Dry eye disease(DED)refers to a condition characterized by reduced stability of the tear film or an imbalance in the microenvironment of the ocular surface, resulting from abnormalities in quality, quantity and kinetics of tear. This condition leads to various ocular discomforts and even visual impairment. The pathogenesis of DED is multifactorial and current treatment mainly focuses on symptom relief and preservation of visual function. Acupuncture has shown effectiveness in treating dry eye, although its underlying mechanism remains incompletely understood. Proteomics technology offers a comprehensive and systematic approach to studying the functions, structures and interactions of proteins. Its application in DED research can provide valuable insights into the dynamic changes in protein levels associated with different etiology or the course of DED and facilitate the identification of potential biomarkers. Furthermore, proteomics can systematically explore the regulatory mechanisms underlying acupuncture treatment for DED, providing a theoretical basis for acupuncture treatment research and contributing to the understanding of its effects at a fundamental level. This paper aims to explore the potential application of proteomics in both clinical and basic research on DED. Ultimately, it strives to offer scientific and effective strategies for the diagnosis and treatment of DED and advance our knowledge of the mechanisms underlying acupuncture therapy.

【Objective】 To investigate the allele frequencies polymorphic distribution of Duffy, Kidd and Diego blood group systems in Dongxiang ethnic group in Gansu Province. 【Methods】 Blood samples of 100 unrelated blood donors were randomly selected from Dongxiang ethnic group in Gansu from January to December 2017. Allelic typing of Duffy, Kidd and Diego blood groups was performed by fluorescence PCR. 【Results】 The allele frequencies of Duffy, Kidd, and Diego blood group systems of Dongxiang ethnic group were 0.835 for Fy^*01, 0.165 for Fy^*02, 0.570 for Jk^*01, 0.430 for Jk^*02, 0.020 for DI^*01, 0.980 for DI^*02, respectively. No Fy(a-b-), Jk(a-b-), Di(a+b-) rare phenotypes were found. The antigen incompatibility rates of Fy^a/Fy^b, Jk^a/Jk^b, Di^a/Di^b of Duffy, Kidd, and Diego blood group systems were 23.76%, 37.01% and 3.84%, respectively. 【Conclusion】 The allele frequencies distribution of Duffy, Kidd and Diego blood group systems in Dongxiang ethnic group in Gansu were polymorphic and has unique ethnic distribution characteristics.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To investigate frequency and function of peripheral CD4+CD28-T cells in immune thrombocytopenia(ITP)patients,to deeply understand pathogenesis of ITP.Methods:A total of 30 ITP patients treated in The Second Affiliated Hospi-tal of Dalian Medical University from January 2021 to June 2022 were recruited,and 30 gender/age-matched healthy volunteers were served as control group.Peripheral anticoagulation was collected and mononuclear cells(PBMC)were extracted,frequencies and func-tions of CD4+CD28-T cells in PBMC was analyzed by flow cytometry,plasma levels of IL-18 and IL-18BP in ITP patients were detected by ELISA,and frequencies of CD4+CD28-T cells before and after treated with IL-18 were determined by flow cytometry.Results:Frequencies of CD4+CD28-T cells in peripheral blood of ITP patients were significantly higher than that of healthy control group,and CD4+CD28-T cells had a stronger ability to secrete IFN-γ and TNF-α;level of IL-18 was higher in plasma from ITP patients;IL-18 could increase frequency of CD4+CD28-T cells in PBMC of ITP patients.Conclusion:Frequency of CD4+CD28-T cells in peripheral blood of ITP patients is significantly increased,and has stronger ability to secrete inflammatory factors.

Objective To investigate the expression of long non-coding RNA(lncRNA),surfactant associated 1 pseudogene(SFTA1P)in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines.Methods Based on the cancer genome atlas(TCGA)database,the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma.Then,the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction(RT-qPCR).SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids(pcDNA3.1-SFTA1P)and small interfering RNAs(si-SFTA1P-1 and si-SFTA1P-2).CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells.Differential gene expression analysis,correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells.Results Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue(P＜0.05).RT-PCR results showed that the expression of SFTA1P was obviously lower in lung squamous carcinoma cells than the human normal lung epithelial cells(P＜0.05).And the expression level of SFTA1P was relatively lower in the SK-MES-1 cells than the H520 cells(P＜0.05).Overexpression of SFTA1P suppressed the proliferation,migration and invasion of lung squamous carcinoma cells(P＜0.05),while its knockdown promoted these abilities(P＜0.05).Differential gene expression analysis,correlation analysis and functional enrichment analysis indicated that SFTA1P may inhibit MYC,G2m checkpoints and E2f signaling pathways in lung squamous cell carcinoma.Conclusion SFTA1P shows anti-cancer function in lung squamous cell carcinoma,and it may affect the biological functions of lung squamous cell carcinoma cells through down-regulating MYC,G2m checkpoints and E2f signaling pathways.

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.
Humans ; Glucose ; Blood Glucose ; Insulin Resistance/physiology* ; Diabetes Mellitus, Type 2/diagnosis* ; Blood Glucose Self-Monitoring ; Time Factors ; Insulin

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Dandy-Walker syndrome is one of the posterior fossa malformations, which is easily confused with arachnoid cyst or cerebellar dysplasia in clinical practice, leading to misdiagnosis. Dandy-Walker syndrome is easy to be combined with hydrocephalus, resulting in increased intracranial pressure, increased head circumference, growth retardation, spastic hemiplegia and other manifestations, and can also be accompanied by other nervous system malformations. On February 27, 2021, a child with Dandy-Walker syndrome with growth retardation as the primary manifestation was admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine. After multiple surgical treatment, the child's hydrocephalus was significantly improved. Through the analysis of the clinical data of the child's operation and the treatment of complications, it is helpful to improve the clinicians' understanding of the surgical treatment of the disease.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.