Objective To investigate the predictive role of transcranial Doppler(TCD)ultrasound combined with invasive intracranial pressure(ICP)monitoring in the early outcomes for patients with moderate-to-severe traumatic brain injury(msTBI)after ICP probe insertion surgery.Methods A retrospective case-control analysis was conducted on the clinical data of 65 msTBI patients who underwent invasive ICP probe insertion surgery within 24 h after injury and routine TCD examination postoperatively in No.904 Hospital of Joint Logistic Support Force of Chinese PLA between January 2021 and March 2025.Based on whether disease progression met the indications for craniotomy,they were divided into a failed conservative treatm ent group(n=28)and a successful conservative treatment group(n=37).Baseline clinical data,and parameters of TCD and ICP monitoring were collected in both groups.Univariate analysis was used for comparing differences in various parameters between the groups.The variables related to ICP and TCD were denoted as Model 1,and variables that significantly affected the outcome were incorporated as potential confounding factors into Model 2 based on clinical experience.Multivariate logistic regression analysis was performed to screen for independent predictors of conservative treatment failure.Receiver operating characteristic(ROC)curves were plotted to evaluate the diagnostic efficacy of each predictive factor.Results Statistical differences were observed between the 2 groups in terms of Glasgow Coma Scale(GCS)score at admission,postoperative mean intracranial pressure(ICPm),postoperative mean cerebral perfusion pressure(CPPm),and pulsatility index(PI)of the ipsilateral internal carotid artery extracranial segment(ICAt),and mean flow velocity(Vm)and pulsatility index(PI)of the ipsilateral middle cerebral artery(MCA)(all P<0.01).After adjusting for age,GCS score at admission,hematoma volum,and mean postoperative brain temperature,multivariate logistic regression analysis revealed that ICPm(OR=1.248,95%CI:1.044～1.491,P=0.015),ipsilateral MCA.Vm(OR=0.964,95%CI:0.933～0.997,P=0.034),and ipsilateral MCA.PI(OR=1.612,95%CI:1.026～2.533,P=0.038)were independent predictors of failure in conservative treatment in msTBI patients.After adjustment,ROC curve analysis demonstrated that the combined model of ipsilateral MCA.PI,ipsilateral MCA.Vm,and ICPm achieved a predictive efficacy of 0.931(95%CI:0.873～0.988),which was obviously higher than that of the single model of ICPm(0.875,95%CI:0.791～0.959).Conclusion Combined monitoring of TCD and ICP can provide a more accurate prediction of the early outcomes for msTBI patients after ICP probe insertion,providing a more effective assessment for clinical diagnosis and treatment.

ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective:To investigate the regulatory role and mechanism of synaptic vesicle protein 2A (SV2A) in apoptosis of drug-resistant epilepsy neurons.Methods:One hundred and fifty specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly numbered; 20 rats were selected as a normal control group (NC group), and the remaining 130 rats were subjected to chronic epilepsy models of lithium-pilocarpine. Phenobarbital and phenytoin sodium for 2 weeks were given to these rats after modeling; fanally, 94 rats with chronic epilepsy were divided into a drug-resistant group (phenobarbital and phenytoin sodium-resistant epilepsy [PRE] group, reduction in episodes<50%, n= 55) and a drug-sensitive group (phenobarbital and phenytoin sodium-sensitive epilepsy [PSE] group, reduction in episodes by≥50%, n=38). Rats in the PRE group were further randomly divided into 5 groups, namely a up-regulated-SV2A PRE group (UPRE group), a down-regulated-SV2A PRE group (DPRE group), a up-regulated-SV2A control group (UPRC group), a down-regulated-SV2A control group (DPRC group), and a non-transfected PRE group; different types of lentivirus were given to the first 4 groups via stereotactic brain injection. Ten days after lentiviral transfection, virus detection was performed; and 2 weeks after lentiviral transfection, occurrence of epileptic seizures was observed, and after that, rats were sacrificed and the hippocampal tissues were collected for subsequent experiments. Western blotting was used to detect the expressions of SV2A, cyclophilin A (CyPA), apoptosis-inducing factor (AIF), and superoxide dismutase 2 (SOD2) in the cell nucleus or mitochondria; coimmunoprecipitation experiment was performed to observe the interaction among SV2A, CyPA and AIF proteins; immunofluorescent co-staining was used to observe the CyPA/AIF localization; mitochondrial damage was detected by electron microscopy; ATP content in the hippocampal tissues was detected by luciferase method, 8-hydroxy-2-deoxyguanosine (8-OHDG) expression was detected by immunofluorescent staining, and neuronal apoptosis rate was calculated by double staining with neuron-specific nuclear protein (NeuN) and TUNEL. Results:(1) Confocal microscopy revealed that the hippocampal tissues in the 4 transfected groups showed green fluorescence inherent to the lentivirus, indicating successful viral infection. Compared with the UPRC group, the UPRE group had significantly reduced frequency of epileptic seizures and seizure duration ( P<0.05). (2) Western blotting showed that, in mitochondria, the UPRE group had significantly higher expressions of SV2A (0.475± 0.105 vs. 0.136±0.043), CyPA (0.473±0.041 vs. 0.175±0.047), AIF (0.443±0.058 vs. 0.131±0.037), and SOD2 (0.457±0.037 vs. 0.152±0.038) compared with the UPRC group ( P<0.05); the DPRE group had significantly decreased expressions of SV2A (0.038±0.013 vs. 0.184±0.047), CyPA (0.041±0.010 vs. 0.214±0.040), AIF (0.040±0.019 vs. 0.175±0.046), and SOD2 (0.043±0.017 vs. 0.187±0.039) compared with the DPRC group ( P<0.05). In the cell nucleus, the UPRE group had significantly lower expressions of AIF (0.336±0.084 vs. 0.649±0.209) and CyPA (0.331±0.086 vs. 0.620±0.162) compared with the UPRC group ( P<0.05); the DPRE group had statistically higher expressions of AIF (0.771± 0.180 vs. 0.519±0.144) and CyPA (0.738±0.223 vs. 0.488±0.091) compared with the DPRC group ( P< 0.05). (3) Co-immunoprecipitation experiment results showed that the bidirectional precipitation results of SV2A and AIF, SV2A and CyPA, and AIF and CyPA were all positive, suggesting existence of interactions. (4) Immunofluorescent co-staining showed that the fluorescence changes of CyPA and AIF were consistent. (5) Electron microscopy showed that mitochondria in the NC group had intact structure; mitochondria in the UPRE group, UPRC group, DPRC group and DPRE group showed swelling and cristae fragmentation; among them, injury in the UPRE group was relatively less severe than that in the UPRC group, while that in the DPRC group was more severe than that in the DPRE group. (6) Compared with the UPRC group, the UPRE group had statistically higher ATP content ( P<0.05); compared with the DPRC group, the DPRE group had significantly lower ATP content ( P<0.05).(7) Immunofluorescent staining results showed that the UPRE group had significantly lower 8-OHDG expression than the UPRC group ( P<0.05); compared with the DPRC group, the DPRE group had statistically higher 8-OHDG expression ( P<0.05). (8) The UPRE group had significantly lower NeuN-TUNEL double staining positive rate than the UPRC group ( P<0.05); compared with the DPRC group, the DPRE group had significantly higher NeuN-TUNEL double staining positive rate ( P<0.05). Conclusion:SV2A can play a role in the apoptosis of hippocampal neurons in rats with drug-resistant epilepsy by regulating the nuclear translocation of AIF/CyPA and mitochondrial damage.

Purpose To investigate the diagnostic value of immunohistochemical(IHC)and molecular markers in diffuse pleural mesothelioma(DPM).Methods A total of 114 cases of DPM were retrospectively analyzed for clinical and imaging manifestations,histologic subtype and tumor grade.The positivity rates of Calretinin,WT-1,CK5/6,MC,D2-40,UPK3B,and GATA3 were assessed by IHC,and the loss rates of BAP-1 and MTAP were determined.The concordance between MTAP IHC and p16 gene fluorescence in situ hybridization(FISH)status was calculated,a-long with the sensitivity and specificity of MTAP IHC relative to p16 FISH.Results Among the 114 DPM patients,66(57.9％)were male and 48(42.1％)were female,with a mean age of 58.1 years(range 16-85 years).Imaging predominantly demonstrated pleural effusion and multiple pleural nodules(55.3％,63/114).Histologically,epitheli-oid,sarcomatoid and biphasic subtypes accounted for 88(77.2％),17(14.9％)and 9(7.9％)cases,respectively.Within the epithelioid group,low and high-grade tumors numbered 69(78.4％)and 19(21.6％),respectively.In epithelioid DPM,the highest IHC positivity rates were observed for Calretinin(92.4％,81/88),D2-40(90.0％,79/88)and WT-1(90.0％,79/88).In sarcomatoid DPM,D2-40(76.5％,13/17),WT-1(64.7％,11/17),and Cal-retinin(29.4％,5/17)showed the greatest positivity.UPK3B was positive in epithelioid(59.1％,39/66)and bi-phasic cases(66.7％,4/6),but was absent in sarcomatoid tumors(0/12).Among all DPM cases,loss rates were 47.3％(53/112)for BAP-1 and 19.2％(20/104)for MTAP by IHC,p16 gene deletion by FISH was 31.5％(34/108);Concordance between MTAP IHC and p16 FISH was 81.0％(81/100);MTAP IHC had a specificity of 95.5％(64/67)and sensitivity of 51.5％(17/33)relative to p16 FISH.Additionally,GATA3 was highly expressed in sarco-matoid DPM(76.5％,13/17).UPK3B positivity differed significantly between thoracoscopic DPM(59.2％,32/54)and percutaneous biopsy samples(36.7％,11/30)in epithelioid DPM(P＜0.05).WT-1 positivity was higher in thoracoscopic than percutaneous samples of sarcomatoid DPM(90.0％ vs 28.6％,P=0.009).Conclusion Calreti-nin,D2-40,and WT-1 are highly sensitive mesothelial markers and should serve as first-line IHC stains in DPM diag-nosis.UPK3B is diagnostically valuable in epithelioid DPM,GATA3 may complement the diagnosis of sarcomatoid DPM,and MTAP IHC can be used as a surrogate or adjunct to p16 FISH.

Objective:To search,evaluate and integrate the best evidence of preventing fire accident in electrical surgery of domestic and international operating room,so as to provide reference for clinical practice of equipment in electrical surgery of operating room.Methods:This study conducted a literature review for domestically and internationally support systems of clinical decision,guideline websites,websites of nursing professional association,and Chinese-English databases.A series of relative literatures of fire accident in electrical surgery of operating room were included,which focused on clinical decisions,guidelines,evidence summaries,systematic evaluations,and expert consensus.The search period covered from the establishment date of database to November 12,2024,and the included literatures only limited to be English and Chinese publications.Two researchers who received evidence-based training independently evaluated the quality of these literatures,and they extracted and integrated information meeting quality standards according to professional judgment.Results:A total of 4,807 literatures were obtained after preliminary search.Then,a total of 12 research literatures were included,including 1 clinical decision,4 guidelines,1 evidence summary,3 systematic reviews and 3 expert consensus.The 20 best evidences of preventing fire accident in electrical surgery of operating room were summarized from three aspects:risk factors,risk assessment and preventive measures.Conclusion:The best evidence of preventing fire accident in electrical surgery of operating room can provide evidence-based evidences for the standardized management for electrical surgery of operation room,and provide basis for formulating management plan of preventing fire accident in electrical surgery of operation room,and for standardizing practice behavior of medical staffs.The evidence transformation should combined with actual clinical situation,and should reasonably select and prudently apply evidences.

Objective To understand the changing profiles of antimicrobial susceptibility of the bacterial strains isolated from patients at Liuzhou Workers'Hospital in Guangxi from 2020 to 2022.Methods The bacteria were isolated,identified,and underwent antimicrobial susceptibility testing using VITEK 2 Compact,disk diffusion method,or E-test.The results were interpreted according to the breakpoints recommended by CLSI M100 32nd Edition in 2022.The data were analyzed using WHONET 5.6 software.Results A total of 26 254 nonduplicate strains were collected from 2020 to 2022,including Gram-positive bacteria(27.9％)and gram-negative bacteria(72.1％).The prevalence of methicillin-resistant strains was 20.0％in SS.aureus(MRSA),and 72.2％in coagulase-negative Staphylococcus(MRCNS).Methicillin-resistant staphylococcal strains were more resistant to most antimicrobial agents than methicillin-susceptible strains(MSSA and MSCNS).None of the staphylococcal strains was resistant to vancomycin,linezolid or tigecycline.Enterococcus faecium strains showed higher resistance rates to most antimicrobial agents than Enterococcus faecalis.None of enterococcal strains was resistant to vancomycin.A few enterococcal strains were resistant to linezolid.Overall,691 strains of the non-meningitis Streptococcus pneumoniae were isolated from children and 123 strains were isolated from adults.The prevalence of penicillin-resistant SS.pneumoniae(PRSP)was 0.4％in the strains from children and 1.6％in the strains from adults.None of S.pneumoniae strains was intermediate to penicillin.The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn)was 1.2％,1.2％,and 13.8％in 2020,2021,and 2022,respectively.The prevalence of carbapenem-resistant P.aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 10.7％and 68.4％in 2020,17.5％and 75.2％in 2021,14.3％and 77.3％in 2022,respectively.About 84.6％of the 1 269 strains of Haemophilus influenzae were isolated from children and 15.4％isolated from adults.The prevalence of beta-lactamase-producing strains was 39.4％in the isolates from children and 46.8％in the isolates from adults.The β-lactamase-producing H.influenzae was resistant to ampicillin.Furthermore,some β-lactamase-nonproducing ampicillin-resistant(BLNAR)H.influenzae strains(27.0％)were also identified.Conclusions Antimicrobial resistance is still serious in this hospital,especially high prevalence of carbapenem-resistant organisms(CRO).Hospital infection prevention and control measures,antibiotic stewardship,and proactive CRO screening should be strengthened.More clinical specimens should be collected for suspected infections.Antimicrobial treatment should be prescribed empirically in time and adjusted when the results of antimicrobial susceptibility testing are available.

Objective To understand the changing profiles of antimicrobial susceptibility of the bacterial strains isolated from patients at Liuzhou Workers'Hospital in Guangxi from 2020 to 2022.Methods The bacteria were isolated,identified,and underwent antimicrobial susceptibility testing using VITEK 2 Compact,disk diffusion method,or E-test.The results were interpreted according to the breakpoints recommended by CLSI M100 32nd Edition in 2022.The data were analyzed using WHONET 5.6 software.Results A total of 26 254 nonduplicate strains were collected from 2020 to 2022,including Gram-positive bacteria(27.9％)and gram-negative bacteria(72.1％).The prevalence of methicillin-resistant strains was 20.0％in SS.aureus(MRSA),and 72.2％in coagulase-negative Staphylococcus(MRCNS).Methicillin-resistant staphylococcal strains were more resistant to most antimicrobial agents than methicillin-susceptible strains(MSSA and MSCNS).None of the staphylococcal strains was resistant to vancomycin,linezolid or tigecycline.Enterococcus faecium strains showed higher resistance rates to most antimicrobial agents than Enterococcus faecalis.None of enterococcal strains was resistant to vancomycin.A few enterococcal strains were resistant to linezolid.Overall,691 strains of the non-meningitis Streptococcus pneumoniae were isolated from children and 123 strains were isolated from adults.The prevalence of penicillin-resistant SS.pneumoniae(PRSP)was 0.4％in the strains from children and 1.6％in the strains from adults.None of S.pneumoniae strains was intermediate to penicillin.The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn)was 1.2％,1.2％,and 13.8％in 2020,2021,and 2022,respectively.The prevalence of carbapenem-resistant P.aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 10.7％and 68.4％in 2020,17.5％and 75.2％in 2021,14.3％and 77.3％in 2022,respectively.About 84.6％of the 1 269 strains of Haemophilus influenzae were isolated from children and 15.4％isolated from adults.The prevalence of beta-lactamase-producing strains was 39.4％in the isolates from children and 46.8％in the isolates from adults.The β-lactamase-producing H.influenzae was resistant to ampicillin.Furthermore,some β-lactamase-nonproducing ampicillin-resistant(BLNAR)H.influenzae strains(27.0％)were also identified.Conclusions Antimicrobial resistance is still serious in this hospital,especially high prevalence of carbapenem-resistant organisms(CRO).Hospital infection prevention and control measures,antibiotic stewardship,and proactive CRO screening should be strengthened.More clinical specimens should be collected for suspected infections.Antimicrobial treatment should be prescribed empirically in time and adjusted when the results of antimicrobial susceptibility testing are available.

Purpose To investigate the diagnostic value of immunohistochemical(IHC)and molecular markers in diffuse pleural mesothelioma(DPM).Methods A total of 114 cases of DPM were retrospectively analyzed for clinical and imaging manifestations,histologic subtype and tumor grade.The positivity rates of Calretinin,WT-1,CK5/6,MC,D2-40,UPK3B,and GATA3 were assessed by IHC,and the loss rates of BAP-1 and MTAP were determined.The concordance between MTAP IHC and p16 gene fluorescence in situ hybridization(FISH)status was calculated,a-long with the sensitivity and specificity of MTAP IHC relative to p16 FISH.Results Among the 114 DPM patients,66(57.9％)were male and 48(42.1％)were female,with a mean age of 58.1 years(range 16-85 years).Imaging predominantly demonstrated pleural effusion and multiple pleural nodules(55.3％,63/114).Histologically,epitheli-oid,sarcomatoid and biphasic subtypes accounted for 88(77.2％),17(14.9％)and 9(7.9％)cases,respectively.Within the epithelioid group,low and high-grade tumors numbered 69(78.4％)and 19(21.6％),respectively.In epithelioid DPM,the highest IHC positivity rates were observed for Calretinin(92.4％,81/88),D2-40(90.0％,79/88)and WT-1(90.0％,79/88).In sarcomatoid DPM,D2-40(76.5％,13/17),WT-1(64.7％,11/17),and Cal-retinin(29.4％,5/17)showed the greatest positivity.UPK3B was positive in epithelioid(59.1％,39/66)and bi-phasic cases(66.7％,4/6),but was absent in sarcomatoid tumors(0/12).Among all DPM cases,loss rates were 47.3％(53/112)for BAP-1 and 19.2％(20/104)for MTAP by IHC,p16 gene deletion by FISH was 31.5％(34/108);Concordance between MTAP IHC and p16 FISH was 81.0％(81/100);MTAP IHC had a specificity of 95.5％(64/67)and sensitivity of 51.5％(17/33)relative to p16 FISH.Additionally,GATA3 was highly expressed in sarco-matoid DPM(76.5％,13/17).UPK3B positivity differed significantly between thoracoscopic DPM(59.2％,32/54)and percutaneous biopsy samples(36.7％,11/30)in epithelioid DPM(P＜0.05).WT-1 positivity was higher in thoracoscopic than percutaneous samples of sarcomatoid DPM(90.0％ vs 28.6％,P=0.009).Conclusion Calreti-nin,D2-40,and WT-1 are highly sensitive mesothelial markers and should serve as first-line IHC stains in DPM diag-nosis.UPK3B is diagnostically valuable in epithelioid DPM,GATA3 may complement the diagnosis of sarcomatoid DPM,and MTAP IHC can be used as a surrogate or adjunct to p16 FISH.