ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

Objective:To investigate the delay in medical care-seeking and diagnosis of human brucellosis cases in Daxing District, Beijing City, and analyze the relevant influencing factors.Methods:Retrospective analysis method was used to collect the information on brucellosis cases reported by the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System in Daxing District, Beijing City from January 1, 2013 to December 31, 2022. And the case information was reviewed, including demographic information, clinical manifestations, medical care-seeking, diagnosis, etc. Binary logistic regression was used to analyze the influencing factors of delayed diagnosis.Results:A total of 120 cases of brucellosis were included, including 91 males and 29 females, with a male-to-female ratio of 3.14 ∶ 1.00. The majority were aged 40 - 79 years, accounting for 81.7% (98/120). Farmers and unemployed household workers were the main occupations, accounting for 67.5% (81/120). The main clinical manifestations were fever (85.8%, 103/120), hyperhidrosis (65.8%, 79/120), fatigue (61.7%, 74/120), and muscle soreness (60.0%, 72/120). The delay rate of medical care-seeking was 33.3% (40/120), with a median medical care-seeking time of 6 days (interquartile range: 2 - 22 days, range: 0 - 727 days). The diagnosis delay rate was 50.8% (61/120), with a median diagnosis time of 10 days (interquartile range: 3 - 22 days, range: 0 - 1 530 days). The results of binary logistic regression analysis showed that the reasons for initial diagnosis were severe or recurrent symptoms ( OR = 6.76, 95% CI: 2.40 - 19.01), serological monitoring or other diseases ( OR = 36.00, 95% CI: 3.57 - 362.72), and delayed medical care-seeking ( OR = 4.30, 95% CI: 1.68 - 11.01) were risk factors for delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city ( OR = 0.27, 95% CI: 0.08 - 0.92) was a protective factor for delayed diagnosis of brucellosis cases. Conclusions:The medical care-seeking and diagnosis of brucellosis cases in Daxing District, Beijing City have been delayed to varying degrees. The reasons of initial diagnosis are severe or recurrent symptoms, serological monitoring or other diseases, and medical care-seeking delay are the risk factors for the delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city is a protective factor for delayed diagnosis of brucellosis cases.

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.

A method of establishing the motion trajectory model of flexible puncture needle based on image processing is proposed to accurately measure the motion track of the flexible needle during needle insertion.The dynamic images of needle insertion are collected through the camera system,and the position coordinates of the flexible needle tip during needle insertion are extracted using the image processing morphology technology.Based on the extracted needle tip data,the least square method is employed for curve fitting,and the second-order polynomial model,exponential function model,and bicycle model are established.The analysis on the goodness of fit,residual,and residual sum of squares of different models reveals that the second-order polynomial model is superior to the other two models in exploring the optimal solution of the trajectory model of flexible puncture needle.

ObjectiveTo explore the effect of virtual reality on upper limb function in stroke patients through diffusion tensor imaging (DTI). MethodsFrom September, 2021 to March, 2023, 80 stroke patients in the Fuzhou Second General Hospital were randomly divided into control group (n = 40) and experimental group (n = 40). Both groups received routine rehabilitation, while the experimental group received virtual reality training additionally, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and Action Research Arm Test (ARAT) before treatment, after treatment and after four-week follow-up; and they were scaned with DTI to measure the fractional anisotropy (FA) and relative anisotropy (RA) of cerebral peduncle and posterior limb of inner capsule of the affected side before and after treatment. ResultsTwo cases dropped in each group. The FMA-UE and ARAT scores increased in both groups after treatment and follow-up (F > 2.790, P < 0.001), and increased more in the experimental group than in the control group (t > 2.297, P < 0.05). FA and RA in the posterior limb of inner capsule increased in both groups after treatment (t > 21.013, P < 0.001), and increased more in the experimental group (t > 2.006, P < 0.05). The d-value of FA of the posterior limb of internal capsule before and after treatment (ΔFA) was positively correlated with the d-value of FMA-UE score (r > 0.362, P < 0.05) in both groups, the ΔFA of the posterior limb of internal capsule was positively correlated with the d-value of ARAT score (r = 0.459, P < 0.01). ConclusionVirtual reality training can promote the recovery of upper limb function in stroke patients, which may associate with the conductivity of posterior limb of inner capsule.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ 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) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had 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 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To investigate the delay in medical care-seeking and diagnosis of human brucellosis cases in Daxing District, Beijing City, and analyze the relevant influencing factors.Methods:Retrospective analysis method was used to collect the information on brucellosis cases reported by the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System in Daxing District, Beijing City from January 1, 2013 to December 31, 2022. And the case information was reviewed, including demographic information, clinical manifestations, medical care-seeking, diagnosis, etc. Binary logistic regression was used to analyze the influencing factors of delayed diagnosis.Results:A total of 120 cases of brucellosis were included, including 91 males and 29 females, with a male-to-female ratio of 3.14 ∶ 1.00. The majority were aged 40 - 79 years, accounting for 81.7% (98/120). Farmers and unemployed household workers were the main occupations, accounting for 67.5% (81/120). The main clinical manifestations were fever (85.8%, 103/120), hyperhidrosis (65.8%, 79/120), fatigue (61.7%, 74/120), and muscle soreness (60.0%, 72/120). The delay rate of medical care-seeking was 33.3% (40/120), with a median medical care-seeking time of 6 days (interquartile range: 2 - 22 days, range: 0 - 727 days). The diagnosis delay rate was 50.8% (61/120), with a median diagnosis time of 10 days (interquartile range: 3 - 22 days, range: 0 - 1 530 days). The results of binary logistic regression analysis showed that the reasons for initial diagnosis were severe or recurrent symptoms ( OR = 6.76, 95% CI: 2.40 - 19.01), serological monitoring or other diseases ( OR = 36.00, 95% CI: 3.57 - 362.72), and delayed medical care-seeking ( OR = 4.30, 95% CI: 1.68 - 11.01) were risk factors for delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city ( OR = 0.27, 95% CI: 0.08 - 0.92) was a protective factor for delayed diagnosis of brucellosis cases. Conclusions:The medical care-seeking and diagnosis of brucellosis cases in Daxing District, Beijing City have been delayed to varying degrees. The reasons of initial diagnosis are severe or recurrent symptoms, serological monitoring or other diseases, and medical care-seeking delay are the risk factors for the delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city is a protective factor for delayed diagnosis of brucellosis cases.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ 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) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had 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 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.