The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Objective: To analyze the spatio-temporal distribution of pulmonary tuberculosis (PTB) among students in Suzhou City, Jiangsu Province from 2015 to 2023, so as to provide the evidence for the prevention and control of PTB in schools. Methods: Data of PTB cases among students in Suzhou City from 2015 to 2023 were collected from Chinese Disease Prevention and Control Information System and Suzhou Report of Investigation and Disposal of Tuberculosis in Schools. The seasonal incidence of PTB among students was analyzed using seasonal index (SI). The spatio-temporal clustering characteristics of PTB among students were analyzed using spatial autocorrelation and retrospective spatio-temporal permutation scanning. Results: Totally 1 374 PTB cases among students were reported in Suzhou City from 2015 to 2023. PTB cases were reported in each month, and the SIs were 100.69%, 124.38%, 108.98%, 135.04%, 106.61% and 106.61% in April, May, July, September, October and November, respectively, indicating the prevalence of PTB among students. Spatial autocorrelation analysis showed there was a positive spatial correlation of PTB among students in 2019 and 2020 (Moran's I=0.053 and 0.089, both P<0.05). From 2015 to 2023, there were high-high clustering sites mainly in Hengtang Street and Shishan Street. Retrospective spatio-temporal permutation scanning showed a primary cluster in Hengtang Street, with aggregation time in 2017, and 6 secondary clusters covering 25 towns (streets). Conclusion From 2015 to 2023, the PTB cases among students in Suzhou City were mainly concentrated in summer and autumn, and were predominantly clustered in Hengtang Street and Shishan Street.

Drug development encompasses multiple processes,wherein protein subcellular localization is essential.It promotes target identification,treatment development,and the design of drug delivery systems.In this research,a deep learning framework called LocPro is presented for predicting protein subcellular localization.Specifically,LocPro is unique in(a)combining protein representations from the pre-trained large language model(LLM)ESM2 and the expert-driven tool PROFEAT,(b)implementing a hybrid deep neural network architecture that integrates convolutional neural network(CNN),fully connected(FC)layer,and bidirectional long short-term memory(BiLSTM)blocks,and(c)developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels.Additionally,a dataset was curated and divided using a homology-based strategy for training and validation.Compar-ative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction.The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization.All in all,LocPro serves as a valuable complement to existing protein localization prediction tools.The web server is freely accessible at https://idrblab.org/LocPro/.

Objective To evaluate the value of 68Ga-DOTATATE and 18F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms(GEP-NEN).Methods This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing 18F-FDG and 68Ga-DOTATATE PET/CT imaging at our hospital from August,2020 to March,2023,including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment.GEP-NEN were classified into G1,G2,and G3 neuroendocrine tumors(NET)and neuroendocrine carcinomas(NEC)based on pathological typing.The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers:68Ga-DOTATATE>18F-FDG(A);68Ga-DOTATATE=18F-FDG(B);68Ga-DOTATATE<18F-FDG(C);and complementation(D).The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis.Results In the 49 patients with GEP-NEN,68Ga-DOTATATE PET/CT was superior to 18F-FDG PET/CT for detecting systemic tumor lesions(P<0.001)and more sensitive for detecting primary/recurrent lesions,lymph node metastasis,liver metastasis,and bone metastasis(P<0.05),while 18F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis(P<0.05).In terms of the detection efficiency,Pattern A was found in 46.9%(23/49)patients,Pattern B in 38.8%(19/49),Pattern C in 12.2%(6/49),and Pattern D in 2.0%(1/49).The complementary value of 18F-FDG PET/CT to 68Ga-DOTATATE PET/CT was 0%in G1 NET patients(0/13),8.3%in G2 NET patients(2/24),50%in G3 NET patients(3/6),and 33.3%in NEC patients(2/6).12.2%(6/49)of the patients had their staging confirmed or changed due to additional lesions detected by 18F-FDG PET/CT imaging,resulting subsequently in establishment or adjustment of their treatment plans.Conclusion 68Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients.Additional 18F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2,G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To explore the impact of changes of myocardial infarct size on left ventricular adverse remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Methods:This was a prospective cohort study. The STEMI patients who underwent primary PCI in the First Medical Center of the Chinese People′s Liberation Army General Hospital, Beijing Anzhen Hospital, Hainan Hospital of the Chinese People′s Liberation Army General Hospital and Guangxi Yulin First People Hospital from January 1, 2017 to January 1, 2022 were enrolled. Cardiac magnetic resonance (CMR) was performed to dynamically assess the myocardial infarct size and calculate the rate of infarct size change between the acute phase (5 to 7 days post-primary PCI) and 6-month follow-up. The endpoint was left ventricular adverse remodeling which was defined as an increase of more than 20% in left ventricular end-diastolic volume (LVEDV) assessed by CMR at 6 months after primary PCI compared with LVEDV at 1 week after primary PCI. Based on serial CMR assessments, the patients were divided into left ventricular adverse remodeling group and non-remodeling group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of infarct size change for left ventricular adverse remodeling, and according to the optimal cutoff value, improved infarct size was defined as a decrease of >20% in the infarct size measured by CMR at 6 months after primary PCI compared with infarct size at 1 week after primary PCI. Multivariate logistic regression analysis was performed to identify the protective factors and risk factors for left ventricular adverse remodeling.Results:A total of 267 patients were enrolled, aged (58±11) years, with 234 males (87.6%). And 73 cases in the left ventricular remodeling group and 194 cases in the non-remodeling group. Infarct size assessed by CMR at 6 months after primary PCI decreased significantly compared with infarct size at 1 week after primary PCI in the left ventricular remodeling group ((23±13)% vs. (27±12)%, P=0.004), the same as in the non-remodeling group ((18±10)% vs. (23±10)%, P<0.001). The area under the ROC curve for the rate of infarct size change in predicting left ventricular remodeling was 0.735 (95% CI 0.670-0.799, P<0.001), a 20% reduction was the optimal cut-off value. Compared to the patients with non-improved infarct size, the incidence of left ventricular adverse remodeling was significantly lower in the patients with improved infarct size (18% (24/133) vs. 37% (49/134), P=0.001). Multivariate logistic regression analysis showed that improvement in IS was a protective factor for left ventricular adverse remodeling ( OR=0.376, 95% CI 0.236-0.721, P=0.002). Conclusion:Patients with STEMI who experience obvious reduction in infarct size after primary PCI have a significantly reduced risk of left ventricular adverse remodeling.

AIM:To investigate the mechanism by which the Z-DNA-binding protein 1(ZBP1)/receptor-in-teracting protein kinase 1(RIPK1)/mixed lineage kinase domain-like protein(MLKL)pathway modulates the necroptosis of neurons in a mouse model of Alzheimer disease(AD).METHODS:Thirty mice were randomly divided into three groups:normal control(NC)group,APP/PS1 model(MOD)group,and necroptosis inhibitor necrostatin-1(Nec-1)group,each with 10 mice.The learning and memory capacities of mice were assessed using the Morris water maze assays.The pathological morphology of hippocampal tissue was examined based on the HE staining assay.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in serum samples were measured by ELISA.The phosphory-lation of amyloid precursor protein(APP),Tau protein and the expression levels of proteins related to the ZBP1/RIPK1/MLKL pathway in hippocampal tissue were measured by Western blot.Immunofluorescence analysis was performed to de-tect the positive expression of p-RIPK1,while the mRNA level of ZBP1 was measured by RT-qPCR.RESULTS:Com-pared with NC group,the escape latency of mice in the MOD group was significantly longer(P<0.05),the number of crossing platforms was reduced(P<0.05),and the arrangement of hippocampal neurons was disordered accompanied with nuclear condensation.The concentration of TNF-α in serum was increased,whereas the concentration level of IL-10 was decreased(P<0.05).The expression levels of APP,p-Ttau and ZBP1 proteins in the hippocampal tissue and the ratios of p-RIPK1/RIPK1,p-RIPK3/RIPK3 and p-MLKL/MLKL were significantly upregulated(P<0.05).Similarly,the positive expression level of p-RIPK1 and the mRNA level of ZBP1 in hippocampal tissue were significantly upregulated(P<0.05).Compared with the MOD group,the cognitive function of AD mice,pathological damage of hippocampal tissue,and the levels of TNF-α and IL-10 in serum were reversed in the Nec-1 group(P<0.05).Moreover,the Nec-1 treatment signifi-cantly downregulated the expression levels of the above proteins(P<0.05),and the positive expression of p-RIPK1 and the mRNA level of ZBP1 were significantly decreased(P<0.05).CONCLUSION:The ZBP1/RIPK1/MLKL pathway is involved in the occurrence of neuronal necroptosis and the pathological process of AD mice.Inhibition of this pathway sig-nificantly ameliorates cognitive dysfunction and neuroinflammatory responses in AD mice.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

The study was aimed at identifying the diversity of tick species in selected areas of Qinghai,to analyze the genetic differentiation characteristics of tick-borne spotted fever group rickettsiae(SFGR),and to provide the theoretical basis for SFGR prevention and control in the region.The 16S rRNA gene was used for molecular biological identification of 446 collected tick samples,and the infection characteristics of SFGR in tick samples were determined according to the SFGR outer membrane protein A(ompA)gene.Haplotype analysis,phylogenetic tree construction,and estimation of differentiation times for SFGR were conducted in DNASP v6,IQ-tree v2.2.0,and BEAST v2.7.4 software.The obtained 446 tick samples belonged to three categories:(1)Haemaphy-salis spp.,including Haemaphysalis qinghaiensis(n=192)and H.danieli(n=37);(2)Dermacentor spp.,including Dermacentor ever-estianus(n=121),D.nuttalli(n=55),and D.silvarum(n=36);and(3)Hyalomma marginatum(n=5).Rickettsia raoultii was de-tected in D.everestianus,D.silvarum,D.nuttalli,H.qinghaiensis,and H.danieli,with infection rates of 95.9%,80.6%,69.1%,4.1%,and 2.7%,respectively.R.sibirica subsp.sibirica BJ-90 was found only in D.silvarum and D.nuttalli,with infection rates of 5.6%and 1.8%,respectively.The Candidatus R.gannanii F107 was found in H.danieli and H.qinghaiensis,with infection rates of 16.2%and 7.8%,respectively.Ca.R.hongyuanensis was detected only in H.qinghaiensis,with a prevalence of 16.3%.The prevalence of R.aeschlimannii was 20%and 2.7%in Hy.marginatum and H.danieli,respectively.Haplotype and nucleotide polymorphism analy-ses revealed 13 haplotypes in R.raoultii,with haplotype H13 as the dominant haplotype(42/192);seven haplotypes in Ca.R.ganna-nii F107,with haplotype H4 as the dominant haplotype(4/18);and three haplotypes in Ca.R.hongyuanensis,with haplotype H1 as the dominant haplotype(11/13).The phylogenetic tree indicated that the sequences of R.raoultii in selected areas of Qinghai and R.rhipicephali clustered into one branch;Ca.R.hongyuanensis and Ca.R.gannanii F107 clustered into one branch;and R.sibirica subsp.sibirica BJ-90 clustered into one branch with R.sibirica.Estimates of differentiation time revealed that the mean differentiation time for the six Rickettsia was approximately 2 000 Mya(95%CI:1 999.08-2 001.02 Mya).The tick species distributed in selected ar-eas of Qinghai are diverse,and this study provides the first report of Hy.marginatum in Qinghai Province.SFGR significantly varied in prevalence among tick species and showed high genetic diversity.