OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease （CKD）. METHODS Fifty male SD rats were randomly divided into a sham surgery group （10 rats） and a modeling group （40 rats）. The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling， the rats were randomly divided into model group， esaxerenone group （positive control）， and TCM low- and high-dose groups， with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone， while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively， the sham surgery group and model group were given an equal volume of physiological saline， all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea （SUr）， serum creatinine （SCr）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels； enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α（TNF-α）； immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α） ， mitochondrial transcription factor A （TFAM）， absent in melanoma 2（AIM2）， caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in renal tissue； real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group， the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction， severe tubular dilation， and increased deposition of blue fibrin； the levels of SUr， SCr， MDA， IL-1β， IL-6， TNF-α，the protein expression of AIM2， GSDMD， caspase-1， IL-1β， IL-18 ， and the mRNA expression of AIM2 were significantly increased or up-regulated （P＜0.01）； the levels of SOD， the protein expression of PGC-1α， TFAM were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function， alleviate renal inflammatory damage and pyroptosis， and exert renal protective effects by regulating the AIM2 pyroptosis pathway.

Aim To investigate the regulatory mecha-nism of butin on the proliferation,migration,cycle blockage and pyroptosis related inflammatory factors in human fibroblast-like synoviocytes of rheumatoid arthri-tis(HFLS-RA).Methods Cell proliferation,migra-tion and invasion were studied using cell migration and invasion assays.Cell cycle was detected by flow cytom-etry,and the expression of the pyroptosis-associated in-flammatory factors IL-1β,IL-18,caspase-1 and caspase-3 was detected by ELISA,RT-qPCR and West-ern blot.Results Migration and invasion experiments showed that the cell proliferation rate of the butin group was lower than that of the blank control group(P＜0.05).Cell cycle analysis demonstrated that in the G0/G1 phase,the DNA expression was elevated in the medium and high-dose groups of butin(P＜0.05),while in the G2 and S phases,the DNA expression was reduced in the medium and high-dose groups of butin(P＜0.05).The results of ELISA,RT-qPCR and Western blot assay revealed that the expression of IL-1β,IL-1 8,caspase-1,and caspase-3 decreased in the butin group compared with the IL-1β+caspase-3 in-hibitor group(P＜0.05).Conclusions Butin inhib-its HFLS-RA proliferation by inhibiting the synthesis of inflammatory vesicles by caspase-1 in the pyroptosis pathway,thereby reducing the production and release of inflammatory factors such as IL-1β and IL-18 down-stream of the pathway,and also inhibits HFLS-RA pro-liferation by exerting a significant blocking effect in the G1 phase,which may be one of the potential mecha-nisms of butin in the treatment of RA.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

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 changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

This study was aimed at examining the influence of meteorological factors on scrub typhus in Xiamen.Scrub ty-phus monitoring data and meteorological factors were collected in Xiamen from 2005 to 2023.Spearman correlation analysis and nonlinear regression were used to analyze the correlation between scrub typhus incidence and meteorological factors.The inci-dence of scrub typhus first increased and subsequently decreased in Xiamen from 2005 to 2023.The highest incidence was be-tween 2014 and 2016,and the peak incidence was from June to October.The monthly incidence of scrub typhus positively cor-related with daily minimum temperature(r=0.637,P＜0.001,daily average temperature(r=0.627,P＜0.001),daily maxi-mum temperature(r=0.612,P＜0.001),sunshine duration(r=0.405,P＜0.001),average relative humidity(r=0.346,P＜0.001),and daily rainfall(r=0.207,P=0.002),and negatively correlated with average atmospheric pressure(r=-0.549,P＜0.001),whereas no correlation was observed with the average wind speed in Xiamen.The regression equation of scrub ty-phus monthly incidence and meteorological parameters was y=-433.869-11.503x1+0.381x1 2+9.150x2-0.197x2 2+3.936 x3-0.132x3 2+0.881x4+0.035x4 2-1.048x5+0.009x5 2+0.186x6-0.023x6 2+0.421x7+6.210×10-5x8-1.051 × 10-10x8 2 in Xiamen,and the R2 was 0.473,thus indicating good model fit.Scrub typhus incidence correlated with the daily minimum av-erage temperature,average temperature,daily maximum tem-perature,sunshine duration,daily rainfall,relative humidity,and average atmospheric pressure in Xiamen.Various meteoro-logical factors had differing effects on scrub typhus.

Exosomes can ameliorate neuronal cell injury induced by hypoxia-ischemia,but the relation-ship between astrocyte-derived exosomes(As-exo)and mitochondrial function,mitochondrial associated ER membrane(MAM)function and whether mitochondrial autophagy is relevant is currently unclear.The aim of this study was to investigate the role of astrocyte-derived exosomes in the regulation of mito-chondrial function,MAM and mitochondrial autophagy in PC 12 cells after oxygen and glucose depriva-tion/reoxygenation(OGD/R).Exosomes were extracted from the supernatant of the astrocyte culture me-dium by ultracentrifugation.Using the live cell imaging system,we observed that fluorescently labeled exosomes could show obvious enrichment in PC 12 cells at 24 h.Meanwhile,co-localization of exosomes with mitochondria could be observed under the laser confocal scanning microscope;mitochondrial pres-sure changes were detected using the Seahorse cellular energy metabolism fractionation instrument.The result showed that basal respiration in the OGD/R group,compared with that in the control group,proton leakage,maximal respiration and ATP-related respiration were significantly reduced(P＜0.05 or P＜0.01),and all four indexes were elevated and statistically significant in the OGD/R+exo group compared with the control group(P＜0.05 or P＜0.01).The results of the co-localization of the mitochondria and ER showed that the structure of the MAM was harmed by oxygen-sugar deprivation and then reoxygen-ation,and the structure of As-exo and the mitochondria appeared to have a distance-reduced polymeriza-tion phenomenon,while the mitochondria and ER co-localized.The co-localization results of mitochondri-a and ER showed that the structure of MAM was damaged by oxygen deprivation and reoxygenation,and the aggregation phenomenon of MAM was weakened by the treatment of As-exo;the flow-through results showed that As-exo could restore the decrease of the mitochondrial membrane potential and the elevation of the ROS by oxygen deprivation to a certain degree.Western blotting showed that As-exo could signifi-cantly inhibit the mitochondrial autophagy-associated tension protein homologue induced hypothetical ki-nase 1(PTEN induced kinase 1(PINK1)and Parkin protein(parkin RBR E3 ubiquitin protein ligase(Parkin))were elevated,and the addition of As-exo decreased LC3 Ⅱ/LC3 Ⅰ protein expression,ele-vated P62 protein expression,and reduced OGD/R-induced mitochondrial autophagy.The results showed that OGD/R treatment can cause mitochondrial dysfunction,MAM structural changes and increased mito-chondrial autophagy in PC12 cells,and As-exo treatment can improve mitochondrial function,attenuate the formation of MAM,and reduce mitochondrial autophagy in PC 12 cells,which can have the potential of preventing the reperfusion injury in ischemic stroke.

Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.

Objective:To investigate the expression level of urothelial carcinoembryonic antigen 1(lncRNA UCA1)in the bone marrow of acute myeloid leukemia(AML)patients,and to explore the clinical significance of lncRNA UCA1 expression level in AML patients.Methods:Bone marrow samples of 50 AML patients were collected as experimental group,and bone marrow samples of 20 iron deficiency anemia(IDA)patients were collected as control group.The relevant clinicopathological characteristics of AML patients were collected.Real-time quantitative PCR(qRT-PCR)was used to detect the expression level of lncRNA UCA1 in the experimental and control groups,and the relationships between lncRNA UCA1 expression and clinical pathological characteristics and prognosis in AML patients were analyzed.Kaplan-Meier curves were used to analyze the effect of lncRNA UCA1 on the overall survival(OS)of AML patients;And Cox regression model was used to analyze the factors affecting the prognosis of AML patients.Results:Compared with the control group,the expression level of lncRNA UCA1 was significantly elevated in patients with AML(P＜0.001);The proportion of patients with hemoglobin lower than 90 g/L in lncRNA UCA1 high expression group was significantly higher than that in lncRNA UCA1 low expression group(P=0.004);The expression level of lncRNA UCA1 was higher in M1,M2,and M4 subtypes,while it was lower in M0 and M5 subtypes,and the difference was statistically significant(P=0.009).There were no significant difference in sex,age,white blood cell(WBC)count,platelet(PLT)count,bone marrow blasts,chemotherapy regimen and efficacy,karyotype,gene mutation,and prognostic risk stratification between patients in UCA1 high expression group and those in UCA1 low expression group(all P＞0.05).The OS of patients with high expression of lncRNA UCA1 was significantly shorter than that of patients with low expression of lncRNA UCA1(P=0.0229).Conclusion:The expression level of lncRNA UCA1 is significantly upregulated in AML patients.High expression of lncRNA UCA1 is associated with poor clinicopathological features and poor prognosis.Therefore,lncRNA UCA1 can be used as a prognostic indicator and a potential therapeutic target for AML patients.