Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

Antineoplastic Agents, Immunological/adverse effects* ; Humans ; Immune Checkpoint Inhibitors ; Myocarditis/chemically induced*

AIM: To systematically evaluate the effects of 0.01%, 0.025% and 0.05% ophthalmic atropine on the change of spherical equivalent(SE)degree and axial length(AL)of myopic children. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Database, VIP and CBM were searched for all publications related to 0.01%, 0.025% and 0.05% atropine to control myopia simultaneously. The publication time is from the database construction to May 2022. The Cochrane handbook was used to evaluate the risk of bias and quality of the included literature, STATA12.0 was used to detect publication bias and Revman5.4 software was used for Meta-analysis. RESULTS: A total of 6 literatures(1 239 eyes)were included, with 5 randomized controlled trials and 1 case-control study. Meta-analysis results showed that 0.025% atropine had better inhibitory effect on SE and AL than 0.01% atropine(SE: WMD=-0.15, 95%CI: -0.23--0.06, P<0.001; AL: WMD=0.07, 95%CI: 0.03-0.10, P<0.001). The inhibitory effect of 0.05% atropine on SE and AL was better than 0.01% atropine(SE: WMD=-0.35, 95%CI: -0.44--0.26, P<0.001; AL: WMD=0.16, 95%CI: 0.12-0.20, P<0.001). The inhibitory effect of 0.05% atropine on SE and AL increase was better than 0.025% atropine(SE: WMD=-0.20, 95%CI: -0.28--0.11, P<0.001; AL: WMD=0.09, 95%CI: 0.06-0.12, P<0.001). CONCLUSION: The concentration of 0.05% atropine is superior to 0.01% and 0.025% atropine in the control of SE and AL. However, the side effects of long-term use remain to be observed.

Animals ; Cadmium/toxicity* ; Dysbiosis/metabolism* ; Gastrointestinal Microbiome ; Glutamine/pharmacology* ; Methionine ; Mice ; Mice, Inbred C57BL ; Ostreidae ; Protein Hydrolysates ; Tyrosine

Objective: To investigate death and attrition in HIV-infected children under initial antiretroviral therapy (ART) and associated factors in Guangxi Zhuang autonomous region. Methods: This retrospective cohort study was conducted in HIV-infected children under initial ART in Guangxi from 2004 to 2019, data from ART information system of National comprehensive AIDS prevention and treatment information system. Cox proportional hazards models were used to assess factors associated with the death and attrition. Results: In 943 HIV-infected children, the overall mortality and attrition rates were 1.00/100 person-years and 0.77/100 person-years, respectively. The mortality and attrition rates within the first year of ART were 3.90/100 person-years and 1.67/100 person-years, respectively. The cumulative survival rate during the first, second, fifth and tenth year after ART was 96.14%, 95.80%, 93.68% and 91.54%, respectively. Multivariate Cox proportional hazards models results showed that being female (aHR=2.00, 95%CI: 1.17-3.40), CD4⁺T lymphocytes (CD4) counts before ART <200 cells/μl (aHR=2.79, 95%CI: 1.54-5.06), weight-for-age Z score before ART <-2 (aHR=2.38, 95%CI: 1.32-4.26), hemoglobin before ART <80 g/L (aHR=2.47, 95%CI: 1.24-4.92), initial ART with LPV/r (aHR=5.05, 95%CI: 1.15-22.12) were significantly associated with death; being female (aHR=2.23, 95%CI: 1.22-4.07) and initial ART with LPV/r (aHR=2.02, 95%CI: 1.07-3.79) were significantly associated with attrition. Conclusions: The effect of ART in HIV-infected children in Guangxi was better, but the mortality and attrition rates were high within the first year of treatment. It is necessary to strengthen the training in medical staff and health education in HIV-infected children and their parents in order to improve the treatment effect.
Anti-HIV Agents/therapeutic use* ; Child ; China/epidemiology* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Proportional Hazards Models ; Retrospective Studies

OBJECTIVE ：To est ablish the method for the determination of 20（S）-protopanaxadiol（PPD）concentration in human plasma. METHODS ：Plasma samples were precipitated with acetonitrile and determined by UPLC-MS/MS ，using finandrogen as internal standard. The determination was performed on Waters ACQUITY UPLC HSS T 3 column with mobile phase consisted of 5 mmol/L ammonium bicarbonate aqueous solution-acetonitrile （gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The ion source was electrospray ion source，and negative ion scanning was carried out with multiple reaction monitoring mode . The ion pairs used for quantitative analysis were m/z 459.40→ 375.20（PPD）and m/z 371.30→315.30（internal standard ）. At the same time ，the method was applied to the determination of clinical samples. RESULTS ：The linear range of PPD was 0.25-30.00 ng/mL（r＝0.999 2），and the limit of quantitation was 0.25 ng/mL. RSDs of intra-batch and inter-batch were all lower than 10％，and relative errors （RE）were －14.61％-12.69％. Extraction method and matrix effect did not affect the quantitative determination of PPD. In ginsenoside CK 100 mg group ，ginsenoside CK 200 mg group and ginsenoside CK 300 mg group ，mean cmax of patients with rheumatoid arthritis after oral administration of corresponding drugs were 18.06，30.03，27.00 ng/mL；median tmax were 12.0，6.0，12.0 h；mean AUC 0-t were 622.52，668.15， 1 155.97 ng·h/mL. CONCLUTIONS ：The method for the determination of PPD concentration in human plasma is successfully established. The method is sensitive ，accurate， kq1907011） stable，easy to operate and less plasma consumption. It can be used for the quantitative determination of clinical samples.

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Intracranial Hemorrhage, Hypertensive/drug therapy* ; Medicine, Chinese Traditional ; Quality of Life ; Randomized Controlled Trials as Topic

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.
Acupuncture Therapy ; Humans ; Intracranial Hemorrhage, Hypertensive/therapy* ; Treatment Outcome

In recent years， the incidence of neurological diseases has been increasing year by year. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of neurological disorders， identify the breakthrough point of integrating TCM with western medicine， and further standardize the clinical diagnosis and treatment of TCM， the China Association of Chinese Medicine organized neurologists in TCM and western medicine to carry out in-depth discussion on the neurological diseases responding specifically to TCM and integrated TCM and western medicine， such as stroke， headache， vertigo， multiple sclerosis， and epilepsy， aiming to formulate a well-recognized and integrated treatment protocol for TCM and western medicine and improve the efficacy of neurological disorders. Furthermore， the treatment suggestions of the corresponding diseases in TCM and western medicine were proposed to provide references for clinical practice and scientific research.

Objective:To establish ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） for the analysis of 18 components of five categories, namely spirosteroid saponins （timosaponin AⅠ，timosaponin AⅡ，timosaponin AⅢ，anemarrhenasaponin Ⅲ，sarsasapogenin），furostane saponins（anemarrhenasaponin Ⅰ，anemarrhenasaponin Ⅰa，anemarsaponin E，officinalisinin I，timosaponin B-Ⅱ，timosaponin B-Ⅲ，anemarsaponin C），flavonoids（icarisin I，baohuoside I），bisphenone（meomangiferin，mangiferin，isomangiferin），and hydroquinone glycoside （β-arbutin）,in order to analyze the differences between the main root and fibrous root of Anemarrhena asphodeloides from different sources and provide reference for the sustainable development of A. asphodeloides resources. Method:0.25 g sample was refluxed and extracted with 25 mL dilute ethanol for 30 min. The chromatographic separation was carried out on Waters Acquity Uplc BEHHILI C₁₈ column（2.1 mm×100 mm，1.7 μm），with 0.1% formic acid water-acetonitrile as the mobile phase for gradient elution，and the volume flow rate was 0.2 mL·min^-1. Electrospray ion source（ESI⁺，ESI^-），and multi-reaction ion monitoring（MRM） were used for detection，external standard method was used to calculate the content of the tested components in medicinal samples，and SMICA14.1 software was used to analyze the differences between the main root and fibrous root samples of A. asphodeloides. Result:The tested components showed a good linear relationship in their respective linear ranges，with a good precision，repeatability and stability. The recovery rate of samples was between 95.22%-101.42%，and RSD was less than 4%. The experimental results showed great differences between the main root and fibrous root of A. asphodeloides, when the multivariate statistical analysis was carried out with 18 main components. Conclusion:This study provides experimental basis for the reuse of fibrous root of A. asphodeloides resources and the quality control of A. asphodeloides.