The incidence of thrombosis-induced cardiovascular diseases is increasing worldwide and poses a serious threat to human health. Three factors, slow speed of blood flow, hypercoagulable blood and vascular damage, have been considered to be causes of thrombosis. Antithrombotic drugs have been classified into three categories based on the mechanism of thrombosis, including anticoagulants, platelet inhibitors and fibrinolytics. The coagulation and anticoagulation systems have drawn increasing attention because of the important role they play in the process of thrombosis. Novel compounds with anticoagulant activity are now emerging, alleviating to some extent some of the problems associated with the clinical use of early approved thrombotic drugs, such as high bleeding risk, slow onset of action and narrow therapeutic windows. In this review, we initially describe the mechanisms of coagulation as well as thrombosis. Meanwhile, a wide range of bioactive compounds and potential antithrombotic candidates reported in recent years have been summarized. In addition, the structure-activity relationship of certain compounds has been discussed, expecting to facilitate the development of molecules with anticoagulant biological activity for the treatment of thrombotic diseases.

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.
Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Hot Temperature ; Medicine, Chinese Traditional ; Prescriptions ; Syndrome

Sacubitril valsartan sodium (LCZ696) is an ionic cocrystal drug. The purpose of this study was to explore the cocrystal features of LC696 by establishing a variety of characterization methods, and thus provide basic research data for effective quality control. The cocrystal characteristics of LCZ696 and its tablets were identified by applying analytical means including powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), Raman spectra (RM), differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). The crystalline water and hygroscopicity of LCZ696 were analyzed by thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), hygroscopicity test and Karl Fischer reaction method. The results show that PXRD, FTIR, DSC and ssNMR can effectively distinguish the features of LCZ696 cocrystal, sacubitril monomer, valsartan monomer, and sacubitril-valsartan (1∶1) mixture. RM can be used as a supplementary approach. Combined with the analysis by TGA, DVS, hygroscopicity test and Karl Fischer reaction method results, LCZ696 contains 2.5 crystalline water molecules and is very hygroscopic; we recommend that LCZ696 be stored in an environment with a relative humidity below 60%. By characterizing the crystal features we can establish quality control measure and evaluate the stability of the drug tablets. This study provides data in support for the establishment of the LCZ696 quality standard.

The current study was designed to evaluate the modulatory effects of paeoniflorin on the dysregulated gut microbiota as well as the disturbed fecal bile acids (BAs) in colitis mice. After approved by Xi'an Jiaotong University Ethics Committees (Approval No. XJTU2019-679), the animals were randomly distributed into the control (Con), colitis, low dose paeoniflorin (PF-L, 25 mg·kg^-1·d^-1), high dose paeoniflorin (PF-H, 50 mg·kg^-1·d^-1) and 5-aminosalicylic acid (5-ASA, 50 mg·kg^-1·d^-1) groups. Colitis was induced by administering 3% (w/v) DSS in drinking water for 7 days. Paeoniflorin and 5-ASA were dissolved in water and administered to the appropriate groups by oral gavage over the 7-day period. The mice were monitored daily, and the disease activity index (DAI) comprising of body weight loss, stool consistency and gross blood was measured. The pathological changes of colon were evaluated by HE staining; the levels of inflammatory cytokines in colonic tissue were determined by ELISA; the gut permeability was measured by FITC-dextran. Microbiota analysis based on 16S rDNA and targeted metabolomics for BAs were used to evaluate the composition of gut microbiota and fecal BAs pool. The results showed that administration of paeoniflorin markedly alleviated the inflammatory response and intestinal barrier dysfunction in DSS-induced colitis. Importantly, these ameliorative effects of paeoniflorin were accompanied by the improvements of disturbed composition of gut microbiota and the dysmetabolism of bile acids in feces. Finally, we performed Spearman's correlation analysis between the fecal BAs and gut microbiota genera, and found that Lactobacillus has a strong positive correlation with DCA and LCA which were reported to confer the beneficial effects of maintaining intestinal homeostasis. Taken together, paeoniflorin might improve the intestinal homeostasis in colitis mice via modulating gut microbiota and fecal BAs metabolism.

Asian Continental Ancestry Group/genetics* ; Charcot-Marie-Tooth Disease/genetics* ; China ; Genetic Profile ; Humans ; Pedigree

Sarcopenia is a process in which skeletal muscle mass and strength are gradually declining, resulting a main health challenge for the old adults. Mitochondria can maintain the integrity of structure and function of skeletal muscle by improving biosynthesis, antioxidant defense, fusion/fission dynamics and mitophagy. Mitochondrial dysfunction is a important factor leading to the complex etiology of sarcopenia. Exercise can regulate mitochondrial quality control pathways by activating mitochondrial biogenesis and mitophagy to maintain optimal mitochondrial function, thereby delaying and preventing the onset and progression of sarcopenia.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult

Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 12, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 post infection, and died at the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of severe COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Fatal Outcome ; Hemorrhage/virology* ; Humans ; Lung/pathology* ; Myocardium/pathology* ; Pandemics ; Pneumonia, Viral/pathology* ; Retrospective Studies ; SARS-CoV-2

Objective To develop a novel strategy for separation and purification of target protein by magnetic molecularly imprinted nanoparticles . Methods Fe3 O4 nanoparticles were synthesized through a hydrothermal method .A sol-gel technique was adopted to prepare imprinting layers .The adsorption capability of magnetic molecularly imprinted nanoparticles was investigated by kinetic , isothermal , and selective binding experiments .Results The imprinted nanomaterials could reach equilibrium within 30 min . The adsorption capacity was 44 .51 mg/g .The imprinting factor and selectivity coefficient were 3 .50 and 2 .92 ,respectively .The resulting imprinted polymers could selectively separate and enrich bovine hemoglobin from a bovine blood sample . Conclusion The prepared imprinted nanomaterials with good specific adsoprtion ability can provide an effective strategy for separation and purification of target protein .

Affinity chromatography (AC)is a type of liquid chromatography that makes use of biological-like interactions for separation and specific analysis of bioactive components. It has been widely used as a high-throughput screening method for the separation,screening and purification of the target molecules from complex samples with advantages such as high selectivity and high recovery efficiency.This article summarizes the biological effects of affinity chromatography, molecular imprinting chromatography, and dye ligands affinity chromatography.The review also encompasses the application of AC in the separation of chiral drugs,screening of active components,purification of target protein,and mechanism of the drug-protein interaction.Moreover,the prospects of its applications are also discussed.