BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of genital herpes in China from 2010 to 2023 and provide evidence for the prevention and control of genital herpes.Methods:The reported data of genital herpes cases in 31 provinces (autonomous regions and municipalities) in China from 2010 to 2023 were collected from the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. Software Joinpoint 5.2.0 was used to analyze the epidemiological characteristics of genital herpes, software ArcGIS 10.5 was used for spatial autocorrelation analysis, and software SaTScan 10.2.3 was used for spatiotemporal scanning analysis.Results:The reported incidence rate of genital herpes increased from 1.58/100 000 to 2.00/100 000 in China from 2010 to 2023, with an average annual percentage change of 0.90%. The upward trend of reported incidence rate was significant ( t=2.35, P=0.037). There was a positive spatial autocorrelation in the reported incidence of genital herpes with the global Moran's I ranging from 0.36 to 0.51 (all P<0.001). Local spatial autocorrelation analysis showed that the number of hotspots increased from 144 in 2010 to 232 in 2023, mainly distributed in provinces Zhejiang, Guangdong, Guangxi, Chongqing and Hunan. The number of hotspots in of Chongqing, Sichuan, Yunnan and Guizhou increased significantly from 7 to 57. A total of 67 spatiotemporal clusters were detected by spatiotemporal scanning analysis, mainly distributed in Guangdong from 2011 to 2015, in Zhejiang and Fujian from 2015 to 2019, and in Chongqing and Guizhou from 2019 to 2023. Conclusions:From 2010 to 2023, the reported incidence of genital herpes in China showed an upward trend, and there was an obvious spatiotemporal clustering of genital herpes. The distribution of hotspots was basically consistent with the distribution of spatiotemporal clustering areas, mainly distributed in the southeastern coastal area and southwestern region, and the spatiotemporal clustering areas gradually changed from the southeast coastal area to the southwest region.

Objective:To investigate and evaluate the correct cognition and influencing factors of mpox expertise among relevant Chinese clinicians and to provide a reference for prevention and control.Methods:A cross-sectional survey was conducted among clinicians in relevant departments using a structured questionnaire compiled by ourselves through a non-random network recruitment method. The content includes demography, clinical specialties, and characteristics of medical institutions, and 37 questions to evaluate the professional cognition of mpox etiology, clinical characteristics, transmission, prevention, and control. Using the modified Bloom's cutoff point to determine the correct answer is greater than or equal to 26 entitled correct cognition. A logistic regression model was used to analyze the factors influencing the correct cognition rate.Results:A total of 4 332 clinicians in 23 provinces (autonomous regions, municipality) in China were investigated by online questionnaires and 4 276 effective questionnaires were collected, with an effective rate of 98.71%. The mean age of the respondents was (39.46±9.54) years old, 61.18% were female. The overall correct cognition rate of mpox expertise was 62.04% (95% CI: 60.59%-63.50%), the correct cognition rates of mpox etiology, clinical characteristics, transmission, prevention and control were 48.25% (95% CI: 46.68%-49.82%), 78.66% (95% CI: 77.38%-79.95%), 68.56% (95% CI: 67.10%-70.02%), respectively. Multivariate logistic regression analysis showed that the relevant factors affecting the overall correct cognition of mpox expertise among Chinese clinicians included gender (female: OR=1.54, 95% CI: 1.31-1.80), region (eastern region: OR=1.46, 95% CI: 1.18-1.79; midwestern region: OR=1.24, 95% CI: 1.04-1.49), professional title (deputy senior: OR=1.43, 95% CI:1.16-1.76; senior: OR=1.72, 95% CI:1.30-2.28), the clinical field (the clinical fields of dermatology and venereal diseases: OR=1.78, 95% CI: 1.42-2.23). Conclusions:The overall correct cognition rate of mpox expertise among relevant Chinese clinicians was low. It was essential to conduct mpox knowledge training for clinicians in males, northeast regions, junior professional title and the clinical fields other than dermatology and venereal diseases to improve their correct cognition rates and epidemic prevention and control ability.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

Objective To investigate the effects of secukinumab combined with E'xian Huaban decoction on traditional Chinese medicine symptom scores and nailfold microcirculation morphology in patients with plaque psoriasis.Methods A total of 120 patients with plaque psoriasis were selected and randomly divided into monotherapy group(n=60)and combination therapy group(n=60).The monotherapy group received secukinumab treatment,while the combination therapy group was treated with secukinumab plus E'xian Huaban Decoction.Clinical therapeutic efficacy,traditional Chinese medicine symptom scores(including skin lesions,pruritus,rough skin,scales and irritabili-ty),relevant scale[Psoriasisarea and Severity Index(PASI),Dermatology Life Quality Index(DLQI)and Visual Analogue Scale(VAS)]scores,inflammatory factors[interleukin-17(IL-17),interleukin-23(IL-23)and vascular endothelial growth factor(VEGF)]levels and nailfold microcircu-lation morphology(loop tube morphology,blood flow state and loop periphery state)were observed in both groups.Results The overall clinical efficacy rate in the combination therapy group was 95.00％,which was significantly higher than 83.33％ in the monotherapy group(P＜0.05).After treatment,traditional Chinese medicine symptom scores(skin lesions,pruritus,rough skin,scales and irritability),inflammatory factors(IL-17,IL-23 and VEGF)levels,scale(PASI,DLQI and VAS)scores as well as loop tube morphology scores,blood flow state scores and loop periphery state scores were signifi-cantly lower compared to pre-treatment values,and these parameters were significantly lower in the combination therapy group than the monotherapy group(P＜0.05).Conclusion Secukinumab combined with E'xian Huaban Decoction can significantly improve clinical symptoms and signs,and enhancing the clinical therapeutic effect.

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

OBJECTIVE To understand the changing trends of use of antibiotics and etiological submission rates in medical institutions of Wuhan and find out the key points of management.METHODS The survey data of Wuhan were collected from the cross-sectional survey databases for nosocomial infections in China of 2016,2018,2020 and 2022,and the data were retrospectively analyzed.RESULTS From 2016 to 2022,a total of 141 284 hospital-ized patients from 117 medical institutions were enrolled in the survey,and the utilization rate of antibiotics was 32.36％;the utilization rate of antibiotics was 32.87％in 2016,31.74％in 2018,28.75％in 2020,34.56％in 2022,showing an upward trend(x2=13.941,P＜0.001).The utilization rates of antibiotics were relatively high in respiratory medicine department and comprehensive ICU,which showed upward trends(x2=16.377,P＜0.001;x2=5.581,P=0.018);the utilization rate of antibiotics showed a downward trend in non-neonates pediatrics de-partment(x2=11.886,P＜0.001).The rates of prophylactic use of antibiotics for type Ⅰ incision surgery were 31.54％,23.53％,28.44％and 13.24％,respectively,showing downward trends(x2=230.333,P＜0.001).The etiological submission rates were 59.98％,55.77％,65.69％and 59.16％,respectively,which were basically same(P=0.072);the etiological submission rates of the medical institutions with less than 300 beds and 300 to 599 beds showed upward trends,while the etiological submission rates of the medical institutions with 600 to 899 beds and no less than 900 beds showed downward trends(x2=42.019,P＜0.001;x2=4.599,P=0.032).The etiological submission rate was 44.87％in 2018 before the treatment with antibiotics,47.80％in 2020,44.45％in 2022,which were basically same(P=0.431);the etiological submission rate of the medical institutions with no less than 900 beds showed a downward trend(x2=14.464,P＜0.001).CONCLUSIONS The use of antibiotics of the hospi-talized patients is generally normalized in the medical institutions of Wuhan,the utilization rate shows an upward trend,the etiological submission rate is basically same,and the rate of prophylactic use of antibiotics for type Ⅰincision surgery shows a downward trend.It is necessary to attach great importance to the etiological submission of large scale metical institutions before the treatment with antibiotics and the use of antibiotic of some key departments.

Objective To understand the current status and influencing factors of microbial contamination of dental unit waterlines(DUWLs)of secondary and lower medical institutions in Wuhan,and provide scientific basis for for-mulating prevention and control measures.Methods A stratified convenience sampling method was adopted to con-duct questionnaire survey on 248 dental medical institutions in 15 districts of Wuhan City,DUWLs from 44 medical institutions were sampled and detected according to hospital levels.Results Among disinfection and maintenance management measures for source water and waterlines,the highest implementation rate was the installation rate of anti-suction dental handpiece(73.39％,182/248),but only 16.48％(30/182)of institutions regularly conducted the detection on anti-suction function;The lowest was the daily disinfection rate of water storage tanks(17.53％,17/97).A total of 132 water specimens were collected from 44 medical institutions,with a qualified rate of microbi-al detection of 56.06％.The qualified rates for secondary,primary,and unclassified medical institutions were 77.78％,50.00％,and 50.72％,respectively,with statistically significant differences(P＜0.05).The qualified rates of microbial detection for source water,handpiece water,and three-way syringe water were 59.09％,50.00％,and 59.09％,respectively,with no statistically significant difference(P＞0.05).Univariate analysis re-sults showed that medical institutions that regularly conducted chemical disinfection on DUWLs,understood DU-WLs waterline cleaning and disinfection standards,regularly performed microbial monitoring on diagnosis and treat-ment water,qualified source water,and flushed waterlines for 3 minutes before and after daily consultations had a higher qualified rate of microbial detection in DUWLs diagnosis and treatment water,and the differences were all statistically significant(all P＜0.05).Conclusion The contamination status of DUWLs in secondary and lower medical institutions in Wuhan is relatively serious.It is recommended to focus on strengthening the training of rele-vant regulations,installing inlet filters,regularly detecting the anti-suction function of dental handpieces,imple-menting chemical disinfection and microbial monitoring on waterlines,standardizing the implementation of flushing before and after diagnosis and treatment,and strengthening the disinfection and use management of independent wa-ter storage tanks to control contamination.

Objective To investigate the anti-hepatocellular carcinoma mechanism of Chloranthus fortunei(A.Gray)Solms-Laub.via network pharmacology,molecular docking techniques and in vitro experiments.Methods Chemical composition of Chloranthus fortunei(A.Gray)Solms-Laub.was searched by literature.Swiss Target Prediction was used to find corresponding targets.STRING was used to construct protein-protein interactions network(PPI).DAVID was used to enrich GO analysis and KEGG pathway.AutoDock Vina 1.1.2 and Pymol visualisation was used for docking and validation.Results Chloranthus fortunei(A.Gray)Solms-Laub.had 61 active components,685 targets,and 279 intersections with disease targets.The PPI showed that the main active components were Luteolin,Chloranthalactone C,Shizukanolide H,Esculetin,7-Hydroxycoumarin.The key targets were GAPDH,VEGFA,STAT3,JUN,HSP90AA1,AKT1,CTNNB1,CASP3,and ALB.Biological process(BP)involved protein phosphorylation,signal transduction,regulation of RNA polymerase II promoter transcription,cell proliferation,apoptosis.Cellular component(CC)involved cytoplasm,nucleus,cell membrane,cellular exosome.Molecular function(MF)involves protein binding,ATPase,threonine kinase,protein kinase activity.KEGG involved cancer pathway,metabolic pathway,PI3K-Akt signalling pathway,cancer proteoglycans,lipids and atherosclerosis,cytomegalovirus infection,microRNAs in cancer,human T-cell leukaemia virus type 1,Ras signalling pathway,MAPK signalling pathway.Molecular docking showed that silverweed lactone H had a strong affinity for each of the other target proteins,indicating that this component plays a key role.The results of RT-qPCR assay and WB assay showed that there were significant differences in gene and protein expression levels before and after drug administration.Conclusion The Chinese medicine in Chloranthus fortunei(A.Gray)Solms-Laub.can treat hepatocellular carcinoma through the MAPK pathway,and the main active ingredients have good docking effects with the core target proteins of the disease.

Objective:To investigate the efficacy and safety of electric microneedling combined with recombinant collagen liquid dressing, compound glycyrrhizin tablets, and hydrocortisone butyrate ointment for the treatment of mild to moderate alopecia areata in children.Methods:This is a prospective study. A total of 72 children with mild to moderate alopecia areata, admitted to the Department of Dermatology, Zunyi Maternal and Child Health Hospital from November 2023 to June 2024, were included in this study. The children were randomly assigned to either the experimental group, which received electric microneedling combined with treatment, or the control group, which received treatment without microneedling, based on the order of their visits. All patients received oral compound glycyrrhizin tablets and topical hydrocortisone butyrate ointment for treatment. In the experimental group, electric microneedling was used to puncture the alopecia lesions while simultaneously applying recombinant collagen liquid dressing. The control group did not receive electric microneedling treatment and only had the recombinant collagen liquid dressing applied to the lesions. The treatment lasted for 12 weeks. The efficacy and incidence of adverse reactions were compared between the two groups. After treatment, all patients were followed up for 3 months to check for any recurrence of this condition.Results:There was no significant difference in response rate between the experimental and control groups [81.58% (31/38) vs. 73.53% (25/34), χ2 = 0.67, P = 0.412). No significant difference in cure rate was observed between the experimental and control groups [57.89% (22/38) vs. 47.06% (16/34), χ2= 0.85, P = 0.358]. The time to effect in the experimental group was shorter than that in the control group [(3.16 ± 0.73) weeks vs. (4.60 ± 1.08) weeks, t = 5.15, P < 0.001]. The incidence of adverse reactions did not differ significantly between the experimental and control groups [7.89% (3/38) vs. 0, Fisher value = 0.24, P = 0.242]. There was no significant difference in recurrence rate between experimental and control groups [6.45% (2/31) vs. 12.00% (3/25), χ2 = 0.06, P = 0.801). Conclusions:The combination of electric microneedling, recombinant collagen liquid dressing, compound glycyrrhizin tablets, and hydrocortisone butyrate ointment provides a rapid onset of effect and is safe and effective for the treatment of mild to moderate alopecia areata in children.