OBJECTIVE To establish the fingerprints of Ardisia crenata， Sophora tonkinensis and their couplet medicines， and to determine the contents of five components in them. METHODS Using water as solvent， single lyophilized powder of A. crenata and S. tonkinensis and combined lyophilized powder of their couplet medicines were prepared by combining lyophilization technology. The fingerprints of three lyophilized powder samples were established by using high-performance liquid chromatography （HPLC）， and the contents of 5 kinds of components such as gallic acid were determined simultaneously. RESULTS There were 5， 10 and 14 common peaks in the fingerprints for single lyophilized powder of A. crenata and S. tonkinensis and combined lyophilized powder of their couplet medicines； the similarities of them with the control fingerprints were all greater than 0.90. For combined lyophilized powder of couplet medicines， peak 3 Δ 基金项目 国家重点研发计划项目（No.2018YFC1708100）；贵 州省科技计划项目（No.黔科合基础-ZK〔2022〕一般483，No.黔科合成 was identified as gallic acid， peak 4 as matrine， peak 6 as 果〔2021〕一般137）；贵州省教育厅高等学校科学研究项目（青年项目） oxymatrine， peak 8 as bergenin， and peak 14 as trifolirhizin. In single lyophilized powder of A. crenata， the average contents of gallic acid and bergenin were 0.499 3 and 4.962 6 mg/g， respectively. In single lyophilized powder of S.tonkinensis， the average contents of matrine， oxymatrine and trifolirhizin were 3.046 0， 2.336 6 and 0.278 6 mg/g， respectively. In combined lyophilized powder of couplet medicines， the average contents of gallic acid， matrine， oxymatrine， bergenin and trifolirhizin were 0.560 6， 2.548 7， 1.382 2， 5.960 7 and 0.279 1 mg/g， respectively. The transfer rates were 8.87%-513.19%. CONCLUSIONS The established fingerprint and content determination methods are stable and feasible， and can be used for the quality control of A. crenata and S. tonkinensis and their couplet medicines. The average contents of matrine and oxymatrine in combined lyophilized powder of A. crenata-S. tonkinensis couplet medicines are decreased.

OBJECTIVE: To explore clinical effect of arthroscopy-assisted rotator cuff tendon transfer in treating irreparable rotator cuff tears (IRCT). METHODS: From May 2015 to May 2018, 23 patients with unrepairable rotator cuff tears were treated with arthroscopy-assisted rotator cuff tendon transfer, and 21 patients were followed up finally, including 8 males and 13 females, aged from 48 to 82 years old with an average of(64.3±9.1) years old;the courses of disease ranged from 6 to 36 months with an average of (14.0±6.4) months. American Rotator and Elbow Surgeons Score(ASES) and Constant-Murley score were used to evaluate clinical efficacy before surgery and at the latest follow-up. RESULTS: All 21 patients were followed up for 36 to 54 months with an average of (39.4±4.4) months. Axillary incision of 1 patient was redness, swelling and exudation after surgery, which healed after 3 weeks of dressing change, and exudate culture was negative. At the latest follow-up, MRI showed partial tearing of the metastatic tendon in 2 patients, but pain and movement of the affected shoulder were still better than before surgery. ASES increased from preoperative (41.0±9.6) scores to the latest follow-up (75.6±14.0) scores, and had statistical difference (t=10.50, P<0.01). Constant-Murley score increased from (49.8±7.1) scores before operation to (67.5±11.6) scores at the latest follow-up (t=11.27, P<0.01). CONCLUSION Arthroscopic assisted latissimus dorsalis tendon transposition restores physiological and anatomical structure of glenohumeral joint by reconstructing balance of horizontal and vertical couples of shoulder joint, thus achieving the stability of the shoulder joint, relieving shoulder pain and improving shoulder joint function.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Rotator Cuff Injuries/surgery* ; Superficial Back Muscles ; Rotator Cuff ; Treatment Outcome ; Shoulder Joint/surgery* ; Tendon Transfer ; Arthroscopy ; Range of Motion, Articular/physiology*

Objective: To establish an ultra-sensitive, ultra-fast, visible detection method for Vibrio parahaemolyticus (VP) . Methods: We established a new method for detecting the tdh and trh genes of VP using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 12a (CRISPR/Cas12a) combined with recombinase polymerase amplification and visual detection (CRISPR/Cas12a-VD). Results: CRISPR/Cas12a-VD accurately detected target DNA at concentrations as low as 10 ^-18 M (single molecule detection) within 30 min without cross-reactivity against other bacteria. When detecting pure cultures of VP, the consistency of results reached 100% compared with real-time PCR. The method accurately analysed pure cultures and spiked shrimp samples at concentrations as low as 10 ² CFU/g. Conclusion The novel CRISPR/Cas12a-VD method for detecting VP performed better than traditional detection methods, such as real-time PCR, and has great potential for preventing the spread of pathogens.
CRISPR-Cas Systems ; Nucleic Acid Amplification Techniques/methods* ; Recombinases/genetics* ; Vibrio parahaemolyticus/genetics*

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, which is characterized in renal tubulointerstitial fibrosis (TIF). The current study was designed to investigate the protective effect of Jujuboside A (Ju A) on TIF in type 2 diabetes (T2DM) mice, and explore its underlying anti-fibrosis mechanism. A mouse T2DM model was established using high fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Then, diabetic mice were treated with Ju A (10, 20 and 40 mg·kg^-1·d^-1, i.g.) for 12 weeks. Results showed that administration of Ju A not only down-regulated fasting blood glucose (FBG) levels, but also improved hyperlipidemia and renal function in diabetic mice. Moreover, the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice, while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs). Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1 (YY1) in the renal cortex of diabetic mice, and reduced the levels of transforming growth factor-β1 (TGF-β1) in the serum and renal cortex of Ju A treated mice. According to invitro studies, the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose (HG) cultured HK-2 cells. Taken together, these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Diabetic Nephropathies/metabolism* ; Fibrosis ; Mice ; Saponins ; Signal Transduction ; Streptozocin ; Transforming Growth Factor beta1/metabolism*

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective To observe the current status of secondary prevention medication usage and their relation with on-treatment platelet reactivity in patients with Acute Coronary Syndrome(ACS) treated with aspirin and clopidogrel. Methods A total of 176 patients hospitalized from 2014 to 2015 due to ACS in the Department of Cardiology, Peking University People's Hospital were enrolled and on-treatment platelet reactivity was tested by thromboelastography(TEG)and CYP2C19*2,*3 and*17 alleles were analysed. Details of secondary prevention medication and patients' clinical characteristics were recorded. The relation of secondary prevention medication and on-treatment platelet reactivity was analyzed by multi-logistic regression after adjusting for CYP2C19 alleles and clinical characteristics covariates.Results A 94.89% of patients was treated with statins while 80.68% with beta blocker. The platelet inhibition rate were (45.33±28.78)% and the high on-treatment platelet reactivity (HTPR) rate tested by TEG was 37.50%. In the multivariate logistic regression analysis, usage of β-blockers during hospitalization as well as phenotypes of CYP2C19*2,*3 and *17,clinical presentation with ST-segment elevation myocardial infarction and the length of stents were associated with HTPR defi ned by TEG. The percentage of HTPR rate was signifi cantly lower in patients treated with than those without β-blockers (72.73% vs. 85.45%,OR 0.18,95%CI 0.06-0.53,P=0.002)after adjusting genetic factors and other covariates.Conclusions There was a signifi cant correlation between beta blockers usage and high clopidogrel on-treatment platelet reactivity.

Brain magnetic resonance imaging (MRI) of the elderly often reveals white matter changes (WMCs) with substantial variability across individuals.Our study was designed to explore MRI features and site-specific factors of ischemic WMCs.Clinical data of consecutive patients diagnosed with ischemic cerebral vascular disease who had undergone brain MRI were collected and analyzed.Multi-logistic regression analysis comparing patients with mild versus severe WMCs was performed to detect independent associations.Analyses of variance (ANOVAs) were used to detect regionally specific differences in lesions.We found that lesion distribution differed significantly across five cerebral areas,with lesions being predominant in the frontal lobe and parieto-occipital area.To explore WMCs risk factors,after adjusting for gender,diabetes mellitus,and hypertension,only age (P＜0.01),creatinine (P=0.01),alkaline phosphatase (ALP) (P=0.01) and low-density lipoprotein cholesterol (LDL-C) (P=0.03) were found to be independently associated with severe WMCs.Age (P＜0.001) was strongly associated with WMCs in the frontal lobe while hypertension was independently related to lesions in the basal ganglia (P=0.048) or infratentorial area (P=0.016).In conclusion,MRI of WMCs showed that ischemic WMCs occurred mostly in the frontal lobe and parieto-occipital area.The infratentorial area was least affected by WMCs.Typically,age-related WMCs were observed in the frontal lobes,while hypertension-related WMCs tended to occur in the basal ganglia and infratentorial area.

Objective To investigate the relationship between ischemic time and thrombus types in patients with ST-segment elevation myocardial infarction (STEMI).Methods Eighty-two STEMI patients undergone emergency percutaneous coronary intervention (PCI) and coronary thrombus aspiration (CTA) from Sep.2012 to Apr.2016 were included and divided into 3 groups according to the ischemic time:≤4 hours (n=36),4-7 hours (n=30) and ＞7 hours (n=16).Visible aspirated thrombi were collected and separated into erythrocyte-rich type,platelet/fibrin-rich type and combined type thrombi by HE dying.The percentage difference of the 3 types thrombi was compared among the 3 groups.Results The percentage of platelet/fibrinrich type,erythrocyte-rich type and combined type thrombi in the 3 groups were as follows:in ≤4h group:61.1％(22/36),8.3％(3/36) and 30.6％(11/36),P=0.019;in 4-7h group:23.3％(7/30),10.0％(3/30) and 66.7％(20/30),P=0.012;and in ＞7h group:43.8％(7/16),12.5％(2/16) and 43.8％(7/16),P=0.913.For platelet/fibrin-rich type thrombi,the percentages in 3 periods were 61.1％(22/36),19.4％(7/36) and 19.4％(7/36),P=0.009;For combined type thrombi,the percentages in 3 periods were 28.9％(11/38),52.6％(20/38) and 18.4％(7/38),P=0.013;For erythrocyte-rich type thrombi,the percentages in 3 periods were 37.5％(3/8),37.5％(3/8) and 25.0％(2/8),P=0.895.Conclusions The types of intracoronary aspirated thrombi differ from various periods.Ischemia time may be an important predicted factor.