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 analyze the incidence, clinical characteristics, and prognosis of basilar artery occlusion (BAO) patients presenting with paroxysmal sympathetic hyperactivity (PSH) as an initial symptom.Methods:A retrospective analysis was conducted on BAO patients with PSH manifestations who received endovascular treatment at Xingtai Central Hospital between January 2018 and August 2024. Demographic characteristics, clinical data, imaging findings, and follow-up information were collected.Results:A total of 136 BAO patients were included, of whom 22 cases (16.2%) were diagnosed with PSH. The age of the patients was (56.81±9.92) years, with males accounting for 86.4%(19/22). On admission, the Glasgow Coma Scale score was 4(3, 5), and the National Institutes of Health Stroke Scale score was 30(25, 35). The successful reperfusion (modified Thrombolysis In Cerebral Infarction 2b-3) rate was 90.9%(20/22). In-hospital mortality was 50.0%(11/22), symptomatic hemorrhagic transformation occurred in 4.5% (1/22), and any type of intracranial hemorrhage occurred in 9.1%(2/22). Clinical features of PSH included tachycardia, tachypnea, hypertension, fever, diaphoresis, and increased muscle tone. Imaging analysis showed a high proportion of cerebellar (100.0%, 22/22) and midbrain (72.7%, 16/22) involvement. The 90-day follow-up showed that 72.7%(16/22) of the patients had poor functional outcomes (modified Rankin Scale score of 4-6), and the 90-day mortality rate was 59.1%(13/22).Conclusions:Among patients with BAO undergoing endovascular therapy, the incidence of PSH as the initial manifestation was 16.2%(22/136). These patients were predominantly middle-aged men and commonly presented with tachycardia, tachypnea, hypertension, fever, diaphoresis, and increased muscle tone. Imaging findings mainly involved the cerebellum and midbrain. Despite a relatively high rate of recanalization, patients with PSH exhibited a higher risk of mortality and poor functional outcomes.

Objective To screen metabolic core genes in colon cancer based on machine learning algorithms and analyze their functional mechanisms.Methods Data were obtained from The Cancer Genome Atlas(TCGA)database and the Gene Expression Omnibus(GEO)database.The TCGA co-hort included 375 tumor samples and 32 adjacent normal tissue samples,while the GSE39582 cohort comprised 419 tumor samples.Univariate Cox regression analysis combined with random forest,sup-port vector machine recursive feature elimination(SVM-RFE),and least absolute shrinkage and selec-tion operator(LASSO)regression algorithms were employed to screen for metabolic core genes.Re-ceiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was used to evaluate the predictive efficacy of the core genes.Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR)and immunohistochemistry(IHC)methods were adopted to detect the ex-pression of the core genes.The core genes were knocked down to explore their roles in colon cancer.Results Three core genes,namely CPT2,SCP2 and NR3C2,were screened based on machine learning algorithms.According to the comparison results of the AUCs of the ROC curves,NR3C2 exhibited the best predictive efficacy.qRT-PCR detection results showed that NR3C2 mRNA was lowly ex-pressed in colon cancer cell lines;IHC detection results revealed that NR3C2 was lowly expressed in colon cancer tissues.Knocking down NR3C2 significantly promoted the proliferation and migration of colon cancer cells.Conclusion NR3C2 is identified as a core metabolic inhibitory gene in colon cancer by cross-applying three machine learning algorithms,which may provide a new strategy for metabolic targeted therapy.

Objective:To analyze the incidence, clinical characteristics, and prognosis of basilar artery occlusion (BAO) patients presenting with paroxysmal sympathetic hyperactivity (PSH) as an initial symptom.Methods:A retrospective analysis was conducted on BAO patients with PSH manifestations who received endovascular treatment at Xingtai Central Hospital between January 2018 and August 2024. Demographic characteristics, clinical data, imaging findings, and follow-up information were collected.Results:A total of 136 BAO patients were included, of whom 22 cases (16.2%) were diagnosed with PSH. The age of the patients was (56.81±9.92) years, with males accounting for 86.4%(19/22). On admission, the Glasgow Coma Scale score was 4(3, 5), and the National Institutes of Health Stroke Scale score was 30(25, 35). The successful reperfusion (modified Thrombolysis In Cerebral Infarction 2b-3) rate was 90.9%(20/22). In-hospital mortality was 50.0%(11/22), symptomatic hemorrhagic transformation occurred in 4.5% (1/22), and any type of intracranial hemorrhage occurred in 9.1%(2/22). Clinical features of PSH included tachycardia, tachypnea, hypertension, fever, diaphoresis, and increased muscle tone. Imaging analysis showed a high proportion of cerebellar (100.0%, 22/22) and midbrain (72.7%, 16/22) involvement. The 90-day follow-up showed that 72.7%(16/22) of the patients had poor functional outcomes (modified Rankin Scale score of 4-6), and the 90-day mortality rate was 59.1%(13/22).Conclusions:Among patients with BAO undergoing endovascular therapy, the incidence of PSH as the initial manifestation was 16.2%(22/136). These patients were predominantly middle-aged men and commonly presented with tachycardia, tachypnea, hypertension, fever, diaphoresis, and increased muscle tone. Imaging findings mainly involved the cerebellum and midbrain. Despite a relatively high rate of recanalization, patients with PSH exhibited a higher risk of mortality and poor functional outcomes.

Perinatal depression is a psychological disorder that occurs during pregnancy and within one year of delivery, which can seriously affect the physical and mental health of pregnant and postpartum women, as well as the cognitive and behavioral abilities of offspring, with potential multigenerational effects. Therefore, it is important to identify its potential modifiable risk factors. Phthalic acid esters (PAEs), as common environmental endocrine disruptors, can affect maternal estrogen through multiple mechanisms and are important potential modifiable risk factors for developing maternal perinatal depression. At present, studies on the correlation between PAEs and perinatal depression are still very limited, and the mechanisms by which PAEs affect perinatal depression have not been clarified. Based on existing epidemiological and toxicological studies at home and abroad, the article briefly introduced the characteristics of multiple pathways, high doses, and long-term exposure to maternal PAEs, focused on reviewing the current status of epidemiological studies, pointed out the possible associations between some specific PAEs exposure and elevated risk of perinatal depression. It also summarized the potential roles of hormone-neurotransmitter pathway, inflammation mediation, gene regulation, and other possible mechanisms in the association between exposure to PAEs and perinatal depression. The article concluded with a look at how future research on the association between exposure to PAEs and perinatal depression can be scientifically validated, with a view to providing more high-quality evidence for the scientific prevention of the onset and progression of maternal depressive symptoms.

Objective To investigate the impact of coronary myocardial bridge(MB)on parameters of proximal pericoronary adipose tissue(PCAT).Methods Totally 287 patients with clinically suspected coronary heart disease but no coronary plaque on CT angiography(CCTA)were retrospectively collected.According to the presence or not of MB in left anterior descending(LAD),the patients were divided into MB group(n=150)and non-MB group(n=137).The length and depth of LAD-MB in MB group were measured,and patients in MB group were divided into deep MB subgroup and superficial MB subgroup according to LAD-MB depth.LAD PCAT parameters,i.e.fat attenuation index(FAI)and fat volume(FV),were compared between groups and subgroups within MB subgroup.Univariate and multivariate linear regression were used to explore the correlations of clinical factors(age,sex,body mass index),MB length,MB depth and PCAT parameters in MB group.Results FAI in MB group was higher,while FV was lower than those in non-MB group(both P＜0.001).Among 150 cases of LAD-MB,superficial type were found in 99 cases(superficial subgroup),while deep type were found in 51 cases(deep subgroup).FAI in superficial subgroup was lower,while FV was higher than those in deep subgroup(both P＜0.001).The median length and median depth of LAD-MB in 150 cases was 20.10 mm and 0.80 mm,respectively.Univariate linear regression analysis showed that for all 287 patients,gender was negatively correlated with FAI,whereas LAD-MB length and LAD-MB depth were positively correlated with FAI but negatively correlated with FV in MB group(all P＜0.05).Multifactor linear regression analysis showed that in MB group,both LAD-MB length and depth were positively correlated with FAI(B=0.105,1.797,both P＜0.05)and negatively correlated with FV(B=-15.585,-162.343,both P＜0.05),while clinical factors were not significantly correlated with FAI and FV(all P＞0.05).Conclusion MB could increase FAI and decrease FV of proximal PCAT.

Objective To investigate the expression of circular RNA(Circ RNAS)Actinin α 4(ACTN4)and platelet thrombin protein 1(THBS1)in intrahepatic cholangiocarcinoma(ICC)and their relationship with clinicopathological characteristics and prognosis,and provide reference for clinical diagnosis and treatment.Method A retrospective analysis was conducted on 84 ICC patients diagnosed and treated in the Second Affiliated Hospital of Xian Jiaotong University from May 2017 to June 2020.The expressions of CircACTN4 mRNA,THBS1 mRNA and protein were detected by real-time fluorescent quantitative PCR and immunohistochemistry.Pearson correlation analysis was used to analyze the correlation between CircACTN4 mRNA and THBS1 mRNA in ICC cancer tissue.The prognostic differences of ICC patients with different CircACTN4 mRNA and THBS1 mRNA expressions were compared by the Kaplan-Meier method(log rank test).COX regression analysis was performed to identify prognostic factors in ICC patients.The prognostic value of CircACTN4 mRNA and THBS1 mRNA in evaluating the risk of death in ICC patients was assessed by receiver operating characteristic(ROC)curve analysis.Results The expression of CircACTN4 mRNA in ICC tissues(3.14±0.42)was higher than that in adjacent tissues(0.76±0.25),with significant difference(t=44.094,P＜0.001).The positive rates of THBS1 mRNA(2.82±0.36)and protein positive rate(92.86％)in ICC tissues were higher than those in adjacent tissues(0.81±0.24,7.14％),and the differences were statistically significant(t/x2=42.068,123.429,all P＜0.001).CircACTN4 mRNA was positively correlated with THBS1 mRNA in ICC cancer tissue(r=0.669,P＜0.001).The expressions of CircACTN4 mRNA,THBS1 mRNA in ICC cancer tissues with TNM stage Ⅲ,low differentiation,and lymph node metastasis were higher than those in TNM stage Ⅰ～Ⅱ,high differentiation,and non-lymph node metastasis cancer tissues,and the differences were statistically significant(x2=7.949,9.164,12.207;23.270,18.625,19.828,all P＜0.001).The 3-year cumulative survival rates of the high expression group of CircACTN4 mRNA and THBS1 mRNA were lower than those of the low expression group of CircACTN4 mRNA(25.00％vs 56.82％)and THBS1 mRNA(19.51％vs 62.79％),and the differences were statistically significant(Log rank x2=13.601,24.310,all P＜0.001).CircACTN4 mRNA(OR=1.839,95％CI:1.228～2.753),THBS1 mRNA(OR=1.744,95％CI:1.245～2.443),lymph node metastasis(OR=1.925,95％CI:1.316～2.816),TNM staging(OR=1.613,95％CI:1.223～2.126),and tumor differentiation(OR=1.510,95％CI:1.205～1.892)were independent factors affecting the prognosis of ICC.The area under the curve of the combination detection of circACTN4 and THBS1 mRNA on the prognosis of death in patients with ICC was 0.868,which was greater than that of the single index(0.812 and 0.784),with significant differences(Z=3.348,3.847,all P＜0.001).Conclusion The expressions of CircACTN4 mRNA and THBS1 mRNA were increased in ICC,and they were associated with TNM stage,differentiation,and lymph node metastasis.These markers may serve as novel indicators to evaluate the poor prognosis of ICC patients.

Objective To investigate the impact of coronary myocardial bridge(MB)on parameters of proximal pericoronary adipose tissue(PCAT).Methods Totally 287 patients with clinically suspected coronary heart disease but no coronary plaque on CT angiography(CCTA)were retrospectively collected.According to the presence or not of MB in left anterior descending(LAD),the patients were divided into MB group(n=150)and non-MB group(n=137).The length and depth of LAD-MB in MB group were measured,and patients in MB group were divided into deep MB subgroup and superficial MB subgroup according to LAD-MB depth.LAD PCAT parameters,i.e.fat attenuation index(FAI)and fat volume(FV),were compared between groups and subgroups within MB subgroup.Univariate and multivariate linear regression were used to explore the correlations of clinical factors(age,sex,body mass index),MB length,MB depth and PCAT parameters in MB group.Results FAI in MB group was higher,while FV was lower than those in non-MB group(both P＜0.001).Among 150 cases of LAD-MB,superficial type were found in 99 cases(superficial subgroup),while deep type were found in 51 cases(deep subgroup).FAI in superficial subgroup was lower,while FV was higher than those in deep subgroup(both P＜0.001).The median length and median depth of LAD-MB in 150 cases was 20.10 mm and 0.80 mm,respectively.Univariate linear regression analysis showed that for all 287 patients,gender was negatively correlated with FAI,whereas LAD-MB length and LAD-MB depth were positively correlated with FAI but negatively correlated with FV in MB group(all P＜0.05).Multifactor linear regression analysis showed that in MB group,both LAD-MB length and depth were positively correlated with FAI(B=0.105,1.797,both P＜0.05)and negatively correlated with FV(B=-15.585,-162.343,both P＜0.05),while clinical factors were not significantly correlated with FAI and FV(all P＞0.05).Conclusion MB could increase FAI and decrease FV of proximal PCAT.

Objective:To investigate the predictive value of neutrophil-lymphocyte ratio (NLR) for Trousseau’s syndrome (TS) in patients with acute multiple cerebral infarctions (AMCI).Methods:The patients with AMCI in Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine from July 2013 to March 2022 were retrospectively enrolled. The demographic and baseline clinical data of patients with TS and those without TS were compared. Multivariate logistic regression analysis was used to determine the independent influencing factors of TS-AMCI, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of NLR for TS-AMCI. Results:A total of 59 patients with AMCI were enrolled, including 43 males and 16 females, aged 64.9±14.0 years. There were 16 patients in the TS-AMCI group and 43 in the non-TS-AMCI group. The proportions of patients with diabetes mellitus, hypertension and previous stroke or transient ischemic attack in the TS-AMCI group were significantly lower than those in the non-TS-AMCI group (all P<0.05), while the proportion of patients with ischemic heart disease were significantly higher than that in the non-TS-AMCI group ( P<0.05). The proportion of patients with bilateral infarction in the TS-AMCI group was significantly higher than that in the non-TS-AMCI group ( P<0.001). The D-dimer, NLR, white blood cell count, neutrophil count, monocyte count, percentage of neutrophils, total cholesterol and low-density lipoprotein cholesterol in the TS-AMCI group were significantly higher than those in the non-TS-AMCI group (all P<0.001), while the lymphocyte count, lymphocyte percentage, red blood cell count, hemoglobin and hematocrit were significantly lower than those in the non-TS-AMCI group (all P<0.001). Multivariate logistic regression analysis showed that high NLR was an independent predictor of TS-AMCI (odds ratio [ OR] 2.897, 95% confidence interval [ CI] 1.270-6.527; P=0.011), while high hemoglobin was independently negatively correlated with TS-AMCI ( OR 0.839, 95% CI 0.723-0.975; P=0.022). ROC curve analysis showed that the area under the curve of NLR for predicting TS-AMCI was 0.929 (95% CI 0.831-0.979; P<0.001). When the NLR cutoff value was 4.01, the corresponding Youden index was 0.744. At this time, the sensitivity and specificity were 100% and 74.42% respectively. Conclusion:NLR has high predictive value for TS-AMCI.

Clinical phenotypes and gene characteristics of a patient diagnosed with Mowat-Wilson syndrome (MWS) with Hirschsprung′s disease (HSCR) and vaginal atresia in the Department of Neonatal Surgery, Beijing Children′s Hospital, Capital Medical University in March 2021 were analyzed retrospectively.The eight-month-old girl was admitted to the hospital with symptoms of constipation for nine days and abdominal distension for two days.Lower digestive tract radiography and rectal mucosa biopsy results suggested HSCR.The child also had specific facial features and motor development delay.Whole exome test showed a de novo heterozygous mutation, ZEB2 gene c. 2761C>T (p.R921*). After laparoscopic-assisted Soave procedure, the child had normal bowel movements, and no surgery-related compli-cations occurred during the follow-up period.The child′s motor development improved after rehabilitation treatment.According to literature review, 2 female cases show similar clinical manifestations to this girl, but the genotypes were different.This patient expands the clinical phenotype of ZEB2 gene pathogenicity.