ObjectiveTo dynamically observe and evaluate the damage to the pulmonary air-blood barrier in mice during the inflammatory cancer transformation process of ulcerative colitis （UC） based on the "lung-intestine correlation" theory. MethodsSixty-five C57BL/6 mice were divided into a normal group （n=25） and a model group （n=40） using a random number table. Azoxymethane/dextran sodium sulfate （DSS） method was used to establish a mouse model of UC inflammation cancer transformation in the modeling group. According to the tissue collection time points at 5， 8， 11， 13， and 15 weeks， the normal group mice were randomly divided into the normal 5w， 8w， 11w， 13w， and 15w groups. The model group mice， 10 mice of which died after the first cycle of DSS administration， were randomly divided into model 5w， 8w， 11w， 13w， and 15w groups. During the experiment， the general condition of the mice was observed daily， and their body weight was measured weekly. At the corresponding tissue collection time points， the colon length of each group was measured. Histopathology of mouse lung and colon tissues was examined using HE staining. Immunofluorescence was used to detect changes in the positive expression of tight junction protein （ZO-1）， vascular endothelial cadherin （VE-cadherin）， and cytoskeletal protein （F-actin） in lung and colon tissues. RT-PCR was used to detect the mRNA expression of apoptosis regulatory proteins B-cell lymphoma-2 （Bcl-2）， BCL2-associated X protein （Bax）， and Cysteine aspartic acid protease-3 （Caspase-3） in lung tissues. Western Blot was employed to measure protein levels of ZO-1， VE-cadherin， and F-actin in lung tissues. ResultsCompared to the normal group at the same time point， the mice in the model group at each time point generally had poorer conditions， with weight loss and shortened colon length （P＜0.05 or P＜0.01）. In the model 5w group， there was significant inflammatory cell infiltration in the colon tissue； in the model 8w group， there was mild atypical hyperplasia； in the model 11w group， the crypt structure was disordered， and moderate to severe atypical hyperplasia occurred； in the model 13w and 15w groups， tumors appeared. Pulmonary interstitial lesions， inflammation， vasculitis， and fibrosis were observed at all stages of UC inflammation cancer transformation. The protein levels of ZO-1， VE-cadherin， and F-actin， as well as Bcl-2 mRNA expression in lung tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period， while the expressions of Bax and Caspase-3 mRNA increased； the expressions of ZO-1， VE-cadherin， and F-actin proteins in colon tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period （P＜0.01 or P＜0.05）. Compared to the model 5w group， the ZO-1 and F-actin protein levels and Bcl-2 mRNA expression in lung tissue in the other model groups increased in the atypical hyperplasia period and canceration period， while the expressions of Bax and Caspase-3 mRNA decreased； the expression of ZO-1 protein in colon tissue increased in the canceration period， and the expression of VE-cadherin protein decreased in the atypical hyperplasia period （P＜0.01 or P＜0.05）. ConclusionIn the process of "inflammatory response-atypical hyperplasia-carcinogenesis" in UC inflammatory cancer transformation mice， there were damage to air-blood barrier.

OBJECTIVE To establish population pharmacokinetic model of levetiracetam （Lev） for Chinese patients with post- stroke epilepsy （PSE）， and provide reference for formulating individualized dosing regimens for Lev therapy in this specific population. METHODS Blood concentration data and clinical diagnosis and treatment information of PSE patients meeting the inclusion criteria were retrospectively collected and divided into model group and validation group at an 8∶2 ratio using a random number method. Based on the model group data， a population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Internal evaluation was performed through goodness-of-fit tests and bootstrap analysis， while external validation was conducted using the validation group data. RESULTS A total of 75 blood concentration measurements from 70 PSE patients were collected， with 60 measurements from 55 patients used for model development and 15 measurements from 15 patients reserved for external validation. The final model estimated a population typical value of clearance at 2.98 L/h. Estimated glomerular filtration rate， daily dose， and homocysteine level significantly influenced clearance of Lev （P＜0.01）. The model demonstrated satisfactory predictive performance， as evidenced by goodness-of-fit tests， bootstrap analysis， and external validation results. CONCLUSIONS Daily dose， estimated glomerular filtration rate， and homocysteine level are identified as significant covariates influencing Lev clearance in Chinese PSE patients. When making clinical decisions， comprehensive consideration should be given to the patient’s treatment response， physiological and pathological conditions， and the occurrence of adverse reactions， etc. The dosage of Lev should be adjusted based on the results of population pharmacokinetic model.

Objective Based on the assumption of spatial heterogeneity,the distribution pattern and risk characteristics of health poverty in middle-aged and elderly people with chronic diseases are described from the perspective of spatial differentiation.In order to providing a theoretical basis for the optimization of subsequent poverty reduction policies and a model policy for other countries.Methods It used factor detector and interaction detector to capture the role of single-factor and multi-factor interactions on the spatial differentiation of health poverty,and risk detectors were utilized to explore the high-risk factors in risky areas Results The single factor explanation of medical assistance and health education activities is prominent,and the factors such as PM2.5,old-age dependency ratio and urban unemployment rate have strong interaction.Furthermore,it identified high-risk factor characteristics in areas at high risk of health poverty.Conclusion The spatial differentiation pattern of health poverty among the middle-aged and elderly chronic disease population in China is the result of the synergistic driving effect of multidimensional factors,and there is variability in the risk characteristics among regions.The government should establish a contextual optimization strategy and pay attention to the joint effect of multiple factors to establish a synergistic management system.

Objective:To investigate the influence of prealbumin on cerebral infarction severity, hemorrhage transformation and 1-year prognosis.Methods:A retrospective study was conducted to select 752 patients with cerebral infarction who were treated in Beijing Tiantan Hospital,Capital Medical University from December 2018 to December 2019 as the study objects. Personal information and laboratory indicators of the patients were collected including prealbumin, hemoglobin, white blood cell count, etc.Patients were divided into group B1 (<238 mg/L) and group B2 (≥238 mg/L) based on median prealbumin. By inquiry patient's case, NIHSS score (<16 was classified as mild, ≥16 as moderate and severe)and cerebral infarction volume (<20 cm 3 as small infarct, >20 cm 3 as large infarct) were recorded to evaluate the severity of the disease, and whether hemorrhage transformation occurred during hospitalization was recorded. Patients were followed up 1 year after discharge, and prognostic information of patients was recorded, including neurological function recovery (mRS score <3 was classified as good recovery, ≥3 as poor recovery),all-cause case fatality rate, and recurrence of cardio-cerebrovascular events. Normally distributed measurement data were expressed as xˉ±s, non-normally distributed measurement data were expressed as median and quartiles[ M( Q1, Q3)], categorical variable were expressed as ratio and percent(%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. Chi-square test were used on comparison between groups of categorical variable. Single-factor comparison, Spearman correlation analysis and multiple Logistic regression were used to analyze the correlation between prealbumin and other laboratory indicators, cerebral infarction severity, hemorrhage transformation and 1-year prognosis, respectively. Results:The NIHSS score and infarct volume of patients in group B1 were 5(2,10) and 3.18(0.72,18.00) cm 3, and those in group B2 were 3(2,7) and 2.0(0.5,10.0) cm 3, respectively, which were higher in group B1 than in group B2, the differences were statistically significant ( Z=3.85, P<0.001, Z=2.81, P=0.005). The proportion of mRS Score ≥3 in group B1 was 28.8%(107/371), and the all-cause case fatality rate was 7.5%(28/371), both higher than 20.5%(78/381) and 3.1%(12/381) in group B2, with statistical significance ( χ2=7.10, P=0.008, χ2=7.22, P=0.007). Hemorrhage transformation and recurrence of cardio-cerebrovascular events were 13.5%(50/371) and 11.6%(43/371) in group B1 and 9.2% (35/381) and 8.7%(33/381) in group B2, respectively, with no significant difference between the two groups ( χ2=3.45, P=0.063, χ2=1.78, P=0.183). Multivariate logistic regression analysis showed that, after adjusted for potential confounding factors, prealbumin was protective factor of NIHSS ( OR and 95% CI: 0.990(0.984-0.997), P=0.035), poor neurological recovery(mRS≥3) ( OR and 95% CI:0.992(0.988-0.997), P<0.001) and all-cause case fatality rate ( OR and 95% CI:0.991(0.983-0.999), while prealbumin had no significant influence on cardiocerebrovascular recurrence events ( OR and 95% CI: 0.999(0.993-1.005), P=0.729). Conclusion:Prealbumin is significantly associated with the severity of cerebral infarction and poor prognosis 1 year after discharge, and low prealbumin was an independent risk factor for NIHSS score(≥16), poor neurological recovery (mRS≥3) and all-cause case fatality rate.

Objectives:To explore the effects of infarct volume, infarct type, inflammation, and coagulation indicators on hemorrhagic transformation in patients with acute cerebral infarction.Methods:711 patients with cerebral infarction admitted to Beijing Tiantan Hospital were retrospectively included as the study objects from December 2018 to December 2019 [535 males and 176 females, age 22-95 years, mean age (59.6±12.1) years]. Clinical data, laboratory indicators such as inflammation and coagulation function of patients were collected, and information such as location, volume and type of infarction were recorded. The patients were divided into hemorrhage transformation group and non-hemorrhage transformation group according to whether hemorrhage transformation occurred during hospitalization. Normally distributed measurement data were expressed as xˉ± s, non-normally distributed measurement data were expressed as median and quartiles [ M( Q1, Q3)], categorical variable were expressed as ratio and percent (%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. χ2 test were used on comparison between groups of categorical variable. Univariate comparison and multivariate Logistic regression were used to analyze the correlation between hemorrhage transformation and infarct volume, infarction type and laboratory indicators, respectively, to explore the risk factors of hemorrhage transformation. ROC curve analysis was used to evaluate the diagnostic value of indicators. Results:The rates of coronary heart disease and atrial fibrillation history in the hemorrhage transformation group were 23.5% (20/85) and 22.4% (19/85), respectively, which were significantly higher than those in the non-hemorrhage transformation group (13.9% (87/626) and 5.8% (36/626), respectively), and the difference between the two groups was statistically significant ( χ2=5.43, χ2=28.90, P=0.020, P<0.001, respectively). The NIHSS score [10(4,17) points] and infarct volume [46.50 (14.21,118.42) mL] in the hemorrhage transformation group were significantly higher than those in the non-hemorrhage transformation group [4(2,7) points, 2.00(0.51,8.94) mL]. The difference between the two groups was statistically significant ( Z values were 6.69 and 10.69, respectively, P<0.001). The results of multivariate Logistic regression analysis showed that atrial fibrillation (OR=2.604, 95% CI: 1.186-5.716, P=0.107), infarct volume (OR=1.009, 95% CI: 1.004-1.015, P=0.001), infarct type of Chinese ischemic stroke subclassfication (OR=1.371, 95% CI: 1.085-1.731, P=0.008) and neutrophil/lymphocyte ratio (OR=1.047, 95% CI: 1.006-1.090, P=0.023) were independent risk factors for hemorrhage transformation. ROC curve analysis showed that the area under curve (AUC) of infarct volume and neutrophil/lymphocyte ratio were 0.861 (0.821-0.901) and 0.684 (0.626-0.741), respectively, which were effective in predicting hemorrhage transformation after cerebral infarction. The prediction of infarct volume was more efficient. Conclusion:History of atrial fibrillation, classification of cardioembolic stroke, infarct volume, and neutrophil/lymphocyte ratio are all risk factors for hemorrhagic transformation after acute cerebral infarction.

The codon was optimized for the bovine nebovirus(BNeV)VP1 gene and the recombi-nant plasmid pFastBac-Dual-VP1 was constructed,and BNeV-VP1 virus-like particles(VLPs)were prepared using a baculovirus expression system,and identified by Western blot,indirect im-munofluorescence and electron microscopy.Successfully validated VLPs were mixed with MF59 adjuvant and CpG-ODG,and mice were immunised by intramuscular injection and evaluated for immunity effects.The results showed that the optimized CAI(codon adaptation index)of VP1 gene was 0.93 and the GC content was 60.4％.The constructed recombinant plasmid was trans-formed into DH10Bac for blue-white spot screening,and after successful verification,it was trans-fected into SF9 cells to obtain recombinant baculovirus Baculo-BNeV-VP1.BNeV virus-like parti-cles with diameters ranging from 35 to 40 nm were observed under the electron microscope,and both IFA and Western blot experiments proved that the target proteins were successfully ex-pressed and biologically active,and protein optimisation revealed that the highest protein expres-sion was found at the infectious dose MOI=0.5.Mice were immunized by intramuscular injection after 50 μg of VLPs were mixed with MF59 adjuvant and CpG-ODN.The results showed that the VLPs immunization group produced IgG antibodies 7 days after the first dose,and the antibody ti-ter increased gradually,reaching a maximum of 1∶102 400,and declined at 35 d,but still main-tained a high level;The blocking titer BT50 is up to 640,which can induce the production of BNeV VP1-specific blocking antibody in mice.In this study,the baculovirus expression system was used to express the VP1 protein of BNeV,and BNeV VLPs were successfully constructed,which could induce humoral immune response in mice,which provided a reference for the follow-up research of BNeV vaccine.

Codon optimization was performed for the M and HN genes of bovine parainfluenza virus type 3(BPIV3),and the recombinant shuttle plasmid Dual-M+HN was constructed.BPIV3 VLPs was prepared using the baculovirus expression system,and verified by Western blot,IFA and elec-tron microscopy.The successfully verified virus-like particle(VLPs)were mixed with MF59 adjuvant and CpG-ODN immunoenhancer to immunize mice by intramuscular-injection,and BPIV3 inactivated vaccine group and adjuvant control group were set up.The immune effect of BPIV3 VLPs was evaluated by monitoring mouse serum specific antibodies,neutralizing antibodies and hemagglutination inhibition antibodies.The results showed that the optimized codon adaptation in-dex(CAI)of the M and HN protein genes were 0.96 and 0.95,respectively,and the CG content reached 54.1％and 53.1％,respectively.The constructed recombinant plasmid was transformed in-to DHI0Bac for blue and white spot screening.The validated recombinant rod particles were trans-fected into Sf9 cells to obtain the rod-shaped virus pFastBac-M+HN.Under electron microscopy,BPIV3 VLPs with a diameter of approximately 180 nm were observed.IFA and Western blot ex-periments confirmed the successful expression and biological activity of the target protein.Through protein optimization,it was found that the protein expression was highest at an infection dose of MOI=5.After mixing 50 μg VLPs with MF59 adjuvant and CpG-ODN,mice were immunized by intramuscular injection.The results showed that the antibodies in the VLPs immunized group be-gan to rise at 2 weeks of the first immunization and reached their peak at 21 days of the second im-munization,with an average IgG antibody titer of 1∶40 228;The average titer of neutralizing anti-bodies is 1∶298;The titer of hemagglutination inhibition antibody is 1∶549,reaching the level of inactivated vaccine(P≥0.05),indicating that the VLPs prepared in this experiment can induce hu-moral immune response in the body.In summary,this study successfully prepared VLPs capable of self-assembly expression of BPIV3 HN and M proteins,and induced humoral immune response in mice,providing research basis for subsequent BPIV3 VLPs vaccine research.

Mitochondria are important organelles which produce the energy required to maintain cell activity.They can produce energy through oxidative phosphorylation(OXPHOS),tricarboxylic acid(TCA)cycle and other pathways,and play an essential role in cell metabolism and many physiological processes.However,mitochondrial dysfunction is associated with neurodegenerative diseases such as Alzheimer's disease(AD).Previous studies have confirmed that mitochondrial oxidative phosphorylation-related proteins,membrane transporters,fusion and fission proteins can affect mitochondrial function and participate in the pathophysiological process of AD via mechanisms such as oxidative stress injury.Therefore,this article reviews the involvement of mitochondrial proteins and its dysfunction in the pathogenesis of AD and the possibility of treating AD by regulating mitochondrial proteins and its functions.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Polycystic ovary syndrome(PCOS)is a complex disease that significantly impacts women's reproductive and metabolic health.The reprogramming of glucose metabolism points to fundamental changes in energy metabolism,which are central to the imbalance in energy metabolism,hormonal abnormalities,increasing insulin resistance,and chronic inflammatory states observed in PCOS.This represents a core pathological link in the pathogenesis of PCOS.The theory of"Spleen Qi to Dispersing Essence"provides a comprehensive overview of spleen function,essential for ensuring the normal operation of organs and the distribution of Qi,blood,and bodily fluids.It serves as a crucial theoretical support for the treatment of PCOS with traditional Chinese medicine.This article explores the role of regulating PCOS based on the theory of"Spleen Qi to Dispersing Essence"with a focus on the reprogramming of glucose metabolism.The mechanism of traditional Chinese medicinal treatments that assist Spleen Qi to Dispersing Essence is closely related to regulating glucose metabolism reprogramming,offering a novel research direction for the treatment of PCOS with TCM.