BACKGROUND: Although pulmonary diffusion capacity (PDC) has been substantially proved in a declining tendency in age-dependent manner, the effects of such related factors as body mass,sex and height within an age range on pulmonary membrane conductance (Dm) and capillary blood volume(CBV),as well as the correlation of Dm with CBV and PDC deserve further investigation.OBJECTIVE:To study the correlation of Dm and CBV with PDC,age,body mass, height and sex in normaladults.DESIGN: With healthy adults as subjects, multiple factor linear correlation and regression analysis was used to elicit correlation coefficient and regression equation while F-test and Q-test were used for comparing the differences between groups.PARTICIPANTS:We randomly selected 100 healthy adults,50 males and 50 females, who came to the clinic of the General Hospital of Chinese PLA for routine physical examination between April and October 1997.The 100 volunteers were divided into five groups according to their age:20-29, 30-39, 40-49, 50-59 and 60-69 years old groups with 20 in each group, half males and half females.METHODS: PDC and Dm of the healthy adults were examined with Sensormedics 2200 pulmonary function detector. CBV was calculated with the following formula (1/PDC=I/ Dm +1/θCBV, θrefers to the combined velocity of CO with Hb,which was in inverse proportion to the inhaled partial oxygen pressure,Dm and CBV were unaffected by θ).Multiple factor linear correlation and progressive regression analysis was used to elicit correlation coefficient of PDC, Dm and CBV. Meanwhile, regression equation was used to reveal the correlation of age,body mass and height with pulmonary functions.MAIN OUTCOME MEASURES: Correlation ofDm and CBV with PDC and age, body mass, height and sex in normal adults.RESULTS:Data of the 100 healthy adults were processed according to the objective and statistically analyzed.① PDC and Dm were proved to decline in age-dependent manner from the onset of 40 years old in the 100 healthy adults (P＜ 0.05), and CBV also declined after 50 years old (P ＜ 0.05).②Relationship between women's age and pulmonary function:Age was proved to have significant negative correlation with PDC,Dm and CBV (r= -0.646 0 to -0.814 6, P＜ 0.01).By contrast,PDC was found to be positively correlated with Dm,CBV and alveolus ventilation volume (AVV) (r=0.949 7, 0.740 0, 0.735 6, P＜ 0.01), and AVV was found to be positively correlated with PDC, Dm and CBV (r=0.482 1-0.740 6,P＜ 0.01).③ Relationship between men's age and pulmonary function:Age had significant negative correlation with PDC, Dm and CBV (r=-0.712 to -0.830 5, P＜ 0.01). However, PDC was found to be moderately or highly positively correlated with Dm,CBV and AVV(r=0.585 2 to 0.946 0, P＜ 0.01), and AVV had moderately positive correlation with PDC, Dm and CBV (r=0.431 3-0.585 2, P＜ 0.01). ④ Regression analysis revealed that age and height were the main variables of the predicting equation of PDC,Dm and CBV.Body mass could not enter regression equation in females,and it was only proved to be correlated with PDC and CBV in males with the regression coefficient of 0.009 4 and 0.654 3, respectively.CONCLUSION:① PDC and Dm begin to decline from the onset of 40 years old in healthy adults (P＜ 0.05),and CBV declines after 50 years old.② PDC, Dm and CBV of healthy adults are proved to decline in age-dependent manner. ③ PDC increases with the increment of Dm and CBV. ④ Age and/or height are the main variables in the regression equation of PDC, Dm and CBV, but body mass is not the key predictor for Dm and CBV.

Objective:To prepare the production of TIGIT-Fc fusion protein using H22 cells stably integrated the gene by lentivirus vector , and to explore the immunoregulatory effect on macrophages by TIGIT-Fc.Methods: TIGIT-Fc fusion gene were constructed by molecular cloning.The fusion gene was then subcloned to plasmids contained the secretion signaling peptide .The secrected TIGIT-Fc fusion gene was inserted into the lentivirus backbone vector.The purified lentivirus vector was the used to infect the murine H22 cell line.TIGIT-Fc protein was purified by protein A column from the ascites of H 22-injected C57BL/6 mice.Macrophages stimulated by lipopolysaccharide ( LPS ) was challenged to TIGIT-Fc treatment or control.Cytokine levels was then detected by ELISA.Results: TIGIT-Fc protein was purified from the ascites of H 22-injected mice.PVR was upregulated in LPS-treated macrophages.IL-10 level was upregulated in TIGIT-Fc treated macrophages.Conclusion: TIGIT-Fc promotes the mature macrophages to secrete anti-inflammatory cytokine IL-10.

Objective To investigate the expression levels of basic leucine zipper and W2 domain 2 (BZW2) and isovaleryl-CoA dehydrogenase (IVD) in hepatocellular carcinoma (HCC) and evaluate their effect on clinical prognosis of liver transplant recipients with HCC. Methods Pathological specimens and clinical data of 87 liver transplant recipients with HCC were collected and retrospectively analyzed. The recurrence and metastasis of HCC after liver transplantation were assessed. Immunohistochemical staining was used to detect the expression levels of BZW2 and IVD. The relationship between BZW2, IVD and clinicopathological parameters of HCC and their effect on postoperative recurrence and clinical prognosis of the recipients was analyzed. Results Among 87 recipients, 31 cases recurred with a recurrence rate of 36%. HCC recurred at postoperative 2-49 months and the median recurrence time was postoperative 7 months. Immunohistochemical staining demonstrated that the positive expression rate of BZW2 in the HCC tissues was significantly higher than that in normal liver tissues (76% vs. 30%), and the positive expression rate of IVD was significantly lower compared with that in normal liver tissues (51% vs. 69%) (both P < 0.01). BZW2 expression was significantly correlated with tumor diameter and tumor capsule (both P < 0.05), whereas IVD expression was significantly associated with tumor diameter, alpha-fetoprotein (AFP) level, tumor, node and metastasis (TNM) staging and whether vascular invasion was found or not (all P < 0.05). In the high BZW2 expression group, the cumulative recurrence rate of HCC was significantly higher and the cumulative survival rate was significantly lower than those in the low BZW2 expression group. In the low IVD expression group, the cumulative recurrence rate of HCC was significantly higher and the cumulative survival rate was significantly lower compared with those in the high IVD expression group (all P < 0.05). Conclusions The expression level of BZW2 protein is up-regulated, whereas that of IVD protein is down-regulated in the HCC tissues. Moreover, the cumulative recurrence rate of HCC is relatively high and the cumulative survival rate is relatively low in liver transplant recipients with high BZW2 expression and low IVD expression.

Objective To evaluate the economic value of using glucagon-like peptide-1 receptor agonist(GLP-1RA)in combination with metformin for the treatment of type 2 diabetes mellitus(T2DM).Methods Based on 7 randomized controlled clinical trials(RCTs),Markov model was built to simulate the dynamic changes of metformin alone or combined with GLP-1RA in the treatment of T2DM patients without or with complications and death from the perspective of China's health system.Quality-adjusted life years(QALYs)was used as a health output indicator and 3 times China's per capita gross domestic product(GDP)in 2023 was set as the willingness-to-pay(WTP)threshold.The cycle was at the rate of 1 year and a total of 20 years cohort simulation in Markov model was applied to obtain long-term cost and effect of each treatment strategy.The incremental cost-utility ratio(ICUR)was analyzed as the primary evaluation indicator and the sensitivity of cost,utility and discount was performed to test the stability of the results.Results Compared with metformin alone,the ICUR of GLP-1RA including liraglutide,dulaglutide,exenatide,loxenatide,semaglutide combined with metformin were all below the WTP threshold,and the increased cost was acceptable.Extending the simulation time to 30 years or 50 years had no effect on results.The results of probability sensitivity analysis showed that the cost effect of semaglutide 0.5 mg combined with metformin had the highest probability of a cost-utility advantage of 99.7％among all the treatment strategies when WTP threshold was 3 times China's per capita GDP in 2023(268 074 yuan).Conclusion GLP-1RA,including liraglutide,dulaglutide,exenatide,lixisenatide,and semaglutide,at the regular recommended dose combined with metformin,would present higher cost-utility compared to metformin monotherapy.

Objective To evaluate the efficacy and safety of glucagon-like peptide 1 receptor agonists(GLP-1RA)in type 2 diabetes mellitus(T2DM)patients with overweight or obese.Methods PubMed,Embase,Cochrane Library,Ovid,ClinicalTrial.gov,SinoMed,CNKI,WanFang Data and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on the efficacy of GLP-1RA in the treatment of T2DM patients with overweight or obese from January 1,2005 to November 1,2023.Two researchers independently screened the literature,extracted data and evaluated the risk of bias of the included studies.R software was then used for meta-analysis.The level of evidence was assessed by using the GRADE system.Results A total of 71 RCTs were included,including 29 476 patients.The results of Meta-analysis showed that compared with other hypoglycemic drugs,GLP-1RA showed superior effects in improving HbAlc status(WMD=-0.55,95％CI-0.65 to-0.45,P＜0.001)and weight loss(WMD=-2.61,95％CI-3.25 to-1.97,P＜0.001),while the effect on fasting plasm glucose was time-dependent(within 16 weeks:WMD=0.25,95％CI-0.17 to 0.66,P=0.250;16 to 52 weeks:WMD=-0.06,95％CI-0.32 to 0.20,P=0.650;over 52 to 104 weeks:WMD=-1.67,95％CI-1.91 to-1.43,P＜0.001).In terms of safety,the incidence of GLP-1RA's adverse reactions was higher than other hypoglycemic drugs(RR=1.11,95％CI 1.07 to 1.15,P＜0.001);the incidence of hypoglycemia was lower with GLP-1RA than with insulin(RR=0.58,95％CI 0.48 to 0.71,P＜0.001)and similar to oral hypoglycemic drugs(RR=0.83,95％CI 0.58 to 1.19,P=0.310).According to the GRADE assessment,only the certainty of the evidence for the results of the incidence of hypoglycemia was moderate,and the certainty of the evidence for the other results was low.Conclusion Current evidence shows that for T2DM patients with overweight or obese,GLP-1RA especially semaglutide,was more effective in lowering blood glucose,controlling body weight and reducing the occurrence of hypoglycemia than placebo,insulin and oral hypoglycemic drugs.

Objective    To investigate whether metformin has protective effect on myocardial injury in patients with coronavirus disease 2019 (COVID-19) combined with coronary heart diseases and diabetes. Methods    COVID-19 patients with coronary heart disease and diabetes who were admitted to Tongji Hospital from January 18 to April 25 in 2020 were enrolled. They were divided into a metformin group and a none-metformin group according to whether the metformin was used. The demographic characteristics, clinical symptoms, laboratory parameters, treatment and clinical outcomes of the two groups were analyzed retrospectively. Results    There were 29 patients in the metformin group, 3 patients (12.0%, 3/25) suffered myocardial injury and 1 (3.4%) died of acute respiratory failure complicated by septic shock; 67 patients were in the non-metformin group and 24 (37.5%, 24/64) had myocardial injury but 15 died in hospital among whom 1 died of septic shock complicated by disseminated intravascular coagulation, 1 acute respiratory failure complicated by possible cerebral hemorrhage, 2 acute respiratory failure, 1 fulminant myocarditis, 3 acute myocardial infarction and 7 cardiac arrest. The incidence of myocardial injury (12.0% vs. 37.5%, P=0.019), hospital mortality (3.4% vs. 22.4%, P=0.034) and mortality of cardiovascular events (0.0% vs. 16.4%, P=0.049) in the metformin group were significantly lower than those in the non-metformin group. Multivariate analysis showed that the use of insulins (OR=11.235, P=0.003) was an influencing factor for in-hospital mortality of patients. The use of metformin (OR=0.154, P=0.013) was positively correlated with the myocardial injury. Conclusion    When patients with coronary heart disease and diabetes are infected with COVID-19, metformin can effectively reduce myocardial damage and has a certain effect on reducing hospital mortality. Combined with clinical considerations, it is worthy of popularization.