This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.
Pyroptosis ; Caspase 3/metabolism* ; Network Pharmacology ; Gasdermins ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism*

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3^rd to May 31^st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Young Adult ; China/epidemiology* ; COVID-19/genetics* ; Nucleic Acids ; Retrospective Studies

OBJECTIVE: To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis. METHODS: Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×10² copies/ml), low load group (>5×10²-<5×10⁵ copies/ml) and high load group (≥5×10⁵copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group. RESULTS: The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×10⁹/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups. CONCLUSION The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.
Humans ; Child ; Female ; Lymphohistiocytosis, Hemophagocytic ; Retrospective Studies ; Risk Factors ; DNA ; Prognosis

Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics, and its safety has always been a concern. This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris. In the experiment, 30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium), low-dose Cinnabaris group(0.2 g·kg~(-1)), high-dose Cinnabaris group(2 g·kg~(-1)), pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose), and pseudogerm-free Cinnabaris group(2 g·kg~(-1)). They were orally administered for 30 consecutive days. Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(Ⅱ)], methylmercury(MeHg), and ethylmercury(EtHg) in different tissue, plasma, urine, and feces of rats. The optimal detection conditions and extraction methods were optimized, and the linearity(R~2>0.999 3), precision(RSD<7.0%), and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied, meeting the requirements of analysis. The results of mercury species detection showed that Hg(Ⅱ) was detected in all the tissue of the five experimental groups, and the main accumulating organs were the intestinal tract, stomach, and kidney. MeHg existed at a low concentration in most tissue, and EtHg was not detected in all groups. In addition, pathological examination results showed that hepatocyte vacuolar degeneration, loose cytoplasm, light staining, and mononuclear cell infiltration were observed in the high-dose Cinnabaris group, low-dose Cinnabaris group, and pseudogerm-free Cinnabaris group, with slightly milder lesions in the low-dose Cinnabaris group. Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group, but there was no significant difference between the other groups and the control group. No abnormal changes were found in the brain tissue of rats in each group. This paper studied the different mercury species and tissue distribution in normal and pseudogerm-free rats after continuous administration of Cinnabaris for 30 days and clarified its effects on the tissue structure of the liver, kidney, and brain, which provided supporting evidence for the safety evaluation of Cinnabaris.
Rats ; Animals ; Mercury/analysis* ; Tissue Distribution ; Methylmercury Compounds/analysis* ; Chromatography, High Pressure Liquid/methods* ; Sodium

Humans ; Otitis Media, Suppurative ; Chronic Disease ; Biofilms ; Otitis Media

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To evaluate the efficacy of daily use of a test emollient combined with topical glucocorticoids applied at the weekend for delaying the recurrence of atopic dermatitis (AD) in children during the maintenance period.Methods:A randomized, blank-controlled, multicenter clinical study was conducted in children with moderate AD from Beijing Children′s Hospital, Capital Medical University, Children′s Hospital of Chongqing Medical University and Shenzhen Children′s Hospital from March 2021 to February 2022. A total of 127 children aged 0 - 12 years with moderate AD were treated with topical glucocorticoids combined with emollients during the run-in period, 112 out of them achieved the investigator′s global assessment (IGA) score ≤ 1 point, and then the 112 patients were randomly divided into a test group (56 cases) and a control group (56 cases) at a ratio of 1∶1. Patients in the test group received treatment with a test emollient twice a day in combination with topical glucocorticoids applied at the weekend, and those in the control group were only treated with topical glucocorticoids at the weekend. Patients in the two groups were followed up at baseline, week 2 (± 3 d), week 4 (± 5 d), and week 12 (±7 d), as well as at the time of AD relapse, and the effect of the test emollient on the remission rate of AD in children during the maintenance period was evaluated, so were its effects on the dosage of topical glucocorticoids, pruritus, sleep, and skin pH. The occurrence of treatment-related adverse events was evaluated and recorded at the same time. Study endpoints were defined as AD relapse during the maintenance period, end of 12-week follow-up, or occurrence of serious adverse events. Comparisons of efficacy indicators between groups were conducted by using chi-square test, Kaplan-Meier survival analysis, Satterthwaite t′ test and Mann-Whitney U test. Results:In the full-analysis set, 45 (80.36%) patients with AD maintained remission in the test group (56 cases) and 30 (53.57%) in the control group (56 cases), and the remission rate difference between the two groups was 26.79% (95% confidence interval [ CI]: 10.09%, 43.49%; χ2 = 9.11, P = 0.003) ; the 12-week follow-up during the maintenance period showed that the time to first relapse was 75.05 ± 25.07 days in the test group, which was significantly longer than that in the control group (49.55 ± 33.92 days, t′ = 4.52, P < 0.001). At the study endpoint, the test group showed significantly decreased AD disease severity score (eczema area and severity index [EASI] score: 0.00 [0.00, 1.20] points vs. 0.60 [0.00, 4.00] points), pruritus visual analog scale (VAS) score (0.00 [0.00, 2.00] points vs. 2. 00 [0.00, 10.00] points), and sleep VAS score (0.00 [0.00, 0.00] points vs. 1.00 [0.00, 4.00] points) compared with the control group ( Z = -2.77, 2.43, 3.48, P = 0.006, = 0.015, < 0.001, respectively), while there was no significant difference in the pH value at the lesional sites between the test group and control group ( t = 0.97, P = 0.335). For the group aged 0 - 2 years, the average daily glucocorticoid dosage at the weekend in AD children during the maintenance period was significantly lower in the test group than in the control group ( Z = -1.97, P = 0.049) ; for the group aged >2 - 12 years, there was no significant difference in the average daily glucocorticoid dosage at the weekend between the two groups ( Z = -0.25, P = 0.802). During the study period, no significant difference was observed in the incidence of treatment-related adverse events between the test group (2/56, 3.57%) and control group (3/56, 5.36%; P = 1.000), and no serious adverse events occurred. Conclusion:Compared with the weekend treatment with topical glucocorticoids alone, the daily use of the test emollient combined with topical glucocorticoids at the weekend could markedly improve the remission rate of AD, prolong the time to relapse, and reduce the disease severity at relapse in children with AD during the maintenance period, which provides a new option for maintenance treatment of children with AD.

Objective: To compare the safety and efficacy of different anticoagulants in patients with indications for anticoagulation after transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Patients who underwent TAVR from April 2016 to February 2022 in Guangdong Provincial People's Hospital and had indications for anticoagulation were included and divided into two groups according to the type of anticoagulants, i.e. non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin, and patients were followed up for 30 days. The primary endpoint was the combination of death, stroke, myocardial infarction, valve thrombosis, intracardiac thrombosis and major bleeding. The incidence of endpoints was compared between two groups, and multivariate logistic regression analysis was applied to adjust the bias of potential confounders. Results: A total of 80 patients were included. Mean age was (74.4±7.1) years, 43 (53.8%) were male. Forty-nine (61.3%) patients used NOAC, 31 used warfarin, and major indication for anticoagulants was atrial fibrillation (76/80, 95.0%). The adjusted risks of the primary endpoint (OR=0.23, 95%CI 0.06-0.94, P=0.040) of NOAC were lower than that of warfarin, mainly driven by a lower risk of major bleeding (OR=0.19, 95%CI 0.04-0.92, P=0.039). Conclusions: The short-term outcome of NOAC is better than that of warfarin in patients with indications for anticoagulation after TAVR. Randomized controlled trials of large sample size with long-term follow-up are needed to further testify this finding.
Humans ; Male ; Aged ; Aged, 80 and over ; Female ; Anticoagulants/therapeutic use* ; Warfarin/therapeutic use* ; Transcatheter Aortic Valve Replacement ; Retrospective Studies ; Hemorrhage ; Stroke/epidemiology* ; Atrial Fibrillation/drug therapy* ; Treatment Outcome ; Administration, Oral

Objective: To compare the safety and efficacy of different anticoagulants in patients with indications for anticoagulation after transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Patients who underwent TAVR from April 2016 to February 2022 in Guangdong Provincial People's Hospital and had indications for anticoagulation were included and divided into two groups according to the type of anticoagulants, i.e. non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin, and patients were followed up for 30 days. The primary endpoint was the combination of death, stroke, myocardial infarction, valve thrombosis, intracardiac thrombosis and major bleeding. The incidence of endpoints was compared between two groups, and multivariate logistic regression analysis was applied to adjust the bias of potential confounders. Results: A total of 80 patients were included. Mean age was (74.4±7.1) years, 43 (53.8%) were male. Forty-nine (61.3%) patients used NOAC, 31 used warfarin, and major indication for anticoagulants was atrial fibrillation (76/80, 95.0%). The adjusted risks of the primary endpoint (OR=0.23, 95%CI 0.06-0.94, P=0.040) of NOAC were lower than that of warfarin, mainly driven by a lower risk of major bleeding (OR=0.19, 95%CI 0.04-0.92, P=0.039). Conclusions: The short-term outcome of NOAC is better than that of warfarin in patients with indications for anticoagulation after TAVR. Randomized controlled trials of large sample size with long-term follow-up are needed to further testify this finding.
Humans ; Male ; Aged ; Aged, 80 and over ; Female ; Anticoagulants/therapeutic use* ; Warfarin/therapeutic use* ; Transcatheter Aortic Valve Replacement ; Retrospective Studies ; Hemorrhage ; Stroke/epidemiology* ; Atrial Fibrillation/drug therapy* ; Treatment Outcome ; Administration, Oral

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*