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.

Based on the analysis of definition and the causes of excessive medical treatment, this paper discus-ses the harm of excessive medical treatment concretely, including increased health care costs, the waste of medical resources, worsening doctor-patient conflicts that influence the development of holistic medicine. And in the per-spective of ethics, professional spirit and the humanistic quality, it puts forward the prevention and countermeasures to solve the problem of excessive medical treatment.

OBJECTIVETo study the effect of rhTNF-alpha on human sperm mitochondrial function and motility in vitro.

METHODSFifty-six semen samples collected by masturbation were analyzed according to WHO protocols. Semen samples from 40 healthy men were prepared using Percoll centrifugation. Sperm suspension was diluted to a concentration of 10 x 10(6)/ml in Ham's F10 medium. Sperm samples were incubated with rhTNF-alpha solution (final concentration 0.03 microg/L, 0.06 microg/L, 0.09 microg/L and 0.27 microg/L, respectively) for 0.5 h, 1 h, 2 h, 3 h and 4 h at 37 degrees C in 5% CO2, and comparative studies were made with a control group. Ten microl sperm samples were examined with CASA technique, 250 microl stained in the presence of 10 microg/ml Rh123 and PI, and mitochondrial function analyzed by flow cytometry.

RESULTSSignificant differences were found between the experimental groups (final concentration 0.06 microg/L, 0.09 microg/L and 0.27 microg/L) and the control group in viability, straight line velocity, curvilinear velocity, average path velocity, progressive motility of human sperm and the number of spermatozoa with normal mitochondrial function (P < 0.01) except the final concentration 0.03 microg/L group (P > 0.05). Motility of human sperm lowered with the increase of rhTNF-alpha concentration and incubation time, and r values were 0.675, 0.691, 0.762, 0.693, 0.724 and 0.571, 0.594, 0.752, 0.791, 0.816, respectively (P < 0.01). The number of spermatozoa with normal mitochondrial function decreased with the increased rhTNF-alpha concentration and incubation time, and r values were 0.615, 0.643, 0.752, 0.691, 0.754 and 0.532, 0.567, 0.782, 0.692, 0.854, respectively (P < 0.01).

CONCLUSIONrhTNF-alpha can reduce human sperm motility function in vitro, possibly by interfering with human sperm mitochondrial function.

Adult ; Dose-Response Relationship, Drug ; Humans ; Male ; Mitochondria ; drug effects ; physiology ; Recombinant Proteins ; pharmacology ; Sperm Motility ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology

Objective To investigate a wavelet-transform-based approach that reduces the noise of medical images, and to compare the difference of the effects by different wavelet types. Methods A soft threshold approach based on the modification of local coefficient of wavelets was proposed. Firstly, a local modulus extrema distribution of the image, M j,m,n is obtained using wavelet transform. Then the modulus maximum was calculated and a threshold Tm was defined according to the statistical properties of the local modulus extrema distribution. If the extremum of the wavelet transform was greater than or equal to the threshold Tm, the corresponding wavelet coefficient was kept unchanged; while if the extremum of the wavelet transform was less than the threshold Tm, its corresponding wavelet coefficient was calculated using the soft threshold approach. Lastly, an inverse wavelet transform was performed according to the wavelet coefficients of these two parts so that the image could be reconstructed. Results The proposed approach could filter out the noise in medical images effectively, and the effects of noise reduction by different wavelets were different. Conclusion A useful wavelet threshold noise reduction algorithm can be obtained by wavelet multi-dimensional decomposition of image with proper selection of wavelet base function, and comparatively ideal effect of noise reduction can be achieved using this algorithm.

Feature extraction of event related potential (ERP) plays an important part in both fundamental and clinical researches for cerebral neurophysiology.Based on the prior knowledge of feature distribution of ERP,this paper introduces an approach to feature extraction of ERP from composite EEG,which is combined with wavelet multiresolution analysis (MRA) and radial basis function neural network (RBFNN).The components related to low-frequency response can be extracted from the wavelet decomposition coefficients by RBFNN.Then signal reconstruction is implemented to obtain the feature of ERP.Experimental result demonstrates that the approach is reliable.