The relationship between the ratio and dynamic changes of lympho-cytes/monocytes and the efficacy of PD-1 inhibitors in the treatment of advanced non-small cell lung cancer / 中国临床药理学与治疗学

AIM:To investigate the relationship between the dynamic changes of Lymphocyte-to-monocytes ratios(LMR)before PD-1 inhibitor treat-ment and the efficacy and prognosis of PD-1 inhibi-tor treatment in patients with advanced non-small cell lung cancer(NSCLC).METHODS:The clinical case data of 83 patients with advanced non-small cell lung cancer admitted to the Cancer Hospital of Wuhu Second People's Hospital from June 2019 to July 2022 were retrospectively analyzed.The rou-tine blood LMR values of all patients before and af-ter treatment were collected,the cut-off value was calculated according to the ROC curve,and the LMR was divided into two groups:high and low be-fore treatment and after treatment.The differenc-es of ORR,DCR,PFS and OS among the patients in each group were analyzed and compared,and the value of LMR value and dynamic changes after treatment on the efficacy and prognosis of patients with PD-1 inhibitors in the treatment of NSCLC pa-tients was analyzed.RESULTS:According to the ROC curve,the critical value of LMR was 1.8,and the LMR was divided into the low LMR group at baseline(LMRB/S<1.8),the high LMR group at base-line(LMRB/S≥1.8)and the low LMR group after treatment(LMRafter<1.8)and the high LMR group af-ter treatment(LMRafter≥1.8).The ORR and DCR after immunotherapy in the high LMRB/S group were high-er than those in the low LMRB/S group(P=0.037;P= 0.0025).Among the patients with low LMRB/S be-fore treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group after treatment(P=0.005).Among the patients with high LMR before treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group(P=0.034).Kaplan-Meier analysis showed that PFS and OS were longer in the high LMRB/S group than in the low LMRB/S group before treat-ment.In the low LMRB/S group before treatment,PFS and OS were longer in patients with LMRafter≥1.8 than those with LMRafter<1.8(P=0.047;P=0.007).Multivariate Cox regression model analysis showed that high LMRB/S value before treatment was an in-dependent risk factor for PFS and OS in NSCLC pa-tients(P=0.006;P=0.033).CONCLUSION:High LMR value of patients before immunotherapy may im-prove the efficacy of PD-1 inhibitors,improve the prognosis of patients,and prolong the survival time.Moreover,the increase of LMR value after treatment may increase the efficacy of patients with low LMR before treatment and improve the prognosis of patients.

The predictive value of combined detection of serum ANGPTL8 and VCAM-1 levels for cerebral vasospasm after intracranial aneurysm embolization / 临床外科杂志

Objective The combined detection of serum angiopoietin-like protein 8(ANGPTL8)and Vascular cell adhesion molecule-1(VCAM-1)levels was analyzed for the predictive value of cerebral vasospasm(CVS)after intracranial aneurysm embolization.Methods A total of 196 patients who underwent intracranial aneurysm embolization in our hospital from March 2019-March 2022 were selected as the study subjects,99 patients with CVS were in the CVS group,and 97 patients without CVS were in the non CVS group.Serum ANGPTL8 and VCAM-1 levels were detected by ELISA;the correlation between serum ANGPTL8 and VCAM-1 levels was analyzed by Pearson method,Logistic regression was used to analyze the influencing factors of CVS in patients undergoing intracranial aneurysm embolization;ROC curve was used to analyze the serum levels of ANGPTL8 and VCAM-1 to predict the cutoff value of CVS in patients undergoing intracranial aneurysm embolization;four grid table method was used to analyze the predictive value of ANGPTL8,VCAM-1 and their combination on the occurrence of CVS in patients undergoing intracranial aneurysm embolization.Results The differences between CVS and non-CVS groups were statistically significant in hypertension,Hunt-Hess grade,and Glasgow coma(GCS)scores(P＜0.05).The serum ANGPTL8 and VCAM-1 levels in the CVS group were significantly higher than those in the non-CVS group(P＜0.05).There was a positive correlation between serum ANGPTL8 and VCAM-1(r=0.468,P＜0.05).Multivariate analysis showed that high level of ANGPTL8(OR=3.652,95％CI:1.434-9.302),high level of VCAM-1(OR=2.619,95％CI:1.212-5.658),Hunt Hess grade Ⅲ-Ⅳ(OR=1.927,95％CI:1.104-3.362),GCS score of 3-8(OR=2.813,95％CI:1.257-6.295)were independent risk factors for CVS in patients undergoing intracranial aneurysm embolization.The AUC of serum ANGPTL8 level in predicting CVS in patients undergoing intracranial aneurysm embolization was 0.844,and the cut-off value was 189.233 U/L;the AUC of serum VCAM-1 level in predicting CVS in patients undergoing intracranial aneurysm embolization was 0.795,and the cutoff value was 17.984 mg/L.The accuracy,sensitivity and specificity of the combined prediction for CVS were 89.81％,93.94％and 85.57％,respectively,which were obviously higher than those of the single prediction.Conclusion The serum levels of ANGPTL8 and VCAM-1 in CVS group are obviously higher than those in non CVS group.The combination of the two has a high predictive value for CVS after intracranial aneurysm embolization.

S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

Analysis of factors influencing the frequency of health check-up and health check-up behavior in healthy population / 中华行为医学与脑科学杂志

Objective:To analyze the relevant factors affecting the frequency and behavior of health check-up among the population of medical examinees.Methods:From January to June 2022, 491 health examinees who had health check-ups at the Second Affiliated Hospital of Shandong First Medical University were included.Basic information of the check-up population and their needs for check-up services (form of check-up, content of check-up, cost of check-up, form of feedback on check-up results, and needs for check-up providers) were obtained based on a questionnaire survey.According to the frequency of previous medical check-up, the examinees were divided into never-check-up group (frequency of check-up was 0, n=45), the irregular check-up group (the interval between two physical examinations >1 year, n=49) and the regular check-up group (frequency of check-up=1 year, n=347). The frequency of previous medical check-up was used as the dependent variable, and the age, gender, education level, income, form of medical check-up and cost of medical check-up were used as independent variables to analyse the relevant factors affecting the frequency of their medical check-ups.The above count data were analyzed by one-way analysis using chi-square test, and the count data with statistically significant differences in one-way analysis were analyzed by binary logistic regression.The statistical software was SPSS 21.0. Results:The study included 491 medical examinees, of which 9.16%(45/491) were in the never-check-up group, 20.16%(99/491) in the irregular check-up group and 70.68%(347/491) in the regular check-up group. The impact of demography characteristics of physical examinees on the frequency of health check-up, and there were statistically significant differences in the frequency of health check-up in terms of gender, job, education, and income ( χ2=21.826, 157.113, 104.764, 45.486, all P<0.05). The understanding of health check-up and the attention paid to one's own health were influencing factors that affected the frequency of health check-up. There were statistically significant differences in the frequency of health check-up in necessity of health check-up, attention to one's own health, health check-up forms, health check-up institutions, health check-up price and health check-up contents ( χ2=9.277, 25.863188.239, 59.115, 39.250, 28.314, all P<0.05). Logistic regression analysis showed gender, job type, monthly income, necessity of health check-up, concerns for items of check-up, forms and institutions of check-up were influencing factor of health check-up frequency(all P<0.05). Conclusion:The health check-up behavior of the population and the frequency of regular medical check-ups are influenced by the factors such as gender, education, occupation, income, form of medical check-up, price of medical check-up, choice of medical check-up institution and the degree of concern for one’s own health. The popularisation of health check-ups for special groups such as men, low-income people, low literacy and insufficient awareness of the importance of one’s own health will help improve the overall health awareness of the population.

Comparative study on the efficacy of transumbilical single port and three port laparoscopic cholecystectomy in the treatment of calculous cholecystitis / 国际外科学杂志

Objective:To explore the efficacy of transumbilical single-port and three-port laparoscopic cholecystectomy (LC) in the treatment of calculous cholecystitis and its influence on immunological indicators and recovery of gastrointestinal function.Methods:One hundred and twenty patients with calculous cholecystitis who were treated in Suzhou Municipal Hospital of Anhui Province from June 2018 to June 2020 were prospectively selected as the research subjects, and the patients were randomly divided into single-hole group and three-hole group by random number table method. Group of 60 cases. The single port group used the transumbilical single port method LC, and the three port group used the transumbilical three port method LC. Compare the 24-hour pain VAS scores and the use of analgesics of the two groups of patients; compare the surgical indicators of the two groups of patients; compare the immunological indicators of the two groups before and after treatment; compare the two groups of patients The recovery of gastrointestinal function after operation; the occurrence of postoperative complications between the two groups was compared.Results:There was no statistically significant difference in intraoperative blood loss, hospitalization expenses, preoperative IgG, IgA, IgM levels, and postoperative complications between the two groups of patients ( P>0.05). The two groups of patients had significantly lower levels of IgG, IgA, and IgM after treatment ( P<0.05). In the single hole group, the pain VAS score, the use rate of analgesics, the time of hospitalization, the time of anal exhaust, the time of bowel sound returning to normal and the time of defecation were (4.65±0.61) points, 11.67%(7/60), (2.52±0.47) d, (13.65±3.72) h, (11.64±3.25) h and (20.31±4.12) h, respectively. The three-hole group were (6.87±0.58) points, 23.33% (14/60), (4.58±0.37) d, (17.36±4.12) h, (15.47±4.12) h and (26.48±4.25) h, respectively. It was significantly lower in the single-hole group than in the three-hole group ( P<0.05). In the single hole group, the operation time, abdominal wall cosmetology score and the levels of IgG, IgA, IgM after treatment were (76.36±4.58) min, (4.72±0.13) points, (1 108.48±42.65) mg/dL, (208.12±10.86) mg/dL, (154.65±8.72) mg/dL, respectively. The three-hole group were (51.37±5.25) min, (3.25±0.35) mg/dL, (1 072.39±28.42) mg/dL, (193.08±10.35) mg/dL and (145.28±8.42) mg/dL, respectively, and those in the single-hole group were significantly higher than those in the three-hole group ( P<0.05). Conclusion:Under the premise of proficiency in surgical operation techniques, the single-port method reduces pain, reduces the use of analgesics, has less impact on immunological indicators, recovers gastrointestinal function faster, and has better postoperative abdominal wall cosmetic effects.

The inhibitory effect of Withaferin A on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism / 中国医师杂志

Objective To investigate the inhibitory effect of Withaferin A ( WFA) on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism of its antitumoral effect. Methods For in vivo model, anti-tumor efficacy of Withaferin A was evaluated in nude mice mod-els of human liver cancer orthotopic xenograft. The nude mice were randomly divided into model group, Sunitinib group,and Withaferin A groups [6, 3 mg/(kg·d)]. All mice were given intraperitoneal injec-tion for 14 days. Tumor volume and tumor weight were observed. Antiangiogenic effects were assessed in vi-vo by the tumor inhibition rate and microvessel density. Quantitative polymerase chain reaction ( QPCR) as-say was used to detect the mRNA expression of vascular endothelial growth factor ( VEGF) , basic fibroblast growth factor (bFGF), angiopoietin-2 (Ang-2), vascular endothelial growth factor receptor 2 (VEGFR2) from tumor tissues. For in vitro experiments, the cell count kit 8 ( CCK8 ) assay was used to detect the effect of Withaferin A on HepG2 cells proliferation. QPCR assay and enzyme-linked immunosorbent assay ( ELISA) were used to detect the mRNA expression of VEGF. Results Compared to the model group, the high-dose Withaferin A group and the Sunitinib group had a significantly lower tumor weight (P<0. 05). The tumor inhibition rate was 42. 69％ in the high-dose Withaferin A group, 20. 22％ in the low-dose With-aferin A group, and 49. 43％ in the Sunitinib group. The growth of HepG2 cells was significantly inhibited by different concentrations of Withaferin A,and the 50％ concentration of inhibition ( IC50 ) of Withaferin A were (2. 64 ± 0. 18)μmol/L at 24 h. Withaferin A (6,3 μmol/L) could inhibit the protein and mRNA ex-pression of VEGF ( P<0. 05 ) . Conclusions Withaferin A significantly reduces the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice via antiangiogenic effect. Downregulation of the protein and mRNA expression of VEGF by WFA may be one mechanism of its anti-liver cancer effect.

Role of PARP-2 in cardiac hypertrophy in rats / 中国病理生理杂志

AIM:To investigate the expression of poly(ADP-ribose) polymerase-2 (PARP-2) during rat car-diac hypertrophy in vitro and in vivo, and to explore the effects of PARP-2 on the cardiac hypertrophy.METHODS:Ab-dominal aortic coarctation ( AAC) was performed to establish a model of pressure overload-induced cardiac hypertrophy in SD rats.The expression of PARP-2 at mRNA and protein levels in the myocardium was determined by real-time PCR and Western blot.The hypertrophy model of the cardiomyocytes was induced by treating the cells with angiotensinⅡ( AngⅡ) . PARP-2 was knocked down by siRNAs in neonatal rat cardiomyocytes and the cardiomyocyte hypertrophy was evaluated by measuring the mRNA levels of ANF, BNP, and β-MHC and the cellular surface area.RESULTS: The expression of PARP-2 at mRNA and protein levels was both increased in the AAC rats as compared with those in the sham animals.The expression of PARP-2 at mRNA and protein levels was also increased in a time-and concentration-dependent manner in AngⅡ-induced hypertrophy model of the cardiomyocytes.In the neonatal rat cardiomyocytes, knockdown of PARP-2 ex-pression by siRNA attenuated AngⅡ-induced cardiac hypertrophy of the cardiomyocytes, indicating that endogenous PARP-2 played a positive regulatory role in cardiac hypertrophy.CONCLUSION:The mRNA and protein levels of PARP-2 in-crease in the in vitro and in vivo models of cardiac hypertrophy.Knockdown of PARP-2 protects cardiomyocytes from hyper-trophy.

The changes of serum tumor markers levels during anti-tuberculosis treatment in active tuberculosis patients / 中华传染病杂志

Objective To evaluate the changes of serum tumor markers of carbohydrate antigen 125 (CA125),carbohydrate antigen 199 (CA199),carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) during anti-tuberculosis treatment in patients with active pulmonary tuberculosis and tuberculous pleurisy.Methods This research was a prospective study.Sixty-three patients with active pulmonary tuberculosis and 24 patients with tuberculous pleurisy underwent blood samplings before treatment,2 and 6 months after treatment.Centaur XP chemiluminescent immunoassay was used to test serum levels of CA125,CA199,CEA and SCC.Thirty healthy subjects were included as controls.Student t-test was used to compare continuous variables,and chi-square test or Fisher exact test was used to compare categorical variables.Serial changes of serum tumor markers levels pre-and post-treatment were analyzed by repeated measures analysis of variance.Binary Logistic regression model was used for multivariate analysis.Results The mean serum CA125 level of the 63 patients with active pulmonary tuberculosis pre-treatment was (64.4± 30.4) U/mL,which was significantly higher than that of healthy controls ([12.7±5.5] U/mL,t=11.98,P＜0.01).The mean serum CA125 level decreased to (16.9±6.1) U/mL after 6 months standardized treatment,which was significantly lower than that before treatment (t=12.74,P＜0.01).While compared with healthy controls,the serum level of CA125 in patients who had completed the standardized treatment was not significantly different (t =0.94,P =0.348).When compared with the healthy controls,serum CA199,CEA,SCC levels in patients with active pulmonary tuberculosis before and after treatment showed no statistically significant difference (P＞ 0.05).Univariate analysis and multivariate analysis by Logistic regression analysis showed that bilateral pulmonary tuberculosis (x2 =7.746,P=0.006; OR=6.99,95％CI:1.73-28.22) and cavity pulmonary tuberculosis (x2 =6.254,P=0.012; OR=7.64,95％CI:1.64-35.35) were associated with increased serum CA125 level.The mean serum CA125 level of 24 cases of tuberculous pleurisy pre-treatment was (81.2 ± 37.6) U/mL,which was both significantly higher than that of patients with active pulmonary tuberculosis (t=2.153,P=0.034) and that of healthy controls (t=12.05,P＜0.01).Similarly,CA125 levels sharply decreased to (15.5 ± 7.3) U/mL after 6 months standardized treatment,which was not statistically significant compared with the control group (t=0.450,P=0.652).However,CA199,CEA and SCC levels in tuberculous pleurisy pre-and post-treatment were all not statistically different from those of healthy controls (all P＞0.05).Conclusion Serum CA125 can be used as a marker for assessing the disease progression and therapeutic efficacy for patients with active pulmonary tuberculosis and tuberculous pleurisy.