[Comparison of the efficacy of PCSK9 inhibitors and statins on dyslipidemia in patients with type 2 diabetes].

Objective: To compare the efficacy of preprotein convertase subtilisin lysozyme 9 (PCSK9) inhibitors with statins in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 140 patients with T2DM (80 males and 60 females) in the People's Hospital Affiliated to Shandong First Medical University from January 2018 to January 2021 were selected, with a mean age of (55±5) years (41-72 years). The patients were divided into observation group (n=68) and control group (n=72) by the random number table method. Both groups were given conventional treatments such as hypoglycemic drugs, the control group was given statins to regulate lipids, and the observation group was given PCSK9 inhibitors to lower lipids. The differences of low-density lipoprotein cholesterol (LDL-C), interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) expression levels and standard-reaching rate of LDL-C between the two groups were compared. The correlation between serum PCSK9 level and fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other indicators in T2DM patients was analyzed by Pearson correlation analysis. Results: After treatment, the LDL-C of the observation group was (2.3±0.7) mmol/L, which was lower than that of the control group [(2.7±0.7) mmol/L] (P=0.024); the standard-reaching rate of LDL-C of the observation group was 89.7% (61/68), which was higher than that of the control group [68.1% (49/72)] (P=0.002); the levels of IL-1, IL-6, TNF-, CRP, IL-10 and IL-8 in the observation group after treatment were (27.6±6.6) ng/L, (36.7±6.9) ng/L, (40.1±8.9) ng/L, (7.8±1.8) ng/L, (19.2±3.3) ng/L, (13.7±3.3) ng/L, respectively, which were lower than those in the control group [(30.6±7.9) ng/L, (40.1±7.3) ng/L, (43.4±9.2) ng/L, (10.4±2.5) ng/L, (30.7±3.7) ng/L, (26.8±3.4) ng/L, respectively] (all P<0.05). After treatment, the PCSK9 level in the observation group was (74±13) µg/L, which was lower than that in the control group [(97±14) µg/L] (P<0.001). The level of PCSK9 in T2DM patients was positively correlated with LDL-C, IL-1, IL-6 and TNF-α (r=0.390, 0.433, 0.398 and 0.562, all P<0.05). Conclusion: PCSK9 inhibitors have better lipid-regulating effects in patients with T2DM and can improve the level of inflammation at the same time.

The Pathogenesis and Influencing Factors of Adult Hypertension Based on Structural Equation Scanning.

Explore the pathogenesis and influencing factors of adult hypertension based on structural equation scanning. Using a multistage random sampling method, randomly select 2 community health service centers in each administrative area of a certain city and conduct a sample survey of residents in the community. According to the predetermined sample size n, multiply by 1.3 (1.3n) to draw a sample. Community doctors and medical students who have been uniformly trained form an investigation team draw up a questionnaire by consulting the literature, seek expert opinions, and then make changes based on the questions in the preinvestigation. Experiment result shows that the average systolic blood pressure of the experimental subjects was 126.13 + 15.36 mmHg and the average diastolic blood pressure was 79.52 + 8.81 mmHg; males are higher than females and increase with age. The prevalence rate of hyperemia is 26.3%, and the prevalence rate of prehypertension among the survey subjects is 55.4%; that of males (62.6%) is higher than that of females (49.2%). The prevalence of isolated systolic hypertension was 7.5%, and that of men (6.9%) was lower than that of women (7.9%). The awareness rate of hypertension was 66.5%, and the treatment rate of hypertension was 62.7%; the control rate of hypertension was 13.2%, and the control rate of hypertension treatment was 25.7%; all the abovementioned rates are higher for women than for men, and they all tend to increase with age which proved that being overweight is a risk factor for hypertension, dyslipidemia, and hypertension. Hypertension, dyslipidemia, and family history of hypertension are risk factors for hypertension. There is a positive correlation between hypertension and dyslipidemia.

Prediction of Renal Function Damage in Patients with Essential Hypertension Based on Stepwise Regression Equation Scanning by AASI.

Detection of arterial stiffness is an important method to predict the occurrence of hypertension complications and to screen patients with high cardiovascular risk. In order to predict the damage of AASI to the renal function of patients with essential hypertension, the prediction of AASI based on stepwise Regression equation scanning for renal function damage in patients with essential hypertension is proposed. Measure the 24 h ambulatory blood pressure of the selected subjects, establish a linear Regression equation scanning, and calculate the slope of the straight line, and finally, the slope is AASI. According to the quartiles, AASI is divided into four parts: group I < 0.53 (n = 49); 0.53 ≤ group II < 0.60 (n = 51); 0.60 ≤ group III < 0.69 (n = 48); group IV ≥ 0.69 (n = 44). Experiment result shows the following: with the increase of AASI, cystatin (CysC) also increased significantly, while CysC-eGFR decreased significantly (P < 0.05). Compared with groups I, II, and III, Scr and CysC in group IV increased (P < 0.05), and Ccr, CysC-eGFR, and (CKD-EPI)-eGFR all decreased (P < 0.05). AASI is positively correlated with CysC performance, and the correlation coefficient r is 0.637. It is negatively correlated with Ccr performance, and r is -0.361. It is negatively correlated with CysC-eGFR, and r is -0.698. And it is negatively correlated with (CKD-EPI)-eGFR, and r is -0.331. Age and 24 h PP also showed an increasing trend with the increase of AASI, and it suggests that age may be an influencing factor that promotes kidney damage caused by hypertension; it also suggests that AASI can be used as a new indicator of arterial compliance; AASI is linearly related to various indicators of renal damage and can be used as a predictive indicator of renal damage caused by essential hypertension; cystatin C and the estimated glomerular filtration rate CysC-eGFR based on cystatin C are better than other indicators reflecting glomerular filtration rate, more sensitively assess the degree of early renal damage. Obesity may also be a factor that promotes kidney damage caused by hypertension.

Ginsenoside Rg2 protects cardiomyocytes against trastuzumab-induced toxicity by inducing autophagy.

Trastuzumab (TZM) significantly improves the outcomes of patients with breast cancer; however, it is associated with severe cardiotoxicity. Ginsenoside Rg2 was reported to exert protective effects against myocardial injury and apoptosis in human cardiomyocytes (HCMs). However, whether ginsenoside Rg2 protects HCMs against TZM-induced toxicity remains unclear. The present study investigated the proliferation of HCMs using a Cell Counting Kit-8 assay and Ki67 immunofluorescence staining. Apoptotic cells were detected by Annexin V/propidium iodide staining and flow cytometry. Furthermore, monodansylcadaverine staining was performed to detect cell autophagy. In addition, western blotting was used to detect the expression levels of phosphorylated (p)-Akt, p-mTOR, beclin 1, microtubule associated protein 1 light chain 3α (LC3) and autophagy protein 5 (ATG5) in HCMs. Pretreatment with ginsenoside Rg2 significantly protected HCMs against TZM-induced cytotoxicity by inhibiting apoptosis. Furthermore, pretreatment with ginsenoside Rg2 induced autophagy in HCMs by upregulating the expression levels of p-Akt, p-mTOR, beclin 1, LC3 and ATG5. The results obtained in the present study suggested that ginsenoside Rg2 could protect HCMs against TZM-induced cardiotoxicity by activating autophagy. Therefore, ginsenoside Rg2 may serve as a potential therapeutic agent to prevent TZM-related cardiotoxicity in patients with breast cancer.

Targeting ZEB2 By microRNA-129 In Non-Small Cell Lung Cancer Suppresses Cell Proliferation, Invasion And Migration Via Regulating Wnt/ß-Catenin Signaling Pathway And Epithelial-Mesenchymal Transition.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of deaths all over the world. Emerging evidence has indicated that microRNA (miR) play key roles in NSCLC progression. We aimed to determine the functions of miR-129 in NSCLC. miR-129 was dramatically downregulated in NSCLC tissue samples and cells. The decreased miR-129 was found to be associated with poorer prognosis and malefic phenotype of NSCLC patients. We demonstrated that miR-129 upregulation could inhibit NSCLC cell growth. Furthermore, we also sought the molecular mechanism by which miR-129 repressed NSCLC development. METHODS: QRT-PCR was applied to detect the expressions of miR-129 in 51 pairs of NSCLC tissue samples. We further performed the Kaplan-Meier analysis to determine the association between miR-129 expressions and the survival rate of NSCLC patients. We then measured the expression levels of miR-129 in NSCLC cell lines. After that, MTT assays were performed to determine the influence of miR-129 on A549 cell proliferation. Transwell assay was then conducted to explore the biological functions of miR-129 in invasion and migration of NSCLC cells. RESULTS: Results showed that ZEB2 was directly targeted by miR-129 in NSCLC cell lines. Moreover, miR-129 restoration could inhibit EMT and Wnt/ß-catenin in NSCLC cell lines. CONCLUSION: In short, all these results indicated that miR-129/ZEB2 axis maybe a useful diagnostic and prognostic biomarker for NSCLC treatment.

Uptake of soil-applied thiamethoxam in orange and its effect against Asian citrus psyllid in different seasons.

BACKGROUND: Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is an important pest of citrus worldwide because it transmits the bacteria causing huanglongbing (HLB). We investigated the effects and persistence of two soil application rates of thiamethoxam on ACP populations in two flushing seasons in the field. Thiamethoxam and clothianidin residues in the fruit were detected to evaluate food safety. RESULTS: Soil application of 50% thiamethoxam water-dispersible granules at concentrations of 4 and 10 g tree-1 significantly decreased ACP populations, and there was a positive correlation between control efficacy and the persistence of thiamethoxam and clothianidin in leaves, providing longer-term protection for up to 90 days in the fall compared with 60 days in the spring. Higher thiamethoxam and clothianidin amounts were observed in new leaves than in old leaves. Thiamethoxam and clothianidin residues at a high rate in fruit were 0.012 and 0.010 mg kg-1 at harvest, respectively, and neither insecticides was detectable at low rates. CONCLUSIONS: These results demonstrate that soil-applied thiamethoxam plays a role in defending ACP, and provides an extended period of control efficacy. This knowledge could provide a reference for the control of ACP by soil application of thiamethoxam to reduce HLB spread. © 2018 Society of Chemical Industry.

[Construction of a recombinant lentiviral vector for VHL and VHL shRNA and its effect on proliferation and apoptosis of renal cell carcinoma cells].

OBJECTIVE: To construct a lentiviral expression vector for human VHL and its shRNA vector, and study the effect of VHL on proliferation and apoptosis of renal cell carcinoma cell lines. METHODS: Lentiviral vectors pZsGreen1-VHL and pLL3.7-shVHL were constructed and transfected into 293T cells with 3 packaging plasmids by Lipofectamine(TM) 2000 reagent. The supernatant was collected to infect A498 and Caki-1 cells, respectively. VHL mRNA and protein levels were detected by RT-PCR and Western blotting, respectively. The effect of VHL on the proliferation, cell cycle and cell apoptosis were analyzed by MTS and flow cytometry. RESULTS: The recombinant lentiviral vectors were successfully constructed. The proliferation of A498 cells with reconstituted wild-type VHL was significantly inhibited, while the proliferation of Caki-1 cells with VHL knockdown was significantly enhanced as compared with the control cells (P<0.05). VHL induced G0/G1-S cell cycle arrest. The apoptosis rate of A498 cells with reconstituted wild-type VHL was significantly increased while that of Caki-1 cells with VHL knockdown was significantly lowered compared with the control cells (P<0.05). CONCLUSION: VHL can inhibit the proliferation and induce apoptosis of renal cell carcinoma cells.

Dexrazoxane protects breast cancer patients with diabetes from chemotherapy-induced cardiotoxicity.

BACKGROUND: To evaluate the cardioprotective effect of dexrazoxane (DEX) on chemotherapy in patients with breast cancer with concurrent type 2 diabetes mellitus (DM2). METHODS: Eighty female patients with breast cancer with DM2 were randomly assigned to receive chemotherapy only or chemotherapy plus DEX. All patients received 80 mg/m epirubicin and 500 mg/m cyclophosphamide by intravenous infusion every 3 weeks for a total of 6 cycles. The group assigned to receive chemotherapy alone received placebo 30 minutes before epirubicin administration. The group assigned to receive chemotherapy plus DEX received 800 mg/m DEX 30 minutes before epirubicin administration. Cardiac function and hematology before and after 6 cycles of chemotherapy were analyzed. RESULTS: There was no difference in baseline systole or diastole function between the 2 DM2 groups. Patients receiving chemotherapy alone experienced significantly greater reductions in Ea and significantly greater elevations in E/Ea and Tei index in comparison with patients receiving chemotherapy plus DEX. After chemotherapy, superoxide dismutase was significantly reduced, and serum malondialdehyde (MDA) was significantly increased in patients with DM2. Serum superoxide dismutase levels were comparable between the 2 groups before and after chemotherapy, MDA levels were comparable between the 2 groups before chemotherapy, whereas serum MDA was significantly higher after chemotherapy in the chemotherapy alone group in comparison with the group that received DEX. CONCULSIONS: DEX protects against cardiotoxicity induced by chemotherapy in patients with breast cancer with concurrent DM2.

The efficacy and safety of ivabradine hydrochloride versus atenolol in Chinese patients with chronic stable angina pectoris.

PURPOSE: The aim of this study was to assess the efficacy and safety of ivabradine (Iva) noninferiority to atenolol (Aten) in Chinese patients with chronic stable angina pectoris. METHODS: In this double-blind, double-dummy trial, patients with symptomatic angina pectoris and positive exercise tolerance test were randomized into the Iva [5 or 7.5 mg bis in die (BID)] or Aten group (12.5 or 25 mg BID) according to computer-generated random numbers for 12 weeks. RESULTS: One hundred and sixty-eight patients were randomized to the Iva group and 166 to the Aten group. In a full analysis set, increases in the total exercise duration (TED) were 54.3 ± 120.1 seconds with Iva 5 mg and 58.8 ± 114.7 seconds with Aten 12.5 mg at the fourth week, and at the 12th week, TED improved by 84.1 ± 130.5 seconds with Iva and 77.8 ± 126.6 seconds with Aten (95%CI: -21.4-34.1 seconds, p = 0.0011 for noninferiority). The analysis of per protocol set yielded similar results (95%CI: -31.4-33.0 seconds, p = 0.0131 for noninferiority). Heart rate was reduced in both groups at rest and during peak exercise. There were small, nonsignificant differences in the number of adverse events between the two groups (66 in Iva and 73 in Aten, p > 0.05). Nine patients (5.42%) were reported to develop phosphenes/luminous phenomena and blurred vision in the Iva group (p = 0.0035). CONCLUSIONS: Iva is effective in reducing heart rates and improving exercise capacity and noninferior to Aten in Chinese patients with chronic stable angina pectoris. Iva is well tolerated and safe.