ObjectiveTo investigate the mechanism by which Wumeiwan suppresses the development and progression of colorectal cancer（CRC） through the regulation of fatty acid metabolic reprogramming， thereby providing new experimental evidence for the prevention and treatment of CRC. MethodsA total of 120 C57BL/6 mice were randomly divided into the blank group， model group， Wumeiwan high-， medium-， and low-dose groups（54， 27， 13.5 g·kg^-1）， and the mesalazine group（0.01 g·kg^-1）， with 20 mice in each group. Except for the blank group， all mice were subjected to azoxymethane（AOM）/dextran sulfate sodium（DSS） treatment to establish an inflammation-associated CRC model. One week after AOM injection， mice in the treatment groups received intragastric administration of the designated drugs， while the blank and model groups received an equal volume of purified water， continuing until 20 d after the intervention endpoint. Hematoxylin-eosin（HE） staining was used to observe colonic histopathological alterations， and immunohistochemistry for vascular endothelial growth factor（VEGF） was performed to evaluate neovascularization and tumor invasion. Metabolomics combined with Kyoto Encyclopedia of Genes and Genomes（KEGG） and metabolite set enrichment analysis（MSEA） was applied to identify key CRC-related metabolic pathways， which were further validated by transcriptomic Gene Ontology（GO） enrichment and gene heatmap analysis. Subsequently， Western blot was performed to determine the expression levels of core proteins in these pathways， and immunofluorescence was used to analyze their localization and co-expression patterns in tissues， thereby elucidating the mechanism of Wumeiwan from multiple biological dimensions. ResultsCompared with the blank group， mice in the model group exhibited a significant decrease in body weight and a significant increase in the disease activity index（DAI） score（P<0.05）， with pronounced colonic mucosal damage accompanied by aggravated tumor invasion. Compared with the model group， Wumeiwan intervention markedly improved body weight loss and reduced DAI score， attenuated mucosal injury， and significantly decreased VEGF expression level（P<0.05）. Multi-omics analysis revealed that differential metabolites and genes across groups were commonly enriched in fatty acid metabolism， fatty acid biosynthesis， and other lipid-related pathways. Relative to the blank group， the model group showed significant upregulation levels of fatty acid synthesis-related genes， including sterol regulatory element-binding protein 1（SREBP1）， fatty acid synthase（FASN）， stearoyl-CoA desaturase 1（SCD1）， as well as saturated fatty acids（P<0.05）. Compared with the model group， treatment with Wumeiwan significantly reduced the expression of key genes involved in fatty acid metabolic pathways， including SREBP1， FASN， and SCD1（P<0.05）. Western blot results further confirmed that proteins in this pathway were significantly elevated in the model group， whereas they were markedly downregulated following Wumeiwan treatment（P<0.05）. Immunofluorescence analysis demonstrated enhanced co-localization of SREBP1 with the cancer-associated fibroblast（CAF） marker α-smooth muscle actin（SMA） in the model group， whereas this co-localization signal was attenuated after Wumeiwan intervention（P<0.05）. ConclusionWumeiwan can improve survival outcomes and alleviate colonic pathological damage in CRC mice， its therapeutic mechanism may be closely associated with the regulation of fatty acid metabolic reprogramming mediated by the SREBP1/FASN/SCD1 signaling pathway.

OBJECTIVE To explore the effects of Polygala tenuifolia compatibility on toxicity， anti-inflammatory and analgesic efficacy of sand-ironing Strychnos nux-vomica （SS）. METHODS The preparation of SS single decoction， SS-P. tenuifolia core-removed （PC） （1∶2.5） or （1∶5） combined decoction， and SS-PC （1∶5） mixture were carried out to investigate their median lethal dose （LD50）. Using aspirin as positive control， the number of writhing movements， analgesic rate， pain latency， ear swelling degree and inflammation inhibition rate induced by the above-mentioned medicinal liquids in mice were compared. The contents of the active and toxic components， strychnine and brucine， in the above-mentioned medicinal liquids were also determined. RESULTS The LD50 values of SS single decoction， SS-PC （1∶2.5） combined decoction， SS-PC （1∶5） combined decoction and SS- PC （1∶5） mixture were 302.00， 614.47， 1 445.44 and 1 778.28 mg/kg， respectively. Compared with control group， the number of writhing movements and ear swelling degree in the mice of the above-mentioned medicinal liquid groups were reduced or decreased significantly （P＜0.05 or P＜0.01）； pain latency [at 90 and 120 minutes in the SS single decoction group， at 60 and 90 minutes in the SS-PC （1∶2.5） combined decoction group， and at 60，90， 120 minutes in the SS-PC （1∶5） combined decoction group and SS-PC （1∶5） mixture group] was significantly prolonged （P＜0.05 or P＜0.01）； analgesic rates of the respective medicinal liquids were 39.30%， 70.87%， 80.00% and 82.46%， and inflammation inhibition rates were 38.08%，TD 57.89%， 76.47% and 50.46%； analgesic and anti-inflammatory effects of combined decoction and mixture were generally better than those of the single decoction （P＜0.05 or P＜0.01）. In the above-mentioned four medicinal liquids， the total contents of strychnine were 0.71%， 0.42%， 0.47% and 0.64%， and the total contents of brucine were 0.88%， 0.63%， 0.57% and 0.88%， respectively. CONCLUSIONS The combination of P. tenuifolia can reduce the toxicity of SS and enhance its anti-inflammatory and analgesic effects. Moreover， there is a tendency for the toxicity-reducing and efficacy-enhancing effects to increase with the increasing dosage of P. tenuifolia. Additionally， the combined decoction of SS and P. tenuifolia can reduce the contents of the active and toxic components， strychnine and brucine， in SS.

OBJECTIVE To analyze the etiological and clinical characteristics of the neonates with early-onset and late-onset purulent meningitis.METHODS A total of 140 neonates who were diagnosed with purulent meningitis and were hospitalized in neonatal intensive care unit(NICU)of Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from Jan.2018 to Dec.2022 were recruited as the research subjects and were divided into the early-onset group with 32 cases and the late-onset group with 108 cases according to the onset time.The clinical data were collected from the enrolled neonates and were retrospectively analyzed.The etiological and clinical char-acteristics of the neonates with purulent meningitis were observed.RESULTS Totally 140 neonates with purulent meningitis were included in the study,the total morbidity rate was 1.03％(140/13644),and it was more common among the male neonates and full-term neonates,dominated by late-onset cases.The incidence rates of perinatal infection,premature rupture of fetal membranes,lethargy/irritability,cyanosis,abnormal muscle tone and septic shock were higher in the early-onset group than in the late-onset group(P＜0.05).There were significant differ-ences in serum PCT,cerebrospinal fluid cell counts,percentage of neutrophils and proteins between the early-on-set group and the late-onset group(P＜0.05).The positive rate of etiological culture of the early-onset group was 43.75％(14/32),higher than 20.37％(22/108)of the late-onset group(P＜0.05);Escherichia coli was the pre-dominant species of pathogen isolated from the two groups.The total proportion of the neonates with abnormal imaging findings was 22.85％among the two groups of neonates;the intracranial hemorrhage,subdural effusion and ventricular enlargement/hydrocephalus were the major abnormal types;the proportion of the neonates with abnormal imaging findings of the early-onset group was 43.75％,higher than 16.67％of the late-onset group(P＜0.05).CONCLUSIONS The neonates with late-onset purulent meningitis are dominant among the neonates with purulent meningitis enrolled in the study.The neonates with early-onset purulent meningitis present with more se-vere clinical manifestations and higher proportion of abnormal imaging findings;there is significant difference in the clinical characteristics between the early-onset neonates and the late-onset neonates.The result of etiological culture shows that E.coli is the predominant species of pathogen among both the early-onset neonates and the late-onset children.

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.

This study explores whether the current external quality assessment (EQA) level and acceptable bias for basic semen analysis in China are clinically useful. We collected data of semen EQA from Andrology laboratories in the Hunan Province (China) in 2022 and searched for data in the published literature from January 2000 to December 2023 in China. On the basis of these data, we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics. We compared these findings with quality specifications based on biological variation from optimal, desirable, and minimum levels of bias to seek a unified and more suitable semen EQA bias evaluation standard for China's national conditions. Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories, ranging from 8.2% to 56.9%. A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility (PR), whereas 100.0% and 75.0% of laboratories met only the minimum quality specifications for sperm concentration and total motility (nonprogressive [NP] + PR), respectively. The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification, whereas the Z value for PR was equivalent only to the minimum performance specification. This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation. These specifications should be unified among external quality control (EQC) centers based on biological variation.
Semen Analysis/standards* ; Humans ; China ; Male ; Quality Control ; Sperm Motility ; Sperm Count/standards*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*