OBJECTIVES: The risk factors and role of mother‒child gut microbiota in pediatric inflammatory bowel disease (PIBD) remain unclear. We aimed to explore the clinical risk factors associated with PIBD, analyze the characteristics of gut microbiota of children and their mothers, and examine the correlation of the microbial composition in mother‒child pairs. METHODS: We conducted a case-control study including children with PIBD and their mothers as the case group, as well as healthy children and their mothers as the control group. Questionnaires were used to collect information such as family illness history and maternal and early-life events. Fecal samples were collected from the children and mothers for microbiota 16S ribosomal RNA (rRNA) sequencing to analyze the composition and its potential association with PIBD. RESULTS: A total of 54 pairs of cases and 122 pairs of controls were recruited. A family history of autoimmune disease and antibiotic use during pregnancy were associated with an increased risk of PIBD, and a higher education level of the father was associated with a decreased risk of PIBD. Children with PIBD and mothers exhibited different gut microbiota compared to healthy children and mothers. Similarities were observed in the gut microbiota of mothers and children in the same groups. Some bacterial biomarkers of mothers discovered in this study had the power to predict PIBD in their offspring. CONCLUSIONS PIBD is influenced by maternal risk factors and has unique gut microbiota characteristics. The mother‒child gut microbiota is closely related, suggesting the transmission and influence of the gut microbiota between mothers and children. This study highlights the potential pathogenesis of PIBD and provides a basis for developing targeted interventions.
Humans ; Gastrointestinal Microbiome ; Female ; Risk Factors ; Case-Control Studies ; Male ; Child ; Inflammatory Bowel Diseases/etiology* ; Adult ; RNA, Ribosomal, 16S/genetics* ; Feces/microbiology* ; Mothers ; Pregnancy ; Child, Preschool

ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription （KXJD） and investigate its effective components and therapeutic targets in the treatment of common psoriasis. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-Q-TOF MS） was used to identify and analyze the chemical components of KXJD and its blood-entering chemical components. The chemical components of the single decoction were further identified to clarify the source of the chemical components in KXJD. Then， all identified blood-entering compounds were screened for effective active ingredients through the Swiss ADME database. The active ingredient targets of KXJD were searched on the Swiss Target Prediction platform. The targets of common psoriasis were searched in OMIM， GEO， GeneCards， and DISGNET databases to obtain drug-disease intersection targets. The protein-protein interaction network of intersection targets was constructed using STRING， and then the core blood-entering component-intersection target network of KXJD was constructed. The core target proteins in the network were selected for molecular docking with the core components of KXJD. Small molecules and proteins were pretreated， and appropriate docking sites were selected. AutoDock Vina software was used for continuous local search and repeated iterations to find molecular docking conformations. PyMOL software and LigPlot+ software were used for analysis and visualization. Subsequently， the verification was carried out through animal experiments. SPF-grade male C57 mice were randomly divided into a blank group， a model group， a positive drug methotrexate group， and a KXJD group. In the model group， the methotrexate group， and the KXJD group， imiquimod was applied to the backs of the mice for modeling. The blank group and the model group were administered normal saline by gavage， while the methotrexate group and the KXJD group were respectively administered 1 mg·kg^-1 suspension and 30.42 g·kg^-1 decoction of traditional Chinese medicine by gavage. Five days after administration， the mice were sacrificed， and samples were collected. Hematoxylin-eosin （HE） staining was used to observe the skin tissue samples of mice， and the effect of KXJD on the pathological manifestations of psoriasis mice was analyzed. The expression areas of tumor necrosis factor-α （TNF-α）， cyclooxygenase 2 （PTGS2）， interleukin （IL）-1β， and IL-6 in the skin tissue of mice were detected by immunohistochemistry （IHC）. The mRNA expressions of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of mice were detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultsIn this study， 208 compounds in KXJD were identified by UPLC-Q-TOF MS， and 44 compounds were detected in serum， including 28 prototype components and 16 metabolites. 12 blood-entering active components were screened， and 1 153 active component targets and 1 076 psoriasis-related targets were identified. Eighty-five targets in the intersection set were drug-disease common targets. PPI network analysis showed that TNF-α， IL-1β， IL-6， PTGS2， and ALB were the key target proteins. The results of molecular docking showed that the binding ability of （+）-hexylphenylglycolic acid to key target proteins such as PTGS2 was stable， and PTGS2 showed high stability with a variety of core compounds. Compared with those in the blank group， the stratum corneum and epidermis in the model group mice were significantly thickened， and the pathological Baker score of the mice's skin in the model group was significantly higher than that of the blank group （P<0.01）. The expression areas of PTGS2， TNF-α， IL-1β， and IL-6 proteins in the skin tissue of the model group mice were significantly increased （P<0.01）， and the expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the model group mice were significantly elevated （P<0.01）. Compared with the model group， the pathological Baker scores of the methotrexate group and the KXJD group were both decreased （P<0.01）， and the expression areas in the skin tissue of the methotrexate group and the KXJD group were significantly reduced （P<0.05， P<0.01）. The expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the methotrexate group and the KXJD group were significantly decreased （P<0.01）. ConclusionKXJD can effectively improve the skin lesions of psoriasis model mice and reduce the expression of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of psoriasis model mice. PTGS2 has a stable binding ability with a variety of compounds in the decoction， which may be a key target for the treatment of psoriasis. The compound （+）-hexylphenylglycolic acid may play a key role.

ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription （KXJD） and investigate its effective components and therapeutic targets in the treatment of common psoriasis. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-Q-TOF MS） was used to identify and analyze the chemical components of KXJD and its blood-entering chemical components. The chemical components of the single decoction were further identified to clarify the source of the chemical components in KXJD. Then， all identified blood-entering compounds were screened for effective active ingredients through the Swiss ADME database. The active ingredient targets of KXJD were searched on the Swiss Target Prediction platform. The targets of common psoriasis were searched in OMIM， GEO， GeneCards， and DISGNET databases to obtain drug-disease intersection targets. The protein-protein interaction network of intersection targets was constructed using STRING， and then the core blood-entering component-intersection target network of KXJD was constructed. The core target proteins in the network were selected for molecular docking with the core components of KXJD. Small molecules and proteins were pretreated， and appropriate docking sites were selected. AutoDock Vina software was used for continuous local search and repeated iterations to find molecular docking conformations. PyMOL software and LigPlot+ software were used for analysis and visualization. Subsequently， the verification was carried out through animal experiments. SPF-grade male C57 mice were randomly divided into a blank group， a model group， a positive drug methotrexate group， and a KXJD group. In the model group， the methotrexate group， and the KXJD group， imiquimod was applied to the backs of the mice for modeling. The blank group and the model group were administered normal saline by gavage， while the methotrexate group and the KXJD group were respectively administered 1 mg·kg^-1 suspension and 30.42 g·kg^-1 decoction of traditional Chinese medicine by gavage. Five days after administration， the mice were sacrificed， and samples were collected. Hematoxylin-eosin （HE） staining was used to observe the skin tissue samples of mice， and the effect of KXJD on the pathological manifestations of psoriasis mice was analyzed. The expression areas of tumor necrosis factor-α （TNF-α）， cyclooxygenase 2 （PTGS2）， interleukin （IL）-1β， and IL-6 in the skin tissue of mice were detected by immunohistochemistry （IHC）. The mRNA expressions of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of mice were detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultsIn this study， 208 compounds in KXJD were identified by UPLC-Q-TOF MS， and 44 compounds were detected in serum， including 28 prototype components and 16 metabolites. 12 blood-entering active components were screened， and 1 153 active component targets and 1 076 psoriasis-related targets were identified. Eighty-five targets in the intersection set were drug-disease common targets. PPI network analysis showed that TNF-α， IL-1β， IL-6， PTGS2， and ALB were the key target proteins. The results of molecular docking showed that the binding ability of （+）-hexylphenylglycolic acid to key target proteins such as PTGS2 was stable， and PTGS2 showed high stability with a variety of core compounds. Compared with those in the blank group， the stratum corneum and epidermis in the model group mice were significantly thickened， and the pathological Baker score of the mice's skin in the model group was significantly higher than that of the blank group （P<0.01）. The expression areas of PTGS2， TNF-α， IL-1β， and IL-6 proteins in the skin tissue of the model group mice were significantly increased （P<0.01）， and the expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the model group mice were significantly elevated （P<0.01）. Compared with the model group， the pathological Baker scores of the methotrexate group and the KXJD group were both decreased （P<0.01）， and the expression areas in the skin tissue of the methotrexate group and the KXJD group were significantly reduced （P<0.05， P<0.01）. The expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the methotrexate group and the KXJD group were significantly decreased （P<0.01）. ConclusionKXJD can effectively improve the skin lesions of psoriasis model mice and reduce the expression of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of psoriasis model mice. PTGS2 has a stable binding ability with a variety of compounds in the decoction， which may be a key target for the treatment of psoriasis. The compound （+）-hexylphenylglycolic acid may play a key role.

Objective: To investigate the coexistence of comorbidity of myopia, overweight/obesity and depressive symptoms among middle school students in Quzhou and its associated factors, so as to provide evidence for integrated prevention and control of common multiple health issues in students. Methods: From September to November 2023, a total of 5 867 middle school students from 6 counties (cities and districts) in Quzhou City were selected by stratified random cluster sampling. Physical and visual examinations were conducted, and the Center for Epidemiological Studies - Depression Scale (CES-D) along with a questionnaire on health status and influencing factors were completed. Multivariate Logistic regression was used to analyze the related factors of coexistence of myopia, overweight/obesity, and depressive symptoms among middle school students, and a nomogram model was constructed based on the results. Results: A total of 161 middle school students in Quzhou City were identified as having comorbid myopia, overweight/ obesity and depressive symptoms, with a detection rate of 2.74%. The results of multivariate Logistic regression analysis showed that the coexistence of myopia, overweight/obesity and depressive symptoms increased among middle school students with older age ( OR =1.11), a greater number unhealthy dietary behaviors (1,2,≥3; OR =2.40, 2.70, 4.63), insufficient sleep( OR =1.78) and alcohol consumption ( OR =2.11)(all P <0.05). Compared with no homework after class, those whose homework duration after class was 1 to < 2 hour had a lower risk of comorbidity of myopia, overweight/obesity and depressive symptoms ( OR =0.53, P <0.05). The results of the nomogram model showed that the AUC (95% CI ) was 0.71 (0.67-0.74). Conclusions The coexistence of myopia, overweight/obesity and depressive symptoms among middle school students in Quzhou City is related to age, sleeping, alcohol consumption, poor dietary behavior and the duration of after school homework. The nomogram model can assist in the early screening and intervention of multiple health issues among students.

ObjectiveTo observe the effect of Coptidis Rhizoma and Ophiopogonis Radix on renal tissue injury and epidermal growth factor receptor （EGFR）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in rats with diabetic nephropathy （DN） and explore its possible mechanism of delaying DN. MethodThirty-six male Wistar rats were randomly divided into a normal group （6 rats） and a model group （30 rats）. The model group was fed with a high-fat and high-sugar diet combined with streptozotocin （STZ） to establish a rat model of type 2 diabetes. After the successful preparation of the model， the rats were randomly divided into the model group， low， medium， and high dose groups of Coptidis Rhizoma and Ophiopogonis Radix （100， 200， 400 mg·kg^-1）， and metformin group （200 mg·kg^-1）. After administration， the levels of fasting blood glucose （FBG）， 24 h urine protein （24 h-UTP）， creatinine （SCr）， urea nitrogen （BUN）， and uric acid （UA） were detected. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes of renal tissue in rats. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the related protein expression of EGFR， PI3K， and Akt and their mRNA expression levels in the renal tissue of rats in each group. ResultsCompared with the normal group， the levels of FBG， SCr， BUN， UA， 24 h-UTP， and kidney index in the model group were significantly increased （P<0.01）， most renal tubular epithelial cells were necrotic， and the content of collagen in glomeruli was significantly increased （P<0.01）. Compared with the model group， the above indexes of rats in each administration group were improved to varying degrees. The FBG， SCr， BUN， UA， 24 h-UTP， and kidney index of rats in each dose group and metformin group were significantly decreased （P<0.01， P<0.05）. The necrosis degree of renal tubular epithelial cells was reduced， and the fibrosis area was decreased （P<0.01）. There related protein and mRNA expressions of EGFR， PI3K， and Akt were significantly increased （P<0.05， P<0.01）. ConclusionCoptidis Rhizoma and Ophiopogonis Radix can alleviate renal tissue injury in rats with DN， and their mechanism may be related to the regulation of the EGFR/PI3K/Akt signaling pathway.

Objective The high incidence, disability, and mortality rates of stroke result in a heavy economic and social burden. The aim of this study was to investigate the relationship between triglyceride-glucose (TyG) index and new-onset stroke to assist in the identification of high-risk groups for stroke and to provide ideas for effective prevention. Methods The study was based on data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018 and included 7630 eligible middle-aged and elderly participants. The association between TyG index and new-onset stroke was assessed by logistic regression modelling and restricted triple spline analysis. Results A total of 431 participants had a new stroke. The TyG index was found to be a risk factor for stroke occurrence when it was >8.523, and there was a positive linear association moderated by gender. Conclusion Elevated TyG index is a risk factor for new stroke. This study provides new ideas for the identification of high-risk groups for stroke and for intervention measures and timing.

OBJECTIVE To identify and classify the chemical components and components absorbed into blood of Sishen Pills u-sing ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry.METHODS SD rats were divided into blank group and drug administration group.The rats in drug administration group were given water extract of Sishen Pills formula intragastrically,and blank and drug-containing plasma were collected respectively.A Hypersil GOLD VANQUISH column(2.1 mm×100 mm,1.9 μm)was used,with 0.1%formic acid water acetonitrile as the mobile phase,gradient elution,volume flow rate of 0.3 mL·min-1,and column temperature of 35℃.Electrospray ion source(ESI)with positive and negative ion scanning mode was used for chromatographic separation and mass spectrometry data acquisition.The chemical components of Sishen Pills were identi-fied by comparing the exact molecular mass,fragment ion information and relative retention time with the map of reference substance,matching with the self-established database and combining with literature reports.On this basis,the components absorbed into blood of Sishen Pills were analyzed by comparing the blank plasma and drug-containing plasma.RESULTS A total of 181 chemical compo-nents were identified from Sishen Pills,mainly including flavonoids,alkaloids,lignans and other components.A total of 49 prototype blood components were identified from the plasma samples,mainly including flavonoids,alkaloids and other components.CONCLU-SION A variety of chemical components in Sishen Pills and drug-containing plasma are comprehensively,accurately and quickly i-dentified,and all of them are assigned to the various medicinal materials in the prescription.This study provides reference for the qual-ity control,basic research on medicinal effect materials and clinical application of Sishen Pills.

Objective To investigate the expression of Bone morphogenetic protein 4(BMP4)in human endometrial stromal cells(hESCs)of patients with recurrent spontaneous abortion(RSA)and the regulation of Forkhead transcription factor 1(FOXO1)by BMP4.Methods The decidua tissues of RSA patients and Healthy control(HC)patients in People's Hospital of Wuhan University were collected,and the expression of BMP4 was analyzed by immunohistochemistry and RT-qPCR.hESC was used in vitro cell experiments,lentivirus was transfected to knock down the expression of BMP4 and establish the cell model of RSA.After decidualization,CCK-8 as-say,inverted microscope,and Western blot assay were used to detect the cell proliferation,morphology,and expression levels of decidual-ization marker genes.To verify whether BMP4 knockdown affects FOXO1 expression,a FOXO1 inhibitor(AS1842856)was used to per-form a response experiment,and the upstream and downstream relationship between FOXO1 and BMP4 was analyzed by CCK-8 experi-ment,inverted microscope,and Western blot.In animal experiments,intraperitoneal injection of LPS-induced abortion in pregnant mice,and the expression of BMP4 in decidua were detected to explore the relationship between BMP4 and abortion in mice.Results Compared with the HC group,the expression of BMP4 in the deciduous tissues of RSA patients was significantly decreased.After BMP4 was knocked down,the decidualization was significantly abnormal,which showed that the proliferation rate increased,the cell morphologi-cal transformation was not obvious,and the expression of decidualization marker genes was down-regulated.FOXO1 was the downstream regulatory molecule of BMP4,knocking down BMP4 could inhibit the expression of FOXO1,and BMP4 could regulate the decidualization of hESC through FOXO1.In animal models,the expression of BMP4 in decidua and placental weight of aborted pregnant mice were signif-icantly reduced.Conclusion The expression of BMP4 was significantly down-regulated in decidual tissues of RSA patients and aborted mice.In cell experiments,BMP4 can promote decidualization of hESC by regulating the expression of FOXO1.Abnormally low expression of BMP4 may be one of the reasons for decidualization defects in RSA patients.

Objective In the future,during the landing and exploration of near-Earth planets(e.g.,Mars,Jupiter,etc.),astronauts may take the initiative to start fasting to reduce the amount of load;and it is even more likely that astronauts will take the initiative to fast in the process of manned deep-space exploration in the future,or they may enter a dormant low-metabolism state to save the amount of load to enable the spaceship to fly for a longer period,and to locate in a deeper and farther position.The ability of an individual to maintain cognitive ability and respond appropriately over a period in a long-term fasting state is important for survival.Therefore,the present study focused on investigating the effects of 15 days of complete fasting on dual cognitive control function and its neural mechanisms.Methods Twenty-four healthy volunteers were recruited to participate in the fasting experiment.Behavioral and electroencephalographic data from the AX-CPT Task were collected with event-related potentials(ERP)to assess the effects of 15 days of complete fasting on dual cognitive control in 16 volunteers.Results(1)Behavioral outcomes had significant main effects on response time[F(1,15)=99.41,P?

Objective:To observe the effect of combination of esketamine and sufentanil on postoperative analgesia and postpartum depression after cesarean section.Methods:A total of 150 primiparous women who underwent lower segment cesarean section under spinal anesthesia and postoperative analgesia at Changsha Maternal and Child Health Hospital from February to October 2021 were selected and randomly divided into three groups: A, B, and C, with 50 cases in each group. All three groups underwent combined spinal epidural anesthesia and received patient-controlled intravenous analgesia (PCIA) after surgery. The group A received low-dose esketamine via intravenous pump after fetal delivery, with PCIA formula esketamine combined with sufentanil; After the delivery of fetuses in the group B and the group C, an equal dose of physiological saline was pumped into the vein. The PCIA formula of esketamine combined with sufentanil for the group B and Sufentanil for the group C. We compared the pain Visual Analogue Scale (VAS) and Edinburgh Postpartum Depression Scale (EPDS) scores of three groups of patients at different time points after surgery, as well as the postoperative pain relief rate and incidence of adverse reactions.Resultsl:There was a statistically significant difference in VAS between the group A and the group B within 48 hours after surgery compared to the group C (all P<0.05), while there was a statistically significant difference in VAS between the group A and the group B within 24 hours after surgery (all P<0.05). The postoperative pain relief rate in the group A and group B was significantly lower than that in the group C, and the incidence of postpartum depression within 7 days after surgery was significantly lower than that in the group C. Moreover, the incidence of postpartum depression in the group A was lower than that in the group B within 3 days after surgery, and the differences were statistically significant (all P<0.05). There was no statistically significant difference in the incidence of postpartum depression among the three groups 42 days after surgery (all P>0.05), and there was no statistically significant difference in the incidence of adverse reactions among the three groups ( P>0.05). Conclusions:Esketamine combined with sufentanil can synergistically enhance the analgesic effect after cesarean section and reduce the incidence of early postpartum depression after surgery.