Familial hyperaldosteronism type Ⅲ(FH-Ⅲ) is extremely rare, and there are no reported cases in China. Herein, we reported two cases with FH Ⅲ, both of which presented with severe hypertension and hypokalemia in their early childhood. One patient had significantly enlarged adrenal glands and developed clinical manifestations of Cushing′s syndrome at the age of 20. Complete relief of symptoms was achieved after bilateral adrenalectomy. The other case had normal adrenal imaging, and with spironolactone treatment, blood pressure and potassium levels were well-controlled. Both cases had germline mutation of KCNJ5 gene which were c. 433G>C(p.Glu145Gln) and c. 452G>A(p.Gly151Glu), respectively.

Objective:To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3).Methods:This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity.Results:Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment.Conclusions:Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

Objective:To investigate the effect of high-dose vitamin B6 on stress-induced liver cell death in rats with severe trauma and its possible mechanism.Methods:Thirty-two male SD rats were selected and divided into sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group by using a random number table, with 8 rats in each group. Rat models of severe trauma were established by inducing abdominal wall injury, bilateral femoral fractures, unilateral cranial injury, and withdrawal of 4 ml blood from the femoral artery. The sham surgery+B6 group and trauma+B6 group were treated with saline solution plus high-dose vitamin B6, while the sham surgery group and trauma group with infusion of saline solution only. At 36 hours after injury, rat liver tissues were collected for the following experiments: (1) the genes differentially expressed in the liver tissues of the rats of the trauma group and the trauma+B6 group were screened with next-generation sequencing, followed by an analysis of the possible involvement of cell death pathways; (2) validation was conducted to ascertain whether high-dose vitamin B6 could influence various cell death pathways in the liver cells in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group: apoptosis was confirmed through terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining; necroptosis was verified by mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining; autophagy was examined via transmission electron microscopy; ferroptosis was confirmed by detecting oxidative malondialdehyde (MDA) levels, oxidized glutathione levels, Prussian blue staining with diaminobenzidine (DAB) enhancement, transmission electron microscopy, and immunohistochemical staining for acyl-CoA synthetase long-chain family member 4 (ACSL4); (3) Biological information analyses [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Enrichment analysis (GSEA)] were performed for biological processes and signaling pathways represented by liver tissue sequencing results of rats between the trauma group and the trauma+B6 group.Results:(1) In the liver tissues of rats, there were 344 significantly differentially expressed genes between the trauma group and trauma+B6 group, comprising 137 upregulated genes and 207 downregulated genes, of which 18 genes were associated with apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. (2) No significant differences were found in TUNEL staining among the sham surgery group, sham surgery+B6 group, trauma group or trauma+B6 group; MLKL protein expression levels in the liver tissues after trauma were improved, of which the trauma+B6 group was lower than that of the trauma group; Electron microscopy showed that autophagic activity in the liver cells were significantly increased after trauma, which was significantly lower of the trauma+B6 group than that of the trauma group; MDA levels in the rat liver tissues were (0.20±0.05)nmol/mg, (0.17±0.07)nmol/mg, (0.69±0.11)nmol/mg and (0.52±0.07)nmol/mg in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group respectively ( P<0.01), with the trauma group having the highest MDA levels and trauma+B6 group having lower MDA levels than the trauma group; Oxidized glutathione levels in the liver tissues of the four groups were (11.75±2.09)μmol/g, (11.69±1.66)μmol/g, (19.75±3.40)μmol/g, and (14.51±1.46)μmol/g respectively ( P<0.01), with the trauma group having the highest levels and trauma+B6 group having lower levels than the trauma group; Significantly increased iron deposition was observed in the liver tissues after trauma, with lower iron deposition in trauma+B6 group than the trauma group; Electron microscopy revealed significantly lower mitochondrial membrane density in the trauma+B6 group compared to the trauma group. ACSL4 protein expression level was lower in the trauma+B6 group compared to the trauma group; (3) GO, KEGG and GSEA enrichment analyses suggested that high-dose vitamin B6 may enhance cholesterol synthesis metabolism in the liver cells and alleviate oxidative stress to reduce liver cell damage and restore normal liver cell function after trauma. Conclusions:High-dose vitamin B6 attenuates stress-induced liver injury in rats with severe trauma by inhibiting the progression of necroptosis, autophagy and ferroptosis. Its molecular mechanism may be associated with enhanced hepatic cholesterol synthesis metabolism and alleviation of oxidative stress in the liver cells.

Chinese expert consensus on neurosurgical treatment of psychiatric disorders is compiled by national experts in neurosurgery,psychiatry,and other related fields.Based on clinical research published up to December 2023 and evidence-based medicine standards,the consensus provides recommendations for neurosurgical treatment of psychiatric disorders.The covered diseases include obsessive-compulsive disorder,depressive disorder,tic disorder,bipolar disorder,anorexia nervosa,substance use-related disorders,and schizophrenia.This expert consensus outlines the safety and efficacy of neurosurgical treatments for psychiatric disorders in clinical practice,and preliminarily standardizes treatment procedures and surgical techniques.The aim is to establish professional standards for the application of surgical treatment techniques for clinical practitioners in the field of psychiatric disorder surgery,thereby maximizing treatment outcomes and promoting the future development of this treatment technology.

Objective:To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods:Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results:Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion:The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

Objective:To investigate alterations in functional connectivity network and brain function activity in childhood absence epilepsy (CAE) based on neuromagnetic signals by using multi-frequency magnetoencephalography.Methods:Twenty-five drug-naive children diagnosed with CAE from the Affiliated Brain Hospital of Nanjing Medical University and the Affiliated Children′s Hospital of Nanjing Medical University during October 2022 and March 2024 and 25 healthy controls matched for age and sex from community were recruited in this cross-sectional study. The interictal data, ictal data of CAE and healthy control children were collected using a CTF-275 channel magnetoencephalography system. Corrected amplitude envelope correlation was used to construct functional connectivity network, and network-based statistics were used to compare network differences between groups. Relative power spectral density was used to describe the distribution characteristics of whole-brain spectral power. Nonparametric permutation tests were conducted 1 000 times to compare spectral power differences between groups.Results:In terms of functional connectivity, significant increases in network activity were observed in the low-frequency bands (δ, θ) during interictal periods in children with CAE. A sub-network with significantly increased functional connectivity, including key nodes of the default mode network, was observed in the δ band. Compared with interictal periods, functional connectivity in the δ band decreased during absence seizures in children with CAE, while connectivity in the mid-to-high-frequency bands (α-γ2) increased. In terms of spectral power, children with CAE during interictal periods exhibited widespread magnetic source activation in the δ band, activation in parts of the parietal and occipital lobes in the θ band, and significantly decreased magnetic source intensity in most areas of the parietal, occipital, and temporal lobes in the α-γ2 band. Compared with interictal periods, children with CAE during absence seizures exhibited widespread magnetic source activation in the δ band, and significantly decreased activation in the θ-γ2 band. According to the magnetic source distribution map, during absence seizures, the frontal lobe replaced the parieto-occipital region in cortical activation in the α band.Conclusion:In the analysis of functional network and spectral power based on multi-frequency neuromagnetic signals, the network pattern and magnetic source activation of children with CAE during interictal periods were significantly different from those of healthy children, and there were characteristic changes in neuromagnetic signals during consciousness impairment caused by absence seizures in children with CAE.

Objective To investigate the difference in blood lipid parameters between acute-on-chronic pre-liver failure (pre-ACLF) and acute-on-chronic liver failure (ACLF) and the risk factors for disease progression. Methods A retrospective analysis was performed for the related data of 118 patients with ACLF (ACLF group) and 44 patients with pre-ACLF (pre-ACLF group) who were treated in The General Hospital of Western Theater Command from January 2012 to December 2020, including baseline age, albumin, creatinine, routine blood test results, and blood lipids. The independent samples t -test was used for comparison between normally distributed continuous data; and the Mann-Whitney U test was used for comparison between non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used for multivariate analysis to identify independent predictive factors. The receiver operating characteristic (ROC) curve was used to compare the sensitivity and specificity of related indicators, and Youden index was used to calculate cut-off values. Results Compared with the pre-ACLF group, the ACLF group had significantly lower levels of total cholesterol (TC)[2.02(1.56-2.37) mmol/L vs 3.01(2.57-3.66) mmol/L, Z =5.411, P < 0.001], high-density lipoprotein [0.40(0.25-0.49) mmol/L vs 0.62(0.47-0.75) mmol/L, Z =4.781, P < 0.001], and low-density lipoprotein (LDL) [1.52(1.22-1.84) mmol/L vs 1.93(1.49-2.36) mmol/L, Z =3.146, P =0.002] and significantly higher levels of total bilirubin [352.13(284.32-451.19) μmol/L vs 135.80(112.80-154.68) μmol/L, Z =-9.775, P < 0.001], international normalized ratio [1.96(1.71-2.51) vs 1.39(1.33-1.44), Z =-9.776, P < 0.001], white blood cell count (WBC) [6.74(5.07-9.19)×10 9 /L vs 5.04(4.13-7.09)×10 9 /L, Z =-3.985, P < 0.001], and neutrophils [4.67(3.40-7.06)×10 9 /L vs 3.30(2.72-5.01)×10 9 /L, Z =-3.676, P < 0.001], while there were no significant differences between the two groups in age, creatinine, albumin, alanine aminotransferase, aspartate aminotransferase, and triglyceride (all P > 0.05). The logistic regression analysis showed that TC (odds ratio [ OR ]=0.003, 95% confidence interval [ CI ]: 0.000-0.068, P < 0.05), LDL ( OR =61.901, 95% CI : 3.354-1142.558, P < 0.05), and WBC ( OR =3.175, 95% CI : 1.097-9.185, P < 0.05) had an independent predictive value, and the ROC analysis showed that the area under the ROC curve of TC was 0.852, the sensitivity of LDL was 0.887, and TC had the best specificity of TC was 0.840. Conclusion There are reductions in blood lipid parameters in the progression from pre-ACLF to ACLF, suggesting that clinicians should pay attention to the changes in lipids in the pre-ACLF stage and adjust the nutritional regimen in a timely manner.

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. Materials and Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Results: Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Patients with spinal cord injury is associated with seriously affected gastrointestinal function and imbalance of intestinal flora, leading to increased inflammation of spinal cord nerves. With the proposal of the theory of gut microbiota-gut-brain axis in recent years, the regulatory role of gut microbiota in the central nervous system and gastrointestinal system has gradually attracted attention. Although a considerable number of studies have focused on the effects of intestinal flora characteristics on spinal cord nerve function repair in patients with spinal cord injury from different perspectives, there are numerous research models for treating spinal cord injury with intestinal flora as intervention targets and remains a lack of unified and effective clinical treatment methods. In this paper, the authors review the research progress in characteristics of intestinal microflora and intestinal microflora-targeted therapeutic methods in patients with spinal cord injury, hoping to provide a reference for the clinical treatment and basic research of spinal cord injury.