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 prevalence of Dengue virus (DENV) infection among voluntary blood donors in Xishuangbanna Dai Autonomous Prefecture, and to evaluate the necessity of implementing nucleic acid testing (NAT) for blood donors during the rainy season (May-October). Methods: Prior to initiating donor screening, the Xishuangbanna Central Blood Center conducted in-house validation of reagent performance and participated in external quality assessment (EQA) organized by the National Center for Clinical Laboratories (NCCL). During the surveillance period (August-October 2024), a total of 2 919 donor samples were screened using a 6-sample mini-pool NAT strategy. Daily internal quality controls were recorded. Samples that tested positive in pooled screening were deconvoluted and retested in duplicate; only those reactive in both replicate wells were sent to the NCCL for confirmatory testing. At NCCL, samples underwent re-testing using five domestic NAT reagents, as well as serological assays for NS1 antigen and DENV-specific IgG/IgM. Confirmed positive samples were further characterized by serotyping, envelope (E) gene sequencing, and phylogenetic analysis using the maximum likelihood method. Results: The DENV NAT reagent demonstrated consistent detection of 40 copies/mL controls in individual donor (ID)-NAT test (mean CT: 35.61±0.40). During the 63-day quality control monitoring, DENV detection remained stable (mean CT: 22.53±0.72). The center achieved full marks in EQA assessments for 2023 and 2024. Three reactive pools were identified in initial screening, and subsequent individual testing confirmed three DENV RNA-positive donors (sample numbers: 2401, 2402, and 2403). The confirmatory test results from NCCL were: all five NAT platforms consistently detected DENV RNA in the three samples; for serological tests, 2 samples (2402, 2403) were positive for NS1 antigen, while all three samples were negative for both IgG and IgM antibodies. DENV serotyping reagents identified DENV-2 in all cases, which were further confirmed as DENV-2 Genotype Ⅱ-Cosmopolitan by E gene sequencing. Phylogenetic analysis indicated that samples 2401 and 2402 clustered with Southeast Asian strains (Thailand/MZ636802.1, Laos/PQ775621.1), while sample 2403 closely matched a previously reported local Yunnan strain (PV544686.1). Conclusion: DENV-2 infection was detected among blood donors in Xishuangbanna during the rainy season, indicating concurrent risks of imported and local transmission. We recommend implementing pooled NAT screening for blood donors in high-risk areas during dengue epidemic seasons, along with strengthened laboratory quality control, to enhance blood safety.

Objective To explore the injury types and characteristics of children hospitalization with accidental injuries in a tertiary general hospital in Guangdong Province,and to provide important data evidences for reducing accidental injuries in children.Methods Children hospitalization of accidence in 2019-2021 from a tertiary general hospital were analyzed.The X2 test analysis was used for comparing different years,sources of patients and age difference between accident types.Results 1 561 children were hospitalized due to accidental injuries.The top three reasons were falling,traffic accidents and external inju-ries.There are significant differences among age groups and types of accident harm(x2=186.606,P＜0.001),and significant differences among different damage rate of surgery(x2=45.017,P＜0.001).The children who underwent surgery after injury were most likely to fall(72.3％).The accidental injuries occurred at home accounted for 88.8％,and therein the upper limb injuries were the main injuries(67.8％).Conclusion Accidental injuries in children's hospitalization are mainly caused by falls,traffic accidents,and external injuries.Targeted prevention should be carried out according to the types of injuries in differ-ent age groups,especially falls,which are the most harmful types of injuries in terms of incidence rate and surgical rate.There-fore,prevention and control should be emphasized.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

OBJECTIVE To observe the clinical efficacy of Kanglaite injection assisted with camrelizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer （NSCLC）. METHODS A total of 192 patients with advanced NSCLC and hospitalized in the TCM oncology department of our hospital from January 1st， 2018 to December 1st， 2022 were retrospectively selected as the study objects， and were divided into observation group （additional use， n＝104） and control group （without additional use， n＝88） according to whether the patients additionally received Kanglaite injection based on camrelizumab combined with chemotherapy （carboplatin+pemetrexed）. The short-term therapeutic effects of 2，4 and 6 cycles were compared between the two groups. The levels of peripheral blood immune function indexes and serum tumor markers were compared before treatment， after 3 cycles of treatment and after treatment. The long-term therapeutic effects as well as the occurrence of adverse drug reaction（ADR） during hospitalization were compared between the two groups. RESULTS After 3 treatment cycles and at the end of treatment， the CD4+ T lymphocyte ratio and CD4+/CD8+ in the observation group were notably greater than the control group （P＜0.05）； the levels of serum carcinoembryonic antigen and cytokeratin 19 fragment antigen 21-1 were significantly lower than those in the control group （P＜0.05）. The overall survival of the observation group was significantly longer than that of the control group （P＜0.05）， and the median overall survival was （185.27±38.21） d and （132.11±34.23） d， respectively. There were no significant differences in the whole ADR and grade ≥3 ADR between the two groups during hospitalization（P＞0.05）. CONCLUSIONS Based on camrelizumab combined with chemotherapy， the addition of Kanglaite injection can enhance immunological response and prolong overall survival in advanced NSCLC patients.

Objective: To evaluate the new compensation mechanism for primary healthcare institutions in Zhejiang province, in terms of fairness, performance, incentive mechanism and sustainability in pilot areas. Methods: Evaluation indicators were constructed based on stakeholder theory, fairness theory, expectation theory and sustainable development theory.Focus group interviews were conducted with stakeholders and quantitative data were collected through questionnaires. Meanwhile, the financial compensation, income and expenditure and work equivalent data were collected from such institutions of the four pilot areas, with quantitative data subject to descriptive analysis. Results: This study found the reform used reasonable proportion of funds allocated(the proportion of basic salary for employees was lower than 50%)and adjustment factors(1.0-1.8)of different primary healthcare institutions to guarantee the fairness of the reform; the increase of work equivalents(the per capita work equivalents of medical staff in pilot counties had increased from 38.435 million in the previous year to 42.590 million work equivalents)reflected the performance outcomes of the reform. The incentive and sustainability of the reforms were the weak parts. These were mainly due to the fact that the internal distribution system of primary healthcare institutions failed to make corresponding reforms. Conclusions The reform of the compensation mechanism based on the equivalent method has changed medical staff′s perception of the distribution of funds. The principle of" more pay for more work" and the use of information technology to capture work equivalents have improved the enthusiasm of primary medical staff and the operational efficiency of these institutions, thus, making reform generally scientific and reasonable.

Objective To investigate the correlation between CYP2C19 gene polymorphism and clopidogrel resistance(CR)in patients with ischemic stroke in the north of China.Methods The patients with ischemic stroke were selected as the research object from the First Hospital of Hohhot during September 2015 to No-vember 2016.The polymorphism of CYP2C19 gene was detected by Taqman probe method.Results The clo-pidogrel resistance ratio of the study population is 59%.There is a strong correlation between the CYP2C19* 2 mutant strains with clopidogrel resistance(P=0.006),and we foundd that the increased glutamic oxala-cetic transaminase was associated with clopidogrel resistance.Conclusion Patients with the CYP2C19*2 al-lele were at greater risk of clopidogrel resistance during antithrombotic therapy.

Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95％CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95％CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.

In China's new healthcare reform, the pilot local governments explore the practice of establishing a new model of hierarchical diagnosis and treatment system.Zhejiang Province has adopted a special policy of effectively allocating hospital resources and human resources, and efficiently improving primary healthcare institution capability and patient satisfaction(hereinafter referred to as double allocation, double improvement), focusing on the implementation of the 'Healthcare Talents Project', in order to fill a vacancy of human resources in primary healthcare institutions.This paper uses system dynamics modeling and the WISN method of WHO to estimate the gap in physician supply in primary healthcare institutions.After building the system dynamics model of 'Healthcare Talents Project', this paper simulates the influence of the policy on the vacancy of doctors in primary healthcare institutions and analyzes the sensitivity of regulatory factors.The simulation results show that, there are a big gap in physician supply of about 14,000 to build the hierarchical diagnosis and treatment system.The project can gradually increase the number of primary doctors, and the policy may fill the vacancy by 2021.However, if the efficiency of the hospital doctors who give assistance to primary institutions is increased by 10%, the targeted training and recruitment 100% achieve the policy plans and objectives, the project goal may be achieved by 2020.Therefore, this project can effectively adjust the human resources structure quickly and reasonably, and it can be used as reference for the reform of hierarchical diagnosis and treatment system.

This study was aimed to compare the pharmacokinetics (PK) of Shengmai injection and Shenmai injection with a single injection administration using a constant speed in subjects with stable angina pectoris.A total of 20 subjects with stable angina pectoris were divided into two groups.Each group was administered with Shengmai and Shenmai injection.The liquid chromatography-mass spectrometry (LC/MS) was adopted to determine concentrations of ginsenosides in plasma at different time points.PK parameters were calculated for comparison.The results showed that after a single intravenous infusion of Shengmai and Shenmai injection,the Cm.of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in Shenmai group were higher than those of the Shengmai group with statistical significance (P ≤0.05).There were differences on the T1/2 of ginsenoside Rg1,AUC0-144h and CL of ginsenoside Rc,as well as Tmax of ginsenoside Rd (P ≤ 0.05).However,there was no significant difference shown on other PK parameters.It was concluded that after a single Shengmai or Shenmai injection,there were PK differences of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in the human body.The clinical medication selection should be based on syndrome differentiation and treatment of patients.