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.

Bladder paraganglioma is a rare neuroendocrine tumor, accounting for only 0.05% of all bladder tumors. This article reports the diagnosis and treatment of a 16-year-old male patient with acute hemorrhage secondary to a giant bladder paraganglioma(approximately 10 cm in maximum diameter). Preoperative imaging evaluation suggested locally advanced disease, and the patient subsequently received three cycles of neoadjuvant chemotherapy with temozolomide. He patient's blood tests revealed hemorrhagic shock. During the waiting period of surgery, hemostasis was successfully achieved through emergency transarterial embolization. Subsequently, the patient underwent emergency radical cystectomy combined with orthotopic ileal neobladder reconstruction under general anesthesia and recovered well after surgery. Postoperative pathological examination confirmed the diagnosis of bladder paraganglioma, with positive immunohistochemical staining for succinate dehydrogenase subunit B and a Ki-67 proliferation index of 3%. At the 6-week follow-up, the patient's blood pressure and endocrine parameters had returned to normal, with a satisfactory quality of life. This case demonstrates that a multidisciplinary team approach can effectively integrate expertise from various specialties to formulate comprehensive and systematic treatment plans, which is crucial for ensuring successful management of such complex cases.

Objective To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B(CHB)receiving peginterferon alfa-2b(PEG-IFN-α-2b)treatment,analyze the effects of various indicators on the HBsAg clearance rate under different characteristics,and construct and evaluate a combined predictive model.Methods We included 125 patients with HBeAg-negative CHB at Kunming Third People's Hospital from May 2021 to May 2023.After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks,they were divided into HBsAg clearance group and HBsAg non-clearance group.Their general information and serological,biochemical,and virological indicators at different time points during treatment were recorded.Continuous data in normal distribution were compared using the t test.Continuous data in non-normal distribution were compared using the Mann-Whitney U test,and comparisons across different time points were performed using the multiple paired-sample Friedman test.Categorical data were compared using the χ2 test.A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.Results Before treatment,there were significant differences in baseline HBsAg level(Z=-3.997,P<0.05)and treatment history(χ2=8.221,P<0.05)between the two groups.During treatment,gradually decreasing trends were observed in white blood cell count(χ2=104.944),neutrophil count(χ2=132.036),platelet count(χ2=162.881),and thyroid-stimulating hormone level(TSH,χ2=83.304,all P<0.05),while alanine aminotransferase(ALT,χ2=157.618)and alpha fetoprotein(χ2=159.472)showed gradually increasing trends(both P<0.05).At 48 weeks of treatment,treatment history(odds ratio[OR]=0.232,95%confidence interval[CI]:0.071-0.753),baseline HBsAg level(OR=13.423,95%CI:3.276-54.997),the extent of decrease in HBsAg from baseline after 12 weeks of treatment(OR=0.143,95%CI:0.040-0.515),the maximum ALT level during treatment(OR=0.986,95%CI:0.980-0.993),and the minimum TSH level during treatment(OR=3.281,95%CI:1.413-7.619)were independent factors affecting HBsAg clearance(all P<0.05).A combined predictive model for HBsAg clearance was built:Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment.The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following:the maximum ALT value during treatment(AUC=0.824),baseline HBsAg value(AUC=0.727),the minimum TSH value during treatment(AUC=0.707),the extent of HBsAg reduction from baseline after 12 weeks of treatment(AUC=0.641),and treatment history(AUC=0.636).The combined model showed better predictive performance than the individual indicators,with the AUC being 0.921(all P<0.05).Conclusion The combined model,constructed with baseline HBsAg value,the extent of HBsAg reduction from baseline after 12 weeks of treatment,the maximum ALT value during treatment,and the minimum TSH value during treatment,has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b,which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.

Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

Objective To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B(CHB)receiving peginterferon alfa-2b(PEG-IFN-α-2b)treatment,analyze the effects of various indicators on the HBsAg clearance rate under different characteristics,and construct and evaluate a combined predictive model.Methods We included 125 patients with HBeAg-negative CHB at Kunming Third People's Hospital from May 2021 to May 2023.After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks,they were divided into HBsAg clearance group and HBsAg non-clearance group.Their general information and serological,biochemical,and virological indicators at different time points during treatment were recorded.Continuous data in normal distribution were compared using the t test.Continuous data in non-normal distribution were compared using the Mann-Whitney U test,and comparisons across different time points were performed using the multiple paired-sample Friedman test.Categorical data were compared using the χ2 test.A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.Results Before treatment,there were significant differences in baseline HBsAg level(Z=-3.997,P<0.05)and treatment history(χ2=8.221,P<0.05)between the two groups.During treatment,gradually decreasing trends were observed in white blood cell count(χ2=104.944),neutrophil count(χ2=132.036),platelet count(χ2=162.881),and thyroid-stimulating hormone level(TSH,χ2=83.304,all P<0.05),while alanine aminotransferase(ALT,χ2=157.618)and alpha fetoprotein(χ2=159.472)showed gradually increasing trends(both P<0.05).At 48 weeks of treatment,treatment history(odds ratio[OR]=0.232,95%confidence interval[CI]:0.071-0.753),baseline HBsAg level(OR=13.423,95%CI:3.276-54.997),the extent of decrease in HBsAg from baseline after 12 weeks of treatment(OR=0.143,95%CI:0.040-0.515),the maximum ALT level during treatment(OR=0.986,95%CI:0.980-0.993),and the minimum TSH level during treatment(OR=3.281,95%CI:1.413-7.619)were independent factors affecting HBsAg clearance(all P<0.05).A combined predictive model for HBsAg clearance was built:Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment.The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following:the maximum ALT value during treatment(AUC=0.824),baseline HBsAg value(AUC=0.727),the minimum TSH value during treatment(AUC=0.707),the extent of HBsAg reduction from baseline after 12 weeks of treatment(AUC=0.641),and treatment history(AUC=0.636).The combined model showed better predictive performance than the individual indicators,with the AUC being 0.921(all P<0.05).Conclusion The combined model,constructed with baseline HBsAg value,the extent of HBsAg reduction from baseline after 12 weeks of treatment,the maximum ALT value during treatment,and the minimum TSH value during treatment,has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b,which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.

Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

Objective To study the role of microRNA(miR)-483-3p in reducing myocardial fibrosis in rats,and explore the relationship between its mechanism and autophagy.Methods A total of 24 male SD rats were randomly divided into sham operation group,model group,blank transfec-tion group and high expression group,with 6 rats in each group.The blank transfection group and the high-expression group were pretreated with a single injection of adeno-associated virus(AAV)-blank transfection and AAV-miR-483-3p(5×1011 vg)in the tail vein,respectively.In 14 d later,the sham group was injected with 2.5 ml/(kg·d)normal saline for 14 d,and rat model of myocardial fibrosis was established by 2 mg/ml isoproterenol[2.5 ml/(kg·d)]injection through tail vein for 14 consecutive days.Myocardial pathological damage,severity of myocardial fibrosis,and expression levels of collagen-Ⅰ,microtubule-associated protein light chain 3(LC3),autoph-agy-related protein 5(Atg5)and autophagy degradation substrate(P62)in cardiomyocytes were evaluated and measured.Results Compared with the sham operation group,the model group had obviously larger myocardial fibrosis area,higher positive expression of Collagen-Ⅰ,and increased protein levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ,and decreased expression level of P62 protein(P＜0.05).The myocardial fibrosis area,positive expression of Collagen-Ⅰ,the expression levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ protein[(13.64±1.51)％vs(27.47±1.55)％,(13.48±3.07)％vs(30.91±2.45)％,0.98±0.17 vs 1.24±0.28,0.66±0.05 vs 1.26±0.09,P＜0.05]were significant-ly decreased,and the expression level of P62 was notably increased(0.91±0.11 vs 0.74±0.06,P＜0.05)in the high expression group than the model group.Conclusion MiR-483-3p attenuates myocardial fibrosis in rats,and the mechanism may be related to the inhibition of cardiomyocyte autophagy.

Objective:To study the effect of permissive hypercapnia on pulmonary infection in patients underwent thoracoscopic combined with laparoscopic radical esophagectomy.Methods:From 2018 to 2020, 90 who patients underwent thoracoscopic laparoscopy combined with radical esophagectomy were divided into 3 groups by random who number table method, including 30 patients in experimental group 1, 30 patients in experimental group 2, and 30 patients in control group.PaCO 2 was maintained in the range of 56 mmHg-65 mmHg in experimental group 1, 46 mmHg-55 mmHg in experimental group 2 and 35 mmHg-45 mmHg in control group. The peak airway pressure (Ppeak) , lung dynamic compliance (Cdyn) and oxygenation index (OI) were observed and compared among the three groups after endotracheal intubation (T1) , 30 min after right artificial pneumothorax (T2) and 30 min after right lung recruitment (T3) ;The clinical pulmonary infection score (CPIS) , serum procalcitonin (PCT) on the 1st, 4th and 7th day after operation were analyzed and compared. Results:At T2, observation group A had the highest dynamic lung compliance (25.13 ± 5.70 vs 22.28 ± 4.26 vs 19.99 ± 4.36), the fastest heart rate (102.04 ± 10.91 vs 96.46 ± 9.91 vs 92.28 ± 8.08) and the lowest airway pressure (17.62 ± 1.79 vs 18.96 ± 1.90 vs 20.39 ± 1.71) ( P < 0.05). Observation group A had the lowest CPIS on the 1st, 4th and 7th day after operation compared with observation group B and control group (1.12±0.77 vs 1.71±0.90 vs 2.64±1.07) (6.08±1.20 vs 7.43±1.10 vs 8.31±1.55) (1.69±1.12 vs 2.32±0.98 vs 3.44±1.25) ( P<0.05) . Conclusion:Permissive hypercapnia can reduce airway resistance, improve lung compliance and reduce the risk of postoperative pulmonary infection.

Objective To evaluate the influence of peritoneal lavage with different concentrations of povidone-iodine on hemodynamics and acid-base balance in rabbits.Methods Twenty-four clean-grade healthy adult male New Zealand white rabbits,aged 3 months,weighing 2.8-3.2 kg,were divided into 4 groups (n=6 each) using a random number table:control group (group C),povidone-iodine 1/3 of original concentration group (group TI),povidone-iodine l/2 of original concentration group (group HI) and povidone-iodine of original concentration group (group OI).Rabbits were anaesthetized with intraperitoneal 3％ pentobarbital 1.5 ml/kg,the left femoral artery was cannulated for invasive blood pressure monitoring,and the abdominal cavity was opened.Peritoneal lavage was performed with normal saline,povidone-iodine diluted with normal saline (1 ∶ 2),povidone-iodine diluted with normal saline (1 ∶ 1) and original povidone-iodine 20 ml at 10 min after opening abdominal cavity in C,TI,HI and OI groups,respectively.The fluid for peritoneal lavage was sucked out using a sterile gauze 2 min later and then the abdominal cavity was closed.Mean arterial pressure (MAP) and heart rate (HR) were recorded immediately before lavage (T0) and at 5,10 and 20 min and 1 and 2 h after the end of lavage (T1-5).Arterial blood samples were collected at T0,T4 and T5 for blood gas analysis,and the pH value,BE and lactic acid level were recorded.The duration of anesthesia before peritoneal lavage,cumulative dose of anesthetics,fluid volume and urine volume at 2 h after anesthesia,and mortality at 3 h after peritoneal lavage were recorded.Results Compared with group C,MAP at T1-5 and HR at T3-5 were significantly decreased in TI,HI and OI groups,pH value was significantly decreased and BE negative value was increased at T4,5 in HI and OI groups,the lactic acid level was significantly increased at T5 in group OI,and the mortality rate were significantly increased in HI and OI groups (P＜0.05).Compared with group TI,MAP at T4,5 and pH value at T5 were significantly decreased,BE negative value was increased at T5,and the lactic acid level was increased at T4,5 in group Ol (P＜0.05).There was no significant difference in each parameter between group OI and group HI (P＞0.05).Conclusion Peritoneal lavage with povidone-iodine dose-dependently leads to hemodynamic deterioration and acid-base imbalance in rabbits.

The effects of different concentrations of vascular endothelial cell growth factor (VEGF) on the fibrovascular ingrowth into rabbits hydroxyapatite orbital implant were investigated. Twelve New Zealand white rabbits were divided into 3 groups and received hydroxyapatite orbital implant surgery in their right eyes. Before and after the operation, the implants were treated with 10 ng/ml VEGF, 100 ng/ml VEGF, or normal saline as control group. The animals received technetium bones scan at 2, 4, and 6 weeks postoperatively. The mean radioactivity counts within region of interest (ROI) of the surgery eye (R) and the non-surgery eye (L) in the same animal were tested, and the R/L ratios were calculated. The implants were harvested at 6th weeks and examined histopathologically. The results showed that at second week, there was no significant difference in mean R/L ratios between VEGF group and control group (F=2.83, P=0.111); At 4th week (F=7.728, P=0.011) and 6th week (F=7.831, P=0.011) postoperatively, the mean ratios in VEGF groups were significantly higher than that in control group. At 6th week postoperatively, the fibrovascularization rates in VEGF groups were higher than in control group significantly (F=8.711, P=0.008). It was suggested that VEGF could promote the fibrovascular ingrowth into hydroxyapatite orbital implant, thus might shorten the time required for complete vascularization of the HA orbital implant.
Animals ; Eye, Artificial ; Hydroxyapatites ; Neovascularization, Physiologic ; drug effects ; Orbit ; blood supply ; Orbital Implants ; Rabbits ; Random Allocation ; Vascular Endothelial Growth Factor A ; pharmacology