Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective To analyze the differences of brain activity between first-episode untreated depressive patients with and without suicidal ideation(SI),and its correlations with clinical characteristics.Methods A total of 40 major depressive disorder(MDD)patients with SI(MDD+SI group),40 patients without SI MDD(MDD+NSI group),and 40 healthy controls(HC)(HC group)were enrolled.The 17-item Hamilton depression scale(HAMD-17)and Beck scale for suicide ideation(BSI)were used to assess the severity of depression and SI,respectively.MRI data were collected.The values of fractional amplitude of low-frequency fluctuation(fALFF)were calculated.Results(1)Compared with the HC group,the MDD+NSI group showed decreases in the fALFF val-ues of the default network and attention network.The fALFF values of the attention network in the MDD+SI group showed decreases.Compared with the MDD+NSI group,the MDD+SI group showed decreases in the fALFF values of the attention network.(2)The fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.55;P<0.001)in the MDD+NSI group,while the fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.53;P<0.001)and the total score of BSI(r=-0.51;P<0.001)in the MDD+SI group.(3)The optimal critical value of fALFF value in left middle frontal gyrus for predicting SI occurrence in MDD patients was-0.039,area under the curve(AUC)was 0.76,sensitivity was 0.63,and specificity was 0.80.Conclusion The decreased local activity intensity in the left middle frontal gyrus of the brain might be the central mechanism for the occurrence of SI in MDD patients.In addition,the left middle frontal gyrus might have certain value in identifying SI and predicting the severity of SI.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Chronic wounds, defined as persistent failure to heal due to specific etiological factors, remain a major clinical challenge. Current standard interventions such as negative pressure wound therapy are limited by complications like hypergranulation and poor patient compliance, while emerging stem cell-based therapies carry potential tumorigenic risks. Consequently, identifying strategies to safely and effectively accelerate wound healing continues to be a critical focus in contemporary clinical research. Platelet-rich plasma derived extracellular vesicles (PRP-EVs) are extracellular vesicles released by platelets after activation. They have the characteristics of autologous origin, higher safety, and more mild and convenient clinical application. Studies have shown that PRP-EVs are rich in bioactive molecules such as lipids, proteins and RNA, which have outstanding performance in regulating wound inflammation, promoting angiogenesis, enhancing cell migration and proliferation, and are expected to become an effective tool for the treatment of chronic wounds. This review discusses the methods, mechanisms of action, and challenges associated with the use of PRP-EVs in chronic wound management, providing a foundation for future research and clinical applications in this field.

The active ingredient of WINREVAIR,sotatercept-csrk,is a recombinant activin receptor ⅡA-Fc(ActRⅡA-Fc)fusion protein that improves pro-proliferation(ActRⅡA/Smad2/3-mediated)and anti-proliferation(BMPRⅡ/Smad 1/5/8-mediated)signals,thereby regulating vascular proliferation.In March 2024,WINREVAIR was approved by the U.S.Food and Drug Administration for the treatment of pulmonary arterial hypertension(PAH)in adults.Clinical studies have shown that WINREVAIR can improve exercise capacity and reduce the incidence of all-cause death or clinical worsening of PAH by 84％.Common adverse drugreactions include headache,epistaxis,rash,etc.

Objective:To investigate the effects of CO2 intracavitary laser combined with pelvic floor magnetic stimulation on surface electromyography(sEMG)values and pelvic floor three-dimensional ultrasound parameters in female patients with stress urinary incontinence(SUI).Methods:A prospective study was conducted on 92 female SUI patients treated at the outpatient department of Meizhou People's Hospital from October 2021 to July 2023.The patients were randomly divided into an observation group and a control group(n=46 each)using a random number table.Both groups received home-based pelvic floor muscle training.The control group additionally received pelvic floor magnetic stimulation,while the observation group was treated with CO2 intracavitary laser combined with pelvic floor magnetic stimulation.The urinary leakage status,treatment efficacy,pelvic floor muscle sEMG,pelvic floor three-dimensional ultrasound parameters,quality of life,and sexual quality of life were compared between the two groups.Assessments included the International Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF),the Incontinence Impact Questionnaire-Short Form(IIQ-7),and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire(PISQ-12).Results:1-hour leakage volume:0 g(observation group)vs.3 g(control group),24-hour leakage episodes:0 times(observation group)vs.0 times(control group),the observed differences were statistically significant(Z=-2.866,-2.355,P<0.05).Total effective rate:95.65%(observation)vs.58.70%(control),the observed differences were statistically significant(x2=4.083,P<0.05).Pelvic floor muscle sEMG(after treatment):Maximal fast contraction:(40.78±3.28)μV(observation)vs.(35.17±5.10)μV(control),Mean tonic contraction:(31.56±4.20)μV(observation)vs.(25.87±3.82)μV(control),Mean endurance contraction:(29.34±2.58)μV(observation)vs.(25.37±2.67)μV(control),all differences between the two groups were statistically significant(t=2.736,19.919,3.025,15.426,P<0.05).After treatment,both groups showed reductions in bladder neck descent(BND)during Valsalva maneuver,bladder-symphysis distance(BSD),urethral rotation angle(URA),and posterior vesicourethral angle(RVA).However,the observation group demonstrated significantly greater reductions compared to the control group(post-treatment data:observation group(24.30±3.21)mm,(2.34±0.23)mm,(56.40±5.87)°,(89.54±9.21)°;control group(26.21±3.48)mm,(3.57±0.35)mm,(60.29±6.45)°,(126.71±13.50)°.These differences were statistically significant(t=2.736,19.919,3.025,15.426,P<0.05).Similarly,both groups exhibited decreased scores on the ICIQ-SF and IIQ-7 scales,along with increased scores on the PISQ-12.Again,the observation group showed superior improvement,with statistically significant differences(t=11.478,13.168,6.631,P<0.05).Conclusion:On the basis of pelvic floor muscle training,CO2 intracavitary laser therapy combined with pelvic floor magnetic stimulation can effectively alleviate urinary incontinence symptoms in patients with female stress urinary incontinence(FSUI),enhance therapeutic efficacy,improve pelvic floor muscle strength and the stability of pelvic support structures,and promote quality of life and sexual function.

AIM To investigate the improvement effect of Qinhuo Formula on obese mice induced by high-fat diet.METHODS Obese mice model was induced by feeding with high-fat diet.The mice successfully established were randomly divided into model group,orlistat group(15.6 mg/kg)and low and high dose groups of Qinhuo Formula(13.5 and 22.5 g/kg),and normal mice were taken as control group,with 10 mice in each group,and the drugs were continuously intervened for 8 weeks.After the drug administration,the body weight,abdominal circumference,fasting blood glucose and glucose tolerance were measured,and area under the curve(AUC)of oral glucose tolerance test(OGTT),Lee's index and fat index were calculated.The serum levels of TC,TG,LDL-C and HDL-C were detected by blood biochemical analyzer.Serum levels of TNF-α,IL-1 β and IL-6 were detected by ELISA.HE staining was used to observe the white fat of epididymis and the pathological changes of liver tissue.RT-qPCR and Western blot were used to detect the mRNA and protein expressions of TLR4,MyD88 and NF-κB in liver tissue.RESULTS Compared with the model group,the body weight,abdominal circumference and Lee's index of mice in each dose group of Qinhuo Formula decreased(P＜0.01);OGTT-AUC decreased(P＜0.01);visceral fat index decreased(P＜0.05,P＜0.01);the levels of serum TG,TC,IL-6 and IL-1 β decreased(P＜0.01);the diameter of epididymal adipocytes decreased,arranged tightly and regularly,the lipid droplet cavities in liver tissue decreased,and the morphology of hepatocytes recovered;the mRNA and protein expressions of TLR4,MyD88 and NF-κB decreased(P＜0.05,P＜0.01).CONCLUSION Qinhuo Formula can effectively improve glucose-lipid metabolism and reduce inflammation in obese mice,and its mechanism may be related to the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.