Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma.

A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.

Comparative study of core needle biopsy and fine needle aspiration in the treatment of metastatic lymph nodes guided by contrast-enhanced ultrasound.

Objectives: To compare the diagnostic efficacy of fine needle aspiration (FNA) and core needle biopsy (CNB) for metastatic lymph nodes guided by contrast-enhanced ultrasound (CEUS), and to provide reference for clinical selection of puncture methods. Methods: A total of 168 patients who were admitted to Baoding No.1 Central Hospital from June 2020 to January 2021 and required puncture of the diseased lymph nodes were included. Seventy six patients were guided by conventional ultrasound, of which 37 received FNA and 39 received CNB. 92 patients were guided by CEUS, of which 41 received FNA and 51 received CNB. The diagnostic accuracy of FNA and CNB guided by conventional ultrasound and CEUS was compared, and the sensitivity, specificity, positive predictive value, and negative predictive value of FNA and CNB in the diagnosis of metastatic lymph nodes guided by CEUS were further compared. Results: The diagnostic accuracy of FNA and CNB guided by CEUS were higher than that guided by conventional ultrasound, with a statistically significant difference (P<0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of FNA and CNB in the diagnosis of metastatic lymph nodes were 95.0%, 95.2%, 95.0%, 95.2%, 100%, 100%, 100%, 100%, respectively, with statistically significant differences (P>0.05). Conclusion: CEUS can guide puncture and improve diagnosis accuracy. No statistical difference can be seen in the diagnostic efficacy of CNB and FNA for metastatic lymph nodes, CNB can provide more diagnostic information, while FNA can replace CNB for metastatic lymph nodes adjacent to blood vessels and difficult to operate.

Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B.

BACKGROUND: Whether interferon (IFN)-α therapy is better than nucleos(t)ide analogs (NAs) in the prevention of adverse outcomes, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is still uncertain or controversial. This study aimed to compare the cumulative incidence of adverse outcomes in patients with CHB on IFN-α- and NA-based therapies. METHODS: This was a retrospective study of patients with CHB on antivirals. Patients treated with IFN-α (IFN-α or peginterferon-α) with or without NAs were defined as the IFN-α group, and those only receiving NAs were defined as the NAs group. Propensity score matching (PSM) was used to minimize baseline bias. Cox regression models were performed to select possible factors related to adverse outcomes development. RESULTS: All 1247 patients were divided into the IFN-α (n = 877) and NAs (n = 370) groups. 26patients (20 and 6 in the NAs and IFN-α groups) developed adverse outcomes (decompensated cirrhosis, liver failure, HCC, liver transplantation and deaths) during a median follow-up of 5.2 years. The cumulative adverse outcomes occurrence at 10 years was significantly lower in the IFN-α group than in the NAs group in all (1.1% vs. 11.9%, P <0.001) and treatment-naïve (1.1% vs. 12.4%, P <0.001) patients. Similar trends were observed after PSM and differentiation of cirrhosis. Multivariate analysis before and after PSM showed that IFN-α-based treatment was independently associated with a lower adverse outcomes incidence (before/after PSM: P = 0.001/P = 0.002). HCC risk stratification analyses revealed that the superiority of IFN-α in preventing HCC was more significant in patients with high-risk HCC. CONCLUSIONS: IFN-α-based therapy was superior to NAs in preventing adverse outcomes in patients with CHB regardless of cirrhosis, and in reducing HCC in those with a high risk of HCC.

[Efficacy of Zaozhu Yinchen Recipe for Treating Non-alcoholic Steatohepatitis and its Effect on Free Fatty Acid and TNF-alpha].

OBJECTIVE: To observe the efficacy of Zaozhu Yinchen Recipe (ZZYCR) on non-alcoholic steatohepatitis (NASH) patients, and to explore its effect on serum free fatty acid (FFA) and tumor necrosis factor alpha (TNF-alpha). METHODS: Totally 120 patients with NASH were randomly assigned to the treatment group (60 cases, treated with ZZYCR, one dose per day) and the control group (60 cases, treated with Silibin Meglumine Tablets, 20 mg each time, thrice per day). The therapeutic course for all was 24 weeks. Serum levels of ALT and AST activities, TC and TG levels were detected before and after treatment. Peritoneal CT was performed in all patients, and CT ratios of liver and spleen calculated. NAFLD activity score (NAS) and degree of hepatic fibrosis were assessed using pathological examinations of liver tissue, and efficacy also evaluated. Serum contents of FFA and TNF-alpha were also detected. RESULTS: Compared with before treatment in the same group, activities of ALT and AST, serum levels of TC, TG, FFA, and TNF-alpha, NAS, scores of symptoms and signs all obviously decreased, degree of hepatic fibrosis was obviously improved in the two groups (P < 0.05, P < 0.01). These changes were more obviously seen in the treatment group (P < 0.05). After 24-week treatment, the total effective rate and total clinical efficacy were 80.00% (48/60 cases) and 85.00% (51/60 cases) in the treatment group, obviously higher than those in the control group [60.00% (36/60 cases) and 73.33% (44/60 cases) respectively], with significant difference (P < 0.05, P < 0.01). CONCLUSION: ZZYCR could improve the clinical efficacy of NASH patients, and its mechanism might be associated with inhibiting serum levels of FFA and TNF-alpha.

[Mechanism of geniposide in improving free fatty acid metabolism in rats with non-alcoholic fatty liver disease].

To observe the effect of geniposide on non-alcoholic fatty liver disease (NAFLD), and discuss the mechanism of geniposide for NAFLD from the aspect of free fatty acid, forty healthy Wistar male rats were randomly divided into normal group, model group, geniposide and Xuezhikang group. The rats in normal group were fed with normal diets, and the rats in other 3 groups were given with high-fat diet for 8 weeks to induce the NAFLD models. From the week 5 to end of week 8, the rats in geniposide and Xuezhikang group were intervened with corresponding medicines. The body weight, liver wet weight, and fat weight of the rats were recorded. Visual and pathological changes in hepatic tissues were observed with HE staining. The contents of TG, FFA, FAS, AMPK, ACCase and Malonyl-CoA in hepatic tissue, contents of CHO and LDL-C in serum and activities of AST and ALT in serum were detected by using corresponding methods. The results showed that the body weight, liver wet weight, and fat weight of the rats, CHO, LDL-C, ALT and AST levels in serum, TG, FFA, FAS, ACCase and Malonyl-CoA levels in hepatic tissues of the rats in model group were significantly higher than those in normal group (P<0.01), while AMPK activity was significantly lower than that of the normal group (P<0.01), with obvious visual and pathological steatosis in hepatic tissues, and inflammatory injury occurred in model group. Compared with the model group, body weight of the rat, fat weight, levels of FFA in hepatic tissues, ALT and AST activities in serum, liver wet weight, TG, FAS, ACCase and Malonyl-CoA levels were significantly decreased in geniposide group (P<0.01), while the AMPK activity in hepatic tissues was significantly increased (P<0.05),with improvement in visual and pathological performance. Compared with the model group, liver wet weight, fat weight, TG and FFA levels in hepatic tissues, and LDL-C level in serum were significantly decreased in Xuezhikang group (P<0.05). Compared with Xuezhikang group, the body weight of rat, fat weight and FFA level in hepatic tissues were significantly lower in geniposide group (P<0.01), but with no significant difference in other aspects. These findings indicated that geniposide was highly effective in improving the pharmacological effect of NAFLD induced by high-fat diet, and the mechanism was achieved through AMPK-ACCase-Malonyl-CoA-FFA axis.

[Treatment of HBeAg positive chronic hepatitis B by xiaoyao powder combined with interferon-alpha: a clinical observation].

OBJECTIVE: To study the efficacy of Xiaoyao Powder (XYP) combined with interferon alpha (IFN-alpha) in treating HBeAg positive chronic hepatitis B (CHB) patients and the effect on their quality of life (QOL). METHODS: Totally 193 patients with HBeAg-positive CHB confirmed by liver biopsy were randomly assigned to 2 groups, Group A (94 cases) and Group B (99 cases). IFN-alpha1b was subcutaneously injected to patients in Group A at the dose of 50 microg, thrice per week. Those in Group B additionally took XYP. The therapeutic course for all was 24 weeks. Clinical efficacy was observed by assessing ALT restoration rate, HBeAg negative rate, HBeAg conversion rate, HBV DNA negative rate, complete response rate, partial response rate, and symptoms integral. The evaluation of QOL was performed by using chronic liver disease questionnaire (CLDQ) score. Adverse reaction occurrence rate was observed in the two groups. RESULTS: Better effects were obtained in Group A on ALT restoration rate, HBeAg negative rate, HBV DNA negative rate, complete response rate, partial response rate, TCM symptoms integral, the total effective rate of TCM sysmptoms, CLDQ score, and adverse reaction rates, showing statistical difference when compared with Group B (P < 0.05, P < 0.01). CONCLUSION: XYP could elevate the efficacy of TCM symptoms of HBeAg-positive CHB patients and anti-viral effect, improve their QOL, and reduce adverse reaction of IFN-alpha.

Expression inhibition of multidrug resistance-associated protein (MRP1) by multi-ribozyme expression system in HEK293 cells.

To study application of multi-ribozyme expression system on expression inhibition of multidrug resistance-associated protein (MRP1) in HEK293 cells, the multi-ribozyme expression system containing 20 cis-acting ribozymes for self-cleavage and 10 trans-acting ribozymes for targeting to MRP1 gene specific site were constructed. HEK293 cells cotransfected multi-ribozyme expression system with MRP1 target gene or full length of MRP1 gene respectively were analyzed by RT-PCR, Western blot analysis and MTT assay. The results showed that multi-ribozyme systems were able to dramatically decrease fluorescent fusion protein expression in HEK293 cells. RT-PCR analysis indicated that the extent of MRP1 target mRNA decrease was correlated with the number of trans-acting ribozyme contained in multi-ribozyme expression system. Similar changes have been observed from Western blot. MTT assay showed that multi-ribozyme systems were able to reverse MDR generated by MRP1 gene in HEK cells. These results suggested that inhibitory effects of multiple copies of ribozymes contained in the system were better than that of single ribozyme contained. Therefore, this strategy could be used in treatment of tumor or other diseases via gene therapy.