Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Association of psychological stress with wives’hypertension across over 10 million Chinese married female population aged 20-49 years

Background:Psychological stress has been reported to be a potential risk factor for hypertension among females,but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women.We examined the associations between stress within the family and hypertension among married women.Methods:Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects(NFPCP)across 31 provinces in China in 2016 and 2017.Perceived stress of wives or husbands was measured with a 5-point Likert-type scale,and assessed from three domains:work/life-related stress,economic stress,and overall stress.Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.Results:Of 10,027,644 couples,261,098(2.60%)women had hypertension.The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women(P_(for trend)<0.001).Compared with non-stressed participants,female participants with the highest stress themselves were at a greater risk of hypertension,with adjusted odds ratio(OR)of 1.31(95%confidence interval[CI]:1.25-1.37);and compared with participants whose husbands had no stress,those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24(95%CI:1.20-1.29).Moreover,compared with non-stressed status for both couples,only-wife-stressed,only-husband-stressed,and both-stressed couples were found to be significantly associated with increased risks of wives’hypertension,with adjusted ORs of 1.28(95%CI:1.25-1.31),1.19(95%CI:1.17-1.21),and 1.28(95%CI:1.26-1.31),respectively.Conclusion:Moderate to severe stress in both spouses might be associated with female hypertension prevalence,which highlights the importance of paying attention to the psychological stresses of couples within the family.

Contribution of oxidative stress to pulmonary arterial hypertension

Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.

Increased Oxidative Stress in Women With Pregnancy-induced Hypertension

Objective To investigate whether pregnancy-induced hypertension （PIH） may increase oxidative stress in women with PIH, and to explore the mechanisms by which PIH may increase oxidative stress and potential free radical damage. Methods Seventy women with PIH and seventy women with uncomplicated normotensive pregnancy （UNP） whose age, nutritional conditions, levels of hemoglobin and albumin were all matched, were enrolled in a randomized controlled trial. Their plasma concentrations of nitric oxide （NO）, vitamin C （VC）, vitamin E （VE）, and β-carotene （β-CAR） as well as their erythrocyte malondialdehyde （MDA）, and activities of superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX） were determined by spcctrophotometry. Results Compared with average values of the above experimental parameters in the women with UNP, the average value of erythrocyte MDA in the women with PIH significantly increased （P〈0.0001）, while the average values of plasma NO, VC, VE, and β-CAR as well as those of erythrocyte SOD, CAT, and GPX in the women with PIH significantly decreased （P〈0.0005-0.0001）. The findings from partial correlation analysis （controlling for age） for 70 women with PIH showed that with elevated systolic blood pressure （SBP） and diastolic blood pressure （DBP）, MDA value gradually increased （P〈0.001）, and NO, VC, VE, β-CAR, SOD, CAT, and GPX values gradually decreased （P〈0.02-0.001）. The findings from reliability analysis for NO, VC, VE, β-CAR, SOD, CAT, GPX, and MDA values used to reflect increased oxidative stress and potential free radical damage in women with PIH showed that the reliability coefficients （alpha, 8 items） = 0.7062, P〈 0.0001, and the standardized item alpha = 0.9116, P〈 0.0001. Conclusion The findings in the present research suggest that pregnancy-induced hypertension can increase oxidative stress and potential free radical damage in women with pregnancy-induced hypertension.

Job Stress, Gene Polymorphism of β_2-AR, and Prevalence of Hypertension

Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. β2-AR genotypes and allele frequencies at amino acid positions 16 （β2-AR-16： Arg→Gly） and 27 （β2-AR-27： Gln→Glu） were identified by PCR-RFLE Results Job stress was related with the prevalence of hypertension in males （P〈0.05）, whereas no significant relationship was found in females （P〉0.05）. Differences in genotypes and allele frequencies of the β2-AR-16 were statistically significant between the hypertension and control groups （P〈0.05）, whereas those of β2-AR-27 were not （P〉0.05）. The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group （P〈0.01 or 0.05）. Conclusion High job stress and polymorphism of β2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.

A prediction of in vivo mechanical stresses in blood vessels using thermal expansion method and its application to hypertension and vascular stenosis

Mechanical stimuli play critical roles in cardiovascular diseases,in which in vivo stresses in blood vessels present a great challenge to predict.Based on the structural-thermal coupled finite element method,we propose a thermal expansion method to estimate stresses in multi-layer blood vessels under healthy and pathological conditions.The proposed method provides a relatively simple and convenient means to predict reliable in vivo mechanical stresses with accurate residual stress.The method is first verified with the opening-up process and the pressure-radius responses for single and multi-layer vessel models.It is then applied to study the stress variation in a human carotid artery at different hypertension stages and in a plaque of vascular stenosis.Our results show that specific or optimal residual stresses exist for different blood pressures,which helps form a homogeneous stress distribution across vessel walls.High elastic shear stress is identified on the shoulder of the plaque,which contributes to the tearing effect in plaque rupture.The present study indicates that the proposed numerical method is a capable and efficient in vivo stress evaluation of patient-specific blood vessels for clinical purposes.

The Association of Psychological Stress Related Cytokines (TNF Alpha, IFN-Gamma) with Essential Hypertension in Ningxia Hui Autonomous Region

The study aimed to explore the association between psychological stress-related cytokines and essential hypertension to provide the theoretical basis for the prevention and control of the essential hypertension. We screened hypertension patients in six communities in Wuzhong City of Ningxia, and chose the healthy people who had lived in the same community for full 5 years as a control group. Finally, we selected 210 pairs of cases and controls randomly, including 108 pairs of Hui and 102 pairs of Han (50% male;age 35 -74). The results showed that the serum TNF alpha levels of hypertension group were higher than the control group (ρ 0.01), and the serum IFN-gamma levels were lower than the control group both in Hui and Han (ρ 0.01). Further analysis showed that the serum TNF alpha level of the Hui hypertension group was higher than the Han hypertension group (ρ 0.01), while the serum IFN-gamma level was lower than Han hypertension group (ρ 0.01). In conclusion, TNF alpha and IFN-gamma were the important related cytokines between psychological stress and hypertension, and taking effective measures to control the level of serum TNF alpha. IFN-gamma may have the vital significance in alleviating or preventing the genesis and development of essential hypertension.

Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats

Objective:To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates(SRH)and in combination with lisinopril against hypertension,endothelial dysfunction,vascular remodeling,and oxidative stress in rats with nitric oxide deficiency-induced hypertension.Methods:Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor,Nω-nitro-L-arginine methyl ester(L-NAME)in drinking water for 6 weeks.Hypertensive rats were administered daily with SRH(500 mg/kg/day),lisinopril(1 mg/kg/day),or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment.Hemodynamic status,vascular reactivity to vasoactive agents,and vascular remodeling were assessed.Blood and aortic tissues were collected for measurements of oxidative stress markers,plasma angiotensin-converting enzyme(ACE)activity,plasma angiotensinⅡ,and protein expression.Results:L-NAME induced remarkable hypertension and severe oxidative stress,and altered contents of smooth muscle cells,elastin,and collagen of the aortic wall.SRH or lisinopril alone reduced blood pressure,restored endothelial function,decreased plasma ACEs and angiotensinⅡlevels,alleviated oxidant markers and glutathione redox status,and restored the vascular structure.The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R expression.The combination of SRH and lisinopril was more effective than monotherapy.Conclusions:SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.

Hypertension and Work Stress among City Hall Workers, Bohicon, Benin

Introduction: In the general population as well as in the workplace, hypertension is one of the main causes of morbidity and mortality in the world. The particularities of hypertension in the world of work remain little studied. The objective of this study was to determine the prevalence and factors associated with hypertension among workers in a town hall in Benin in 2019. Methods: This was a descriptive, analytical cross-sectional study conducted from December 2018 to January 2019. A comprehensive recruitment was conducted. Data were collected during a face-to-face interview, supplemented by measurement of anthropometric parameters and blood pressure as well as a work stress assessment. Frequencies were compared using the chi-square test and Fisher’s test. The significance level was 5%. Results: A total of 86 workers were included. Their mean age was 41.55 ± 9.82 years with a sex ratio of 6.1. The prevalence of hypertension was estimated to be 18.6% [95% CI: 11.96% - 29.75%]. Hypertension was higher in workers under work stress (41.18%) as opposed to non-stressed workers (14.49%) (p = 0.032);in those who were overweight (30.77) as opposed to non-overweight (2.94%) (p Conclusion: Work stress and obesity are modifiable factors associated with hypertension in workers at the Bohicon city hall. These factors deserve to be corrected by occupational health promotion and prevention actions.

Effects of Xintongding and labellol on hemorheology, oxidative stress and inflammatory endothelial factor in patients with gestational hypertension

Objective:To explore the effects of Xintongding and labellol on hemorheology, oxidative stress and inflammatory endothelial factor in patients with gestational hypertension.Methods:104 patients with gestational hypertension admitted to our hospital from March 2016 to January 2018 were selected as the research object. 52 patients in the control group and 52 patients in the observation group were randomly divided into two groups. The control group was treated with Xintongding, while the observation group was treated with Labellol on the basis of the control group. The changes of blood pressure, hemorheology, oxidative stress index and inflammatory endothelial factors were compared and analyzed between the two groups.Results:Before treatment, there were no significant differences in the levels of SBP, DBP, LBV, HBV, PV, FIB, LPO, MDA, SOD, TNF-α, CRP, VEGF and PLGF. After treatment, the levels of SBP, DBP, LBV, HBV, PV, FIB, LPO, MDA, TNF-α and CRP were significantly decreased, while the levels of SOD, VEGF and PLGF were significantly higher than before treatment, and the levels of SBP, DBP, LBV, HBV, PV, FIB, LPO, MDA, TNF-α and CRP in the observation group were significantly lower than those in the control group, and the levels of SOD, VEGF and PLGF were significantly higher than the control group. Conclusions: Xintongding combined with labetalol in the treatment of hypertensive disorder in pregnancy can effectively improve blood pressure, blood rheology and oxidative stress, reduce inflammation and promote angiogenesis, and has clinical significance.

Effect of low-dose aspirin and Danshen injection on hemorheology, vascular endothelial function and oxidative stress in pregnancy-induced hypertension

Objective:To investigate the effect of low dose aspirin and salvia miltiorrhiza injection on hemorrheology, endothelial function and oxidative stress in patients with pregnancy induced hypertension.Methods: One hundred and eighty pregnancy-induced hypertension patients treated in our hospital from April 2015 to November 2016 were selected as study subjects and randomly divided into control group and observation group with 90 cases in each group. The control group was given routine treatment. The observation group was treated with low-dose aspirin plus Salvia miltiorrhiza in the control group. After treatment, blood rheology, vascular endothelial function and oxidative stress were measured in two groups.Results: The levels of MAP and 24 h Upro in both groups were significantly lower than those before treatment. After treatment, the MAP and 24 h Upro levels in the observation group were significantly lower than those in the control group. After treatment, the level of PT was significantly higher than that before treatment, while the level of DD and Fg was significantly lower than that before treatment. Comparing the two groups after treatment showed that the PT level, and the levels of DD and Fg were significantly lower than those in the control group;After treatment, NO levels in both groups were significantly higher than those before treatment, ET-1 and ET-1/NO levels were significantly lower than before treatment, after treatment, ET-1, NO and ET The NO level in the observation group was significantly higher than that in the control group, while ET-1 and ET-1/NO levels were significantly lower than those in the control group;Compared with those before treatment, the levels of SOD in the two groups were significantly increased and MDA significantly decreased after treatment. The SOD and MDA levels in the two groups after treatment showed that the SOD level in the observation group was significantly higher than that in the control group, while MDA level was significantly lower than that of the control group.Conclusion: The combination of low-dose aspirin and Salvia miltiorrhiza injection has significant therapeutic effect on gestational hypertension, and can effectively improve the hemorheological parameters and endothelial function of patients and reduce the oxidative stress injury in patients. It is worth further clinical promotion.

Fetal middle cerebral artery blood flow characteristics of gestational hypertension combined with fetal distress in uterus as well as their correlation with hypoxia

Objective:To study the fetal middle cerebral artery blood flow characteristics of gestational hypertension combined with fetal distress in uterus as well as their correlation with hypoxia. Methods: Puerperae with hypertensive disorders in pregnancy and fetal distress in uterus, puerperae with hypertensive disorders in pregnancy alone and healthy puerperae who gave birth in our hospital between January 2013 and January 2016 were included in group A, group B and group C of the study respectively. At 34-36 weeks of pregnancy, color Doppler ultrasonography was conducted to determine fetal middle cerebral artery blood flow parameters;after childbirth, umbilical arterial blood was collected to determine blood gas analysis parameters, and the placenta tissue was collected to determine oxidative stress and mitochondria damage indexes.Results:Fetal middle cerebral artery S/D, PI and RI of group A were significantly higher than those of group B and group C while umbilical artery pH value and PaO2 as well as HCO3- and BE content were significantly lower than those of group B and group C;fetal middle cerebral artery S/D, PI and RI as well as umbilical artery pH value, PaO2, HCO3- and BE content of group B were not significantly different from those of group C;Nrf2, ARE, NQO1, VitC, SVCT1, SVCT2, ATP, PGC-1α, PGC-1β, NRF1 and NRF2 content in placenta tissue of group A were significantly lower than those of group B and group C while ROS content was significantly higher than those of group B and group C;Nrf2, ARE, NQO1, VitC, SVCT1, SVCT2, ATP, PGC-1α, PGC-1β, NRF1 and NRF2 content in placenta tissue of group B were significantly lower than those of group C while ROS content was significantly higher than that of group C. Fetal middle cerebral artery S/D, PI and RI were negatively correlated with umbilical artery pH value, PaO2, HCO3- and BE content as well as Nrf2, ARE, NQO1, VitC, SVCT1, SVCT2, ATP, PGC-1α, PGC-1β, NRF1 and NRF2 content, and were positively correlated with ROS content.Conclusions:Gestational hypertension combined with fetal distress in uterus can lead to increased fetal middle cerebral artery blood flow resistance and decreased blood perfusion, and the changes of middle cerebral artery blood flow characteristics can assess the degree of hypoxia and oxidative stress damage.

Effects of Endoplasmic Reticulum Stress on Pulmonary Hypertension in Rat Induced by Chronic Hypoxia and Hypercapnia

Objective: To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension. Methods: 1) 40 SD rats were randomly divided into four groups: normoxic control group (N), hypoxia hypercapnia group (HH), endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid group (4-PBA), ERS pathway agonist tunicamycin group (TM). 2) The mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RV/(LV + S)) were measured in each group. 3) Identification of pulmonary artery smooth muscle cells (PASMCs) in each group by immunofluorescence α-SMA. 4) Morphological changes of lung tissue and pulmonary artery were observed by electron microscope. 5) The apoptotic index of PASMCs in each group was detected by TUNEL. 6) Reverse transcription polymerase chain reaction (RT-PCR) and Western Blot (WB) were used to detect the expression of ERS related protein and mRNA (GRP78, CHOP, JNK, Caspase-12) in each group. Results: 1) Compared with the N group, the mPAP, RV/(LV + S) and vascular wall area (WA)/total area (TA) value of HH group, 4-PBA group and TM group were increased (P < 0.01), and the vascular lumen area (LA)/TA values, PASMCs apoptosis index were significantly decreased. GRP78, CHOP, JNK, Caspase-12 expression were increased, and the differences were statistically significant. 2) Compared with the HH group, the mPAP, RV/(LV + S) and WA/TA of 4-PBA group were decreased (P < 0.01);the LA/TA value and PASMCs apoptosis index were increased (P < 0.05);and the mRNA and protein expression of CHOP, JNK, Caspase-12 and GRP78 had a significant decrease (P < 0.05). 3) Compared with the HH, the mPAP, RV/(LV + S) and WA/TA of TM group were increased (P P P < 0.01);and? PASMCs apoptotic index was increased (P < 0.01). Meanwhile, the mRNA expression of Caspase-12, CHOP, JNK and GRP78 was increased to varying degrees (P < 0.05), and the protein expression of Caspase-12, CHOP and JNK was also increased significantly (P Conclusion: Hypoxia and hypercapnia induced pulmonary vascular remodeling may be related to the proliferation of PASMCs, and ERS related factors (JNK, Caspase12 and CHOP) are involved in the regulation of hypoxic hypercapnia.

Grain Yield,Biomass Accumulation,and Leaf Photosynthetic Characteristics of Rice under Combined Salinity-Drought Stress

Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinity-drought stress poses a major threat to rice production.In this study,two salinity levels(NS,non-salinity;HS,high salinity)along with three drought treatments(CC,control condition;DJ,drought stress imposed at jointing;DH,drought stress imposed at heading)were performed to investigate their combined influences on leaf photosynthetic characteristics,biomass accumulation,and rice yield formation.Salinity,drought,and their combination led to a shortened growth period from heading to maturity,resulting in a reduced overall growth duration.Grain yield was reduced under both salinity and drought stress,with a more substantial reduction under the combined salinity-drought stress.The combined stress imposed at heading caused greater yield losses in rice compared with the stress imposed at jointing.Additionally,the combined salinity-drought stress induced greater decreases in shoot biomass accumulation from heading to maturity,as well as in shoot biomass and nonstructural carbohydrate(NSC)content in the stem at heading and maturity.However,it increased the harvest index and NSC remobilization reserve.Salinity and drought reduced the leaf area index and SPAD value of flag leaves and weakened the leaf photosynthetic characteristics as indicated by lower photosynthetic rates,transpiration rates,and stomatal conductance.These reductions were more pronounced under the combined stress.Salinity,drought,and especially their combination,decreased the activities of ascorbate peroxidase,catalase,and superoxide dismutase,while increasing the contents of malondialdehyde,hydrogen peroxide,and superoxide radical.Our results indicated a more significant yield loss in rice when subjected to combined salinity-drought stress.The individual and combined stresses of salinity and drought diminished antioxidant enzyme activities,inhibited leaf photosynthetic functions,accelerated leaf senescence,and subsequently lowered assimilate accumulation and grain yield.

Carvedilol vs. metoprolol: A comparison of effects on endothelial function and oxidative stress in response to acute hyperglycemia in patients with type 2 diabetes and hypertension

Introduction: The GEMINI trial compared the effects of treatment with metoprolol versus carvedilol in patients with type 2 diabetes. Carvedilol demonstrated a more favorable effect on factors associated with the metabolic syndrome than metoprolol. We hypothesize that carvedilol will have additional beneficial effects on markers of inflammation, oxidative stress, and endothelial function than metoprolol. Methods: Twenty subjects were randomized to either carvedilol or metoprolol. Study procedures including assessment of metabolic parameters and endothelial function, while fasting and after a 75 g oral glucose tolerance were conducted at baseline and following 5 months of treatment. Results: Following 5 months of treatment, PAI-1 increased significantly from baseline in the metoprolol group. There were no changes in PAI-1 in the carvedilol group. While not reaching statistical significance, there was a trend toward worsening insulin resistance with metoprolol treatment compared to carvedilol treatment. Flow mediated vasodilation increased in both groups following the 2-hr OGGT during the baseline study. After five months of treatment, there was a non-significant increase in flow-mediated vasodilation under both fasting and post OGTT conditions in the carvedilol group compared to baseline. Conversely, there was no change in fasting flow mediated vasodilation in the metoprolol group. Additionally, metoprolol treatment blunted the increase in flow mediated vasodilation following OGGT compared to baseline (p < 0.05). Conclusion: Treatment with metoprolol was associated with adverse metabolic effects including increases in PAI-1 and trends toward worsening insulin resistance and endothelial function compared to treatment with carvedilol.

Effect of nifedipine combined with Magnesium Sulfate on oxidative stress,hemorheology,platelet active substances and renal function in patients with pregnancy-induced hypertension

Objective: To investigate effect of nifedipine combined with Magnesium Sulfate on levels of oxidative stress, blood rheology, platelet active substance and renal function in patients with pregnancy-induced hypertension. Methods: A total of 99 cases of patients with pregnancy-induced hypertension were selected as the study object, according to random data table, they were divided into control group (n=50) and observation group (n=49), patients in control group were treated with Magnesium Sulfate, while patients in the observation group received Magnesium Sulfate combined with nifedipine treatment, levels of blood pressure and oxidative stress, blood rheology, platelet activity and renal function index before and after treatment of both groups were compared. Results: There were no significant difference of the level of DBP, SBP, Tac, MDA, SOD, high/low shear blood viscosity, PV, HCT, CD62P, CD63, GPⅡb/Ⅲa, SCr and BUN before treatment between control group and the observation group. Compared with intragroup before treatment, the levels of DBP, SBP, MDA, high/low shear blood viscosity, PV, HCT, CD62P, CD63, GPⅡb/Ⅲa, SCr and BUN after treatment of the two groups were significantly decreased, and the levels of the observation group after treatment was significantly lower than those in the control group, the difference was statistically significant;Compared with level of SOD and Tac, after treatment, the levels of SOD and Tac of the two groups were significantly higher than those in the same group before treatment, and levels of the observation group was significantly higher than in the control group, the difference was statistically significant. Conclusion: Nifedipine combined with magnesium sulfate treatment of pregnancy-induced hypertension, which can effectively reduce the blood pressure level of patients, improve the levels of oxidative stress, blood rheology and platelet active substance, protect renal function, with an important clinical value.

Heat stress induced hepatocyte apoptosis in largemouth bass Micropterus salmoides via IRE1α/TRAF2/ASK1/JNK pathway

Heat stress(HS)has been shown to adversely affect fish livers and can lead to extensive apoptosis.To investigate the relationship between endoplasmic reticulum(ER)stress and HS-induced apoptosis in fish livers,we isolated and cultured primary hepatocytes of largemouth bass,Micropterus salmoides by trypsin method,then established an in-vitro model of liver cells under HS(35℃).The contents of lactic dehydrogenase(LDH)and hydrogen peroxide(H2O2)were determined to evaluate the effects of HS on hepatocyte injury and oxidative stress.RT-qPCR was performed to discover the key genes in unfolded protein response(UPR)pathways involved at different HS duration.ERS inhibitor 4-PBA and IRE1αinhibitor 4μ8C were used to further investigate the effects of HS on IRE1αapoptosis pathway in hepatocytes.Results show that HS led to significant increases in the release of LDH,the content of H2O2,and the expressions of oxidative protein folding genes(ero1αand pdi)under HS,suggesting severe hepatocyte injury and oxidative stress happened in heat-stressed largemouth bass hepatocytes.The continuous activation of IRE1αpathway genes(grp78,grp94,atf6,perk,eif2a,atf4,chop,ire1α,traf2,ask1,jnk1,and jnk2)indicated that HS led significantly to ER stress.In particular,the mRNA expression levels of ER stress-related genes(grp78,grp94,atf6,perk,ire1α,chop,jnk1,and jnk2)in the high temperature(HT)+4-PBA group and the HT+4μ8C group were significantly down-regulated under HS.After 4μ8C treatment,the expression levels of apoptosis-related genes(caspase-2,caspase-3,caspase-6,caspase-7,caspase-8,caspase-9,and caspase-10)and LDH content were significantly decreased,whereas the cell survival rate was significantly increased when given 4-PBA or 4μ8C treatment.These findings demonstrate that HS could induce liver apoptosis of largemouth bass through the IRE1αpathway,which may act as a key switch mediating liver apoptosis of largemouth bass under HS.

Stress tensor determination by modified hydraulic tests on pre-existing fractures:Method and stress constraints

The hydraulic testing of pre-existing fractures(HTPF)is one of the most promising in situ stress measurement methods,particularly for three-dimensional stress tensor determination.However,the stress tensor determination based on the HTPF method requires at least six tests or a minimum of 14-15 tests(under different conditions)for reliable results.In this study,we modified the HTPF method by considering the shear stress on each pre-existing fracture,which increased the number of equations for the stress tensor determination and decreased the number of tests required.Different shear stresses were attributed to different fractures by random sampling;therefore,the stress tensors were obtained by searching for the optimal solution using the least squares criterion based on the Monte Carlo method.Thereafter,we constrained the stress tensor based on the tensile strength criterion,compressive strength criterion,and vertical stress constraints.The inverted stress tensors were presented and analyzed based on the tensorial nature of the stress using the Euclidean mean stress tensor.Two stress-measurement campaigns in Weifang(Shandong Province,China)and Mercantour road tunnel(France)were implemented to highlight the validity and efficiency of the modified HTPF(M-HTPF)method.The results showed that the M-HTPF method can be applied for stress tensor inversion using only three to four tests on pre-existing fractures,neglecting the stress gradient.The inversion results were confined to relatively small distribution dispersions and were significantly reliable and stable due to the shear stresses on the fractures and the stress constraints employed.The M-HTPF method is highly feasible and efficient for complete stress tensor determination in a single borehole.

Three-dimensional stress variation characteristics in deep hard rock of CJPL-Ⅱ project based on in-situ monitoring

In deep hard rock excavation, stress plays a pivotal role in inducing stress-controlled failure. While the impact of excavation-induced stress disturbance on rock failure and tunnel stability has undergone comprehensive examination through laboratory tests and numerical simulations, its validation through insitu stress tests remains unexplored. This study analyzes the three-dimensional stress changes in the surrounding rock at various depths, monitored during the excavation of B2 Lab in China Jinping Underground Laboratory Phase Ⅱ(CJPL-Ⅱ). The investigation delves into the three-dimensional stress variation characteristics in deep hard rock, encompassing stress components and principal stress. The results indicate changes in both the magnitude and direction of the principal stress during tunnel excavation. To quantitatively describe the degree of stress disturbance, a series of stress evaluation indexes are established based on the distances between stress tensors, including the stress disturbance index(SDI), the principal stress magnitude disturbance index(SDIm), and the principal stress direction disturbance index(SDId). The SDI indicates the greatest stress disturbance in the surrounding rock is 4.5 m from the tunnel wall in B2 Lab. SDIm shows that the principal stress magnitude disturbance peaks at2.5 m from the tunnel wall. SDId reveals that the largest change in principal stress direction does not necessarily occur near the tunnel wall but at a specific depth from it. The established relationship between SDI and the depth of the excavation damaged zone(EDZ) can serve as a criterion for determining the depth of the EDZ in deep hard rock engineering. Additionally, it provides a reference for future construction and support considerations.

Disturbance failure mechanism of highly stressed rock in deep excavation:Current status and prospects

This article reviews the current status on the dynamic behavior of highly stressed rocks under disturbances.Firstly,the experimental apparatus,methods,and theories related to the disturbance dynamics of deep,high-stress rock are reviewed,followed by the introduction of scholars’research on deep rock deformation and failure from an energy perspective.Subsequently,with a backdrop of highstress phenomena in deep hard rock,such as rock bursts and core disking,we delve into the current state of research on rock microstructure analysis and residual stresses from the perspective of studying the energy storage mechanisms in rocks.Thereafter,the current state of research on the mechanical response and the energy dissipation of highly stressed rock formations is briefly retrospected.Finally,the insufficient aspects in the current research on the disturbance and failure mechanisms in deep,highly stressed rock formations are summarized,and prospects for future research are provided.This work provides new avenues for the research on the mechanical response and damage-fracture mechanisms of rocks under high-stress conditions.