Objective To explore the synergistic therapeutic effect of sodium butyrate and Sishen pill on mice with diarrhea with kidney-yang deficiency syndrome,and provide experimental evidence for the contemporary application of classical prescriptions.Methods The diarrhea with kidney-yang deficiency syndrome mouse model was construc-ted by gavage of adenine combined with Folium sennae.Mice were given 100％Sishen pill decoction,50 mg/kg so-dium butyrate+75％Sishen pill decoction,100 mg/kg sodium butyrate+50％Sishen pill decoction,200 mg/kg so-dium butyrate+25％Sishen pill decoction,and 300 mg/mL sodium butyrate decoction by intragastric administra-tion,respectively.General condition,food and water intake,anal temperature,body weight,fecal water content,organ index,intestinal microbiota,and enzyme activity of the mice were compared.Results After treatment,the general condition,food and water intake,anal temperature,and fecal water content of the mice gradually recovered.The body weight of mice from the natural recovery group,the 200 mg/kg sodium butyrate+25％ Sishen pill group,and the 50 mg/kg sodium butyrate+75％ Sishen pill group still showed statistical differences from the normal group(P＜0.05).The body weight of mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group(34.23±4.93)g increased,close to the body weight of mice from the normal group(35.69±4.78)g.Spleen index of the mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group recovered to normal,showing significant difference from mice from the natural recovery group(P＜0.05).There were no significant differences in thymus index of mice from different groups(P＞0.05).After treatment,the mice intestinal microbiota began to recover,with no signifi-cant differences in the number of bacteria among groups(P＞0.05).Compared with the natural recovery group,the number of Escherichia coli in mice from each treatment group reduced significantly(P＜0.01),and the mice from 100 mg/kg sodium butyrate+50％ Sishen pill group had the smallest number of Escherichia coli.The number of Bifidobacteria in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group and the 50 mg/kg sodium bu-tyrate+75％ Sishen pill group recovered to the level of the normal group(P＞0.05).The mice from 100 mg/kg so-dium butyrate+50％ Sishen pill group showed a significant effect on the recovery of Lactobacillus number(P＜0.05).The amylase,lactase,and protease activities in mice from the natural recovery group were all higher than those from the normal group(all P＜0.05),and the enzyme activities in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group were closer to those from the normal group.Compared with the natural recovery group,lactase activity of mice from the 100％ Sishen pill group reduced significantly(P＜0.01),and the xylanase activity in mice from the 100 mg/kg sodium butyrate+50％ Sishen pill group was closest to the normal group.Conclusion The synergistic effect of sodium butyrate enhances the therapeutic efficacy of Sishen pill.100 mg/kg sodium buty-rate+50％ Sishen pill group showed significant improvement in mice mental status,diarrhea symptoms,intestinal enzyme activity,and microbial stability compared with other groups using sodium butyrate or Sishen pill alone.

Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.

Background:Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy.Raw pieces of Rhei Radix et Rhizoma(RP)are known for their strong laxative effects,often accompanied by side effects,while steamed Rhei Radix et Rhizoma pieces(SP)possess a milder laxative effect and are widely used clinically.However,there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness,particularly from a bioavailability perspective.Objective:This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics,tissue distribution,and excretion assays.Methods:An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites.Pharmacokinetic,tissue distribution,and excre-tion assays were conducted in constipation rats following oral administration of RP and SP.Blood,tissue,urine,and fecal samples were collected and analyzed to compare the absorption,distribution,metabolism,and excretion profiles of anthraquinones,high-lighting differences in bioavailability and safety between RP and SP.Results:Compared with the RP group,the SP group showed significantly reduced area under the plasma concentration-time curve,mean residence time,and half-life time values for rhein-8-O-β-D-glucopyranoside,rhein,emodin,aloe-emodin,and their glucuronide metabolites.The clearance values were significantly increased in the SP group.These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP.Additionally,these compo-nents were primarily distributed in the large intestine,where they exerted their laxative effects.Glucuronide metabolites were mainly excreted through urination,while prototype components were excreted in both urine and feces.Notably,the cumulative excretion of aloe-emodin,emodin,rhein,and their glucuronide metabolites was significantly higher in both urine and feces after SP administra-tion,indicating that SP enhances the excretion of these components compared with RP.Conclusion:The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion,demonstrating that the steaming process significantly promotes the elimination of key components.This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma,offering a scientific basis for the improved safety and clinical use of SP.These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines.This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Objective To develop the Ego Depletion Scale for Type 2 Diabetes Patients and evaluate its reliability and validity,and to provide a specific assessment tool for evaluating ego-depletion in self-management.Methods Guided by the self-control strength model,the initial scale was constructed through literature review,semi-structured interviews,2 rounds of expert consultation,and a pilot survey.A convenience sampling method was employed to recruit 460 patients with Type 2 Diabetes from the endocrinology department of a tertiary hospital in Wuhan,Hubei Province,between April and July 2024.They were randomly divided into 2 subsets for exploratory factor analysis and confirmatory factor analysis.Results A total of 451 valid questionnaires were collected.Exploratory factor analysis extracted 6 common factors,with a cumulative variance contribution of 73.231％.In confirmatory factor analysis,an item was deleted due to failing to meet the standardized loading value criterion.The revised Ego Depletion Scale for Type 2 Diabetes Patients comprised 6 dimensions and 22 items.The total Cronbach's α coefficient was 0.911;split-half reliability was 0.744;the content validity index was 0.860.Correlation coefficients between the total score and scores of each dimension of the scale and the total score of the Self-Regulatory Fatigue Scale ranged from 0.558 to 0.946(P＜0.001).Conclusion The scale exhibits robust reliability and validity,serving as a scientifically instrument for assessing ego depletion in patients with Type 2 Diabetes.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the effect of bone morphogenetic protein-9(BMP9)overexpression on inflammatory response and apoptosis of alveolar epithelial cells induced by lipopolysaccharide(LPS).Methods:A549 cells were stimulated with 0.1 μg/ml LPS,expressions and changes of BMP9 protein at different time points(LPS stimulation for 0 h,6 h,12 h,24 h)were detected by Western blot.Expression of BMP9 in A549 cells was up-regulated by transfection of BMP9 plasmid,and the transfection efficiency was verified by Western blot and qPCR.After 12 h of LPS stimulation,levels of inflammatory factors TNF-α,IL-6,IL-1β in cell supernatant were detected by ELISA,expressions of anti-apoptotic protein(Bcl-2)and pro-apoptotic protein(Bax)were detected by Western blot,and apoptosis of cells was detected by TUNEL staining.Results:With the extension of LPS stimulation time,expression of BMP9 was down-regulated.Overexpression of BMP9 successfully up-regulated expression of BMP9 in A549 cells.LPS stimulation promoted secretions of TNF-α,IL-6 and IL-1β from A549 cells,increased apoptosis,promoted Bcl-2 expression while inhibited Bax expression.Overexpression of BMP9 inhibited TNF-α,IL-6 and IL-1β releasing,decreased apoptosis,inhibited Bcl-2 expression,while promoted Bax expression.Conclusion:In LPS-stimulated A549 cells,BMP9 expression is gradually decreased at a time-depen-dent manner.Overexpression of BMP9 can inhibit LPS-induced inflammatory response and apoptosis in A549 cells.

With the rapid rise of large language models(LLM),the natural language generation capabilities of deep learning have demonstrated significant value in the medical field.However,the"closed nature"of model parameters makes them prone to generating"hallucinations",making it difficult to provide accurate answers to the latest knowledge,and the reasoning process lacks transparency and traceability.Retrieval-augmented generation(RAG)technology addresses these issues by actively connecting external information sources such as document databases and knowledge graphs during the generation process.This significantly reduces the dependence of LLM on outdated training data and introduces verifiable evidence and real-time knowledge updates into their responses.In the medical field,RAG technology effectively addresses the high-accuracy and traceability requirements of literature retrieval and clinical decision support.It is widely applied in areas such as drug discovery,pharmacovigilance,and the diagnosis and treatment of rare diseases.By integrating emerging technologies such as reinforcement learning,multimodal processing,and compliant privacy protection,RAG technology is evolving towards a more open and highly customizable direction,providing innovative intelligent solutions for medical information retrieval and decision-making support.

Objective To investigate the correlation between the clinical characteristics of allergic rhinitis(AR)in adults located in Shenzhen area and the traditional Chinese medicine(TCM)constitutions.Methods A cross-sectional survey of adult AR patients in Shenzhen was conducted.From June 2022 to December 2023,adult AR patients admitted to the Department of Otolaryngology outpatient clinic of Bao'an Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine(Shenzhen Bao'an District Hospital of Traditional Chinese Medicine)were selected as the study subjects.The clinical baseline data,Total Nasal Symptoms Score(TNSS),and Total Non-Nasal Symptoms Score(TNNSS)of the patients were collected for the analysis of clinical characteristics,and TCM constitutions were differentiated based on the information collected by TCM constitutions questionnaire.After that,the correlation between the biased TCM constitutions and clinical characteristics were explored by using analysis of variance,non-parametric test and Logistic regression analysis.Results(1)A total of 215 cases of adult AR patients from Shenzhen were included.Most of the patients were male(60.93％),and the patients were usually aged 18-29 years old(accounting for 48.84％).AR in adults often arose in the spring(33.49％)and fall(30.70％).(2)Lung qi deficiency-cold syndrome was the predominated TCM syndrome type of AR in adults,accounting for 40.93％,and then came kidney yang deficiency syndrome(26.98％),spleen qi deficiency syndrome(20.00％),and heat accumulation in lung meridian syndrome(12.09％).Lung qi deficiency-cold syndrome and heat accumulation in lung meridian syndrome were more common in young males,and kidney yang deficiency syndrome was frequently seen in middle-aged and elderly males.(3)The leading three TCM constitution types of AR in adults were qi deficiency constitution(30.23％),yang deficiency constitution(24.65％),and inherited special constitution(15.81％).In adult AR patients with lung qi deficiency-cold syndrome,the commonly-seen TCM constitution types were qi deficiency constitution,inherited special constitution,and balanced constitution.In adult AR patients with spleen qi deficiency syndrome,the commonly-seen TCM constitution types were inherited special constitution,phlegm-damp constitution,and yang deficiency constitution.In adult AR patients with kidney yang deficiency syndrome,the commonly-seen TCM constitution types were yang deficiency constitution,qi stagnation constitution,and inherited special constitution.In adult AR patients with heat accumulation in lung meridian syndrome,the commonly-seen TCM constitution types were damp-heat constitution,yin deficiency constitution,and blood-stasis constitution.The leading five TNSS scores were shown in adult AR patients with inherited special constitution,qi deficiency constitution,yang deficiency constitution,phlegm-damp constitution,and qi stagnation constitution,respectively.And the leading five TNNSS scores were shown in adult AR patients with yang deficiency constitution,inherited special constitution,qi stagnation constitution,yin deficiency constitution,and damp-heat constitution,respectively.(4)The results of statistical analysis showed that the differences in gender among the adult AR patients with various TCM constitution types were not statistically significant(P＞0.05),but the differences in age groups,TCM syndrome types,TNSS scores and TNNSS scores were statistically significant(P＜0.01 or P＜0.001).(5)The results of Logistic regression analysis showed that the TNSS scores and TNNSS scores were all positively correlated with qi deficiency constitution,yang deficiency constitution,and inherited special constitution,and spleen qi deficiency syndrome was negatively correlated with damp-heat constitution,the differences being all statistically significant(P＜0.01 or P＜0.001).Conclusion The onset of AR in adults from Shenzhen area is closely related to age,gender,season,and TCM constitutions.The adult AR patients usually have the biased constitutions,in particular qi deficiency constitution,yang deficiency constitution,and inherited special constitution.In adult AR patients,higher TNSS scores are correlated with inherited special constitution,higher TNNSS scores are correlated with yang deficiency constitution,and the primary TCM syndrome type of lung qi deficiency-cold syndrome is correlated with qi deficiency constitution.

Background:Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy.Raw pieces of Rhei Radix et Rhizoma(RP)are known for their strong laxative effects,often accompanied by side effects,while steamed Rhei Radix et Rhizoma pieces(SP)possess a milder laxative effect and are widely used clinically.However,there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness,particularly from a bioavailability perspective.Objective:This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics,tissue distribution,and excretion assays.Methods:An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites.Pharmacokinetic,tissue distribution,and excre-tion assays were conducted in constipation rats following oral administration of RP and SP.Blood,tissue,urine,and fecal samples were collected and analyzed to compare the absorption,distribution,metabolism,and excretion profiles of anthraquinones,high-lighting differences in bioavailability and safety between RP and SP.Results:Compared with the RP group,the SP group showed significantly reduced area under the plasma concentration-time curve,mean residence time,and half-life time values for rhein-8-O-β-D-glucopyranoside,rhein,emodin,aloe-emodin,and their glucuronide metabolites.The clearance values were significantly increased in the SP group.These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP.Additionally,these compo-nents were primarily distributed in the large intestine,where they exerted their laxative effects.Glucuronide metabolites were mainly excreted through urination,while prototype components were excreted in both urine and feces.Notably,the cumulative excretion of aloe-emodin,emodin,rhein,and their glucuronide metabolites was significantly higher in both urine and feces after SP administra-tion,indicating that SP enhances the excretion of these components compared with RP.Conclusion:The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion,demonstrating that the steaming process significantly promotes the elimination of key components.This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma,offering a scientific basis for the improved safety and clinical use of SP.These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines.This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Objective To develop the Ego Depletion Scale for Type 2 Diabetes Patients and evaluate its reliability and validity,and to provide a specific assessment tool for evaluating ego-depletion in self-management.Methods Guided by the self-control strength model,the initial scale was constructed through literature review,semi-structured interviews,2 rounds of expert consultation,and a pilot survey.A convenience sampling method was employed to recruit 460 patients with Type 2 Diabetes from the endocrinology department of a tertiary hospital in Wuhan,Hubei Province,between April and July 2024.They were randomly divided into 2 subsets for exploratory factor analysis and confirmatory factor analysis.Results A total of 451 valid questionnaires were collected.Exploratory factor analysis extracted 6 common factors,with a cumulative variance contribution of 73.231％.In confirmatory factor analysis,an item was deleted due to failing to meet the standardized loading value criterion.The revised Ego Depletion Scale for Type 2 Diabetes Patients comprised 6 dimensions and 22 items.The total Cronbach's α coefficient was 0.911;split-half reliability was 0.744;the content validity index was 0.860.Correlation coefficients between the total score and scores of each dimension of the scale and the total score of the Self-Regulatory Fatigue Scale ranged from 0.558 to 0.946(P＜0.001).Conclusion The scale exhibits robust reliability and validity,serving as a scientifically instrument for assessing ego depletion in patients with Type 2 Diabetes.