Objective To explore the effectiveness of the cumulative sum (CUSUM) and the exponentially weighted moving average (EWMA) for early warning of influenza epidemic using two datasets of reported influenza cases and influenza-like illness (ILI) cases. Methods Using the reported cases of influenza and ILI in Daxing District, Beijing, from week 23 of 2018 to week 22 of 2024 as data sets, the CUSUM and EWMA models were established, respectively. The positive rate of influenza etiology was used as the ^“gold standard^”, and the Youden index was used as the evaluation index to compare the early warning effect of the two models under different data sets and different parameters. Results In CUSUM, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.751 and 0.635, respectively. In EWMA, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.544 and 0.464, respectively. The optimal EWMA and CUSUM models could both issue early warning signals in advance of the ^“gold standard^”. Conclusion In the influenza epidemic early warning in Daxing District, Beijing, the CUSUM model established with the reported cases of influenza can achieve good early warning effects, but the model parameters need to be dynamically adjusted according to the local epidemic characteristics.

BACKGROUND:The small-diameter blood vessel prosthesis faces the problem of lumen stenosis or even occlusion due to thrombogenesis and intimal hyperplasia after transplantation.The application of stem cells as seed cells to achieve endothelialization of blood vessel prosthesis helps to improve the long-term patency rate after vascular graft transplantation. OBJECTIVE:To summarize the research progress of the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis. METHODS:The relevant articles published on PubMed and WanFang databases from 2013 to 2023 were retrieved by the first author.Chinese and English search terms included"vascular graft,tissue-engineered blood vessel/vascular tissue engineering,endothelialization,stem cells,endothelial progenitor cells,mesenchymal stem cells,induced pluripotent stem cells,embryonic stem cells."The relative articles in the domestic and overseas about the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis in the past 10 years were retrieved.A total of 552 articles were initially found and we finally selected 81 articles to review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)The low long-term patency rate restricts the application of small-diameter blood vessel prosthesis in clinic.The main causes of low long-term patency rate are thrombogenesis and intimal hyperplasia.The endothelium of native vessels has the function of anti-thrombogenesis and intimal hyperplasia.Endothelialization can simulate the function of native vessels,which is an effective way to improve long-term patency rate.(2)The small-diameter blood vessel prosthesis will undergo in vivo endothelialization after being implanted,but it is difficult to form complete endothelium.Stem cells have the potential to differentiate into endothelial cells.Recruiting stem cells in vivo or seeding them on the inner surface of blood vessel prosthesis in vitro is research strategy to achieve endothelialization.(3)The long-term patency rate of small-diameter blood vessel prosthesis has been improved to a certain extent through seeding endothelial progenitor cells,mesenchymal stem cells,induced pluripotent stem cells,and embryonic stem cells.Each has its own advantages.Endothelial progenitor cells are easy to obtain and can be directly used for seeding.Mesenchymal stem cells come from a wide range of sources and have the function of paracrine and immunological regulation.Induced pluripotent stem cells are rich in sources and the immunogenicity can be eliminated.Embryonic stem cells have a strong proliferative ability and can differentiate into many cells.(4)The application of stem cells in blood vessel prosthesis has not yet been transformed into clinic.Further researches are needed to promote clinical translation.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

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.

Ribosomal protein(RP)is an important part of ribosome,which is very important for the assembly and function of ribosome.Recent studies have shown that RP is closely related to the processes of growth,senescence,apoptosis,invasion and drug resistance of tumor cells.The drug resistance of tumors is one of the main reasons for the low cure rate of tumors.RP can affect the drug resistance of tumor cells through a variety of mechanisms,such as changes in signal pathway,epithelial-mesenchymal transformation,cancer stem cells and tumor microenvironment,resulting in a poor prognosis of cancer patients.Ribosome tar-geting therapy is a promising method for the treatment of cancer patients.This review summarizes the mecha-nism of RP and many kinds of cancer drug resistance,provides new ideas for elucidating the mechanism of tumor drug resistance,and then provides new strategies for clinical prevention and reduction of tumor drug re-sistance.

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 molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

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.

Objective To study the therapeutic effect of Xuefu Zhuyu Capsule combined with sacubitril valsartan on dilated cardiomyopathy.Methods A total of 70 patients with dilated cardiomyopathy who were hospitalized in the Hospital from January to December 2020 were selected as the research objects and random-ly divided into control group and experimental group,with 35 cases in each group.The control group was only treated with sacubitril valsartan,and the experimental group was treated with Xuefu Zhuyu Capsule combined with sacubitril valsartan.According to the patient's blood pressure and renal function,sacubitril valsartan was titrated from a small dose to the maximum dose.Xuefu Zhuyu Capsule was uesd 2.4 g each time,twice a day,and the treatment time was three months.The symptoms of heart failure,glycosylated hemoglobin(HbA1c),low density lipoprotein(LDL),total cholesterol(TC),triglyceride(TG),ALT,AST,N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular end-systolic diameter(LVEDd),left ventricular end-dias-tolic diameter(LVEDs),ejection fraction(EF)and the incidence of arrhythmia were observed in the two groups after treatment.Results After treatment,the level of NT-proBNP in the experimental group was sig-nificantly lower than that in the control group(P＜0.05).There was no significant difference in LDL,TC,TG,LVEDd,LVEDs and EF between the two groups(P＞0.05).The incidence of atrial tachycardia and ven-tricular premature beat in the experimental group was higher than that in the control group(P＜0.05).Con-clusion Xuefu Zhuyu Capsule combined with sacubitril valsartan can significantly improve the symptoms of patients with heart failure and reduce the level of NT-proBNP,but it may increase the proportion of patients with atrial tachycardia and ventricular premature beats.

Objective:To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique; To explore the possibility of its treatment for cough variant asthma.Methods:The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot.Results:Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased ( P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased ( P<0.05). Conclusion:Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.