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To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19).This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate.A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P0.01). No serious adverse events occurred during treatment.BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).

Objective: To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019 (COVID-19) vaccination. Methods: We systematically searched PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang Data, and VIP Database from the inception of each database to August 31, 2021. Randomized controlled clinical trials (RCTs) on the safety of different types of COVID-19 vaccines were retrieved and analyzed. A random or fixed-effects model was used with an odds ratio as the effect size. The quality of each reference was evaluated. The incidence of the adverse reactions of the placebo group and the vaccination group was compared. Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses. Results: A total of 13 articles were included, with 81 287 subjects. Compared with the placebo group, the vaccination group showed a higher combined risk ratio (RR) of total adverse reactions (RR=1.67, 95% CI: 1.46-1.91, P

The composition of cell contacts in the endometrium plays an important role in the process of embryo implantation and the establishment of pregnancy. In previous studies, we showed an induction of the tight junction protein claudin-3 in the developing decidua from day 6.5 of pregnancy onward. To evaluate the role of this specific claudin-3 distribution, we here evaluated the effect of an endometrial claudin-3 deletion in implantation and embryo development in claudin-3 knockout mice. Claudin-3 knockout mice were fertile but revealed a slightly reduced amount of implantation sites as well as of litter size. Though implantation sites showed morphologically regularly developed embryos and deciduas, depth of ectoplacental cone invasion was reduced in tendency compared to controls. The weight of the implantation sites on day 6.5 and 8.5 of pregnancy as well as the weight of the embryos on day 17.5 of pregnancy, but not of the placentas, was significantly reduced in claudin-3 knockout mice due to a maternal effect. This could be due to an impairment of decidualization as substantiated by a downregulation of the transcription of various decidua-associated genes in the early implantation sites of claudin-3 knockout mice. The fact that claudin-3 knockout mice are nevertheless fertile possibly may be compensated by the presence of other claudins like claudin-4 and claudin-10.

Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology.Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.

Anaerobic ammonium oxidation (anammox) process exhibits advantages in treating high-ammonium livestock wastewater, while the anammox bacteria is vulnerable to heavy metal and antibiotics. Arsenic and sulfonamides extensively existed in livestock wastewater; unfortunately, their effects on the anammox process have not yet been investigated. This work comprehensively evaluated the single and joint effects of As(III) and sulfamethoxazole (SMX) on the anammox process and revealed the related inhibitory mechanism. Anammox had extraordinary resistance to As(III) stress (0–50 mg L−1), while nitrogen removal sharply deteriorated under the stress from 50 mg L−1 As(III) and 3 mg L−1 SMX. Exogenous As(III) damaged the protection of extracellular polymeric substance (EPS) and aggravated the inhibition of SMX. As(III) had direct toxic effects on anammox bacteria, while enhanced denitrifying capacity was the reason for inhibition of anammox by SMX. Moreover, the host arsenic resistance genes were changed under SMX inhibition. The findings of this study enrich our knowledge of the anammox response to various pollutants, and provide the operational guidance for anammox process to treat wastewater containing antibiotic and heavy metal.