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.

AIM: To investigate variation patterns of corneal biomechanical parameters and binocular symmetry among children of different genders aged 8-16 years.METHODS:A retrospective study was conducted, and children who underwent optometric examinations at the ophthalmology department of our hospital were enrolled between January 2022 and December 2024. Measurements included the flat keratometry(K1), steep keratometry(K2), and mean curvature(Km)of the anterior corneal surface, horizontal visible iris diameter(HVID), central corneal thickness(CCT), corneal endothelial cell density(CECD), average cell size(ACS), coefficient of variation(CV), and hexagonality(HEX). Corneal parameters and binocular differences were compared between genders and across age groups.RESULTS:A total of 621 children(1 242 eyes)were enrolled in this study, including 284 males(568 eyes), 337 females(674 eyes), 528 children aged 8-12 years(1 056 eyes), and 93 children aged 13-16 years(186 eyes). In children aged 8-16 years, the K1, K2, Km and CV of both eyes, as well as the interocular CCT differences in boys were significantly lower than those in girls(all P<0.05), while the HVID and HEX of both eyes, as well as the CCT of the left eye in boys were significantly higher than those in girls(all P<0.05). Children aged 8-12 years had significantly higher K1, Km, CECD and HEX in both eyes, and significantly lower ACS in both eyes than those aged 13-16 years(all P<0.05). K1, K2, Km, CECD and HEX in both eyes were negatively correlated with age(P<0.05); ACS in both eyes was positively correlated with age(P<0.001); K1 and Km of the right eye were positively correlated with the CECD of the right eye(P<0.05), and K1 and CCT of the left eye were positively correlated with the CECD of the left eye(P<0.05).CONCLUSION:Significant gender differences exist in corneal parameters among children aged 8 to 16 years, while binocular symmetry remained stable.

OBJECTIVE: This study aimed to explore the interplay between the life-course body mass index (BMI) trajectories and insulin resistance (IR) on incident diabetes. METHODS: This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3-8 times between 1989 and 2009, as well as glucose and insulin measured in 2009. BMI trajectories were identified using a latent class growth mixed model. The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method. Logistic regression and mediation models were used to estimate the interaction and mediation effects, respectively. RESULTS: Three distinct BMI trajectory groups were identified: low-stable ( n = 1,625), medium-increasing ( n = 613), and high-increasing ( n = 98). Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant ( P < 0.05). The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity (IS) obesity group (18.9% vs. 5.8%, P < 0.001). After adjusting for covariates, the odds ratios (95% confidence intervals) of the IR, IS-obesity, and IR-obesity groups vs. the normal group were 3.22 (2.05, 5.16), 2.05 (1.00, 3.97), and 7.98 (5.19, 12.62), respectively. IR mediated 10.7% of the total effect of BMI trajectories on incident diabetes ( P < 0.001). CONCLUSION We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes. IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.
Humans ; Insulin Resistance ; Body Mass Index ; Male ; Female ; Middle Aged ; China/epidemiology* ; Adult ; Longitudinal Studies ; Incidence ; Diabetes Mellitus/epidemiology* ; Aged ; Obesity/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; East Asian People

Objective To investigate the value of cranial CT cisternal grading combined with D-dimer(D-D)and Glasgow Coma Scale(GCS)score in predicting the short-term postoperative prog-nosis of patients with severe traumatic brain injury.Methods A total of 165 patients with severe trau-matic brain injury who were treated in the hospital from January 2019 to May 2024 were selected as study subjects,all underwent craniotomy surgery.Postoperative follow-up was conducted for 3 months to analyze the differences in clinical data and preoperative indicators such as cranial CT cisternal grad-ing,D-D levels,and GCS scores between patients with poor and good prognosis.The value of cranial CT cisternal grading,D-D levels,and GCS scores in predicting short-term postoperative poor prognosis in patients with severe traumatic brain injury was also analyzed.Results Compared with patients with good prognosis,patients with poor prognosis had higher proportion of age,cranial CT cisternal grading of Ⅰ to Ⅱ,D-D levels,and GCS scores＜6(P＜0.05).There were no statistically significant differences in C-reactive protein,prothrombin time,activated partial thromboplastin time,international normalized ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol levels between patients with poor and good prognosis(P＞0.05).Cranial CT cisternal grading,D-D levels,and GCS scores were influencing factors for short-term postoperative poor prognosis in patients with severe traumatic brain injury(P＜0.05).The area under the curve for poor prognosis by three indicators in combination was 0.941(95％CI,0.906 to 0.975),which was higher than the area under the curve for the individual predictions of cranial CT cisternal grad-ing,D-D levels,and GCS scores(P＜0.05).Conclusion The influencing factors for short-term postoperative prognosis in patients with severe traumatic brain injury include cranial CT cisternal grading,D-D levels,and GCS scores.The model based on these three indicators has certain appli-cation value in predicting patient prognosis.

Objective:To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation.Methods:A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS.Results:A total of 169 patients with EGFR rare mutations were included, and the age [ M (IQR)] was 63 years (12 years); there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years; 70 (41.4%)males and 99 (58.6%) females; 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation; 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55); in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups ( χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups ( P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups ( P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation; brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024; unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions:Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.

Objective To investigate the therapeutic effect of transcutaneous auricular vagus nerve stimulation(taVNS)on overweight/obesity patients,and to explore its central mechanism.Methods Twenty-six overweight/obesity patients were randomly divided into two groups,12 cases in the taVNS test group(shortened as the taVNS group)and 14 cases in the lifestyle intervention control group(shortened as the control group).The patients in the control group were treated with online lifestyle intervention of calorie-restricted diet(CRD),and the patients in the taVNS group were treated with taVNS on the basis of the intervention for the control group.The taVNS was performed on unilateral acupoints of spleen and endocrine,twice(in the morning and at evening)per day,for five days a week.The treatment for the two groups covered four weeks.The obesity indicators such as body weight,body mass index(BMI)and waist circumference of the patients in the two groups were observed before and after treatment.Moreover,the resting-state cerebral functional magnetic resonance imaging(fMRI)data of the patients were collected after treatment,and then the regulatory effect of taVNS on the regional homogeneity(ReHo)of local cerebral area of the patients was observed.Results(1)During the trial,one case in each group dropped off,and a total of 24 patients(including 13 cases in the control group and 11 cases in the taVNS group)were finally included in the statistical analysis of the observation indicators.(2)After treatment,the body weight,BMI and waist circumference of patients in the taVNS group were decreased compared with those before treatment(P＜0.05),while the obesity indicators in the control group only showed a downward trend compared with those before treatment,the differences being not statistically significant(P＞0.05).The improvement of the obesity indicators of body weight,BMI,and waist circumference in the taVNS group was significantly superior to that in the control group,and there were statistically significant differences in the post-treatment indicators and in the pre-and post-treatment difference values of the indicators between the two groups(P＜0.05 or P＜0.01).(3)After treatment,the taVNS group had greater ReHo values in the left prefrontal lobe and medial frontal gyrus than the control group,and the control group had greater ReHo value in the right parietal lobe than the taVNS group,which indicated that compared with the control group,the ReHo of the left prefrontal lobe and medial frontal gyrus in the taVNS group was increased and the ReHo of the right parietal lobe was decreased(Pvoxel＜0.001,Pcluster＜0.05,corrected by FWE level).Conclusion As a non-invasive treatment method,taVNS exerts certain efficacy for the treatment of overweight/obesity patients.The central response mechanism for treatment of obesity is probably related with the modulation of taVNS on the functional areas of left prefrontal lobe,medial frontal gyrus,and right parietal lobe of the patients.

Purpose To investigate the clinicopathological significance and prognostic value of oral cancer overexpressed 1(ORAOV1)in esophageal squamous cell carcinoma(ESCC).Methods The mRNA expression of ORAOV1,ERK1 and ERK2 in 140 ESCC and 39 esophageal squamous intraepithelial neoplasia(ESIN)and 140 adjacent normal mucosal tissues were detected by RT-PCR.The relationship between their overexpres-sion and clinicopathological features was analyzed in ESCC pa-tients.Spearman correlation analysis was used to explore the correlation between ORAOV1 and ERK1 and ERK2.Results The expression level of ORAOV1 mRNA(13.158±2.246)with ESCC was significantly higher than that of low-grade ESIN(4.974±1.317),high-grade ESIN(7.398±1.891)and adja-cent tissues(1.000±0).The differences were significant(P＜0.01).High expression of ORAOV1 mRNA was positively cor-related with ESCC clinical stage and lymph node metastasis(all P＜0.05).Spearman analysis showed that the expression level of ORAOV1 mRNA was positively correlated with the expression levels of ERK1 mRNA and ERK2 mRNA in ESCC.Kaplan-Meier survival curve analysis showed that the overall survival of ESCC patients with high expression of ORAOV1 was significantly lower than that of patients with low expression,and the differ-ence was significant(P＜0.05).Conclusion The expression level of ORAOV1 gradually increases during the occurrence and development of ESCC,which is an independent prognostic factor of ESCC and is expected to become a new molecular target for early diagnosis and treatment of ESCC.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA