ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

Hepatic encephalopathy(HE)is a common complication of severe liver disease in the end stage,and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE.The liver is a crucial hub for immune regulation,and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE.As the main metabolites of intestinal flora,short-chain fatty acids(SCFAs)play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function.Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways,thereby playing an important role in the diagnosis,treatment,and prognostic evaluation of HE.Starting from the immunoregulatory effect of SCFAs,this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE,in order to provide new ideas for optimizing clinical prevention and treatment strategies.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. METHODS: A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to "multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands. RESULTS: The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T>G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T>G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T>G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T>G missense mutation resulted in the failure of forming 1 disulfide bond. CONCLUSION The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.
Humans ; Pedigree ; Arthrogryposis/genetics* ; Male ; Female ; Heterozygote ; Phenotype ; Mutation ; Child ; Metalloendopeptidases

In order to investigate the mitigating effect of Yin Chen aqueous extract on liver injury induced by LPS combined with D-GalN in mice,a mouse liver injury model was established by in-traperitoneal injection of LPS and D-GalN,and the mice were group-fed by instillation of saline,bi-phenyl dibenzyl ester,and Yin Chen aqueous extract with different concentrations of LPS and D-GalN.The liver index of mice was calculated,pathological tissue sections were observed,and the expression of ALT,AST,inflammatory cytokines,oxidative stress,hepatic enzymes,and IL-17/TNF pathway were detected in serum to investigate the effects and mechanisms of the aqueous ex-tracts of Yin Chen in alleviating the liver injury in mice.The results showed that the liver index of mice in the model group was significantly elevated,the serum levels of ALT and AST were signifi-cantly elevated,the levels of IL-iβ,IL-8 and TNF-α in liver tissue were significantly elevated,the levels of IL-4 were significantly reduced,the levels of GSH-Px,CAT and SOD were significantly reduced,the levels of ROS and MDA were significantly elevated,CYP2E1 and CYP1A2 protein content and mRNA expression were significantly up-regulated,and the expression levels of TNF,TNFR1,IL-17A,ACT1 and IL-6 mRNA were significantly up-regulated.The study showed that the aqueous extract of Yin Chen had a certain alleviating effect on the liver injury caused by LPS combined with D-GalN in mice.The mechanism of action includes decreasing the metabolic level of hepatic drug enzymes,alleviating oxidative stress,inhibiting the expression of IL-17/TNF pathway and down-regulating the level of inflammatory factors in mice.

This study examined the effect of islet macrophages on β-cell function changes during type 2 diabetes mellitus (T2DM) progression based on the traditional Chinese medicine theory that " moderate fire generating qi, hyperactive fire consuming qi" . T2DM is closely associated with chronic low-grade inflammation, with islet macrophages playing a central role in this process. Under physiological conditions, islet macrophages secrete anti-inflammatory and growth factors to regulate the immune response, promote cell proliferation, and support islet β-cell survival and function, reflecting the concept of " moderate fire generating qi" . However, during the pathological process of T2DM, islet macrophages become over-activated and dysfunctional, secreting large amounts of pro-inflammatory factors that trigger severe inflammatory responses and oxidative stress. This process damages islet β-cells, disrupts the islet microenvironment and blood supply, exacerbates local inflammation and structural damage, and worsens the survival environment of β-cells. Ultimately, this leads to fewer β-cells and function loss, aligning with the " hyperactive fire consuming qi" theory, where excessive fire depletes qi and blood. This study enhances the understanding and application of traditional Chinese medicine theories in modern medicine, offering a new perspective on T2DM prevention and treatment. Regulating islet macrophage function and reducing their pro-inflammatory responses may become key strategies for preserving β-cell function and slowing T2DM progression.

Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder caused by a combination of genetic and environmental factors.The epigenetic transcriptional modifications after RNA transcription can affect gene expression and glucose homeostasis.N6-methyladenine(m6A),as an RNA methylation modification,plays an important role in the pathogenesis of T2DM.This article reviews the research progress of m6A methylation in T2DM.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Kidney transplantation is widely recognized as the optimal treatment for children with end-stage renal disease(ESRD),offering significant improvements in growth,development,and long-term quality of life compared with prolonged dialysis.However,kidney transplantation in low-age(＜5 years old)and low-weight(＜15 kg)children presents significant clinical challenges due to their delicate vas-cular structures,limited surgical space,and complex perioperative management.This report presents two cases of kidney transplantation in low-age,low-weight children performed at Peking University People's Hospital.Case 1:a 2-year-3-month-old boy(8.8 kg),presenting a preoperative serum creatinine of 248μmol/L post-dialysis and the estimated glomerular filtration rates(eGFR)of 35.17 mL/(min·1.73 m2).Case 2:a 3-year-8-month-old girl(11.25 kg),presenting a preoperative creatinine of 281 μmol/L post-dialysis and the eGFR of 22.63 mL/(min·1.73 m2).Both recipients underwent transplantation via the extraperitoneal approach,with end-to-side anastomosis of the donor renal artery and vein to the recipient's common iliac artery and vein,respectively.The ureters were anastomosed to the bladder using the tunnel technique,and double-J stents were placed intraoperatively.The surgeries were uneventful,and both pa-tients exhibited rapid recovery of renal function.Postoperatively,serum creatinine levels decreased to 26μmol/L(Case 1)and 39 μmol/L(Case 2)by the third day,with the eGFR reaching 245.23 mL/(min·1.73 m2)and 164.12 mL/(min·1.73 m2),respectively.No complications,such as vascular thrombosis,ureteral stenosis,or abdominal compartment syndrome were observed during follow-up.A comprehensive literature review was conducted to contextualize these cases within global advancements in pediatric renal transplantation.Current evidence highlights the growing adoption of kidney transplantation for low-age,low-weight children,though debates persist regarding optimal surgical strategies(specifical-ly,the intraperitoneal versus extraperitoneal approaches).This case report underscores the feasibility of the extraperitoneal approach in overcoming anatomical limitations of low-weight pediatric recipients,with distinct advantages including reduced gastrointestinal complications and enhanced accessibility for post-operative ultrasound monitoring.Furthermore,mean arterial pressure(MAP)and central venous pressure(C VP)were systematically monitored intraoperatively to ensure optimal renal blood perfusion and graft viability.Our single-center experience provides valuable insights into surgical strategy selection and peri-operative management for this high-risk population.Nevertheless,larger multicenter studies are warranted to validate long-term outcomes and refine standardized protocols.

Objective:To compare the changes of maximun flow rate and residual urine volume after tension-free vaginal tape(TVT)and trans-obturator tape(TOT)in the treatment of stress urinary incon-tinence in women.Methods:The clinical data of female patients with stress urinary incontinence who underwent transvaginal midsection tension-free urethral suspension in Peking University People's Hospital from January 2022 to January 2024 were retrospectively analyzed.All the patients were followed up 1 month,6 months and 12 months after surgery.Urodynamics were performed to evaluate urethral sphincter function before surgery.At the same time,B-ultrasonography was improved to determine the residual uri-nary volume of the bladder,and urgent incontinence,detrusor weakness and bladder outlet obstruction were excluded,and the diagnosis was clearly stress incontinence.Maximum flow rate and residual urinary volume were measured during follow-up,and combined with the urinary incontinence questionnaire of the International Urinary Incontinence Advisory Committee,the surgical effect was judged to be cured,im-proved or ineffective according to the degree of improvement of urinary leakage symptoms after surgery.Results:A total of 150 female patients with stress urinary incontinence were included in the study,the average age of the patients was(55.12±10.23)years old,and the follow-up time was 12 months.All patients completed postoperative follow-up,of whom 60 underwent TVT and 90 underwent TOT.The overall effective rates(cure+improvement)1,6,and 12 months after surgery in the TVT group were 93.3％(56/60),91.7％(55/60),and 91.7％(55/60),and those in the TOT group were 92.2％(83/90),90.0％(81/90),90.0％(81/90),respectively,and there was no statistical difference be-tween the two groups.The average maximum urinary flow rates 1,6,and 12 months after surgery in the TVT group were(17.21±4.22)mL/s,(18.05±5.33)mL/s,and(18.37±4.92)mL/s,and those in the TOT group were(18.21±5.32)mL/s,(19.05±4.33)mL/s,and(19.27±4.92)mL/s,re-spectively,and there was no statistical difference between the two groups.The mean residual urine volume 1,6,and 12 months after surgery in the TVT group was(13.21±5.22)mL,(18.25±5.33)mL,and(16.37±7.92)mL,and those in the TOT group was(11.21±6.32)mL,(13.05±5.33)mL,and(11.27±5.92)mL,respectively,and there was no statistical difference between the two groups.Compared with preoperative levels,there were no significant differences in the average maximum flow rate and the residual urine volume in both group at 1,6,and 12 months after surgery.Conclusion:Both TVT and TOT are effective in the treatment of stress incontinence,and have no effect on postopera-tive maximum flow rate and residual urine volume.