BACKGROUND:Intestinal acute graft-versus-host disease is one of the most aggressive complications after allogeneic hematopoietic stem cell transplantation with high lethality.How to improve intestinal inflammation and regulate autophagy by applying traditional Chinese medicine in order to treat intestinal acute graft-versus-host disease is a worthwhile research issue nowadays. OBJECTIVE:To investigate the mechanism of Huangqintang modulating intestinal flora for the treatment of intestinal acute graft-versus-host disease. METHODS:CB6F1 mice were irradiated with 60Co X radiation at a total dose of 8 Gy,and then single nucleated cell suspensions(bone marrow cells+splenocytes)from Balb/c H-2d mice were injected into the tail vein in order to prepare a model of intestinal acute graft-versus-host disease.These samples were randomly divided into the model group and the high-,moderate-,and low-dose Huangqintang groups.After modeling,the model,high-,moderate-,and low-dose groups received different doses of Huangqintang or an equal volume of saline by continuous gavage for 14 days.Clinical acute graft-versus-host disease grading,and survival time was recorded.Small intestinal tissues from each group were stained with hematoxylin and eosin for small intestinal mucosal pathology scoring.The intestinal flora of mice in each group was detected using 16S rDNA sequencing.Autophagy-related markers were detected using immunofluorescence,immunohistochemistry,and PCR. RESULTS AND CONCLUSION:(1)Compared with the model group,the survival time of mice was significantly prolonged(P<0.01);the clinical acute graft-versus-host disease scores were significantly reduced(P<0.01);the pathological grading scores of the small intestinal mucosa were significantly diminished(P<0.01);the levels of the small intestinal tissue inflammatory factors tumor necrosis factor-α,interleukin-1β,and interleukin-6,were significantly decreased(P<0.01);the structural integrity of the small intestinal mucosal epithelium was partially restored in mice after the intervention of moderate and high-dose Huangqintang.(2)The study of intestinal flora found that compared with the model group,the pro-inflammatory strain Enterococcus was significantly reduced(P<0.05),while beneficial bacteria such as Clostridium_innocuum and Rhodococcus,a pro-autophagy bacterium,were significantly elevated(P<0.05)in the moderate-dose Huangqintang group.(3)Compared with the model group,the autophagy markers were significantly elevated in the moderate-dose Huangqintang group(P<0.05);under transmission electron microscopy,the number of autophagic vacuoles of moderate-dose Huangqintang group increased significantly.(4)The results showed that Huangqintang significantly reduced the abundance of conditionally pathogenic bacteria and the level of inflammatory factors in small intestinal tissues,and increased the relative abundance of beneficial bacteria and promoted the expression of autophagy in the small intestinal mucosa,which resulted in a significant improvement of intestinal symptoms in mice with acute graft-versus-host disease.

Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI: 0.9768, 0.9996, P＜0.05; adjusted model: RR=0.988, 95%CI: 0.9764, 0.9993, P＜0.05). A mediating effect of placental cortisol between prenatal depression and the risk of neurodevelopmental delay in 3-month-old offspring was found statistically significant (P=0.045), accounting for 67.0% of the total effect. Conclusion Prenatal depression is associated with elevated placental cortisol levels, and higher cortisol levels are found to be related to a lower risk of neurodevelopmental delay in infants. Placental cortisol mediates the relationship between prenatal depression and infant neurodevelopment.

Background Job burnout and depressive symptoms are prevalent among occupational populations, with a close relationship between them. Sleep quality, as a potential mediating factor, significantly affects the mental health of workers. Objective To explore the relationship between job burnout, sleep quality, and depressive symptoms, and determine whether sleep quality mediates the relationship between job burnout and depressive symptoms. Methods From April 25 to May 1, 2024, this study employed cluster sampling to conduct a questionnaire survey among individuals engaged in various occupations across five cities in the Ningxia Hui Autonomous Region. The questionnaires included socio-demographic information, as well as the Chinese Maslach Burnout Inventory (CMBI), the Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-9 (PHQ-9) for assessing burnout, sleep quality, and depressive symptoms, respectively. Out of the 4106 questionnaires distributed, a total of 3837 questionnaires were valid, and the valid recovery rate was 93.45%. The distribution among demographic variables in burnout, sleep quality and depressive symptoms were statistically analyzed. A binary logistic regression model was used for multifactor correlation analysis; Pearson correlation was used to test the correlation between burnout, sleep quality, and depressed mood. Modelling and mediated effect path mapping were performed using Amos 24.0 software. Results The postive rate of occupational burnout in the workers was 97.49% (3741/3837), the positive rate of poor sleep quality was 66.77% (2526/3837), and the positive rate of depressive symptoms was 75.68% (2904/3837). There were statistically significant differences in depressive symptoms by ages, shift types, working years, marital status, smoking habits, drinking habits, and exercising frequency (P < 0.05). The logistic model indicated that working years, drinking habits, job burnout, and overall sleep quality were significant factors influencing the occurrence of depressive symptoms (P < 0.05). The correlation analysis revealed positive correlations between depressive symptom scores and job burnout scores (r=0.045, P < 0.01), between depressive symptom scores and sleep quality scores (r=0.480, P < 0.01), and between job burnout scores and sleep quality scores (r=0.054, P < 0.01). Furthermore, the indirect effect of job burnout on depressive symptoms through sleep quality was 0.100 (95%CI: 0.204, 0.252; P < 0.01). Conclusion Job burnout and sleep quality are significant factors associated with the occurrence of depressive symptoms among occupational populations, and sleep quality plays a partial mediating role in depressive symptoms associated with job burnout. This finding may provide a scientific basis for developing intervention strategies to control depressive symptoms among workers.

Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

Objective:To discuss the influencing factors of angina pectoris in the patients with diabetes mellitus(DM),to construct a Bayesian network model to explore the network relationships among the influencing factors,and to predict the risk of angina pectoris in the patients with DM.Methods:Based on the UK Biobank(UKB)database,the Logistic regression aralysis model was used to screen the influencing factors of angina pectoris in the patients with DM.The taboo search algorithm was used for structure learning,and the Bayesian parameter estimation method was used for parameter learning to construct the Bayesian network model.Results:A total of 22 712 DM patients were included.The influencing factors of angina pectoris in the patients with DM included 14 variables:gender,age,body mass index(BMI),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HbA1c),hypertension,maternal smoking around delivery,smoking status,alcohol consumption,regular exercise,insomnia,sleep duration,and childhood relative body size(P<0.05).A Bayesian network model was constructed with 15 nodes and 22 directed edges.Among them,age,HbA1c,hypertension,regular exercise,BMI,and sleep duration were directly associated with the occurrence of angina pectoris in the patients with DM,while gender,smoking status,alcohol consumption,TC,TG,insomnia,childhood relative body size,and maternal smoking around delivery were indirectly associated with the occurrence of angina pectoris in the patients with DM.Conclusion:Age,HbA1c,hypertension,regular exercise,BMI,and sleep duration are direct influencing factors of angina pectoris in the patients with DM.Controlling HbA1c,blood pressure,and BMI levels,engaging in regular exercise,and maintaining appropriate sleep duration are beneficial for reducing the risk of angina pectoris in the patients with DM.

Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.

Objective:To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality.Methods:This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone.Results:A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions:RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

ObjectiveTo predict the potential nephrotoxic components in traditional Chinese medicine health food products based on the Traditional Chinese Medicine Toxicity Alert System and Basic Toxicology Database （TCMTAS-BTD）， screen and validate the predicted components by cell and animal experiments， and decipher the mechanism of nephrotoxicity by network pharmacology. MethodTCMTAS-BTD was utilized to predict the toxicity of 3 540 compounds found in the catalogue of traditional Chinese health food ingredients. In the cell experiment， the top 5 compounds with high toxicity probability were screened by measurement of cell proliferation and viability （CCK-8） and high-content screening. ICR mice were randomized into a control group， a low-dose （2.91 mg·kg^-1·d^-1） ecliptasaponin A， and a high-dose （29.1 mg·kg^-1·d^-1） ecliptasaponin A group， with 10 mice in each group， and treated continuously for 28 days. During the experiment， the general conditions of the rats were observed， and the kidney index was calculated. The levels of serum creatinine （SCr） and blood urea nitrogen （BUN） in the serum as well as the content of malondialdehyde （MDA） and superoxide dismutase （SOD） in the renal tissue were measured. The pathological changes of the kidney were observed. Network pharmacology was employed to predict the potential pathways of nephrotoxicity. Finally， the pathway-associated proteins were validated by Western blot. ResultThe top 5 compounds with high probability of nephrotoxicity were ecliptasaponin A， chrysophanol， rutaecarpine， tanshinoneⅠ， and geniposidic acid. In the cell experiment， CCK-8 results showed that 10 μmol·L^-1 ecliptasaponin A， 60 μmol·L^-1 chrysophanol， 40 μmol·L^-1 rutaecarpine， and 20 μmol·L^-1 tanshinone I altered the viability of HK-2 cells. High-content analysis showed that 10 μmol·L^-1 ecliptasaponin A， chrysophanol， rutaecarpine， and tanshinone Ⅰ reduced the cell number （P<0.05， P<0.01）. The animal experiment showed that the mice in the high-dose ecliptasaponin A group presented slow movement， slow weight gain （P<0.01）， increased kidney index （P<0.01）， elevated SCr， BUN， and MDA levels （P<0.01）， and lowered SOD level （P<0.01）. Mild histopathological changes were observed in the high-dose ecliptasaponin A group. The network pharmacology results showed that the key targets of nephrotoxicity induced by ecliptasaponin A were mainly enriched in the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， prostatic cancer and lipid and atherosclerosis pathways. Western blot results verified that high dose of ecliptasaponin A raised the phosphorylation levels of PI3K and Akt （P<0.01）. ConclusionOn day 28 of administration， 29.1 mg·kg^-1 ecliptasaponin A was found to induce renal injury in rats. The mechanism may be related with the PI3K/Akt signaling pathway， which implied that excessive and prolonged usage of Ecliptae Herba may increase the incidence of adverse drug reactions.

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.