Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Background Climate change has resulted in long-term impacts on human health. Implementing efficient adaptation strategies among primary healthcare facilities is well determined by whether staff of different genders recognize the health risks related to climate change and are willing to take active measures. Objective To investigate gender differences on perceptions of health risks and attitude towards adaptation strategies among primary healthcare workers in China, and provide relevant suggestions. Methods By adopting a multi-stage cluster sampling method, we selected 21 urban and 10 rural healthcare facilities in Guangdong Province to collect information with a questionnaire. Then chi-square test, Wilcoxon rank sum test, and logistic regression analysis were used to explore the gender differences in climate change-related health risk cognition, knowledge acquisition channels, attitudes towards adaptation strategies, main obstacles, and resource requirements among the healthcare workers. Results Of 733 participants, 38.47% (282 participants) were male and 61.53% (451 participants) were female. The percentages of male healthcare workers who agreed that climate change is happening and recognized the causes of climate change (70.21%, 60.99%) were higher than the percentages of female counterparts (59.87%, 49.00%) (both Ps＜0.05), but no obvious gender differences existed in recognizing health risks of heatwaves and infectious diseases as well as sensitive population identification (all Ps＞0.05). Most of the participants (92.50%) received climate change and health-related information from mass media like TV, radio, and newspapers. Meanwhile less men chose new media channels than women (OR=0.62, 95%CI∶ 0.41-0.94). Only 30.56% of the participants (33.69% of men and 28.60% of women) reported involvement of relevant training and lectures. Most of them (90.96%) agreed to take active measures to deal with the health threats associated with climate change without gender differences for various measures (all Ps＞0.05). The leading obstacles were hard to integrate health adaptation to climate change into main work of institutions (most female agreed, 72.28%) and the lack of funds (most male agreed, 77.66%). Increasing funding for primary health care was regarded as the most needed resource by male (86.88%) and female (89.14%). After controlling the influence of other social factors, more men agreed with the lack of funds than women (OR=1.57, 95%CI∶ 1.10-2.24). Conclusion There are some gender differences in the perceptions of health risks and adaptation strategies of climate change among primary healthcare workers: Male staff are more likely to agree with climate change and regard the lack of funds as the main obstacle, while women prefer to choose new media channels to obtain information. It’s suggested that the government and relevant institutions focus on the learning and training of climate change and health-related knowledge and expand diversified information access, and promote capacity building to cope with health threats at grass-root level, in the light of recognized gender differences among primary healthcare workers.

【Objective】 To explore the establishment methods of transgenic human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) based on the transposons, and attempt to apply it on the nude mice mode with glioma. 【Methods】 PiggyBac transposon system specially designed by us was used to prepare non-targeting and Her2-targeting hUC-MSCs that can stably express TRAIL through puromycin screening. The glioma cells expressing firefly luciferase (U87MG-LUC) were injected into the skull of the immunodeficient mice (BALB/c-nu/nu) with 1×10⁶ cells per mouse. After 7 days of injection, the mice transplanted with U87MG were detected with a small animal living imager to determine the size and location of the tumors in skull. Then we injected the glioma-transplantation nude mouse with two kinds of transgenic hUC-MSCs expressing TRAIL (named as untarget-TRAIL and target-TRAIL, respectively), or the non-transgenic hUC-MSCs (all 1×10⁶ cells per mouse) or PBS (named as WT-MSCs and PBS for negative control) respectively, and then monitored the changes of tumor signals by a small animal living imager every week for 3~4 weeks. 【Results】 After six passages to expand the cells, the both transgenic cell lines can stably express TRAIL gene. Their ratio of green fluorescent protein (GFP) positive cells can reach 93%-97%, and the positive ratio of their MSC-specific surface markers still maintained normal (CD34⁺, CD45⁺, and HLA-DR⁺ all <0.1%, CD90>99%, CD73>88%, and CD105 >60%). The median survival time (d) of U87MG-transplanted nude mice in the groups of untarget-TRAIL, target-TRAIL, WT-MSCs, and PBS was 41 vs 39 vs 24 vs 23(P<0.05). 【Conclusion】 The transgenic hUC-MSCs overexpressing TRAIL gene can significantly prolong the survival time of nude mice with brain glioma.

Objective:The aim of this study was to compare the efficacy and safety of iguratimod (IGU) or leflnomide (LEF) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods:This was a multicenter, randomized, double-blinded, double dummy and controlled clinical trial. Patients with moderate or high active RA were randomized in a 1∶1 ratio to receive IGU+MTX (Group A) or LEF+MTX (Group B) treatment. The efficacy and safety were assessed at week 12, 24 and 52, respectively. The primary endpoint was the American Colleague of Rheumatology 20 (ACR20) response rates at the 52th week. Pearson chi square test and two-way Analysis of Variance (ANOVA) were used to compare the improve- ment of ACR20 and DAS28 at 52 weeks. Pearson chi square test or Fisher exact probability test were used to compare the ACR 20 and ACR70 rate between the two groups after treatment. The measurement data of the two groups were compared by independent sample t-test or nonparametric test. Results:A total of 240 RA patients were enrolled in the present study. As a result, 84.1% and 81.0% of patients achieved ACR20 criteria at the 52th week in Group A and Group B, respectively ( χ2=0.35, P=0.56). And the ACR50/70 response rates, disease activity score 28 (DAS28), simplified disease activity index (SDAI) and the absolute decrease of DAS28 from baseline were not statistically different between the two groups at week 12, 24 and 52. The rates of adverse events were lower in Group A than those in Group B (60.0% vs 79.0%, P<0.01). The elevations of glutamic pyruvic transaminase/glutamic oxalacetic transaminase levels, concomitant use of hepatinica and white blood cell decrease were more common in Group B ( P<0.05). Conclusion:IGU in combination with MTX is an efficacious and safe treatment regimen, which is comparable in efficacy in control active RA but superior in safety to LEF combined with MTX.

Objective:To investigate the effect of lncRNA HOTTIP on the radiosensitivity of four non-small cell lung cancer cell lines cultured in vitro by regulating the expression of miR-663a. Methods:Four non-small cell lung cancer cell lines (H838, H157, A549, and H1299) were irradiated with different radiation intensities (0, 2, 4, 6, and 8 Gy). Cell survival was detected by colony formation assay. The expression levels of HOTTIP and miR-663a were detected by qRT-PCR. A549 and H1299 cells were selected for the subsequent experiment. After silencing HOTTIP and/or over-expressing miR-663a, cell survival was detected by colony formation assay. Cell apoptosis was detected by flow cytometry. The expression levels of Cleaved caspase-3, Cleaved PARP andγ-H 2AX were quantitatively measured by Western blot. The targeting relationship between HOTTIP and miR-663a was vefiried by dual luciferase reporter assay and qRT-PCR. Results:The expression of HOTTIP was up-regulated, whereas that of miR-663a was down-regulated in the radiation-resistant H157, A549 and H1299 cells. Silencing HOTTIP or over-expressing miR-663a inhibited the survival of A549 and H1299 cells (radiosensitization ratios were 1.562 and 1.507, respectively), promoted the expression of Cleaved caspase-3, Cleaved PARP and γ-H 2AX, and accelerated cell apoptosis induced by radiation exposure. miR-663a was a target gene of HOTTIP, and HOTTIP negatively regulated the expression of miR-663a. The inhibition of miR-663a reversed the effect of silencing HOTTIP on the radiosensitivity of non-small cell lung cancer cells. Conclusion:Silencing HOTTIP can suppress the survival of non-small cell lung cancer cells and promotes cell apoptosis by up-regulating the expression of miR-663a, thereby enhancing the radiosensitivity of non-small cell lung cancer cell lines.

OBJECTIVE:To observe therapeutic efficacy and safety of cefoperazone sodium and sulbactam sodium combined with Shenmai injection in the treatment of elderly stroke associated pneumonia(SAP). METHODS:A total of 84 SAP patients in Dazhou Municipal Central Hospital during Mar. 2016-Mar. 2017 were divided into control group(42 cases)and observation group (42 cases)according to random number table. Based on routine treatment,control group was additionally given Cefoperazone sodium and sulbactam sodium for injection 3 g added into 5% Glucose injection 100 mL,intravenously,twice a day;suitable antibiotics were selected according to the results of pathogenic examination and drug sensitivity test. Observation group was additionally given Shenmai injection 100 mL added into 5% Glucose injection 250 mL intravenously,once a day,on the basis of control group. Both groups were treated for consecutive 2 weeks. Clinical efficacies of 2 groups were observed,and the levels of T-lymphocyte subsets(CD4+,CD8+,CD4+/CD8+)and inflammatory markers(TNF-α,hs-CRP,PCT),length of hospital stay before and after treatment. The ADR was recorded. RESULTS:The total response rate(95.24%)and marked response rate (47.62%)of observation group were significantly higher than those of control group(83.33%,23.81%);length of hospital stay in observation group [(15.24±3.53)d] was significantly shorter than control group [(18.43±4.21)d],with statistical significance (P<0.05).After treatment,the levels of CD4+and CD4+/CD8+in 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group;the levels of CD8 +,TNF-α,hs-CRP and PCT in 2 groups were significantly lower than before treatment;the observation group was significantly lower than the control group,with statistical significance(P<0.05);there was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Based on routine treatment,cefoperazone sodium and sulbactam sodium combined with Shenmai injection treat SAP significantly,can effectively improve immune function, reduce inflammation level and shorten the length of hospital stay without increasing the occurrence of ADR.

Objective To investigate the curative effect of transarterial embolization (TAE) for the treatment of spontaneous rupture with bleeding of hepatocellular carcinoma (HCC),and to discuss the factors influencing prognosis.Methods A total of 57 patients with HCC complicated by spontaneous rupture and bleeding,who received initial TAE during the period from June 2012 and June 2016,were enrolled in this study.The last follow-up visit was in October 2016.Kaplan-Meier method was used to calculate the cumulative survival rate,and Cox regression model was adopted to analyze prognostic factors.Results In this series of 57 patients,the median survival time was 208 days.The 6-month,1-year and 2-year cumulative survival rates were 50.3％,35.9％ and 14.7％,respectively.Multivariate Cox regression analysis indicated that tumor size,Child-Pugh classification,history of shock,and the used embolization materials were the independent prognostic factors.Conclusion The use of selective TAE,as an initial therapy,for HCC complicated by spontaneous rupture and bleeding is safe and effective.This study reveals that larger diameter of the tumor,poor Child-Pugh classification,the presence of shock history indicate a poor prognosis.TACE using lipiodol combined with gelatin sponge particles can expect a better prognosis than TACE using PVA particles alone.

Objective To evaluate the safety and efficacy of peripheral chemoembolization by using ethanol-soaked gelatin sponge (ESG) combined with chemotherapeutic drugs and/or iodized oil in treating patients with hepatocellular carcinoma (HCC) complicated by moderate-to-severe hepatic arterio-portal shunts (APS).Methods The clinical data of 106 HCC patients associated with moderate-to-severe APS,who were treated with ESG chemoembolization during the period from June 2008 to December 2015,were retrospectively analyzed.The postoperative improvement of APS,the procedure-related complications,the tumor response,the survival time,the prognostic factors,etc.were statistically analyzed.Results In the 106 HCC patients associated with moderate-to-severe APS,the median survival time was 278 days,and the 6-,12-and 18-month cumulative survival rates were 70.8％,36.1％ and 16％,respectively.Univariate analysis showed that sex,total bilirubin level,maximal tumor diameter,history of previous treatment,tumor response and postoperative improvement of APS were closely correlated with the patient's prognosis.Multivariate regression analysis indicated that tumor response and postoperative improvement of APS were the independent protection factors,while the female sex and the maximal tumor size ≥5 cm were the independent risk factors.Conclusion For the treatment of HCC complicated by moderate-to-severe hepatic APS,transarterial chemoembolization by using ESG combined with chemotherapeutic drugs and/or iodized oil is safe and effective.The presence of tumor response to treatment and the postoperative improvement of APS indicate a better prognosis.The female sex and the maximal tumor size ≥5 cm are the independent prognostic risk factors.

AIM:Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation ( AF) .Al-though tumor necrosis factor ( TNF)-αlevels are increased in patients with AF , the role of TNF-αin the pathogenesis of AF remains unclear.Recent research has revealed that T-type Ca2+currents ( ICa,T ) play an important role in the pathogenesis of AF .METH-ODS:In this study , we used the whole-cell voltage-clamp technique and biochemical assays to explore the role of TNF-αin the regula-tion of ICa,T in atrial myocytes.RESULTS:We found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit mRNA levels were decreased , while TNF-αexpression levels were increased , in human atrial tissue from patients with AF .In murine atrial myocyte HL-1 cells, after cultured for 24 h, 12.5, 25 and 50 μg/L TNF-αsignificantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner .The peak current was reduced by the application of 12.5 or 25μg/L TNF-αin a concentration-dependent manner [from ( -15.08 ±1.11) pA/pF in controls to ( -11.89 ±0.83) pA/pF and (-8.54 ±1.55) pA/pF in 12.5 and 25 μg/L TNF-αgroups, respectively].TNF-αapplication also inhibited voltage-dependent inactivation of ICa,T shifted the inactivation curve to the left .CONCLUSION:These results suggest that TNF-αis involved in the path-ogenesis of AF, probably via decreasing ICa,T function in atrium-derived myocytes through impaired channel function and down -regula-tion of channel protein expression .This pathway thus represents a potential pathogenic mechanism in AF .