Exosomes can ameliorate neuronal cell injury induced by hypoxia-ischemia,but the relation-ship between astrocyte-derived exosomes(As-exo)and mitochondrial function,mitochondrial associated ER membrane(MAM)function and whether mitochondrial autophagy is relevant is currently unclear.The aim of this study was to investigate the role of astrocyte-derived exosomes in the regulation of mito-chondrial function,MAM and mitochondrial autophagy in PC 12 cells after oxygen and glucose depriva-tion/reoxygenation(OGD/R).Exosomes were extracted from the supernatant of the astrocyte culture me-dium by ultracentrifugation.Using the live cell imaging system,we observed that fluorescently labeled exosomes could show obvious enrichment in PC 12 cells at 24 h.Meanwhile,co-localization of exosomes with mitochondria could be observed under the laser confocal scanning microscope;mitochondrial pres-sure changes were detected using the Seahorse cellular energy metabolism fractionation instrument.The result showed that basal respiration in the OGD/R group,compared with that in the control group,proton leakage,maximal respiration and ATP-related respiration were significantly reduced(P＜0.05 or P＜0.01),and all four indexes were elevated and statistically significant in the OGD/R+exo group compared with the control group(P＜0.05 or P＜0.01).The results of the co-localization of the mitochondria and ER showed that the structure of the MAM was harmed by oxygen-sugar deprivation and then reoxygen-ation,and the structure of As-exo and the mitochondria appeared to have a distance-reduced polymeriza-tion phenomenon,while the mitochondria and ER co-localized.The co-localization results of mitochondri-a and ER showed that the structure of MAM was damaged by oxygen deprivation and reoxygenation,and the aggregation phenomenon of MAM was weakened by the treatment of As-exo;the flow-through results showed that As-exo could restore the decrease of the mitochondrial membrane potential and the elevation of the ROS by oxygen deprivation to a certain degree.Western blotting showed that As-exo could signifi-cantly inhibit the mitochondrial autophagy-associated tension protein homologue induced hypothetical ki-nase 1(PTEN induced kinase 1(PINK1)and Parkin protein(parkin RBR E3 ubiquitin protein ligase(Parkin))were elevated,and the addition of As-exo decreased LC3 Ⅱ/LC3 Ⅰ protein expression,ele-vated P62 protein expression,and reduced OGD/R-induced mitochondrial autophagy.The results showed that OGD/R treatment can cause mitochondrial dysfunction,MAM structural changes and increased mito-chondrial autophagy in PC12 cells,and As-exo treatment can improve mitochondrial function,attenuate the formation of MAM,and reduce mitochondrial autophagy in PC 12 cells,which can have the potential of preventing the reperfusion injury in ischemic stroke.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.

Objective:To investigate the influences of blood pressure fluctuation and biochemical parameters in early cognitive impairment in patients with basal ganglia hypertensive intracerebral hemorrhage (HICH).Methods:A total of 148 patients with basal ganglia HICH, admitted to Department of Neurosurgery, Second Affiliated Hospital of Soochow University from January 2022 to January 2024 were enrolled. Four weeks after onset, these patients accepted Montreal cognitive assessment (MoCA) and were divided into cognitive impairment group (MoCA scores<26, n=62) and non-cognitive impairment group (MoCA scores≥26, n=86) accordingly. Clinical data and average blood pressure on 7 consecutive d (since admission) were collected, and differences of clinical data, mean systolic blood pressure (MSBP), mean diastolic blood pressure (MDBP), and long-term blood pressure variability indexes were compared between the two groups. Multivariate Logistic regression analysis was used to screen the independent influencing factors for cognitive impairment; spearman rank correlation was used to analyze the correlation between independent influencing factors and MoCA score; and receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of independent influencing factors in cognitive impairment. Results:Compared with the non-cognitive impairment group, the cognitive impairment group had significantly longer hypertension duration, statistically higher interleukin-6 (IL-6), MSBP, MDBP and 7 d-duration standard deviation of systolic blood pressure (7dSSD), and significantly lower albumin ( P<0.05). Multivariate Logistic regression analysis showed that hypertension duration ( OR=1.258, 95% CI: 1.134-1.396, P<0.001), MSBP ( OR=1.770, 95% CI: 1.267-2.473, P=0.001), 7dSSD ( OR=1.139, 95% CI: 1.038-1.249, P=0.006), and IL-6 ( OR=1.156, 95% CI: 1.076-1.241, P<0.001) were independent influencing factors for early cognitive impairment in patients with basal ganglia HICH. Spearman rank correlation showed that hypertension duration, MSBP, 7DSSD, and IL-6 were negatively correlated with MoCA score ( rs=-0.271, P=0.001; rs=-0.493, P<0.001; rs=-0.264, P=0.001; rs=-0.412, P<0.001). Area under ROC curve of combined use of MSBP, 7dSSD, hypertension duration and IL-6 in diagnosing early cognitive impairment was 0.932, with sensitivity of 0.855 and specificity of 0.895. Conclusion:MSBP, 7dSSD, hypertension duration and IL-6 might be hemodynamic and serological monitoring indexes for predicting early cognitive impairment in patients with basal ganglia HICH.

Aim To explore the effect of γ-ray on the mRNA,protein expression levels and metabolic activity level of the key drug metabolic enzyme CYP3A1 in rat liver. Methods Wistar rats were randomly divided into control group, 24 h post-radiation group and 72 h post-radiation group. The experimental group was exposed to total body irradiation of single 6 Gy γ-ray. Blood was collected from the orbital venous plexus for blood routine examination and biochemical analysis 24 h and 72 h after irradiation, and liver tissue was prepared for quantifying expression of CYP3A1 mRNA and liver-specific microRNA (miR-122-5p) through RT-PCR. The expression level of CYP3A1 protein was analyzed by Western blot, and the metabolic activity level of CYP3A1 detected by the specific substrate midazolam combined with LC-MS method. Results Com¬pared with the control group, the weights of the rats in the radiation group significantly decreased, and the number of white blood cells was markedly reduced. Simultaneously, the activities of alanine aminotrans-ferase and alkaline phosphatase continuously descended, as well as the levels of total bilirubin and bile acid significantly increased, which indicated that the liver may be damaged after radiation. The relative expression of CYP3A1 mRNA continued to increase significantly 24 h and 72 h after irradiation. CYP3A1 protein expression and metabolic activity levels showed an obvious increasing trend 24 h after irradiation, and rose significantly 72 h after irradiation compared with the control group. At the same time, the expression of miR-122-5p in liver of rats in the 24 h and 72 h post-radiation group continued to decrease rapidly compared with the control group. Conclusions γ-ray radiation may arouse damage effect on liver, which leads to the continuous up-regulation of the mRNA and protein expression levels of the capital metabolic enzyme CYP3A1 in liver tissue, as well as the elevation of the metabolic activity level. The regulatory mechanism might be related to miR-122-5p.

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg^-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between C_max and AUC_0-5d in the two groups. The liquid preparation was the reference preparation, with C_max ratio of 101.6% and AUC_0-5d ratio of 101.9%, the 90% confidence interval of C_max was 79.42%-129.92%, and the 90% confidence interval of AUC_0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.
Child ; Coronary Aneurysm/etiology* ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Infant ; Infliximab/adverse effects* ; Male ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.
DNA Methylation/genetics* ; Drugs, Chinese Herbal ; Hematologic Neoplasms/genetics* ; Humans ; Materia Medica ; Medicine, Chinese Traditional

Objective: To explore the effect of three interventions including caloric restriction, rope-skipping exercise and caloric restriction combined with rope-skipping exercise on cardiometabolic risk factors in overweight or obese college students. Methods: This study was a pilot randomized controlled trial. Overweight or obese students who met the inclusion criteria were recruited at Sun Yat-sen University in September 2019 and were randomly divided into four groups: caloric restriction group (CR), rope-skipping group (RS), combined group (CR-RS) and control group (CT). The intervention in each group lasted 8 weeks, specifically: the daily energy intake of CR was 100% to 110% of the basal metabolic energy; RS was instructed to rope three times a week, and CR-RS combined caloric restriction with rope-skipping. At the baseline and end of 8-week intervention, basic information, anthropometric indicators and fasting vein blood of students were collected. Paired t test and Wilcoxon paired-samples signed rank test were used for comparison before and after intervention, and analysis of covariance was used for comparison between groups after intervention. Results: A total of 29 students completed the trial and were included in the final analysis (7, 9, 7 and 6 students in CR, RS, CR-RS and CT, respectively). The mean age of students were (19.00±1.00) years, including 11 males and 18 females. The baseline characteristics of four groups were comparable. After 8 weeks of intervention, compared with CT, there was an increase in the body fat percentage and fat mass index in CR and CR-RS (P<0.05). Insulin level decreased in CR-RS (P<0.05). Systolic blood pressure in CR and diastolic blood pressure in CR-RS were higher (P<0.05). Compared with baseline, fat mass index decreased in CR (P<0.05), while body weight, BMI, and fat mass index decreased in CR-RS (P<0.05). Conclusion: It is suggested that the caloric restriction alone and calorie restriction combined with rope-skipping exercise can benefit overweight or obese college students with cardiometabolic risk factors.
Adolescent ; Adult ; Caloric Restriction ; Cardiometabolic Risk Factors ; Female ; Humans ; Insulins ; Male ; Obesity ; Overweight ; Students ; Weight Loss/physiology* ; Young Adult

External apical root resorption is among the most common risks of orthodontic treatment, and it cannot be completely avoided and predicted. Risk factors causing orthodontic root resorption can generally be divided into patient- and treatment-related factors. Root resorption that occurs during orthodontic treatment is usually detected by radiographical examination. Mild or moderate root absorption usually does no obvious harm, but close attention is required. When severe root resorption occurs, it is generally recommended to suspend the treatment for 3 months for the cementum to be restored. To unify the risk factors of orthodontic root resorption and its clinical suggestions, we summarized the theoretical knowledge and clinical experience of more than 20 authoritative experts in orthodontics and related fields in China. After discussion and summarization, this consensus was made to provide reference for orthodontic clinical practice.
Humans ; Tooth Movement Techniques/adverse effects* ; Root Resorption/etiology* ; Consensus ; Dental Cementum ; Risk Factors

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER NCT03620565, https://register.clinicaltrials.gov.
China ; Female ; Gynecologic Surgical Procedures/adverse effects* ; Humans ; Pelvic Floor/surgery* ; Pelvic Organ Prolapse/surgery* ; Surgical Mesh/adverse effects* ; Treatment Outcome ; Vagina