PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

OBJECTIVE: To understand clinical and laboratory characteristics of acute myeloid leukemia, myelodysplasia-related (AML-MR). METHODS: Blood sample of one patient with AML-MR admitted to our hospital in September 2021 was collected and synthetically analyzed by using techniques including complete blood cell count, peripheral blood and bone marrow cell morphology, bone marrow pathology and immunohistochemistry, hematology examination, flow cytometry (FCM), chromosome karyotype analysis and molecular pathology. The clinical and laboratory characteristics of AML-MR were analyzed and summarized according to the World Health Organization (WHO) standards. RESULTS: The patient showed pancytopenia and increased proportion of blasts in smear of peripheral blood cells. Bone marrow cytology and pathological examination showed significant proliferation of hematopoietic cells. Pathological immunohistochemistry showed increased expression of CD61, CD34, and CD117, while MPO, CD13, and CD33 were positive. FCM showed that abnormal myeloid progenitor cells accounted for approximately 18.61% of the total number of nuclear cells, with expression of CD34, CD13, CD117, HLA-DR, and CD33 (small amount). Additionally, 36.34% of the cells were primitive/immature red blood cells which expressed CD36, CD71, and CD117 (small amount). Chromosome karyotype analysis and molecular pathology detected three kinds of abnormalities including -5 and two kinds of TP53 related gene mutation, respectively. CONCLUSION AML-MR patient shows pancytopenia and increased proportion of blasts in smear of peripheral blood cells. Bone marrow cytology and pathological examination show significant proliferation of hematopoietic cells. FCM can detect myeloid progenitor cells and primitive/immature red blood cells, while chromosome karyotype analysis can detect three abnormal karyotypes.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Myelodysplastic Syndromes ; Flow Cytometry ; Karyotyping ; Male ; Middle Aged ; Mutation

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate how dietary supplementation with tetrahydrocurcumin(THC)improves kidney injury in type 2 dia-betic mellitus(T2DM)and its mechanism of action using transcriptome sequencing(RNA-seq).Methods C57BL/6J mice were randomly assigned to the control,T2DM,and T2DM+THC groups.After a high-fat meal and streptozotocin injection,the body weights and fasting blood glucose levels of each mouse with T2DM were measured.Hematoxylin and eosin staining,Oil red O staining,and RNA-seq were performed to examine kidney pathology,lipid deposition,and differentially expressed genes,respectively,in the mice.Results Mice in T2DM group exhibited significantly higher fasting blood glucose levels(P＜0.001),renal tubule degeneration,glomeruli enlargement,disordered epithelial cells,and increased kidney lipid deposition after 12 weeks compared with those of the control group.THC adminis-tration alleviated all these conditions(P＜0.001).RNA-seq analysis revealed significant gene expression variations among the control,T2DM,and T2DM+THC groups.THC may protect against T2DM-induced kidney injury and lipid deposition by regulating the cell cycle(apoptosis),P53 signaling pathway,and PPARγ signaling path way,as indicated by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In mice with T2DM,THC intervention may upregulate the expression of Cd36,Lpl,PPARγ,and Plin4 genes in renal tissues,while downregulating Ccnb1,Ccnb2,Cdk1,Bub1,and Cdc25c gene expressions.The proteins encoded by the four upregulated genes interact,as do those encoded by the five downregulated genes.Conclusion THC administration improves fasting blood glucose levels,reduces renal damage,and decreases fat deposition in mice with T2DM.The processes may involve decreasing apoptosis,blocking the P53 signaling pathway,and activating the PPARγ signaling pathway.

Objective:To build an evaluation index system for Huimin Insurance and provide reference for promoting the steady and sustainable development of Huimin Insurance.Methods:The evaluation indicators were initially constructed through literature analysis method and further revised and improved.The entropy weight TOPSIS method was used to evaluate and analyze 84 Huimin Insurance products with complete evaluation indicator data in 21 provinces across the country.Results:The constructed evaluation index system for Huimin Insurance includes 4 first-level indicators,10 second-level indicators and 28 third-level indicators.The weights of the first-level indicators,from high to low,are the sustainability indicator of Huimin Insurance(0.335 0),the guarantee ability indicator(0.235 1),the fairness indicator of participation in insurance(0.229 9)and the guarantee level indicator(0.200 0).The evaluation results show that the top ranked products are mainly concentrated in Zhejiang and Guangdong.Conclusion:The evaluation results of the entropy weight TOPSIS method are suitable for the comprehensive evaluation of Huimin Insurance and are comprehensive and scientific.They can be used to evaluate the operation and development of Huimin Insurance products,laying a good foundation for further evaluation of the sustainability of Huimin Insurance.

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P＜0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P＜0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P＜0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P＜0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.