This study aims to investigate the effects of Pulsatilla powder(PP)on colonic intestinal flora and tryptophan metabolism in piglets with diarrhea.Twenty-four weaned piglets were ran-domly divided into the normal control group,model group,self-healing group,and PP group.The model of piglet diarrhea was established by the compound factor of external evil+internal injury+epi-demic virus,and treated with PP.During the modeling period,the body weight,mental status and fecal patterns of piglets were monitored daily.After the experiment,the colon tissues were collect-ed for histopathological observation,and the inflammatory factors IL-1β and IL-6 in the colon tis-sue was detected by ELISA,16S rRNA was used to analyze colonic intestinal flora and RT-qPCR was used to determine the expression of genes related to tryptophan metabolism in the colon.The results showed that,compared with the model group,PP significantly improved the pathological status of the colon in piglets with diarrhea,with elevated body mass and a significant increase in goblet cells(P＜0.05);and significantly reduced the levels of IL-1β and IL-6 in the colon of diar-rhea piglets(P＜0.05).The results of intestinal flora showed that PP increased the abundance of Firmicutes(P＜0.01),Spirochaeota(P＜0.01)and Lactobacillus(P＜0.05),reduced the abun-dance of Bacteroidota(P＜0.05)、Prevotella_NK3B31_group(P＜0.05)and Clostridium_sensu_stricto 1(P＜0.01).Meanwhile,PP significantly reduced the expression level of TPH1 mRNA(P＜0.05),increased the expression levels of AhR(P＜0.05)and IL-22 mRNA in the co-lon of diarrhea piglets.These results indicates that PP may alleviate diarrhea in piglets by regula-ting colonic intestinal flora and genes related to intestinal tryptophan metabolism.This study pro-vides data support for the subsequent investigation of piglet diarrhea prevention and treatment.

Objective To explore the correlation between the systemic immune-inflammation index(SII)and the clinical and pathological characteristics of patients with IgA nephropathy(IgAN).Methods A total of 350 patients who underwent renal biopsy and were initially diagnosed with primary IgAN were selected.The clinical and pathological data of the patients were collected,and SII was calculated.According to the median SII level of 554.78 in peripheral blood,the IgAN patients were divided into the low SII group(SII≤554.78,175 cases)and the high SII group(SII>554.78,175 cases).Based on the presence or absence of endocapillary hyperplastic(E)lesion,350 patients were also divided into the E0 group(279 cases,79.7%)and the E1 group(71 cases,20.3%).Multivariate Logistic regression analysis was conducted to determine the influencing factors of E1 in IgAN patients.A predictive model was established,and the predictive value of the model was evaluated using the receiver operating characteristic(ROC)curve.Results There were higher systolic blood pressure(SBP),platelet count(PLT),neutrophil count(NEU),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),total cholesterol(TC),serum creatinine(Scr),serum C3 and 24-hour urine protein levels in the high SII group than those of the low SII group,while the lymphocyte count(LYM)was lower(P＜0.05).In terms of pathological manifestations,the proportion of E1 was higher in the high SII group than that of the low SII group(P＜0.05).There were lower PLT,NEU,NLR,PLR,Scr and 24-hour urine protein in patients of the E0 group than those of the E1 group,while higher Hb,LYM and ALB levels in the E0 group than those of the E1 group(P＜0.05).Multivariate Logistic regression analysis showed that elevated SII,Scr and 24-hour urine protein levels were independent risk factors for E1 lesion in IgAN patients(P＜0.05).The area under the curve(AUC)of the predictive model for E1 lesion in IgAN patients was 0.781(95%CI:0.722-0.840).Conclusion SII can reflect the clinical and pathological severity in IgAN patients,providing new insights for clinical evaluation of the disease progression in IgAN patients.

Danggui Buxue decoction(DBD)is a classic prescription with immunomodulatory and hematopoietic effects.Previous studies have shown the DBD has potential to be used as an oral im-mune booster.However,its immunomodulatory effects and mechanism of action have not been thoroughly studied,especially the protective mechanism of immunomodulatory regulation in the state of immunosuppressive is still unclear.The aim of this study was to explore the protective mechanism of DBD in the immunosuppressive state using network pharmacology combined with animal experiments verification.The active components,core targets and signaling pathways of DBD in treating immunosuppression were obtained using network pharmacology tools.On this ba-sis,the active components of DBD were identified using HPLC-MS,and in vivo studies were con-ducted at the same time.The key active components of DBD obtained using network pharmacology included quercetin,kaempferol and formononetin.The core targets included TP53,RELA,TNF,AKT1,and IL-6.KEGG pathway enrichment analysis showed that phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)may play an important role in the treatment of immunosuppres-sive diseases using DBD.Molecular docking confirmed that each core target had good binding activ-ity with its corresponding compounds.Animal experiments showed that after DBD intervention,the mRNA gene and protein expression of RELA,TNF,and IL-6 in the serum was significantly down-regulated.The mRNA expression of PI3K and AKT in the ileum and PI3K protein expression were also downregulated.In conclusion,DBD exerts its role in treating immunosuppressive diseases by regulating the PI3K-AKT signaling pathway.

Objective To explore the correlation between the systemic immune-inflammation index(SII)and the clinical and pathological characteristics of patients with IgA nephropathy(IgAN).Methods A total of 350 patients who underwent renal biopsy and were initially diagnosed with primary IgAN were selected.The clinical and pathological data of the patients were collected,and SII was calculated.According to the median SII level of 554.78 in peripheral blood,the IgAN patients were divided into the low SII group(SII≤554.78,175 cases)and the high SII group(SII>554.78,175 cases).Based on the presence or absence of endocapillary hyperplastic(E)lesion,350 patients were also divided into the E0 group(279 cases,79.7%)and the E1 group(71 cases,20.3%).Multivariate Logistic regression analysis was conducted to determine the influencing factors of E1 in IgAN patients.A predictive model was established,and the predictive value of the model was evaluated using the receiver operating characteristic(ROC)curve.Results There were higher systolic blood pressure(SBP),platelet count(PLT),neutrophil count(NEU),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),total cholesterol(TC),serum creatinine(Scr),serum C3 and 24-hour urine protein levels in the high SII group than those of the low SII group,while the lymphocyte count(LYM)was lower(P＜0.05).In terms of pathological manifestations,the proportion of E1 was higher in the high SII group than that of the low SII group(P＜0.05).There were lower PLT,NEU,NLR,PLR,Scr and 24-hour urine protein in patients of the E0 group than those of the E1 group,while higher Hb,LYM and ALB levels in the E0 group than those of the E1 group(P＜0.05).Multivariate Logistic regression analysis showed that elevated SII,Scr and 24-hour urine protein levels were independent risk factors for E1 lesion in IgAN patients(P＜0.05).The area under the curve(AUC)of the predictive model for E1 lesion in IgAN patients was 0.781(95%CI:0.722-0.840).Conclusion SII can reflect the clinical and pathological severity in IgAN patients,providing new insights for clinical evaluation of the disease progression in IgAN patients.

Danggui Buxue decoction(DBD)is a classic prescription with immunomodulatory and hematopoietic effects.Previous studies have shown the DBD has potential to be used as an oral im-mune booster.However,its immunomodulatory effects and mechanism of action have not been thoroughly studied,especially the protective mechanism of immunomodulatory regulation in the state of immunosuppressive is still unclear.The aim of this study was to explore the protective mechanism of DBD in the immunosuppressive state using network pharmacology combined with animal experiments verification.The active components,core targets and signaling pathways of DBD in treating immunosuppression were obtained using network pharmacology tools.On this ba-sis,the active components of DBD were identified using HPLC-MS,and in vivo studies were con-ducted at the same time.The key active components of DBD obtained using network pharmacology included quercetin,kaempferol and formononetin.The core targets included TP53,RELA,TNF,AKT1,and IL-6.KEGG pathway enrichment analysis showed that phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT)may play an important role in the treatment of immunosuppres-sive diseases using DBD.Molecular docking confirmed that each core target had good binding activ-ity with its corresponding compounds.Animal experiments showed that after DBD intervention,the mRNA gene and protein expression of RELA,TNF,and IL-6 in the serum was significantly down-regulated.The mRNA expression of PI3K and AKT in the ileum and PI3K protein expression were also downregulated.In conclusion,DBD exerts its role in treating immunosuppressive diseases by regulating the PI3K-AKT signaling pathway.

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

In recent years,the incidence of heat-related diseases has been on a steady upward trend,which is closely associated with environmental factors such as climate change and air pollution.Exposure to a hot environment and/or strenuous physical activities can progress to heat stroke(HS),an acute disease that can lead to death.Current research indicates that gut injury occupies the most crucial initiating position in the pathophysiological changes and pathogenesis of HS.Probiotics can reduce the incidence and mortality of HS through maintaining the health of the gut microbiota,regulating the intestinal immune system,and other effects.In addition,the gut microbiota can construct axis systems to interact with multiple organs such as the liver,lungs,and brain,which is of great significance for alleviating the damage to distant organs caused by HS.This paper reviews the regulation of the gut microbiota by probiotics to improve the intestinal heat tolerance ability and barrier function,aiming to provide references for the prevention and treatment of heat stroke in clinical practice.

Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.