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.

OBJECTIVE To explore dianhydrogalactitol(DAG)-induced neurodevelopmental toxicity and mechanisms in zebrafish embryos and larvae. METHODS On the basis of general toxicity evaluation, zebrafish embryos were exposed to DAG in groups, and the effects of DAG on zebrafish nerves and behaviors were observed by means of autonomic locomotor response and light stimulation response of juvenile fish; the effects of DAG on zebrafish brain tissues were observed by means of histopathological examination of brain and acridine orange staining. The relative expression of dopamine neuron-related genes(DAT, TH, GCH1) and neural inhibition/promotion of apoptosis-related genes(Bax, Bcl-2) was determined by real-time fluorescence quantitative PCR in zebrafish larvae. RESULTS DAG inhibited the voluntary movement of zebrafish under the 20, 40, 75 mg·L-1, and the inhibition rate of voluntary movement showed obvious concentration correlation; DAG inhibited the reaction speed of zebrafish under the 20, 40, 75 mg·L-1, and the rate of decrease of reaction ability showed concentration correlation; the brain tissue became smaller, but the tissue structure of zebrafish did not show any significant abnormality in the various concentration groups of DAG; acridine orange staining was used to detect the apoptosis of the overall embryonic cells of zebrafish, and it was found that the administration of DAG inhibited the apoptosis of zebrafish. Acridine orange staining was used to detect apoptosis in the whole embryonic cells of zebrafish, and it was found that the green fluorescence in the head of the administered group was more obvious than that in the control group, indicating that apoptosis increased, and apoptosis increased in a dose-dependent manner, which was in accordance with the apparent observation; DAG in 75, 150, 300, 425, 600 mg·L-1 of the experimental condition could lead to a downward regulation of the relative expression of mRNA of the genes related to the zebrafish juvenile dopaminergic neuron, DAT, TH and GCH1. The Bax/Bcl-2 relative mRNA expression was up-regulated with increasing drug concentration. CONCLUSION The neurodevelopmental toxicity of DAG in zebrafish embryos and juveniles may be related to the inhibition of dopaminergic neurons.

To reveal the relationship between endophytic fungi and the functional components, saccharides and flavonoids in the mycelia or fermented liquor of 21 endophytic fungi in D.officinale were detected using HPLC and UV spectrophotometer.The results showed that the ethyl acetate extracts from 21 fungal strains all contain flavonoids.According to the chromatographic retention time of HPLC and UV spectra characteristics of flavonoids, strain DO49 was found produce naringenin, strains DO23, DO81 and DO83 were found produce rutin.The water-soluble extracts from 21 strains all had polysaccharides.However, there was difference in the composition of monosaccharides derived from polysaccharides among different strains.According to the composition of monosaccharides and the peak area ratio of mannose and glucose, the fungal strains including DO23, DO26, DO81, DO54, DO55, DO83 product polysaccharides associated with D.officinale were selected.In conclusion, based on the saccharides and flavonoids, the excellent endophytic fungal strains DO23, DO81 and DO83 were selected, which could produce the same flavonoids and similar polysaccharides in D.officinale.

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.

BACKGROUND:Lymph-targeted tracing and therapy based on carbon nanotubes have been one of the hottest researches on targeting tumor diagnosis and treatment. To evaluate the accumulation of carbon nanotubes in axil ary lymph node can provide experimental evidences for developing nano-tracers and drug carriers which are more lymph-specific and more biocompatible. OBJECTIVE:To study the accumulation of the intravenously injected carboxylated single-wal ed carbon nanotubes in axil ary lymph nodes of Sprague-Dawley rats, and to evaluate their effect on blood cel s. METHODS:Sixty-four Sprague-Dawley rats were randomly divided into two groups. Rats in testing group were injected with carboxylated single-wal ed carbon nanotubes suspension (2 mg/kg), while those in control group were injected with 5%glucose solution (1 mL/kg), both through the tail vein, three times per week. Four periods of 7, 60, 90 and 120 days were set (the 120-day period referred to 90 days of administration fol owed by 30 days of drug withdrawal). At the end of each period, eight rats from each group were randomly picked out, to col ect blood samples via the abdominal aorta for blood routine test. Final y the axil ary lymph nodes were observed, and the lymph node samples of rats in the testing group were col ected and analyzed at 120 days by transmission electron microscope. RESULTS AND CONCLUSION:Compared with the control group, black staining of axil ary lymph nodes of rats in testing group was not obvious at the end of the 7-day period. However, with the increase of the dosing periods, the lymph nodes of the rats in the testing group became enlarged, firm and black stained, coupled with a significant rising in the percentage of blood neutrophils. After 30 days of drug withdrawal, the size of the rat axil ary lymph nodes was reduced and black staining partly faded, with the decreasing of blood neutrophil percentage. Under the transmission electron microscope, abundant carboxylated single-wal ed carbon nanotubes were uptaken by lymphocytes to form a large number of phagocytic vacuoles after drug withdrawal for 30 days. It indicates that the short-term tracing of rat axil ary lymph nodes by carboxylated single-wal ed carbon nanotubes injected through the tail vein is relatively weak, while the long-term intravenous injection can cause their accumulation in rat axil ary lymph nodes, coupled with the increase of neutrophils;after drug withdrawal, the carboxylated single-wal ed carbon nanotubes can be slowly cleared by the lymph nodes.