Background and purpose: It was reported that activins, members of transforming growth factor-β superfamily, could induce several tumor cells into apoptosis. This study was designed to observe the effects of recombination human activin A on proliferation and apoptosis ofA549 cells. Methods: A549 cells were cultivated by routine method, then treated with different concentrations of recombination human activin A. Inhibitory effect of activin A on A549 cell proliferation was detected by MTT assay, and apoptosis of A549 cells was determined by flow cytometry. The expression of type Ⅱ receptors of activin (ActR Ⅱ and ActR Ⅱ B) was detected by Western blot. Results: Recombination human activin A inhibited the proliferation ofA549 cells in time-dependent and dose-dependent manners. Increases of apoptosis in A549 cells and expression of ActR I] and ActR ⅡB occurred dose-dependently after treated with acfivin A. Conclusion: Recombination human activin A inhibited cell proliferation and induced apoptosis in A549 cells, at least in part, by inducing expression of type Ⅱ receptors of activin and activation of its downstream signaling.

Objective To analyze the effect of N-acetyl-L-cysteine(NAC)on endoplasmic reticulum stress mediated HepG2 cells apoptosis and evaluate the role of NAC in the treatment of liver injury.Methods HepG2 cells were treated with thapsigargin(TG)to establish the model of oxidative endoplasmic reticulum stress mediated apoptosis,and NAC was used to intervene in apoptosis.To evaluate the apoptosis,various methods such as MTT assay,flow cytometry,DNA ladder and Western blot were performed.Results After treated with 2 μmol/L TG for 0,24,36 and 48 hours,the vitality of HepG2 cells decreased.The ratio of apoptotic cells increased along with the prolonged treatment duration of TG(0.7%±0.5%,27.6%±6.3%,29.7%±3.3%,47.9%±3.5% respectively,P<0.05),and the production of reactive oxygen species(ROS)also increased in time-dependent manner(14.0%±0.5%,36.1%±3.0%,38.2%±6.0%,48.3%±12.4%,P<0.05).The HepG2 cells showed typical morphologic change of endoplasmic retieulum stress induced by 2 μmol/L TG after 36 h and 48 h.DNA ladder was observed at the same concentration and time point correspondingly.Endoplasmic reticulum stress mediated-apoptosis was confirmed by Western blot.Both 10 mmol/L and 20 mmol/L NAC could protect ceils from apoptosis.The ratio of apoptotic cells decreased to 14.0%±1.3% and 11.0%±0.3%,respectively.The production of ROS decreased to 34.7%±0.8% and 31.5%±2.9%,respectively.The effect was related to the concentration of NAC.Conclusions As a Ca2+-adenosine triphoshatase inhibitor,TG may disrupt intracellular calcium homeostasis,which can induce endoplasmie reticulum stress and apoptosis.NAC,the precursor of the synthesis of-SH,can directly inhibit the ROS reaction and alleviate liver damage,which may play a role in the treatment of liver failure.

Objective To evaluate the clinical and histological outcomes in a cohort of chronic hepatitis B (CHB) patients who had histologically confirmed severe liver fibrosis and received lamivudine (LAM) therapy for up to 10 years. Methods Thirty-nine CHB patients with severe liver fibrosis (Ishak fibrosis score≥4) were treated with LAM for up to 10 years. Disease progression liver histological improvement, virological and biochemical responses were evaluated during follow-up. Data were analyzed using paired t test, Fisher exact test and Willcoxon test. Results Twenty-eight patients completed the 10-year follow-up. There were 5 (17.9% ) patients with disease progression.At the end of follow up, 16 patients received a second liver biopsy, which showed significant improvement of histological activity index (1.1 ± 1.4 vs 7. 1 ± 3.2, t =- 0.82, P＜0.01 ) and Ishak fibrosis score (3.6±2.2 vs 5.3±0.7, t= -2.89, P＜0.05) compared to baseline. There were 3 cases with Ishak fibrosis score improved from F5 to F0. Among 27 patients, 3(11% ) cases achieved hepatitis B surface antigen (HBsAg) loss and 2 (7 % ) achieved HBsAg seroconversion. At the end of follow-up, 19 out of 23 (83% ) hepatitis B e antigen (HBeAg) positive patients obtained HBeAg loss and 9 (39 % ) obtained HBeAg seroconversion. During LAM treatment, 11 patients experienced virological breakthrough or detected documented LAM-related resistance mutation. The viral loads of all patients were below 1 ×103 copy/mL at the end of follow-up after rescued by add-on or switch to another nucleotide analog.Conclusions Long-term LAM therapy can delay the disease progression in CHB patients with severe liver fibrosis, increase HBsAg and HBeAg loss rates, sustain suppression of HBV replication at a low level and even totally reverse the liver fibrosis in some patients. The effect of LAM resistance mutation on disease outcomes would be reduced by rescue therapy.

Objective To explore the relationship among cytokine levels and Toll-like receptor (TLR) 2,4 in hepatitis B virus (HBV) related cirrhosis. Methods Heparin anticoagulated venous blood of 35 randomly selected HBV related cirrhosis and 35 healthy volunteers were collected aseptically. Plasma tumor necrosis factor (TNF)-α concentration was determined using enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) were separated and stained with anti-TLR2,4 monoclonal antibodies, then analysed by flow cytometry. Total RNA was extracted from PBMC and TLR2,4 mRNA expression levels were evaluated by real-time quantitative polymerase chain reaction (PCR) using SYBR Green detection. Means of normal distribution were compared by t test and one factor analysis of variance. The data of abnormal distribution were analyzed using Mann-Whithey U test, Kruskal-Wallis H test and Spearman correlation analysis. Results The plasma concentration of TNF-α in the cirrhotic patients was significantly higher than that in the healthy controls (33.52 ng/L vs 6.07 ng/L, Z=-6.584, P<0. 01), which was parellel with Child-Pugh score. TLR2 positive rate in PBMC from the cirrhotic patients was significantly higher than that from the healthy controls (20.65% vs 12.04%, Z=-4.458, P<0.01), which was positively correlated with plasma TNF-α level (r= 0.448 3, P<0.05), and parellel with Child-Pugh score. Between the cirrhotic and healthy groups, there was no significant difference of TLR4 positive rate in PBMC. The mRNA expression level of TLR2/GAPDH in PBMC from the cirrhotic patients was significantly higher than the controls (0.234 2 vs 0.043 1, Z=-6.83, P<0.01), which was positively correlated with plasma TNF-α level (r=0.411 1, P<0.05), and parellel with Child-Pugh score. Between the two groups, there was no significant difference of TLR4 mRNA expression level in PBMC. Conclusions The expression of TLR2 in PBMC from cirrhotic patients is significantly elevated, which is positively correlated with plasma TNF-α level and the severity of liver disease. The expression of TLR4 in PBMC from cirrhotic patients is unchanged. It suggests that TLR2 but not TLR4, plays an important role in the progression of liver cirrhosis.

Objective To compare the diagnostic values of γ-glutamyl transpeptidase-to-platelet ratio index (GPRI) ,aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (Fib-4) for chronic hepatitis B (CHB) fibrosis and cirrhosis .Methods According to the Metavir score ,262 CHB patients were divided into F0 — F1 group (n= 131) ,F2 — F3 group (n= 102) and F4 group (n = 29 ) . The age , gender , alanine aminotransferase (ALT ) , aspartate aminotransferase (AST ) ,γ-glutamyl transpeptidas (γ-GT ) and platelet count were recorded .GPRI ,APRI ,Fib-4 scores were calculated separately .Statistical analysis was performed by t test ,Kruskal-Wallis H test ,and χ2 test .The correlations between serum models and liver fibrosis stages were analyzed using the Spearman test .Results The scores of GPRI in F0 — F1 group ,F2 — F3 group and F4 group were 0 .39 (0 .21 , 0 .95) ,1 .05 (0 .38 ,2 .39) and 2 .11 (1 .12 ,3 .33) ,respectively .The difference was statistically significant (χ2 = 40 .645 ,P< 0 .01) .APRI scores in the three groups were 0 .49 (0 .32 ,0 .97) ,0 .77 (0 .52 ,1 .52) and 1 .12 (0 .77 ,2 .50) ,respectively .The difference was statistically significant (χ2 = 32 .636 , P < 0 .01) . Fib-4 scores in the three groups were 1 .36 (0 .92 ,2 .05) ,2 .34 (1 .28 ,4 .35) and 3 .86 (3 .03 ,8 .99) , respectively .The difference was statistically significant (χ2 = 48 .943 , P< 0 .01) .Age ,γ-GT ,AST and liver fibrosis were all positively correlated with liver fibrosis (r = 0 .322 ,0 .301 and 0 .199 ,respectively , all P< 0 .05) .Platelet was negatively correlated with liver fibrosis (r = — 0 .455 , P< 0 .05) ,while ALT was not significantly associated with hepatic fibrosis (r= 0 .111 ,P= 0 .073) .GPRI ,APRI and Fib-4 were positively correlated with liver fibrosis (r = 0 .625 ,0 .417 and 0 .399 ,respectively ,all P < 0 .05) .The areas under the operating characteristic curve of GPRI for significant hepatic fibrosis , advanced liver fibrosis and cirrhosis were 0 .818 ,0 .864 and 0 .837 ,respectively .APRI for significant hepatic fibrosis , advanced liver fibrosis and cirrhosis were 0 .694 ,0 .766 and 0 .722 ,respectively ,while Fib-4 were 0 .696 , 0 .770 and 0 .724 ,respectively .The low cutoff values of GPRI for various stages of liver fibrosis were 0 .99 ,1 .04 and 1 .06 ,respectively ,and the sensitivity ,specificity ,positive predictive value (PPV ) and negative predictive value (NPV) were all higher than those of APRI and Fib-4 .The high cutoff values of GPRI for liver fibrosis at each stage were 2 .49 ,3 .69 and 6 .77 , respectively , and the sensitivity , specificity ,PPV and NPV of the diagnosis were all higher than those of APRI and Fib-4 .Conclusion The diagnostic value of GPRI for CHB liver fibrosis is higher than those of APRI and Fib-4 .

The incidence of cancer is closely correlated with age,as 75％of non-small cell lung cancer(NSCLC)patients are aged at least 65 years.The availability of immune checkpoint inhibitors(ICIs)has altered the available NSCLC therapeutic pattern.Limited studies on elderly patients have demonstrated that ICIs as monotherapy provide substantial ben-efits for patients aged 65-75 years,showing no significant difference compared to younger patients.This benefit is also observed in combination with immune-combined chemotherapy or radiotherapy.For individuals older than 75 years,the survival effect was not evident,though.Immune-related adverse events(irAEs)with ICIs alone were similar in incidence across age catego-ries.Immune-combination chemotherapy resulted in a higher incidence of irAEs than chemotherapy alone,and patients ≥75 years of age were more likely to experience higher-grade irAEs.Besides the fact that immunosenescence in older patients influ-ences the immune milieu in a multifaceted manner,which in turn impacts the effectiveness of immunotherapy,the prognosis is also influenced by the Eastern Cooperative Oncology Group performance status(ECOG PS)score,among other factors.For certain individuals aged ≥75 years or in poor physical health,immunotherapy combined with low-intensity chemotherapy has emerged as a viable treatment option.However,there are fewer related studies,so there should be a conscious effort to increase the number of elderly patients enrolled in the trial and a comprehensive assessment to explore individualized treatment op-tions.To provide additional references and guidance for immunotherapy in elderly NSCLC patients and to propose new thera-peutic perspectives in combination with their characteristics,this review aims to summarize and analyze the pertinent studies on the application of programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)inhibitors in these patients.

Background and objective The malignant tumor that has the highest global morbidity and death rate is lung cancer,which primarily affects the elderly.The therapy landscape for non-small cell lung cancer(NSCLC)has trans-formed with the introduction of immune checkpoint inhibitors(ICIs).The purpose of this study was to compare the safety and efficacy of immune monotherapy and immunotheray combined with chemotherapy in patients with advanced NSCLC aged 75 years and above.Methods This study retrospectively analyzed 111 patients with advanced NSCLC who were at least 75 years old and received treatment at the First or Fifth Medical Centers of the People's Liberation Army General Hospital from January 2018 to October 2022.These patients underwent first-line or second-line treatment,with 70 receiving immunotherapy combined with chemotherapy and 41 receiving immunotherapy alone.Propensity score matching(PSM)was used to match the baseline characteristics of the patients,including age,Eastern Cooperative Oncology Group performance status(ECOG PS)score,and the number of treatment lines.The study endpoints included objective response rate(ORR),progression-free survival(PFS),overall survival(OS),and safety assessment.Results The median OS for the immunotherapy combined with chemother-apy group was 27.87 months,and the median PFS was 11.50 months.The median OS for the immune monotherapy group was 34.93 months,and the median PFS was 17.00 months.There were no significant differences in OS(P=0.722)and PFS(P=0.474)between the two groups,but a significant difference was observed in ORR(P=0.025).After PSM matching,each group comprised 27 patients.The median OS for the immunotherapy combined with chemotherapy group was 17.70 months,the median PFS was 8.97 months.The median OS for the immune monotherapy group was 17.87 months,and the median PFS was 11.53 months.No significant differences were observed in OS(P=0.635),PFS(P=0.878)and ORR(P=0.097).In terms of safety,the overall inci-dence of adverse events(AEs)before matching was 62.86％ in the immunotherapy combined with chemotherapy group,which was higher than 41.46％ in the immune monotherapy group(P=0.029),while there was no difference in the incidence of AEs of grade 3 or above between the two groups(P=0.221).After matching,AEs occurred in 17(62.96％ )patients in the immunotherapy combined with chemotherapy group and 13(48.15％ )in the immune monotherapy group.There were no significant differences in the overall incidence of AEs(P=0.273)or the incidence of grade 3 or above(P=0.299)between the two groups.Conclusion Im-munotherapy combined with chemotherapy does not significantly improve OS or PFS in patients with NSCLC aged 75 years and above when compared to immunotherapy alone,and this conclusion was further validated by the analysis after PSM.The safety assessment suggests that before matching,the incidence of AEs of any grade in the immunotherapy combined with chemotherapy group was higher.Still,the two groups had no difference in the incidence of AEs of grade 3 or above.Following matching,the tol-erability of the treatment was similar in both groups.According to the safety assessment,the unique circumstances and course of treatment for geriatric patients with advanced NSCLC should be considered.