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.

Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6％(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P＜0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P＜0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P＜0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P＜0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P＜0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.

The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.

Objective:To analyze the application value of autophagy related molecular markers in placenta tissue in predicting fetal growth restriction in pregnant women with preeclampsia.Methods:A total of 46 pregnant women admitted to Changsha Hospital for Maternal and Child Health Care from January 2021 to August 2023 were collected. A cross-sectional study was conducted, and they were divided into a normal delivery group (control group, 23 cases) and an observation group with preeclampsia combined with fetal growth restriction (observation group, 23 cases) based on pregnancy outcomes. Transmission electron microscopy was used to observe the occurrence of autophagic vesicles in trophoblast cells in the placental tissue of both groups; The expression of Beclin-1, LC3, and P62 in placental tissues of two groups was detected by immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and Western blot.Results:The transmission electron microscopy results showed that the presence of autophagic vesicles could be observed in the placental trophoblast cells of both the control group and the observation group, but the number of autophagic vesicles in the trophoblast cells of the observation group was higher than that in the control group ( P<0.05). The immunohistochemical results showed that the colorimetric values of Beclin-1 and LC3 in the placental tissue sections of the observation group were higher than those of the control group (all P<0.001), while the colorimetric values of p62 were lower than those of the control group ( P<0.001). The qRT-PCR and Western blot results showed that the mRNA and protein expression levels of Beclin-1 and LC3 in the observation group were significantly higher than those in the control group (all P<0.001), while the expression levels of p62 mRNA and protein were lower than those in the control group (all P<0.001). Conclusions:The autophagy activity of placental tissue trophoblasts in patients with preeclampsia combined with fetal growth restriction is enhanced, indicating a close correlation between elevated autophagy levels and the occurrence of preeclampsia combined with fetal growth restriction. Excessive autophagy may be involved in the occurrence of preeclampsia combined with fetal growth restriction.

Health insurance fund regulation (HIFR) is a vital issue in the modernization of healthcare security governance, with its importance as a primary task of the healthcare security department continually reinforced in policy practice. This study focused on the 22 specialized policies issued by the National Healthcare Security Administration from its establishment in 2018 to March 2024, deeply analyzed their issue characteristics, and summarized the evolutionary trends of policy changes, as well as the knowledge production patterns that existed in the series of policy formulation, implementation, and feedback processes. Our analysis revealed that the diverse issue characteristics had led to heterogeneous directions in HIFR policies. The policy development process presented distinct composite evolutionary trends, mainly manifested in four aspects: the integration of regulatory system and content, the convergence of professional and societal forces, the parallelism of special governance and regular supervision, and the complementarity of conventional and emerging methods. Additionally, the study demonstrated that the knowledge production embedded in policy evolution encompassed four different dimensions: problem rectification, norm setting, pilot experience, and technical absorption. Together with issue characteristics and policy evolution, they formed an integrated, dynamic, and open system of knowledge production, continuously promoting the renewal and iteration of regulation policies.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Telephone follow-up is one of the important ways to follow up patients. High-quality follow-up can benefit both doctors and patients. However, clinical research-related follow-up is often faced with problems such as time-consuming, laborious and poor patient compliance. The authors belong to a team that has been committed to the study of patient-reported outcomes for a long time. The team has carried out long-term follow-up of symptoms, daily function and postoperative complications of more than 1 000 patients after lung cancer surgery, and accumulated certain experience. In this paper, the experience of telephone follow-up was summarized and discussed with relevant literatures from the aspects of clarifying the purpose of clinical research follow-up, understanding the needs of patients in follow-up, and using follow-up skills.

Objective:To explore the relationship between liver iron deposition and steatosis in patients with non-alcoholic fatty liver disease (NAFLD) through MRI.Methods:163 cases of liver biopsy underwent MRI examination. R2* was used to measure liver iron content. Dixon-based proton density fat fraction (PDFF) was used to measure liver fat content. One-way ANOVA, r-correlation, ROC curve, and others were used to assess the relationship between clinical case data, serological indices, and imaging results in accordance with the pathological results of the liver biopsy.Results:R2* gradually increased as the pathological steatosis grade rose. The R2* that corresponded to no steatosis (< 5%), mild steatosis (14.95%±8.55%), moderate steatosis (46.30%±9.32%), and severe steatosis (73.86%±6.35%) were 27.56±4.40, 31.06±5.95, 38.06±4.80, and 48.10±5.55 ( P < 0.001), respectively. There was a positive correlation between R2* and liver steatosis content ( r= 0.769, P < 0.05). The area under the ROC curve and cut-off value were 0.88 and 31.77, respectively, and there was no distinct relationship with liver inflammation or fibrosis. Conclusion:R2* can quantitatively and non-invasively evaluate liver iron deposition in patients with NAFLD. A distinct relationship exists between liver steatosis and iron deposition, and iron deposition tends to increase as the steatosis aggravates.

Ischemic preconditioning (IPC) is a potential intervention known to protect the heart against ischemia/reperfusion injury, but its role in the no-reflow phenomenon that follows reperfusion is unclear. Dihydrotanshinone I (DT) is a natural compound and this study illustrates its role in cardiac ischemic injury from the aspect of IPC. Pretreatment with DT induced modest ROS production and protected cardiomyocytes against oxygen and glucose deprivation (OGD), but the protection was prevented by a ROS scavenger. In addition, DT administration protected the heart against isoprenaline challenge. Mechanistically, PKM2 reacted to transient ROS via oxidization at Cys423/Cys424, leading to glutathionylation and nuclear translocation in dimer form. In the nucleus, PKM2 served as a co-factor to promote HIF-1α-dependent gene induction, contributing to adaptive responses. In mice subjected to permanent coronary ligation, cardiac-specific knockdown of Pkm2 blocked DT-mediated preconditioning protection, which was rescued by overexpression of wild-type Pkm2, rather than Cys423/424-mutated Pkm2. In conclusion, PKM2 is sensitive to oxidation, and subsequent glutathionylation promotes its nuclear translocation. Although IPC has been viewed as a protective means against reperfusion injury, our study reveals its potential role in protection of the heart from no-reflow ischemia.