Objective To explore the changes of serum angiopoietin-like protein 4(ANGPTL4)and NOD-like receptor protein 3(NLRP3)levels after traumatic brain injury(TBI)and their diagnostic value for sec-ondary massive cerebral infarction.Methods A total of 100 TBI patients admitted to the hospital from Au-gust 2019 to August 2021 were enrolled as the TBI group,meantime,100 healthy people in the hospital were enrolled as the control group.The serum levels of ANGPTL4 and NLRP3 were detected by enzyme-linked im-munosorbent assay(ELISA).The clinical characteristics of TBI patients with and without secondary massive cerebral infarction were compared.Receiver operating characteristic(ROC)curve was applied to analyze the serum levels of ANGPTL4 and NLRP3 on their diagnostic value for TBI patients with secondary massive cere-bral infarction.Multivariate Logistic regression analysis was applied to analyze the factors affecting the occur-rence of secondary massive cerebral infarction in TBI patients.Results The serum ANGPTL4 level in TBI group was lower than that in the control group,and the serum NLRP3 level was higher than that in the con-trol group(P<0.05).There were obvious differences in proportion of brain hernia,proportion of subarach-noid hemorrhage,serum levels of ANGPTL4 and NLRP3 between patients with secondary massive cerebral infarction and patients without secondary massive cerebral infarction(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum ANGPTL4 and NLRP3 in diagnosing secondary massive cere-bral infarction in TBI patients was 0.792 and 0.812 respectively,with sensitivity of 77.80%and 83.30%re-spectively,and specificity of 86.60%and 64.60%respectively.The sensitivity,the specificity and AUC of the combined detection were 83.30%,82.90%and 0.867 respectively.Multivariate Logistic regression analysis showed that serum NLRP3 level was a risk factor for TBI patients with secondary massive cerebral infarction(P<0.05).After treatment,it was found that serum ANGPTL4 level increased and NLRP3 level decreased in TBI patients(P<0.05).Conclusion The serum level of ANGPTL4 in TBI patients decreases,while the level of NLRP3 increases,and the level of ANGPTL4 in the serum of patients with secondary massive cerebral in-farction decreases and the level of NLRP3 increases,both of them are of great significance in the diagnosis of secondary massive cerebral infarction in TBI patients.

BACKGROUND:Multiple clinical observational studies have suggested a close relationship of serum trace elements and nutrients with osteonecrosis,but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients on osteonecrosis. OBJECTIVE:To investigate the causal effects of serum trace elements and nutrients on osteonecrosis using the Mendelian randomization approach. METHODS:The exposure factors of serum trace elements and vitamins with mononucleotide polymorphisms were obtained from the published UK Biobank database and publicly available databases of genome-wide association studies.The outcome event of osteonecrosis was derived from the FinnGen Biobank database.Mendelian randomization methods were employed to explore the causal relationship between seven trace elements and three nutrients with osteonecrosis.Causal inference was conducted using inverse variance weighting,MR-Egger,and weighted median methods.F-statistic was calculated to ensure the robustness of instrumental variables.Cochran's Q test and leave-one-out method were used for heterogeneity testing.MR-Egger regression and MR-PRESSO were employed for horizontal pleiotropy testing.PhenoScanner database was utilized to remove mononucleotide polymorphisms with horizontal pleiotropy to ensure the reliability of the results. RESULTS AND CONCLUSION:Causal relationships were found between serum selenium,phosphate,vitamin C,vitamin E,and osteonecrosis through Mendelian randomization analysis.Serum selenium,vitamin C,and vitamin E were found to have a protective effect on osteonecrosis,while excessive intake of phosphate increased the risk of osteonecrosis.No heterogeneity or horizontal pleiotropy was observed during the study,and Mendelian randomization statistical power(Power value>80%)indicated the reliability of the aforementioned four results.These findings have important clinical implications for the development of targeted preventive and therapeutic measures for osteonecrosis.

OBJECTIVE To explore the moisture and components change law of Peucedani Radix slices during microwave vacuum drying, and effectively improve the drying efficiency and slice quality of Peucedani Radix slices, by carring out drying characteristics analysis and simulation of Peucedani Radix Slices during microwave vacuum drying. METHODS Microwave vacuum drying experiments of Peucedani Radix slices under different drying conditions (microwave power density, vacuum degree and slice thickness) were carried out. The changes of moisture ratio and drying rate during drying process were studied. The contents of three coumarin ingredients (praeruptorin A, praeruptorin B and praeruptorin E) in dried Peucedani Radix slices were determined by HPLC. Weibull function was used to simulate and analyze the moisture ratio curve during drying process. RESULTS Microwave vacuum drying process of Peucedani Radix slices has three stages: acceleration, constant speed and deceleration. Compared with vacuum degree and slice thickness, increasing microwave power density could shorten drying time and improve drying efficiency more effectively. In the range of experimental parameters, the optimum drying conditions were as follows: microwave power density was 3.0 W·g–1, vacuum degree was 800 Pa, and slice thickness was 2 mm. The changes of all drying conditions had no significant effect on the content of coumarins in dried Peucedani Radix slices. The results of Weibull function simulation and analysis showed that the scale parameters under different drying conditions ranged from 17.43 to 45.38, and the smaller the value, the shorter the drying time. The shape parameters ranged from 1.41 to 1.77 and were all greater than 1, indicating that the drying process was controlled by internal and external water diffusion. CONCLUSION The research work not only provides important theoretical basis and technical support for the process improvement and quality control of microwave vacuum drying process of Peucedani Radix slices, but also provides important reference for the standardization of Peucedani Radix slices drying and the formation of quality characteristics.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.

Objective To investigate the protective effect of NDUFA13 protein against acute liver injury and liver fibrosis in mice and explore the possible mechanisms.Methods BALB/C mice(7 to 8 weeks old)were divided into normal group,CCl4 group,CCl4+AAV-NC group and CCl4+AAV-NDU13 group(n=18).Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4 twice a week for 3,5 or 7 weeks,and the recombinant virus AAV8-TBG-NC or AAV8-TBG-NDUFA13 was injected via the tail vein 7-10 days prior to CCl4 injection.After the treatments,pathological changes in the liver of the mice were observed using HE and Masson staining.Hepatic expression levels of NDUFA13 and α-SMA were detected with Western blotting,and the coexpression of NDUFA13 and NLRP3,TNF-α and IL-1β,and α-SMA and collagen Ⅲ was analyzed with immunofluorescence assay.Results HE and Masson staining showed deranged liver architecture,necrotic hepatocytes and obvious inflammatory infiltration and collagen fiber deposition in mice with CCl4 injection(P<0.001).NDUFA13 expression markedly decreased in CCl4-treated mice(P<0.001),while a significant reduction in inflammatory aggregation and fibrosis was observed in mice with AAV-mediated NDUFA13 overexpression(P<0.001).In CCl4+AAV-NDU13 group,immunofluorescence assay revealed markedly weakened activation of NLRP3 inflammasomes(P<0.001),significantly decreased TNF-α and IL-1β secretion(P<0.001),and inhibited hepatic stellate cell activation(P<0.05)and collagen formation in the liver(P<0.001).Conclusion Mitochondrial NDUFA13 overexpression in hepatocytes protects against CCl4-induced liver fibrosis in mice by inhibiting activation of NLRP3 signaling.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective To investigate the protective effect of NDUFA13 protein against acute liver injury and liver fibrosis in mice and explore the possible mechanisms.Methods BALB/C mice(7 to 8 weeks old)were divided into normal group,CCl4 group,CCl4+AAV-NC group and CCl4+AAV-NDU13 group(n=18).Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4 twice a week for 3,5 or 7 weeks,and the recombinant virus AAV8-TBG-NC or AAV8-TBG-NDUFA13 was injected via the tail vein 7-10 days prior to CCl4 injection.After the treatments,pathological changes in the liver of the mice were observed using HE and Masson staining.Hepatic expression levels of NDUFA13 and α-SMA were detected with Western blotting,and the coexpression of NDUFA13 and NLRP3,TNF-α and IL-1β,and α-SMA and collagen Ⅲ was analyzed with immunofluorescence assay.Results HE and Masson staining showed deranged liver architecture,necrotic hepatocytes and obvious inflammatory infiltration and collagen fiber deposition in mice with CCl4 injection(P<0.001).NDUFA13 expression markedly decreased in CCl4-treated mice(P<0.001),while a significant reduction in inflammatory aggregation and fibrosis was observed in mice with AAV-mediated NDUFA13 overexpression(P<0.001).In CCl4+AAV-NDU13 group,immunofluorescence assay revealed markedly weakened activation of NLRP3 inflammasomes(P<0.001),significantly decreased TNF-α and IL-1β secretion(P<0.001),and inhibited hepatic stellate cell activation(P<0.05)and collagen formation in the liver(P<0.001).Conclusion Mitochondrial NDUFA13 overexpression in hepatocytes protects against CCl4-induced liver fibrosis in mice by inhibiting activation of NLRP3 signaling.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective To investigate the predictive value of Rotterdam CT score combined with serum soluble cluster of differentiation antigen 40 ligand (sCD40L) and fibulin-5 for prognosis of patients with severe traumatic brain injury (sTBI). Methods A total of 186 sTBI patients were divided into good prognosis group (n=104) and poor prognosis group (n=82). CT images were analyzed and Rotterdam CT scores were obtained; the enzyme-linked immunosorbent assay (ELISA) was used to detect serum sCD40L and fibulin-5 levels on the 1st, 3rd and 7th day of admission; the Spearman analysis was used to assess the correlations of serum sCD40L and fibulin-5 levels on the first day of admission with the Rotterdam CT score and Glasgow Coma Scale (GCS) score; the Multivariate Logistic regression analysis was conducted to explore the risk factors for poor prognosis in sTBI patients; the receiver operating characteristic (ROC) curve was performed to analyze the predictive value of Rotterdam CT score combined with serum sCD40L and fibulin-5 levels on the first day of admission for prognosis of sTBI patients. Results On the 1st, 3rd and 7th day of admission, compared with the good prognosis group, the serum levels of sCD40L and fibulin-5 in the poor prognosis group were significantly elevated (P < 0.05); serum sCD40L and fibulin-5 levels were negatively correlated with GCS scores (r=-0.505, -0.421, P < 0.05) and positively correlated with Rotterdam CT score (r=0.495, 0.397, P < 0.05); sCD40L (OR=2.768, 95%CI, 1.537 to 4.983) and fibulin-5 (OR=2.539, 95%CI, 1.301 to 4.953) were independent risk factors for poor prognosis in sTBI patients (P < 0.001); the area under the curve (AUC) of Rotterdam CT score combined with serum sCD40L and fibulin-5 levels on the first day of admission for predicting poor prognosis in sTBI patients was 0.969 (95%CI, 0.933 to 0.989), with a sensitivity of 86.59% and a specificity of 94.23%; the diagnostic performance of Rotterdam CT score combined with sCD40L and fibulin-5 was superior to that of each individual indicator (Z=4.233, 4.274, 4.433, P < 0.001); the Bootstrap internal validation results showed that the predictive performance curve of the combined prediction model was consistent with the actual clinical occurrence curve. Conclusion Rotterdam CT score combined with serum sCD40L and fibulin-5 has certain predictive value for poor prognosis in sTBI patients.

Humans ; Abdomen ; Dantrolene ; East Asian People ; Malignant Hyperthermia