Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.

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.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective To establish a mouse model of liver aging induced by irradiation combined with hepatectomy.Methods A model was established via single irradiation combined with hepatectomy.The survival rate,body weight,liver index and liver function of the mice were detected.The expressions of senescence-associated secretory phenotype factors in serum were detected with enzyme-linked immunosorbent assay(ELISA)and flow cytometry.The mRNA levels of senescence-associated secretory phenotype factors and telomerase in liver tissue were detected by real-time quantitative PCR(qPCR).The expressions of cyclin dependent kinase inhibitor 1A(CDKN1A)and cyclin dependent kinase inhibitor 2A(CDKN2A)were determined by Western blotting.ELISA was used to calculate senescence-associated β-galactosidase(SA-β-Gal)and lipofuscin levels.Tissue malondialdehyde levels were measured using the thiobarbituric acid(TBA)method.The size of hepatocyte nuclei and lipid accumulation were detected by hematoxylin-eosin(HE)stainingand oil-red-O while triglyceride levels in the liver were studied with the weighing method.Results After irradiation combined with hepatectomy,the body weight of mice was significantly reduced,the liver index was not significantly affected,but the transaminase level was significantly increased.The levels of SA-β-Gal and lipofuscin increased while telomerase activity decreased significantly,and the nucleus size increased.The expressions of cyclin dependent protein kinase inhibitors CDKN1A and CDKN2A increased.The levels of senescence-associated secretory phenotype factors were significantly increased.Hepatic lipid deposition and oxidative damage were aggravated.Conclusion A mouse model of liver aging induced by irradiation combined with hepatectomy has been established.

Objective To explore the changes in gut microbiota and levels of short-chain fatty acids(SCFA)in infants with cow's milk protein allergy(CMPA),and to clarify their role in CMPA.Methods A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group,and 25 healthy infants were selected as the control group.Fecal samples(200 mg)were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites.Microbial diversity was analyzed in conjunction with metabolites.Results Compared to the control group,the CMPA group showed altered gut microbial structure and significantly increased α-diversity(P＜0.001).The abundance of Firmicutes,Clostridiales and Bacteroidetes was significantly decreased,while the abundance of Sphingomonadaceae,Clostridiaceae_l and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group(P＜0.001).Metabolomic analysis revealed reduced levels of acetic acid,butyric acid,and isovaleric acid in the CMPA group compared to the control group,and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia(P＜0.05).Conclusions CMPA infants have alterations in gut microbial structure,increased microbial diversity,and decreased levels of SCFA,which may contribute to increased intestinal inflammation.[Chinese Journal of Contemporary Pediatrics,2024,26(3):236-243]

Objective:To establish a morphologic classification system for characterizing blast cells in patients with acute promyelocytic leukemia(APL)and analyze the correlation of different APL morphologic characteristics with conventional tests and genetic variants.Methods:Based on the morphological characteristics of APL blast cells,a classification system of 14 categories was established to characterize the inter-and intra-individual cellular morphological heterogeneity of patients.The classification system was used for the morphological analysis of 40 APL patients,and the classification results were statistically analyzed with the patients'conventional test indexes and gene variant characteristics to analyze the correlation of different APL blast cell morphological features with conventional test indexes and gene variants.Results:In the FLT3-ITD mutation-positive group,there were significantly fewer cells with regular nuclear shape,hyper granularity,and missing Auer rods(category 1)than in the FLT3 mutation-negative group(P＜0.05).The activated partial thromboplastin(APTT)was significantly longer in the group with regular nucleus compared to the group with irregular nucleus(P＜0.05).In the hypo-granular group,the APTT was also significantly longer compared to the hyper-granular group(P＜0.01),and the proportion of myeloid blast cells was relatively lower(P＜0.05).The peripheral blood white blood cell counts,D-dimer,lactate dehydrogenase and proportion of bone marrow blast cells were significantly higher in the Auer rods(-)group than Auer rods increasing group(all P＜0.05).Conclusion:The newly established morphologic classification system in this study can objectively characterize different types of APL blast cells,which helps to better assess the intra-and inter-individual heterogeneity of APL blast cells,and further use in accurately analyzing the correlation of morphological phenotypes with biological properties of APL.

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Abelmoschus/chemistry* ; Podocytes ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition ; Flavones/pharmacology* ; Insulin Resistance ; Reactive Oxygen Species ; Diabetes Mellitus

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
Rats ; Animals ; Abelmoschus ; Reactive Oxygen Species/metabolism* ; Flavones/pharmacology* ; Endoplasmic Reticulum Stress ; Diabetic Nephropathies/drug therapy* ; Apoptosis ; Diabetes Mellitus

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (β = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.
Humans ; Male ; Antiviral Agents/therapeutic use* ; China ; Hepatitis C/drug therapy* ; Hepacivirus ; Logistic Models