OBJECTIVE To investigate the independent risk factors for carbapenem-resistant Klebsiella pneumoniae （CRKP） infection， develop a nomogram prediction model and validate it. METHODS Clinical data of hospitalized patients infected with CRKP between April 2020 and May 2023 at Kunming First People’s Hospital were retrospectively collected and matched 1∶1 with patients infected with carbapenem-susceptible Klebsiella pneumoniae （CSKP） during the same period as the modeling group. Using the same criteria， data from patients hospitalized and infected with CRKP and matched CSKP between June 2023 and June 2024 were collected as the validation group. Univariate analysis， LASSO regression and multivariate Logistic regression were conducted to identify independent risk factors for CRKP infection and to develop a nomogram prediction model. Internal validation of the model was performed using Bootstrap resampling， and external validation was carried out using the data of validation group. The predictive performance of the model was evaluated using receiver operating characteristic （ROC） curves and calibration plots. RESULTS A total of 530 patients were enrolled， with 372 in the modeling group and 158 in the validation group. Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agents were identified as independent risk factors for CRKP infection （P＜0.05）. The nomogram predicting CRKP infection risk achieved an area under ROC of 0.729 and 0.803 in internal and external validations， respectively. Calibration curves indicated a high degree of consistency between predicted and observed probabilities. CONCLUSIONS Cerebrovascular disease， indwelling gastric tube， mechanical ventilation， exposure to carbapenem antibiotics， and exposure to β-lactamase inhibitor compound agent are independent risk factors for CRKP infection. The developed nomogram model for predicting CRKP infection risk demonstrates good predictive performance and can aid in the early identification of patients at high risk for CRKP infection.

Objective: To investigate the relationship between relative grip strength and hyperuricemia (HUA) levels in university freshmen, and to explore the potential value of muscle function indicators in HUA prevention among young populations, so as to provide new scientific evidences for HUA control in the demographic. Methods: Utilizing health examination data from 1 744 freshmen enrolled in a Shaanxi Province university in September 2024, absolute grip strength was measured using CAMRY electronic dynamometers, with relative grip strength subsequently calculated. Spearman correlation analysis was employed to examine relationships between student characteristics and relative grip strength, and binary Logistic regression models assessed the association strength between relative grip strength and HUA. Results: The overall HUA detection rate among freshmen was 29.8%, with significant gender differences (male:43.1%; female:24.0%; χ 2=64.62, P <0.01). Correlation analysis revealed significant associations between relative grip strength, body weight, height, body mass index (BMI) and HUA in both genders (boys: r =-0.27, 0.54, 0.11 , 0.53; girls: r =-0.18, 0.33, 0.08, 0.33, all P <0.05). Binary Logistic regression demonstrated that each standard deviation increase in relative grip strength reduced HUA risk by 77% in males ( OR=0.23, 95%CI =0.14-0.37) and 80% in females ( OR=0.20, 95%CI =0.11-0.36) (both P <0.01). Conclusions Relative grip strength represents a significant factor associated with HUA in university students. Incorporating muscle strength training into HUA prevention programs and establishing muscle function based HUA risk warning systems should be considered.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma(IPT-like FDCS)is a very rare malignant tumor that is considered to be associated with Epstein-Barr virus.Two patients in this report were generally healthy,and the spleen tumor was found during physical examination.After completing the examination,laparoscopic total splenectomy was performed,and the pathological result showed IPT-like FDCS.Postoperative chemoradiotherapy was not performed in either case.The disease has no characteristic clinical manifestations,and imaging overlaps with sarcoma.Microscopic manifestation showed CD21,CD23 and EBER positive spindle tumor cells in the inflammatory background with matted arrangement.Due to the interwoven distribution of tumor cells and lymphocytes,diagnosis is difficult.In this article,we report this two cases with literature review and summarize their clinical and pathological features to improve diagnostic cognition.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

Objective:To investigate the status of medical care seeking delay and diagnosis delay of pulmonary tuberculosis (PTB) patients in Tongzhou District and Changping District of Beijing, analyze the related factors and put forward suggestions for early detection and scientific management of PTB patients.Methods:A retrospective epidemiological survey was conducted to collect the incidence data of PTB registered in Tongzhou and Changping from January 1 to December 31, 2021 by using the Chinese Tuberculosis Information Management System, and telephone interview were used for information supplement. Multivariate logistic regression model and decision tree model were used to analyze the influencing factors of medical care seeking delay and diagnosis delay of PTB patients.Results:In 2021, the medical care seeking delay time M( Q1, Q3) in the PTB patients in Tongzhou and Changping was 11 (5, 26) days, with a delay rate of 41.71%. Results from multivariate logistic regression model analysis revealed that factors influencing the medical care seeking delay included regular health check-up ( OR=0.033, 95% CI: 0.008-0.147), coughing for less than 2 weeks or showing any symptom of PTB before medical care seeking ( OR=0.378, 95% CI: 0.215-0.665), showing other symptoms before medical care seeking( OR=2.791, 95% CI: 1.710-4.555), no work or school in medical care seeking ( OR=2.990, 95% CI: 1.419-6.298). The diagnosis delay time M( Q1, Q3) in the PTB patients was 8 (0, 18) days, with a delay rate of 35.20%. Multivariate logistic regression model analysis revealed that the factors influencing the diagnosis delay of PTB included being diagnosed at a specialized tuberculosis hospital ( OR=0.426, 95% CI: 0.236-0.767) or a tuberculosis prevention and control institution ( OR=1.843, 95% CI: 1.061-3.202) and being traced as a source of infection ( OR=2.632, 95% CI: 1.062-6.521). The overall performance of the multivariate logistic regression model was comparable to that of the decision tree model, with the decision tree model exhibiting higher sensitivity but lower specificity. Conclusions:The medical care seeking delay rate and diagnosis delay rate of tuberculosis in Tongzhou and Changping were at low levels in 2021. However, it is still necessary to strengthen the health education and active screening, improve the public awareness of PTB prevention and control, and further improve the level of medical services and medical access to reduce the medical care seeking delay and diagnosis delay of PTB patients.

Objective To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract(TAAE)for synovial pannus formation in rats with college-induced arthritis(CIA).Methods Sixty male SD rats were randomized into normal control group,CIA model group,TGT group,3 TAAE treatment groups at low,medium and high doses(n=10).Except for those in the normal control group,all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline,TGT or TAAE by gavage once daily for 35 days.The severity of arthritis was assessed using arthritis index(AI)score,and knee joint synovium pathologies were examined with HE staining.Serum levels of TNF-α,IL-6,and IL-1β were detected with ELISA;the protein expressions of PI3K,Akt,p-PI3K,p-Akt,VEGF,endostatin,HIF-1α,MMP1,MMP3,and MMP9 in knee joint synovial tissues were determined using Western blotting,and the mRNA expressions of TNF-α,IL-6,IL-1β,VEGF,HIF-1α,PI3K,and Akt were detected with RT-PCR.Results Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling,lowered AI scores,and reduced knee joint pathology,neoangiogenesis,and serum levels of inflammatory factors.TAAE treatment obviously increased endostatin protein expression,downregulated p-PI3K,p-Akt,MMP1,MMP3,MMP9,VEGF,and HIF-1α proteins,and reduced TNF-α,IL-6,IL-1β,PI3K,Akt,VEGF,and HIF-1α mRNA levels in the synovial tissues,and these changes were comparable between high-dose TAAE group and TGT group.Conclusion TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α,VEGF,endostatin,MMP1,MMP3,and MMP9 via the PI3K/Akt signalling pathway.

Objective Using the weighted gene co-expression network analysis(WGCNA)to explore the key genes of aging associated with Alzheimer's disease(AD).Methods GSE132903 was selected from GEO database as the analysis dataset.The differential expressed genes(DEGs)of AD were screened,and visualized with volcano and heat map.Aging and senescence-associated genes(ASAGs)were downloaded from MsigDB,Aging Altas and CellAge databases.WGCNA screened the gene modules with the highest correlation with AD,and genes of key modules subsequently performed with gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.AD age-related differential expressed genes(ARDEGs)were obtained by taking intersection genes of DEGs,key module genes of WGCNA and ASAGs.Protein-protein interaction(PPI)network analysis was performed using the STRING database to find key node genes.The co-expression networks and associated functions of key genes were analyzed using the GeneMANIA database.The key genes were validated in Alzdata database.Results 226 DEGs,606 ASAGs and 8 ARDEGs were obtained.The top 5 key genes selected by PPI were SYP,STXBP1,VAMP2,CPLX1 and STX1A.Alzdata database verified that the expressions of 5 key genes in other brain regions of AD were down-regulated,except for no significant changes of VAMP2 in hippocampus and STXBP1 in frontal cortex,as well as no expression of CPLX1 in frontal cortex.The differential expression of VAMP2,STXBP1 and STX1A appeared in the early stage of AD,and CPLX1 was related to the pathological process of Tau.SYP and STXBP1 were related to the pathological processes of amyloid β-protein and Tau.Conclusion SYP,STXBP1,VAMP2,CPLX1 and STX1A are ARDEGs,which are expected to be potential diagnostic and therapeutic targets for AD.

Objective To investigate the clinical efficacy of therapy of clearing heat,percolating dampness and lowering turbidity combined with Silibin Meglumine Tablets in the treatment of non-alcoholic steatohepatitis(NASH)patients with abnormal alanine aminotransferase(ALT)level of damp-heat accumulation type.Methods A retrospective study was conducted.According to the medication,80 patients with NASH with abnormal ALT level of damp-heat accumulation type were divided into control group and observation group,with 40 cases in each group.The control group was treated with Silibin Meglumine Tablets,and the observation group was treated with therapy of clearing heat,percolating dampness and lowering turbidity on the basis of treatment for the control group.The course of treatment covered 12 weeks.The changes of liver function indicators of ALT,aspartate aminotransferase(AST),and gamma glutamyl transpeptidase(GGT),blood lipid indicators of total cholesterol(CHOL)and triglyceride(TRIG),and the degree of hepatic steatosis in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 12 weeks of treatment,the total effective rate of the observation group was 95.00%(38/40),and that of the control group was 77.50%(31/40).The curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the levels of ALT,AST and GGT in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of ALT,AST and GGT in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of CHOL and TRIG in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of CHOL and TRIG in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the degree of hepatic steatosis in the two groups was significantly lower than that before treatment(P＜0.05),and the decrease of the degree of hepatic steatosis in the observation group was significantly superior to that in the control group(P＜0.05).(5)During the treatment,no obvious adverse reactions occurred in the two groups,indicating high safety.Conclusion The therapy of clearing heat,percolating dampness and lowering turbidity combined with Silibin Meglumine Tablets exerts certain effect in the treatment of NASH patients with abnormal ALT level of damp-heat accumulation type,and the therapy can significantly enhance the clinical efficacy of Silibin Meglumine Tablets alone for NASH.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To explore the efficacy and safety of modified meibomian gland massage combined with ultrasonic atomization and drug therapy for dry eye in high-altitude military personnel.Methods A total of 180 patients(360 eyes)with dry eye who were diagnosed and treated by the medical team of General Hospital of Central Theater Command of Chinese PLA from July to October 2022 in Linzhi,Tibet(average altitude of 3100 meters)were selected as the research subjects.Patients were divided into four block groups based on the course of the disease:＜1 month,1-3 months,3-6 months,and≥6 months,and each block group was randomly assigned to control group,traditional group and modified group by random number table method,with 60 cases in each group.Control group received routine treatment(artificial tear drops and atomization fumigation);on the basis of routine treatment,traditional group underwent traditional meibomian gland massage,and modified group underwent modified meibomian gland massage.After 3 months of treatment,the scores of symptoms and signs,total effective rate,duration of treatment and incidence of adverse events were compared among the 3 groups.Results In the intra-group comparison before and after treatment,except for control group's symptom scores difference which was not statistically significant(P＞0.05),all other scores decreased significantly(P＜0.05).In the inter-group comparison after treatment,the scores of both traditional group and modified group were significantly better than those of control group(P＜0.05),but no significant difference was observed in symptom and sign scores between traditional and modified groups(P＞0.05).Compared with control group,the total effective rates of traditional group and modified group both significantly increased(P＜0.01),but there was no significant difference in total effective rate between traditional and modified groups(P＞0.05).The treatment time in modified group was significantly longer than that in control group(P＜0.05),but significantly shorter than that in traditional group(P＜0.05).The incidence of adverse events was significantly lower in modified group than that in traditional group(P＜0.001).Conclusion In high-altitude areas,modified meibomian gland massage combined with ultrasonic atomization and local drug therapy for dry eye is safe and effective,non-invasiveness and easy to perform,and suitable for promoting and application in military field training.