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

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

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

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*

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

OBJECTIVE: To study the effect of freshening technique on docking site in tibial bone transport management. METHODS: Retrospective cohort study was conducted about the effect of freshening technique on docking site in 20 cases(15 males and 5 females) treated with tibial bone transport from January of 2014 to December of 2019. The age of patients ranged from 19 to 62 years old, with an average of (42.3±11.5)years old. Seven patients had infectious bone defect and 13 patients had non-infectious. Application of freshening technique immediately after docking included resection of invaginated skin or soft tissue, removal of closed sclerotic bone, re-apposition, increasing the contact, acute compression of freshened docking site and grafting from adjacent medullary or bone debris, followed by post-operative gradual compression. RESULTS: The amount of segmented bone defect ranged from 5 to 15 cm, with an average of(9.2±2.9) cm. Time required from osteotomy to contact of butt end ranged from 26 to 243 days, with an average of(109.1±51.1) days. The duration needed from 3 to 7 months with an average of(3.7±1.1) months before reaching radiological healing criterion in docking site. Fourteen out of 15 concurrent fibular osteotomy were united. Consolidation time for distracted callus ranged from 5 to 28 months, with an average of (15.0±6.5) months. Bone healing index(BHI) ranged from 0.8 to 2.8 months/cm, with an average of (1.6±0.5) months. One surgical site infection (5%) in tibial was noted. No refractures were found in follow-up ranged from 12 to 73 months, with an average of(37.6±20.3) months after fixator removal. CONCLUSION Freshening technique immediately after docking had advantages of the shorter healing time, avoidance of refracture, and independance of necessity for remote autograft harvest.
Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Osteotomy ; Retrospective Studies ; Tibia/surgery* ; Tibial Fractures/surgery* ; Treatment Outcome ; Ilizarov Technique ; Osteogenesis, Distraction

In order to meet the needs of prevention and control of intestinal infectious diseases， a comprehensive surveillance for diarrheal diseases has been innovated and explored in Shanghai since 2012. The surveillance has extensive distribution of sentinel hospitals， systematic sampling， multi-pathogen collection， and hospital information system （HIS） as the basis， which has achieved “One system for surveillance of multiple diseases and one sample for detection of multiple pathogens". Continual active surveillance for the whole population has been conducted， covering demography， clinical information， epidemiology， pathogen detection， and drug sensitivity test for diarrhea cases. The surveillance has obtained preliminary achievements as follows. First， diarrheal diseases and their periodic changes have been characterized， in which the most prevalent pathogen of diarrhea is determined to be norovirus in Shanghai. Second， some rare pathogens and serotypes have been identified that may provide clues to the sources of outbreaks. Third， it facilitates the information sharing between public health institutions and clinical institutions， and provides scientific evidence for clinical diagnosis and treatment. In the future， Shanghai diarrhea comprehensive surveillance will be improved for expanding range and depth of surveillance， artificial intelligence assisted diagnosis and treatment， early warning of outbreaks， prediction of epidemic trends， and application of new detection technologies.

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.