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.

Aim To explore the mechanism by which the compound Chaijin Jieyu formula(CCJJY)regulates the TLR4/NLRP3 signaling pathway to inhibit central oxidative stress and improve hippocampal synaptic plasticity damage in depression.Methods SD rats were randomly divided into the control group,chronic unpredictable mild stress group,sleep deprivation group,chronic unpredictable mild stress combined with sleep deprivation group,positive drug group(venlafax-ine+melatonin),low-dose group of CCJJY,medium dose group of CCJJY,and high-dose group of CCJJY,with nine rats in each group.Except for the control group,a rat model of depression complicated with in-somnia was established using chronic unpredictable mild stress combined with sleep deprivation.Depres-sion-like and sleep behaviors in rats were evaluated through weight,food intake,water maze,and pento-barbital sodium tests.ELisa was used to detect ROS,AANAT,and HPLC-EC was used to detect 5-HT con-tent,while Western blot/RT-PCR was used to detect the expression of IL-1β,TLR4,NLRP3,PSD-95,and SYN related proteins and mRNA.HE and Golgic stai-ning were used to observe the pathological changes in the third ventricle,hippocampus,and neuronal synap-ses.Results Compared with the control group,the depression-like behaviors of the model group rats were significant.The expression of IL-1β,TLR4,and NL-RP3 in the hippocampus increased,while the expres-sion of PSD-95 and SYN decreased.Activation of NL-RP3 inflammasomes led to "sleeve like" pathological changes in the third ventricle,with hippocampal neu-rons undergoing apoptosis and significant damage to neuronal synaptic plasticity.Compared with the model group,after intervention with CCJJY,the expression of ROS,IL-1β,TLR4,and NLRP3 decreased,while the expression of AANAT,5-HT,PSD-95,and SYN in-creased.Pathological damage to the third ventricle and hippocampal neurons was repaired.Conclusion The CCJJY improves hippocampal synaptic plasticity dam-age in depression by regulating the TLR4/NLRP3 sig-naling pathway to inhibit central oxidative stress.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Objective To investigate the efficacy of Ustekinumab combined with fecal microbiota transplantation in the treatment of inflammatory bowel disease(IBD)and its impact on intestinal mucosal barrier and immune function.Methods A total of 106 IBD patients treated from January 2023 to March 2024 were selected and divided into the Usteinumab group and the Usteinumab combined with fecal microbiota transplantation group(combination group)by random number table method,with 53 patients in each group.The Ustekinumab group was treated with Ustekinumab,while the combination group was treated with Ustekinumab combined with fecal microbiota transplantation.The clinical efficacy,intestinal mucosal barrier indicators,immune function indicators,scores of the Inflammatory Bowel Disease Quality of Life Questionnaire(IBDQ)and the total incidence of adverse reactions were compared between the two groups.Results The total effective rate of the combination group was 94.34%(50/53),which was higher than that of the Ustekinumab group[73.58%(39/53)](P<0.05).After treatment,the levels of endotoxin,D-lactic acid and diamine oxidase in the combination group were all lower than those in the Ustekinumab group,while the levels of CD3+,CD4+,CD4+/CD8+and the scores of IBDQ were all higher than those in the Ustekinumab group(P<0.05).There was no significant difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion The clinical efficacy of Ustekinumab combined with fecal microbiota transplantation is remarkable in the treatment of IBD.It can effectively alleviate intestinal mucosal injury,promote the recovery of intestinal mucosal barrier function,improve the intestinal microbial environment,enhance the immune function of patients,effectively control the progression of the disease,and has high safety.

Objective:To investigate the effect of KRAS,NRAS and BRAF gene mutations on the efficacy of pre-operative short-course radiotherapy combined with chemotherapy and postoperative liver metastasis in patients with stage Ⅱ～Ⅲ mid-low rectal cancer.Methods:The clinical data of 149 patients with stage Ⅱ～Ⅲ low rectal cancer admitted to Dongnan Hospital of Xiamen University from January 2017 to June 2020 were retrospectively analyzed.All patients received neoadjuvant therapy with preoperative short-course radiotherapy combined with chemotherapy and radical surgery,and were followed up until June 30,2023.The mutations of KRAS,NRAS and BRAF genes were de-tected by pathological tissue before surgery.The effect of neoadjuvant therapy was evaluated according to tumor re-gression grade(TRG).The risk factors of postoperative liver metastasis were analyzed by Logistic multivariate analysis.Results:There were 44 cases of KRAS,10 cases of NRAS and 12 cases of BRAF gene mutation in 149 patients with stage Ⅱ～Ⅲ low rectal cancer,and the mutation rates were 29.53%,6.71%and 8.05%.The incidence of positive vas-cular invasion in patients with KRAS gene mutation was higher than negative(P＜0.05).In NRAS mutation patients,the incidence of positive lymph node metastasis was higher than negative(P＜0.05),and the incidence of maximum tumor diameter≥5 cm was higher than that of maximum tumor diameter＜5 cm(P＜0.05).The clinical stage of BRAF muta-tion was higher in stage Ⅲ than in stage Ⅱ(P＜0.05),and the incidence of positive lymph node metastasis was higher than negative(P＜0.05).During the follow-up period,liver metastasis occurred in 42 patients,and the liver metastasis rate was 28.18%.The KRAS,NRAS and BRAF gene mutations in the effective group were 25.81%,2.15%and 3.23%,lower than those in the ineffective group(35.71%,14.29%and 17.07%,P＜0.05).Multiple factors found clinical stage Ⅲ(OR=10.620,95%CI:2.645～22.575),lymph node metastasis was positive(OR=8.774,95%CI:1.878～19.645),neoadju-vant therapy failed(OR=3.373,95%CI:1.014～11.218),KRAS gene mutation(OR=6.245,95%CI:1.876～20.789),BRAF gene mutation(OR=9.497,95%CI:1.754～19.335)were independent risk factors for postoperative liver metastasis of stage Ⅱ～Ⅲ mid-low rectal cancer.Conclusion:Mutations in the KRAS and BRAF genes of middle are associated with poorer efficacy of neoadjuvant therapy in patients with stage Ⅱ～Ⅲ mid-low rectal cancer and are also indepen-dent risk factors for postoperative liver metastasis.

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by anorexia.Methods:This cross-sectional study included patients registered in the RealDTC study from May 2023 to December 2023. Demographic data, COPD Assessment Test (CAT) score, modified Medical Research Council (mMRC) dyspnea questionnaire score, Clinical COPD Questionnaire (CCQ) score, forced expiratory volume in one second (FEV 1), forced expiratory volume in the first second predicted of percentage (FEV 1%pred), FEV 1/forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, GOLD group, number of acute exacerbations and hospitalizations in the past year, and score of the Functional Assessment of Anorexia Cachexia Therapy-Anorexia/Cachexia Subscale-12 (FAACT-A/CS-12) were collected. Patients with a FAACT-A/CS-12 score ≤30 were diagnosed as having anorexia. Multivariate logistic regression analysis was used to evaluate the influencing factors of anorexia in COPD patients. Results:A total of 617 COPD patients were included, of whom 109(17.7%) had anorexia. Compared with non-anorexia patients, COPD patients with anorexia had higher age, CAT, mMRC and CCQ scores, and more acute exacerbations and hospitalizations in the past year, while body mass index, FEV 1, FEV 1%pred and FEV 1/FVC were lower (all P<0.05). The proportions of patients with primary education or below, GOLD 3-4 grade and GOLD E group were higher in COPD patients with anorexia (all P<0.05). Logistic regression analysis showed that a CAT score of 10-<20 [odds ratio ( OR)=4.017, 95% confidence interval ( CI): 1.673-59.645], a CAT score of 20-<30 ( OR=9.686, 95% CI: 3.777-24.842), a CAT score of ≥30 ( OR=78.286, 95% CI: 7.654-800.689) and ≥1 hospitalization in the past year ( OR=2.050, 95% CI: 1.292-3.254) were independent risk factors for anorexia in COPD patients (all P<0.05). Conclusions:COPD patients with anorexia have poor lung function, high symptom burden and high risk of acute exacerbation. Clinicians should pay attention to the management of COPD patients with anorexia and take corresponding intervention measures.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Clinical pharmacist training is an important way to strengthen the clinical pharmacist team's construction and improve their pharmaceutical service capabilities and levels.The Pharmacy Administration and Pharmacy Practice in Healthcare Institutions-Part 4-8-1:Pharmacy Administration-Pharmacy Training Management-Clinical Pharmacist Training was based on the relevant requirements of the current clinical pharmacist training system of the Chinese Hospital Association,and formulated by sor-ting out relevant materials,such as standards,policies and regulations,technical specifications,literature,the current situation of clinical pharmacist training in China,and expert opinions.A total of 15 key elements of clinical pharmacist training were selected and divided into three aspects(base management,training process and assessment,and the quality management,evaluation and improvement).This article mainly introduced the construction method and content of the clinical pharmacist training standard,to deepen the understanding of the standard for relevant units and to promote the implementation of the standard.