Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

Objective:To investigate the clinical value of AB classification combined with Arima classification for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCC).Methods:From July 2017 to December 2022, 76 cases of SESCC receiving endoscopic submucosal dissection and intra-epithelial papillary capillary loops (IPCL) AB classification as type B2 in Ningbo Medical Center Lihuili Hospital and Jiangsu Province Hospital of Chinese Medicine were included in the study. IPCL was reclassified according to Arima classification. The depth of infiltration determined by pathology was the gold standard. The sensitivity, the specificity, the positive predictive value and the negative predictive value of B2-Arima combined classification in predicting the invasion depth of SESCC were analyzed.Results:In the 76 cases of type B2 IPCL lesions, 31 cases (40.79%) were T1a-MM/T1b-SM1 SESCC. The sensitivity, the specificity, the positive predictive value, the negative predictive value and the diagnostic accuracy of type B2 IPCL to predict T1a-MM/T1b-SM1 SESCC were 70.45% (31/44), 79.64% (176/221), 40.79% (31/76), 93.12% (176/189), and 78.11% (207/265), respectively. After Arima classification, the above corresponding indicators of type B2-4ML and type B2-AVA-4M IPCL in predicting T1a-MM/T1b-SM1 SESCC were 61.36% (27/44), 88.24% (195/221), 50.94% (27/53), 91.98% (195/212), 83.77% (222/265) and 38.64% (17/44), 94.57% (209/221), 58.62% (17/29), 88.56% (209/236), 85.28% (226/265), respectively.Conclusion:B2 IPCL combined with Arima classification can improve the diagnostic accuracy of T1a-MM/T1b-SM1 ESSCC.

Objective: Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. Methods: We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. Results: Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. Conclusion Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

Objective:To investigate the clinical, endoscopic and pathological features, and treatment and prognosis of gastric adenocarcinoma of fundic gland type of chief cell predominant type (GA-FG-CCP).Methods:Data of 40 GA-FG-CCP patients with 41 lesions diagnosed by histopathology at Ningbo Medical Center Lihuili Hospital and Shanghai East Hospital from January 2018 to May 2023 were collected. Their clinical and endoscopic features, pathological features, immunohistochemical results, endoscopic treatment, and prognosis were analyzed.Results:Among the 40 GA-FG-CCP patients, there were 15 males and 25 females, and the mean age was 60.03 years. Most of them had no obvious clinical symptoms or family history of tumor. Except one case, others had no helicobacter pylori infection. The endoscopic features of white light observation were: ① the main location was the upper part of the gastric body (63.41%, 26/41); ② faded or whitish mucosal surface (56.10%, 23/41); ③ dilated vessels with branch architecture (78.05%, 32/41); ④ no background mucosal atrophy (100.00%, 41/41). The features of magnifying endoscopy with narrow band imaging (ME-NBI) were: ① no obvious demarcation line (85.37%, 35/41); ② enlargement of the crypt opening (87.80%, 36/41); ③ widening of the intervening part (92.68%, 38/41); ④ lack of irregular microvascular pattern (95.12%, 39/41). All patients were confirmed gastric adenocarcinoma of the fundic gland by biopsy. The glands showed a low degree of dysplasia, similar to the differentiation of chief cell predominant pattern, also with scattered parietal cells, forming irregular and anastomosing cords. In the 40 patients, 20 did not receive endoscopic therapy. Twelve out of 21 lesions in 20 cases treated with endoscopic resection infiltrated into the submucosa (20-520 μm), 9 cases were intramucosal carcinoma. There was no lymphatic or venous infiltration, and horizontal and vertical margins were negative. Immunohistochemical staining results showed that the tumor was postive for pepsinogen-Ⅰ and MUC 6, with scattered postive for H +-K +-ATPase, but negative for MUC5AC, MUC2 and CD10, and the Ki-67 labeling index was low. No patients had recurrence or metastasis during mean follow-up of 15.85 months. Conclusion:GA-FG-CCP is rare and very well differentiated. Its clinical symptoms are not obvious, but there is endoscopic characteristics. The detection rate of GA-FG-CCP can be improved by white light and ME-NBI, and the diagnosis can be confirmed by pathology and immunohistochemical staining.