated patient. Vancomycin was extracted from plasma samples and analyzed using a validated HPLC method.

Results: Fifty-three critically ill patients with a total of 212 blood samples from June 2019 to June 2021 were included in this study. There was a significant correlation between baseline GFR, baseline serum creatinine, trough and peak concentrations, AUCτ, AUC24h, Cl, and Vd values with vancomycin-induced AKI. Based on trough concentration values, 66% of patients were under-dosed (trough concentration <15 μg/ml) and 18.9% were over-dosed (trough concentration ≥20 μg/ml). Also, based on AUC24h values, about 52.2% were under-dosed (AUC24h < 400 μg h/ml), and 21.7% were over-dosed (AUC24h > 600 μg h/ml) that emphasizes on the superiority of AUC-based monitoring approach for TDM purposes to avoid nephrotoxicity occurrence.

Conclusion: The AUC-based monitoring approach would be superior in terms of nephrotoxicity prediction. Also, to avoid vancomycin-induced AKI, trough concentration and AUCτ values should be maintained below the cut-off points.
Recent findings in the regulation of G6PD and its role in diseases
Authors: Meng Qingfei , Zhang Yanghe , Hao Shiming , Sun Huihui , Liu Bin , Zhou Honglan , Wang Yishu , Xu Zhi-Xiang
Published: August 2022

Glucose-6-phosphate dehydrogenase (G6PD) is the only rate-limiting enzyme in the pentose phosphate pathway (PPP). Rapidly proliferating cells require metabolites from PPP to synthesize ribonucleotides and maintain intracellular redox homeostasis. G6PD expression can be abnormally elevated in a variety of cancers. In addition, G6PD may act as a regulator of viral replication and vascular smooth muscle function. Therefore, G6PD-mediated activation of PPP may promote tumor and non-neoplastic disease progression. Recently, studies have identified post-translational modifications (PTMs) as an important mechanism for regulating G6PD function. Here, we provide a comprehensive review of various PTMs (e.g., phosphorylation, acetylation, glycosylation, ubiquitination, and glutarylation), which are identified in the regulation of G6PD structure, expression and enzymatic activity. In addition, we review signaling pathways that regulate G6PD and evaluate the role of oncogenic signals that lead to the reprogramming of PPP in tumor and non-neoplastic diseases as well as summarize the inhibitors that target G6PD.
Creatinine accelerates APAP-induced liver damage by increasing oxidative stress through ROS/JNK signaling pathway
Authors: Liu Fang , Liu Yan , Peng Qifeng , Wang Guodong , Tan Qing , Ou Zhongyue , Xu Qishan , Liu Chixiang , Zuo Daming , Zhao Jianbo
Published: August 2022

Serum creatinine is an endogenous biomarker to estimate glomerular filtration rate (GFR) and is commonly used to assess renal function in clinical practice. Acetaminophen (APAP), the most available analgesic and antipyretic medication, is recommended as the drug of choice for pain control in patients with renal diseases. However, an overdose of APAP can lead to severe acute liver injury, which is also the most common cause of acute liver failure in western countries. The role of creatinine in APAP-induced liver injury is unclear and should be further explored. Herein, clinical data on patients with drug-induced liver injury revealed that the creatinine concentration between 82-442 μmol/L for female and 98–442 μmol/L for male is positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST). While there was no correlation between creatinine and ALT and AST when creatinine concentration is over 442 μmol/L. In addition, mice were administrated with creatinine intraperitoneally for 1 week before APAP injection to investigated the pathophysiological role of creatinine in APAP-induced acute liver injury. The results showed that creatinine administration aggravated hepatic necrosis and elevated serum lactate dehydrogenase (LDH) and ALT levels in mice upon APAP injection. The mechanism study demonstrated that creatinine could increase the production of reactive oxygen activation (ROS) and the activation of c-Jun N-terminal kinase (JNK). Furthermore, the liver injury was alleviated and the difference between APAP-treated mice and APAP combined with creatinine-treated mice was blunted after using specific ROS and JNK inhibitors. Significantly, creatinine stimulation aggravates APAP-induced cell death in HepaRG cells with the same mechanism. In summary, this study proposed that creatinine is closely related with liver function of drug-induced liver injury and exacerbates APAP-induced hepatocyte death by promoting ROS production and JNK activation, thus providing new insight into the usage of APAP in patients with kidney problems.
Autophagy in renal fibrosis: Protection or promotion?
Authors: Dai Rong , Zhang Lei , Jin Hua , Wang Dong , Cheng Meng , Sang Tian , Peng Chuyi , Li Yue , Wang Yiping
Published: August 2022

Autophagy is a process that degrades endogenous cellular protein aggregates and damaged organelles via the lysosomal pathway to maintain cellular homeostasis and energy production. Baseline autophagy in the kidney, which serves as a quality control system, is essential for cellular metabolism and organelle homeostasis. Renal fibrosis is the ultimate pathological manifestation of progressive chronic kidney disease. In several experimental models of renal fibrosis, different time points, stimulus intensities, factors, and molecular mechanisms mediating the upregulation or downregulation of autophagy may have different effects on renal fibrosis. Autophagy occurring in a single lesion may also exert several distinct biological effects on renal fibrosis. Thus, whether autophagy prevents or facilitates renal fibrosis remains a complex and challenging question. This review explores the different effects of the dual regulatory function of autophagy on renal fibrosis in different renal fibrosis models, providing ideas for future work in related basic and clinical research.
Using an untargeted metabolomics approach to analyze serum metabolites in COVID-19 patients with nucleic acid turning negative
Authors: Chen Wenyu , Yao Ming , Chen Miaomiao , Ou Zhao , Yang Qi , He Yanbin , Zhang Ning , Deng Min , Wu Yuqi , Chen Rongchang , Tan Xiaoli , Kong Ziqing
Published: August 2022

Background: The coronavirus disease of 2019 (COVID-19) is a severe public health issue that has infected millions of people. The effective prevention and control of COVID-19 has resulted in a considerable increase in the number of cured cases. However, little research has been done on a complete metabonomic examination of metabolic alterations in COVID-19 patients following treatment. The current project pursues rigorously to characterize the variation of serum metabolites between healthy controls and COVID-19 patients with nucleic acid turning negative via untargeted metabolomics.

Methods: The metabolic difference between 20 COVID-19 patients (CT ≥ 35) and 20 healthy controls were investigated utilizing untargeted metabolomics analysis employing High-resolution UHPLC-MS/MS. COVID-19 patients’ fundamental clinical indicators, as well as health controls, were also collected.

Results: Out of the 714 metabolites identified, 203 still significantly differed between COVID-19 patients and healthy controls, including multiple amino acids, fatty acids, and glycerophospholipids. The clinical indexes including monocytes, lymphocytes, albumin concentration, total bilirubin and direct bilirubin have also differed between our two groups of participators.

Conclusion: Our results clearly showed that in COVID-19 patients with nucleic acid turning negative, their metabolism was still dysregulated in amino acid metabolism and lipid metabolism, which could be the mechanism of long-COVID and calls for specific post-treatment care to help COVID-19 patients recover.
Dietary stilbenes as modulators of specific miRNAs in prostate cancer
Authors: Levenson Anait S.
Published: August 2022

Accumulated experimental data have suggested that natural plant products may be effective miRNA-modulating chemopreventive and therapeutic agents. Dietary polyphenols such as flavonoids, stilbenes, and lignans, among others, have been intensively studied for their miRNA-mediated cardioprotective, antioxidant, anti-inflammatory and anticancer properties. The aim of this review is to outline known stilbene-regulated miRNAs in cancer, with a special focus on the interplay between various miRNAs and MTA1 signaling in prostate cancer. MTA1 is an epigenetic reader and an oncogenic transcription factor that is overexpressed in advanced prostate cancer and metastasis. Not surprisingly, miRNAs that are linked to MTA1 affect cancer progression and the metastatic potential of cells. Studies led to the identification of MTA1-associated pro-oncogenic miRNAs, which are regulated by stilbenes such as resveratrol and pterostilbene. Specifically, it has been shown that inhibition of the activity of the MTA1 regulated oncogenic miR-17 family of miRNAs, miR-22, and miR-34a by stilbenes leads to inhibition of prostatic hyperplasia and tumor progression in mice and reduction of proliferation, survival and invasion of prostate cancer cellsin vitro. Taken together, these findings implicate the use of resveratrol and its analogs as an attractive miRNA-mediated chemopreventive and therapeutic strategy in prostate cancer and the use of circulating miRNAs as potential predictive biomarkers for clinical development.
Recent advances of IDH1 mutant inhibitor in cancer therapy
Authors: Tian Wangqi , Zhang Weitong , Wang Yifan , Jin Ruyi , Wang Yuwei , Guo Hui , Tang Yuping , Yao Xiaojun
Published: August 2022

Isocitrate dehydrogenase (IDH) is the key metabolic enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate (α-KG). Two main types of IDH1 and IDH2 are present in humans. In recent years, mutations in IDH have been observed in several tumors, including glioma, acute myeloid leukemia, and chondrosarcoma. Among them, the frequency of IDH1 mutations is higher than IDH2. IDH1 mutations have been shown to increase the conversion of α-KG to 2-hydroxyglutarate (2-HG). IDH1 mutation-mediated accumulation of 2-HG leads to epigenetic dysregulation, altering gene expression, and impairing cell differentiation. A rapidly emerging therapeutic approach is through the development of small molecule inhibitors targeting mutant IDH1 (mIDH1), as evidenced by the recently approved of the first selective IDH1 mutant inhibitor AG-120 (ivosidenib) for the treatment of IDH1-mutated AML. This review will focus on mIDH1 as a therapeutic target and provide an update on IDH1 mutant inhibitors in development and clinical trials.
Peristaltic flow of a viscous fluid in a curved duct with a rectangular cross section
Authors: Riaz Arshad , Ahammad N. Ameer , Alqarni M. M. , Hejazi Hala A. , Tag-ElDin ElSayed M.
Published: August 2022

Most flow systems in the human body are duct shaped, such as the pancreatic, bile, and gallbladder ducts. Such flow systems are also common in industrial applications like HVAC systems. This study presents a novel mathematical model to analyze the peristaltic motion of a viscous fluid in a three-dimensional curved duct with a rectangular cross section; specifically, such geometries are used more in industrial and medical applications. In the current investigation, the constraints of lubrication theory are considered, and a perturbation technique is used to solve the Navier–Stokes partial differential equations. The major focus of this work is on the aspect ratio of the duct and curvature of the flow axis. Curvilinear coordinates of cylindrical systems are considered for the derivations because of the curved geometry; homogeneous no-slip boundary conditions are proposed at the flexible surfaces, and the expression for pressure increase is found numerically using the NIntegrate tool of computing software Mathematica. A comprehensive graphical discussion is presented to determine the effects of all salient physical factors related to the problem. The results show that the large curvature and aspect ratio reduce the fluid speed gradually but that the flow rate promotes fluid velocity. The pumping rate is a decreasing function of the curvature and aspect ratio; however, reverse pumping can occur for large curvature values. Streamline evaluations suggest that large wave amplitudes increase the number of circulating boluses.
Predicting autologous hamstring graft diameter and finding reliable measurement levels in the Zhuang population using preoperative ultrasonography
Authors: Huang Xiao-Li , Zheng Hong-Yu , Shi Ze-Feng , Yang Hui-Hui , Zhang Bing , Yang Xiao-Chun , Wang Hong , Tan Ru-Xin
Published: August 2022

Purpose: To evaluate the feasibility of using ultrasonography to preoperatively predict the autologous hamstring graft diameter for anterior cruciate ligament (ACL) reconstruction in the Zhuang population and determine a reliable measurement level using ultrasound.

Methods: Twenty-four Zhuang patients who were scheduled for ACL reconstruction using four-strand semitendinosus tendon (ST) and gracilis tendon (G) (4S-STG) autografts were included in this study. Ultrasonographic examinations of the ST and the G on the damaged side were conducted before the operation. We recorded the transverse diameter (TD), anterior–posterior diameter (APD), cross-sectional area (CSA), and perimeter (P) of the tendons. The measurements were obtained from two levels of the tendons: the widest point of the medial femoral epicondyle (level 1) and the myotendinous junction of the sartorius (level 2). We also calculated the combined (ST + G) TD, APD, CSA, and p values. Then, we obtained the intraoperative measurements. The correlation between the ultrasonic and intraoperative measurements was analyzed, and the advantages of the ultrasonic measurements at the two different levels were compared.

Results: When we measured at level 1, we found that part of the ultrasonic measurements were correlated with intraoperative measurements. The preoperative CSA of the G (P-GCSA) can be used to distinguish a 4S-STG autograft diameter of ≥8 mm (p < 0.01, mean difference = 3.7). The area under the P-GCSA curve was 0.801 (p < 0.05). A P-GCSA of 8.5 mm2 could be used to predict a 4S-STG autograft diameter of ≥8 mm with a sensitivity of 61.1% and specificity of 83.3%. However, there was no correlation between the ultrasonic and intraoperative measurements at level 2.

Conclusion: Preoperative ultrasound can be used to predict the sufficient diameter of 4S-STG autografts when considering patients from Zhuang who are undergoing ACL reconstruction. The ultrasonic measurement should be obtained at the widest point of the medial femoral epicondyle.
Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif
Authors: Wang Liang , Lu Yahui , Cai Guanhui , Chen Hongyu , Li Gen , Liu Luwei , Sun Lian , Guan Zhaolan , Sun Wen , Zhao Chunyang , Wang Hua
Published: August 2022

Human adipose-derived stem cells (hASCs) have multi-directional differentiation potential including osteogenic differentiation. Mechanical stimulation is thought to be a key regulator of bone remodeling and has been proved to promote osteogenic differentiation of mesenchymal stem cells. However, the mechanism how mechanical tension-induced osteogenesis of hASCs still remains poor understood. Polycystin-2 (PC2), a member of the transient receptor potential polycystic (TRPP) family, is involved in cilia-mediated mechanical transduction. To understand the role of PC2 in osteogenic differentiation under mechanical stimuli in hASCs, PKD2 gene was stably silenced by using lentivirus-mediated shRNA technology. The results showed that mechanical tension sufficiently enhanced osteogenic differentiation but hardly affected proliferation of hASCs. Silencing PKD2 gene caused hASCs to lose the ability of sensing mechanical stimuli and subsequently promoting osteogenesis. PC2 knock-out also reduced the cilia population frequency and cilia length in hASCs. TAZ (transcriptional coactivator with PDZ-binding motif, also known as Wwtr1) could mediate the genes regulation and biological functions of mechanotransduction signal pathway. Here, mechanical tension also enhanced TAZ nuclear translocation of hASCs. PC2 knock-out blocked tension-induced upregulation of nuclear TAZ and suppress tension-induced osteogenesis. TAZ could directly interact with Runx2, and inhibiting TAZ could suppress tension-induced upregulation of Runx2 expression. In summary, our findings demonstrated that PC2 mediate mechanical tension-induced osteogenic differentiation of hASCs by activating TAZ.
The shared mother-child epigenetic signature of neglect is related to maternal adverse events
Authors: León Inmaculada , Herrero Roldán Silvia , Rodrigo María José , López Rodríguez Maykel , Fisher Jonah , Mitchell Colter , Lage-Castellanos Agustín
Published: August 2022

Studies of DNA methylation have revealed the biological mechanisms by which life adversity confers risk for later physical and mental health problems. What remains unknown is the “biologically embedding” of maternal adverse experiences resulting in maladaptive parenting and whether these epigenetic effects are transmitted to the next generation. This study focuses on neglectful mothering indexed by a severe disregard for the basic and psychological needs of the child. Using the Illumina Human Methylation EPIC BeadChip in saliva samples, we identified genes with differentially methylated regions (DMRs) in those mothers with (n = 51), versus those without (n = 87), neglectful behavior that present similar DMRs patterns in their children being neglected versus non-neglected (n = 40 vs. 75). Mothers reported the emotional intensity of adverse life events. After covariate adjustment and multiple testing corrections, we identified 69 DMRs in the mother epigenome and 42 DMRs in the child epigenome that were simultaneously above the α = 0.01 threshold. The common set of nine DMRs contained genes related to childhood adversity, neonatal and infant diabetes, child neurobehavioral development and other health problems such as obesity, hypertension, cancer, posttraumatic stress, and the Alzheimer’s disease; four of the genes were associated with maternal life adversity. Identifying a shared epigenetic signature of neglect linked to maternal life adversity is an essential step in breaking the intergenerational transmission of one of the most common forms of childhood maltreatment.
LncRNA-mRNA modules involved in goat rumen development: Insights from genome-wide transcriptome profiling
Authors: Zhong Tao , Zhao Juan , Zhan Siyuan , Wang Linjie , Cao Jiaxue , Dai Dinghui , Guo Jiazhong , Li Li , Zhang Hongping , Niu Lili
Published: August 2022

The rumen is an essential digestive and absorption organ of ruminants. During fetal life, lactation, and post-weaning period, goat rumen undergoes drastic morphological and metabolic-functional changes triggered by potential regulated genes and non-coding RNA molecules. As the essential regulatory factors, long non-coding RNAs (lncRNAs) have vital functions in various biological activities. However, their roles during rumen development are still poorly explored in ruminants. To explore the genome-wide expression profiles of lncRNAs and mRNAs in the goat rumens, we generated 5,007 lncRNAs and 19,738 mRNAs identified during the fetal and prepubertal stages by the high-throughput RNA sequencing. Notably, 365 lncRNAs and 2,877 mRNAs were considered to be differentially expressed. The weighted gene co-expression network analysis and functional analysis were performed to explore the regulatory roles of those differentially expressed molecules. The cis-and trans-target genes of differently expressed lncRNAs were enriched for pathways related to focal adhesion, cGMP-PKG signaling pathway, alpha-linolenic acid metabolism, arachidonic acid metabolism, and fat digestion and absorption. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses showed that the differently expressed genes mainly participated in mitotic cytokinesis, desmosome, fatty acid degradation, cell adhesion molecules, and fatty acid metabolism. The prediction of lncRNA-mRNA interaction networks further revealed transcripts potentially involved in rumen development. The present study profiles a global overview of lncRNAs and mRNAs during rumen development. Our findings provide valuable resources for genetic regulation and molecular mechanisms of rumen development in ruminants.
The field phenotyping platform's next darling: Dicotyledons
Authors: Li Xiuni , Xu Xiangyao , Chen Menggen , Xu Mei , Wang Wenyan , Liu Chunyan , Yu Liang , Liu Weiguo , Yang Wenyu
Published: August 2022

The genetic information and functional properties of plants have been further identified with the completion of the whole-genome sequencing of numerous crop species and the rapid development of high-throughput phenotyping technologies, laying a suitable foundation for advanced precision agriculture and enhanced genetic gains. Collecting phenotypic data from dicotyledonous crops in the field has been identified as a key factor in the collection of large-scale phenotypic data of crops. On the one hand, dicotyledonous plants account for 4/5 of all angiosperm species and play a critical role in agriculture. However, their morphology is complex, and an abundance of dicot phenotypic information is available, which is critical for the analysis of high-throughput phenotypic data in the field. As a result, the focus of this paper is on the major advancements in ground-based, air-based, and space-based field phenotyping platforms over the last few decades and the research progress in the high-throughput phenotyping of dicotyledonous field crop plants in terms of morphological indicators, physiological and biochemical indicators, biotic/abiotic stress indicators, and yield indicators. Finally, the future development of dicots in the field is explored from the perspectives of identifying new unified phenotypic criteria, developing a high-performance infrastructure platform, creating a phenotypic big data knowledge map, and merging the data with those of multiomic techniques.