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 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.

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 analyze the risk factors associated with early recurrence after surgery for concomitant exo-tropia and establish a Nomogram prediction model.Methods A retrospective analysis was conducted on 243 cases(486 eyes)of concomitant exotropia treated in the Ophthalmology Department of our hospital from October 2015 to October 2021.The patients were divided into a training set(n=170)and a validation set(n=73)at a ratio of 7∶3.The Lasso re-gression,Boruta algorithm,and random forest algorithm were used to screen risk variables related to postoperative recur-rence of concomitant exotropia.The Spearman correlation analysis and variance inflation factor(VIF)were used to assess collinearity among variables,and a Nomogram prediction model was established using multivariate Cox regression.The re-ceiver operating characteristic curve,calibration curve,and clinical decision curve of the model at 6 months,18 months,and 24 months after surgery were used to assess the efficacy of the model.Results Three machine learning methods in-cluding Lasso regression,Boruta algorithm,and random forest algorithm identified six significant variables that might con-tribute to early recurrence after strabismus surgery from 22 risk variables in both training and validation sets.No collineari-ty was found among the six variables(r＜0.6,VIF＜5).Multivariate Cox regression revealed that strabismus type(inter-mittent exotropia),preoperative strabismus angle,best-corrected visual acuity(BCVA)in the right eye,BCVA in both eyes,and surgical procedures(unilateral lateral rectus recession)were risk factors for early recurrence after surgery for concomitant exotropia.Meanwhile,a Nomogram prediction model was constructed based on these 6 factors.The receiver operating characteristic,calibration,and clinical decision curves indicated that the prediction model had good accuracy,consistency,and clinical applicability.Conclusion Nomogram prediction model can effectively predict the risk of early recurrence after surgery for concomitant exotropia,and provides a reference for ophthalmologists to intervene early in pa-tients.

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 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.

Objective To analyze the changing trend of the disease burden of age-related macular degeneration(AMD)in China from 1990 to 2021 and the impact of age,period,and cohort effects,and to predict the standardized prev-alence and disability-adjusted life year(DALY)rate of AMD in China from 2022 to 2035.Methods The data on the preva-lence of AMD,the number of AMD patients,DALYs,and DALY rates in China from 1990 to 2021 were obtained from the Global Burden of Disease(GBD 2021).The segmented regression model was used to analyze the trend changes in the prev-alence and DALY of patients with AMD in China,the age-period-cohort(APC)model was employed to estimate the age,period,and cohort effects related to the prevalence risk and DALY risk of AMD,and the Bayesian age-period cohort model was used to analyze the standardized prevalence and DALY rate of AMD in China from 2022 to 2035.Results Compared with 1990,the number of AMD patients and the prevalence of this disease in China in 2021 increased by 199.94％and 148.02％,respectively,and the DALYs and DALY rate increased by 183.95％and 134.80％,respectively,with the higher value of relevant indicators observed in females compared with males.From 1990 to 2021,the standardized prevalence of AMD in China showed an increasing trend,with the average annual percentage change(AAPC)being 0.17％.In contrast,the standardized DALY rate of AMD showed a decreasing trend,with the AAPC being-0.03％.The results of the age-peri-od-cohort model showed that the longitudinal age curves for both the prevalence and DALY rate of AMD in China showed an increasing and then decreasing trend,peaking at 85-89 years of age.Over time,the prevalence risk of AMD increased and then decreased,while the DALY risk continued to decline.The birth cohort analysis results showed that the overall fluctua-tion of the AMD prevalence risk cohort effect in China was small,with a decline first and then a fluctuating increase.Mean-while,the DALY risk gradually decreased as the birth cohort moved backward.It can be predicted that both the standard-ized prevalence and the standardized DALY rate of AMD may present an upward trend in China from 2022 to 2035.Conclu-sion From 1990 to 2021,the standardized prevalence of AMD in China displays an upward trend,while its standardized DALY rate exhibits a downward trend.Notably,the disease burden is more pronounced in the female population compared with the male population.With the continued aging of the population,it can be predicted that both the standardized preva-lence and DALY rate of AMD will escalate from 2022 to 2035.This finding underscores the need for targeted interventions,particularly for elderly women.Meanwhile,it is necessary to enhance health education for the whole population and formu-late effective public health policies to alleviate the disease burden associated with AMD in China.