Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Charcot-Marie-Tooth Disease/genetics* ; DNA-Binding Proteins/genetics* ; Humans ; Mutation ; Transcription Factors/genetics*

ObjectiveTo explore the effect of Gegen Qinliantang （GQL） on vulnerable plaque of atherosclerosis based on the macrophage pyroptosis mediated by nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1 pathway. MethodA total of 12 normal C57BL/6CNC mice were used as the control group， and 60 ApoE^-/- mice of the same line were randomized into 5 groups： model group， low-dose， medium-dose， and high-dose GQL groups （GQL-D， GQL-Z， GQL-G groups， respectively）， and western medicine group. The control group and model group were given （ig） equal volume sterile distilled， and GQL-D， GQL-Z， GQL-G and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. Aortic plaques were observed based on hematoxylin and eosin （HE） staining. Serum levels of interleukin （IL）-1β and IL-18 were detected by enzyme-linked immunosorbent assay （ELISA）， protein levels of macrophage mannose receptor （CD206）/apoptosis-associated speck-like protein containing a CARD （ASC） and CD206/NLRP3 by double-labeling immunofluorescence， and C-terminal gasdermin D （GSDMD）， N-terminal GSDMD， NLRP3， pro-cysteinyl aspartate specific proteinase 1 （pro-Caspase-1） and NF-κB p65 by Western blot. ResultCompared with the control group， model group demonstrated serious pathological changes， rise of the levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and decrease of CD206 level （P<0.05）. As compared with model group， the administration groups showed alleviation of the lesions in aortic wall， decrease in levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and rise of CD206 level， with significant difference between some groups （P<0.05）. ConclusionGegen Qinliantang alleviates vulnerable plaque of atherosclerosis by regulating NF-κB/NLRP3/Caspase-1 pathway and further relieving macrophage pyroptosis.

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*

Objective To evaluate and analyze the panel composition and conflict of interest management of clinical practice guidelines of rehabilitation.Methods Clinical practice guidelines of rehabilitation were systematically retrieved from PubMed, EMBASE, China Biology Medicine disc, CNKI, Wanfang Data and Medlive database, the National Institute for Health and Care Excellence, National Guideline Clearinghouse, The Scottish Intercollegiate Guidelines Network, World Health Organization (WHO) and Guidelines International Network until January 11, 2020. Two researchers independently screened and cross-checked the literatures, and extracted the basic information of included guidelines, including the title, formulating institution, published journol, as well as the expert group, the number of expert group, the specific division of labor and their discipline, affiliation and the geographic location, the statement and management of conflict of interest, types of conflicts of interest, and whether to accept fund and the source of the fund.Results A total of 84 guidelines were finally included, 17 domestic ones and 67 foreign ones, in which, 52 (61.9%) reported the expert panel; 22 (26.2%) reported the number of expert panel groups, 21 (25.0%) indicated the specific division of work among the members of the expert panel, 74 (88.1%) reported the names of the members of the expert panel, 47 (56.0%) reported the subjects and specialties of the panelists, 70 (83.3%) reported the affiliation and location of panelists, 14 (16.7%) mentioned the management of conflicts of interest, and 25 (29.8%) reported if there were conflicts of interest. Only five of the 16 funded guidelines stated that there was no conflict of interest between the funding and the development of the guidelines. Among them, the reporting rate of expert panel was significantly higher in foreign countries than in China (χ2 = 9.542, P < 0.01), the reporting rate of name of expert panel members and specific division of labor were higher in foreign countries than in China ( χ2 > 4.155, P < 0.05), and the reporting rate of conflict of interest management was also higher in foreign countries than in China ( P < 0.05). There was no significant difference in whether there was a conflict of interest, whether it was funded and the type of funding at home and abroad ( P > 0.05). Conclusion In gerenal, clinical practice guidelines of rehabilitation published at home and abroad are necessary to be improved in the reporting quality of expert group formulation and division of labor, conflict of interest reporting and management. It is proposed that future guideline developers should follow the WHO Handbook for Guideline Development, assign roles of experts, strengthen the management and reporting of conflicts of interest, and standarderize the development process and reporting of the guidelines.

Objective To analyze the contents of the recommendations of stroke clinical rehabilitation guidelines in order to provide advice for the development and implementation of stroke rehabilitation guidelines.Methods PubMed, EMBASE, CNKI, China Biology Medicine disc, Wanfang databases and guideline-related websites were retrieved from the date of establishment to January 2020, to collect stroke clinical rehabilitation guidelines. The main content, recommendations based on evidence, the type of evidences, and the scope of evidence classification had been explored based on World Health Organization Handbook for Guideline Development-2nd Edition.Results A total of twelve guidelines were included in this study, one in Chinese and eleven in English. They were from the United States (3 guidelines), United Kingdom (3 guidelines), Canada (3 guidelines), Australia (2 guidelines) and China (1 guidelines), and published from September, 2005 to February, 2019. Three articles (25.0%) used the Appraisal of Guidelines for Research and Evaluation (AGREE) for quality evaluation, and two articles (16.7%) used Grading of Recommendations Assessment, Development and Evaluation (GRADE) as the grading system. The recommendations covered the areas such as: cognitive dysfunction (4 dimensions) with a recommendation of cognitive function assessment at most (7 guidelines, 66.7%), language and swallowing dysfunction (5 dimensions) with a recommendation of swallowing-related complications at most (10 guidelines, 83.3%), motor dysfunction (6 dimensions) with a recommendation of spasm treatment at most (10 guidelines, 83.3%), and psychological and behavioral dysfunction (4 dimensions) with a recommendation for assessment or monitoring at most (6 guidelines, 50.0%). There were many recommendations in these areas, but the types of evidence were different, and observational studies and/or randomized controlled trials accounted for most.Conclusion There are different types of evidence and levels of recommendation strength. It is proposed for future guideline developers in stroke rehabilitation to follow World Health Organization Handbook for Guideline Development-2nd Edition to improve the quality and the overall implementation of the rehabilitation guidelines, and to improve the quality and safety of rehabilitation.

Objective: To study on the physical and chemical properties of dichroa alkali hydrochloride and to establish a method for the determination of entrapment efficiency of dichroa alkali hydrochloride liposomes. Method: HPLC was used to determine the content of dichroa alkali hydrochloride with mobile phase of acetonitrile-water-triethylamine-glacial acetic acid(9:91:0.35:0.75) and detection wavelength at 265 nm.The oil-water partition coefficient of this compound in different pH range was measured by shake flask method.The stability of the dichroa alkali hydrochloride in phosphate buffer solution with different pH after sterilization at 125℃ for 30 min was investigated.Ammonium sulfate gradient method was used to prepare dichroa alkali hydrochloride liposomes.The microcolumn was prepared by dextran gel and cation exchange resin,respectively.Then the free drug and liposome were separated by centrifugation,the drug content was measured,and the encapsulation efficiency was calculated.The t-test was performed using SPSS 20.0 software,the differences between these two methods were compared. Result: In the pH 6-9,the oil-water partition coefficient of dichroa alkali hydrochloride increased with increasing of pH,which was between 0.016 and 1.44;the recovery rate of dichroa alkali hydrochloride after sterilization was 37.16%-57.91%.Between the dextran gel microcolumn centrifugation and the cation exchange resin microcolumn centrifugation,there was no significant difference in the entrapment efficiency of the liposomes. Conclusion: Dichroa alkali hydrochloride is suitable for preparation of liposomes.However,its stability is not ideal,so the experimental temperature should be strictly controlled in the preparation process.Dextran gel microcolumn centrifugation and cation exchange resin microcolumn centrifugation can be used to determine the entrapment efficiency of dichroa alkali hydrochloride liposomes,and the cation exchange resin microcolumn centrifugation is suggested after comparison.

Objective The level of lactic acid in blood can reflect the degree of ischemia and hypoxia of brain tissue and cerebral perfusion pressure. The aim of this paper is to explore the value of blood lactate and lactate clearance in evaluating the survival rate and neurological outcome of patients with craniocerebral trauma. Methods The clinical data of 497 craniocerebral trauma patients admitted to our hospital from September 2017 to July 2018 were collected and retrospectively analyzed. Patients were divided into groups with different 6 h lactate clearance rates and admission lactate levels, and the differences in mortality and outcome of neurological function in each group were compared. Results The serum admission lactate levels、serum lactate levels at 6 hours, 28-day mortality and 28-day poor nerve function prognosis rate of patients with different 6h lactate clearance rates were statistically significant differences(P < 0. 05). The efficacy of 6h lactic acid to predict the mortality rate of patients was better than that of admission lactic acid and 6h lactate clearance rate (Z=3.71、Z=3.95,P<0.05). However, in predicting the neurological function of patients, the lactate clearance rate is not better than blood lactate level at any time(Z=1.30，Z=0.81，P>0.05). Conclusion 6h lactic acid has the best ability to judge the mortality of patients while lactic acid clearance rate is not better than the blood lactate level at any time in predicting the neurological function of patients.