Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

OBJECTIVE To compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system. METHODS Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted. RESULTS The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ￥125143.88/quality adjusted life year(QALY) and ￥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ￥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical. CONCLUSION Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.

ObjectiveTo explore the antioxidant and anti-human cervical cancer HeLa cell effect and mechanisms of Andrographis paniculata polysaccharide （APP）. MethodCell function assays were conducted to assess the effects of APP （400， 450， 500 mg·L^-1） on the proliferation， migration， and invasion of HeLa cells using the cell counting kit-8 （CCK-8） assay， scratch assay， and Transwell assay. Molecular mechanism experiments were conducted to detect the effects of APP on HeLa cell apoptosis and cell cycle-related mRNA and protein expression using flow cytometry， real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）， and Western blot analysis. The antioxidant activity of APP was tested using DPPH⁺， OH^-， and reducing power assays. ResultCompared with the blank group， APP （400， 450， 500 mg·L^-1） significantly inhibited the migration， proliferation， and invasion abilities of HeLa cells in a time- and dose-dependent manner （P<0.05， P<0.01）. Flow cytometry with propidium iodide （PI） single staining was used to detect cell cycle. The results showed that compared with the blank group， the proportion of HeLa cells in the G₂/M phase increased after 48 hours of treatment with APP （400， 450， 500 mg·L^-1）， indicating that APP can arrest HeLa cells in the G₂/M phase. Flow cytometry with fluorescein isothiocyanate （Annexin V-FITC）/PI apoptosis kit was used to detect cell apoptosis. Compared with the blank group， the proportion of early and late apoptotic HeLa cells increased in a dose-dependent manner after 48 hours of APP （400， 450， 500 mg·L^-1） treatment （P<0.05， P<0.01）， indicating that APP promotes HeLa cell apoptosis. The results of Real-time PCR and Western blot assay showed that compared with the blank group， after 48 hours of APP （400， 450， 500 mg·L^-1） treatment resulted in decreased mRNA and protein expression of cell cycle-dependent kinase-1 （CDK-1）， Cyclin B₁， and B-cell lymphoma-2 （Bcl-2）， and increased mRNA and protein expression of cysteine aspartate protease （Caspase）-3， Caspase-8， Caspase-9， and Bcl-2-associated X protein （Bax） （P<0.05， P<0.01）. These findings were consistent with the flow cytometry results and showed a dose-dependent effect. In vitro antioxidant tests demonstrated that different concentrations of APP （50-1 000 mg·L^-1） were able to scavenge DPPH⁺ and OH^- radicals， indicating certain antioxidant activity. ConclusionAPP possesses antioxidant activity and can inhibit the viability of HeLa cells while promoting their apoptosis.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Background::Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.Methods::We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.Results::A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility ( n = 3304, 43.1%) and a lack of trust in primary healthcare institutions ( n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half ( n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs. Conclusions::Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

Objective:To screen ferroptosis genes related to prognosis of malignant pleural mesothelioma(MPM),explore the relationship between ferroptosis and tumor immune microenvironment and provide a new perspective for targeting and immunotherapy of MPM patients.Methods:The differentially expressed genes(DEGs)in MPM tumor group and normal group were analyzed in GEO database;intersection of DEGs and ferroptosis genes to obtain differentially expressed ferroptosis-related genes(DE-FRGs).GO,KEGG function enrichment and protein protein interaction(PPI)were used to identify the signal pathways mainly involved by DE-FRGs.The prognosis related ferroptosis genes were identified by univariate COX analysis.LASSO regression analysis was used to screen the best DE-FRGs for establishing the risk prediction model,and a risk prognosis model based on the best DE-FRGs was estab-lished by multivariate cox analysis to verify the prediction effect of the model.Finally,CIBERSORT and other algorithms were used to analyze tumor immune cell infiltration and evaluate immune microenvironment.Results:Twenty-four prognosis related DE-FRGs were screened,which were mainly concentrated in ferroptosis,transcriptional regulation and response to inorganic substances.A MPM risk prediction model based on five ferroptosis-related genes(ALDH3A2,CAV1,HRAS,CDCA3 and RRM2)was established and vali-dated.In the model,the proportion of CD8+T cells and macrophages in high-risk group were higher,while the proportion of B lympho-cytes was lower.In addition,PD-1,CTLA-4 and their ligands at immune checkpoint had higher expression status in high-risk group.Conclusion:The MPM risk prediction model based on five ferroptosis-related genes is established,and the immune status in the model is clarified.It provides a certain research basis for targeting and immunotherapy of MPM.The predictive ability of this model in MPM needs to be further verified in clinical practice to better predict disease stratification and treatment management.

Objective:To explore the relationship between metabolic score for insulin resistance (METS-IR) and chronic kidney disease (CKD) and albuminuria in the Chinese population.Methods:This cross-sectional study was conducted from January to December 2018 among residents aged 20 to 70 years in ten regions of eight provinces in China; all residents had lived in their region for more than 5 years. Various parameters were measured, included fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin (HbA 1c), blood lipids, renal function, urinary albumin/creatinine ratio (UACR), etc. Data of 5 060 subjects meeting the criteria were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml·min -1·1.73 m -2 or UACR≥30 mg/g. Albuminuria was defined as UACR≥30 mg/g. METS-IR was calculated and categorized into quartiles: Q1, METS-IR≤32.19; Q2, METS-IR 32.20-37.10; Q3, METS-IR 37.11-42.58; and Q4, METS-IR>42.58. The correlation between METS-IR and CKD and albuminuria was analyzed by binary logistic regression, and subgroup analyses were performed. Results:There were 1 266, 1 266, 1 265, and 1 263 participants included in Q1-Q4 groups, respectively. With the increase of METS-IR quartile, various parameters increased, including age, fasting blood glucose, HbA 1c, triglycerides, serum uric acid, waist circumference, body mass index, and systolic and diastolic blood pressure, and the proportion of males also increased (all P<0.05). The proportion of patients with CKD and albuminuria increased significantly with the increase in interquartile range (Q) of METS-IR (all P<0.05). Logistic regression analysis showed that for every 1-unit increment of METS-IR, the risk of CKD and albuminuria were both increased by 2% [for both: odds ratio ( OR)=1.02, 95% confidence interval ( CI) 1.01-1.03]. Compared with the lowest METS-IR group (Q1), the ORs for CKD and albuminuria in the highest METS-IR group (Q4) were 1.57 (95% CI 1.17-2.10) and 1.46 (95% CI 1.09-1.96), respectively. In the subgroup analyses, increased METS-IR was significantly associated with CKD and albuminuria among women (CKD: OR=1.62, 95% CI 1.14-2.31; albuminuria: OR=1.53, 95% CI 1.07-2.18), individuals with HbA 1c<7% ( OR=1.64, 95% CI 1.21-2.23; OR=1.55, 95% CI 1.14-2.11), individuals with eGFR≥90 ml·min -1·1.73 m -2 ( OR=1.78, 95% CI 1.27-2.49; OR=1.80, 95% CI 1.28-2.53), and the Chinese Han population ( OR=1.56, 95% CI 1.13-2.17; OR=1.41, 95% CI 1.01-1.96). Conclusions:METS-IR is significantly associated with CKD and albuminuria in a Chinese population. Furthermore, the higher the METS-IR, the higher the risk of CKD and albuminuria.

Objective:To assess the relationship between appendicular skeletal muscle mass (ASM) and ankle brachial index (ABI) among patients with type 2 diabetes.Methods:In this cross-sectional study, from July 2018 to March 2019, a total of 278 patients with type 2 diabetes treated in Zhongda Hospital were enrolled in this study, and there were 158 males and 120 females. General information and clinical biochemical parameters and ABI in the patients were collected. The appendicular muscle mass was quantitatively measured with body composition analyzer to achieve ASM. And the appendicular skeletal muscle mass index (ASMI), skeletal muscle index (SMI), and appendicular skeletal muscle mass/body mass index (ASM/BMI) were calculated respectively. Correlation analysis and multiple linear regression analyses with different adjustment models were conducted to analyze the correlation between ABI and above-mentioned indexes.Results:The Pearson correlation analysis showed that ABI had significant positive correlation with ASM, ASMI and ASM/BMI ( r=0.14, 0.13, 0.13, all P<0.05), but a marginal relation with SMI ( r=0.116, P=0.053). Multiple linear regression analysis suggested that ASMI ( β=0.053, 95% CI: 0.006-0.101, P=0.027) and AMI/ABI ( β=0.347, 95% CI: 0.040-0.654, P=0.027) were significantly related to ABI. Conclusion:ASM is positively associated with ABI in patients with type 2 diabetes.

Objective:To explore the change in cerebral blood flow when healthy subjects swallow hot and ice water, and to verify the sensitivity of functional near-infrared spectroscopy (fNIRS) in identifying liquid temperatures while swallowing as a basis for applying it in diagnosis and intervention.Methods:Sixteen healthy subjects swallowed hot and ice water in randomized order while the process was recorded using fNIRS. The activation at rest and when swallowing hot and ice water was compared pairwise.Results:Compared with the resting state, 19 channels were activated during the swallowing of the hot and ice water. The common activated areas were S1, M1, PMC, SMA, Wernicke′s area, the somatosensory association cortex, the visual association cortex and the frontal eye field. However, the dorsal lateral prefrontal cortex was activated only when swallowing hot water, and the subcentral area was activated only when swallowing ice water. The SMA and PMC were significantly more activated when swallowing hot water than ice water.Conclusions:Multiple brain regions are activated and participate in regulating swallowing. The PMC and SMA areas can distinguish hot water from ice water swallowing.