This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

The intelligent oxygen management system is a software designed with various algorithms to automatically titrate inhaled oxygen concentration according to specific patterns. This system can be integrated into various ventilator devices and used during assisted ventilation processes, aiming to maintain the patient's blood oxygen saturation within a target range. This paper employs a scoping review methodology, focusing on research related to intelligent oxygen management systems in neonatal intensive care units. It reviews the fundamental principles, application platforms, and clinical outcomes of these systems, providing a theoretical basis for clinical implementation.
Humans ; Intensive Care Units, Neonatal ; Infant, Newborn ; Oxygen/administration & dosage* ; Oxygen Inhalation Therapy/methods* ; Respiration, Artificial

The glucagon receptor (GCGR) is a critical target for the treatment of metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity. Activation of GCGR enhances systemic insulin sensitivity through paracrine stimulation of insulin secretion, presenting a promising avenue for treatment. However, the discovery of effective GCGR agonists remains a challenging and resource-intensive process, often requiring time-consuming wet-lab experiments to synthesize and screen potential compounds. Recent advances in artificial intelligence technologies have demonstrated great potential in accelerating drug discovery by streamlining screening and efficiently predicting bioactivity. In the present work, we propose DeepGCGR, a two-layer deep learning model that leverages graph convolutional networks (GCN) integrated with a multiple attention mechanism to expedite the identification of GCGR agonists. In the first layer, the model predicts the bioactivity of various compounds against GCGR, efficiently filtering large chemical libraries to identify promising candidates. In the second layer, DeepGCGR classifies high bioactive compounds based on their functional effects on GCGR signaling, identifying those with potential agonistic or antagonistic effects. Moreover, DeepGCGR was specifically applied to identify novel GCGR-regulating compounds for the treatment of T2DM from natural products derived from traditional Chinese medicine (TCM). The proposed method will not only offer an effective strategy for discovering GCGR-targeting compounds with functional activation properties but also provide new insights into the development of T2DM therapeutics.
Deep Learning ; Drug Discovery/methods* ; Humans ; Diabetes Mellitus, Type 2/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

AIM To compare the in vivo pharmacokinetics of paeoniflorin,paeoniflorin,liquiritin,isoliquiritin,liquiritigenin and glycyrrhizic acid from Shaoyao Gancao Decoction in normal and gastric ulcer rats.METHODS Six rats were randomly assigned into two groups,after which the 75%ethanol-induced gastric ulcer model was established,the gastric tissues were collected.Twelve rats were randomly assigned into two groups and given intragastric administration(9.9 g/kg),after which blood collection was made at different time points,UPLC-MS/MS method was adopted in the determination of plasma concentrations,and main pharmacokinetic parameters were calculated.RESULTS Prolonged Tmax(P＜0.05,P＜0.01)of various active constituents,prolonged T1/2,MRT0-t(P＜0.05,P＜0.01),increased Cmax,AUC(P＜0.05,P＜0.01)and decreased Vd/F,CL/F(P＜0.05,P＜0.01)of paeoniflorin,increased Cmax,AUC(P＜0.05,P＜0.01)and decreased CL/F(P＜0.05)of albiflorin,prolonged MRT(P＜0.05),increased AUC(P＜0.05)and decreased CL/F(P＜0.01)of liquiritin,prolonged MRT(P＜0.05,P＜0.01)and decreased Vd/F(P＜0.05)of isoliquiritin,no obviously changed pharmacokinetic parameters(except for Tmax)of liquiritigenin(P＞0.05),and prolonged T1/2,MRT0-∞(P＜0.05,P＜0.01),increased Cmax,AUC(P＜0.05,P＜0.01)and decreased CL/F(P＜0.01)of glycyrrhizic acid were observable in the model group as compared with those in the normal group.CONCLUSION Gastric ulcer exhibits certain influences on the velocities and degrees of in vivo absorption and metabolism of active constituents from Shaoyao Gancao Decoction.

Objective To explore the selection rules of acupuncture and moxibustion for treating ovarian dysfunction-related diseases by applying data mining technology.Methods Computer searches were conducted to find clinical research literature on acupuncture and moxibustion for ovarian reserve dysfunction-related diseases(including diminished ovarian reserve,premature ovarian insufficiency,premature ovarian failure)in major databases,such as China National Knowledge Infrustructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and China Science and Technology Journal Database(VIP),Excel 2021 was used to establish a prescription database of acupoints selection,and SPSS Modeler 18.0 and SPSS Stastics 26.0 software were used to analyse the frequency,meridian tropism,site,special acupoints,analysis of association rule,and cluster analysis of acupoints to study the rules of acupuncture and moxibustion for treating ovarian reserve dysfunction-related diseases.Results A total of 215 articles were screened to meet the requirements,in which,96 acupoints were used,with a total frequency of 2 110 times.The high-frequency used acupoints were Guanyuan(RN4),Sanyinjiao(SP6),and Shenshu(BL23),etc,.The commonly used meridians were the conception vessel(CV)and bladder meridian of foot-taiyang,and the acupoints were mostly located in the abdomen and lower limbs,with the majority being the five-shu point and the yuan front-mu points.The core acupoints and four effective clusters were analysed.Conclusion The acupoint selection of acupuncture and moxibustion for ovarian reserve dysfunction-related diseases focuses on tonifying qi and blood,cultivating the vital essence and tonifying the kidneys.Most of the meridians related to reproduction were selected in this method,which aiming at regulating menstruation and tonifying blood,and pre-cultivating its loss.This research focuses on the matching of neighboring point and distant point selection,and pays attention to the use of specific acupoints,and treates multiple organs simultaneously.

Objective To investigate the effects of laparoscopic radiofrequency ablation(LRFA)and percutaneous radiofrequency ablation(PRFA)on anti-tumor immunity,complication rate and recurrence rate in patients with primary liver cancer.Methods A total of 81 patients with primary liver cancer treated in Dazhou Central Hospital from January 2020 to August 2022 were selected and divided into observation group(LRFA,n=42)and control group(PRFA,n=39)according to the treatment plan.Compare the total ablation rate,postoperative complication rate,recurrence rate of the two groups,as well as tumor necrosis factor-α(TNF-α),carbohydrate antigen 199(CA199),interleukin-6(IL-6),Golgi protein 73(GP73),C-reactive protein(CRP),alpha-fetoprotein(AFP)and peripheral blood T lymphocyte subpopulation levels before and after surgery.Results There was no significant difference between the observation group(95.24％)and the control group(92.31％)(P＞0.05).At 1 d postoperatively,IL-6 was(124.63±45.41)pg/ml and(168.28±51.26)pg/ml,CRP was(19.14±5.03)ng/L and(28.26±7.47)ng/L,and TNF-α was(94.32±18.49)pg/ml and(108.41±20.11)pg/ml;at 3 d postoperatively,IL-6 was(92.37±24.11)pg/ml and(105.83±27.45)pg/ml in the observation group and the control group,respectively,CRP was(14.87±4.37)ng/L and(17.25±5.06)ng/L,and TNF-α was(75.41±12.10)pg/ml and(82.64±16.83)pg/ml,which were all higher than that of preoperative period(P＜0.05).At 7 d postoperatively,CD3+in the observation group and control group were(66.27±7.82)％and(65.14±7.63)％,AFP was(156.23±30.27)μg/mland(160.84±32.33)μg/ml,GP73 was(65.21±10.26)μg/L and(67.44±11.03)μg/L,CA199 was(44.89±11.41)U/L and(45.12±13.07)U/L,CD4 was(32.02±6.03)％and(31.53±6.11)％,and CD4+/CD8+was(1.31±0.39)and(1.29±0.37)respectively;at 14 d postoperatively,CD3+was(71.25±6.83)％and(70.89±6.76)％,AFP was(48.52±18.31)μg/ml and(50.11±19.12)μg/ml,GP73 was(48.25±8.46)μg/L and(49.12±10.12)μg/L,CA199 was(19.27±5.16)U/L and(20.07±5.39)U/L,and CD4 was(38.25±7.7)U/L and(20.07±5.39)U/L,respectively,in the observation and control groups.g/L,CA199 was(19.27±5.16)U/L and(20.07±5.39)U/L,CD4 was(38.25±7.45)％and(37.61±7.92)％,and CD4+/CD8+was(1.49±0.42)and(1.47±0.45),respectively,which were higher than that of preoperative period(P＜0.05),but the difference between the two groups was not statistically significant(P＞0.05).The postoperative complication rate of 42.86％and recurrence rate of 2.38％in the observation group were lower than 66.67％and 17.95％in the control group(P＜0.05).The 12-month postoperative survival rate of 97.62％in the observation group was not statistically significant compared with 94.87％in the control group(P＞0.05).Conclusion The efficacy of LRFA and PRFA in the treatment of primary hepatocellular carcinoma is comparable,which can effectively improve the body's anti-tumor immunity and reduce the release of serum tumor markers;however,LRFA has less stressful reaction,reduces the occurrence of postoperative complications,and has a lower recurrence rate,which is especially advantageous in the treatment of hepatocellular carcinoma at special sites.

Objective:To discuss the correlation between homocysteine(Hcy)and inflammatory responses as well as oxidative stress,and to analyze its role in the occurrence and development of acute ischemic stroke(AIS).Methods:Thirty-eight patients with their first incidence of AIS were selected as AIS group,and according to the principles of case-control study,45 healthy individuals undergwent routine health examination during the same period were selected as control group.The levels of homocysteine and inflammatory cytokine interleukin(IL)-6,and tumor necrosis factor α(TNF-α)in serum of the subjects in two groups were detected by enzyme-linked immunosorbent assay(ELISA)method;the level of highly sensitive C-reactive protein(hs-CRP)of the subjects in two groups was detected by immunoturbidimetry;the levels of malondialdehyde(MDA)and activities of superoxide dismutase(SOD)in serum of the subjects in two groups were detected by chemical colorimetry;Pearson's correlation analysis was used to analyze the correlation between serum Hcy level and levels of inflammatory markers and oxidative stress indicators of the AIS patients.Results:Compared with control group,the levels of Hcy,hs-CRP,TNF-α,IL-6,and MDA in serum of the patients in AIS group were significantly increased(P<0.05),while the activity of SOD was significantly decreased(P<0.05).The level of Hcy in serum of the AIS patients was positively correlated with the levels of hs-CRP,TNF-α,IL-6,and MDA(r=0.615,P<0.05;r=0.632,P<0.05;r=0.598,P<0.05;r=0.612,P<0.05),and negatively correlated with the activity of SOD(r=-0.325,P<0.05).Conclusion:The Hcy level in serum of the AIS patients is closely associated with the inflammatory factors and oxidative damage.Hcy can promote the production of oxidative free radicals and inflammatory factors and cause damage to the endothelial cells and play a significant clinical role in the occurrence and development of AIS.

Objective To analyze the risk factors and clinical characteristics of uveitis in children with juvenile idiopathic arthritis (JIA).Methods A retrospective case-control study was conducted on 30 children with JIA-associated uveitis (JIA-U )and 36 age-and gender-matched children diagnosed as simple JIA admitted to Children's Hospital of Chongqing Medical University from June 2016 to June 2023.The clinical data,laboratory indicators and radiological findings were collected,and analyzed for the risk factors for JIA-U with univariate and multivariate analysis.Results In this study,JIA-U mostly occurred in both eyes (63.3％,19/30),with anterior uveitis as the main cause (86.7％,26/30),insidious onset,and mostly occurred after JIA diagnosis (60.0％,18/30),and only 30％ showing ocular discomfort or visual impairment.Univariate analysis showed that the JIA children with oligoarthritis JIA,negative rheumatoid factor (RF)and negative anti-cyclic citrullinated peptide antibody (anti-CCP)were prone to be complicated with uveitis (P<0.05 ). Multivariate logistic regression analysis indicated that RF negativity was an independent risk factor for development of JIA-U (OR=5.400,95％ CI:1.033～28.227,P=0.046). Conclusion JIA-U of ten develops in both eyes,anterior uveitis is the most common,and it mostly diagnosed after JIA.It has no obvious eye symptoms in the early stage and thus is not easily recognized.Oligoarthritis JIA,RF-negative,and anti-CCP antibody-negative are the high-risk factors for the complication of JIA-U in children with JIA.

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.