Synthesis of di/trifluoromethyl cyclopropane-dicarbonitriles via [2+1] annulation of fluoro-based diazoethanes with (alkylidene)malononitriles.

Herein, we describe a [2+1] annulation reaction of di/trifluorodiazoethane with (alkylidene)malononitriles. This protocol offers a streamlined synthesis of a wide range of stereospecific and densely functionalized difluoromethyl and trifluoromethyl cyclopropane-1,1-dicarbonitriles. Further functional group interconversions or skeletal elaborations afford structurally distinct cyclopropyl variants.

Microbiota and mycobiota in bronchoalveolar lavage fluid of silicosis patients.

BACKGROUND: The contribution of bronchoalveolar lavage fluid (BALF) microbiota and mycobiota to silicosis has recently been noticed. However, many confounding factors can influence the accuracy of BALF microbiota and mycobiota studies, resulting in inconsistencies in the published results. In this cross-sectional study, we systematically investigated the effects of "sampling in different rounds of BALF" on its microbiota and mycobiota. We further explored the relationship between silicosis fatigue and the microbiota and mycobiota. METHODS: After obtaining approval from the ethics board, we collected 100 BALF samples from 10 patients with silicosis. Demographic data, clinical information, and blood test results were also collected from each patient. The characteristics of the microbiota and mycobiota were defined using next-generation sequencing. However, no non-silicosis referent group was examined, which was a major limitation of this study. RESULTS: Our analysis indicated that subsampling from different rounds of BALF did not affect the alpha- and beta-diversities of microbial and fungal communities when the centrifuged BALF sediment was sufficient for DNA extraction. In contrast, fatigue status significantly influenced the beta-diversity of microbes and fungi (Principal Coordinates Analysis, P = 0.001; P = 0.002). The abundance of Vibrio alone could distinguish silicosis patients with fatigue from those without fatigue (area under the curve = 0.938, 95% confidence interval [CI] 0.870-1.000). Significant correlations were found between Vibrio and haemoglobin levels (P < 0.001, ρ = -0.64). CONCLUSIONS: Sampling in different rounds of BALF showed minimal effect on BALF microbial and fungal diversities; the first round of BALF collection was recommended for microbial and fungal analyses for convenience. In addition, Vibrio may be a potential biomarker for silicosis fatigue screening.

Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss.

Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given its inherent complexity, few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive. Here, we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors, including anesthesia with surgery (AS), systemic inflammation, and neurotransmission modulation. We found that both bacterial lipopolysaccharide (LPS) and cholinergic receptor antagonist scopolamine (Scop) induction reduced neuronal activities in the delirium-related brain network, with the latter presenting a similar pattern of reduction as found in delirium patients. Consistently, Scop injection resulted in reversible cognitive impairment with hyperactive behavior. No loss of cholinergic neurons was found with treatment, but hippocampal synaptic functions were affected. These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.

Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin ß3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.

Clinical Characteristics of Aggressive NK-Cell Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore and summarize the clinical characteristics and treatment of aggressive NK-cell leukemia (ANKL), and provide new insights for clinical diagnosis and treatment of this disease.@*METHODS@#The clinical data of 7 patients with ANKL admitted to the First Affiliated Hospital of Wannan Medical College from March 2014 to July 2021 were retrospectively analyzed, and their clinical characteristics, laboratory and imaging results, treatment and outcomes were analyzed.@*RESULTS@#Among the 7 patients, 5 were males and 2 were females, with a median age of 47 (33-69) years old. The morphology of bone marrow cells in 7 patients showed similar large granular lymphocytes. Immunophenotyping revealed abnormal NK cells in 5 cases. By the end of follow-up, 6 cases died and 1 case survived, with a median survival time of 76.9 (4-347) days.@*CONCLUSION@#ANKL is a rare disease with short course and poor prognosis. If combined with hemophagocytic syndrome (HPS), the prognosis is even worse. There is no unified treatment method at present, and the use of PD-1 inhibitors may prolong the survival in some patients.

Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.@*RESULTS@#Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.@*CONCLUSION@#PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

Phylogenetic analysis of chloroplast genome of Tussilago farfara L / 药学学报

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

Pulvinatusia (Brassicaceae), a new cushion genus from China and its systematic position.

The new genus and species Pulvinatusiaxuegulaensis (Brassicaceae) are described and illustrated. The species is a cushion plant collected from Xuegu La, Xizang, China. Its vegetative parts are most similar to those of Arenariabryophylla (Caryophyllaceae) co-occurring in the same region, while its leaves and fruits closely resemble those of Xerodrabapatagonica (Brassicaceae) from Patagonian Argentina and Chile. Family-level phylogenetic analyses based on both nuclear ITS and plastome revealed that it is a member of the tribe Crucihimalayeae, but the infra-/intergeneric relationships within the tribe are yet to be resolved.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Experimental study on rabbit lamellar corneal transplantation with double-layer corneal stromal lens attactched by fibrin sealant / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the biocompatibility of double-layer corneal stromal lens attactched by fibrin sealant(FS)<i>in vivo</i>, and to explore the feasibility of using this material for corneal transplantation.<p>METHODS: Fifteen healthy and clean New Zealand white rabbits were selected for a self-control study. The right eye of the rabbit was used as the experimental eye and the left eye was used as the control eye. The experimental eyes used FS adhesived double-layer corneal stromal lens as the material for lamellar keratoplasty, and the control eyes did not undergo manual intervention. At 7,14, and 28d after surgery, a hand-held slit lamp was used to observe the cornea of the rabbits and then score the biocompatibility. The corneas of both eyes were taken for histopathological examination by HE staining to observe the corneal recovery at the same time.<p>RESULTS: Slit lamp observation results showed that by 28d after the operation, the corneal epithelium of the experimental eyes grew well, the degree of corneal transparency was basically restored, the degree of edema was reduced, the growth of neovascularization to the corneal edge was not aggravated, and no rejection reaction such as epithelial and endothelial rejection lines were seen; The control eyes had clear corneas and smooth corneal epithelium. The results of biocompatibility score showed that the degree of corneal implant edema gradually decreased, the transparency gradually recovered, the rejection reaction was less, and the biocompatibility of corneal implants was better in the experimental eyes after corneal transplantation. There were no differences in the degree of corneal transparency, edema and neovascularization growth between the experimental and control eyes at 28d after surgery(<i>P</i>>0.01). The results of histopathological examination showed that by 28d after corneal transplantation, there were 4-5 layers of corneal epithelial cells covering the surface of the implant in the experimental eyes, the corneal collagen was neatly and regularly arranged, no obvious inflammatory cell infiltration was seen in the implant, the boundary between the two lenses disappeared, the interlayer FS was completely absorbed by the organism, the implant was fused with the implant bed, and no obvious demarcation was seen.<p>CONCLUSION:Using FS pasted double-layer corneal stroma lens as a graft for lamellar keratoplasty has better recovery, less rejection and better biocompatibility, and can be used for lamellar keratoplasty.

A regulatory miRNA-mRNA network is associated with transplantation response in acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a life-threatening complication characterized by rapid decline in renal function, which frequently occurs after transplantation surgery. However, the molecular mechanism underlying the development of post-transplant (post-Tx) AKI still remains unknown. An increasing number of studies have demonstrated that certain microRNAs (miRNAs) exert crucial functions in AKI. The present study sought to elucidate the molecular mechanisms in post-Tx AKI by constructing a regulatory miRNA-mRNA network. RESULTS: Based on two datasets (GSE53771 and GSE53769), three key modules, which contained 55 mRNAs, 76 mRNAs, and 151 miRNAs, were identified by performing weighted gene co-expression network analysis (WGCNA). The miRDIP v4.1 was applied to predict the interactions of key module mRNAs and miRNAs, and the miRNA-mRNA pairs with confidence of more than 0.2 were selected to construct a regulatory miRNA-mRNA network by Cytoscape. The miRNA-mRNA network consisted of 82 nodes (48 mRNAs and 34 miRNAs) and 125 edges. Two miRNAs (miR-203a-3p and miR-205-5p) and ERBB4 with higher node degrees compared with other nodes might play a central role in post-Tx AKI. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that this network was mainly involved in kidney-/renal-related functions and PI3K-Akt/HIF-1/Ras/MAPK signaling pathways. CONCLUSION: We constructed a regulatory miRNA-mRNA network to provide novel insights into post-Tx AKI development, which might help discover new biomarkers or therapeutic drugs for enhancing the ability for early prediction and intervention and decreasing mortality rate of AKI after transplantation.

Comparative Study of Oral Bacteria and Fungi Microbiota in Tibetan and Chinese Han Living at Different Altitude.

Knowledge about the impact of altitude and ethnicity on human oral microbiota is currently limited. To obtain the baseline of normal salivary microbiota, we analyzed the bacteria and fungi composition in Tibetan (HY group) and Han population (CD group) living at different altitudes by using next-generation sequencing (NGS) technology combined with PICRUSt and FUNGuild analyses. There were significant differences in oral microbiota composition between the two groups at phylum and genus levels. At the phylum level, the HY group had higher relative abundances of Firmicutes and Ascomycota, whereas the Bacteroidetes and Basidiomycota in the CD group were richer. These changes at the phylum level reflected different dominant genus compositions. Compared with the Han population, Candida, Fusarium, Zopfiella, Streptococcus, Veillonella and Rothia in Tibetan were higher. Surprisingly, the Zopfiella was found almost exclusively in the Tibetan. The PICRUSt and FUNGuild analysis also indicated that the function of the bacterial and fungal communities was altered between the two groups. In conclusion, our results suggest that there are significant differences in oral microbial structure and metabolic characteristics and trophic modes among Tibetan and Han population living at different altitudes. We first established the oral microbiota framework and represented a critical step for determining the diversity of oral microbiota in the Tibetan and Han population.

Zinc-Enabled Annulation of Trifluorodiazoethane with 2H-Azirines to Construct Trifluoromethyl Pyrazolines, Pyrazoles, and Pyridazines.

A diethylzinc-promoted unconventional annulation reaction of 2,2,2-trifluorodiazoethane with 2H-azirines is described. This transformation involves two [3 + 2] cycloaddition steps and one dinitrogen extrusion process in one pot, thus giving a broad array of 3-trifluoromethyl pyrazolines in good yields with excellent diastereoselectivities. Further transformations provide facile access to 3-trifluoromethyl pyrazoles and 3,5-ditrifluoromethyl pyridazines with good efficiency.

The role of SARC-F scale in predicting progression risk of COVID-19 in elderly patients: a prospective cohort study in Wuhan.

BACKGROUND: Since the outbreak of COVID-19, it has been documented that old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, it is unknown whether sarcopenia, a common geriatric syndrome, is associated with poor prognosis among older COVID-19 patients. The aim of our prospective cohort study is to investigate the association between sarcopenia risk and severe disease among COVID-19 patients aged ≥60 years. METHOD: A prospective cohort study of 114 hospitalized older patients (≥60 years) with confirmed COVID-19 pneumonia between 7 February, 2020 and 6 April, 2020. Epidemiological, socio-demographic, clinical and laboratory data on admission and outcome data were extracted from electronic medical records. All patients were assessed for sarcopenia on admission using the SARC-F scale and the outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards model to identify the association between sarcopenia and progression of disease defined as severe cases in a total of 2908 person-days. RESULT: Of 114 patients (mean age 69.52 ± 7.25 years, 50% woman), 38 (33%) had a high risk of sarcopenia while 76 (67%) did not. We found that 43 (38%) patients progressed to severe cases. COVID-19 patients with higher risk sarcopenia were more likely to develop severe disease than those without (68% versus 22%, p < 0.001). After adjustment for demographic and clinical factors, higher risk sarcopenia was associated with a higher hazard of severe condition [hazard ratio = 2.87 (95% CI, 1.33-6.16)]. CONCLUSION: We found that COVID-19 patients with higher sarcopenia risk were more likely to develop severe condition. A clinician-friendly assessment of sarcopenia could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.

Bioactivity-guided discovery of quality control markers in rhizomes of Curcuma wenyujin based on spectrum-effect relationship against human lung cancer cells.

BACKGROUND: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs. PURPOSE: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method. METHODS: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively. RESULTS: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC50) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, ß-elemene and ß-caryophyllene. CONCLUSION: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.

The association of sleep quality and sleep duration with nutritional status in older adults: Findings from the WCHAT study.

OBJECTIVE: To identify the associations between sleep quality, sleep duration and nutritional status in older adults. METHODS: Data from a total of 6792 community-dwellings adults aged 50 and over from the baseline of the West China Health and Aging Trend (WCHAT) study were analyzed. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). PSQI scores >5 were categorized as poor sleep quality. Duration of sleep was classified as <6 h, 6-7 h, 7-8 h, 8-9 h and ≥9 h. The Mini Nutritional Assessment Short Form (MNA-SF) was used to assess nutritional status and a score <12 was identified as indicating a risk of malnutrition. Logistic regression models were used to explore the associations. RESULTS: Of 6792 participants (mean age 62.4 ±â€¯8.3 years, 62.5 % women), 1831 (27.0 %) were at risk of malnutrition. The prevalence of poor sleep quality was 47.1 %. In the logistic regression model adjusted for potential confounders, poor sleep quality was significantly associated with a risk of malnutrition (OR = 1.62, 95 %CI = 1.44, 1.82). Sleep durations of less than 6 h and of more than 9 h were shown to increase the odds of malnutrition risk (OR = 1.42, 95 %CI = 1.16, 1.73 and OR = 1.24, 95 %CI = 1.05, 1.47, respectively). CONCLUSIONS: Sleep disorders were significantly associated with malnutrition risk among older adults. Our results highlight the importance of good sleep quality and enough sleep in order to maintain good nutritional status in older adults.

The association between systemic inflammatory markers and sarcopenia: Results from the West China Health and Aging Trend Study (WCHAT).

BACKGROUND: Increased evidence suggests chronic inflammation is significant in the progression of sarcopenia in older adults. In this study, we aimed to compare the level of systemic inflammation markers (White blood cells, neutrophils, lymphocytes, platelets and their derived ratios) between sarcopenic and non-sarcopenic individuals and investigate the association of these inflammatory markers with sarcopenia. METHODS: This cross-sectional study included 4224 adults (1514 men and 2710 women) from the West China Health and Aging Trend (WCHAT) study. Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia (AWGS). The value of systemic inflammatory markers was based on laboratory data. Multiple logistic regression analysis was used to explore the association between inflammatory markers and sarcopenia after adjusting for covariates. RESULTS: Among 4224 participants (mean age 62.3 ±â€¯8.2 years, 64.2 % women), 814 (19.3 %) were diagnosed as sarcopenia. After adjusting for potential confounders, logistic regression analysis indicated that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were significantly associated with sarcopenia. Participants in the highest NLR, PLR and SII value group had higher odds for sarcopenia than those in the lowest value group (OR [95 %CI]: 1.233 [1.002,1.517], 1.455 [1.177,1.799] and 1.268 [1.029,1.561], respectively). CONCLUSIONS: Higher NLR, PLR, and SII level are associated with an increased prevalence of sarcopenia in middle-aged and older adults. Since these systemic inflammatory markers are inexpensive and can be obtained easily from routine blood tests, regular follow-up of NLR, PLR and SII may be an effective strategy in sarcopenia screening and management.

Ethnopharmacology, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Radix Astragali / 中国结合医学杂志

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients