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Objective To investigate the effect of Tripterygium wilfordii polyglycosides(TWPS) on inflammatory response found in mouse models with Sjgren's syndrome(SS). Methods Mice were randomly divided into control group, Sjgren's syndrome model group, hydroxychloroquine sulfate treatment group (20 mg/kg hydroxychloroquine sulfate intragastric administration), TWPS low-dose, medium-dose and high-dose groups (10, 20, 30 mg/kg TWPS), TWPS + Wortmanin (PI3K/Akt/eNOS signaling pathway inhibitor) group (30 mg/kg TWPS and 0.6 mg/kg Wortmannin viajugular vein).Saliva flow rate, water intake, whole blood viscosity and plasma viscosity were recorded. Serum IL-6, IL-17, IgG and eNOS were detected by ELISA. Western blot was used to detect PI3K/Akt/eNOS pathway related proteins. Results Compared with control group, the saliva flow rate of the model group decreased and the quantity of drinking water increased(P＜0.05). Compared with model group, saliva flow rate increased and water consumption decreased in low, medium and high dose TWPS groups, which alleviated the change of model group(P＜0.05). Compared with the low, medium and high dose TWPS +Wortmanin groups, saliva flow rate decreased and water intake increased (P＜0.05). The whole blood and plasma viscosity of model group increased compared with control group(P＜0.05). The whole blood and plasma viscosity of TWPS low-dose, medium-dose and high-dose groups were lower than that of model group(P＜0.05). The whole blood and plasma viscosity of TWPS+Wortmanin group was higher than that of low, medium and high dose TWPS groups(P＜0.05). Compared with the control group, the levels of serum IL-6, IL-17 and IgG in model group were increased, while the level of eNOS was decreased(P＜0.05). The serum levels of IL-6, IL-17 and IgG in TWPS low-dose, medium-dose and high-dose groups were lower than those in model group, while the levels of eNOS were higher than those in model group(P＜0.05). The serum level of IL-6, IL-17 and IgG in TWPS +Wortmanin group increased as compared to those in low, medium and high dose TWPS +Wortmanin group, while the level of eNOS decreased as compared to those in low, medium and high dose TWPS +Wortmanin group(P＜0.05). The level of p-PI3K/PI3K, p-Akt/Akt and p-ENOS /eNOS in model group was lower than those in control group(P＜0.05). Compared with model group, p-PI3K/PI3K, p-Akt/Akt and p-ENOS/eNOS levels of TWPS in low, medium and high dose groups all increased(P＜0.05); The level of p-PI3K/PI3K, p-Akt/Akt and p-ENOS /eNOS in TWPS +Wortmanin group was lower than those in low, medium and high dose TWPS groups(P＜0.05). Conclusions TWPS alleviates inflammatory response and improves symptoms of mouse models with Sjgren's syndrome.

Backgrounds There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. Methods Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. Results Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P  < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P  < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P  = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P  = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P  < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P  < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P  < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P  < .05). Conclusion ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background and Aim: The purpose of the current study was to investigate the predictive value of hepatitis B core‐related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Methods: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. Results: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40–4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44–5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta‐analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26–2.32, P < 0.001, I2 = 7.89%, P = 0.031). Conclusions: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions. [ABSTRACT FROM AUTHOR]

Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69–5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83–14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93–2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02–3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44–1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45–1.08). Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC. [ABSTRACT FROM AUTHOR]

The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs. The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS). Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40–0.56; PFS:HR = 0.39, 95%CI:0.33–0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82–2.89; PFS:HR = 2.34, 95%CI = 1.69–3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41–0.62; PFS:HR = 0.39, 95%CI:0.30–0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16–0.71; PFS:HR = 0.22, 95%CI:0.10–0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment. AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy. The review was not registered. [ABSTRACT FROM AUTHOR]

The present study investigated the sensitization of 5-fluorouracil (5-FU)-resistant colon cancer cells in vitro, using oxymatrine, a Chinese herb, and a quinolizidine alkaloid compound extracted from the root of Sophora flavescens. The HCT-8 colon cancer cell line and its 5-FU-resistant subline HCT-8/5-FU were treated with 5-FU and oxymatrine, alone or in combination, at various doses. The cells were subsequently assessed for changes in cell viability, apoptosis and morphology and analyzed by fluorescence microscopy and western blotting. The data demonstrated that HCT-8/5-FU markedly increased the dose of 5-FU required for the suppression of tumor cell viability (78.77±1.90 µg/ml vs. 9.20±0.96 µg/ml in parental HCT-8 cells), whereas HCT-8/5-FU induced the tumor cell epithelial-mesenchymal transition (EMT). By contrast, oxymatrine alone and in combination with 5-FU altered HCT-8/5-FU cell morphology, apoptosis and EMT phenotypes. The combination of oxymatrine and 5-FU reduced the protein expression of snail family transcriptional repressor 2 and vimentin, phosphorylated p65 and induced the expression of E-cadherin, by inhibiting the nuclear factor κB (NF-κB) signaling pathway. In conclusion, the data from the present study demonstrated that EMT was associated with 5-FU chemoresistance in HCT-8/5-FU colon cancer cells, and that oxymatrine treatment was able to reverse such resistance. Oxymatrine may regulate tumor cell EMT and inactivate the NF-κB signaling pathway, and may therefore serve as a potential therapeutic drug to reverse 5-FU resistance in colon cancer cells. [ABSTRACT FROM AUTHOR]

AIM:To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi'an and to determine the association between overexpression of P53 and these risk factors.METHODS: All cases (89) and controls (97) were permanent residents in urban areas of Xi'an, all cases of primary EC had been histologically confirmed, controls were inpatients with non-cancer and nonsmoking-related disease. Cancer tissues and tissues adjacent to the cancer of 65 cases and 24 available normal esophageal tissues of controls were detected for P53 overexpression by the immunohistochemical method.RESULTS: The smoking and familial history of cancer were significantly associated with EC in Xi'an inhabitants. The laboratory assay indicated that P53 positive stain in EC was 50.0%(34/65)and 6.1%(4/65) in tissues adjacent to the cancer, but no positive stain was found in normal esophageal tissues of controls. The results showed that P53 overexpression in EC was closely related to smoking and cases with familial history of cancer.CONCLUSION: Smoking and familial cancer history were important risk factors for EC,and the alteration of P53 gene may be due to smoking and inheritance factors.