Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b⁺ and CD54⁺ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b⁺ neutrophils were significantly higher in AKI compared to non-AKI (4.71×10⁹/L vs 3.31×10⁹/L, Z=-2.14, P<0.05). Similarly, the CD54⁺ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×10⁹/L vs 1.79×10⁹/L, Z=-2.99, P<0.05), during rewarming (3.12×10⁹/L vs 1.62×10⁹/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×10⁹/L vs 2.14×10⁹/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b⁺ and CD54⁺ neutrophil levels of AKI were 1.74 folds (4.83×10⁹/L vs 2.77×10⁹/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×10⁹/L vs 1.42×10⁹/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective To investigate the therapeutic mechanism of Shen Wu Yizhi Capsule in the treatment of post-stroke cognitive impairment(PSCI)by using network pharmacology methods and clinical trial validation.Methods A prospective trial was carried out in 90 cases of patients with PSCI admitted to Taihe Traditional Chinese Medicine Hospital Affiliated to Anhui University of Chinese Medicine from August 2022 to February 2024.The patients were randomly divided into the control group and the trial group by random number table method,with 45 cases in each group.The control group was treated with conventional treatment for PSCI,and the trial group was treated with Shen Wu Yizhi Capsule orally on the basis of treatment for the control group.The treatment course for the two groups covered 28 days.The changes of Mini-Mental State Examination(MMSE)score,Montreal Cognitive Assessment(MoCA)score,and the serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in the patients of the two groups were observed before and after treatment.Moreover,the incidences of adverse events in the two groups were recorded,thus to evaluate the safety of the treatment regimens in the two groups.And then the network pharmacological research was performed.TCMSP and literature review were used to obtain the active ingredients of Shen Wu Yizhi Capsule,GeneCards and other databases were used to obtain the PSCI disease targets,and the common targets were inputted into the STRING database to construct the PPI network.Cytoscape 3.9.0 was used to construct the network diagram of Shen Wu Yizhi Capsule-PSCI-targets,DAVID was used to perform GO and KEGG pathway enrichment analysis,and then molecular docking was used to verify the binding activity.Results(1)The results of clinical trial showed that after 28 days of treatment,the MMSE and MoCA scores of patients in the two groups were increased compared with those before treatment(P<0.05),and the increase of the scores in the trial group was significantly superior to that in the control group(P<0.05).The serum levels of TNF-α and IL-6 were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.05).During the trial,both groups of patients did not show obvious adverse reactions,with high safety.(2)The network pharmacological research of Shen Wu Yizhi Capsule yielded 92 active ingredients,803 targets,5 209 disease targets and 556 intersection targets.The core targets were AKT1,TNF,IL-6,TP53 and IL-1B,and the key compounds were deoxyharringtonine,senkyunone and genkwanin.The GO enrichment analysis obtained 1 812 GO entries,of which 154 entries were related with cellular component(CC),1 332 entries were related with biological process(BP),and 326 entries were related with molecular function(MF).The KEGG pathway enrichment analysis yielded 195 signaling pathways.The molecular docking results showed that the key compounds of Shen Wu Yizhi Capsule had good binding activities with the core targets.Conclusion The clinical efficacy of Shen Wu Yizhi Capsule in the treatment of PSCI is remarkable,and its therapeutic mechanism is probably related with multiple components through the signaling pathways such as AKT1,TNF,and IL-6.The results will provide reference for the in-depth study of Shen Wu Yizhi Capsule.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To explore the impact of preoperative fibrinogen levels on the 1-year adverse outcomes after endovascular revascularization in patients with diabetes complicated with lower extremity arteriosclerosis obliterans(LEASO).Methods We collected the baseline clinical data of 289 patients with diabetes complicated with LEASO,who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to December 2022 for endovascular revascularization.All patients were followed up for 13 to 24 months after interventional therapy,with the follow-up information including major adverse cardiovascular events(MACEs)such as all-cause death,acute myocardial infarction and acute stroke,as well as major adverse lower extremity events(MALEs)such as rest pain in the lower extremities,ulcers or skin defects,gangrene,reocclusion and amputation.A multivariable Cox regression model was used to analyze the related risk factors for adverse outcomes 1 year after endovascular revascularization in patients with diabetes complicated with LEASO,and receiver operating characteristic(ROC)curves were constructed to evaluate the predictive efficacy and optimal cutoff value of fibrinogen levels for endpoint events,and Kaplan-Meier survival curves were drawn.Sensitivity analysis was made to assess the differences in the impact of fibrinogen on endpoint events across various subgroups.Results We recruited a total of 289 patients(55 patients in MACEs and 234 in non-MACEs;68 patients in MALEs and 221 in non-MALEs),with a mean age of 67.6±9.3 years,including 215 males.Multivariate Cox regression analysis showed that elevated plasma fibrinogen was an independent risk factor for MACEs(HR=1.250,95％CI:1.053-1.484,P=0.011)and all-cause death(HR=1.297,95％CI:1.030-1.633,P=0.027)in the cohort followed up 1 year after interventional therapy,but had no significant impact on the occurrence of MALEs(P=0.625).Baseline plasma fibrinogen level 4.32 g/L was the optimal cutoff value for predicting MACEs(sensitivity=0.673,95％CI:0.582-0.767;specificity=0.688,95％CI:0.562-0.775)and all-cause death(sensitivity=0.679,95％CI:0.483-0.880;specificity=0.651,95％CI:0.465-0.755).The AUC for predicting MACEs and all-cause death after interventional therapy was 0.652(95％CI:0.564 2-0.739 1)and 0.619(95％CI:0.507-0.733),respectively.After a median follow-up of 14.03 months,patients with preoperative fibrinogen level ≥ 4.32 g/L had a significantly higher risk of MACEs and all-cause death compared to patients with preoperative fibrinogen＜4.32 g/L(P＜0.001),and there were no significant differences in different subgroups,including gender(male/female,interaction P=0.836),age(＜65 years/≥65 years,interaction P=0.211),smoking status(never smoked/current or former smoker,interaction P=0.779),chronic kidney disease(yes/no,interaction P=0.360),and heart failure(yes/no,interaction P=0.114).Conclusion Preoperative plasma fibrinogen≥4.32 g/L is an effective indicator for predicting MACEs and all-cause mortality following endovascular revascularization in patients with diabetes and LEASO.

Objective To explore the effects of air pressure, humidity, wind, and sunshine on the incidence of cardiovascular and cerebrovascular diseases (CVD) in Guiyang, and to provide reference for the prevention of CVD. Methods Using CVD incidence data from September 2021 to August 2022 in Guiyang City and meteorological data including average air pressure, average humidity, wind, and sunshine during the same period, the effects of meteorological factors on CVD incidence were explored and the importance of each factor was analyzed. Results When air pressure was below 868 hPa, above 887 hPa, or between 877 and 883 hPa, and when air pressure dropped less than 5.3 hPa within 24 hours, there was a higher risk of CVD. When the humidity was above 81%, the wind speed was small (<1.2 m/s) or high (>4m/s), and there was less sunlight (less than 3 hours), the risk of CVD was higher. Low humidity (<60%) was not conducive to the onset of CVD. There were highest risks at lag 5~10 days and 4-25 days for high pressure and low sunlight, respectively. When the relative humidity was saturated, there was an immediate effect. When the wind speed was low and high, the immediate effect and hysteresis effects were significant. Among the above meteorological factors, the impact of 24-hour variation of pressure and high or low atmospheric pressure on the incidence of CVD was the most significant, while the impact of sunlight and humidity was the weakest. The impact of diurnal variations in wind and atmospheric pressure was not clear. Conclusion The impact of air pressure on the incidence of CVD does not exhibit a simple linear relationship. The risk of CVD is high in high humidity, low light, and moderate or strong winds. It is necessary to fully consider changes in meteorological factors for CVD prevention and control.

Objective : To investigate the regulatory mechanism of nucleotide excision repair(NER) in hepatocellular carcinoma(HCC). Methods : Based on the expression levels of genes in the NER pathway, we performed molecular typing of HCC using the TCGA database. HCC cell lines were constructed through the knockdown of RNA binding motif protein 39(RBM39) using siRNA. HCC cell lines were constructed through the overexpression ofRBM39usingRBM39plasmid. Cells were treated with Indisulam, a reagent that induces RBM39 protein degradation. Western blot and real-time fluorescence quantitative PCR were used to detect the expression levels and changes of mRNA and protein of RBM39 and excision repair cross complementation group 1(ERCC1); flow cytometry was used to detect NER efficiency; CCK-8 assay was used to detect cell viability. Results : HCC patients were categorized into three types—C1, C2, and C3—based on NER activity, with the C3 subtype showing the highest NER activity(P<0.000 1). In the groups transfected with RBM39 siRNA or treated with Indisulam, the NER repair efficiency decreased compared to the control group(P<0.01), the cell survival rate decreased(P<0.01), and both the mRNA and protein expression of ERCC1 were reduced(P<0.01). In contrast, in the RBM39 overexpression group, the mRNA and protein expression of ERCC1 were enhanced compared to the control group(P<0.01). Conclusion RBM39 may influence NER repair efficiency by regulating ERCC1 expression in HCC.

Objective:To investigate the effect of glioma cell-derived apoptotic extracellular vesicles(apoEVs)on glioma tumorigen-esis and temozolomide(TMZ)resistance and its mechanism.Methods:The extracted apoEVs were characterized using nanoparticle tracking analysis and transmission electron microscopy,and Western blot,flow cytometry,CCK-8 assay,colony formation assay,and Transwell assay were used to investigate the effect of apoEVs on cell proliferation,migration,invasion,and apoptosis.Results:ApoEVs promoted TMZ resistance in glioma cells,significantly increased the half-maximal inhibitory concentration of TMZ(t=9.326,P=0.001),and inhibited cell apoptosis,and this effect could be reversed by the exosome inhibitor GW4869.ApoEVs also promoted the migration and invasion of glioma cells,increased the expression of vimentin and Twist proteins(t=8.762,P=0.002;t=7.941,P=0.004),and inhibited the expression of cleaved caspase-3(t=9.217,P=0.002).Further studies showed that apoEVs affected TMZ resistance of glioma cells by regulating the LncRNA-XIST/miR-29c/O6-methylguanine-DNA methyltransferase(MGMT)axis.Silencing of LncRNA-XIST could reduce the expression of MGMT and increase the expression of miR-29c,thereby enhancing the sensitivity to TMZ and inhibiting cell migration and invasion.Conclusion:Glioma cell-derived apoEVs promote the malignant progression and temo-zolomide resistance of glioma by delivering LncRNA-XIST to regulate the miR-29c/MGMT axis.