[Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines].

Due to the lack of specialized guidance, the post-marketing research on clinical effectiveness of Chinese patent medicines demonstrates varied quality and lacks high-quality evidence, failing to meet the demands of policy-making, clinical decision-making, and industrial decision-making. To address this issue, this project gathered experts in clinical medicine, clinical pharmacy, evidence-based medicine, drug epidemiology, medical ethics, and policy and regulation in China. They referred to the model of international post-marketing research on medicines and developed Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines under the framework of relevant laws and regulations and technical guidance documents in China. The guidelines were developed with consideration to the characteristics of Chinese patent medicines, China's national conditions, and all the stakeholders including marketing authorization holders, clinical researchers, drug administration, and users. The development of the guidelines followed the requirements for developing group standards set by the China Association of Chinese Medicine. The guidelines fully implement the concept of full life-cycle research, emphasizing the combination of traditional Chinese medicine(TCM) theory, human use experience, and clinical trials and pay attention to the compliance, scientificity, and ethics of research. The guidelines clarify the topic selection and decision-making path of the post-marketing research on effectiveness of Chinese patent medicines through six steps: determining research purpose, analyzing drug characteristics, evaluating research basis, proposing clinical orientation, clarifying research purpose, and implementing classified research. The general principles of research design and implementation were clarified from eight aspects: research type, research objects, sample size, efficacy indicators, bias, missing data, evidence level, and practicality. It focuses on the research on the TCM syndrome-based efficacy evaluation, clinical value-oriented mechanism of action, and the effectiveness of Chinese patent medicines with different routes of administration. The guidelines provide a universal methodological basis for the post-marketing research on clinical effectiveness of Chinese patent medicines.

Single-center experience of transitioning from video-assisted laparoscopic to robotic Heller myotomy with Dor fundoplication for esophageal motility disorders.

BACKGROUND: Video-assisted laparoscopic Heller myotomy (LHM) has become the standard treatment option for achalasia. While robotic surgery offering some specific advantages such as better three-dimensional (3D) stereoscopic vision, hand-eye consistency, and flexibility and stability with the endowrist is expected to be shorter in learning curve than that of LHM for surgeons who are proficient in LHM. The aim of this study was to describe a single surgeon's experience related to the transition from video-assisted laparoscopic to robotic Heller myotomy with Dor fundoplication. METHODS: We conducted a retrospective observational study based on the recorded data of the first 66 Heller myotomy performed with laparoscopic Heller myotomy with Dor fundoplication (LHMD, 26 cases) and with the robotic Heller myotomy with Dor fundoplication (RHMD, 40 cases) by the same surgeon in Department of Thoracic Surgery of The First Affiliated Hospital of Nanchang University in China. The operation time and intraoperative blood loss were analyzed using the cumulative sum (CUSUM) method. Corresponding statistical tests were used to compare outcomes of both serials of cases. RESULTS: The median operation time was shorter in the RHMD group compared to the LHMD group (130 [IQR 123-141] minutes vs. 163 [IQR 153-169]) minutes, p < 0.001). In the RHMD group, one patient (2.5%) experienced mucosal perforation, whereas, in the LHMD group, the incidence of this complication was significantly higher at 19.2% (5 patients) (p = 0.031). Based on cumulative sum analyses, operation time decreased starting with case 20 in the LHMD group and with case 18 in the RHMD group. Intraoperative blood loss tended to decline starting with case 19 in the LHMD group and with case 16 in the RHMD group. CONCLUSIONS: Both RHMD and LHMD are effective surgical procedures for symptom relief of achalasia patients. RHMD demonstrates superior outcomes in terms of operation time and mucosal perforation during surgery compared to LHMD. Proficiency with RHMD can be achieved after approximately 16-18 cases, while that of LHMD can be obtained after around 19-20 cases.

Corticosteroids and Mesalamine Versus Corticosteroids for Acute Severe Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. METHODS: This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. RESULTS: Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). CONCLUSIONS: In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. CLINICALTRIALS: gov ID: NCT01941589.

[Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions"].

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Comparison of synchronous dual wavelength diode laser versus conventional endo-knives for esophageal endoscopic submucosal dissection: an animal study.

BACKGROUND: Endoscopic submucosal dissection (ESD) is widely used for en bloc resection in early gastrointestinal cancer. However, it is technically complex with long procedure time and high adverse event rates with using conventional knives. The aim of this animal study was to verify the feasibility of ESD using a novel 980/1470 nm dual diode laser (DDL-ESD) in comparison with conventional knives (C-ESD) in esophagus. METHODS: This was an in vivo animal study using eight porcine models. Four were allocated in DDL-ESD group and four were in C-ESD group. Every model underwent two ESDs to remove half circumferential esophageal mucosa. Each model's esophagus was harvested during postmortem at 24 h after ESD. Each specimen underwent gross inspection and histopathological examination was carried out. Procedure time, completeness of en bloc resection, adverse events (bleeding and perforation) and histological injury to muscularis propria were assessed. RESULTS: A total of 16 ESD procedures were performed with 100% en bloc resection rate. The procedure speed in DDL-ESD group was significantly faster as compared to C-ESD group (0.27 cm2/min vs. 0.21 cm2/min, p = 0.001). The number of intraoperative bleeding points and the use of haemostatic forceps were significantly lesser in DDL-ESD group (4 ± 2 vs. 8 ± 3, p = 0.016; 1 ± 1 vs. 3 ± 2, p = 0.029). Histological assessment showed that injury to muscularis propria in DDL-ESD was milder than C-ESD. There was no perforation observed in both groups. CONCLUSIONS: DDL-ESD technique appears to be safer and faster than C-ESD with less bleeding and injury to deep tissues.

Proactive health interventions in the workplace: The role of spatial playfulness in promoting mental health.

BACKGROUND: The high prevalence of mental illnesses has a serious impact on productive life and there is an urgent need to intervene using a variety of active and effective measures. OBJECTIVE: The concept of playfulness in space is introduced into the design of work spaces oriented towards active health interventions, creating a close interaction between the body and the space through play, thus developing a positive effect on the promotion of the physical and mental health of the staff. METHODS: With the help of the spatial order theory, the analysis of the interaction between body and space is attempted to explore the form, structure and scene of space in order to optimize the body's perception, cognition and behavior in the space, thus creating an indoor workspace model with positive intervention effects on human health. RESULTS: Based on the idea of spatial playful participation in active health interventions, this study explores the interaction between the body and the architectural space to enhance the perception and cognitive guidance of the space for the individual and to have a pleasant spiritual experience in the interaction to relieve work stress and enhance mental health. CONCLUSION: This series of discussions on the relationship between architectural space and the human body is of great relevance in improving the public health of occupational groups.

Direct endovascular treatment versus bridging therapy in patients with acute ischemic stroke eligible for intravenous thrombolysis: systematic review and meta-analysis.

OBJECTIVE: In this review and meta-analysis we sought to compare the efficacy and safety of direct endovascular thrombectomy (EVT) and bridging therapy for intravenous thrombolysis (IVT)-eligible patients with acute ischemic stroke caused by large vessel occlusions (AIS-LVO). METHODS: We searched Medline, Embase, and the Cochrane Library for published randomized clinical trials (RCTs) and observational studies providing outcomes of patients with IVT-eligible AIS-LVO who have undergone EVT with or without IVT. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as an mRS score of 0 or 1 at 90 days, (2) mortality at 90 days, (3) symptomatic intracranial hemorrhage (sICH), (4) any type of intracranial hemorrhage (ICH), (5) successful recanalization, and (6) clot migration. RESULTS: We included three RCTs and six observational studies (4 of which were propensity score-adjusted studies) with a total of 3133 patients. In unadjusted and adjusted analyses, no differences in the rates of mRS scores 0-2, mRS scores 0-1, mortality at 90 days, sICH or successful recanalization were detected between patients with AIS-LVO who underwent direct EVT or bridging therapy. The patients treated with direct EVT had a lower risk ratio for any type of ICH and clot migration than did the patients treated with bridging therapy. CONCLUSION: Compared with bridging therapy, direct EVT may be equally effective and yield a lower rate of ICH and clot migration in patients with AIS. TRAIL REGISTRATION NUMBER: PROSPERO: CRD42021236691.

Application of a buprenorphine transdermal patch for the perioperative analgesia in patients who underwent simple lumbar discectomy.

This study aimed to investigate the perioperative analgesic effect of a buprenorphine transdermal patch in patients who underwent simple lumbar discectomy.In total, 96 patients were randomly divided into parecoxib intravenous injection (Group A), oral celecoxib (Group B), and buprenorphine transdermal patch groups (Group C). The pain status, degree of satisfaction, adverse effects, and condition in which the patient received tramadol hydrochloride for uncontrolled pain were recorded on the night before surgery, postoperative day 1, postoperative day 3, and postoperative day 5.The degree of patient satisfaction in Group C was higher than that in Groups A and B, with minimal adverse effects.The buprenorphine transdermal patch had a better perioperative analgesic effect in patients who underwent simple lumbar discectomy.

Meta-Analysis of the Safety and Efficacy of Interferon Combined With Dacarbazine Versus Dacarbazine Alone in Cutaneous Malignant Melanoma.

The aim of this study was to compare the efficacy and safety of interferon (IFN) combined with dacarbazine (DTIC) (experimental group) versus DTIC alone (control group) in cutaneous malignant melanoma. After searching all available databases, eligible articles were identified and subjected to quality assessment. Meta-analysis was performed using RevMan 5.3; combined relative risk (RR) and 95% confidence intervals (95% CIs) were calculated for survival rates, response rates, and adverse events. Eight randomized controlled trials published between 1990 and 2014 involving 795 patients were included in the meta-analysis. Compared with DTIC alone, IFN combined with DTIC significantly increased the overall response rate (RR = 1.59, 95% CI 1.21-2.08, P = 0.0008),the complete response rate (RR = 3.30, 95% CI 1.89-5.76, P < 0.0001), 2-year survival (RR = 1.59, 95% CI 0.99-2.54, P = 0.050) grade ≥3 hematologic toxicity (RR = 2.30, 95% CI 1.32-4.02, P = 0.003), neurotoxicity (RR = 18.15, 95% CI 5.34-61.74, P < 0.00001), and flu-like symptoms (RR = 6.31, 95% CI 1.95-20.39, P = 0.002). The partial response rate, grade ≥3 nausea and vomiting, treatment-related, and 1- and 3-year survival were not significantly different between IFN combined with DTIC and DTIC alone. IFN combined with DTIC may moderately improve the complete response rate, but increases the incidence of adverse events and has no significant effect on 1- and 3-year survival in cutaneous malignant melanoma.

Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus.

Middle East respiratory syndrome (MERS), an emerging infectious disease caused by MERS coronavirus (MERS-CoV), has garnered worldwide attention as a consequence of its continuous spread and pandemic potential, making the development of effective vaccines a high priority. We previously demonstrated that residues 377-588 of MERS-CoV spike (S) protein receptor-binding domain (RBD) is a very promising MERS subunit vaccine candidate, capable of inducing potent neutralization antibody responses. In this study, we sought to identify an adjuvant that optimally enhanced the immunogenicity of S377-588 protein fused with Fc of human IgG (S377-588-Fc). Specifically, we compared several commercially available adjuvants, including Freund's adjuvant, aluminum, Monophosphoryl lipid A, Montanide ISA51 and MF59 with regard to their capacity to enhance the immunogenicity of this subunit vaccine. In the absence of adjuvant, S377-588-Fc alone induced readily detectable neutralizing antibody and T-cell responses in immunized mice. However, incorporating an adjuvant improved its immunogenicity. Particularly, among the aforementioned adjuvants evaluated, MF59 is the most potent as judged by its superior ability to induce the highest titers of IgG, IgG1 and IgG2a subtypes, and neutralizing antibodies. The addition of MF59 significantly augmented the immunogenicity of S377-588-Fc to induce strong IgG and neutralizing antibody responses as well as protection against MERS-CoV infection in mice, suggesting that MF59 is an optimal adjuvant for MERS-CoV RBD-based subunit vaccines.

Microbial community related to lysozyme digestion process for boosting waste activated sludge biodegradability.

Waste activated sludge from a lab-scale sequencing batch reactor was used to investigate the potential relation of microbial community with lysozyme digestion process for sludge solubilization. The results showed the microbial community shifted conspicuously as sludge suffered lysozyme digestion. Soluble protein and polysaccharide kept an increasing trend in solution followed with succession of microbial community. The rise of lysozyme dosage augmented the dissimilarity among communities in various digested sludge. A negative relationship presented between community diversity and lysozyme digestion process under various lysozyme/TS from 0 to 240min (correlation coefficient R(2) exceeded 0.9). Pareto-Lorenz curves demonstrated that microbial community tended to be even with sludge disintegration process by lysozyme. Finally, with diversity (H) decrease and community distribution getting even, the SCOD/TCOD increased steadily in solution which suggested the sludge with high community diversity and uneven population distribution might have tremendous potential for improving their biodegradability by lysozyme digestion.

Temozolomide for Treating Malignant Melanoma.

Melanoma is one of the most malignant forms of skin cancer; with a rapidly increasing prevalence. Early-stage melanoma is curable, but advanced metastatic melanoma is almost always fatal, and patients with such advanced disease have short median survival. Surgery and radiotherapy play a limited role in the treatment of metastatic melanoma. Rather, chemotherapy remains the mainstay of treatment, although other approaches, including biotherapy and gene therapy, have been attempted. The authors hereby, evaluated the use of temozolomide (TMZ) for treating metastatic melanoma compared to dacarbazine (DTIC), the effectiveness of TMZ for treating brain metastases, as well as TMZ resistance and how the efficacy of TMZ in malignant melanoma can be increased. Two chemotherapeutic regimens are commonly used for palliative treatment of malignant melanoma: intravenous administration of DTIC and oral administration of the alkylating agent temozolomide (TMZ). Compared to DTIC, TMZ is very well tolerated and has an advantage in terms of improving the quality of life of patients with metastatic melanoma. While the prognosis is currently unpromising, chemotherapy plays a palliative role for patients with metastatic melanoma. The toxicity of treatment regimens based on DTIC and TMZ do not differ significantly, although TMZ is costlier. These findings provide a reference for future researchers via a comprehensive analysis of the relevant literature.

Emergency contraception by low-dose mifepristone: observation of 150 cases.

For various reasons, each community may vary in their measures taking for emergency contraception, which has been a frequent necessity especially in the out-patient department of gynecology. In this article, the authors report the effect of single oral administration of low-dose mifepristone (25 mg) in emergency contraception, with a total effective rate of 80.89%.