ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Alzheimer’s disease （AD） is mainly characterised by irreversible progressive cognitive dysfunction， which is complex in its pathogenesis and difficult to cure， and seriously affects the quality of life of patients. MicroRNA （miRNA） is a type of small non-coding RNA with high targeting specificity and potential for multi-pathway regulation. This paper takes miRNA as the entry point to systematically elaborate the mechanism of action of traditional Chinese medicine intervening in AD by regulating miRNA. The results revealed that the active ingredients of traditional Chinese medicine （e.g. notoginsenoside R1， salidroside， catalpol， madecassoside， baicalin， dihydromyricetin， osthole， berberine， ursolic acid， parthenolide， thymoquinone， plumbagin）， the extracts of traditional Chinese medicine （e.g.， Ganoderma extract and Ginkgo biloba leaf extract）， and the compound formulas of traditional Chinese medicine （e.g.， Dihuang yinzi decoction， modified Shuyu pill， and Anshen dingzhi formula） can regulate miRNA to reduce the production and deposition of β-amyloid protein， inhibit the over-phosphorylation of τ protein， and inhibit the neuroinflammatory response and programmed neuronal death by regulating miRNA， thus playing a role in intervening in AD.

Objective:To investigate risk factors for the efficacy for appropriate medication use in elderly patients with type 2 diabetes mellitus(T2DM)and to establish a risk prediction model for the efficacy for appropriate medication use by using Logistic regression analysis and the receiver operating characteristic(ROC)curve.Methods:A total of 305 elderly patients with T2DM admitted to pharmacy department of our hospital from Jan.2018 to Aug.2018 were enrolled in this retrospective study.Of the 305 patients, 166(54.4%)were female, with a mean age of (74.9±7.2) years old, a disease course of (15.2±9.6) years and a hospital stay of (10.4±3.2) d, receiving (2.0±0.9) types of antidiabetic drugs.Patients were assessed by the Self-Efficacy for Appropriate Medication Use Scale(SEAMS), the Morisky Medication Adherence Scale-8(MMAS), the Adherence to Refills and Medications Scale(ARMS), the Charlson Comorbidity Index(CCI)and the Mini Mental State Exam(MMSE). Main biochemical indicators were recorded.The influencing factors for appropriate medication use efficacy were analyzed by Logistic regression analysis, and a risk prediction model was consequently established by the ROC curve.Results:According to SEAMS results, 233 patients(76.4%)had sufficient efficacy(≥26 points)and 72 patients(23.6%)had insufficient efficacy(<26 points). There were significant differences in parameters including age, disease course, hospital stay and fasting blood glucose(FBG)between the above two groups( P<0.05). Logistic regression analysis showed that age, FBG level and ARMS score had correlation with self-efficacy for appropriate medication use( P<0.05). ROC curves showed that the predictive efficiency of joint predictor Y [Logit(P)=-15.164+ 0.434X ARMS score-0.067X age-0.082X FBG reaching standard]was better than that of the other three single factors(AUC=0.910, 95% CI: 0.873-0.947, P<0.01)and could be used as an optimal predictor for the evaluation of self-efficacy for appropriate medication use. Conclusions:Compared with MMAS, ARMS is more suitable for medication adherence assessment in elderly T2DM patients.In clinical practice, pharmacists can provide individualized medication services through evaluating the efficacy of rational drug use and the risk prediction model, in order to elevate the ability of self-medication management and quality of life.

Radiomics and radiogenomics are used to provide comprehensive tumor biological characte-ristics and further clinical information by extracting,screening and analyzing the most valuable quantitative ra-diomics features. In recent years,numerous studies have shown that radiomics plays a role in the diagnosis, treatment and predicting efficacy and prognosis of lung cancer. Radiogenomics shows a great value in the pre-diction of lung cancer gene phenotype and individualized precision treatment by combining radiomics features with genomics,proteomics and so on. Radiomics and radiogenomics are non-invasive,quantitative,and repro-ducible,and they can provide multidirectional tumor biological characteristics,which are expected to be widely used in the precise medical treatment of lung cancer in the future.

Objective To explore the determinants of serum uric acid (UA) levels and the relationship between UA and cardiovascular disease in elderly patients.Methods A cross-sectional design was used.A total of 1 066 elderly patients were consecutively recruited in the study.Anthropometric measurement and lifestyle survey were performed,and serum UA,lipid profile,glucose,homocysteine (Hcy) and superoxide dismutase (SOD) were measured.The determinants of serum UA levels and correlation between UA and cardiovascular disease were analyzed by regression.Results The prevalence of hyperuricemia was 21.9％ (25.9％ in men and 18.7％ in women).Partial correlation analysis showed the level of serum UA was positively correlated with Hcy (r=0.163,P=0.000),body mass index (r=0.128,P=0.004) and triglyceride (r=0.133,P=0.003),and negatively correlated with HDL-C (r=-0.103,P=0.021).After adjustment for potential confounding factors,multivariate analysis showed eGFR (β =-2.044,t =-10.544,P =0.000),gender (β =42.065,t=4.700,P=0.000),Hcy (β=1.367,t=3.714,P=0.000),BMI (β=3.370,t=2.706,P=0.007),TG (β=14.120,t=2.589,P=0.010) and SOD (β=-0.636,t=-3.079,P=0.002) were independent determinants for UA levels in elderly patients.Logistic regression analysis indicated that mild elevation of UA levels was a risk factor of hypertension (OR=1.925,95％ CI=1.124-3.295) in women and OR=1.780 (95％ CI=1.010-3.136) in men].High UA levels increased the risk of coronary heart disease in women [OR=1.710 (95％ CI=1.157-2.526)],but decreased the risk of ischemic stroke in men [OR=0.524 (95％ CI=0.335-0.820)].Conclusions In elderly patients,serum UA levels were affected by renal function,gender,BMI and serum Hcy,TG and SOD.Mildly elevated UA levels increased the risk of hypertension.High UA levels increased the risk of coronary heart disease in women and decreased the risk of ischemic stroke in men.

Objective To investigate the effects of risk factors on non thyroidal Illness syndrome (NTIS) in elderly inpatients.Methods A total of 819 elderly inpatients who met inclusion criteria were consecutively recruited in thiscross-sectional study.Physicalmeasurements and mini nutritional assessment using the mini nutritional assessment-short form (MNA-SF) score were conducted.A serum levels of thyroid stimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4),brain natriuretic peptide (BNP) and C-reactive protein (CRP) were examined.Data were analyzed with multivariatelogistic regression.Results The significant differences were found between NTIS group (n=145) versus control group (n=674)inage (78.5±8.1) years vs.(75.1±8.6) years(t=5.422,P＜0.01),in body mass index (23.0 ±3.8) kg/m2 vs.(24.1±3.6) kg/m2,in MNA-SF score 11.2±2.3 vs.12.3± 1.8(t=-3.315,6.754,P＜0.01),in level of serum albumin (36.0±4.5) g/L vs.(38.4±3.6) g/L (t=-6.977,P＜0.01),in triglyceride level (1.3± 0.9) mmol/L vs.(1.5±1.0) mmol/L(t=-3.039,P＜0.01),inCRP (Z=-8.857,P＜0.01)),and in BNP (t=6.331,P＜0.01).Logistic regression analysis revealed that age＞ =80 years (OR=2.433,95％CI:1.357 4.361),malnutrition (OR=1.946,95％CI:1.261-3.001),renal insufficiency (eG FR＜60 ml/min,OR =2.131,95％ CI:1.367-3.322),and high level of CRP (10 mg/L and 50 mg/L:OR=3.446,95％CI:2.117-5.611;over 50 mg/L:OR =10.029,95％CI:4.693-21.432,all P＜0.01)) were risk factors for NTIS.Conclusions Non-thyroidal illness syndrome in elderly inpatients is correlated with advanced age,renal insufficiency,malnutrition and stress,which are the independent risk factors.

Objective To explore the role of T cell-mediated immunity in the pathogenesis of venous thromboembolism ( VTE ) by analyzing the differential expression of T cell immune-related gene mRNAs peripheral blood mononuclear cells (PBMCs) between VTE patients and controls with GeneChip Human Genome. Methods Human eDNA microarray analysis was employed in PBMCs from 20 VTE patients and 20 hypertensive controls,and random variant model (RVM) corrected t-test was used for statistical analysis of differential gene expression.Results Six mRNA stripes including CD247,CD3D,CD3G,Granzyme A (GzmA),Granzyme B (GzmB) and Zeta-chain-associated protein kinase 70 (ZAP70)were found to be associated with T cell-mediated immunity.Significant down-regulation of these six mRNAs was found in the VTE group compared with the controls ( 15.3050 ± 0.6346 vs 15.8053 ± 0.5567,13.7878 ±0.7731 vs 14.3820 ±0.4857,13.3299 ± 0.9104 vs 14.1246 ± 0.6011,14.8893 ± 0.8675 vs 15.5305 ±0.4624,15.9113 ±0.8123 vs 16.4553 ±0.5055,14.3652 ±0.7717 vs 14.3652 ±0.7717;all P values ＜ 0.05 ).Conclusions T cells' function including antigen recognition,signal transduction and cytotoxicity was impaired in VTE patients.T cell-mediated immunity dysfunction probably plays an important role in the pathogenesis of VTE.

Objective To analyze the efficacy and safety of glimepiride treatment as initial monotherapy in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Methods This was a subgroup analysis of the GREAT study,which investigated the efficacy and safety of glimepiride as initial monotherapy in Chinese patients with T2DM.This analysis was performed in 209 patients with disease duration less than 6 months and never received any anti-diabetic drugs.The change of HbA1C,fasting plasm glucose (FPG),2 h postprandial blood glucose (2hPPG),homeostasis model assessment for β-cell function index (HOMA-β),homeostasis model assessment for insulin-resistance index(HOMA-IR),the percentage of patients with HbA1C ＜ 7.0％ at endpoint and the incidence of hypoglycemia were evaluated after 16-weeks treatment.Results After 16-weeks glimepiride treatment,HbA1C value reduced significantly from baseline to endpoint,the reduction was statistically significant (9.21％ ± 1.65％ to 6.69％±0.83％,P＜0.001),69.7％ of the patients achieved HbA1C ＜7.0％ at study endpoint.Glimepiride-treated patients also achieved a significant improvement in FPG [from (10.15 ± 2.13) mmol/L to (7.23 ± 1.50) mmol/L,P＜0.001] and 2hPPG [from (17.21 ±4.14) mmol/L to (11.62 ± 3.34) mmol/L].HOMA-β was improved from 17.21± 15.19 [11.62 (2.90,115.8)] to 41.13 ± 44.12 [28.00 (5.1,360.00)],and HOMA-IR was reduced from 2.32± 1.90 [1.76 (0.60,12.80)] to 2.07 ± 1.74 [1.63 (0.4,12.3)].The incidence of all reported symptomatic hypoglycemia was 18.2％,and the incidence of confirmed hypoglycemia was 3.8％.Conclusion This analysis showed that glimepiride treatment as an initial mono-therapy could effectively improve blood glucose control in newly diagnosed patients with T2DM,and the treatment may improve islet β cell function,and the safety profile is reasonably good.

Objective To investigate the change of HR,RR and arterial blood gas in the treatment of BiPAP ventilation in patients with acute pulmonary.Methods Fifty eight patients with acute pulmonary edema were randomized into two groups.The control group(n =29)were given conventional general treatment only,but treatment group(n =29)were given BiPAP ventilation besides conventional treatment.4 h later,heart rate (HR),respiratory rate(RR),SaO2,pH,PaO2 and PaCO2 were compared between the two groups.Hospitalization duration and incidence of invasive mechanical ventilation were recorded after discharge.Results Compared with pre-treatment,HR,RR,SaO2 and PaO2 in treatment group were improved significantly(HR 124 ± 12 beat/min vs 83 ±6 beat/min,t =5.372,P ＜0.01)(RR 37 ±5 beat/min vs 19 ± 8 beat/min,t =4.285,P ＜0.01)(SaO2 81.4％ ±5.4％ vs94.1％ ±4.2％,t=2.731,P＜0.05)(PaO2 53.2±5.4 mm Hg vs 89.1 ±8.5 mm Hg,t=5.763,P ＜0.O1).And these four indicators were also improved in control group after treatment,(HR 123 ± 10 beat/min vs 95 ± 8 beat/min,t =t =3.459,P ＜ 0.01)(RR 36 ± 7 beat/min vs 24 ± 6 beat/min,t =3.127,P ＜0.01)(SaO2 81.8％ ±5.7％ vs 88.3 ±4.5％％,t =2.314,P ＜0.05)(PaO2 53.5 ±4.6 mm Hg vs 72.8 ±9.5 mm Hg,t =3.756,P ＜0.01).HR,RR,SaO2 and PaO2 in treatment group were more significantly improved than that of control group(P ＜ 0.01 or P ＜ 0.05).Hospitalization duration in treatment group was significantly shorter than that of control group(9 d vs 15 d,t =3.763,P ＜ 0.01).The incidence of invasive ventilation were lower than that of control group too(but P ＞ 0.05.Conclusion These results suggested that BiPAP ventilation can regulate HR RR and blood gas value to accetable levels,shorten hoptipitalization duration and reduce the incidence of invasive ventilation.It is proved to be an effective therapeutic technique in the treatment of acute pulmonary edema patients.

This investigation was directed to the metabolic syndrome and the islet beta-cell secretory function in the first-degree relatives (FDR) of type 2 diabetic patients in Sichuan province. A large cohort study was designed. Totally 1929 subjects were investigated. They were in two groups: FDR group comprising 505 first-degree relatives of type 2 diabetic patients, and Control group comprising 1424 controls without positive family history of Diabetes. Blood pressure, weight, waist, plasma glucose, lipids and insulin were measured. HOMA-IR and HOMA-beta indexes were used to evaluate insulin resistance and beta-cell secretion function. The insulin sensitivity index (ISI) and glucose disposition index (DI) were also used to evaluate insulin resistance. After adjustment for age and sex, HOMA-IR increased, ISI, DI and HOMA-beta decreased in FDR group when compared with controls (P < 0.05). The incidence of co-existed three or more metabolic disorders and metabolic syndrome was higher in FDR group than that in control group (P < 0.05). In FDR group, HOMA-IR increased, HOMA-beta, DI and ISI decreased while the number of co-existing metabolic disorders increased. But when the number of co-existing metabolic disorders > or = 4, HOMA-IR increased no longer and ISI decreased no more. Metabolic disorders occurred more frequently in FDR of diabetic patients than those in individuals without positive family history. As the number of co-existing metabolic disorders increased, the beta-cell secretion function and insulin sensitivity became worse. Our study indicated that it is necessary to keep on monitoring the metabolic index in FDR of type 2 diabetes and provide early preventive interventions.
Adult ; China ; epidemiology ; Cohort Studies ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; Islets of Langerhans ; physiopathology ; Male ; Metabolic Syndrome ; epidemiology ; genetics ; Middle Aged ; Surveys and Questionnaires