Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective To explore the protective effect of baicalin on nerve damage in rats with cerebral microbleeds through the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/endothelial nitric oxide synthase(eNOS)pathway.Methods The rat model of cerebral microbleeds was established by intraventricular injection of lipopolysaccharide(LPS),and rats were separated into the model group,the baicalin group(20 mg/kg),the LY294002 group(PI3K inhibitor,10 mg/kg)and the baicalin+LY294002 group(20 mg/kg baicalin and 10 mg/kg LY294002).Rats without LPS injection were served as the control group.The nerve function was evaluated in five groups of rats.Triphenyltetrazolium chloride(TTC)staining was used to evaluate the cerebral infarction status.Hematoxylin-eosin(HE)staining was used to observe the pathological morphology of brain tissue of rats in each group.TUNEL method was used to detect neuronal apoptosis in brain tissue.Enzyme linked immunosorbent assay(ELISA)was performed to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-17(IL-17)in brain tissue of rats in each group.In addition,Western blot assay was used to measure B-cell lymphoma 2(Bcl-2),Caspase-3,Bcl-2 associated X protein(Bax),PI3K,phosphorylated(p)-AKT,AKT,p-eNOS and eNOS proteins in brain tissue of rats.Results Compared with the control group,neurons in the model group was sparse,with fewer cells and disordered arrangement,the nerve function score,infarct area,TNF-α,IL-1β,IL-17,apoptosis rate,Bax and Caspase-3 proteins were increased,and Bcl-2,PI3K,p-AKT and p-eNOS proteins were decreased(P＜0.05).Compared with the model group,the baicalin group showed clear improvement in brain pathological damage,the nerve function score,infarct area,apoptosis rate,Bax and Caspase-3 proteins,TNF-α,IL-1β and IL-17 were decreased,while protein expressions of Bcl-2,PI3K,p-AKT and p-eNOS were increased(P＜0.05).However,the brain tissue damage of the LY294002 group was further aggravated,and the nerve function score,infarct area,TNF-α,IL-1β,IL-17,apoptosis rate and the expression of apoptosis proteins Bax and Caspase-3 were increased,the Bcl-2,PI3K,p-AKT and p-eNOS proteins were decreased(P＜0.05).Intervention with LY294002 on basis of baicalin treatment could reverse the improvement effect of baicalin on the above indicators in rats with cerebral microbleeds(P＜0.05).Conclusion Baicalin may exert a protective effect on nerve damage in rats with cerebral microbleeds by activating PI3K/AKT/eNOS pathway.

Objective To explore the protective effect of baicalin on nerve damage in rats with cerebral microbleeds through the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/endothelial nitric oxide synthase(eNOS)pathway.Methods The rat model of cerebral microbleeds was established by intraventricular injection of lipopolysaccharide(LPS),and rats were separated into the model group,the baicalin group(20 mg/kg),the LY294002 group(PI3K inhibitor,10 mg/kg)and the baicalin+LY294002 group(20 mg/kg baicalin and 10 mg/kg LY294002).Rats without LPS injection were served as the control group.The nerve function was evaluated in five groups of rats.Triphenyltetrazolium chloride(TTC)staining was used to evaluate the cerebral infarction status.Hematoxylin-eosin(HE)staining was used to observe the pathological morphology of brain tissue of rats in each group.TUNEL method was used to detect neuronal apoptosis in brain tissue.Enzyme linked immunosorbent assay(ELISA)was performed to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-17(IL-17)in brain tissue of rats in each group.In addition,Western blot assay was used to measure B-cell lymphoma 2(Bcl-2),Caspase-3,Bcl-2 associated X protein(Bax),PI3K,phosphorylated(p)-AKT,AKT,p-eNOS and eNOS proteins in brain tissue of rats.Results Compared with the control group,neurons in the model group was sparse,with fewer cells and disordered arrangement,the nerve function score,infarct area,TNF-α,IL-1β,IL-17,apoptosis rate,Bax and Caspase-3 proteins were increased,and Bcl-2,PI3K,p-AKT and p-eNOS proteins were decreased(P＜0.05).Compared with the model group,the baicalin group showed clear improvement in brain pathological damage,the nerve function score,infarct area,apoptosis rate,Bax and Caspase-3 proteins,TNF-α,IL-1β and IL-17 were decreased,while protein expressions of Bcl-2,PI3K,p-AKT and p-eNOS were increased(P＜0.05).However,the brain tissue damage of the LY294002 group was further aggravated,and the nerve function score,infarct area,TNF-α,IL-1β,IL-17,apoptosis rate and the expression of apoptosis proteins Bax and Caspase-3 were increased,the Bcl-2,PI3K,p-AKT and p-eNOS proteins were decreased(P＜0.05).Intervention with LY294002 on basis of baicalin treatment could reverse the improvement effect of baicalin on the above indicators in rats with cerebral microbleeds(P＜0.05).Conclusion Baicalin may exert a protective effect on nerve damage in rats with cerebral microbleeds by activating PI3K/AKT/eNOS pathway.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

OBJECTIVE: To evaluate the inhibitory effect of cordycepin on oral cancer xenograft in nude mice and explore the underlying mechanisms. METHODS: Sixteen BALB/c mice bearing subcutaneous human tongue squamous cell carcinoma (TSCC) TCA-8113 cell xenografts were randomized into model group and cordycepin treatment group for daily treatment with saline and cordycepin for 4 weeks. After the treatment, the tumor xenografts were dissected and weighed to assess the tumor inhibition rate. Histological changes in the heart, spleen, liver, kidney, and lung of the mice were evaluated with HE staining, and tumor cell apoptosis was examined using TUNEL staining; The expressions of Bax, Bcl-2, GRP78, CHOP, and caspase-12 in the xenografts were detected using RT-qPCR and Western blotting. RESULTS: Cordycepin treatment resulted in a tumor inhibition rate of 56.09% in the nude mouse models, induced obvious changes in tumor cell morphology and significantly enhanced apoptotic death of the tumor cells without causing pathological changes in the vital organs. Cordycepin treatment also significantly reduced Bcl-2 expression (P < 0.05) and increased Bax, GRP78, CHOP, and caspase-12 expressions at both the RNA and protein levels in the tumor tissues. CONCLUSION Cordycepin treatment can induce apoptotic death of TCA-8113 cell xenografts in nude mice via the endogenous mitochondrial pathway and endoplasmic reticulum stress pathways.
Humans ; Animals ; Mice ; Carcinoma, Squamous Cell/drug therapy* ; Heterografts ; Mice, Nude ; Tongue Neoplasms/drug therapy* ; Cordyceps ; Caspase 12 ; Endoplasmic Reticulum Chaperone BiP ; bcl-2-Associated X Protein ; Tongue

Objective:To explore the endoscopic features of early gastric cancer (EGC) related to non-curative endoscopic resection, and to construct an assessment model to quantify the risk of non-curative resection.Methods:From August 2006 to October 2019, 378 lesions that underwent endoscopic resection and were diagnosed pathological as EGC in the Department of Gastroenterology, Peking Union Medical College Hospital were included in this case-control study.Seventy-eight (20.6%) non-curative resection lesions were included in the observation group, and 234 lesions which selected from 300 lesions of curative resection were included in the control group according to the difference of operation year ±1 with the observation group, and the ratio of 1∶3 of the observation group to the control group. Univariate and multivariate logistic regression analysis were performed to explore the risk factors for non-curative resection. The independent risk factor with the minimum β coefficient was assigned 1 point, and the remaining factors were scored according to the ratio of their β coefficient to the minimum. A predictive model was established to analyze the 378 lesions.The non-curative resection rates of lesions of different scores were calculated. Results:Univariate analysis showed that the lesion diameter, the location, redness, ulcer or ulcer scar, fold interruption, fold entanglement, and invasion depth observed with endoscopic ultrasonography (EUS) were associated with non-curative resection of EGC lesions ( P<0.05), and contact or spontaneous bleeding may be associated with non-curative resection ( P=0.068). Multivariate logistic regression analysis showed that submucosal involvement (VS confined to the mucosa: β=0.901, P=0.011, OR=2.46, 95% CI: 1.23-4.92), lesion diameter of 3-<5 cm (VS <3 cm: β=0.723, P=0.038, OR=2.06, 95% CI: 1.04-4.09), lesion diameter of ≥5 cm (VS <3 cm: β=2.078, P=0.003, OR=7.99, 95% CI: 2.02-31.66), location in the upper 1/3 of the stomach (VS lower 1/3: β=1.540, P<0.001, OR=4.66, 95% CI: 2.30-9.45), and fold interruption ( β=2.287, P=0.008, OR=1.93, 95% CI: 0.95-3.93) were independent risk factors for non-curative resection of EGC lesions. The factor of lesion diameter of 3-<5 cm and submucosal involvement were assigned 1 point respectively, location in the upper 1/3 of the stomach was assigned 2 points, diameter of ≥5 cm and fold interruption were assigned 3 points respectively, and other factors were assigned 0 point. Then the analysis of 378 lesions showed that the probability of non-curative resection at ≥2 points was 41.9% (37/93), 4 times as much as that at 0 [11.5% (25/217)]. Conclusion:EGC lesions with diameter ≥3 cm, located in the upper 1/3 of the stomach, interrupted folds or submucosal involvement are highly related to non-curative resection. The predictive model based on these factors achieves satisfactory efficacy, but it still needs further validation in larger cohorts.

BACKGROUND: Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression. METHODS: The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan-Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression. RESULTS: Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression. CONCLUSIONS Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.
Biopsy ; Carcinoma in Situ ; Endoscopy ; Humans ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/diagnosis*

Objective To evaluate the efficacy, safety and risk factors of endoscopic treatment for patients with early gastric cancer. Methods A retrospective study was conducted in a single center and data was collected from 186 early gastric cancers in 168 pathologically confirmed patients who received endoscopic treatment in Peking Union Medical College Hospital from January 2006 to December 2015. The cases were divided into different groups according to indications of endoscopic treatment. The curative resection rate and complication rate were analyzed. Post-resection outcomes were evaluated by long-term surveillance. Results The curative resection rate was 86. 9%( 73/84) in the group with absolute indications, 61. 7%(50/81)in the group with expanded indications, and 33. 3%(7/21) in the group beyond indications (P＜0. 01). Multivariate analysis revealed that the significant independent predictors for curative resection included lower third location of stomach, no ulceration,≤2 cm at diameter, no adhesion, and well-differentiation in histopathology. In the expanded indications group, discordance of differentiation type and deeper invasion mainly resulted in non-curative resection in en bloc lesions. The rate of bleeding and perforation was 4. 8%( 9/186) and 3. 8%( 7/186), respectively. The perforation rate was significantly lower in the lesions located in the lower third of stomach, without adhesion or performed by en bloc resection. During a median follow-up period of 22. 3 months, 154 patients were followed successfully. The incidence of synchronous and metachronous gastric cancers in curative resected lesions was 7. 5%( 8/106) and 0. 9%(1/106), respectively. Conclusion Endoscopic resection is an optimal treatment with high curative resection rate for early gastric cancer patients with absolute indications. Patients with expanded indications should take precise preoperative evaluation to avoid higher risk of non-curative resection endoscopically. Close follow-up is necessary for synchronous and metachronous gastric cancers after endoscopic resection.

Objective:To study the qualitative identification and quantitative analysis of Paeoniae radix Rubra in Fufang Fuqing lotion. Methods:TLC was used to identify Paeoniae radix Rubra. The content of paeoniflorinl was determined by HPLC. The mobile phase was acetonitrile-0. 01% phosphonic acid (13 ∶87), and the detection wavelength was 230 nm,the flow rate was 1. 0ml·min-1, the column temperature was 40℃,and the sample size was 10μl. Results:The results of TLC showed that the relevant spots were clear without any interference from the negative sample. The calibration curve of paeoniflorinl was linear within the range of 0. 070-4. 500 μg (r=1. 000 0). The average recovery was 98. 36% with RSD of 2. 73%(n=6). Conclusion:The methods are accurate and quick in the qualitative identification and quantitative assay of the preparation, which can be used for the quality control of Fufang Fuqing lo-tion.

Objective To investigate the clinical features , treatment regimen , and prognosis evaluation of tertiary peritonitis (TP). Methods Seventy-eight cases with TP were randomly enrolled into 2 groups, including the simple western medicine-treated group (32 cases) and the integrated traditional Chinese and western medicine-treated group (46 cases). The prognoses were evaluated according to the acute physiology and chronic health evaluationⅢ (APACHEⅢ, APⅢ) scoring. Results The mortality rate was 71.9% (23 of 32) in patients received the simple western medicine and was 32.6%(15 of 46) in patients received the integrated traditional Chinese and western medicine with significant difference between these two groups (P < 0.01). There was a significant correlation between AP Ⅲscore and actual mortality (r=0.73,P<0.01), and predicted mortality (r=0.76, P<0.01). Conclusions The therapeutic effect is acceptable and satisfactory for the TP patients received the integrated traditional Chinese and western medicine. The AP Ⅲ scoring system can be used to predict the prognosis of TP patients.