OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective:To investigate the prognostic value of tumor mutation burden(TMB)in pancreatic neuroendocrine tumours(PanNETs).Methods:Data of 96 PanNETs patients was in-cluded in the study and cut-off value of TMB was determined according to the time dependent re-ceiver operator characteristic(ROC)curve and area under the curve(AUC).Logistic regression analysis was used to determine the clinical and pathological features associated with TMB.Cox re-gression analysis was used to detect the correlation between TMB and the overall survival time(OS)of patients.Kaplan-Meier method was used to construct the survival curve.Results:Ac-cording to the time dependent ROC curve and AUC,the optimal truncation value of TMB was deter-mined to be 0.6 mut/Mb.Logistic regression analysis indicated that high TMB was independently correlated with age[OR=1.126(1.057-11.199),P＜0.001]and extrapancreatic spread[OR=15.931(2.228-113.892),P=0.006].Kaplan-Meier curve showed that patients with high TMB had a poor OS[HR=5.042(1.41917.917),P=0.012].Multivariate Cox regression analysis indicated that TMB was an independent prognostic factor of PanNETs[HR=7.578(1.409-40.744),P=0.018].Conclusion:TMB is independently correlated with age and extrapancreatic spread,and is an independent prog-nostic factor for PanNETs patients and PanNETs patients with high TMB have a poorer prognosis.

Cells are the fundamental structural and functional units of biological organisms,with inherent differences in composition and interactions with exogenous substances,known as cellular heterogeneity.Single cell inductively coupled plasma-mass spectrometry(SC-ICP-MS)allows for the high-throughput introduction of individual cells,enabling the highly sensitive detection and quantification of elements within a single cell,thus effectively providing information on cellular heterogeneity.This review outlined the SC-ICP-MS sample preparation process for different types of cells(single-cell systems,aggregation-prone and adherent cell systems,animal tissues,and plant tissues),including steps such as separation,washing,and fixation,as well as the advantages and existing issues of the current sample introduction systems and quantification methods.The recent applications of SC-ICP-MS in detecting endogenous substances(endogenous elements and proteins),exogenous substances(heavy metals,metal-based drugs and nanoparticles),and the simultaneous detection of both endogenous and exogenous substances were summarized.Finally,the perspectives on the future development of SC-ICP-MS in analytical methods and application fields were presented,including the optimization of single-cell sample preparation,transport efficiency,evaluation standards of ionization efficiency,and the establishment of multiparametric cell analysis platforms.

OBJECTIVE To investigate the effect of Huangqi-Ezhu-Chonglou combination on macrophage polarization and its mechanism of inhibiting colorectal cancer(CRC)cells proliferation and migration.METHODS THP-1 cells were stimulated with phorbol 12-myristate 13-acetate(PMA)and interleukin-4(IL-4)to establish M2 macrophage polarization model.The experiment was divided into M0 group(PMA treatment),M2 group(PMA+IL-4 treatment),and M2+ Huangqi-Ezhu-Chonglou combination group(PMA+IL-4+Huangqi-Ezhu-Chonglou combination treatment).The effect of Huangqi-Ezhu-Chonglou combination freeze-dried powder on the viability of macrophage was detected by CCK-8 method.The expression of macrophage polarization markers,glu-taminase(GLS)mRNA and protein was detected by qPCR and Western blot.The levels of interleukin-10(IL-10),transforming growth factor-β(TGF-β)and tumor necrosis factor-α(TNF-α)in cell supernatant were detected by ELISA.CCK-8 method and Tr-answell assays were used to detect the proliferation and migration of HCT116 cells intervened by the supernatant of macrophage culture treated with Huangqi-Ezhu-Chonglou combination,namely conditioned medium(CM).RESULTS Compared with the M0 group,the expression levels of IL-10,mannose receptor(CD206),arginase 1(ARG1),and GLS mRNA and protein in the M2 group were significantly increased(P<0.01,P<0.001),the levels of IL-10 and TGF-β secreted by macrophages were significantly increased(P<0.01,P<0.001);compared with the M2 group,the M2+ Huangqi-Ezhu-Chonglou combination group had significantly reduced IL-10,CD206,ARG1,and GLS mRNA and protein expression(P<0.05,P<0.01),the mRNA and protein levels of TNF-α and in-ducible nitric oxide synthase(iNOS)were significantly increased(P<0.05,P<0.01,P<0.001),the interleukin-1β(Interleukin-1β,IL-1β)mRNA expression significantly increased(P<0.01),and the contents of IL-10 and TGF-β in the cell supernatant sig-nificantly decreased(P<0.05,P<0.01),while TNF-α content significantly increased(P<0.01).CCK-8 and Transwell results showed that compared with the M0-CM group,the M2-CM promoted the proliferation and migration of HCT116 cells(P<0.01,P<0.001),the M2+ Huangqi-Ezhu-Chonglou-CM group significantly inhibited HCT116 cell proliferation and reduced cell migration compared to the M2-CM group(P<0.01,P<0.001).CONCLUSION Huangqi-Ezhu-Chonglou combination can inhibit colorectal cancer cells proliferation and migration by regulating macrophage polarization,and its mechanism may be related to the changes in the expression of GLS,a key enzyme in glutamine metabolism.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.