Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

This article discussed the significance of latent pathogen theory in the understanding of pathogenesis and prevention and treatment of epidemic diseases such as novel coronavirus infection(COVID-19).Latent-qi is the cause of epidemic febrile disease,and it is also the yang-heat qi of human body.The stagnant yang-heat qi hidden in the body can induce the latent heat constitution.The latent heat constitution is particularly closely related to the development and progression of epidemic febrile disease,and is susceptible to the warm pathogen.The significance of the latent pathogen theory on the prevention and treatment of epidemic diseases such as COVID-19 with traditional Chinese medicine is as follows:abnormal climate is an important early warning and is the external condition for the development of epidemic diseases;latent pathogen is easily assimilated into the newly-attacked pathogenic factors for the assimilation of similar nature,and then injuries taiyin-spleen,which causes spleen deficiency and dampness accumulation and then results in latent dampness;preventing and treating epidemic diseases based on the latent pathogen theory is helpful for identifying the key syndromes,formulating the core regimen indicated for the pathogenesis,and cutting off the progression of the disease.Based on the latent pathogen theory,dampness-removing therapy for latent dampness is important for the prevention and early treatment of COVID-19,and our research group has developed a Chinese herbal formula of Wuzhi Fangguan Prescription(composed of Fici Simplicissimae Radix,Coicis Semen,Poria,Herba Polygoni Chinensis,Atractylodis Rhizoma,Pogostemonis Herba,and Glycyrrhizae Radix et Rhizoma)to prevent COVID-19 early by using a variety of dampness-removing methods such as drying dampness,resolving dampness,draining dampness,and invigorating spleen.The prescription is indicated for the prevention and early treatment of COVID-19.The mechanism of dampness-removing therapy is mainly related to the improvement of the disordered immune function and restoration of the body's resistance to diseases.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To describe the changing trend and related factors of prevalence rates of healthcare-associa-ted infection(HAI)in a tertiary hospital in the past 10 years,and analyze the influencing factors for HAI.Methods A cross-sectional survey on HAI was conducted for 10 consecutive years from 2013 to 2022(one day was selected as the survey day each year),data were collected.The distribution and related factors of prevalence rates of HAI were analyzed by trend-x2 test and Pearson correlation coefficient.Multivariate logistic regression and multilayer percep-tron(MLP)models were constructed to analyze the independent effect and significance of factors.Results From 2013 to 2022,the prevalence rates of HAI ranged from 4.66％to 8.07％in this hospital,showing a linear upward trend.The proportions of ICU patients and utilization rate of central venous catheters within 2 days before the sur-vey showed linear upward trends,while the proportion of patients with urinary catheters within 2 days before the survey and proportion of patients undergoing surgery within 30 days before the survey decreased.The MLP model revealed that the top 3 important factors for HAI were length of hospital stay＞10 days,admission in ICU,and in-dwelling central venous catheters within 2 days before the survey.Multivariate logistic regression model indicated that length of hospital stay＞10 days,indwelling central venous catheters or urinary catheters within 2 days before the survey,surgery within 30 days before the survey,and admission in ICU were independent influencing factors for HAI.Conclusion The incidence of HAI in this hospital presents a linear increase in recent 10 years,the causes should be further analyzed and the direction of intervention should be determined through targeted surveillance.Adopting trend test statistical analysis method,logistic regression,MLP multi-factor model can further explore the data value of HAI prevalence survey.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

Sucrose synthase plays a crucial role in the plant sugar metabolism pathway by catalyzing the production of uridine diphosphate (UDP)-glucose, which serves as a bioactive glycosyl donor for various metabolic processes. In this study, a sucrose synthase gene named CtSus was cloned from Cistanche tubulosa, a traditional Chinese medicine known for its rich content of diverse glycosides, based on transcriptome analysis results. The open reading frame of CtSus was 2 418 bp long encoding 805 amino acids. Sequence analysis revealed conserved domains associated with the plant sucrose synthase family at both the N-terminal and C-terminal regions of CtSus protein. Phylogenetic analysis demonstrated that CtSus shares a close evolutionary relationship with sucrose synthases from other plants within the same order. Functional identification of CtSus was performed through whole-cell catalysis coupling with UGT71BD1, a characterized glycosyltransferase enzyme. The results showed that the introduction of CtSus significantly enhanced the conversion rate of glycosylation catalyzed by UGT71BD1. The soluble expression of CtSus in Escherichia coli was further achieved using the pCold^TM TF expression vector. In vitro enzymatic assay indicated the activity of CtSus to catalyze the formation of UDP-glucose in the presence of sucrose and UDP. Real-time quantitative-polymerase chain reaction results showed that the expression patterns of CtSus gene in different parts of C. tubulosa and the suspension cell cultures of C. tubulosa under drought stress correlated with the accumulation patterns observed for phenylethanol glycosides, respectively. Furthermore, key amino acids and their interactions between enzyme and substrate were explored based on protein structure prediction and molecular docking results. Overall, our findings identify a sucrose synthase CtSus responsible for the supply of the active glycosyl donor UDP-glucose during the biosynthesis of glycoside products in C. tubulosa and have also provided a gene element that can be utilized in engineering strain construction for glycoside products production.

Janus kinase (JAK) and histone deacetylase (HDAC) referred to as crucial targets in autoimmune diseases and cancers have achieved quite success in the treatment of these diseases. Until now, several JAK and HDAC inhibitors have been approved. Recently, developing single multi-targeting inhibitors including JAK/HDAC dual inhibitors based on network pharmacology has made significant progress in improving therapeutic efficacy, reducing toxic and side effects, and overcoming drug resistance. In this review, we summarize novel JAK/HDAC dual inhibitors as well as JAK/HDAC-based triple-targeting inhibitors, in order to provide reference for the discovery of novel JAK/HDAC dual inhibitor.

Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ² test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ²=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ²=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m²(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.