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Adrenal insufficiency is a disease characterized by insufficient secretion of adrenocortical hormones, usually treated with glucocorticoid replacement therapy. The routine drugs have two forms-short-acting and long-acting. The shorter one should be taken 2-3 times a day resulting hormone level of patients fluctuating greatly within a day. Although long-acting drugs reduce the frequency of administration, it is easy to lead to excessive replacement, resulting in adverse effects on metabolism. New alternative treatments for adult patients have emerged, including modified-release hydrocortisone and hydrocortisone subcutaneous infusion pumps. In this review, we briefly introduce these new therapies, emphasizing the pharmacodynamics and pharmacokinetics of the replacement, the effects on metabolism and drug safety, aiming at contributing to the future clinical practice.
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Objective:To evaluate early left ventricular myocardial work in patients with metabolic syndrome (MS) by pressure-strain loops (PSL).Methods:From September 2020 to April 2021, 70 MS patients in the First Hospital of Qinhuangdao Affiliated to Hebei Medical University without left ventricular remodeling were selected as MS group and 65 normal controls as control group, PSL was used to obtain the myocardial power parameters, including global work index (GWI), global work efficiency (GWE), global constructive work (GCW) and global wasted work (GWW). The changes of the parameters were compared between the two groups and their correlations with biochemical parameters were performed in MS group.Results:The left ventricular global longitudinal strain (GLS), GWI, GCW and GWE in MS group were lower than those in normal group, while GWW was higher than that in normal group ( P<0.05). Pearson correlation analysis showed that GWI was positively correlated with high-density lipoprotein cholesterol (HDL-C) ( r=0.194, P<0.05), and negatively correlated with diastolic blood pressure (DBP), waist circumference (WC), fasting blood glucose (Glu), triglyceride (TG) and GLS ( r=-0.257, -0.452, -0.239, -0.193, -0.758, all P<0.05). GWE was negatively correlated with SBP, DBP, WC, Glu, TG and GLS ( r=-0.360, -0.269, -0.326, -0.352, -0.265, -0.663, all P<0.01), and positively correlated with HDL-C ( r=0.201, P<0.05). GCW was negatively correlated with WC and GLS ( r=-0.299, -0.737; all P<0.001). GWW was positively correlated with SBP, DBP, WC, Glu, TG and GLS ( r=0.435, 0.308, 0.413, 0.547, 0.272, 0.400, all P<0.01), and negatively correlated with HDL-C ( r=-0.336, P<0.001). Conclusions:PSL can quantitatively evaluate the changes of early myocardial work in MS patients with good repeatability and has certain clinical value.
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Pericytes are located between capillary endothelial cells, astrocytes and neurons. They have many functions such as maintaining the integrity of blood-brain barrier and regulating cerebral blood flow. Loss of pericytes can lead to pathological processes such as brain microcirculation dysfunction and blood-brain barrier destruction, and is associated with a variety of diseases, but there are few studies on the correlation between them and cerebral small vessel disease. This article mainly reviews the role of pericytes in the pathogenesis of cerebral small vessel disease.
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The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
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Objective:To validate the role of color Doppler ultrasound in an animal model to detect early heterotopic ossification (HO) after brain-traumatic/burn/tenotomy.Methods:Forty-four rats were randomly divided into two groups. Rats in experimental group ( n=22) were operated to build brain-traumatic/burn/tenotomy model and others in control group ( n=22) underwent only skin incision injury. Color Doppler ultrasound, X-ray film examination at 2, 3, 4, 6, 8 and 10 weeks post-injury were performed to follow up the progression of HO in both groups respectively. Histology was used to confirm bone formation. Results:In the experimental group, disorder structure with a hypoechoiccore in treated Achilles tendon was visualized using color Doppler ultrasound in the 2nd week. Additional tiny hyperechoic foci were observed in the 3rd week, which increased in the fourth week and fused into a mineralized island in the sixth week. No obvious abnormality was found in control group at the aforementioned time point. X-ray could detect heterotopic bone tissue in the sixth week in the experimental group but not in the control group. X-ray and HE stainning had confirmed bone formation in the tenth week in the experimental group.Conclusions:Color Doppler ultrasound can detect early HO and continuously follow up the progression of HO.
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A large number of studies have confirmed that endothelial dysfunction is one of the important pathogenesis of cerebral small vessel disease (CSVD). Endothelial dysfunction interacts with blood-brain barrier dysfunction, chronic cerebral hypoperfusion, oxidative stress, inflammation and other mechanisms to jointly promote the occurrence and development of CSVD. This article reviews the role of endothelial dysfunction in the pathogenesis of CSVD and its intervention strategies.
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Objective: To explore the clinical value of longitudinal layers-strain technology for assessing myocardial function in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Methods: Twenty-five ACS patients who underwent successful PCI (PCI group) and 25 normal subjects (control group) were collected. M-mode echocardiography, biplane Simpson, tissue Doppler imaging and longitudinal layers-strain were used to analyze left ventricular function and myocardial function respectively in both groups. Results: Longitudinal layers strain and global longitudinal layers strain in PCI group decreased gradually from endocardium to epicardium, and all parameters reduced compared with those of control group (all P<0.05). The gradient of global longitudinal strain between endocardium and epicardium (△GLS) existed in both groups, while the absolute value of △GLS apparently reduced in PCI group compared with control group (P<0.05). Conclusion: Longitudinal strain decreased from endocardium to epicardium in ACS patients after PCI. Longitudinal layers-strain might be a sensitive index of myocardial and left ventricular dysfunction in ACS patients after PCI.
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OBJECTIVE：To establish the method for content determination of related substances in Paracetamol tablets. METHODS：HPLC method was adopted. The determination was performed on Agilent 5HC-C8 column with mobile phase A consisted of methanol-water-glacial acetic acid （50 ∶ 950 ∶ 1，V/V/V）and mobile phase B consisted of methanol-water-glacial acetic acid（500 ∶ 500 ∶ 1，V/V/V）（gradient elution ）at the flow rate of 0.9 mL/min. The detection wavelength was set at 254 nm，and column temperature was 40 ℃. The sample size was 5 μL. RESULTS：Under the chromatographic condition ，the resolutions of main component （paracetamol），6 known impurities （p-aminophenol，p-chloroacetanilide，impurity A ，B，D，F），3 specific excipients（methyl hydroxybenzoate ，ethyl hydroxybenzoate ，propyl hydroxybenzoate ）and 1 unknown impurity were all higher than 1.5. The linear range of 6 known impurities were 0.539-1.617，0.026-0.384，0.237-17.799，0.257-19.271，0.239-17.955， 0.246-18.462 μg/mL（r≥0.999 8），respectively. Correction factors of impurity A ，B，D，F were 2.9，1.0，1.2，6.2. The limits of detection were 0.009 6，0.024 2，0.164 0，0.051 1，0.055 9，0.422 0 ng；the limits of quantitation were 0.032 0，0.080 6，0.546 0，0.170 0，0.186 0，1.406 0 ng. Average recoveries were 95.96％-111.09％（RSDs were 0.05％-2.42％）. The RSDs precision test were low than 15％，and the durability were good. p-aminophenol（all were 0.006％），impurity B （0.016％-0.017％）and unknown impurity（0.002 0％-0.002 1％）were detected in 3 batches of sample. p-choroacetanilide，impurity A ，D and F were not detected. CONCLUSIONS：The method is specific ，accurate and suitable for the determination of related substance in Paracetamol tablets.
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@#To investigate the material basis and mechanism of Liupao tea on preventing COVID-19 by network pharmacology and molecular docking.The active ingredients and targets of Liupao tea were searched through the literature and the TCMSP databases and the network between the two was built by Cytoscape 3.7.1.Then using GenCards platform to predict the disease targets,mapping the common targets between Liupao tea and disease.The common targets were imported into the STRING database for exploring the protein-protein interaction.Core targets were enriched by gene ontology (GO) enrichment analysis and KEGG (kyoto encyclopedia of genes and genomes) pathway enrichment analysis using DAVID database etc..Finally,the screened active components were docked with the receptor protein SARS-CoV-2 3CL hydrolase (Mpro).Six active ingredients of Liupao tea were screened,such as (-)-epigallocatechin gallate (EGCG),(+)-catechin,(-)-catechin gallate,α-spinasterol,pelargonidin chloride and squalene,and 156 targets were identified.Among them,there were 112 common targets and 38 core targets with COVID-19.GO enrichment analysis (P<0.01) involved lipopolysaccharide,cell response to hypoxia,etc..And the KEGG pathway enrichment analysis (P<0.01)was conducted to obtain the HIF-1,IL-17,T cell receptor and other signaling pathways associated with COVID-19.The results of molecular docking showed that the active ingredients of Liupao tea were well bound to the receptor protein Mpro.The active ingredients of Liupao tea may control HIF-1,IL-17,T cell receptors signaling pathways by binding Mpro hydrolase and acting on inflammation and immune related targets such as MAPK1,TNF to prevent COVID-19.The EGCG of Mpro activity was determined ,and the IC50 was 3.4 μmol/L,which confirmed that EGCG was a certain inhibition effect on Mpro.
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Objective To investigate the effects of Maiqi-Jiangtang pill on the glycolipid level in type 2 diabetic ob/ob mice.Methods The 8-week old male ob/ob mice were randomly divided into Maiqi-Jiangtang pill high- (8 g/kg), medium- (4 g/kg), low- (2 g/kg) dose groups. All the mice orally adiministered with the drugs once a day for 10 weeks. The same week age normal C57BL/6J control mice and ob/ob model group mice were orally administered with the equal volume solvent. The body weight per week were recorded. The fasting blood-glucose (FBG) was measured by glycemic instrument. The content of TG, TC, HDL-C, LDL-C in serum, and TG and TC content in liver were determined by biochemical method. The liver index was calculated.Results Compared with ob/ob model group, there was no significant change in body weight of mice administered with Maiqi-Jiangtang pill for 10 weeks. Compared with the model group, the low-, medium- dose Maiqi-Jiangtang pill could significantly decrease the FBG (7.43 ± 1.71 mmol/L,7.84 ± 1.09 mmol/L vs.8.95 ± 0.96mmol/L), the high- dose Maiqi-Jiangtang pill could significantly reduce the TG (0.93 ± 0.16 mmol/L vs.1.18 ± 0.26 mmol/L) and LDL-C (2.10 ± 0.51 mmol/L vs.2.56 ± 0.44 mmol/L) content in serum of ob/ob mice (P<0.05), increase the HDL-C/LDL-C ratio (2.40 ± 0.39vs.1.96 ± 0.24) in serum (P<0.01), decrease the liver weight (3.52 ± 0.26 gvs. 3.98 ± 0.35 g) and the liver index (0.063 ± 0.004vs. 0.071 ± 0.006) (P<0.05). Compared with the model group, the low dose Maiqi-Jiangtang pill could also significantly decrease the TG level (0.63 ± 0.25 mmol/gvs. 1.05 ± 0.67 mmol/g) in liver and significantly increase the HDL-C/LDL-C ratio (2.30 ± 0.44vs. 1.96 ± 0.24) in serum (P<0.05).Conclusions The Maiqi-Jiangtang pill can reduce lipid in serum and liver of ob/ob mice while it can decrease the blood glucose, which need to further study its mechanism.
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OBJECTIVE:To establish the method for simultaneous determination of the content of berberine hydrochloride, baicalin and osthole in Jinchan zhiyang capsules. METHODS:HPLC method was adopted. The determination was performed in Hypersil BDS C18 column with mobile phase consisted of methanol-acetonitrile-0.1%phosphoric acid-three triethylamine(50∶30∶19∶1, V/V/V/V) at the flow rate of 1.0 mL/min. The detection wavelengths were set at 265 nm (berberine hydrochloride),280 nm (baicalin)and 322 nm(osthole). The column temperature was set at 30 ℃,and sample size was 10 μL. RESULTS:The linear range of berberine hydrochloride,baicalin and osthole were 80-800 ng(r＝0.999 8),60-600 ng(r＝0.999 9),60-600 ng(r＝0.999 6),respectively. RSDs of precision,stability and reproducibility tests were all lower than 2.0%. The limits of quantitation were 80,60,60 ng,respectively,and the limits of detection were 24,20,20 ng,respectively. The recovery rates were 97.4%-98.3%(RSD＝0.33%,n＝6),98.4%-99.6%(RSD＝0.42%,n＝6)and 96.9%-99.0%(RSD＝0.92%,n＝6),respectively. RSDs of durability tests were all lower than 1.2%. CONCLUSIONS:The method is simple, accurate, precise, stable, reproducible and durable. It can be used for simultaneous determination of berberine hydrochloride,baicalin and osthole in Jinchan zhiyang capsules.
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Objective To explore the effect of time management on the on-time rate of implementation of the first selective operation.Methods Five hundred and two selective operations from January to May of 2013 without time management were set as control group, while another five hundred and twenty with time management as experiment group. The two groups were compared in terms of on-time rate of the first selective operation, time for nurse’s extra shift, number of nurses at extra shift, numbers of operations and satisfaction level.Results After time management, the experiment group was significantly better than the control in terms of the on-time rate of operations, time for nurse’s extra shift, number of nurses at extra shift, numbers of operations and satisfaction level (all P<0.01).Conclusion Time management used in the operation room can significantly improve the on-time rate of selective operations and doctors’satisfaction and work efficiency, thus decrease nurses’overworking time.
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Objective To assess the volume and function of right atrium(RA) in patients with chronic pulmonary hypertension(PH) by echocardiography and explore the influencing factors of these changes.Methods The study include 20 healthy participants as the control group and 57 patients with chronic PH as the case group.The patients were divided into three groups: low-grade PH, midrange PH and severe PH.Maximal RA volume index(VmaxI), minimal RA volume index(VminI), pre-atrial contraction RA volume index( VpreI), reservoir volume index(RVI), conduit volume index(CVI), contraction-chamber volume index (CCVI) were measured and calculated.The diameter of tricuspid valve and the late-diastole peak velocity of the bloodstream(Va) were measured,and then RA ejection force(RAEF) could be calculated.Systolic strain rate(RASRs), early diastolic strain rate (RASRe), and late diastolic strain rate (RASRa) of RA free wall were measured respectively.The correlation between pulmonary arterial systolic pressure (PASP), right ventricular ejection fraction(RVEF),the tissue Doppler of RV free wall(Ea/Aa) and the parameters of RA were analysed,and the main factors influencing the volume and function of RA were exploxed.Results With the rising of PASP, the RA volume changed obviously.And CCVI, RAEF, RVI, RASRs and the absolute value of RASRa increased gradually, but CVI decreased gradually.PASP, RVEF and Ea/Aa correlated with the parameters of RA.The main factors influencing the Vprel were EDVI, Ea/Aa and the course of disease,and VpreI and PASP mainly influenced the RAEF.Conclusions In patients with chronic PH the volume and function of RA changed,and some index of which was infuenced by PASP, RVEF, Ea/Aa and so on.
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Objective To investigate right ventricular(RV) dyssynchrony in patients with pulmonary hypertension(PH)by strain imaging.Methods Sixty PH patients were divided into three groups according to the pulmonary artery systolic pressure(PASP),20 healthy volunteers served as control group.RV structures parameters included RV end-diastolic area(RVEDA),end-systolic area(RVESA),the ratio of RV diameter and LV diameter(RVTD/LVTD).RV function parameters included RV fractional area change (RVFAC)and Tei index.RV strain parameters included the maxmal differences of the peak systolic strain(Max-ΔPST)and the maxmal differences of the time to peak systolic strain(Max-ΔT_(Q-S))of each segment.Results Compared with control group, Max-ΔT_(Q-S) and Max-ΔPST of PH groups were significantly larger (P<0.01).Max-ΔT_(Q-S) had strong correlations with PASP and RV structure and function parameters(P<0.01).Max-ΔPST had good correlations with PASP and Tei-index(P<0.05,P<0.01).Conclusions PH patients exhibit right ventricular dyssynchrony which correlates with right ventricular function and structure parameters.Right ventricular dyssynchrony parameters could evaluate right ventricular function in PH patients early by strain imaging.