1.Efficacy and safety of coblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets in treatment of patients with chronic hepatitis C virus infection
Chunyan MOU ; Danqing XU ; Huan MU ; Jiangyan ZHANG ; Lixian CHANG ; Yuanqiang HE ; Yingyuan ZHANG ; Weikun LI ; Xiuling ZHANG ; Xiliang HE ; Qin PENG ; Li LIU
Journal of Clinical Hepatology 2025;41(9):1779-1787
ObjectiveTo investigate the therapeutic efficacy, influencing factors, and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus (HCV) infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1, 2021 to May 31, 2024 were enrolled, among whom there were 86 patients with compensated liver cirrhosis (CLC group) and 167 patients with chronic hepatitis C (CHC group). The patients were treated with coblopasvir hydrochloride capsules (60 mg)/sofosbuvir tablets (400 mg) with or without ribavirin tablets for 12 weeks, and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment (SVR12) and safety, and the secondary outcome measures were the changes in liver function, renal function, blood routine, and liver stiffness measurements (LSM) after 4 weeks of treatment, after 12 weeks of treatment, and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups, and the Friedman test was used for comparison between multiple groups, while the Bonferroni method was used for paired comparison within each group; the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years, and there were 151 male patients (59.7%). Of all patients, 33.99% (86/253) had liver cirrhosis, 25.69% (65/253) had hypertension, 10.67% (27/253) had HIV infection, 8.70% (22/253) had diabetes, 3.95% (10/253) had liver cancer, 1.98% (5/253) had chronic hepatitis B, and 7.91% (20/253) were treatment-experienced patients. As for genotype distribution, 2.77% (7/253) had genotype 1, 12.65% (32/253) had genotype 2, 66.01% (167/253) had genotype 3, 16.60% (42/253) had genotype 6, and 1.98% (5/253) had unknown genotype. The patients had an overall SVR12 rate of 92.09%, with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age (odds ratio [OR]=1.086, 95% confidence interval [CI]: 1.007 — 1.170, P=0.032) and HCC (OR=9.178, 95%CI: 1.722 — 48.912, P=0.009) were independent influencing factors for sustained virologic response. Compared with baseline data, the CLC group had significant reductions in alanine aminotransferase (ALT) (χ2=107.103, P0.05), aspartate aminotransferase (AST) (χ2=90.602, P0.05), and LSM (χ2=42.235, P0.05) after 12 weeks of treatment, while the CHC group had significant reductions in total bilirubin (χ2=15.113, P0.05), ALT (χ2=202.237, P0.05), AST (χ2=161.193, P0.05), and LSM (χ2=37.606, P0.05). The incidence rate of serious adverse events was 1.58%, and none of the patients withdrew from drug therapy; the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%, among which fatigue (17.39%) and nausea (2.37%) were the most common adverse events, and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.
2.Anticancer effect of bleomycin combined with cisplatin on human gastric cancer cells in vitro
Zi YANG ; Yonghui CUI ; Zhihan LI ; Zhiheng ZHENG ; Xiliang ZHANG ; Huijie GAO
Chinese Journal of Endocrine Surgery 2023;17(4):474-479
Objective:To explore the in vitro anticancer effect of bleomycin (Ble) combined with cisplatin (DDP) on human gastric cancer cells.Methods:CCK-8 experiment was conducted to detect the effect of Ble and DDP alone or in combination on the proliferation of gastric cancer cells; Flow cytometry was used to detect changes in cell apoptosis and changes in reactive oxygen species. Cell scratch test was employed to detect cell migration; Western blot experiment was conducted to detect protein expression.Results:The results of CCK-8 showed that 20 μM DDP could inhibit the proliferation of six types of gastric cancer cells by 40%, while the effect of 20 μM Ble was only about 20%. When used in combination, the inhibitory rate on six types of gastric cancer could reach over 60%, with the strongest inhibitory effect on AGS cells. When 10 μM Ble and 10 μM DDP were combined, the proportion of AGS apoptotic cells reached 75.68%, higher than that of the two drugs treated with 20%, respectively 20 μM processing effect. When 10 μM Ble and 10 μM DDP were used in combination, the number of migrating and invading cells was significantly reduced, and the inhibition rate reached 50%. Compared with single use, the difference was statistically significant ( P<0.05). Flow cytometry results showed that the combination of Ble and DDP promoted cancer cell apoptosis by up-regulating the level of reactive oxygen species in cells; Western blot results showed that the expression of p-JAK2 and p-STAT3 decreased after Ble and DDP were combined, indicating that the JAK2/STAT3 signal pathway was inhibited. Conclusions:The combination of Ble and DDP can inhibit the proliferation and migration of gastric cancer cells, promote the apoptosis of gastric cancer cells, and play a synergistic anti-cancer effect. Its mechanism may be related to the up-regulation of ROS levels in cells, thereby inhibiting the activation of the JAK2/STAT3 pathway.
3.Correlation between preoperative serum γ-gultamyl transferase level and postoperative survival in patients with renal cell carcinoma
Yijing ZHANG ; Sha MA ; Jin WEI ; Xiliang CAO ; Wei CHEN ; Yuekun QI
Cancer Research and Clinic 2021;33(9):668-672
Objective:To investigate the correlation between preoperative serum γ-glutamyl transferase (GGT) level and the postoperative survival of patients with renal cell carcinoma.Methods:The clinical data of 235 patients with renal cell carcinoma who underwent nephrectomy from December 2005 to December 2011 in the Affiliated Hospital of China University of Mining and Technology were retrospectively analyzed. According to the preoperative serum GGT level at 1.5 times the upper limit of normal value 90 U/L (the upper limit of normal value of samples in this study was 60 U/L), patients were divided into 2 groups: GGT ≤ 90 U/L group (218 cases) and GGT>90 U/L group (17 cases). The correlation between GGT and clinicopathological characteristics as well as postoperative survival of patient with renal cell carcinoma was also analyzed.Results:There were statistically significant differences in gender, age, the level of the aspartate aminotransferase (AST), the level of alanine aminotransferase (ALT), the neutrpphil-to-lymphocyte ratio (NLR), lymph node metastasis, distant metastasis, neoplasm staging between GGT ≤ 90 U/L group and >90 U/L group (all P < 0.05). Kaplan-Meier survival analysis showed that the median overall survival time was 84 months and 54 months, respectively in GGT ≤ 90 U/L group and GGT > 90 U/L group, and the difference was statistically significant of both groups ( χ2 = 4.334, P = 0.037). Univariate Cox proportional risk regression model showed that pathologic type, pathology T staging, preoperative GGT level, lactate dehydrogenase (LDH) level, ALT level were influencing factors of postoperative overall survival in patient with renal cell carcinoma (all P < 0.05). The multivariate Cox regression model analysis showed that the pathological type ( HR = 2.323, 95% CI 1.228-4.396, P = 0.010), GGT level ( HR = 2.406, 95% CI 1.077-5.376, P = 0.032), LDH level ( HR = 2.320, 95% CI 1.080-4.981, P = 0.031) were independent influencing factors of postoperative overall survival in patient with renal cell carcinoma. Conclusions:Preoperative elevated serum GGT level is associated with poor prognosis of patients with renal cell carcinoma, and the monitoring of it may help to evaluate the prognosis of patients and provide guidelines for individual treatment method.
4.Arthroscopic superior capsular reconstruction for massive irreparable rotator cuff tears using the long head of biceps tendon: the biomechanical and clinical study
Xiliang SHANG ; Jingyi LYV ; Shurong ZHANG ; Yang WU ; Liang HAO ; Shiyi CHEN
Chinese Journal of Orthopaedics 2021;41(9):559-567
Objective:To investigate the biomechanical characteristics and clinical outcomes of arthroscopic superior capsular reconstruction for massive irreparable rotator cuff tears (MIRCT) using the long head of biceps tendon (LHBT) with tenotomizing its distally or not (the "Chinese way" ).Methods:Eight fresh-frozen cadaveric shoulders were used to create a MIRCT model by detaching the footprints of the supraspinatus and infraspinatus tendons on the greater tuberosity. LHBT autograft was transferred and securely fixed onto the footprint of supraspinatus tendon for superior capsular reconstruction. Further, all cadaveric specimens were assigned to the tenotomy group or reservation group (4 cadaveric specimens in each group) according to whether the distal part of LHBT was tentomized or not. Biomechanical tests were conducted to observe the stiffness, ultimate load of fixed LHBT and to measure the length between LHBT tear site and its insertion on the superior labrum. A total of 41 patients with MIRCT who underwent arthroscopic superior capsular reconstruction using LHBT autograft between July 2016 and December 2018 were enrolled in the study. There were 17 males and 24 females, aged from 46 to 76 years (62.6±7.3 years). All patients were assigned to the tenotomy group (23 cases) or reservation group (18 cases) according to whether the distal part of LHBT was tentomized or not. The visual analogue scale (VAS), University of California, Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score and Fudan University Shoulder Score (FUSS) were used to evaluate the clinical outcomes. The range of motion (ROM) of shoulder was recorded before and after operation. Magnetic resonance imaging was used to assess the structural integrity of reconstructed tissue at 12 months after operation (refers to the failure of the transposed LHBT, which may be accompanied by a retear of partial repaired supraspinatus tendon).Results:Biomechanical research showed that the stiffness, ultimate load of fixed LHBT and the length between LHBT tear site and its insertion on the superior labrum in the reservation group (54.0±6.6 N/mm, 141.8±15.9 N, 93.3±12.4 mm, respectively) were significantly higher than those in the tenotomy group (25.7±4.2 N/mm, 80.8±8.0 N, 47.4±2.0 mm, respectively) ( P<0.05). All patients were followed up for 12-18 months (14.5±1.8 months) without significant complications and adverse reactions. No matter the distal part of LHBT was tentomized or not, the ROM and clinical scores (VAS score, UCLA score, Constant-Murley score, ASES score and FUSS) of patients improved significantly at 1 year follow-up than that before operation ( P<0.05). However, there were no significant differences between the reservation group and tenotomy group in terms of postoperative ROM [flexion, abduction, external rotation at side, internal rotation (vertebral level) were 144.3°±15.5° vs. 148.0°±10.3°, 145.1°±14.1° vs. 142.3°±11.2°, 67.3°±14.4° vs. 62.7°±11.7°, 8.3±2.1 vs. 7.8±2.5, respectively], VAS scores (2.3±1.6 vs.1.5±1.2), functional scores (Constant-Murley score, UCLA score, ASES score and FUSS were 88.2±11.4 vs. 85.6±9.6, 29.3±2.8 vs. 31.4±3.5, 86.8±11.8 vs. 82.6±9.2, 92.1±10.1 vs. 88.3±8.2, respectively) and structural failures (35.2% vs. 30.0%, P>0.05). Conclusion:Arthroscopic superior capsular reconstruction using LHBT with reserving its distal part could achieve higher mechanics strength. However, the short-term follow-up showed that tenotomizing the distal part of LHBT exerted no obvious influence on postoperative function and structural integrity.
5.Direct Comparative Analyses of 10X Genomics Chromium and Smart-seq2
Wang XILIANG ; He YAO ; Zhang QIMING ; Ren XIANWEN ; Zhang ZEMIN
Genomics, Proteomics & Bioinformatics 2021;19(2):253-266
Single-cell RNA sequencing (scRNA-seq) is generally used for profiling transcriptome of individual cells.The droplet-based 10X Genomics Chromium (10X) approach and the plate-based Smart-seq2 full-length method are two frequently used scRNA-seq platforms,yet there are only a few thorough and systematic comparisons of their advantages and limitations.Here,by directly comparing the scRNA-seq data generated by these two platforms from the same samples of CD45-cells,we systematically evaluated their features using a wide spectrum of analyses.Smart-seq2 detected more genes in a cell,especially low abundance transcripts as well as alterna-tively spliced transcripts,but captured higher proportion of mitochondrial genes.The composite of Smart-seq2 data also resembled bulk RNA-seq data more.For 10X-based data,we observed higher noise for mRNAs with low expression levels.Approximately 10%-30% of all detected tran-scripts by both platforms were from non-coding genes,with long non-coding RNAs (lncRNAs)accounting for a higher proportion in 10X.10X-based data displayed more severe dropout prob-lem,especially for genes with lower expression levels.However,10X-data can detect rare cell types given its ability to cover a large number of cells.In addition,each platform detected distinct groups of differentially expressed genes between cell clusters,indicating the different characteristics of these technologies.Our study promotes better understanding of these two platforms and offers the basis for an informed choice of these widely used technologies.
6.Study on the Effects of Danhong Injection on Gene Expression Profile of Acute Myocardial Infarction Model Rats by Gene Chip Technique
Yang SHI ; Guanwei FAN ; Baolin HOU ; Dengfeng FAN ; Wei ZHANG ; Xiliang LU ; Xiaoli CHEN ; Min HE
China Pharmacy 2019;30(22):3042-3048
OBJECTIVE: To investigate the effects of Danhong injection (DHI) on gene expression profile of acute myocardial infarction (AMI) model rats. METHODS: Male SD rats were randomly divided into sham operation group, model group and DHI group (0.76 mL/kg), with 10 rats in each group. AMI model was established by ligation of left anterior descending coronary artery in model group and DHI group. After modeling, sham operation group and model group were given constant volume of normal saline intramuscularly, and DHI group was given relevant medicine intramuscularly, once a day, for consecutive 14 days. After last administration, myocardial tissue in the marginal zone of infarction was separated. The change of gene expression profile was detected by gene chip technique. Using fold-change of relative expression as index, differentially expressed microRNA (miRNA) were screened. On the basis of retrieving their corresponding genes, gene ontology (GO) and KEGG pathway enrichment analysis were carried out by using DAVID bioinformatics resource database and KEGG pathway database, respectively. TargetScan database was used to predict the target gene messenger RNA (mRNA) corresponding to differentially expressed miRNA. Cytoscape 3.6.1 software was used to construct and analyze the miRNA-mRNA network. Agilent GeneSpring GX v11.5 software was used to screen target genes and miRNA related to inflammation in the above networks. RESULTS: Compared with sham operation group, there were 22 differentially expressed miRNAs in model group, 5 up-regulated and 17 down-regulated. Compared with model group, there were 26 differentially expressed miRNAs in DHI group, and all of them were up-regulated. The differentially expressed miRNAs related to DHI therapy for AMI included rno-let-7a-5p, rno-let-7d-5p, rno-let-7f-5p, rno-miR-26b-5p, rno-miR-29b-3p, cel-miR-39-3p, cel-miR-39-5p, rno-miR-142-5p, rno-miR-191a-5p, rno-miR-409a-3p. Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in membrane-bound organelles, cytoplasm, endometrial system and other cell components. The molecular functions such as protein binding and ion binding were exerted through biological processes such as anatomical structure development, multicellular tissue development and development process,which were mainly enriched in calcium signaling pathway, PPAR signaling pathway, VEGF signaling pathway, cell apoptosis, glycosylphosphatidylinositol anchored biosynthesis, valine, leucine and isoleucine degradation, etc. miRNA-mRNA network analysis showed that there were 25 target gene mRNAs corresponding to differentially expressed miRNA and 24 miRNAs related to it. There were 6 inflammation-related target genes (IL6, IL1b, TNF, TLR4, CRP, CXCL12) in this network, involving 19 differentially expressed miRNAs. CONCLUSIONS: The therapeutic effect of DHI on AMI may be related to regulating the expression of related miRNA, affecting signal transduction of calcium ion, PPAR and VEGF pathways, and regulating the secretion of inflammatory markers such as interleukin, chemokine and C-reactive protein.
7.Impact of blood glucose level on recurrence of liver cancer after laparoscopic surgery
Chuan JIANG ; Chuxiao SHAO ; Jinde ZHU ; Chaoyong TU ; Xiliang Lü ; Qiaomei LIN ; Kun ZHANG
China Journal of Endoscopy 2017;23(8):66-70
Objective To investigate the impact of blood glucose level on the recurrence of liver cancer after laparoscopic surgery. Methods The clinical data of 98 patients with primary hepatocellular carcinoma from January 2012 to January 2015 were retrospectively analyzed. All patients were treated by laparoscopic radical resection of hepatocellular carcinoma. Patients were divided into elevated blood glucose group (n = 23) and control group (n = 75) according to whether the fasting blood glucose was ≥6.1 mmol/L. The recurrence of liver cancer in 1 year and 2 years after operation was compared. The factors influencing the recurrence of liver cancer were analyzed by univariate and multivariate analysis. Results The recurrence rates were 47.82% and 21.33% respectively in the patients with elevated blood glucose and the control group. The recurrence rates were 73.91% and 36.00%respectively in the 2-year postoperative patients with blood glucose and 1 year and 2 years. The recurrence rate was higher than that of the control group, the difference was statistically significant (P < 0.05). Logistic multivariate analysis showed that fasting blood glucose was high, Child-Pugh grade B, intraoperative blood transfusion, lymphatic invasion, high clinical pathology stage, postoperative alpha-fetoprotein (AFP) high, no postoperative adjuvant therapy (P < 0.05). Conclusion The recurrence rate of patients with elevated liver cancer after laparoscopic surgery is high, and fasting blood glucose is high, Child-Pugh grade is B grade, blood transfusion is high, there is lymphatic invasion, high clinical pathology stage after AFP high, no postoperative adjuvant therapy for its postoperative recurrence of risk factors, should strengthen the monitoring of high-risk patients, reduce postoperative recurrence rate.
8.Comparison of the Clinical Efficacy of Minimally Invasive Locking Plate and Traditional Open Reduction with Internal Fixation in the Treatment of Proximal Humerus Fractures
Xiliang DANG ; Haopeng LI ; Jian ZHANG ; Yumin LI ; Dongsheng WU
Progress in Modern Biomedicine 2017;17(27):5369-5372
Objective:To discuss the clinical efficacy of minimally invasive locking plate and the traditional open reduction with internal fixation in the treatment of proximal humerus fractures.Methods:89 cases of patients with proximal humeral fractures were selected and divided into two groups according to different surgical methods.The observation group (45 cases) was given minimally invasive locking plate,while the control group (44 cases) was treated with the traditional open reduction and internal fixation.The operation time,hospitalization time,fracture healing time,intraoperative blood loss,Neer score and Constant-Murley score at 1 month after postoperatiion were compared between two groups.Results:The operation time,hospitalization,fracture healing time of observation group were significantly shorter than those of the control group,and the bleeding amount of observation group was less than that of the control group (P<0.05).At 1 months after operation,the Constant-Murley scores of observation group were significantly better than those of the control group (P<0.05).The For Neer scores,excellent rate of observation group (91.1%) were significantly higher than those of the control group (68.1%,P<0.05).Conclusion:Compared with the traditional open reduction with internal fixation,minimally invasive locking plate was better,safer,faster and more effectively for promoting the recovery of shoulder function of patient with proximal humerus fractures.
9.Difference in blood microcirculation recovery between normal frostbite and high-altitude frostbite
Mingke JIAO ; Lin LOU ; Jie HU ; Lin JIAO ; Wenjuan XU ; Peng ZHANG ; Xiliang GENG ; Jing FENG ; Zhongming WANG
Medical Journal of Chinese People's Liberation Army 2017;42(1):66-69
Objective To determine the difference in blood microcirculation recovery between normal frostbite and high-altitude frostbite during the wound healing.Methods Twenty four male rats were randomly divided into control group (n=8), normal frostbite group (n=8), and high-altitude group (n=8). The normal frostbite group rats were frozen to produce mid-degree frostbite models by controlling the freezing time with liquid nitrogen penetration equipment. The high-altitude frostbite group rats were acclimated to a hypoxic and low-pressure environment for 1 week, and then the high-altitude frostbite models were constructed by the same way with liquid nitrogen penetration apparatus. On days 3, 7, 11, 15, 19, and 23 after modeling, the recovery situation of blood circulation of each group was observed with contrast ultrasonography by injecting SonoVue micro-bubble into rats' tail. Finally, the micro-bubble concentration (MC) was calculated to confirm the blood circulation recovery with software Image Pro. ResultsAt different time points, the wound area of the high-altitude frostbite group was bigger than that of the normal frostbite group, and the MC of control group was always about (27±0.2)×109/ml. On day 3, 7, 11, 15, 19, and 23, the MC was significantly lower in the high-altitude frostbite group than in the control group and normal frostbite group (P<0.05). The MC of normal frostbite group was significantly lower than that of the control group on day 3, 7, 11, 15 and 19 (P<0.05). In addition, no obvious difference in MC was found between normal group and control group on the 23th day (P<0.05).Conclusion The blood microcirculation recovery after high-altitude frostbite is significantly slower than the normal frostbite.
10.Study on the pulsed electromagnetic fields promoting cure of plateau stress ulcer
Mingke JIAO ; Jing FENG ; Lin LOU ; Peng ZHANG ; Xiliang GENG ; Saidazimu YIMITI ; Yanhui SHI
Chinese Medical Equipment Journal 2017;38(5):36-38
Objective To determine the effects of non-thermal biological effect of low frequency pulsed electromagnetic field (LFPEF) with 15 Hz and 30 mT on ulcer wound during the plateau stress ulcer cure.Methods Thirty male Sprague-Dawley rats were assigned to three equal groups:control,normal cure group (NC) and exposure treatment groups (ET).The plateau rats stress ulcer models were constructed with the combination method of a hypoxic and low-pressure acclimation and the stimulation of absolute ethyl alcohol irrigating stomach.The LFPEF equipment generated the LFPEF of 15 Hz,40% duty cycle and 30 mT to expose and treat the rats' stomach of ET group with the frequency of 3 hours each day.After 6 days of exposure treatment,the stress ulcer cure situation of each group was evaluated by the methods of macroscopic observation,the gastric juice pH values detection and ulcer index (UI) measurement.Results After 6 days of model,the macroscopic observation showed that the ulcer of NC group was worse than the that of ET group (P<0.05).The pH values and UI of ET group were significantly different with those of NC group,and closed to those of the control group.Conclusion The nonthermal biological effect of LFPEF could promote the plateau stress ulcer cure.

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