Lymphocyte subsets and inflammatory factors as predictors of immunotherapy efficacy in patients with hepatocellular carcinoma.

We aimed to investigate the correlation between lymphocyte subpopulations expressing inhibitor receptors, IL-6 levels, and the efficacy of immunotherapy in patients with hepatocellular carcinoma. Blood samples were prospectively collected before and after immunotherapy from patients with intermediate and advanced hepatocellular carcinoma who were treated with immunotherapy at the Fifth Medical Center of the PLA General Hospital from August 2022 to October 2023. According to the efficacy of the patients, patients were divided into effective and ineffective groups, with 40 in the effective group and 44 in the ineffective group. We compared changes in lymphocyte subsets and IL-6 levels between the two groups. Optimal cut-off value was determined using ROC curves. Then, patients were categorized into high and low groups based on cut-off value, and the disease control rates and progression free survival were compared. Before immunotherapy, there were no significant differences in the baseline levels of lymphocyte subsets (PD1 + TIM3 + T/T, TIGIT + T/T, TIM3 + T/T, CTLA4 + T/T, LAG3 + T/T, PD1 + T/T) and IL-6 between the two groups (P > 0.05). After immunotherapy, the levels of PD1 + TIM3 + T/T, TIGIT + T/T, and IL-6 in the effective group were lower than those in the ineffective group and these differences were statistically significant (P = 0.001, P = 0.008, P = 0.000). However, the levels of other lymphocyte subsets showed no significant difference. Using the ROC curve to assess efficacy prediction, PD1 + TIM3 + T/T, TIGIT + T/T and IL-6 demonstrated high predictive ability (AUC = 0.79, AUC = 0.81, AUC = 0.78). The predictive value of efficacy was further improved when all three factors were combined (AUC = 0.92, P = 0.000). Based on the ROC curve, we identified optimal cut-off value for three factors. Notably, patients with values below the optimal cut-off value had higher disease control rate and progression free survival. The levels of PD1 + TIM3 + T/T, TIGIT + T/T, and IL-6 after 2 cycles of immunotherapy may serve as predictors of treatment efficacy in patients with hepatocellular carcinoma.

Paired box 5 increases the chemosensitivity of esophageal squamous cell cancer cells by promoting p53 signaling activity / 中华医学杂志(英文版)

BACKGROUND@#Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear.@*METHODS@#To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification.@*RESULTS@#PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.@*CONCLUSIONS@#As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.

New progress of multidisciplinary treatment for colon cancer / 国际外科学杂志

Colonic neoplasms is the third most commonly diagnosed cancer in men and second most commonlv diagnosed cancer in women worldwide.The morbidity of Colonic neoplasms is increasing year by year.Despite the fact that surgery is still the main treatment for patients with colon cancer,surgery alone hasn't improved the treatment effectiveness.The current management of colon cancer has come to multidisciplinary team (MDT) modality.MDT modality could offer the optimal treatment option and the internal communication.Under the pattern of MDT which integrates the surgery,chemotherapy,radiotherapy,interventional therapy,targeted therapy and immune therapy,there has been a big progress in the diagnosis and treatment of colon cancer.Patients with metastatic colon cancer should undergo a discussion by a multidisciplinary team before the initial treatment.

The correlation between expression of carcinoembryonic antigen mRNA in preoperative peritoneal lavage fluid and prognosis of operation in patients with gastric cancer / 中国医师进修杂志

Objective To investigate the correlation between expression of carcinoembryonic antigen (CEA) mRNA in preoperative peritoneal lavage fluid and prognosis of operation in patients with gastric cancer.Methods The expression levels of CEA mRNA in preoperative peritoneal lavage fluid of 68 patients with gastric cancer and 30 patients with gastric benign tumor were measured by reverse transcription polymerase chain reaction.The correlation between the expression level of CEA mRNA in preoperative peritoneal lavage fluid and clinicopathological features,prognosis of postoperative were analyzed.Results The expression level of CEA mRNA in preoperative peritoneal lavage fluid of patients with gastric cancre was 1.74 ± 0.25 and with gastric benign tumor was 0.19 ± 0.04,and there was statistical difference (P ＜ 0.05).The expression level of CEA mRNA in preoperative peritoneal lavage fluid had a correlation with the tumor infiltration depth,tumor differentiation,lymph node metastasis,distant metastasis and TNM stage (P ＜ 0.05).There was statistical difference in the recurrent / metastasis rate and survival rate 1 year after operation between low (34 cases) and higher (34 cases) expression level of CEA mRNA in preoperative peritoneal lavage fluid of gastric cancer patients:47.06％ (16/34) vs.82.35％ (28/34) and 79.41％ (27/34) vs.55.88％ (19/34),P ＜ 0.05.Conclusion The expression of CEA mRNA in preoperative peritoneal lavage fluid has close correlation with the clinicopathologic features,and the high expression of CEA mRNA indicats poor prognosis,indicating that CEA mRNA in preoperative peritoneal lavage fluid could be used as a prognostic marker in patients with gastric cancer.

Clinical effect of bicyclol combined with polyene phosphatidyl choline in elderly non-alcoholic fatty liver disease / 中国医师进修杂志

Objective To observe the clinical effect of bicyclol combined with polyene phosphatidyl choline in elderly non-alcoholic fatty liver disease (NAFLD).Methods One hundred and twenty elderly patients with NAFLD were divided into 3 groups by block randomization method,40 cases in each group.Therapeutic group was treated by bicyclol combined with polyene phosphatidyl choline; bicyclol group was only treated by bicyclol; and polyene phosphatidyl choline group was only treated by polyene phosphatidyl choline.The blood biochemical indexes,liver ultrasound score and clinical curative effect of 3 groups were compared after treated for 24 weeks.Results The total cholesterol (TC),triglyceride (TG),alanine aminotransferase (ALT),aspartate aminotransferase (AST) and gamma glutamine transferase (GGT) in 3 groups after treatment were lower than those before treatment,and the difference was statistically significant (P ＜ 0.05) ; TC,TG and ALT levels in therapeutic group after treatment were significantly lower than those in bicyclol group and polyene phosphatidyl choline group [(1.36 ± 0.84) mmol/L vs.(2.77 ± 1.27),(2.84 ±1.35) mmol/L; (1.32 ±0.71) mmol/L vs.(1.89 ±0.87),(1.92 ±0.90) mmol/L; (38.26 ± 12.75) U/L vs.(57.83 ± 16.67),(62.07 ± 18.16) U/L],and the difference was statistically significant (P ＜ 0.05).The liver ultrasound score in 3 groups after treatment was significantly decreased compared with that before treatment,and the difference was statistically significant (P ＜ 0.05).Liver ultrasound scores in therapeutic group after treatment were significantly lower than those in bicyclol group and polyene phosphatidyl choline group [(2.08 ± 0.93) scores vs.(3.17 ± 1.14),(3.34 ± 1.07) scores],and the difference was statistically significant (P ＜ 0.05).The total effective rate in therapeutic group was significantly higher than that in bicyclol group and polyene phosphatidyl choline group [85.0％ (34/40) vs.67.5％ (27/40),65.0％ (26/40)],and the difference was statistically significant (P ＜0.05).Conclusions Bicyclol combined with polyene phosphatidyl choline has better clinical effect in elderly patients with NAFLD.It is better than single bicyclol and polyene phosphatidyl choline and worth clinical promotion.