Objective To investigate the effect and mechanism of curculigoside(CUR)on hippocampal neuron injury in epileptic rats.Methods Forty-eight rats were selected,and the epileptic rat models were established by induction with 35 mg/kg pentylenetetrazol.The epileptic rats were randomly divided into the epilepsy group,the epilepsy+low-dose CUR group(the epilepsy+CUR-L group),the epilepsy+high-dose CUR group(the epilepsy+CUR-H group),and the epilepsy+CUR-H+PI3K activator 740Y-P group(the epilepsy+CUR-H+740Y-P group),with 12 rats in each group.Another 12 rats that were intraperitoneally injected with the same amount of normal saline were taken as the control group.Four weeks after administration,the behavioral changes of rats in each group were observed.Nissl staining was applied to determine the neuronal changes in hippocampal tissue.Immunohistochemistry was applied to detect the number of microglia in hippocampal tissue.ELISA was applied to detect the levels of interleukin-6(IL-6),IL-1β,and gamma-aminobutyric acid(GABA)in hippocampal tissue.TUNEL staining was applied to analyze the level of neuronal apoptosis in hippocampal tissue.Western blot was applied to detect the phosphorylation levels of PI3K,Akt and mTOR in hippocampal tissue.Results Compared with the control group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy group were obviously increased(P<0.05),while the level of GABA in hippocampal tissue was obviously reduced(P<0.05),and the arrangement of neurons in hippocampal tissue was disordered,with neuronal loss.Compared with the epilepsy group,the Racine score,and the frequency of epileptic seizures in rats,and the number of microglia,levels of IL-6,levels of IL-1β,the apoptosis rates of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-L group and the epilepsy+CUR-H group were significantly decreased(P<0.05),while the levels of GABA in hippocampus tissue were significantly increased(P<0.05),the loss and necrosis of neurons in hippocampus tissue were decreased,and the disorder of cell arrangement was improved.Compared with the epilepsy+CUR-H group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-H+740Y-P group were significantly increased(P<0.05),while the level of GABA in hippocampus tissue was significantly decreased(P<0.05),the loss and necrosis of hippocampal neurons increased,and the cell arrangement was disordered.Conclusion CUR may reduce hippocampal neuron damage in epileptic rats by downregulating the PI3K/Akt/mTOR signaling pathway.

AIM:To investigate the therapeutic ef-fect of crocetin on diabetic lower limb ischemia and explore its underlying mechanism.METHODS:Male C57BL/6J mice aged 8 weeks were used to es-tablish a diabetic mouse model through intraperito-neal injection of streptozotocin(STZ).Following successful induction of diabetes,femoral artery li-gation(FAL)surgery was performed to create a model of diabetic lower limb ischemia.Fourteen days after STZ injection,the mice were treated with crocetin(3 mg/kg and 6 mg/kg)by gavage for 21 consecutive days.Post-FAL surgery,Doppler flowmetry was employed to assess blood flow in the mice of each group.Immunofluorescence stain-ing techniques were utilized to observe the expres-sion levels of platelet-endothelial cell adhesion molecule(CD31),α-smooth muscle actin(α-SMA),and inflammatory-related factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),in-terleukin-6(IL-6),and transforming growth factor-β(TGF-β)in the gastrocnemius muscle of diabetic mice with lower limb ischemia.RESULTS:Com-pared to the normal group,the model group exhib-ited significantly elevated blood glucose levels and significantly reduced lower limb blood flow(P＜0.05).While CD31 and α-SMA expression showed no significant change,the expression levels of TNF-α,IL-1β,IL-6,and TGF-β were significantly in-creased(P＜0.05,P＜0.01,P＜0.05,P＜0.05).Com-pared to the model group,crocetin-treated groups showed no significant change in blood glucose lev-els but demonstrated significantly increased lower limb blood flow(P＜0.05).The high-dose crocetin group(6 mg/kg)significantly enhanced CD31 andα-SMA expression(P＜0.0001,P＜0.05)and signifi-cantly reduced the expression levels of IL-1β,IL-6,and TGF-β(P＜0.001,P＜0.05,P＜0.05).CONCLU-SION:Crocetin may exert its beneficial effects on diabetic lower limb ischemia through anti-inflam-matory and angiogenic mechanisms.

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Objective:To explore and demonstrate the effect of general-specialty hierarchical management mode for chronic heart failure (CHF) in community.Methods:This was a single-blind, randomized, controlled study. A total of 530 CHF inpatients who attended Weifang Community Health Service Center (WCHSC) in Pudong New Area from February 2018 to September 2019 were consecutively enrolled. A random number table method was used to divide the patients into the management group ( n=265) and control group ( n=265). The demographic data and past medical history were collected 1 day before enrolment (baseline), and patients were assessed for New York Heart Association (NYHA) cardiac function classification and tested for blood N-terminal B-type natriuretic peptide proteins (NT-proBNP) levels, while Doppler echocardiography was performed to obtain the relevant indexes. The management group used a comprehensive management mode, co-delivered by both WCHSC (offering primary care) and RHSJUSM (offering specialty care) at Renji-Weifang CHF Studio in WCHSC , using the jointly developed CHF hierarchical CHF diagnosis and treatment criteria and referral procedure under the condition of sharing drugs and laboratory test results for CHF. The control group received routine heart failure care. Intergroup comparisons were made on baseline data obtained before follow-up and on NT-proBNP , left ventricular ejection fraction (LVEF), NYHA functional class , re-hospitalization rate and mortality rate at the end of the 6-month follow-up. Results:A total of 506 cases completed the follow-up. There were 253 patients in the management group, aged (68.26±9.41) years, 117 males (46.2%); 253 were in the control group, aged (66.98±9.63) years, 115 males (45.5%). There were no statistically significant differences in age, sex, marital status, education level, and comorbidities between the two groups (all P>0.05). At baseline, the differences in LVEF and NT-proBNP between the two groups were not statistically significant (all P>0.05), and at 6 months of intervention, LVEF, and NT-proBNP had significantly improved in both groups (all P<0.05) . Moreover, LVEF was higher in the management group than in the control group, and NT-proBNP was lower than in the control group (both P<0.01). At baseline, there were 166 cases (65.6%) in the control group with NYHA class Ⅲ/Ⅳ, and 145 cases (57.3%) in the comprehensive management group. There was no statistically significant difference between the two groups ( P>0.05). At 6 months of intervention, the percentage of NYHA class Ⅲ/Ⅳ patients in the comprehensive management group was lower than at baseline ( P<0.01),while that in the control group was higher than at baseline ( P<0.01), and the comprehensive management group was lower than that in the control group ( P<0.01). During the follow-up period, the rehospitalization rate for CHF in the management group was 13.83%(35/253), which was lower than that in the control group, which was 26.88%(68/253) ( P<0.001). Conclusion:The comprehensive management mode of CHF in the community through collaboration between general and specialized departments can significantly improve the management effect, suggesting that this mode is effective and can be promoted.

Objective:To investigate the adjunctive diagnostic value of retinal imaging structural parameters combined with apolipoprotein E (ApoE) gene polymorphisms for Alzheimer′s disease (AD).Methods:It was a case-control study, 71 confirmed AD patients who attended the Department of Neurology in Sichuan Provincial People′s Hospital from May 2023 to June 2024 and 156 healthy medical checkups who participated in medical checkups in the Health Management Center were continuously with convenience sampling method; the subjects were included as the AD case group and healthy control group, respectively. Optical coherence tomography (OCT) was used to measure the structural parameters of retinal imaging such as the thickness of the retinal nerve fiber layer (RNFL) and the retinal nerve fiber layer-inner plexiform layer (RNFL-IPL) in the study subjects. Information on demographic characteristics and disease history of the study participants were collected through a questionnaire, and venous blood was collected to test for ApoE gene polymorphisms. The retinal imaging structural parameters, ApoE gene polymorphisms and other related indicators were included in a multifactorial logistic regression model to analyze the main factors affecting the risk of AD. Based on the results of the multifactorial analysis, the receiver operating characteristic (ROC) curves were plotted and the areas under the curve (AUC) were calculated to evaluate the efficacy of different models in the adjunctive diagnosis of AD.Results:Of the 227 study subjects included in the analysis, 153 were females and 74 were males; there were 71 cases in the AD case group with a mean age of (66.73±8.83) years, and there were 156 subjects in the healthy control group with an average age of (61.95±8.21) years. Educational attainment of elementary school and below ( OR=4.683, 95% CI: 2.133-10.282), living visual acuity<0.5 ( OR=2.716, 95% CI: 1.12-6.583), and carrying ≥1 ApoE ε4 genes ( OR=5.331, 95% CI: 2.309-11.891) were positively correlated with the risk of AD. RNFL thickening ( OR=0.923, 95% CI: 0.854-0.998) was negatively associated with the risk of AD (all P<0.05). The AD risk assessment model (Model 4), which included fundus imaging features and ApoE gene polymorphisms, had the highest predictive efficacy (AUC=0.857, P<0.001). Conclusion:Retinal imaging structural parameters differ significantly between AD patients and healthy examinees, and a risk assessment model combining retinal imaging structural parameters and ApoE gene polymorphisms has high predictive value and is expected to serve as an auxiliary diagnostic tool for AD.

Objective To establish the therapeutic effect prediction model of platelet transfusion in hematological patients,and receiver operating characteristic(ROC)curve and clinical cases are used to evaluate the clinical application value of the predic-tion model.Methods A total of 485 patients with hematological diseases who received platelet transfusion therapy in Kailuan General Hospital from January 2020 to December 2023 were selected,corrected count increment(CCI)was used to divide the patients into platelet transfusion effective group(n=340)and transfusion ineffective group(n=145).Multivariate Logistic regres-sion analysis was used to establish the prediction model of platelet infusion efficacy,and ROC curve was used to evaluate the application effect of the forcasting model.109 clinical cases were used to verify the practical application effect of the model,and the sensitivity,specificity and accuracy were calculated.Results Among 485 patients with hematological diseases,the incidence of ineffective platelet transfusion was 29.90%(145/485).Compated with the effective group,the ineffective group had more previous platelet transfusions was higher,and the difference was statistically significant(t=-4.435,P<0.05).In the ineffective group,there were more cases of hyperplenism,aplastic anemia and lymphoma,higher infection rate and higher positive rate of platelet antibody,and the differences were statistically significant(χ2=6.301～37.522,all P<0.05).Multivariate Logistic regres-sion analysis found that previous platelet infusion times,infection,leukemia,aplastic anemia and platelet antibodies were risk factors for ineffective platelet transfusion in patients with hematological diseases(Wald χ2=5.224～21.548,all P<0.05).Based on these risk factors,platelet infusion effect prediction models 1 and 2 were constructed.ROC curve was used to evaluate the application effect of the prediction model.The area under the curve(AUC),cut-offpoint,sensitivity and specificity of model 1 were 0.884,0.042,82.35%,88.89%.The AUC,cut-offpoint,corresponding sensitivity and specificity of prediction model 2 were 0.910,59.784,81.18%,94.44%,respectively.The Z values of model 1 and model 2 were 12.159 and 13.151,respectively.The prediction effect of model 2 was better than that of model 1.The actual application results showed that the sensitivity,specificity and accuracy of prediction model 1,2 were 85.71%,92.05%,90.89%and 90.48%,93.18%,92.66%,respectively.Conclusion The ineffective rate of platelet transfusion in hematological patients is relatively high.The prediction models 1 and 2 for platelet transfusion effectiveness have good results in predicting ineffective platelet transfusion,and prediction model 2 is better than pre-diction model 1,which can provide reliable basis for hematological patients on accurate platelet transfusion.

AIM:To investigate the therapeutic ef-fect of crocetin on diabetic lower limb ischemia and explore its underlying mechanism.METHODS:Male C57BL/6J mice aged 8 weeks were used to es-tablish a diabetic mouse model through intraperito-neal injection of streptozotocin(STZ).Following successful induction of diabetes,femoral artery li-gation(FAL)surgery was performed to create a model of diabetic lower limb ischemia.Fourteen days after STZ injection,the mice were treated with crocetin(3 mg/kg and 6 mg/kg)by gavage for 21 consecutive days.Post-FAL surgery,Doppler flowmetry was employed to assess blood flow in the mice of each group.Immunofluorescence stain-ing techniques were utilized to observe the expres-sion levels of platelet-endothelial cell adhesion molecule(CD31),α-smooth muscle actin(α-SMA),and inflammatory-related factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),in-terleukin-6(IL-6),and transforming growth factor-β(TGF-β)in the gastrocnemius muscle of diabetic mice with lower limb ischemia.RESULTS:Com-pared to the normal group,the model group exhib-ited significantly elevated blood glucose levels and significantly reduced lower limb blood flow(P＜0.05).While CD31 and α-SMA expression showed no significant change,the expression levels of TNF-α,IL-1β,IL-6,and TGF-β were significantly in-creased(P＜0.05,P＜0.01,P＜0.05,P＜0.05).Com-pared to the model group,crocetin-treated groups showed no significant change in blood glucose lev-els but demonstrated significantly increased lower limb blood flow(P＜0.05).The high-dose crocetin group(6 mg/kg)significantly enhanced CD31 andα-SMA expression(P＜0.0001,P＜0.05)and signifi-cantly reduced the expression levels of IL-1β,IL-6,and TGF-β(P＜0.001,P＜0.05,P＜0.05).CONCLU-SION:Crocetin may exert its beneficial effects on diabetic lower limb ischemia through anti-inflam-matory and angiogenic mechanisms.