Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

A number of drugs for the treatment of type 2 diabetes mellitus(T2DM)are currently under clinical investigation,including the sodium-dependent glucose transporters 2(SGLT2)inhibitor rongliflozin,the SGLT1/2 inhibitor LIK066,the di-peptidyl peptidase-4(DPP-4)inhibitor DBPR108,the glucagon-likepeptide-1 receptor(GLP-1R)ago-nist CJC-1134-PC,the G-protein-coupled receptor 40(GRP40)agonist SCO-267 and the Glucokinase(GK)agonist PB201.This article briefly reviews the clinical research progress of drugs targeting the above targets in the field of T2DM treatment,in or-der to provide reference for the treatment of T2DM patients.

Objective:To explore the relationship between psychological distress and intimacy in stroke patients and the mediating effect of different dyadic coping style, to provide theoretical guidance for improving the intimate relationship of stroke patients.Methods:A convenient sampling method was used to select 203 patients with stroke who visited the General Hospital of Ningxia Medical University, the People's Hospital of Ningxia Hui Autonomous Region and the Department of Neurology of Yinchuan First People's Hospital from December 2020 to July 2021 as the survey objects. The general information questionnaire, Kessler Psychological Distress Scale, Quality of Relationship Index and Dyadic Coping Inventory were used to investigate patients.Results:The scores of psychological distress, intimate relationship, positive dyadic coping and negative dyadic coping were 19.33 ± 7.46, 32.75 ± 6.79, 86.25 ± 13.22, and 16.46 ± 4.08, respectively. Correlation analysis showed that psychological distress was negatively correlated with intimate relationship and positive dyadic coping ( r=-0.195, -0.204, both P<0.01), psychological distress was positively correlated with negative dyadic coping ( r=0.229, P<0.01). The mediating effect of positive dyadic coping and negative dyadic coping on psychological distress and intimate relationship was 35.87% and 53.26%, respectively. Conclusions:The psychological distress indirectly affects the intimate relationship of stroke patients through positive dyadic coping and negative dyadic coping. Health care workers can guide patients to actively cope with the disease and encourage couples to strengthen communication, so as to enhance the intimacy of couples and promote their physical and mental health development.

Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi, of which cycloastragenol-type glycosides are the most typical and major bioactive compounds. This kind of compounds exhibit various biological functions including cardiovascular protective, neuroprotective, etc. Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis, re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides. However, the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps. Herein, guided by transcriptome and phylogenetic analyses, a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus. AmCAS1, the first reported cycloartenol synthase from Astragalus genus, is capable of catalyzing the formation of cycloartenol; AmUGT15, AmUGT14, AmUGT13, and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation, 3-O-glucosylation, 25-O-glucosylation/O-xylosylation and 2'-O-glucosylation of cycloastragenol glycosides, respectively. These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants, also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.

Objective:To explore the effect of perceived stress on fatigue and its mechanism, so as to provide theoretical support for relieving the fatigue of the main caregivers of stroke patients.Methods:From December 2020 to August 2021, 311 main caregivers of stroke patients hospitalized in the Department of Neurology of Class Ⅲ Grade A hospitals in Yinchuan were selected by convenient sampling. The caregivers were investigated with the General Information Questionnaire, Perceived Stress Scale, Resourcefulness Scale, Social Support Rating Scale and Fatigue Scale.Results:In this study, a total of 311 questionnaires were distributed, and 308 valid questionnaires were recovered, with an effective recovery rate of 99.04%. The total scores of perceived stress, fatigue, resourcefulness and social support of the main caregivers of stroke patients were (24.98±6.36) , (5.31±2.86) , (83.98±12.85) and (39.76±6.21) respectively. Perceived stress were negatively correlated with resourcefulness and social support ( r=-0.313, -0.274, P<0.01) , and positively correlated with fatigue ( r=0.261, P<0.01) . Fatigue were negatively correlated with resourcefulness and social support ( r=-0.305, -0.268; P<0.01) . There was a positive correlation between resourcefulness and social support ( r=0.210, P<0.01) . The results of intermediary test showed that the direct effect of perceived stress on fatigue was valid, and the respective intermediary effect of resourcefulness and social support between perceived stress and fatigue, and the chain intermediary effect of resourcefulness and social support were also valid, with the amount of intermediary effect being 26.92%, 15.38% and 3.85% respectively. Conclusions:The chain mediation between perceived stress and fatigue is established between the resourcefulness and social support of the main caregivers of stroke patients. In the future, the mental and physical pressure of stroke patients can be alleviated by improving the resourcefulness of their main caregivers and providing social support.

Objective:To form the expert consensus on screening and evaluation of dysphagia with oral cancer patients (abbreviated as Consensus) , so as to standardize the relevant contents of screening and evaluation of dysphagia in the whole cycle of oral cancer. Methods:By referring to domestic and foreign literature related to dysphagia, combining with the specialty characteristics of oral cancer and the clinical experience of experts, a preliminary consensus was formed through in-depth interviews with experts. A total of 21 experts were selected for three rounds of expert letter consultation and expert meeting, the corresponding items were sorted out, analyzed and modified based on expert opinions, and the Consensus was finally formed. Results:The effective recovery rates of the three rounds of correspondence were 100.00% (21/21) , the expert authority coefficient was 0.91, the variation coefficient of each item was 0.04-0.20, and Kendall's harmony coefficient was 0.05 ( P<0.05) . The final consensus included four aspects, such as the effect of oral cancer on swallowing, the clinical manifestations of dysphagia, the basic procedures of screening and evaluation and the prevention and treatment of complications during evaluation. Conclusions:This Consensus is scientific and practical, which can provide clinical guidance for the screening and evaluation of dysphagia in the whole cycle of oral cancer.

Objective:To investigate the preparation methods and quality control of 177Lu-labeled radiopharmaceuticals, and conduct preliminary clinical application research. Methods:177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-Phe1-Tyr3-octreotide (TOC) and 177Lu-prostate specific membrane antigen (PSMA)-I&T were labeled by manual labeling and automatic labeling, respectively. Factors such as the amount of precursor and nuclide, reaction temperature, pH value, reaction time, labeling yield and specific activity were investigated. Quality control of the products were carried out, such as clarity, pH value, sterility, bacterial endotoxin and stability in vitro. 177Lu-PSMA-I&T was applied to the treatment of prostate cancer patients, and the efficacy was evaluated by SPECT/CT imaging. Paired t test was used to analyze the data. Results:The amount of precursor and nuclide, reaction temperature, pH value and reaction time of the two methods were basically the same, both with high yield and specific activity. The yield of 177Lu-DOTA-TOC automatic labeling was significantly higher than that of manual labeling (99.2±0.4)% vs (95.3±1.5)% ( t=7.17, P<0.001), and the specific activity were (91.6±13.7) vs (89.1±13.2) GBq/μmol. The yield of 177Lu-PSMA-I&T automatic labeling was also significantly higher than that of manual labeling (99.6±0.3)% vs (95.7±1.3)% ( t=8.24, P<0.001), and the specific activity were (96.1±14.3) vs (93.2±13.8) GBq/μmol. The labeled products were colorless clear solution with pH value of 6.5-7.0. The sterility and bacterial endotoxin met the requirements. The radiochemical purity of the labeled products was more than 95% after 48 h, which showed good stability. The clinical application of 177Lu-PSMA-I&T in patients with prostate cancer showed that both primary and metastatic lesions had good uptake. Conclusions:The labeling of 177Lu radiopharmaceuticals is simple and has high yield and stability. The application of automatic labeling can simplify the process, improve the yield and reduce irradiation.

Sesquiterpenoids are comprised of three C₅ units and derived from farnesyl diphosphate. In these C₁₅ family of terpenoids, drimane-type sesquiterpenoids are unique as their chemical structure of decahydronaphthalene along with the methyl group decorations resemble the A/B rings of labdane derived diterpenoids and the eastern part of many meroterpenoids. In the past decades, based on their chemical structural features and diverse bioactivities, great efforts have been made to perform chemical and biological research on this family of natural products, leading to the characterization of a large of new compounds and a few biosynthetic pathways. In this review, we collected 164 new drimane-type sesquiterpenoids from fungi between January 2004 and October 2021 and classified them into three major subfamilies, so as to highlight their diverse chemical structures, biological activities, and biosynthetic pathways,.
Polycyclic Sesquiterpenes ; Sesquiterpenes/chemistry* ; Fungi ; Terpenes/chemistry* ; Diterpenes