Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective To establish an HPLC method for the simultaneous determination of 10 components in the active parts of Uygur medicine Dracocephalum Moldavica L.Methods The determination was performed on a Shim-pack ODS(4.6 mm×250 mm,5 um)column with the mobile phase consisting of acetonitrile(A)-0.5%formic acid(B)in aqueous solution in a gradient elution mode(0-30 min,17%A;30-60 min,17%→ 28%A;60-78 min,28%A)at a flow rate of 1.0 mL·min-1.The temperature of the chromatographic column was 35℃and the detection was monitored by a UV detector at 330 nm.Results Cof-feic acid,p-coumalic acid,cynaroside,luteolin-7-O-β-D-glucuronide,apigenin 7-O-glucuronide,rosmarinic acid,diosmetin7-O-β-D-glucuronide,salvianolic acid A,tilianin,apigenin were well separated under this chromatographic condition,and the linear relation-ship were good in the concentration range examined(r＞0.999 2).The overall recoveries ranged from 91.83%to 106.43%with the RSD ranging from 0.38%to 2.22%.Conclusion The established content determination method is highly accurate and reproduci-ble,and suitable for the analysis and quality control of the active parts of Dracocephalum Moldavica L.

To perform a comprehensive analysis of the pathogenic causes of a food poisoning case in a district of Wuhan Cit-y,we investigated the molecular epidemiological relationships among pathogenic bacteria,to aid in traceability analysis of food-borne disease outbreaks,as well as clinical diagnosis and treatment.The pathogenic bacteria in this food poisoning case were i-solated and identified according to GB789.4-2016.The isolated strains were subjected to genotyping with pulsed field gel elec-trophoresis(PFGE).Drug resistance gene analysis,multi-locus sequence typing(MLST),and genome-wide single-nucleotide polymorphism analysis(wgSNP)were conducted via whole genome sequencing(WGS).The evolutionary tree for cluster analy-sis was constructed in fasttree software.Drug susceptibility testing was conducted with the broth microdilution method.A total of 12 strains of Salmonella were detected in seven anal swab samples and two fecal samples from the case,as well as three anal swab samples from unaffected individuals.The serotype of the strains was Salmonella typhimurium.The strain exhibited severe multiple drug resistance,including resistance to amikacin,ampi-cillin,cefazolin,gentamicin,piperacillin,and tetracycline,but susceptibility to other antibiotics.The coincidence rate between drug resistance genes and drug resistance phenotypes was high.PFGE revealed that nine strains from this food poisoning case were highly homologous.WGS revealed that the MLST type was ST19,and varying numbers of SNPs(1-6)were present a-mong strains.The phylogenetic tree revealed nine isolated strains forming a distinct cluster,differing from other Salmonella strains in the database and belonging to a novel clonal branch.The single nucleotide site in the strains was highly homologous to that of GCF in Jiangxi_020221795.1.The food poisoning case was caused by Salmonella typhimurium ST19,and all nine iso-lated strains originated from the same source.The chef is closely connected to this food poisoning case.This strain of Salmo-nella typhimurium belongs to a new clonal branch and exhibits multiple drug resistance.

Objective:To explore the prognostic value of MUC13 expression in gastric cancer(GC)patients and its impact on the biological behavior of GC cells.Methods:Comprehensive anal-ysis of the expression pattern of MUC genes in GC tissues based on the TCGA database to screen for differentially expressed genes.Spearman correlation analysis determined the correlation of ex-pression between MUC genes in GC tissues.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment analysis were used to explore the potential biological functions of MUC genes.Univariate COX regression analysis was performed to explore the relationship between all differentially expressed MUC genes and the prog-nosis of GC patients to screen out MUC genes that were significantly related to the prognosis of GC.Clinical GC tissue samples were used to further verify the expression of MUC13 through im-munofluorescence,and its relationship with the clinicopathological characteristics and prognosis of GC was analyzed.siRNA was used to silence the expression of MUC13 in GC cells,and the effect of MUC13 on cell proliferation,migration and invasion was analyzed through CCK-8,colony forma-tion and Transwell experiments.Results:Among all MUC members,the expression levels of MUC1,MUC2,MUC3A,MUC4,MCU5B,MUC12,and MUC13 were significantly upregulated in GC tissues(P＜0.05).There are certain interactions between these MUC genes,and they are mainly en-riched in pathways related to digestive system processes,epithelial structure maintenance,apical plasma membrane,saliva secretion,etc.Importantly,upregulation of MUC13 in GC tissues indicates poor patient prognosis(Log-rank P＜0.05).In addition,MUC13 expression was significantly correlat-ed with the age(P＜0.001)of GC patients and tumor size(P=0.035).Further cell function experiments showed that after silencing MUC13,the proliferation ability of GC cells was significantly reduced(P＜0.05),while their migration and invasion abilities were not significantly affected(P＞0.05).Con-clusions:Highly expressed MUC13 is closely related to the poor prognosis of gastric cancer,par-ticipates in the regulation of tumor progression and is a potential therapeutic target and prognostic marker for gastric cancer.

Lipid and glucose metabolism play crucial roles in maintaining energy homeostasis, and their dysregulation can lead to the development of metabolic disorders, such as obesity and diabetes. Studies indicate that the skeleton, involved in lipid and glucose metabolism, functions as an endocrine organ, regulating systemic metabolism through bone-derived molecules. Sclerostin is a protein mainly produced by osteocytes, possessing the ability to inhibit bone formation, and its antibodies have become therapeutic targets for treating osteoporosis. Recent evidence suggests that sclerostin also plays a role in lipid and glucose metabolism disorders. Therefore, through summarizing in vitro and in vivo researches, this article reviews the role of sclerostin in lipid and glucose metabolism, its relationship with obesity and diabetes, and potential role in the treatment of metabolic diseases in the future.

Objective:To investigate the correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease (CKD) patients, and to find biomarkers and potential therapeutic targets that can take into account both osteoporosis and sarcopenia.Methods:It was a single-centre cross-sectional study. The clinical data of CKD stage 5 patients undergoing maintenance hemodialysis regularly and CKD stage 1-5 non-dialysis inpatients in the Hemodialysis Centre of Guangzhou Red Cross Hospital from March 2021 to March 2023 were collected retrospectively. The enzyme-linked immunosorbent assay was used to detect the level of serum sclerostin. The anthropometric data such as height, weight, upper arm circumference, upper arm muscle circumference, skinfold thickness, pinch strength and handgrip strength were measured. Body composition analyzer was used to measure the body composition. The patients were divided into CKD stage 1-3 group, CKD stage 4-5 group, and stage 5 hemodialysis group. One-way ANOVA, Kruskal-Wallis H test, and chi-square test were used to compare the differences of demographics and clinical characteristics in different stages of CKD. Spearman correlation analysis and multiple linear stepwise regression analysis were utilized to analyze the correlation between serum sclerostin and sarcopenia-related indicators in CKD patients. Results:The study included 104 patients with CKD stage 5 hemodialysis and 104 patients with CKD stage 1-5 non-dialysis patients, with age of (61.8±13.7) years old and 114 males (54.8%). There were 89 patients (42.8%) with diabetic nephropathy and 67 patients (32.2%) with sarcopenia. As renal injury progressed, serum sclerostin levels were 0.4 (0.3, 0.9) ng/L, 0.5 (0.3, 1.1) ng/L, and 1.1 (0.6, 2.3) ng/L in patients with CKD stage 1-3, stage 4-5, and stage 5 undergoing hemodialysis ( χ2=8.934, P<0.001), and the prevalence of sarcopenia was 16.4% (10/61), 34.9% (15/43), and 40.4% (42/104) ( χ2=10.312, P=0.006), respectively. Spearman correlation analysis showed that serum sclerostin was negatively correlated with estimated glomerular filtration rate ( r=-0.314, P<0.001), pinch strength ( r=-0.229, P=0.007), skinfold thickness ( r=-0.254, P<0.001), appendicular skeletal muscle index ( r=-0.169, P=0.010), body cell mass ( r=-0.174, P=0.020), and phase angle ( r=-0.264, P<0.001), and positively correlated with serum phosphorus ( r=0.227, P=0.002) and intact parathyroid hormone ( r=0.297, P<0.001). Multiple linear stepwise regression analysis showed that lg[appendicular skeletal muscle index] was negatively correlated with male ( β=0.330, t=5.675, P<0.001) and serum sclerostin ( β=-0.125, t=-2.143, P=0.033), and positively correlated with body mass index ( β=0.474, t=8.090, P<0.001). Conclusion:Serum sclerostin can be used as a good index and a potential therapeutic target for sarcopenia in CKD patients.

Objective To observe the severity of cerebral edema after mechanical thrombectomy in the patients with acute ischemic stroke caused by large vessel occlusion,and to statistically analyze the related fac-tors affecting the prognosis quality of the patients,so as to guide the patients to conduct scientific interven-tion.Methods Ninety-one patients with acute ischemic stroke due to anterior circulation large vessel occlusion treated with mechanical thrombectomy in this hospital from October 2021 to October 2022 served as the ana-lytic subjects.According to the severity of brain edema,they were divided into the group Ⅰ(mild),group Ⅱ(moderate),and group Ⅲ(severe);after 12-week treatment,the improved Rankin scale was used to evaluate the prognosis.The patients with good prognosis were included in the excellent group,and the patients with poor prognosis were included in the poor group.Single factor and multifactor logistic analysis was used to ana-lyze the influencing factors and prognostic related factors of different degrees of brain edema.Results The univariate analysis showed that the percentage of patients with NIHSS score at admission ≥15,time from on-set to thrombolysis ≥6 h,history of hypertension,successful vascular recanalization and good collateral circu-lation were significantly different among the groups Ⅰ,Ⅱ and Ⅲ(P＜0.05);the multivariate logistic regres-sion analysis results showed that the NIHSS score at admission ≥15,time from onset to thrombolysis ≥6 h,and hypertension history were the risk factors leading to severe cerebral edema,while successful recanalization of blood vessels was a protective factor for cerebral edema(P＜0.05).The univariate analysis showed that in the good prognosis group the percentage of patients had good circulation of lateral branches,successful reca-nalization of blood vessels,severe cerebral edema,hypertension,time from onset to thrombolysis ≥6 h,and NIHSS score ≥15 at admission were significantly different from those in the poor prognosis group(P＜0.05).The multivariate logistic regression analysis results showed that severe cerebral edema,time from onset to thrombolysis ≥6 h and NIHSS score ≥15 at admission were the risk factors for poor prognosis,while good collateral circulation and successful recanalization of blood vessels were the positive factors for good prognosis(P＜0.05).Conclusion Mechanical thrombectomy patients with hypertension and time from onset to throm-bolysis ≥6 h and NIHSS score at admission ≥15 have more severe brain edema after treatment;severe brain edema,time from onset to thrombolysis ≥6 h,NIHSS score at admission ≥15 were the adverse factors affect-ing the prognosis of the patients with mechanical thrombectomy.

OBJECTIVE To systematically summarize the working model of pharmacy consultation in medical institutions in China， and to provide reference for the normalization of process， standardization of content and homogenization of services of pharmacy consultation. METHODS A systematic search of Chinese and English literature databases was conducted to incorporate the literature on the working model of pharmacy consultation published by medical institutions in China. Two researchers screened and extracted the key information， and ultimately conducted qualitative summary and descriptive analysis. RESULTS Based on the included 11 articles， the pharmacy consultation working models were explored by clinical pharmacists in China. The contents of consultation mainly involved anti-infection， parenteral nutrition， cancer pain， etc. The general concept of pharmacy consultation should refer to the constructed flowchart， specific consultation problems could refer to the pathway， mind map， or decision tree and other framework guidance to carry out the work. Finally， consultation opinions could be written according to the consultation system or specialty consultation templates， and the adoption of a new working model （such as pharmacist active consultation） could also promote the number and acceptance rate of pharmacy consultation. CONCLUSIONS A series of working models of pharmacy consultation have been initially explored in medical institutions in China. However， it is not yet perfect and lacks a unified quality control and evaluation system for pharmacy consultation， which should be the focus of future research and practice.

Objective To observe the clinical effect of Tongyuan Acupuncture combined with Modified Linggui Zhugan Decoction in the treatment of polycystic ovary syndrome(PCOS)with spleen deficiency and phlegm-damp syndrome.Methods A total of 86 patients with PCOS of spleen deficiency and phlegm-damp type were randomly divided into observation group and control group,43 cases in each group.The control group was treated with Metformin Hydrochloride Tablets combined with Ethinylestradiol and Cyproterone Acetate Tablets.The observation group was treated with Tongyuan Acupuncture combined with Modified Linggui Zhugan Decoction on the basis of the treatment of the control group.Both groups were treated for three consecutive months.After three months of treatment,the clinical efficacy of the two groups was evaluated.The changes of sex hormone indexes estradiol(E2),testosterone(T),luteinizing hormone(LH),follicle stimulating hormone(FSH)and prolactin(PRL)expression levels were observed before and after treatment in the two groups.The changes of glucose metabolism levels including insulin resistance index(HOMA-IR),fasting insulin(FINS)and fasting blood glucose(FPG)expression levels were compared before and after treatment between the two groups.Results(1)The total effective rate was 90.70%(39/43)in the observation group and 74.42%(32/43)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,HOMA-IR,FINS and FPG in the two groups were significantly improved(P＜0.05),and the improvement of HOMA-IR,FINS and FPG in the observation group was superior to that in the control group,the difference being significant(P＜0.05).(3)After treatment,the levels of E2,T,LH,FSH and PRL in the two groups were significantly improved(P＜0.05),and the levels of E2,T,LH,FSH and PRL in the observation group were significantly superior to those in the control group,the differences were statistically significant(P＜0.05).Conclusion Tongyuan Acupuncture combined with Modified Linggui Zhugan Decoction in the treatment of spleen deficiency and phlegm-damp type of PCOS can effectively improve the sex hormone level of patients and regulate the glucose metabolism of patients.The clinical effect is significant.

Objective To observe the therapeutic effect and mechanism of Astragaloside Ⅳ liposomes for influenza A virus infection in mice.Methods Fifty BALB/c mice were randomly divided into normal group(10 mice)and modeling group(40 mice).The modeling group mice were injected with A/PR/8/34(H1N1)influenza virus liquid via nasal drip.The modeling mice were randomly divided into model group,Oseltamivir group,and Astragaloside Ⅳ Liposomes high-and low-dose groups,with 10 mice in each group.The drug was administered by gavage two hours after infection for five days continuously.The appearance of the mice was observed,the body mass,survival condition and lung index as well as viral load in lung were assessed,pathological feature of lung tissue was observed by hematoxylin-eosin(HE)staining method,and mRNA expression levels of monocyte chemoattractant protein 1(MCP-1),macrophage inflammatory protein 1β(MIP-1β),and interferon γ(IFN-γ),CXC chemokine ligand 1(CXCL-1),interleukin(IL)-6,and IL-1β in lung tissues were detected by quantitative polymerase chain reaction(qPCR)method.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the contents of granulocyte-macrophage colony-stimulating factor(GM-CSF)and regulated on activation normal T-cell expressed and secreted(RANTES)in mouse lung tissue.Results Compared with the normal group,mice in the model group showed significant decrease of body mass,shortened survival time(P＜0.001),significantly increased lung index(P＜0.001),significantly increased viral load in lung(P＜0.001),and significantly increased mRNA expression levels of MIP-1β,IFN-γ,CXCL-1,IL-6,IL-1β and MCP-1 in lung tissue(P＜0.05 or P＜0.001),and the structure destruction of lung tissue could be seen in pathology.Compared with the model group,mice in the Astragaloside Ⅳ liposomes high-dose group showed that the decrease in body mass was slowed down,the survival time and survival rate were higher(P＜0.05),and the lung index was significantly decreased(P＜0.05),the viral load in lung was decreased(P＜0.001)and the mRNA expression levels of MIP-1β,IFN-γ,CXCL-1,IL-6,IL-1β and MCP-1 in lung tissue were decreased,and the alveolar structure was relatively intact,and a little connective tissue hyperplasia was seen.Conclusion Astragaloside Ⅳ liposomes can improve the survival time and reduce the viral load of lung tissue in mice with influenza A virus infection,and its mechanism may be related to the inhibition of the expression of inflammatory factors,thus playing an antiviral role.