Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

To develop a portable transport vehicle for single injured soldier in field warfare,so as to meet the target of completing emergency transshipment for single injured solider in both peacetime and wartime.The main body of the transport vehicle consists of a general stretcher and an additional wheel device.The stretcher provides a supporting platform for lying down and prone position of injured solider.The device of additional wheel is a foldable portable structure with two-wheels,which composed of 2 wheels,2 sets of frames,a crossbeam,connecting rods,buckles,and hooks.When transport task for injured solider needs to be performed,it can be connected to the stretcher to be expanded as a stretcher cart for transporting injured solider.In normal times,it can be folded for storage in a backpack.The use of the portable transport vehicle for single injured soldier in field warfare can reduce the number of personnel who carries out the stretcher from 2-3 person to 1 person,and can significantly reduce the frequency of transport,and shorten the overall time of transport,and remarkably improve efficiency of transport.Moreover,the scores of medical members for the performance of labor-saving and the recommendation level of transport vehicle in this study were higher than general stretcher,and the differences were significant(t=9.52,3.60,P<0.05).This transport vehicle has a reasonably structural design,favorable portability and safety.It can greatly improve the efficiency of transporting injured solider under limited conditions,and enhance the possibility that successfully rescue injured solider,and meet the requirement of grass-roots unit of army for practical combat in transporting injured solider,which is a suitable transport tool.

Objective:To investigate the clinical features, treatment strategies and prognosis of adult thrombotic thrombocytopenic purpura (TTP) patients and improve the clinicians' understanding of TTP.Methods:It was a case series analysis study. The clinical data of TTP patients admitted to ZhongDa Hospital affiliated to Southeast University from August 2013 to November 2024 were retrospectively collected. The clinical manifestations, laboratory tests, treatment methods and prognosis of TTP patients were analyzed. Kaplan-Meier method and multivariate Cox proportional hazards regression model were utilized to assess the association between rituximab treatment and survival outcomes.Results:The study included 24 TTP patients, with age of (58.38±15.03) years (21 to 87 years), 14 females (58.33%) and 10 males (41.67%). The first symptoms were often neurological abnormalities (lethargy, coma, sudden glossolalia or unconsciousness (10 patients, 41.67%). Five patients (20.83%) had the quinary syndrome, including fever, microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency and neurological symptoms, and 13 patients (54.17%) had the triad syndrome, including neurological syndromes, microangiopathic hemolytic anemia and thrombocytopenia. Twenty-three patients (95.83%) had anemia. Twenty patients (83.33%) presented with neurological abnormalities, among which 10 patients died of neurological events. Renal insufficiency occurred in 14 patients (58.33%). Nine patients (37.50%) presented with large areas of skin ecchymosis. Except for 1 patient complicating with lung adenocarcinoma and 1 patients complicating with bone metastasis tumor, the other patients had no active tumors. All 24 patients had PLASMIC scores ≥ 4 points, of which 11 patients (45.83%) had PLASMIC scores ≥ 6 points. Fourteen patients (58.33%) received the treatment for plasma exchange, and 7 patients (29.17%) did not undergo plasma exchange and received component transfusion and glucocorticoids therapy with poor prognosis due to rapid disease progression, old age or severe disease. Furthermore, 3 patients (12.50%) were only treated with component transfusion and glucocorticoids therapy for economic reasons, and died shortly after hospital discharge. Eight patients received plasma exchange, glucocorticoids combined with rituximab, of which one died, four survived, and three were lost to follow-up. Finally, fifteen patients (62.50%) died, 4 patients survived, and 5 patients were lost to follow-up (still alive before hospital discharge). Kaplan-Meier survival analysis demonstrated that mortality in the rituximab group was significantly lower than that in the non-rituximab group (Log-rank test, χ2=13.185, P<0.001). Multivariate Cox proportional hazards regression analysis further confirmed that no receiving rituximab was an independent correlated factor of death ( HR=10.453, 95% CI 1.309-83.436, P=0.027). Conclusions:TTP usually starts with neurological symptoms, and can affect multiple systems. The patients with neurological abnormalities have a poor prognosis. The patients with TTP have a rapid disease progression and a high mortality rate. Rapid identification and timely treatment are crucial for improving the prognosis of TTP. Combining rituximab based on plasma exchange and glucocorticoids may reduce mortality of TTP patients.

Objective:To explore the demographic composition of type 2 diabetes mellitus (T2DM) with metabolic associated fatty liver disease (MAFLD) and the role of energy metabolism in the progression of MAFLD in order to provide theoretical support for improving the prognosis of MAFLD.Methods:A cross-sectional study was conducted. Ninety-four cases with T2DM combined with MAFLD admitted to the Endocrinology Department of Tianjin Third Central Hospital from July 2014 to July 2019 were selected. Patients were divided into three groups: non-metabolic associated steatohepatitis (MASH) group (25 cases), borderline MASH group (49 cases), and MASH group (20 cases) according to the non-alcoholic fatty liver disease activity score (NAS). Patients were further divided into two groups: non/mild fibrosis (F0-1) group (74 cases) and the significant fibrosis (F2-4) group (20 cases) in accordance with liver fibrosis scores. The differences in general clinical and biochemical indicators, body composition, and energy metabolism indicators among the groups were compared. Binary logistic regression analysis was conducted to explore factors affecting liver inflammation and fibrosis severity degree in patients with MAFLD.Results:The visceral fat area (VFA) and body fat percentage (PBF) were significantly higher in the MASH group than in the non-MASH group ( P<0.05), while the skeletal muscle mass index and body mass index (SMI-BMI) were significantly lower in the MASH group than in the marginal MASH group ( P<0.05) during the comparison of body composition and substrate metabolism at different stages of MASH. Alanine aminotransferase (ALT) and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the fibrotic group than in those in the no/mild fibrosis group ( P<0.05) when comparing clinical and biochemical indicators, body composition, and substrate metabolism at different stages of fibrosis. The skeletal muscle mass (SMM), SMI-BMI, SMM-Weight, resting energy expenditure (REE), and fat oxidation rate (FAT OXR) were significantly lower in the fibrotic group than those in the no/mild fibrosis group ( P<0.05). The respiratory quotient and carbohydrate functional ratio (%CHO) were significantly higher in the fibrotic group than in the no/mild fibrosis group ( P<0.05). Correlation analysis indicated a positive correlation between the NAS score, reflecting the severity of liver inflammatory lesions, with VFA and PBF ( r=0.258 and 0.323, P<0.05); while the F score was positively correlated with the respiratory quotient, %CHO, and VFA ( r=0.292, 0.303, and 0.239, P<0.05), and negatively correlated with REE, the energy ratio from fat, FAT OXR, SMM, SMI-Weight, and SMI-BMI ( r=-0.209, -0.214, -0.333, -0.240, -0.250, and -0.305, P<0.05). Logistic regression analysis indicated that SMI-Weight and FAT OXR were independent factors affecting the progression of liver fibrosis. Conclusion:The reduction of skeletal muscle, particularly because of energy metabolism, is a factor affecting the progression of fibrosis in MAFLD.

[Objective]To explore the effects of exosomal CXCL on the biological behavior of cervical cancer cells and its underlying mechanisms.[Methods]Chemokine CXCL was first screened through bioinformatics databases.The GEPIA database was analyze CXCL expression in cervical cancer tissues and adjacent normal cervical tissues.Western blot was performed to detect CXCL expression levels in cervical cancer cells(Caski)and normal cervical epithelial cells(H8).The successful isolation of exosomes was confirmed by nanoparticle tracking analysis,transmission electron microscopy(TEM)and Western blot.ELISA was employed to detect the expression level of exosomes CXCL was determined by ELISA.After CXCL knockdown via siRNA transfection,cells were divided into three groups:blank control,negative control and experimental groups.Cell proliferation was evaluated using the CCK-8 assay,while cell migration and invasion were assessed by Transwell assays.[Results]Exosomal CXCL expression was significantly upregulated in cervical cancer cells compared with normal cervical epithelial cells(P<0.01),and also markedly elevated in cervical cancer tissues compared with adjacent normal tissues.After low expression of CXCL knockdown significantly reduced CXCL expression in both cancer cells and their derived exosomes(P<0.05).Low expression markedly inhibited the proliferation,invasion and migration abilities[Conclusion]Silencing exosomal CXCL may inhibit the malignant biological behavior of cancer cells.

To develop a portable transport vehicle for single injured soldier in field warfare,so as to meet the target of completing emergency transshipment for single injured solider in both peacetime and wartime.The main body of the transport vehicle consists of a general stretcher and an additional wheel device.The stretcher provides a supporting platform for lying down and prone position of injured solider.The device of additional wheel is a foldable portable structure with two-wheels,which composed of 2 wheels,2 sets of frames,a crossbeam,connecting rods,buckles,and hooks.When transport task for injured solider needs to be performed,it can be connected to the stretcher to be expanded as a stretcher cart for transporting injured solider.In normal times,it can be folded for storage in a backpack.The use of the portable transport vehicle for single injured soldier in field warfare can reduce the number of personnel who carries out the stretcher from 2-3 person to 1 person,and can significantly reduce the frequency of transport,and shorten the overall time of transport,and remarkably improve efficiency of transport.Moreover,the scores of medical members for the performance of labor-saving and the recommendation level of transport vehicle in this study were higher than general stretcher,and the differences were significant(t=9.52,3.60,P<0.05).This transport vehicle has a reasonably structural design,favorable portability and safety.It can greatly improve the efficiency of transporting injured solider under limited conditions,and enhance the possibility that successfully rescue injured solider,and meet the requirement of grass-roots unit of army for practical combat in transporting injured solider,which is a suitable transport tool.