Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Since 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)posed a great threat to human health and social economy, which has brought out hundreds of millions infection and caused millions of deaths worldwide. With the increasing research on SARS-CoV-2, angiotensin-converting enzyme 2(ACE2)has been regarded as a significant functional receptor for SARS-CoV-2 invasion. ACE2 is distributed in many tissues of human body, not only expressed in lung, cardiovascular, kidney tissues, but also in conjunctiva, cornea, uvea, retina and optic nerve tissue. More and more cases of SARS-CoV-2 infection through ocular tissues have been found; however, whether ocular ACE2 plays a role in SARS-CoV-2 infection is not completely clear. Therefore, study on expression and distribution of ACE2 in the ocular tissues can not only provide an in-depth understanding of the mechanism of SARS-CoV-2 infection, but also supply a comprehensive acquaintance with the mechanism of ACE2 action in the ocular tissues. In this paper, we review recent research progress about the expression and distribution of ACE2 in ocular tissues and hope to better understand the mechanism of ACE2 in the pathophysiological processes of ocular tissues.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Aim To investigate the effect of microinjection of EX527, a selective SIRT1 antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced conditioned place preference (CPP), and to explore the role of CREB/BDNF in it. Methods The cannulas were implanted bilaterally in the VLO of rats by brain stereotaxis surgery, and the model of morphine-induced CPP was established. The behavioral experiment consisted of four stages:habituation (d 1), pre-test (d 2-4), conditioning training (d 5-14) and test (d 15). At the stage of conditioning training, EX527 (1 μL, 5 g·L

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety. METHODS: A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR). RESULTS: We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR. CONCLUSION Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.
Humans ; Cross-Sectional Studies ; Pandemics ; COVID-19/epidemiology* ; Burnout, Psychological ; Health Personnel

In recent years, emerging technology medical devices have developed rapidly. How to more scientifically and more efficiently regulate these novel medical devices so as to improve access to advanced medical technology while ensuring safety and effectiveness is a new challenge faced by regulatory authorities, and is also the core topic of regulatory science. New tools, new standards and new methods are important means to achieve regulatory science. "Medical Device Development Tool" proposed by the U.S. FDA is a novel medical device regulatory science tool, which can help medical device developers to predict and evaluate product performance more efficiently. It is also helpful for regulatory authorities to make regulatory decisions more efficiently. This study introduces the concept, qualification process, role of MDDT in medical device regulation and MDDT examples, and makes some discussion on the device evaluation from the perspective of reliability and validity. MDDT can facilitate the developing of novel medical device.
United States ; Medical Device Legislation ; Reproducibility of Results ; United States Food and Drug Administration ; Technology ; Device Approval

Objective: To develop effective alternatives to natural enzymes, it is crucial to develop nanozymes that are economical, resource efficient, and environmentally conscious. Carbon nanomaterials that have enzyme-like activities have been extensively developed as substitutes for traditional enzymes. Methods: Carbide-derived carbons (CDCs) were directly synthesized via a one-step electrochemical method from a MAX precursor using an ammonium bifluoride electrolyte at ambient conditions. The CDCs were characterized by systematic techniques. Results: CDCs showed bienzyme-like activities similar to that of peroxidase and superoxide dismutase. We systematically studied the dependence of CDC enzyme-like activity on different electrolytes and electrolysis times to confirm activity dependence on CDC content. Additionally, the synthesis mechanism and CDC applicability were elaborated and demonstrated, respectively. Conclusion The demonstrated synthesis strategy eliminates tedious intercalation and delamination centrifugation steps and avoids using high concentrations of HF, high temperatures, and halogen gases. This study paves the way for designing two-dimensional material-based nanocatalysts for nanoenzyme and other applications.
Ammonium Compounds/chemical synthesis* ; Carbon/chemistry* ; Electrochemical Techniques ; Enzymes ; Fluorides/chemical synthesis* ; Humans ; Nanostructures ; Oxidation-Reduction

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

ObjectiveTo investigate an outbreak of norovirus diarrhea in a welfare home for the elderly in Shanghai， and to analyze the epidemiology and virus genotype characteristics of the epidemic， thus providing a scientific basis for the prevention and control of norovirus epidemic. MethodsCase definition was clarified. After case definition， a standardized questionnaire was used to carry out case investigation to make comprehensive analysis in combination with field epidemiological investigation and laboratory tests results. ResultsThe epidemic lasted for 14 days， and 23 cases were reported with an incidence rate of 12.37% （23/186）， including 3 males and 20 females. There were more cases on the 1st， 4th and 6th floor of the main building in the welfare home， accounting for 52.17% （12/23） of total cases. 19 cases were reported in the main building， with an incidence rate of 11.59% （19/164）； 4 cases were reported in the auxiliary building， with an incidence rate of 18.18% （4/22）. There was no significant difference in the morbidity between the main building and the auxiliary building （χ²=0.779，P>0.05）. The main clinical manifestations were vomiting and diarrhea. There was a significant difference in the incidence of vomiting symptoms among the elderly， nursing staff and other staff in the welfare home （χ²=10.216， P<0.05）. But there was no significant difference in the incidence of diarrhea among the elderly， nursing staff and other staff （χ²=1.218， P>0.05）. Fecal samples were collected from 23 cases， 1 case family member， 68 risk personnel and 14 environmental surface swab samples. Norovirus GⅡ was detected in stool samples of 19 cases， 1 family member and 36 risk personnel. ConclusionOutbreak of norovirus infection is reported in a welfare home in Shanghai. The close contact between the elderly and health workers might lead to the outbreak.