Telbivudine-Induced Myopathy: Clinical Features, Histopathological Characteristics, and Risk Factors

Min-Yu Lan,Hui-Chen Lin,Tsung-Hui Hu,Shu-Fang Chen,Chien-Hung Chen,Yung-Yee Chang,King-Wah Chiu,Tsu-Kung Lin,Shun-Sheng Chen 대한신경과학회 2023 Journal of Clinical Neurology Vol.19 No.1

Background and Purpose Oral nucleos(t)ide analogs (NAs) are the mainstay treatment for chronic hepatitis B (CHB). Myotoxicity is an important extrahepatic effect related to NA treatment. Telbivudine is the NA for CHB that is frequently associated with muscle-related side effects. The risk factors for telbivudine-induced myopathy (TIM) are not yet clear. Methods This study characterized the clinical, magnetic resonance images (MRI), and pathological features of 12 TIM cases. A group of telbivudine-tolerant (TT) patients with CHB who received regular telbivudine treatment during the same period without the occurrence of myopathy was collected. Demographic and clinical factors were compared between the patients with TIM and the TT controls. Factors independently associated with TIM were identified using logistic regression analysis. Results The patients with TIM (males/females: 7/5, mean age: 57 years) developed myopathy after using telbivudine for a median period of 19.5 months. Muscle histopathology revealed abnormal proliferation, subsarcolemmal or sarcoplasmic accumulations, and ultrastructural defects of mitochondria. When compared with TT cases, patients with TIM had a lower estimated glomerular filtration rate and were more frequently positive for hepatitis B e antigen (HBeAg). Conclusions Mitochondrial abnormalities are characteristic histopathological features, and impaired renal function and HBeAg positivity are risk factors for TIM. Telbivudine-induced mitochondrial dysfunction and immune activation related to mitochondrial damage and HBeAg serostatus changes may underlie TIM. Constant clinical surveillance of myopathy during telbivudine treatment is needed due to the significant latency of its development. Dose adjustment for impaired renal function does not eliminate the risk of TIM occurrence.

Risk Factors for Anxiety in Major Depressive Disorder Patients

Li-Min Xin,Lin Chen,Zhen-Peng Ji,Suo-Yuan Zhang,Jun Wang,Yan-Hong Liu,Da-Fang Chen,Fu-De Yang,Gang Wang,Yi-Ru Fang,Zheng Lu,Hai-Chen Yang,Jian Hu,Zhi-Yu Chen,Yi Huang,Jing Sun,Xiao-Ping Wang,Hui-Chun 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.3

Objective: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). Methods: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. Results: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=−4.39, p<0.001), were older (t=−4.69, p<0.001), reported more lifetime depressive episodes (z=−3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ2=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. Conclusion: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.

miRNA-103a-3p Promotes Human Gastric Cancer Cell Proliferation by Targeting and Suppressing ATF7 in vitro

Hu, Xiaoyi,Miao, Jiyu,Zhang, Min,Wang, Xiaofei,Wang, Zhenzhen,Han, Jia,Tong, Dongdong,Huang, Chen Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.5

Studies have revealed that miR-103a-3p contributes to tumor growth in several human cancers, and high miR-103a-3p expression is associated with poor prognosis in advanced gastric cancer (GC) patients. Moreover, bioinformatics analysis has shown that miR-103a-3p is upregulated in The Cancer Genome Atlas (TCGA) stomach cancer cohort. These results suggest that miR-103a-3p may function as an oncogene in GC. The present study aimed to investigate the role of miR-103a-3p in human GC. miR-103a-3p expression levels were increased in 33 clinical GC specimens compared with adjacent nontumor stomach tissues. Gain- and loss-of-function studies were performed to identify the correlation between miR-103a-3p and tumorigenesis in human GC. Inhibiting miR-103a-3p suppressed GC cell proliferation and blocked the S-G2/M transition in MKN-45/SGC-7901 cells, whereas miR-103a-3p overexpression improved GC cell proliferation and promoted the S-G2/M transition in vitro. Bioinformatics and dual-luciferase reporter assays confirmed that ATF7 is a direct target of miR-103a-3p. Analysis of the TCGA stomach cancer cohort further revealed that miR-103a-3p expression was inversely correlated with ATF7 expression. Notably, silencing ATF7 showed similar cellular and molecular effects as miR-103a-3p overexpression, namely, increased GC cell proliferation, improved CDK2 expression and decreased P27 expression. ATF7 overexpression eliminated the effects of miR-103a-3p expression. These findings indicate that miR-103a-3p promotes the proliferation of GC cell by targeting and suppressing ATF7 in vitro.

Characterization of Ribose-5-Phosphate Isomerase B from Newly Isolated Strain Ochrobactrum sp. CSL1 Producing L-Rhamnulose from L-Rhamnose

( Min Shen ),( Xin Ju ),( Xinqi Xu ),( Xuemei Yao ),( Liangzhi Li ),( Jiajia Chen ),( Cuiying Hu ),( Jiaolong Fu ),( Lishi Yan ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.7

In this study, we attempted to find new and efficient microbial enzymes for producing rare sugars. A ribose-5-phosphate isomerase B (OsRpiB) was cloned, overexpressed, and preliminarily purified successfully from a newly screened Ochrobactrum sp. CSL1, which could catalyze the isomerization reaction of rare sugars. A study of its substrate specificity showed that the cloned isomerase (OsRpiB) could effectively catalyze the conversion of L-rhamnose to L-rhamnulose, which was unconventional for RpiB. The optimal reaction conditions (50oC, pH 8.0, and 1 mM Ca²⁺) were obtained to maximize the potential of OsRpiB in preparing L-rhamnulose. The catalytic properties of OsRpiB, including K_m, K_cat, and catalytic efficiency (K_cat/K_m), were determined as 43.47 mM, 129.4 sec^-1, and 2.98 mM/sec. The highest conversion rate of L-rhamnose under the optimized conditions by OsRpiB could reach 26% after 4.5 h. To the best of our knowledge, this is the first successful attempt of the novel biotransformation of L-rhamnose to L-rhamnulose by OsRpiB biocatalysis.

An Improved B-Spline Fitting Method with Arc-Length Parameterization, G2-Continuous Blending, and Quality Refinement

Kang Min,Yanyan Sun,Chen-Han Lee,Pengcheng Hu,Shanshan He 한국정밀공학회 2019 International Journal of Precision Engineering and Vol.20 No.11

In computer numerical control machining, tool paths are typically represented with piecewise linear segments (GO1s), which lack G1 and G2 continuity and cause fluctuation of feed rate and acceleration. To improve the continuity of tool paths, some method, e.g., B-spline tool path fitting, is preferred. However, none of the currently B-spline fitting method satisfies all tool-path fitting requirements of arc-length parameterization, G2 continuity and smoothness across the whole path. The aim of this research is to derive an industrial-strength method for B-spline tool path fitting, satisfying all of the named requirements. The improvements cover the arc-length based parameterization, G2 continuity as well as numerically measure to improve the quality of B-spline tool paths. To achieve arc-length parameterization, a preliminary fitting is added to evaluate arc-length and guide the parameterization (i.e., knot vector assignment); for joint G2-continuity, a five-control-point B-spline which satisfies chord error and shape-preserving constraints is constructed to blend adjacent B-splines; and a method based on the Hausdorff distance between the fitted B-splines and the original polylines is used to evaluate the fitting quality, and an additional refinement procedure is employed when the evaluation finds any disqualification. Simulation and experiment results prove that the proposed methods are effective.

Characterization and Functional Analysis of Bacillus aryabhattai CY for Acrylic Acid Biodegradation: Immobilization and Metabolic Pathway

Yi Chen,Min Zhao,Liyong Hu,Zeyu Wang,Dzmitry Hrynsphan,Jun Chen 한국생물공학회 2021 Biotechnology and Bioprocess Engineering Vol.26 No.6

Acrylic acid has been widely used in various industrial applications but is harmful to human health and the environment. A novel and efficient degrading acrylic acid bacterium was isolated and identified as Bacillus aryabhattai CY. In this study, batch experiments were conducted to evaluate the biodegradation of acrylic acid by B. aryabhattai CY, which were immobilized in calciumalginate beads under different conditions. The components of the alginate beads were optimized by the response surface method, and the degradation performance of the immobilized cells was determined. Relative to the free cells, experiment results showed that the immobilized cells can achieve complete degradation of 100 mg/L acrylic acid in 24 h under the optimal conditions of SA 6% (w/v), CaCl2 1% (w/v), and immobilization time of 6 h. According to Haldane's model, the maximum specific growth rate (μmax) of the free cells and immobilized cells were 0.165/h and 0.210/h, respectively. Experiment data revealed that acrylic acid showed an inhibitory effect on biodegradation by B. aryabhattai CY, especially at concentration higher than 100 mg/L. Furthermore, the reusability of the immobilized cells revealed that the acrylic acid removal rate was above 93.70% within the eight cycles. The immobilized cells also showed higher removal efficiencies in wider ranges of temperature (20°C-60°C) and pH (5.0-10.0) than the free cells. Moreover, the possible degradation intermediates were proposed during the biodegradation of acrylic acid by GC-MS analysis. Results indicated that immobilized beads might have a potential environmental implication in the purification of practical acrylic acid wastewater.

Adsorptive Granulocyte and Monocyte Apheresis in the Treatment of Ulcerative Colitis: The First Multicenter Study in China

( Ya-min Lai ),( Wei-yan Yao ),( Yao He ),( Xuan Jiang ),( Yu-bei Gu ),( Min-hu Chen ),( Yu-lan Liu ),( Yao-zong Yuan ),( Jia-ming Qian ) 대한소화기학회 2017 Gut and Liver Vol.11 No.2

Background/Aims: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective deple-tion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy out-comes based on patients` baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. Methods: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endo-scopic activity index and the Mayo score. Results: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. Conclusions: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Addition-ally, GMA was well tolerated and had a good safety profile. (Gut Liver 2017;11:216-225)

All-trans-retinoic Acid Promotes Iodine Uptake Via Up-regulating the Sodium Iodide Symporter in Medullary Thyroid Cancer Stem Cells

Tang, Min,Hou, Yan-Li,Kang, Qiang-Qiang,Chen, Xing-Yue,Duan, Li-Qun,Shu, Jin,Li, Shao-Lin,Hu, Xiao-Li,Peng, Zhi-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Recently, the main therapy of medullary thyroid cancer (MTC) is surgical, but by which way there is a poor prognosis with a mean survival of only 5 years. In some cases, some researchers found that it is the medullary thyroid cancer stem cells (MTCSCs) that cause metastasis and recurrence. This study aimed to eradicate MTCSCs through administration of all-trans-retinoic acid (ATRA). Here we demonstrate that MTCSCs possess stemlike properties in serum-free medium. The ABCG2, OCT4 and sodium iodide symporter (NIS) were changed by ATRA. Additionally, we found that ATRA can increase the expression of NIS in vivo. All the data suggested that ATRA could increase the iodine uptake of MTCSCs through NIS.

miRNA-103a-3p Promotes Human Gastric Cancer Cell Proliferation by Targeting and Suppressing ATF7 in vitro

Xiaoyi Hu,Jiyu Miao,Min Zhang,Xiaofei Wang,Zhenzhen Wang,Jia Han,Dongdong Tong,Chen Huang 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.5

Studies have revealed that miR-103a-3p contributes to tumor growth in several human cancers, and high miR-103a-3p expression is associated with poor prognosis in advanced gastric cancer (GC) patients. Moreover, bioinformatics analysis has shown that miR-103a-3p is upregulated in The Cancer Genome Atlas (TCGA) stomach cancer cohort. These results suggest that miR-103a-3p may function as an oncogene in GC. The present study aimed to investigate the role of miR-103a-3p in human GC. miR-103a-3p expression levels were increased in 33 clinical GC specimens compared with adjacent nontumor stomach tissues. Gain- and loss-of-function studies were performed to identify the correlation between miR-103a-3p and tumorigenesis in human GC. Inhibiting miR-103a-3p suppressed GC cell proliferation and blocked the S-G2/M transition in MKN-45/SGC-7901 cells, whereas miR-103a-3p overexpression improved GC cell proliferation and promoted the S-G2/M transition in vitro. Bioin-formatics and dual-luciferase reporter assays confirmed that ATF7 is a direct target of miR-103a-3p. Analysis of the TCGA stomach cancer cohort further revealed that miR-103a-3p expression was inversely correlated with ATF7 expression. Notably, silencing ATF7 showed similar cellular and molecular effects as miR-103a-3p overexpression, namely, increased GC cell proliferation, improved CDK2 expression and decreased P27 expression. ATF7 overexpression eliminated the effects of miR-103a-3p expression. These findings indicate that miR-103a-3p promotes the proliferation of GC cell by targeting and suppressing ATF7 in vitro.

Exploration and Validation of the Performance of Hemoglobin A1c in Detecting Diabetes in Community-Dwellers With Hypertension

Shan-hu Qiu,Ziwei Du,Weiling Li,Juan Chen,Hang Wu,Jingbao Liu,Min Cai,Bei Wang,Haijian Guo,Zi-lin Sun 대한진단검사의학회 2020 Annals of Laboratory Medicine Vol.40 No.6

Background: Diabetes can complicate hypertension management by increasing the risk of cardiovascular disease (CVD) and all-cause mortality. Studies targeting diabetes detection in hypertensive individuals demonstrating an increased risk of diabetes are lacking. We aimed to assess the performance of hemoglobin A1c (HbA1c) and its cut-off point in detecting diabetes in the abovementioned population. Methods: Data from 4,096 community-dwellers with hypertension but without known diabetes were obtained from the Study on Evaluation of iNnovated Screening tools and determInation of optimal diagnostic cut-off points for type 2 diaBetes in Chinese muLti-Ethnic (SENSIBLE) study; these data were randomly split into exploration (70% of the sample) and internal validation (the remaining 30%) datasets. The optimal HbA1c cut-off point was derived from the exploration dataset and externally validated using another dataset from 2,431 hypertensive individuals. The oral glucose tolerance test was considered the gold-standard for confirming diabetes. Results: The areas under the ROC curves for HbA1c to detect diabetes were 0.842, 0.832, and 0.829 for the exploration, internal validation, and external validation datasets, respectively. An optimal HbA1c cut-off point of 5.8% (40 mmol/mol) yielded a sensitivity of 76.2% and a specificity of 74.5%. Individuals who were not diagnosed as having diabetes by HbA1c at 5.8% (40 mmol/mol) had a lower 10-year CVD risk score than those diagnosed as having diabetes (P=0.01). HbA1c≤5.1% (32 mmol/mol) and ≥6.4% (46 mmol/mol) could indicate the absence and presence of diabetes, respectively. Conclusions: HbA1c could detect diabetes effectively in community-dwellers with hypertension.