OBJECTIVE To systematically evaluate the influential factors for all-cause mortality in patients with carbapenem-resistant Gram-negative bacteria （CR-GNB） treated with polymyxin B. METHODS PubMed， Embase， the Cochrane Library， Web of Science， Wanfang Data， VIP， CBM and CNKI were searched to collect clinical studies on all-cause death within 30 days or 28 days after treatment with polymyxin B in patients with CR-GNB infection from database establishment to July 2025. After literature screening， data extraction and evaluation of literature quality， meta-analysis was performed using RevMan 5.4 software. RESULTS A total of 12 studies were included， involving 1 326 patients， among whom 529 patients died， with a mortality rate of 39.89%. Meta-analysis results showed that combined with cardiovascular disease [OR＝2.06， 95%CI （1.37， 3.09）， P ＝0.005 ] ， increased Sequential Organ Failure Assessment （SOFA） score [OR＝1.20， 95%CI （1.07， 1.35）， P ＝0.003 ] ， mechanical ventilation [OR＝2.35， 95%CI （1.65， 3.34）， P ＜0.001 ] ， continuous renal replacement therapy （CRRT） [OR＝2.58， 95%CI （1.67， 3.97）， P ＜0.001 ] ， bloodstream infection [OR＝3.24， 95%CI （2.19， 4.78）， P ＜0.001 ] ， multiple-site infection [OR＝1.51， 95%CI （1.03， 2.20）， P ＝0.03 ] ， septic shock [OR＝3.19， 95%CI （1.94， 5.24）， P ＜0.001 ] ， use of vasoactive drugs [OR＝2.90， 95%CI （1.97， 4.27）， P ＜0.001 ] ， and the occurrence of acute kidney injury （AKI） [OR＝2.17， 95%CI （1.41， 3.36）， P ＜0.001 ] were risk factors for all-cause mortality in patients with CR-GNB infection treated with polymyxin B. Conversely， an extended duration of polymy xin B treatment [OR＝0.92， 95%CI （0.86， 0.99）， P ＝0.03 ] and early administration after CR-GNB infection [OR＝0.47， 95%CI （0.25， 0.85）， P ＝0.01 ] were protective factors. CONCLUSIONS Patients with cardiovascular disease， receiving mechanical ventilation or CRRT， having bloodstream infection， multiple-site infection or septic shock， combining with vasoactive drugs， with AKI and increased SOFA scores have a higher risk of all-cause mortality. Conversely， extending the duration of polymyxin B treatment （beyond 7 days） and early administration within 48 hours after confirmed CR-GNB infection can significantly reduce the risk of all-cause mortality.

Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

Cervical cancer (CC) is the fourth leading cause of cancer-related deaths among women worldwide in 2022, and conventional treatment modalities offer limited efficacy for patients with advanced or recurrent disease. Natural killer (NK) cells are a subset of lymphocytes capable of non-specifically eliminating tumor cells and virus-infected cells without prior sensitization, and have emerged as a research focus in the field of cancer immunotherapy. However, the systematic elucidation and in-depth analysis are required in the dual regulatory mechanisms of NK cells within the cervical cancer microenvironment and the bottlenecks hindering their clinical translation. This article reviews the application of NK cell-based immunotherapy in CC, summarizes the mechanisms of action and therapeutic advances of NK cells in CC, identifies the major obstacles to current clinical translation, and proposes corresponding solutions.

Objective To investigate the effects of high-altitude hypoxic environment on the pharmacokinetic characteristics and brain tissue distribution of phenytoin sodium in epileptic rats.Methods A total of 70 male SPF-grade Wistar rats aged 2 months and weighing(200±20)g were used in the study.An epilepsy model was induced in the rats using the lithium chloride-pilocarpine method.The successfully modeled rats were randomly assigned to a normoxic treatment group and a high-altitude hypoxic treatment group.Phenytoin sodium was administered via intragastric gavage at a dose of 50 mg/kg in both groups.Blood samples were collected from the orbital venous plexus before treatment and 0.5,1,2,3,4,6,8,10,and 24 h post treatment.The animals were euthanized after the final blood collection,and samples of the liver and the whole brain tissue were collected.In the brain tissue distribution experiment,brain tissue samples were collected at 0.5,1,2,and 4 h after drug administration.The concentration of phenytoin sodium in rat plasma and brain tissue was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the pharmacokinetic parameters were calculated using WinNolin 8.1 software.The expression levels of CYP2C9 in liver tissue and those of P-gp in brain tissue of epileptic rats were determined by Western blot.Results Compared with those in the normoxia group,the peak concentration,peak time,and half-life of phenytoin sodium in the high-altitude hypoxia group were significantly decreased by 46.0%,42.3%,and 55.5%,respectively(all P<0.05);the clearance rate was significantly increased by 162.0%(P<0.05);and the area under the curve of plasma concentration-time curve was decreased by 45.6%(P<0.01).At 0.5,1,and 2 hours after administration,compared with that in the normoxia treatment group,the concentration of phenytoin sodium in the brain tissue of the high-altitude hypoxia treatment group was significantly decreased by 78.1%,63.5%,and 32.5%,respectively(all P<0.05).Western blot results showed that the expression levels of CYP2C9 in the liver tissue and P-gp in the brain tissue of rats in the high-altitude hypoxia group were approximately 1.78 and 1.65 times higher than those in the normoxia group,respectively(both P<0.05).Conclusion The hypoxic environment at high altitudes can promote the metabolism of phenytoin sodium,reduce its absorption efficiency,and change the characteristics its distribution in the brain,which may be related to the up-regulation of the expression of CYP2C9 in the liver and that of P-gp in the brain.

Objective To investigate the effects of physical activity and disease burden on self-ef-ficacy and quality of life in patients with inflammatory bowel disease(IBD).Methods A total of 312 IBD patients were selected by convenience sampling method.General information of patients was col-lected.Self-efficacy[Chronic Disease Management Self-Efficacy Scale(CDM-SES)],physical activi-ty[International Physical Activity Questionnaire-Short Form(IPAQ-SF)],disease burden[Inflamma-tory Bowel Diseases Disk(IBD-disk)Scale]and quality of life[Inflammatory Bowel Disease Ques-tionnaire(IBDQ)]were assessed in IBD patients.The chain-mediating effects of physical activity and disease burden on self-efficacy and quality of life in IBD patients were analyzed.Results There were statistically significant differences in self-efficacy of IBD patients with different ages,body mass index(BMI),places of residence,marital status,educational background and disease stages(P＜0.05);there were statistically significant differences in physical activity among IBD patients with different gen-der,age,place of residence,marital status,education background,disease stage and whether to use biological agents(P＜0.05);there were statistically significant differences in the disease burden of IBD patients with different BMI,place of residence,marital status,education background,payment method and disease stage(P＜0.05);there were statistically significant differences in the quality of life of IBD patients with different ages,places of residence,marital status,education levels,pay-ment methods,disease stages and whether to use biological agents(P＜0.05).The quality of life of IBD patients was positively correlated with self-efficacy and physical activity(r=0.605,0.482,P＜0.01),and negatively correlated with disease burden and disease stage(r=-0.550,-0.362,P＜0.01).Physical activity and disease burden partially mediated between self-efficacy and quality of life in IBD patients.Conclusion IBD patients exhibited moderate levels of self-effi-cacy,low levels of physical activity,and high disease burdens.Clinical healthcare professionals should actively take measures to improve patients'self-efficacy and physical activity levels to reduce disease burden.

Objective:The minimal ablative margin (MAM) after radiofrequency ablation (RFA) was evaluated based on magnetic resonance imaging (MRI) image registration to analyze its effect on the prognosis of patients with hepatocellular carcinoma (HCC).Methods:Clinical data of 120 patients with HCC undergoing RFA in the General Hospital of Ningxia Medical University from January 2017 to April 2022 were retrospectively analyzed, including 88 males and 32 females, aged (58.4±8.5) years. The enhanced MRI images of patients before and after treatment were imported into a 3D Slicer software to show the ablative margin, and patients were divided into two groups according to whether MAM exceeded the peritumor safety boundary of 5 mm: MAM<5 mm group ( n=75) and MAM≥5 mm group ( n=45). Clinical data were recorded such as gender, age, tumor length and location. Patients were followed up by outpatient review to record whether local tumour progression occurred. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Cox regression analysis was performed to analyze the risk factors of local tumour progression after RFA in patients with HCC. Results:There were significant differen-ces in tumor volume, whether the tumor is located around the vessels, and the mode of RFA guidance between the two groups (all P<0.05). The cumulative local tumour progression-free survival rates at 6, 12 and 24 months after RFA were 100%, 100% and 98% in MAM ≥5 mm group, superior to those in MAM<5 mm group (92%, 84% and 69%, respectively, χ2=47.22, P<0.001). Multivariate Cox regression analysis showed that MAM<5 mm ( OR=9.992, 95% CI: 4.358-22.913), tumor diameter ≥2 cm ( OR=1.758, 95% CI: 1.025-3.015) and perivascular tumor ( OR=2.344, 95% CI: 1.379-3.985) were risk factors for local tumour progression after RFA in patients with HCC (all P<0.05). Conclusion:The MAM evaluated based on MRI image registration is an influential factor on prognosis of patients with HCC. Patients with MAM<5 mm suffer an increased risk of postoperative local tumour progression.

Objective:To construct a prediction model for local tumor progression (LTP) in patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) based on the radiomics features of enhanced MRI.Methods:Clinical data of 120 patients with HCC undergoing RFA in the General Hospital of Ningxia Medical University from June 2017 to June 2022 were retrospectively analyzed, including 90 males and 30 females, aged (58.2±8.2) years. The patients were divided into training set ( n=84) and validation set ( n=36) in a ratio of 7∶3. According to whether LTP occurred within 2 years after RFA, the patients in training set were divided into LTP positive group ( n=32) and LTP negative group ( n=52). Logistic regression analysis was performed to analyze the risk factors for LTP after RFA in patients with HCC in training set. In the advanced arterial phase of preoperative enhanced MRI, the region of interest of tumor and peritumoral 5 mm area were mapped, and the radiomics features were extracted. The maximum correlation-minimum redundancy algorithm, the minimum absolute value shrinkage and selection operator algorithm were used to screen the radiomics features closely related to LTP, and the radiomics score was established. A nomogram model was constructed by combining the radiomics score with clinical tumor characteristics. The predictive performance and clinical practical value of different models were compared by the area under the receiver operating characteristic curve, calibration curve, clinical decision curve analysis (DCA) and clinical impact curve (CIC). Results:Tumor located around the blood vessels ( OR=4.574, 95% CI: 1.454-14.393, P=0.009) and ablation margin <5 mm ( OR=5.724, 95% CI: 1.996-16.420, P=0.001) were independent risk factors for LTP in patients with HCC after RFA. Five higher-order radiomics features were extracted and screened, including three tumoral features (glrlm_ShortRunHighGrayLevelEmphasis, ngtdm_Complexity and glcm_Imc1) and two peritumoral features (firstorder_Mean and glszm_SmallAreaHighGrayLevelEmphasis). Delong test showed that the area under curve of the combined model was higher than that of the radiomics model ( Z=2.90, P=0.004) and the clinical tumor characteristic model ( Z=2.56, P=0.010). Calibration curves, DCA and CIC curves all show that the combined model had a better clinical net benefit. Conclusion:Combining the radiomics features extracted from enhanced MRI images with clinical tumor characteristics can effectively predict the risk of LTP in patients with HCC after RFA.

OBJECTIVE To analyze the pathogenic characteristics and clinical features of patients with invasive pul-monary aspergillosis(IPA)and summarize the risk factors for poor prognosis.METHODS The clinical data of 89 patients diagnosed with IPA based on microbial identification of Aspergillus from sputum or bronchoalveolar lav-age fluid cultures and diagnostic criteria,who were admitted to Zhongda Hospital Southeast University from Aug.2022 to Jul.2024 and were queried by electronic case system,were analyzed retrospectively.The distribu-tion of Aspergillus pathogens and clinical features of patients with IPA were analyzed,and the risk factors for poor prognosis were summarized.RESULTS A total of 107 Aspergillus strains were isolated from 89 cases,including 55 strains of Aspergillus fumigatus(51.40％),30 strains of Aspergillus flavus(28.04％)and 10 strains of As-pergillus niger(9.34％).There were 63 m ale patients(70.79％),and 34 cases had poor prognosis.Baseline pe-ripheral blood lymphocyte count(＜0.645×109)(OR=6.653,95％CI:2.013-21.990,P=0.002)and ICU admission(OR=8.303,95％CI:1.283-53.741,P=0.026)were identified as risk factors for poor prognosis in patients with IPA.Receiver operating characteristic curve analysis showed that the cut-off point for baseline pe-ripheral blood lymphocyte count in predicting prognosis in patients with IPA was 0.645 ×109/L,with a sensitivity of 85.22％and a specificity of 69.67％.CONCLUSIONS Baseline peripheral blood lymphocyte count and ICU ad-mission are risk factors for poor prognosis in patients with IPA.The alert value for baseline peripheral blood lym-phocyte count is 0.645 × 109/L,which has good predictive value for the occurrence of poor prognosis.

Objective To establish a technical system for allogeneic kidney transplantation surgery in pigs using the Banna miniature pig inbred strain,and to evaluate it through routine blood tests,liver and kidney function tests,thus providing reference data for the preparation of allogeneic kidney transplantation models.Methods A total of 4 cases of allogeneic kidney transplantation surgeries were performed,including 1 case of single kidney transplantation in a healthy pig,2 cases of kidney transplantation after unilateral nephrectomy,and 1 case of kidney transplantation after bilateral nephrectomy.Before kidney transplantation,cross-matching and complement-dependent cytotoxicity(CDC)tests were used for matching between donor and recipient pigs.After kidney transplantation,peripheral blood samples were regularly collected from pigs for routine blood tests,liver function tests,and kidney function tests,and color Doppler ultrasound technology was used to detect blood supply to the transplanted kidneys.After reaching the experimental endpoint,both kidneys of pig DR1 and the left kidney of pig DR3 were collected and hematoxylin-eosin(HE)staining was performed to evaluate pathological changes in the transplanted kidneys.Results Recipient pigs DR1 and DR3 died at 17 days and 30 days after surgery respectively,while recipient pigs R and DR2 remained in good condition during the 30-day observation period.The results of liver and kidney function test showed that in pig DR1,alanine aminotransferase(ALT)levels increased on postoperative day 1(＞1 000 U/L),peaked on postoperative day 7(1 300 U/L),and aspartate aminotransferase(AST)levels peaked on postoperative day 1(＞3 000 U/L).On postoperative day 17,ALT and AST levels remained high(ALT,500 U/L;AST,700 U/L).In pigs R,DR2,and DR3,ALT and AST levels returned to normal around day 17.Serum creatinine(Crea)levels in pig R remained stable without postoperative increase.Crea levels in pigs DR1 and DR2 showed transient elevation on postoperative day 1,then gradually returned to normal(＜100 μmol/L).Crea levels in pig DR3 remained below 500 μmol/L from postoperative days 2-10,but increased between days 11-28,reaching up to 1 500 μmol/L,indicating gradual loss of kidney function.Ultrasound results showed that the preoperative resistive index(RI)of recipient pig R was 0.91.On postoperative day 24,renal cortex and medulla showed abundant blood flow signals with RI value of 0.88,which was close to the pre-transplantation RI value.For pig DR2,the RI value on postoperative day 17 was 0.89,with poor renal cortex blood flow and relatively good renal medulla blood flow.In pig DR1 on postoperative day 17,no blood flow signals were detected in the transplanted kidney.HE staining results showed that the non-transplanted healthy right kidney of pig DR1 had normal structure,while the transplanted left kidney showed blurred glomerular structure and nuclear dissolution,indicating that the left kidney had lost function before removal.In the transplanted left kidney of pig DR3,large numbers of red blood cells and lymphocyte infiltration were observed in glomeruli and renal tubules,indicating possible coagulation dysfunction and rejection reactions after kidney transplantation.Conclusion Banna miniature pig inbred strain is used as experimental animals to perform four cases of allogeneic pig-to-pig kidney transplantation.The physiological parameters of the recipient pig and the function of the transplanted kidney are monitored after surgery using routine blood tests,liver and kidney function tests,color Doppler ultrasound,and pathological examinations.The allogeneic pig-to-pig kidney transplantation technical system established in the study can provide a foundation for clinicians to conduct kidney transplantation surgeries.

BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.