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.

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.

Amyloidosis is a rare disease.This paper reports a case of localized secondary hypopharyngeal amyloidosis presenting with pulmonary tuberculosis as the initial symptom.The patient lacked specific clinical manifestations and primarily exhibited symptoms such as cough,sputum production,acid reflux,belching,and abdominal pain.Chest CT indicated bronchiectasis with infection and pulmonary tuberculosis.Digestive endoscopy revealed a white mucosal elevation at the right pyriform sinus of the hypopharynx.Pathological diagnosis confirmed amyloid deposits in the hypopharyngeal mucosal tissue.The patient tested positive for anti-amyloid A antibodies,Congo red staining(+),and periodate Schiff staining(+).Amyloidosis commonly affects the digestive system and may have various etiologies,often presenting with symptoms that overlap with other digestive system diseases,leading to frequent misdiagnosis and missed optimal treatment opportunities.The hypopharynx,a highly folded and narrow chamber that serves as a common passage for the digestive and respiratory tracts,can be effectively evaluated for amyloidosis using digestive endoscopy.

Objective:To investigate the mechanism by which non-enterotoxin-producing Bacteroides fragilis (NTBF) inhibits TNF-α-induced inflammatory responses in human normal colonic epithelial cells hcoEPIC, and explore new probiotic therapies for the prevention and treatment of colitis. Methods:The co-culture system of NTBF and hcoEPIC cells was established, and the adhesion and invasion ability of NTBF were detected, respectively. TNF-α was added to induce cellular inflammation after 4 h of co-culture of NTBF and hcoEPIC cells, and cell survival and apoptosis were detected by the CCK-8 assay and the AnnexinⅤ-FITC/PI assay respectively after 24 h. Key proteins of the NF-κB signalling pathway in hcoEPIC cells in different treatment groups were detected by Western blot and RT-qPCR, and the expression of downstream cytokines of this pathway incluing IL-1β, TNF-α and IL-10 were detected by ELISA. The effect of NTBF intervention on dextran sodium sulfate(DSS)-induced colitis mice was assessed by in vivo animal experiments. Results:NTBF adhered to hcoEPIC cells, and was non-toxic to the cells. Compared with control group, NTBF treatment alone did not affect cell survival and apoptosis of hcoEPIC cells ( P>0.05), but significantly reduced cell damage and apoptosis induced by TNF-α ( P<0.05); Compared with the TNF-α treatment alone group, the expression levels of p-NF-κB p65 and p-IκBα protein as well as NF-κB and IκBα mRNA were significantly reduced ( P<0.05); the production of IL-1β and TNF-α in the cell supernatant was reduced and the release of IL-10 was increased ( P<0.05). Animal experiments demonstrated that NTBF was indeed effective in alleviating DSS-induced colitis in ulcerative colitis model mice, which was mainly manifested by inhibiting weight loss, lowering DAI scores, improving colonic shortening, and attenuating colonic pathological damage in colitis-induced mice. Conclusions:NTBF may inhibit TNF-α-induced inflammatory responses in colonic epithelial cells by down-regulating the NF-κB pathway.

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.

Objective : To evaluate the quality of neonatal inherited metabolic diseases screening in Chaoyang District, Beijing Municipality from 2012 to 2021, so as to provide insights into improvements in the screening quality and efficiency of neonatal inherited metabolic diseases. Methods: Data pertaining to screening of neonatal inherited metabolic disease in Chaoyang District from 2012 to 2021 were captured from Beijing Center for Neonatal Disease Screening. The percentage of screening, eligible rate of blood smears collection, re-examination rate of suspected cases, and definitive diagnosis of congenital hypothyroidism (CH), phenylketonuria (PKU) and congenital adrenal hyperplasia (CAH) were analyzed to evaluate the quality of neonatal inherited metabolic diseases screening in Chaoyang District. Results: There were 484 002 live neonates in Chaoyang District from 2012 to 2021, and 481 395 neonates were screened for inherited metabolic diseases, with a screening rate of 99.46% and 99.71% eligible rate of blood smears collection. A total of 4 305 suspected positive cases were screened, including 4 148 cases recalled for re-examinations, with a 96.35% re-examination rate of suspected cases, and the re-examination rates of CH, PKU and CAH were 96.37%, 96.79% and 95.65%, respectively. Totally 482 neonates were definitively diagnosed with inherited metabolic diseases, with an overall incidence rate of 1/999, and the incidence rates of CH (307 cases), hyperthyrotropinemia (103 cases), PKU (66 cases) and CAH (6 cases) were 1/1 568, 1/4 674, 1/7 294 and 1/20 233, respectively. Conclusions The screening rate and re-examination rate of neonatal inherited metabolic diseases was both more than 95% in Chaoyang District from 2012 to 2021. Improving the management of neonatal inherited metabolic diseases screening and the recall of suspected cases is required.

To analyze and summary the setting of admission standards, training methods and certification and assessment methods of specialized nursing teachers, in order to lay the foundation for the homogenization training of specialized nursing teachers in China, and at the same time, provide guarantee for the improvement of the homogenization level of national specialized nursing training bases.

ObjectiveTo understand the cooperative work and mechanism in the corona virus disease 2019 containment action by the support-to-Hebei epidemiological investigation group formed by five provinces， summarize the existing challenges， and discuss the relevant mechanism， so as to provide evidence for future support actions. MethodsA questionnaire survey was used to investigate the members from five provinces of the support-to-Hebei epidemiological investigation team. The content included basic information， work situation， problems in cooperative work， and suggestions in support mechanisms. ResultsA total of 104 questionnaires were issued， of which 101 valid questionnaires were collected with an effective response rate of 97.12%. The proportions of respondents who participated in the epidemic-related data preparation， case investigation， technical training， supervision of key venues， and specimen collection was 93.07%， 85.15%， 81.19%， 65.35%， and 44.55%， respectively. The respondents believed that information sharing channel of local epidemic situation was blocked （95.05%）， coordination mechanism among local departments was insufficient （84.16%）， communication and coordination mechanism among the dispatch institutions， support team， and local departments was unperfect （84.16%）， management of the dispatch institutions to the support team was relatively loose （79.21%）， dispatch institutions failed to make full use of professional advantages of the support team （72.28%）， and majority of the support team members engaged in a single profession （59.41%）. The respondents suggested that local departments should improve the information sharing mechanism （95.05%）， strengthen communication and coordination among the dispatch institutions， support team， and local departments （92.08%）， and dispatch institutions should clarify the tasks and responsibilities of the support team （91.09%）， formulate cross-regional emergency support plans （87.13%） and evaluation plans of support action （72.28%）. ConclusionIn order to ensure the efficiency and accuracy of future support actions， it is necessary to improve the mechanism of emergency coordination， communication and matching， response procedures， team management， and support evaluation.