OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Progressive familial intrahepatic cholestasis type 8 (PFIC8). METHODS A child with PFIC diagnosed at Beijing Children's Hospital Affiliated to Capital Medical University in September 2025 was selected as the study subject. Peripheral venous blood samples were collected from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Beijing Children's Hospital Affiliated to Capital Medical University (Ethics No.: 2023-E-126-Y). RESULTS: The proband, a 2-month-old female infant, had manifested jaundice of the skin and sclera, and slightly distended abdomen. She had no visible abdominal wall varicose veins, soft abdomen, and no palpable masses. Biliary atresia was ruled out by intraoperative cholangiography. WES revealed that she has harbored compound heterozygous variants of KIF12 gene, namely c.809C>T (p.Ala270Val) and c.1313G>A (p.Arg438Lys), which were verified by Sanger sequencing to have derived from her mother and father, respectively. According to the ACMG guidelines, both variants were classified as variants of uncertain significance (VUS). Based on the pre-defined search strategy, 10 articles were retrieved, which involved 25 PFIC cases, including 5 from China. Together with the proband of this study, the 26 PFIC patients have primarily presented with high GGT cholestasis, with the genetic cause in all cases attributed to variants of the KIF12 gene. CONCLUSION The c.809C>T and c.1313G>A compound heterozygous variants of the KIF12 gene probably underlay the pathogenesis of cholestatic liver disease in this child. Above findings have enriched the mutational and phenotypic spectra of PFIC8.
Humans ; Kinesins/genetics* ; Female ; Cholestasis, Intrahepatic/genetics* ; Infant ; Heterozygote ; Mutation ; Exome Sequencing ; Male

Objective:To investigate the effect of zine finger BED domain-containing protein 2(ZBED2)on immune escape of hepatocellular carcinoma(HCC)through glycolysis pathway and its potential mechanism.Methods:Expression of ZBED2 in HCC tis-sues and binding sites of them were analyzed in bioinformatics database,the pathway regulated by ZBED2 was analyzed,as well as the correlation between ZBED2 and glycolysis genes.qPCR and Western blot were used to detected expressions of ZBED2 and pro-grammed death-ligand 1(PD-L1)in HCC cells,cell viability was detected by MTT,toxicity of CD8+T cells was detected by cytotoxicity assay,and cytokine expression was detected by ELISA.Extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)were detected by extracellular flow analyzer,glycolytic gene expression was detected by qPCR,and glycolytic index was detected by kit.Expression of CD8+T cell in tumor tissues was detected by immunohistochemical staining.Results:ZBED2 was up-regulated in HCC,overexpression of ZBED2 could promote expression of PD-L1,while inhibit cytotoxicity of CD8+T cells to HCC.Overexpression of ZBED2 inhibited CD8+T cell activity in HCC by activating glycolysis pathway,and further addition of glycolysis inhibitor 2-DG at-tenuated the above results.In vivo experiments showed that ZBED2 knockdown inhibited tumor growth,inhibited PD-L1 expression,while promoted CD8+T cell infiltration in vivo.Conclusion:ZBED2 induces expression of PD-L1 in HCC through glycolytic metabo-lism,and promotes immune escape.

Objective To investigate the occurrence of dysphagia in patients with congenital esophageal atre-sia(EA)after surgery and study the associated risk factors.Methods A retrospective analysis was conducted on clinical data of 103 children who underwent surgery for congenital EA at Beijing Children's Hospital,Capital Medi-cal University,from July 2016 to August 2023.Results A total of 103 eligible cases of congenital EA were includ-ed in this study,among which 74 cases experienced dysphagia,with an incidence rate of 71.8％.Single-factor anal-ysis revealed that primary surgery(x2=4.017,P=0.045),endoscopic surgery(x2=8.315,P=0.004),long-seg-ment defects(x2=10.975,P＜0.001),gastroesophageal reflux(x2=16.973,P＜0.001),vocal cord paralysis(x2=4.017,P=0.045),tracheomalacia(x2=5.778,P=0.016),and arytenoid movement disorder(x2=10.420,P=0.001)were significantly associated with postoperative dysphagia.Further binary logistic regression analysis indi-cated that endoscopic surgery(OR=24.373,P=0.016),tracheomalacia(OR=17.556,P=0.010),and anasto-motic stenosis(OR=20.453,P=0.032)were independent risk factors for increased incidence of postoperative dys-phagia.Moreover,stratified analysis of dysphagia duration using unordered multinomial logistic regression revealed that tracheomalacia(OR=16.883,P=0.007;OR=4.337,P=0.045),long-segment defects(OR=0.040,P=0.049;OR=0.040,P=0.036),and arytenoid movement disorder(OR=0.127,P=0.039;OR=0.510,P=0.028)were closely associated with dysphagia duration.Conclusion Dysphagia is a common symptom in children with congenital EA after surgery across all age groups.Endoscopic surgery,long-segment defects,tracheomalacia,and anastomotic stenosis are independent factors contributing to postoperative dysphagia.Additionally,tracheoma-lacia,long-segment defects,and arytenoid movement disorder are closely related to the duration of dysphagia.

Biliary atresia (BA) is a serious neonatal disease, which can eventually develop into cholestatic cirrhosis due to inflammation and progressive fibrosis of bile ducts inside and outside the liver.Kasai portoenterostomy (KP) is the main management strategy of BA that can help children rebuild bile drainage channels.However, the progress of intrahepatic diseases will cause portal hypertension, liver fibrosis, end-stage liver disease and other complications to varying degrees after KP in children, affecting their short-term and long-term prognosis and health.It is also possible that children need liver transplantation within one year after operation.At present, there is no consensus strategy for the prediction of the prognosis of KP in clinical practice.There is a need to find a reliable non-invasive method with high sensitivity and specificity to predict the prognosis after KP.Recently, many examination strategies have been proposed for predicting the prognosis after KP.In this paper, these non-invasive or minimally invasive methods were reviewed according to the source of predictors.

Objective:To investigate the effect of zine finger BED domain-containing protein 2(ZBED2)on immune escape of hepatocellular carcinoma(HCC)through glycolysis pathway and its potential mechanism.Methods:Expression of ZBED2 in HCC tis-sues and binding sites of them were analyzed in bioinformatics database,the pathway regulated by ZBED2 was analyzed,as well as the correlation between ZBED2 and glycolysis genes.qPCR and Western blot were used to detected expressions of ZBED2 and pro-grammed death-ligand 1(PD-L1)in HCC cells,cell viability was detected by MTT,toxicity of CD8+T cells was detected by cytotoxicity assay,and cytokine expression was detected by ELISA.Extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)were detected by extracellular flow analyzer,glycolytic gene expression was detected by qPCR,and glycolytic index was detected by kit.Expression of CD8+T cell in tumor tissues was detected by immunohistochemical staining.Results:ZBED2 was up-regulated in HCC,overexpression of ZBED2 could promote expression of PD-L1,while inhibit cytotoxicity of CD8+T cells to HCC.Overexpression of ZBED2 inhibited CD8+T cell activity in HCC by activating glycolysis pathway,and further addition of glycolysis inhibitor 2-DG at-tenuated the above results.In vivo experiments showed that ZBED2 knockdown inhibited tumor growth,inhibited PD-L1 expression,while promoted CD8+T cell infiltration in vivo.Conclusion:ZBED2 induces expression of PD-L1 in HCC through glycolytic metabo-lism,and promotes immune escape.

Objective To investigate the occurrence of dysphagia in patients with congenital esophageal atre-sia(EA)after surgery and study the associated risk factors.Methods A retrospective analysis was conducted on clinical data of 103 children who underwent surgery for congenital EA at Beijing Children's Hospital,Capital Medi-cal University,from July 2016 to August 2023.Results A total of 103 eligible cases of congenital EA were includ-ed in this study,among which 74 cases experienced dysphagia,with an incidence rate of 71.8％.Single-factor anal-ysis revealed that primary surgery(x2=4.017,P=0.045),endoscopic surgery(x2=8.315,P=0.004),long-seg-ment defects(x2=10.975,P＜0.001),gastroesophageal reflux(x2=16.973,P＜0.001),vocal cord paralysis(x2=4.017,P=0.045),tracheomalacia(x2=5.778,P=0.016),and arytenoid movement disorder(x2=10.420,P=0.001)were significantly associated with postoperative dysphagia.Further binary logistic regression analysis indi-cated that endoscopic surgery(OR=24.373,P=0.016),tracheomalacia(OR=17.556,P=0.010),and anasto-motic stenosis(OR=20.453,P=0.032)were independent risk factors for increased incidence of postoperative dys-phagia.Moreover,stratified analysis of dysphagia duration using unordered multinomial logistic regression revealed that tracheomalacia(OR=16.883,P=0.007;OR=4.337,P=0.045),long-segment defects(OR=0.040,P=0.049;OR=0.040,P=0.036),and arytenoid movement disorder(OR=0.127,P=0.039;OR=0.510,P=0.028)were closely associated with dysphagia duration.Conclusion Dysphagia is a common symptom in children with congenital EA after surgery across all age groups.Endoscopic surgery,long-segment defects,tracheomalacia,and anastomotic stenosis are independent factors contributing to postoperative dysphagia.Additionally,tracheoma-lacia,long-segment defects,and arytenoid movement disorder are closely related to the duration of dysphagia.

Biliary atresia (BA) is a serious neonatal disease, which can eventually develop into cholestatic cirrhosis due to inflammation and progressive fibrosis of bile ducts inside and outside the liver.Kasai portoenterostomy (KP) is the main management strategy of BA that can help children rebuild bile drainage channels.However, the progress of intrahepatic diseases will cause portal hypertension, liver fibrosis, end-stage liver disease and other complications to varying degrees after KP in children, affecting their short-term and long-term prognosis and health.It is also possible that children need liver transplantation within one year after operation.At present, there is no consensus strategy for the prediction of the prognosis of KP in clinical practice.There is a need to find a reliable non-invasive method with high sensitivity and specificity to predict the prognosis after KP.Recently, many examination strategies have been proposed for predicting the prognosis after KP.In this paper, these non-invasive or minimally invasive methods were reviewed according to the source of predictors.

Objective In order to address the issues of inconvenience,high medical costs,and lack of universality associated with traditional knee rehabilitation equipment,a portable intelligent wheelchair for knee rehabilitation was designed in this study.Methods Based on the analysis of the knee joint's structure and rehabilitation mechanisms,an electric pushrod-driven rehabilitation institution was developed.A multi-functional module was designed with a modular approach,and the control of the wheelchair body and each functional module was implemented using an STM32 single-chip microcomputer.A three-dimensional model was established using SolidWorks software.In conjunction with Adams and Ansys simulation software,kinematic and static analyses were conducted on the knee joint rehabilitation institution and its core components.A prototype was constructed to verify the equipment's actual performance.Results According to the prototype testing,the actual range of motion for the knee joint swing rod is 15.1°～88.9°,the angular speed of the swing rod ranges from-7.9 to 8.1°/s,the angular acceleration of the swing rod varies from-4.2 to 1.6°/s2,the thrust range of the electric pushrod is-82.6 to 153.1 N,and the maximum displacement of the load pedal is approximately 1.7 mm,with the leg support exhibiting a maximum deformation of about 1.5 mm.Conclusion The intelligent knee joint rehabilitation wheelchair meets the designed functions and its actual performance aligns with the design criteria,thus validating the rationality and feasibility of the structural design.

Objective To investigate the expression characteristics of serum resistin(RETN)and Beclin-1 in patients with gouty arthritis(GA),and to analyze the relationship between RETN and GA clinical charac-teristics and clinical efficacy.Methods A total of 82 GA patients(GA group)and 60 healthy volunteers(con-trol group)in Dongguan People's Hospital from January 2019 to December 2022 were enrolled in the study.The expressions of serum RETN and Beclin-1 in GA patients were detected before and after treatment(on the physical examination day of the control group),and the differences of serum RETN and Beclin-1 in GA pa-tients with different clinical characteristics and efficacy were compared.Pearson correlation analysis was used to investigate the correlation between serum RETN,Beclin-1 expression and uric acid(UA)level in GA pa-tients.The diagnostic value of serum RETN and Beclin-1 in GA was analyzed using the receiver operating characteristic(ROC)curve.Results The serum RETN level in the GA group was higher than that in the con-trol group,and the expression of Beclin-1 was lower than that in the control group(P<0.05).The serum RETN levels in GA patients with acute stage,disease duration≥5 years,affected joints≥5,annual attack fre-quency≥3 times were higher than those in GA patients with chronic stage and intermittent stage,disease du-ration<5 years,affected joints<5,annual attack frequency<3 times(P<0.05),and the expression of Bec-lin-1 were lower than those in GA patients in chronic and intermittent stages,disease duration<5 years,af-fected joints<5,annual frequency<3 times(P<0.05).The serum UA level in GA patients was positively correlated with RETN(r=0.674,P<0.05),and negatively correlated with Beclin-1 expression(r=-0.568,P<0.05).After treatment,the serum expression of level RETN in the effective group was lower than that in the ineffective group,while the level Beclin-1 was higher than that in the ineffective group(P<0.05).The ar-ea under the curve of combined RETN and Beclin-1 diagnosis for GA was 0.921,which was higher than that of individual diagnosis(Z=3.752,3.154,P<0.05).Conclusion Serum RETN level increases,and Beclin-1 ex-pression decreases in GA patients,which is associated with increased UA level,prolonged acute stage and course of GA,increased number of affected joints and annual attack frequency,and treatment ineffectiveness.RETN and Beclin-1 could serve as biomarkers for GA diagnosis.

[摘 要] 目的：探究虎杖苷通过Hippo/Yes相关蛋白（YAP）通路对人甲状腺癌8505C细胞的恶性生物学行为和顺铂（DDP）敏感性的影响。方法：体外培养8505C细胞，构建其DDP耐药细胞8505C/DDP，用CCK-8法检测0、25、50、75、100 nmol/L虎杖苷处理8505C和8505C/DDP细胞的增殖能力，以筛选虎杖苷的最佳作用浓度。将8505C细胞分为对照组、虎杖苷组、空载组、虎杖苷+YAP1过表达组；将8505C/DDP细胞分为对照组、DDP组、DDP+虎杖苷组、DDP+空载组、DDP+虎杖苷+YAP1过表达组。WB法检测各组8505C细胞中Hippo/YAP通路[YAP1、转录辅激活因子（TAZ）]和EMT（E-cadherin、N-cadherin）相关蛋白，8505C/DDP细胞中YAP1、TAZ、耐药相关蛋白[P-糖蛋白（P-gp）、多药耐药相关蛋白1（MRP1）]、凋亡相关蛋白（C-caspase-3、BAX、Bcl-2）的表达。Transwell小室和细胞划痕实验分别检测各组8505C、8505C/DDP细胞的侵袭、迁移能力。结果：虎杖苷可显著抑制8505C细胞的增殖活性（P<0.05）明显抑制8505C细胞中YAP1、TAZ蛋白、N-cadherin的表达（均P<0.05），提升E-caderin蛋白的表达（P<0.05），显著抑制8505C细胞的迁移和侵袭能力（均P<0.05），而8505C/DDP细胞对低浓度的虎杖苷具有耐药性（P<0.05）；过表达YAP1则可逆转虎杖苷对8505C细胞的影响。50 nmol/L虎杖苷明显抑制DDP处理的8505C/DDP细胞中YAP1、TAZ、P-gp、MRP1、Bcl-2的蛋白的表达（均P<0.05），提升cleaved caspase-3、BAX蛋白的表达（均P<0.05）并诱导其细胞凋亡（P<0.05），过表达YAP1则可逆转虎杖苷对8505C/DDP细胞的影响。结论：虎杖苷抑制Hippo/YAP信号通路，从而抑制8505C细胞的恶性生物学行为和增强其对的DDP敏感性。