Age-specific differences in hypertension combination management and associated factors influencing treatment choice.

The current hypertension guideline emphasizes combination therapy, especially single-pill combination therapy (SPC). However, few studies compared the prevalence and factors associated with initial therapy choice across heterogeneous age groups in a current population. First, the authors consecutively identified 964 treatment naïve hypertensive patients in a large academic hospital from 01/31/2019 to 01/31/2020. All patients were grouped into (1) young aged, age < 55; (2) middle-aged, 55≤age < 65; and (3) older aged, age ≥65. The multivariable regression model examined the factors associated with the combination therapy by age group. Overall, 80 (8.3%) were young, 191 (19.8%) were middle, and 693 (71.9%) were older aged. Compared with older age, younger patients were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular-related comorbidities, with a lower systolic but higher diastolic pressure. Only one in five patients used SPC, and the prevalence decreased with age. Besides hypertension grade, young patients without catheterization or echo test were less likely to receive multiple therapies, while older patients who were male with lower weight and lower risk levels were less likely to receive multiple therapies. In conclusion, combination therapy, especially SPC, was underused in the targeted hypertensive population. Our contemporary population study showed that young patients (<55) without a history of catheterization or echo examination and male older-aged (≥65) patients with low-risk classification were the population most likely to be neglected. Such information can help triage medical care resources in improving SPC use.

EFFECTS OF SHENFU INJECTION ON SUBLINGUAL MICROCIRCULATION IN SEPTIC SHOCK PATIENTS: A RANDOMIZED CONTROLLED TRIAL.

ABSTRACT: Background and Objective: The optimization of macrocirculatory hemodynamics is recommended by current sepsis guidelines. However, microcirculatory dysfunction is considered the cause of severe sepsis. In the present study, we designed to verify whether the application of Shenfu injection (SFI) restores microcirculation, thereby improving tissue perfusion and inhibiting organ dysfunction, resulting in improved outcomes. Design: We conducted a prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Intervention: Patients were randomly assigned to group receiving SFI (n = 20) or placebo (n = 20) for 5 days. We administered SFI or glucose injection for 5 days and blinded the investigators and clinical staff by applying light-proof infusion equipment that concealed therapy allocation. Measurements and Results: We measured the systemic dynamics and lactate levels, biomarkers of endothelial dysfunction, and inflammatory cytokines in the plasma. The parameters of sublingual microcirculation were assessed using side-stream dark-field imaging. Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) score, total dose, and duration of vasopressor use, emergency intensive care unit (EICU) stay, and 28-day mortality were evaluated. After treatment with SFI, the disturbance of the sublingual microcirculation was considerably alleviated, as indicated by the significant increase in total vessel density, perfused vessel density, and microvascular flow index. Moreover, the plasma biomarker levels of endothelial dysfunction, including Ang-2, Syn-1, and ET-1, were reversed after SFI treatment. Importantly, the SFI group had a more favorable prognosis than the control group in terms of the APACHE-II score, SOFA score, duration of vasopressor administration, and length of EICU stay. However, the difference in mortality at day 28 was not statistically different between the SFI (15%, 3/20) and placebo (25%, 5/20) groups ( P = 0.693). Conclusions : Shenfu injection provided apparent effects in improving sublingual microcirculatory perfusion in patients with septic shock, and this protection may be related with the inhibition of endothelial dysfunction and vasodilatory effects.

Cyclophosphamide Combined with Bone Marrow Mesenchymal Stromal Cells Protects against Bleomycin-induced Lung Fibrosis in Mice.

INTRODUCTION: To examine the effects and possible mechanism of the immunosuppressant agent cyclophosphamide (CP) combined with bone marrow mesenchymal stromal cells (BM-MSCs) on bleomycin induced lung fibrosis in mice. METHODS: BM-MSCs labeled with red fluorescence protein (RFP) from male Friend virus B-type(FVB) mice were cultured in vitro. Pulmonary fibrosis(PF) was induced in female wild type FVB mice and mice were randomly divided into five groups: control, model, CP, BM-MSCs, and BM-MSCs+CP. Pathological changes and distribution of RFP (+) BMSC in lung tissue were observed and hydroxyproline (Hyp) content in the lungs was measured. Changes in TGF-ß mRNA, PDGF mRNA, and SDF-1mRNA expression in lung tissue were measured. RESULTS: PF and Hyp levels in the BM-MSCs and BM-MSCs+CP groups were significantly alleviated (p<0.01) compared to the model group. The RFP (+) cells were distributed in the periphery of the alveolar space and endomembrane of bronchus. Hyp levels were reduced in the BM-MSCs+CP group compared to the BM-MSCs group (p<0.05). TGF-ß and PDGF levels in the BM-MSCs and BM-MSCs+CP groups were higher than in the control or model group (p<0.05). SDF-1 level in the CP group showed no significant differences compared to the control group, in the other groups were higher than in the control group (p<0.05) and in the BM-MSCs+CP group was lower than in the BM-MSCs group (p<0.05). CONCLUSION: It was concluded that CP alone does not improve PF and may be harmful. In contrast, combined application of BM-MSCs with CP provided better protection against PF and may serve as an effective therapy.

Prevention of Pulmonary Fibrosis via Trichostatin A (TSA) in Bleomycin Induced Rats.

PURPOSE: To investigate the effects of non selective histone deacetylase inhibitors Trichostatin A (TSA)on bleomycin-induced pulmonary fibrosis. To investigate the effects of non selective histone deacetylase inhibitors Trichostatin A ( TSA ) on HDAC2, p-SMAD2, HDAC2 mRNA, SMAD2mRNA in pulmonary fibrosis rats and investigate impossible mechanism. METHODS: 46 SPF level male SD rats were randomly divided into four groups: ten for normal control group, fourteen for model control group I, twelve for model control group II and ten for treatment group. Rat pulmonary fibrosis was induced by bleomycin(5mg/kg) via single intratracheal perfusion in the two model control groups and treatment group. Normal control mice were instilled with a corresponding volume of 0.9% saline intratracheally. Treatment group was treated by the dilution of TSA 2mg/kg DMSO 60ul and0.9% saline 1.2ml intraperitoneal injection from the next day ,once a day for three days. Model control group II was treated by the dilution of DMSO 60ul and0.9% saline 1.2ml intraperitoneal injection from the next day once a day for three days. Model control group I and normal control group were treated by 0.9% saline 1.2ml intraperitoneal injection from the next day once a day for three days. All the animals were sacrificed on the 21 day after modeling. The pathological changes were observed by hematoxylin and eosin(HE)stain and masson trichrome stain. The expression of HDAC2 mRNA,SMAD2 mRNA were measured by real-time PCR. The protein level of HDAC2 and p-SMAD2 in serum was measured by Western blot. RESULTS: The pulmonary fibrosis in treatment group were significantly alleviated compared to the two model control groups (P<0.05). Real-time PCR showed that the treatment group had lower expression of lung tissue HDAC2 mRNA than the two model control groups and normal control group (P<0.05). The expression of lung tissue SMAD2 mRNA increased in the two model control groups and treatment group (P<0.05),but there were no significant differences among the three groups(P>0.05). Western blot indicated that the protein level of HDAC2 and p-SMAD2 in serum increased in the two model control groups compared with normal control group(P<0.05).But treatment group had lower protein level of HDAC2 (P<0.05) and no significant difference in the protein level of p-SMAD2 compared to the two model control groups (P>0.05). CONCLUSION: Non selective histone deacetylase inhibitors of Trichostatin A (TSA) can reduce the bleomycin induced pulmonary fibrosis in rats. TSA attenuates pulmonary fibrosis and it can inhibit HDAC2 expression at the gene and protein level. Bleomycin induced fibrosis has the relationship with p-SMAD2 in gene and protein levels, but TSA inhibit bleomycin-induced lung fibrosis effect with no relation with SMAD2 phosphorylation pathways.

The present/null polymorphism in the GSTT1 gene and the risk of lung cancer in Chinese population.

The present/null polymorphism in the GSTT1 gene has been implicated in susceptibility to lung cancer in Chinese population. A large number of studies have reported inconclusive results. The aim of the current study was to investigate the relationship between the present/null polymorphism in the GSTT1 gene and lung cancer risk in Chinese population by meta-analysis. The Pubmed, Embase, CNKI, and Wanfang databases were searched. The statistical analysis was performed by using Revman4.2 and Stata10.0. In summary, a total of 2,211 lung cancer cases and 3,115 controls in 18 case-control studies were included for data analysis. The results suggested that the null genotype carriers may contribute to increased risk of lung cancer in Chinese population when compared with the present genotype carriers (odds ratio = 1.24, 95% confidence interval = 1.02-1.49). The current meta-analysis suggested that the present/null polymorphism in the GSTT1 gene might contribute to the risk of lung cancer in Chinese population. Future studies are needed to validate these results.