BACKGROUND:Spinal cord injury often leads to neurogenic bladder with hyperreflexia of the forced urethral muscle,but there is a lack of clear understanding of its pathogenesis and treatment,and establishing a stable and reliable animal model has an important impact on revealing its pathomechanisms and exploring therapeutic approaches.OBJECTIVE:To investigate the effect of the number of times to urinate on neurogenic model rats after complete spinal cord transection in order to improve the postoperative survival and modeling rate of neurogenic model rats.METHODS:Out of 46 female Sprague-Dawley rats,6 were selected as the sham-operated group using the random number table method,and the remaining 40 rats were randomly divided into 0,1,3,and 5 times daily urination groups after complete spinal cord transection modeling,with 10 rats in each group.The residual urine volume was measured every 3 days within 19 postoperative days,and the survival and modeling were observed on the 19th day after the operation,and urodynamics tests and contraction experiments of isolated forced urethra muscle strips were performed.RESULTS AND CONCLUSION:(1)Survival and modeling rate:there was 10%survival rate and 10%modeling rate in the group of 0 times daily urination;20%survival rate and 10%modeling rate in the group of 1 time daily urination;70%survival rate and 70%modeling rate in the groups of 3 and 5 times daily urination.(2)Residual urine volume:compared with the sham-operated group,the residual urine volume of the groups of 3 and 5 times daily urination was significant increased on postoperative days 3,6,9,12,and 15(P<0.01);the residual urine volume of the groups of 3 and 5 times daily urination was increased on the 18th day after surgery(P<0.05).Compared with the 3 times daily urination group,the residual urine volume was decreased in the 5 times daily urination group on the 6th day after surgery(P<0.05),while there was no significant difference in the residual urine volume between the 3 and 5 times daily urination groups on the 3rd,9th,12th,15th,and 18th days after surgery.(3)Urodynamics:Compared with the sham-operated group,the differential pressure at the point of leakage was significantly reduced(P<0.01)and the maximal volume was significantly increased(P<0.01)in the 3 and 5 times daily urination groups.There was no statistical difference in the differential pressure at the point of leakage and the maximal volume between the 3 and 5 times daily urination groups.(4)Muscle-strip contraction test of isolated detrusor muscles:Compared with the sham-operated group,the contraction amplitude and frequency of detrusor muscle strips were significantly reduced in the 3 and 5 times daily urination groups(P<0.01).There was no statistically significant difference in the contraction amplitude and frequency of detrusor muscle strips between the 3 and 5 times daily-urination groups.In conclusion,assisted urination is one of the keys to establish a successful neurogenic model of urethral reflexes,and there is no significant difference in the effects of urinating 3 or 5 times a day on the neurogenic model.It is recommended to urinate at least 3 times a day based on the actual workload and the modeling rate.

Objective:This study aimed to evaluate the value of CT-based radiomics machine learning models in predicting spread through air spaces(STAS)in lung adenocarcinoma(LUAD)and to determine the optimal peritumoral analysis region.Methods:Data from 378 pa-tients who underwent non-small cell lung cancer surgery at Zhejiang Cancer Hospital between January 2013 to January 2017 were retro-spectively analyzed.Logistic regression,random forest,and XGBoost models were constructed using regions extending 0,3,6,9,and 12 mm outward from the tumor margin.Results:The XGBoost model using the 6 mm peritumoral region performed best on the test set,with an AUC-ROC of 0.855(95%CI:0.756-0.950),followed by the XGBoost model using the 9 mm region.Decision curve analysis(DCA)indicated that the XGBoost models for the 6 mm and 9 mm regions had higher net clinical benefits.Feature analysis revealed that some wavelet trans-form features significantly contributed to STAS prediction.Conclusions:This preliminary study suggests that CT-based radiomics machine learning models have predictive value for STAS.The XGBoost model based on the 6 mm peritumoral region demonstrated the best perform-ance,and holds promise in assisting preoperative assessment.

Objective:This study aimed to evaluate the value of CT-based radiomics machine learning models in predicting spread through air spaces(STAS)in lung adenocarcinoma(LUAD)and to determine the optimal peritumoral analysis region.Methods:Data from 378 pa-tients who underwent non-small cell lung cancer surgery at Zhejiang Cancer Hospital between January 2013 to January 2017 were retro-spectively analyzed.Logistic regression,random forest,and XGBoost models were constructed using regions extending 0,3,6,9,and 12 mm outward from the tumor margin.Results:The XGBoost model using the 6 mm peritumoral region performed best on the test set,with an AUC-ROC of 0.855(95%CI:0.756-0.950),followed by the XGBoost model using the 9 mm region.Decision curve analysis(DCA)indicated that the XGBoost models for the 6 mm and 9 mm regions had higher net clinical benefits.Feature analysis revealed that some wavelet trans-form features significantly contributed to STAS prediction.Conclusions:This preliminary study suggests that CT-based radiomics machine learning models have predictive value for STAS.The XGBoost model based on the 6 mm peritumoral region demonstrated the best perform-ance,and holds promise in assisting preoperative assessment.

Objective To analyze the efficacy of arsenic-containing TCM compounds in treating high-risk myelodysplastic syndromes(HR-MDS)with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome;To provide references for the clinical treatment of HR-MDS.Methods The medical records of HR-MDS with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome treated with arsenic-containing TCM compounds in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into arsenic-containing TCM compounds combined with demethylation drugs(HMAs)treatment group and arsenic-containing TCM compounds combined with androgen treatment group.The clinical efficacy of both groups were evaluated,including overall response rate(ORR),median overall survival(OS),1-,2-and 3-year survial rates,median progression free survival(PFS),and 1-,2-and 3-year PFS rates.Results Among 200 cases of HR-MDS,68 cases were treated with arsenic-containing TCM compounds combined with HMAs,and 132 cases were treated with arsenic-containing TCM compounds combined with androgen.The ORR was 30%,and the OS of HR-MDS after treatment was 42 months.The 1-,2-and 3-year survival rates were 78.6%,60.4%and 50.2%respectively.The median PFS was 15 months,and the 1-year,2-year and 3-year PFS rates were 57.8%,28.8%and 18.2%respectively.The ORR of 68 cases HR-MDS treated with arsenic-containing TCM compounds combined with HMAs was 44.1%.After treatment,the median OS of HR-MDS was 42 months,and the survival rates of 1-,2-and 3-years were 84%,75.6%and 61.9%respectively,and the median PFS was 24 months,and the PFS rates of 1-,2-and 3-years were 74.3%,48.5%and 35.2%,respectively.The ORR of 132 cases of HR-MDS treatmented with arsenic-containing TCM compounds combined with androgen was 26.5%,including 33.3%in the high-risk group of HR-MDS and 13.3%in the extremely high-risk group of HR-MDS.There was statistical significance between the two groups(P=0.014).After treatment,the median OS of HR-MDS was 29 months,and the survival rates of 1-,2-and 3 years were 78.6%,54.1%and 45.1%respectively.The median PFS was 13 months,and the PFS rates of 1-,2-and 3 years were 54.1%,28.2%and 12.9%respectively.Conclusion The arsenic-containing TCM compounds combined with HMAs can significantly prolong survival and delay disease progression in HR-MDS.Although the arsenic-based TCM compounds combined with androgen therapy demonstrate inferior efficacy compared to HMAs-based regimens,it has achieved significantly higher OS and PFS than historical controls,serving as an effective alternative for patients intolerant to HMAs.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

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.

There are a variety of mechanical signals in the microenvironment of cells,which have temporal and spatial variability,which jointly regulate the histological processes such as cell proliferation,differentiation and migration.Piezo1 is a mechanically sensitive cationic channel.As a force sensor,it transmits signals to downstream pathways and participates in a variety of life activities in response to changes in the cell microenvironment.In this paper,the common signal pathways of Piezo1 were reviewed in order to identify the downstream signaling pathways regulated by Piezo1,thereby providing theoretical basis for inhibiting or delaying related diseases.

OBJECTIVE To investigate the regulatory effects of salvianolic acid C(SAC)on the level of cuproptosis and inflammatory injury in cardiomyocytes after myocardial infarction(MI).METHODS①C57BL/6 mice were divided into a sham group,an MI model group,and SAC(5,10 and 20 mg·kg-1)groups,with 10 mice in each group.Mice in the SAC groups were pretreated with oral gavage of SAC for 1 week,while those in the sham and model groups received an equal volume of saline.One week later,an MI model was established in the model and SAC groups by ligating the left anterior descending coronary artery,while the sham group underwent thoracotomy without ligation.MI size was assessed using triphenyltetrazolium chloride(TTC)staining.Cardiomyocyte apoptosis was evaluated by TUNEL staining.The ultrastructure of cardiomyocyte mitochondria was observed under a transmission electron microscope.② Mouse cardiomyocytes HL-1 were divided into a control group,an oxygen-glucose deprivation(OGD)model group,OGD+SAC 1,5 and 10 μmol·L-1 groups,and a OGD+SAC(5 μmol·L-1)+nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor ML385(2 μmol·L-1)group.Cells in the OGD+SAC groups were pretreated with SAC for 24 h while those in the OGD+SAC+ML385 group were pretreated with both SAC 5 μmol·L-1 and ML385 2 μmol·L-1 for 24 h.Except for the control group,an OGD model was established in HL-1 cells.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in mouse serum and HL-1 cell culture supernatants.The Cu+detection kit was used to measure Cu+levels in myocardial tissue and HL-1 cells.Cell viability was assessed using the CCK-8 kit.Apoptosis rates of HL-1 cells were detected by flow cytometry.Reactive oxygen species(ROS)levels in HL-1 cells were measured using a ROS detection kit.Western blotting analysis was performed to detect the expression levels of Nrf2,heme oxygenase-1(HO-1),and cupro-ptosis markers,ferredoxin 1(FDX1)and solute carrier family 31 member 1(SLC31A1)in myocardial tissue and HL-1 cells.RESLUTS ① Compared with the sham group,the MI model group exhibited increased myocardial infarction size,elevated cardiomyocyte apoptosis rates,mitochondrial swelling,vacuolation,and cristae rupture in cardiomyocytes,increased serum levels of TNF-α,IL-6,and IL-1β,elevated Cu+levels and expressions of FDX1 and SLC31A1 in myocardial tissue,and decreased expressions of Nrf2 and HO-1(P<0.01).Compared with the model group,the SAC 5,10 and 20 mg·kg-1 groups showed reduced MI size,decreased cardiomyocyte apoptosis rates,alleviated mitochondrial swelling,vacuola-tion,and cristae rupture,lower serum levels of TNF-α,IL-6 and IL-1β,decreased Cu+levels and expres-sions of FDX1 and SLC31A1 in myocardial tissue,and increased expressions of Nrf2 and HO-1(P<0.05,P<0.01).② Compared with the cell control group,the OGD model group demonstrated signifi-cantly decreased HL-1 cell viability,increased cell apoptosis rates,Cu+and ROS levels,expressions of FDX1 and SLC31A1,elevated levels of TNF-α,IL-6 and IL-1β in cell culture supernatants,and decreased expressions of Nrf2 and HO-1(P<0.01).Compared with the OGD model group,the SAC 1,5 and 10 μmol·L-1 groups showed increased HL-1 cell viability,decreased cell apoptosis rates,Cu+and ROS levels,expressions of FDX1 and SLC31A1,reduced levels of TNF-α,IL-6 and IL-1β in cell culture supernatants,and increased expressions of Nrf2 and HO-1(P<0.05,P<0.01).Compared with the SAC 5 μmol·L-1 group,the SAC 5 μmol·L-1+ML385 2 μmol·L-1 group exhibited decreased cell viability,increased cell apoptosis rates,Cu+and ROS levels,expressions of FDX1 and SLC31A1,elevated levels of TNF-α,IL-6,and IL-1β in cell culture supernatants,and decreased expressions of Nrf2 and HO-1(P<0.01).CONSLUSION SAC can activate the Nrf2/HO-1 signaling pathway,alleviate cuproptosis in cardiomyocytes after MI,and reduces inflammatory damage.

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.