Objective:To explore the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (SOF/VEL/VOX±RBV) for salvage treatment of chronic hepatitis C patients who have failed direct-acting antivirals (DAAs).Methods:Patients with chronic hepatitis C who failed DAAs±RBV treatment and were treated in five hospitals in Chongqing, Guangdong, Guizhou, and Guangxi from January 2022 to December 2023 were included in this retrospective study. One or more courses of DAAs±RBV therapy were evaluated for all patients who had been previously treated. Virological rebound occurrence was observed during the follow-up. SOF/VEL/VOX±RBV was used for one course of salvage treatment. Virological and biochemical indicators were analyzed before salvage therapy, post-treatment, and drug discontinuation at 12 weeks. Adverse drug events were recorded during treatment. Data between groups were compared using t-tests or non-parametric tests.Results:A total of 26 cases of chronic hepatitis C who had failed DAAs±RBV were included in this study, with an age of (52.9±9.6) years. Twenty-one cases (80.8%) were male, sixteen (61.5%) had a history of drug abuse, two (7.7%) had combined human immunodeficiency virus infection, and fourteen (53.8%) had combined cirrhosis. The previous DAA regimen of 21 cases (80.8%) included SOF/VEL. The baseline HCV RNA load of salvage treatment was (5.8±1.6) log 10 IU/ml, and 16 cases (61.5%) were genotype 3. All patients completed the 12-week SOF/VEL/VOX±RBV salvage treatment and achieved sustained virological response (SVR) at the end of treatment. All 22 cases were followed up for 12 weeks following treatment completion and attained SVR12, including patients with genotype 3 and cirrhosis. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had normalized return rates of 94.1% and 93.8%, respectively, following therapy. ALT, AST, FIB-4 index, APRI, and aPMAP scores were significantly lower than those before treatment ( Z=-3.980, -3.875, -3.461, -3.582, P<0.05). The proportion of patients in the high-risk group of liver cancer dropped (52.6% before treatment and 33.3% after treatment), and more patients were reclassified to medium-and low-risk groups. Two cases (7.7%) experienced nausea and diarrhea, one case (3.8%) had a headache, and one case (3.8%) had fatigue, all of which were well managed during treatment. There were no serious adverse events, deaths, or interruptions of treatment due to adverse reactions. Conclusions:SOF/VEL/VOX is a safe and effective salvage treatment option for chronic hepatitis C patients who have failed DAAs therapy, and may be particularly beneficial to refractory populations infected with genotype 3 and combined with cirrhosis.

Objective:To explore the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (SOF/VEL/VOX±RBV) for salvage treatment of chronic hepatitis C patients who have failed direct-acting antivirals (DAAs).Methods:Patients with chronic hepatitis C who failed DAAs±RBV treatment and were treated in five hospitals in Chongqing, Guangdong, Guizhou, and Guangxi from January 2022 to December 2023 were included in this retrospective study. One or more courses of DAAs±RBV therapy were evaluated for all patients who had been previously treated. Virological rebound occurrence was observed during the follow-up. SOF/VEL/VOX±RBV was used for one course of salvage treatment. Virological and biochemical indicators were analyzed before salvage therapy, post-treatment, and drug discontinuation at 12 weeks. Adverse drug events were recorded during treatment. Data between groups were compared using t-tests or non-parametric tests.Results:A total of 26 cases of chronic hepatitis C who had failed DAAs±RBV were included in this study, with an age of (52.9±9.6) years. Twenty-one cases (80.8%) were male, sixteen (61.5%) had a history of drug abuse, two (7.7%) had combined human immunodeficiency virus infection, and fourteen (53.8%) had combined cirrhosis. The previous DAA regimen of 21 cases (80.8%) included SOF/VEL. The baseline HCV RNA load of salvage treatment was (5.8±1.6) log 10 IU/ml, and 16 cases (61.5%) were genotype 3. All patients completed the 12-week SOF/VEL/VOX±RBV salvage treatment and achieved sustained virological response (SVR) at the end of treatment. All 22 cases were followed up for 12 weeks following treatment completion and attained SVR12, including patients with genotype 3 and cirrhosis. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had normalized return rates of 94.1% and 93.8%, respectively, following therapy. ALT, AST, FIB-4 index, APRI, and aPMAP scores were significantly lower than those before treatment ( Z=-3.980, -3.875, -3.461, -3.582, P<0.05). The proportion of patients in the high-risk group of liver cancer dropped (52.6% before treatment and 33.3% after treatment), and more patients were reclassified to medium-and low-risk groups. Two cases (7.7%) experienced nausea and diarrhea, one case (3.8%) had a headache, and one case (3.8%) had fatigue, all of which were well managed during treatment. There were no serious adverse events, deaths, or interruptions of treatment due to adverse reactions. Conclusions:SOF/VEL/VOX is a safe and effective salvage treatment option for chronic hepatitis C patients who have failed DAAs therapy, and may be particularly beneficial to refractory populations infected with genotype 3 and combined with cirrhosis.

Here we report the diagnosis and treatment of a rare IgG4-related kidney disease with nephrotic syndrome as the first manifestation. A 62-year-old male patient, presented with edema in both lower limbs and foam urine, had a history of "lung malignant tumor with brain and lymph node metastasis". The increase of IgG4 and decrease of glomerular filtration rate were detected at admission, and the pathological consideration of renal biopsy was membranous nephropathy with IgG4-related tubulointerstitial nephritis. After the combination of low-dose glucocorticoids therapy and rituximab treatment, the patient showed good prognosis in a 9 month follow-up.

Objective:To explore the speech features of female patients with anhedonic depression and their recognition of pleasure deficient symptoms.Methods:A total of 102 female depression patients who were hospitalized at Nanjing Brain Hospital from September 2020 to October 2021 were selected, including 62 anhedonic depression patients (anhedonic group) and 40 non-anhedonic depression patients (non-anhedonic group). A total of 50 female healthy controls were recruited during the same period.All participants were evaluated by the 17-item Hamilton depression scale (HAMD-17), Snaith-Hamilton pleasure scale (SHAPS), and the temporal experience of pleasure scale (TEPS), as well as voice acquisition.SPSS 23.0 software was used for data processing.Statistical analysis was conducted using one-way ANOVA, non-parametric tests, Logistic regression, and receiver operating characteristic curve.Results:Compared with the non-anhedonic group, the anhedonic group showed significant changes in 15 voice features(all P<0.05), including Mel-frequency cepstral coefficients, formant frequencies, intensity, and energy features.Among these features, Mel-frequency cepstral coefficients exhibited the highest accuracy in identifying anhedonic depression, with sensitivity of 47.5%, specificity of 91.9%, area under curve (AUC) of 0.751, 95% CI=0.686-0.866.Formant frequencies could identify female anhedonic depression, with a sensitivity of 90.0%, a specificity of 40.3%, an AUC of 0.647, and 95% CI=0.605-0.824.Energy features could identify anhedonic deficient depression, with a sensitivity of 60.0%, a specificity of 74.2%, an AUC of 0.679, and 95% CI=0.587-0.804.Intensity features could identify female anhedonic depression, with a sensitivity of 70.0%, a specificity of 58.1%, an AUC of 0.640, and 95% CI=0.554-0.769. Conclusion:Mel-frequency cepstral coefficients, formant frequencies, intensity features, and energy features may have specific changes in female patients with anhedonic depression.The Mel-frequency cepstral coefficients has the highest recognition accuracy for anhedonic symptoms in female depression patients, and is expected to become an objective evaluation index for female anhedonic depression.

Rutin,a flavonoid found in fruits and vegetables,is a potential anticancer compound with strong anti-cancer activity.Therefore,electrochemical sensor was developed for the detection of rutin.In this study,CoWO4 nanosheets were synthesized via a hydrothermal method,and porous carbon(PC)was prepared via high-temperature pyrolysis.Successful preparation of the materials was confirmed,and character-ization was performed by transmission electron microscopy,scanning electron microscopy,and X-ray photoelectron spectroscopy.A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin.The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability.PC has a high surface-to-volume ratio and superior conductivity.Moreover,the hydrophobicity of PC allows large amounts of rutin to be adsorbed,thereby increasing the concentration of rutin at the electrode surface.Owing to the syn-ergistic effect of the 3D CoWO4 nanosheets and PC,the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity.The sensor showed a good linear range(5-5000 ng/mL)with a detection limit of O.45 ng/mL.The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Objective:To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury (AKI).Methods:The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected, and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively. The Kaplan-Meier method was used to calculate the cumulative incidence of patients' remission.Results:There were 13 patients enrolled, including 8 females, and aged (35.23±15.92) years old. The urinary protein/creatinine ratio was (5.22±1.57) g/g before rituximab treatment. Four patients were on dialysis at admission, and 9 patients without dialysis had serum creatinine of (223.22±85.73) μmol/L. Eight patients were confirmed as proliferative lupus nephritis by renal biopsies, including 7 cases with crescent formation and 1 case with thrombotic microangiopathy (TMA), and the other 5 cases without renal biopsies were clinically diagnosed as TMA. The dose of rituximab was (815±516) mg (200-2 100 mg), and all the patients reached the state of peripheral blood B cells clearance (CD19 + B cell count was<5/μl). After the first treatment of rituximab, the median time to B-cell clearance was 21(15, 35) days, and 8 patients reached B-cell depletion (CD19 + B cell count was 0). The remission rate was 12/13 (two cases reached complete remission, and 10 cases reached partial remission). Three cases stopped dialysis, and 1 case (with glomerulosclerosis of 52.94%) entered maintaining dialysis. The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from (1.57±0.53) times in a median history of 60(20, 109) months to (0.43±0.79) times in a median history of 18(10, 23) months after the use of rituximab ( P=0.015). After using rituximab, the incidence of infection was 7/13. The median time from the use of rituximab to infection was 26(4, 44) days. Pulmonary infection (5/13) was the most common type and all infected patients recovered after anti-infection treatment. Conclusions:Rituximab can be used in the treatment of active lupus nephritis with AKI, especially in patients with crescent formation and TMA, but the infection should be paid close attention to and prevented.

Objective:To compare the effects of laparoscopic and surgical catheterization on catheter-related complications and microinflammation in uremic peritoneal dialysis (PD) patients.Methods:According to different catheterization methods, 98 uremic patients who were scheduled to undergo peritoneal dialysis in the First People's Hospital of Jiande from January 2014 to March 2019 were divided into group A (38 cases), group B (60 cases). Laparoscopic catheterization was used in group A, and incision catheterization was used in group B. Surgical parameters, catheter complications, microinflammation and survival rate of early catheterization were observed in the two groups.Results:The operation time of group A was (35.00±3.14)min, which was shorter than that of group B [(50.00±5.17)min], and the operation cost of group A was (5 800.0±318.9)CNY, which was higher than that of group B [(3 400.0±297.4)CNY], and the visual analogue score (VAS) of group A was (2.33±0.31)points, which was lower than that of group B [(3.25±0.49)points], there were statistically significant differences between the two groups ( t=11.540, 9.317, 10.328, 36.578, all P<0.05). The incidence of catheter-related complications in group A was 10.53%(4/38), which was significantly lower than 28.33%(17/60) in group B (χ 2=4.383, P<0.05). There were no statistically significant differences in high-sensitivity C-reactive protein (hs-CRP), interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels between group A and group B before catheterization (all P>0.05). After catheterization, the levels of hs-CRP, IL-6 and TNF-alpha in group B were (12.52±3.75)mg/L, (12.02±3.76)ng/L, (15.92±5.72)ng/L, respectively, which were higher than those in group A [(9.63±2.36)mg/L, (9.11±3.54)ng/L, (13.41±5.61)ng/L] ( t=4.244, 4.081, 4.510, all P<0.05). After 2 months of follow-up, the survival rate of dialysis tube technique was 89.47%(34/38) in group A and 71.67%(43/60) in group B, there was statistically significant difference between the two groups (χ 2=4.382, P<0.05). Conclusion:Application of laparoscopic catheterization in uremic PD patients has satisfactory effect, light pain, fewer complications, mild inflammation and high survival rate of early catheterization technology, which is worthy of clinical promotion.

Objective To study the clinical value of enhanced recovery after surgery (ERAS) in the perioperative treatment of type Ⅰ (Todami,1975) biliary dilatation (BD) of children.Methods To retrospectively analyze the data of children with type Ⅰ BD who were treated in the General Surgery Department of Zhengzhou Children's Hospital from June 2014 to May 2018.A total of twenty children with type Ⅰ BD treated with ERAS and 20 children treated with the traditional method in our department were selected in this study using the random number table method.Postoperative indicators (including operation time,first defecation time,changes in amylase in blood and abdominal cavity exudates,length of hospital stay,and hospitalization fee) and relevant postoperative complications (including sore throat,nausea and vomiting,urethral pain,upper respiratory tract infection,incision wound infection,adhesive intestinal obstruction,anastomotic leakage and pancreatic fistula) of the ERAS group and the control group were compared.Results The first defecation time,length of hospital stay and hospitalization fee were significantly lower in the ERAS group than the control group (all P ＜ 0.05) [first defecation time (1.98 ± 0.25) d vs.(2.25 ± 0.31) d;length of hospital stay (6.91 ± 1.25) d vs.(9.95 ± 1.53) d;hospitalization fee (23.32 ± 2.25)thousand yuan vs.(25.99 ±3.10) thousand yuan].Moreover,the incidences of sore throat,nausea and vomiting,urethral pain and upper respiratory tract infection were significantly lower in the ERAS group than the control group (all P ＜ 0.05) [the incidences of sore throat (5.0％ vs.45.0％);the incidences of sickness and vomiting (5.0％ vs.30.0％);the incidences of urethral pain (5.0％ vs.45.0％);the incidences of upper respiratory tract infection (5.0％ vs.40.0％)].On the other hand,there were no significant differences in the mean operation times,changes in amylase levels in the blood or abdominal cavity exudates,incision wound infection,and incidences of adhesive intestinal obstruction,anastomotic leakage and pancreatic fistula (all P ＞ 0.05).Conclusions ERAS for type Ⅰ BD surgery was safe and reliable in children.It effectively promoted recovery of postoperative gastrointestinal function and reduced the incidence of complications.

Objective To evaluate the safety and clinical efficacy of the treatment for symptomatic uterine fibroids with MR guided focused ultrasound surgery(MRgFUS)in China. Methods Twenty five selected patients with symptomatic uterine fibroids underwent MRgFUS treatment in our perspective clinical study. Immediately after treatment the patients accepted pelvic enhanced MRI scans, and recorded the non-perfused volume(NPV)and calculated the non-perfused volume ratio(NPV%). We recorded the symptom severity score(SSS) and standard SSS change(ΔSSS)of the patients before, during and 1 week after treatment together with 1, 3, 6, 12 months and several years follow-up. The patients accepted pelvic enhanced MRI scans in the follow-up of 12 months after treatment,and recorded the volume and the volume change(ΔV) of fibroids. We observed the adverse reactions during the treatment and the follow-ups. Wilcoxon test or t test and Pearson or Spearman correlation analysis were used to analyze the data. Results Totally 31 fibroids of 25 patients were completed the treatment. Twenty two patients completed the 12 months follow-up and 15 patients completed the long-term follow-up which was during 34 to 66 months, median follow-up duration was(55 ± 11)months. The NPV was 4.5 to 295.0 cm3, median was 37.0 cm3. The NPV%was 6%to 94%, average was(64 ± 23)%. According to our follow up, the standard SSS continued to decline. Compared with screening standard SSS, all the follow-up standard SSS had significant difference(P<0.05), except for that of the first week. Among all the follow up, only the standard SSS change of 1 week after the treatment had a correlation with NPV%(r=0.552,P=0.005), and the others had no significant correlation with NPV%(P>0.05). The uterine fibroids volume decreased in the 12 months follow-up, which had a significant difference with the volume before treatment(P<0.05). And there was also correlation between the fibroids volume change and NPV(r=0.587,P=0.017). There was no correlation between the volume or volume change and standard SSS or standard SSS change(all P>0.05). None serious adverse effects occurred in all cases. Conclusion MRgFUS is a safe and effective way to treat uterine fibroids.

Background Researches showed that transforming growth factor-β2 (TGF-β2) promotes the activity of human Tenon capsular fibroblasts (TFs),which plays a role in the scarring of filtering blebs after antiglaucoma surgery.However,its mechanism is not fully clear.Lysyl oxidases (LOXs) are important extracellular matrix proteases which can catalyze the cross-linking of collagen and elastin.Investigating the impact of TGF-β2 on the expression of LOXs has a great significance for the understanding of the pathogenesis of filtering bleb scarring and its prevention.Objective This study was to investigate the effect of TGF-β2 on the expression of LOXs in cultured human TFs.Methods The TFs at 4-8 generations were divided into normal control group and different concentrations of TGF-β2 treated-groups,and 100,200,400,800 μ1 of TGF-β2 with the final concentration of 2,4,8 and 16 ng/ml was added into the medium to treat human TFs respectively for 24 hours.The LOXs in the cells were detected by Western blot to determine the optimal dose of TGF-β2.The 4 ng/ml TGF-β2(200 μ1) was used to treat human TFs for 6,12,24 and 48 hours respectively,and the change of LOXs expression in the cells over time was assayed by Western blot.The expression and distribution of LOX protein in the normal cells and TGF-β2-treated cells was detected by using immunofluorescence technique.This study was approved by Daping Hospital of Third Military Medical University Ethic Commission.The guardians of the patients who offered the specimen knew the purpose of the study and signed informed consent.Results Western blot assay showed that the expressions of LOX,LOXL1,LOXL2,LOXL3 and LOXL4 in the cells were gradually elevated from the normal control group and 2,4,8,16 ng/ml TGF-β2-treated groups,showing significant differences among the groups (F =37.338,13.438,31.067,11.767,15.167,all at P＜0.01).The expression of LOXL2 protein in the cells was 0.68±0.07,1.09±0.10,1.32±0.07,1.50± 0.06 and 1.89±0.12 in the normal control group and 6-,12-,24-and 48-hour groups respectively after 4 ng/ml TGF-β2 treatment,with a significant increase over time (F =82.832,P=0.000).The expression of LOX was weak in the normal cultured TFs,while the fluorescence intensity of LOX expression was evidently enhanced in the cytoplasm of the cells in the TGF-β2-treated group.Conclusions TGF-β2 upregulates the expressions of LOXs in human TFs in a dose-and time-dependent manner,which probably offers a basis for the further study on the prevention of filtering bleb scarring after glaucoma surgery.