Objective To investigate the association between 8 insulin resistance(IR)surrogate markers and incident atherosclerotic cardiovascular disease(ASCVD)in population with cardiovascular-kidney-metabolic syndrome(CKM)of stages 0-3,and to identify the surrogate marker with the best predictive performance.Methods A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort.A Cox proportional hazards model was used to calculate hazard ratios(HRs)between each IR surrogate marker and incident ASCVD.Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD.The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs(RHRs).Time-dependent area under the receiver operating characteristic curve(TDAUC)and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD.Based on the PREVENT equation components and the 8 surrogate markers under analysis,random forest feature selection was used to determine the contribution of each marker to accurate prediction.Results During a follow-up period of82 741.93 person-years,1447 incident cases of ASCVD were recorded,with an incidence density of 17.49 per 1000 person-years.Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL)and the TyG/(TG/HDL)index were not associated with incident ASCVD(P＞0.05).The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence.The most promising indicator,TyG index with waist-to-height ratio(TyG_WHtR),exhibited an inverted J-shaped association with incident ASCVD(P for nonlinearity=0.045;TDAUC=0.640;C=0.634),while the TyG index with body mass index(TyG_BMI),waist circumference(TyG_WC),and waist-to-hip ratio(TyG_WHR)showed positive linear associations(all P for trend＜0.05),with relatively lower predictive performance(C=0.564,0.588,and 0.598,respectively).Although both the TyG index and the metabolic score for insulin resistance(METS-IR)were associated with increased ASCVD risk(TyG:Q2 vs.Q1,HR=1.23 and Q4 vs.Q1,HR=1.24;METS-IR:P for non-linearity=0.045),they exhibited poor predictive performance for incident ASCVD.Conclusion The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM.Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.

Objective To investigate the association between rest-activity rhythm(RAR)and the risks of rheumatoid arthritis(RA),and to evaluate whether genetic susceptibility modifies this relationship.Methods This prospective cohort study utilized data from the UK Biobank,including 88 060 participants who did not have RA at baseline.RAR parameters(e.g.,relative amplitude)were calculated using data obtained through wrist-worn accelerometers.The participants'genetic susceptibility to RA was assessed using a polygenic risk score.Cox proportional hazards models were employed to analyze the association between RAR and RA risk,with interaction terms incorporated to evaluate the effect modification by genetic susceptibility.Results Over a median follow-up period of 7.97 years,660 incident RA cases were identified.After adjusting for age,sex,ethnicity,educational attainment,Townsend deprivation index,drinking status,smoking status,dietary score,body mass index,and polygenic risk score for incident RA,the dose-response analysis revealed a linear relationship between the RAR-related parameters,including the average amplitude during the most active 10 h(M10),interdaily stability(IS),intradaily variability(IV),and the risk of developing RA(P>0.05).In contrast,relative amplitude and the average amplitude during the least active 5 h(L5)showed a nonlinear relationship with the risk of developing RA(P<0.05).Compared to those in the the highest quartile of relative amplitude,participants in the lowest quartile had a 49%increase in the risk of developing RA(hazard ratio[HR]=1.49;95%CI,1.17-1.90).Compared to those in the lowest quartile,participants in the highest quartile of L5 had a 40%increased risk of developing RA(HR=1.40;95%CI,1.12-1.75).Every time M10 increased by one standard deviation,the risk of developing RA decreased by 12%(HR=0.88;95%CI,0.80-0.96).No evidence of effect modification by genetic susceptibility was observed in the RAR-RA association(P>0.05).Conclusion Disrupted rest-activity rhythm is associated with an increased risk of RA,which is independent of genetic susceptibility to RA.Our findings suggest that improving rest-activity rhythm may help reduce RA risks.

Objective:To observe the effects of Jiaji electroacupuncture combined with treadmill running training on tibial bone density,volume and number of blood vessels and VEGF expression after sciatic nerve amputation injury in rats,and provide theoretical basis for promoting tibial reconstruction after Jiaji electroacupuncture combined with treadmill running training. Method:A total of 180 SD rats were randomly divided into normal control group,model control group,Jiaji electroacupuncture group,treadmill group,combination treatment group(Jiaji electroacupuncture+treadmill),with 36 rats in each group.After 2,4 and 8 weeks of postoperative intervention,the rats were divided into 3 subgroups,12 in each subgroup.The model was made by suture of sciatic nerve dissociation injury.The normal control group received no intervention;the model control group received no intervention post-modeling.The Jiaji electroacupuncture group,treadmill group and combined group began to receive Jiaji electroacupunc-ture,treadmill training and combined treatment respectively on the 3rd day after surgery.Bone density of tibia was analyzed by Micro-CT scan.The number and volume of the proximal tibial vessels were analyzed by angi-ography.The expression of VEGF mRNA and protein in tibia was detected by RT-PCR and Western Blot.VEGF concentration in tibial bone marrow was determined by ELISA. Result:At 2,4 and 8 weeks post-intervention,the model control group showed significantly lower tibial bone mineral density,proximal vascular volume and quantity,VEGF mRNA and protein expression in bone tissue,and VEGF concentration in bone marrow compared to the normal control group at the same time point(P＜0.05).However,overtime,the tibial bone mineral density,the volume and number of proximal blood ves-sels,VEGF mRNA and protein expression in bone tissue and VEGF concentration in bone marrow of rats in the Jiaji electroacupuncture group,treadmill group and combination group were significantly higher than those in the model control group at the same time point(P＜0.05),and the combination group showed the most pro-nounced effects(P＜0.05). Conclusion:Jiaji electroacupuncture combined with treadmill training may improve tibial bone mineral density by up-regulating the expression of VEGF in tibia and bone marrow.

Bitter taste receptors,also known as type 2 taste receptors(T2Rs),are found not only in the mouth's taste bud cells but also in various tissues and cells,including macrophages.Macrophages,known for their re-markable plasticity,play a crucial role in regulating innate immunity,managing inflammation,and orchestrating immune responses to antigens,pathogens,and environmental factors.Recently,the study of the expression and function of bitter taste receptors within macrophages has garnered significant interest.This review summarizes the expression levels and dis-tribution characteristics of bitter taste receptors in macrophages and examines their effects on macrophage polarization,phagocytosis,and chemotaxis,as well as their potential molecular mechanisms.The purpose of this review is to provide in-sight and perspectives for research on the regulatory role of T2Rs in macrophage functions.

Humans ; Dapsone/adverse effects* ; Drug Hypersensitivity/etiology* ; Hypersensitivity ; Syndrome

Objective:To investigate the prevalence of Mycoplasma pneumoniae ( Mp) in children undergoing physical examination. Methods:This study randomly enrolled 1 303 children at the age of 6-12 years who underwent physical examination in 2023. Their oral and pharyngeal swabs as well as venous blood samples were collected. The prevalence of Mp in these subjects was detected using isolation and culturing, nucleic acid detection and serological test. Chi-square test was used for statistical analysis. Results:Among the 1 303 children, the detection rate of Mp was 4.1% (53/1 303) by culturing, 7.3% (95/1 303) by nucleic acid detection and 13.6% (177/1 303) by serological test. Statistical analysis showed that there were significant differences in the the detection rates of Mp among children undergoing physical examination between the three methods ( P<0.05). Conclusions:The detection rate of Mp in children undergoing physical examination in 2023 was about 4.1%. Isolation and culturing was more accurate than nucleic acid detection and serological test in the detection of Mp in healthy population as the latter two methods would overestimate the rate.

ObjectiveTo observe the effect of Jiaji electroacupuncture combined with neurodynamic mobilization on nerve conduction velocity and the expression of Netrin-1, Slit2 and Rho GTPases after sciatic nerve injury in rabbits. MethodsA total of 216 New Zealand rabbits were randomly divided into nomal control group (NC), vector virus group (VV), Jiaji electroacupuncture combined with neurodynamic mobilization group (EN), Netrin-1 group (N1), Slit2 group (S2) and N1+S2 group. Each group was divided into three subgroups according to the postoperative treatment time points (one, two and four weeks), with twelve rabbits in each subgroup. The rabbit model of Sunderland Ⅲ degree injury of the left sciatic nerve was established by clamping method. There was no intervention in NC, and virus was injected during the preparation of the model. Jiaji electroacupuncture and neurodynamic mobilization were administrated three days after operation in EN group. Nerve conduction velocity of sciatic nerve was measured with electromyography. The sciatic nerve and L_4-6 spinal cords were obtained, the expression of Netrin-1 and Slit2 mRNA were detected real-time quantitative polymerase chain reaction and immunofluorescence double staining, and the expression of Rac1, Cdc42 and RhoA protein were observed via Western blotting. ResultsOne, two and four weeks after modeling, the nerve conduction velocity was more in EN group and N1+S2 group than in N1 group and S2 group (P < 0.05); the Netrin-1 and Slit2 mRNA expression were higher in the EN group and N1+S2 group than in the VV group and NC group (P < 0.05); the protein expression of Rac1 and Cdc42 were higher, and the protein expression of RhoA was lower in EN group and N1+S2 group than in N1 group, S2 group and VV group (P < 0.05). ConclusionJiaji electroacupuncture combined with nerve mobilization may promote the axonal regeneration by regulating the expression of Netrin-1 and Slit2, adjusting the imbalance of Rho GTPases enzyme system, and then promoting cytoskeleton reorganization and peripheral nerve regeneration after injury.

Objective:To explore the diagnostic process and outcomes of patients with aplastic anemia (AA) who received outpatient treatment in a real-world setting.Methods:The diagnostic processes, treatment regimens, and outcomes of 176 patients with AA treated in outpatient centers from January 2018 to December 2019 were reviewed.Results:The median interval from the onset of symptoms to the first visit was 7 (5-120) months. Complaints during the first visit included bleeding (52.3% ) , anemia (51.7% ) , and infection (6.8% ) . For diagnosis, 168 patients (95.5% ) underwent bone marrow aspiration; however, only 22 of them (17.1% ) consented aspiration in multiple sites (sternum) . The completion rate of bone marrow biopsy was 85.1% (143/168) ; flow immunophenotype and karyotype analyses were performed on 59.5% (100/168) and 58.9% (99/168) of AA patients, respectively, and the culture of clonal forming units by bone marrow mononuclear cells was performed on 26.8% (45/168) of AA patients. The most preferred regimen was cyclosporine combined with androgen and levamisole (43.8% , 77 patients) , followed by cyclosporine combined with androgen (25.6% , 45 patients) . Cyclosporine alone was administered in 24 patients (13.6% ) and androgen alone in 16 patients (9.1% ) . Furthermore, 14 patients (7.9% ) did not consent to any drugs or only chose traditional Chinese medicine. The patients were divided according to the frequencies of follow-up: regular follow-up group (≥4 times/year, n=130) and irregular group (<4 times/year, n=46) . The former had a higher 6-month remission rate (52.5% vs 28.0% , P=0.005) , a greater high-quality remission rate in 12 months (40.7% vs 16.7% , P=0.027) , and a lower relapse rate in 24 months (4.4% vs 36.4% , P=0.001) . Conclusion:In real-world settings, bone marrow aspiration in multiple sites should be addressed in outpatient treatment for AA diagnostic work-up, including PNH clone screening, flow immunophenotype, chromosome karyotype analysis, and culture of clonal forming units. Patients with AA who follow regular visits were more likely to achieve high-quality remission and a lower relapse rate. Visits at least four times per year are recommended for AA patients undergoing outpatient treatment.

Objective:To investigate the distribution of pathogens and the antibiotic resistance profile of bloodstream infections in adult patients with hematological diseases in the period 2014-2018 to provide evidence for the rational use of antibiotics.Methods:We retrospectively analyzed the bloodstream infections in patients with hematological diseases from January 2014 to December 2018 at the institute of Hematology & Blood Diseases Hospital; this included an assessment of the clinical characteristics, distribution of pathogens, and antibiotic resistance data.Results:There were 1935 episodes of BSIs in the 1478 patients who were studied; among these, 1700 episodes occurred in the neutropenic phase. The 7-day and 30-day all-cause mortality rates were 5.5% and 8.2%, respectively. Bloodstream infection was usually accompanied by respiratory tract, perianal zone mucositis, and digestive tract symptoms; the respective proportions were 12.4%, 12.3%, and 9.1%, respectively. Total 2025 strains were isolated; 1551 (76.6%) of the pathogens were gram-negative bacteria, mainly Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa; 423 (20.9%) were gram-positive bacteria, mainly Staphylococcus spp. and Streptococcus spp. Viridans; 51 (2.5%) were fungi, mainly Candida tropicalis. The resistance rates of Enterobateriaceae to piperacillin/tazobactam, carbapenems, amikacin were <10%. The resistance rates of K. pneumoniae to cefepime, piperacillin/tazobactam and meropenem increased annually. The resistance rates of Pseudomonas aeruginosa to piperacillin/tazobactam, quinolones, Aminoglycosides were <5% even when compared to carbapenems. Eleven stains of methicillin-resistant S. aureus and 1 stain of vancomycin-resistant Enterococcus faecium were detected.Conclusion:The pathogens of bloodstream infection in adult patients with hematological diseases are widely distributed. The resistance rates of different strains vary; the rates in some species had a tendency to increase. Antibiotics should be selected rationally as per the distribution of pathogens and resistance to antibiotics in different patient groups.

Objective:To investigate the microbiologic and clinical characteristics of bloodstream infection in neutropenic pediatric patients with hematological malignancies and provide data support for the rational use of antimicrobial agents in these patients.Methods:A retrospective analysis was performed on the clinical data, pathogen species distribution, and drug sensitivity data of bloodstream infection in neutropenic pediatric patients with hematological malignancies from the Institute of Hematology & Blood Diseases Hospital from January 2014 to December 2018.Results:Total 537 episodes of bloodstream infections occurred in 427 neutropenic children with hematological malignancies; the 30-day all-cause mortality rate was 3.7%. The clinical feature of 44.7% patients with bloodstream infection was only fever, and the pathogenic bacteria were mainly enterobacteriaceae bacteria. Bloodstream infection was usually accompanied by oral mucosa (20.7%) , respiratory tract (20.5%) , and digestive tract (14.3%) symptoms. The distribution of pathogens in patients with different symptoms of bloodstream infection varied ( χ2=40.561, P=0.001) . Total 550 strains of pathogens were isolated, and the top 5 bacteria were Streptococcus aureus (109 strains, 19.8%) , Escherichia coli (99 strains, 18.0%) , Staphylococcus epidermidis (75 strains, 13.6%) , Klebsiella pneumoniae (67 strains, 12.2%) , and Staphylococcus aureus (32 strains, 5.8%) . The resistance rates of Enterobacteriaceae and Pseudomonas aeruginosa to piperacillin/tazobactam and carbapenems were <5%. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) in Staphylococcus aureus was 9.7%. Conclusion:The proportion of pathogenic bacteria gram-positive cocci and gram-negative bacilli in the bloodstream infection of neutropenic children with hematological malignancies was approximately the same, suggesting that the use of antimicrobial agents should be broad-spectrum. Carbapenems, glycopeptides, and enzyme inhibitor complexes still have good effects.