AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P＜0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P＜0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P＜0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P＜0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.

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.

AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P＜0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P＜0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P＜0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P＜0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.

Objective To explore method for improving the colonization efficiency of Helicobacter pylori(Hp)in the mouse stomach and to determine if the proton pump inhibitor(PPI)pantoprazole can act as a colonization adjuvant to enhance Hp colonization,with the aim of providing an effective tool for establishing an Hp infection mouse model.Methods The Hp Sydney strain 1(SS1)was introduced and solid plate and liquid culture systems were established.The effects of different doses of pantoprazole on gastric acid secretion in mice were compared.The impact of Hp inoculation,alone or combined with pantoprazole pretreatment,on Hp colonization efficiency was analyzed using rapid urease tests,bacterial plate cultures,and TaqMan quantitative polymerase chain reaction.Results PPI pretreatment inhibited gastric acid secretion and promoted Hp colonization in the mouse stomach,to some extent.Conclusions PPI can serve as colonization adjuvants to enhanc e the efficiency of constructing Hp infection mouse models.

Objective:To evaluate the safety and efficacy of early precise lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures.Methods:A restropective multi-center study was conducted to enroll the eligible 120 patients with malleolar fracture who received the same surgical treatment from March 2023 to December 2023 at the trauma centers in 7 tertiary hospitals according to the inclusion criteria. They were assigned into a study group ( n=60) for precise lower limb weight-bearing functional rehabilitation with the assistance of intelligent lower limb walking rehabilitation crutches and a control group ( n=60) for conventional weight-bearing functional rehabilitation which was gradually increased according to their own feelings under the protection of a walking boot. All the 60 patients in the study group completed their final follow-ups. They were 25 males and 35 females, with an age of (43.8±16.6) years and a body mass index of (25.3±2.3) kg/m 2. Only 51 patients in the control group completed their final follow-ups. They were 27 males and 24 females, with an age of (45.1±16.4) years and a body mass index of (24.7±2.3) kg/m 2. When their incisions healed and their sutures were removed 2 weeks after operation, the patients were guided to start lower limb weight-bearing functional rehabilitation, and exercises for foot and ankle joint mobility and lower limb muscles. The end point of follow-up was 12 weeks after operation. The 2 groups were compared in terms of the crutch-off rates, thigh circumferences, calf circumferences, dorsiflexions, plantarflexions, ankle swellings, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, and visual analog scale (VAS) pain scores at 6 and 12 weeks after operation. The complications were also recorded in the 2 groups. Results:No statistically significant differences were observed in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). At 6 and 12 weeks after operation, the crutch-off rates [41.7% (25/60) and 100.0% (60/60)], dorsiflexions (69.3%±21.6% and 82.9%±26.3%) and AOFAS ankle-hindfoot scores [(68.5±7.6) points and (96.9±3.7) points] in the study group were significantly better than those in the control group [13.7% (7/51) and 39.2% (20/51), 61.5%±16.5% and 72.0%±14.3%, (61.9±9.3) points and (90.1±7.2) points] ( P<0.05). At 6 weeks after operation, the thigh circumference (97.4%±1.9%), calf circumference (97.3%±1.9%), and plantarflexion (76.6%±19.8%) in the study group were significantly higher than those in the control group (95.9%±2.5%, 94.6%±3.2%, and 63.9%±16.9%) ( P<0.05). There were no significant differences between the 2 groups in ankle swelling at 6 or 12 weeks after operation, or thigh or calf circumference, plantarflexion, or VAS pain score at 12 weeks after operation ( P>0.05). No wound complications, secondary fracture displacement, or loosening of internal fixation occurred in either group during the follow-up period. There were no cases of nonunion or delayed union. Conclusions:Early lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures demonstrates good safety. Precise weight-bearing rehabilitation accelerates functional recovery of the ankle, enabling earlier return to normal daily activities.

Objective To assess the effectiveness of the evaluation of military physical function(EMPF)system in predicting the occurrence of military training injuries among new recruits to provide scientific guidance and methodological choice for military training.Methods A total of 527 new recruits from 5 grassroots units from July 2016 to February 2018 were selected for the study.The recruits underwent EMPF testing,and their military training injuries were monitored over a 2-year follow-up period.Those who sustained injuries during training were divided into injury group(n=163),while the remaining recruits were placed in healthy group(n=364).The predictive ability of the total EMPF score for training injuries was assessed using the receiver operating characteristic curve(ROC),and the correlation between the total EMPF score,individual test scores,and military training injuries were analyzed using binary logistic regression.Results The total EMPF score of new recruits in injury group(19.52±1.97)was significantly lower than that of healthy group(24.31±1.54)(P<0.001),which also demonstrated a high diagnostic value in predicting the risk of military training injuries,with an area under the curve(AUC)of ROC of 0.971(P<0.001).A cut-off value of 22 scores was found to have the highest accuracy in predicting future training injuries,with an odds ratio(OR)of 25.63,sensitivity of 0.939,specificity of 0.879,positive likelihood ratio of 7.76,and a post-test probability of 0.67.Binary logistic regression analysis revealed that 6 EMPF tests,including holding the ball over and leaning back,bending forward and touching the ground with the ball,lunge squat and twist,swallow balance with holding the ball afterward,vertical jump,and respiratory pattern assessment,were negatively associated with the risk of military training injuries(P<0.0001).Conclusion The EMPF system can effectively predict the risk of military training injuries,with military personnel whose total EMPF score is less than 22 being at higher risk of sustaining such injuries.

Objective:To analyze the effects of enteral nutrition on interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),pulmonary surfactant protein A(SPA),and clinical pulmonary infection score(CPIS)in patients with hospital-acquired pneumonia(HAP)after stroke.Methods:A retrospective review was conducted of the clinical records of 90 patients with hospital-acquired pneumonia following stroke admitted to the Geriatric Medicine Department of Nanjing Brain Hospital between January 2022 and February 2023.Participants were divided into a control group and a study group based on the use of enteral nutrition,with 45 patients in each group.The control group received standard treatment(conventional stroke management combined with meropenem for infection control),while the study group received standard treatment supplemented with enteral nutrition.Within the study group,cases were classified as non-severe(n=33)and severe(n=12)based on disease severity.Peripheral blood levels of IL-6,TNF-α,and SPA,alongside the Clinical Pulmonary Infection Score(CPIS),were collected.Results:Before treatment,baseline data between the study group and control group showed no statistically significant differences,with no significant differences in IL-6,TNF-α,SPA,or CPIS scores between groups(P>0.05).Following enteral nutrition therapy,the study group exhibited significantly lower levels of IL-6,TNF-α,and SPA,as well as lower CPIS scores compared to the control group,with statistically significant differences(P<0.05).Before treatment,statistically significant differences existed between severe and non-severe cases within the study group for IL-6,TNF-α,SPA,and CPIS scores(P<0.05).After therapy,no statistically significant differences were observed between non-severe and severe patients in the study group for IL-6,TNF-α,SPA levels,or CPIS scores(P>0.05).Patients in the study group demonstrated shorter symptom resolution times,overall hospital stays,and recovery times for IL-6,TNF-α,and SPA levels compared to the control group,with all differences being statistically significant(P<0.05).Conclusion:Enteral nutrition significantly reduces peripheral blood levels of IL-6,TNF-α,and SPA in patients with post-stroke HAP,lowers CPIS scores,shortens symptom resolution time and overall hospital stay,and accelerates recovery of IL-6,TNF-α,and SPA levels.

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.