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.

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 track and evaluate the implementation and application of the occupational health standard Radiation shielding requirements for radiotherapy room—Part 4: Radiotherapy room of ²⁵²Cf neutron afterloading (GBZ/T 201.4-2015) by radiation health technical service agencies, medical institutions, health supervision agencies, and radiotherapy facility design units, and to provide a scientific basis for the further revision and implementation of this standard. Methods Following the Guideline for health standards tracking evaluation (WS/T 536-2017) and the project implementation plan, relevant practitioners were randomly selected for a questionnaire survey. The survey primarily focused on their awareness, standard training, application, and revision suggestions of GBZ/T 201.4-2015. The results were summarized and analyzed. Results A total of 168 evaluation questionnaires were collected from relevant practitioners in 28 provinces. Only 31.6% of the respondents reported being “well familiar” or “ familiar” with the standard, 27.4% of the respondents believed that the standard was widely used, and 45.2% of the respondents believed that the standard could meet the needs of their work. Only 14.9% of the respondents had received relevant training on the standard, more than half of the respondents had not applied the standard within the past 10 years, and 45.2% of the respondents believed that the standard "needs to be revised". Conclusion Due to the small number of californium-252 neutron afterloading radiotherapy devices in operation on the market, the overall awareness of the standard is low, suggesting that relevant authorities need to strengthen training and publicity of the standard, and that certain sections of the standard need to be revised or merged.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

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.

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 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 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.

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: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.