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 evaluate the long-term survival of patients with T1a-bN0M0 non-small cell lung cancer (NSCLC) after sublobar resection. Methods Patients with T1a-bN0M0 NSCLC who underwent sublobar resection from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database, and divided into a segmentectomy group and a wedge resection group according to the resection method. After propensity-score matching at a ratio of 1:1, the overall survival (OS) and disease-specific survival (DSS) of patients were analyzed using Cox regression model, log-rank test, and restricted mean survival time (RMST). Results A total of 3262 patients were included in the study, including 1321 males and 1941 females, with a median age of 69.0 years. Among them, 2419 patients were in the wedge resection group and 843 patients were in the segmentectomy group. After matching, 843 pairs of patients were obtained. The results showed that the 10-year DSS rate (68.0% vs. 60.6%, P=0.011) and 10-year OS rate (40.8% vs. 37.0%, P=0.049) of the segmentectomy group were better than those of the wedge resection group, while there was no statistical difference in the 5-year DSS rate (82.9% vs. 79.5%, P=0.112) or 5-year OS rate (68.9% vs. 64.9%, P=0.096). Multivariate Cox regression analysis revealed that male gender [HR=1.54, 95%CI (1.28-1.86), P<0.001] and age [HR=1.02, 95%CI (1.01-1.03), P<0.001] were independent risk factors for DSS, while increased number of regional nodes dissected (RND) [HR=0.98, 95%CI (0.96-1.00), P=0.018] and segmentectomy [HR=0.82, 95%CI (0.68-0.98), P=0.030] served as protective factors. For OS, male gender [HR=1.54, 95%CI (1.35-1.75), P<0.001], age [HR=1.04, 95%CI (1.03-1.04), P<0.001], and histological subtypes of squamous cell carcinoma [HR=1.62, 95%CI (1.41-1.86), P<0.001] or large cell carcinoma [HR=1.64, 95%CI (1.07-2.52), P=0.023] were identified as independent risk factors, whereas increased RND was a protective factor [HR=0.98, 95%CI (0.97-0.99), P=0.002]. Surgical approach was not an independent prognostic factor for OS. Subgroup analysis showed that segmentectomy had a better 10-year OS-RMST in patients with adenocarcinoma (P=0.045), right lower lobe tumor (P=0.014), and tumor diameter ≤1.6 cm (P=0.006). Conclusion Increasing lymph node dissection during sublobar resection may improve prognosis. Compared with wedge resection, segmentectomy may improve the long-term DSS rate of patients with T1a-bN0M0 NSCLC.

Objective: To analyze the epidemiological characteristics, etiological distribution and risk factors of recurrent hand, foot and mouth disease (HFMD) in Jiaxing City, so as to provide scientific evidence for developing targeted prevention and control strategies. Methods: Based on the China Disease Prevention and Control Information System, data of all reported HFMD cases in Jiaxing City from January 1, 2016 to December 31, 2024 were collected. Epidemiological and etiological distribution characteristics of recurrent HFMD cases were described. The Kaplan-Meier method was applied to estimate the cumulative risk probability of reinfection, and the Cox proportional hazards regression model was used to identify risk factors for HFMD reinfection. Results: A total of 3 105 recurrent HFMD cases were reported in Jiaxing City during 2016-2024, with a reinfection rate of 3.99%. The majority of reinfections were second episodes (97.68%). HFMD reinfection was associated with sex, age, population category and etiological serotype ( χ 2=26.44, 609.92, 459.72, 32.01, all P <0.01). The incidence of recurrent HFMD exhibited a bimodal seasonal pattern, with peaks occurring from June to July and September to November. Spatial distribution indicated that Nanhu District, Jiashan County and Tongxiang City accounted for 49.02% of all recurrent cases citywide. Among 264 laboratory confirmed recurrent cases, EV-A71 was the predominant pathogen (29.92%). The proportion of EV-A71 showed a trend of initial decline followed by rebound, while the proportion of CV-A6 increased over time ( χ 2 trend =6.94, 47.43, both P <0.05). Of 51 patients with ≥2 etiological test results, 56.86 % experienced reinfection with a different serotype. The median time to HFMD reinfection was 17.23 (0.50, 105.03) months after the primary episode. The reinfection probability was 0.61% at 6 months, 3.68% at 36 months, and remained approximately 5% at 64.37 months. Multivariate Cox regression revealed that male sex ( HR =1.23), age ≤ 3 years ( HR = 1.84), and scattered children and preschool children ( HR =3.78, 3.47, respectively) were independent risk factors for HFMD reinfection (all P <0.05). Conclusions Recurrent HFMD in Jiaxing City presents temporal and population heterogeneity, and its etiology shows an alternating serotype evolution pattern. Enhanced surveillance should be implemented among priority populations and high incidence regions, and multivalent vaccines should be developed to confer broader protection.

Objective To explore the influencing factors of medication errors （ME） in the intravenous admixture service center of a tertiary hospital in Xi’an and construct a prediction model. Methods A retrospective cohort study design was adopted, with 200 cases of ME recorded in the hospital’s intravenous dispensing center from January 1, 2023 to December 31, 2024, as the ME group. 400 cases of routine medication records without ME were randomly selected as the ME group. Baseline data from two groups were collected and compared, the influencing factors of ME in the hospital’s static fitting center were analyzed, and a decision tree mode was constructed. Results There was a statistically significant difference （P<0.05） in incomplete medical order information, high-risk drugs, preparation time, and pharmacist training frequency between the ME group and the non ME group. However, there was no statistically significant difference （P>0.05） in other data between the groups; Through logistics regression analysis, it was found that incomplete medical order information, high-risk drugs, preparation time, and pharmacist training frequency were all influencing factors for ME occurrence in hospital intravenous dispensing centers （OR>1, P<0.05）; The constructed decision tree model selected a total of four explanatory variables, among which the configuration time was the important root node variable. The AUC of the decision tree model was 0.808 （95% CI: 0.774−0.842）, the sensitivity was 0.840, the specificity was 0.635, and the Youden index was 0.475. Conclusion The occurrence of ME in the hospital's static dispensing center from 2023 to 2024 was related to incomplete medical order information, high-risk drugs, preparation time, and pharmacist training frequency. The decision tree model constructed based on the above indicators had certain predictive value for ME in the static dispensing center.

ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L^-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L^-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L^-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）. ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.

Objective:To observe the clinical efficacy of traditional Chinese medicine(TCM)essential oil Tuina(Chinese therapeutic massage)combined with conventional Western medication in treating hypertension and its influence on TCM symptoms and anxiety.Methods:Eighty patients with hypertension were included and divided into an observation group and a control group using the random number table method,with 40 cases in each group.The control group was treated with conventional oral Western medication once a day.The observation group was treated with additional TCM essential oil Tuina once every other day.The two groups were treated for 4 weeks.The changes in blood pressure,TCM symptom score,and anxiety,as well as safety,were observed after treatment.Results:After treatment,the systolic blood pressure,diastolic blood pressure,TCM symptom score,and Hamilton anxiety scale score in the two groups were lower than those before treatment(P<0.05),and those of the observation group were lower compared to the control group with statistically significant differences(P<0.05).There were no adverse reactions,such as allergy and dry cough,in the two groups.Conclusion:Based on conventional Western medication,TCM essential oil Tuina was safe and effective in the treatment of hypertension,which both reduced blood pressure and improved clinical symptoms and anxiety.

Objective To investigate the association between nutritional status and serum hepcidin and pentraxin 3(PTX3)levels in patients undergoing maintenance hemodialysis(MHD).Methods A total of 76 patients with MHD who met the inclusion criteria were recruited from the hemodialysis center at the Affiliated Hospital of Chengde Medical University.Nutritional status was assessed using the Subjective Global Assessment(SGA),which categorizes patients into three grades:SGA-A,SGA-B,and SGA-C.Serum levels of PTX3 and hepcidin were mea-sured by enzyme-linked immunosorbent assay(ELISA).Statistical analyses were conducted using SPSS software.One-way analysis of variance(ANOVA)was applied to compare differences across the three SGA groups.Logistic regression analysis was performed to identify influencing factors,and receiver operating characteristic(ROC)curve analysis was used to evaluate diagnostic value.Among the participants,45 patients were classified as malnourished based on SGA-B and SGA-C scores,while those with SGA-A constituted the well-nourished control group.Results Among the 76 MHD patients,59.2%were malnourished.We then compared clinical characteristics across the three groups.The results showed that the malnourished group was older and exhibited significantly higher levels of hs-CRP,PTX3,and hepcidin(P<0.05),while serum albumin,creatinine,and phosphorus levels were significantly lower(P<0.05).Pearson correlation analysis revealed positive correlations between SGA grades and hs-CRP,PTX3,and hepcidin levels(all P<0.05).Logistic regression analysis with"malnutrition"as the dependent variable indicated that elevated hs-CRP,PTX3,and hepcidin levels,along with age and male gender,were associated with increased risk of malnutrition in MHD patients,whereas higher serum phosphorus and creatinine levels were protec-tive factors.Further multivariate logistic regression analysis demonstrated that serum PTX3 level was an independent risk factor for malnutrition(P=0.032),while higher creatinine level was an independent protective factor(P=0.047).ROC curve analysis showed that the combination of serum PTX3 and creatinine levels had a high diagnostic value for identifying malnutrition in MHD patients,yielding an AUC of 0.789(P<0.001),a Youden index of 0.448,sensitivity of 77.8%,and specificity of 71.0%.Conclusions Elevated levels of PTX3 and hepcidin,along with reduced serum creatinine levels,are associated with an increased risk of malnutrition in patients undergoing MHD.Notably,elevated serum PTX3 and decreased serum creatinine independently predict malnutrition in this population and demonstrate high predictive value.

BACKGROUND:In the occurrence and development of demyelinating diseases of the central nervous system,neuroinflammation caused by microglia is the main pathological feature,so inhibiting the inflammatory response is very important to alleviate demyelination.Hydroxysafflor yellow A can protect the blood-brain barrier,inhibit neuronal apoptosis,and improve neurological function.OBJECTIVE:To explore the mechanism of hydroxysafflor yellow A inhibiting bicyclohexanone oxalyl dihydrazone-induced demyelination in mice.METHODS:(1)In vivo:Thirty healthy male C57BL/6 mice were randomly divided into three groups:normal group,cuprizone group,and hydroxysafflor yellow A group.The mice in the cuprizone group and the hydroxysafflor yellow A group were fed with 0.2％cuprizone diet for 6 weeks to establish mouse models of demyelination.The mice in the normal group were fed with normal diet.At the end of the 4th week,the mice in the hydroxysafflor yellow A group were intraperitoneally injected with hydroxysafflor yellow A 20 mg/kg per day.The mice in the normal and cuprizone groups were intraperitoneally injected with normal saline for 2 weeks.The behavioral changes of mice were evaluated by open field test and elevated plus maze test.The loss of myelin sheath in corpus callosum was detected by black gold staining,myelin basic protein and degraded myelin basic protein immunofluorescence staining.The activation of microglia and the expression of inflammatory factors were detected by I ba-1 immunofluorescence staining and ELISA,respectively.The protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 in the brain of mice in each group were detected by western blot assay.(2)In vitro experiment:The inflammation model of BV2 microglia was established by lipopolysaccharide induction.BV2 cells were divided into normal group,lipopolysaccharide group(1 μg/mL),and lipopolysaccharide(1 μg/mL)+hydroxysafflor yellow A(25 μmol/L)group.The expression levels of tumor necrosis factor α and interleukin 6 in the supernatant were detected by ELISA.RESULTS AND CONCLUSION:(1)Compared with the normal group,the mice in the cuprizone group had severe anxiety,abnormal autonomic movement ability,and a large amount of myelin sheath loss in the corpus callosum.The average fluorescence intensity of myelin basic protein was significantly reduced,and the average fluorescence intensity of degraded myelin basic protein was significantly increased.The number of lba1+microglia increased,the contents of interleukin 1β,tumor necrosis factor α,and interleukin 6 in the brain increased,and the protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 increased significantly.The above symptoms and indexes of mice were reversed after hydroxysafflor yellow A treatment.(2)Hydroxysafflor yellow A significantly inhibited the expression of inflammatory factors such as tumor necrosis factor α,and interleukin 6 induced by lipopolysaccharide in BV2 microglia.(3)The above results demonstrate that hydroxysafflor yellow A can significantly improve cuprizone-induced demyelination in mice.The mechanism of action is related to the inhibition of microglial activation-mediated inflammatory response through the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor κB p65 signaling pathway.