Aim To analyze the blocking effect of ( ± ) doxazosin [ ( ± ) DOX ] , ( -) doxazosin [ ( -) DOX] and ( +) doxazosin [( +) DOX] on the vaso-constriction of rat isolated mesenteric arterioles media-ted by α1-adrenoceptors. Methods The vasoconstric-tion induced by phenylephrine ( Phe) in the rat isola-ted mesenteric arterioles ( the second- and third-order branches) was recorded using DMT wire myograph sys-tem 620M, and theα1-adrenoceptor antagonistic activ-ity of ( ± ) DOX and its enantiomers was analyzed. Results The inner diameter of second- and third-or-der branches of the rat mesenteric artery was (162. 5 ± 5. 3) μm (n=11) and (103. 1 ± 2. 3) μm (n=23), respectively. The values of normalized preload of the second-and third-order branches, which were calculat-ed by the LabChart software, were (2. 93 ± 0. 51) mN ( n =11 ) and ( 2. 64 ± 0. 50 ) mN ( n =23 ) ( P >0. 05 ) . Vasoconstrictive responses to Phe in the sec-ond-order branche of rat mesenteric artery under nor-malized preloads were not significantly different from those under 5 mN preload;however, the Emax values of the Phe-induced vasoconstriction under 10 mN, 15 mN and 20 mN preloads were decreased by 12%, 29%and 43% ( P<0. 01 ) respectively compared with those under normalized preload. The concentration-response curves for Phe were shifted to right in a concentration dependent manner by ( -) DOX or ( +) DOX at 0. 001 , 0. 01 and 0. 1 μmol · L-1 without significant change in their Emax values in the second-and third-or-der branches of rat mesenteric artery. Schild plot anal-ysis indicated that ( -) DOX, ( +) DOX and ( ± ) DOX non-competitively inhibited the vasoconstrictive responses to Phe in the second-order branches, and the rank order of pKB values was ( +) DOX ( 8. 67 ± 0. 10 ) , ( ± ) DOX ( 8. 53 ± 0. 090 ) , ( -) DOX (7. 85 ± 0. 09). However, schild plot analysis indica-ted that ( -) DOX and ( +) DOX competitively inhibi-ted the vasoconstrictive responses for Phe in the third-order branch, and the rank order of their pKB values was ( ± ) DOX ( 8. 68 ± 0. 17 ) , ( +) DOX ( 8. 48 ± 0. 10 ) , ( -) DOX ( 7. 48 ± 0. 140 ) . Conclusion The α1-adrenoceptor blocking activity of ( -) DOX is much weaker than that of ( +) DOX or ( ± ) DOX in the rat isolated mesenteric arterioles, and there is a tendency to enhance the activity of ( ± ) DOX in third-order branches of the rat mesenteric artery though theα1-adrenoceptor blockade effect of ( ± ) DOX is not significantly different from ( +) DOX.

Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium.Methods We analyzed the positive inotropic response to (-)doxazosin and the negative inotropic response to (+)doxazosin in the left atrium of rat u-sing receptor-pharmacological technique.Results In the preparation treated with verapamil,the positive in-otropic responses to 3 μmol·L-1 (-)doxazosin were significantly inhibited from the control level (245.7 1 ± 44.29)mg to (172.50 ±43.34)mg,(P<0.05).In the preparation treated with methylene blue,the posi-tive inotropic responses to 3 μmol·L-1 (-)doxazosin were significantly potentiated from the control level (245.7 1 ±44.29 )mg to (303.33 ±45 .90 )mg,(P<0.05 ).In the preparation treated with H-89 ,the positive inotropic responses to 3,10 and 30 μmol · L-1 (-)doxazosin were (338.57 ±96.86 ) mg, (471.43 ±107.61)mg and (520.00 ±103.44)mg, which were significantly (P<0.05 ~0.01)larger than the control levels of (245.71 ±44.29)mg,(314.29 ±90.34)mg and (357.14 ±68.49 )mg.Treatment with phenoxybenzamine,atropine,propranolol or indo-methacin did not significantly affect the responses to doxazosin enantiomers.Conclusion The positive ino-tropic responses to (-)doxazosin in the isolated left a-trium of rat are partially involved in L-type Ca2+chan-nels and intracellular cGMP level.However,α-adre-noceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.

Objective To evaluate the relationship between liver cell type A receptor (EphA) expression and androgen receptor (AR) signaling in androgen-dependent prostate cancer cells. Methods RT-PCR and Western blot assay were used to determine mRNA and protein levels of EphA3 and AR in prostate cancer LNCaP and 22Rv1 cells, respectively. The variations of EphA3, AR and prostate specific antigen (PSA) expressions were also measured in these cells after dihydrotes?tosterone (DHT) treatment for 48 h. The constructed EphA3-Luc (-789-+146) luciferase reporter plasmid was co-transfect?ed with pcDNA3.1(+)-AR or siAR in 22Rv1 cells to analyze the effects of different AR expression levels on EphA3 tran?scription activity. Results The expression pattern of EphA3 was similar to AR, showing a lower level in prostate stromal cell line WPMY-1 and a higher level in prostate cancer cell lines LNCaP and 22Rv1. When stimulated with 10 nmol/L DHT, the expression levels of AR, PSA and EphA3 were significantly increased in 22Rv1 cells, and the protein levels of these genes were also increased in LNCaP cells. Moreover, AR expression levels markedly influenced the activity of EphA 3 pro?moter. Conclusion AR up-regulates EphA3 expression by increasing the activity of EphA3 promoter.

Sepsis is a common critical disease in children with a high morbidity and mortality,and is an important cause of death in children.Its pathogens include bacteria,viruses,fungi and parasites,among which bacterial infections account for the majority,so antimicrobial drugs have been the most powerful agents in the treatment of sepsis,and have played a great role in saving the lives of infected children.However,the use of antimicrobial agents is based on a certain etiological basis,and due to the timeliness of pathogen testing,early combination of the clinical characteristics of children,susceptible factors and local epidemiology to assess the possible infection is very important to choose antibiotic treatment scientifically and reasonably.This article reviews the literature on etiological analysis of paediatric sepsis in recent years and summarizes its etiological characteristics.

OBJECTIVETo investigate the transcriptional regulation of pacemaker channel I(f) mediated by vasoactive peptide endothelin-1 (ET-1) in neonatal rat ventricular myocytes and its mechanism.

METHODSNeonatal rat ventricular myocytes were enzymatically isolated. I(f) current was recorded using the whole-cell patch-clamp technique. The expression of hyperpolarization-activated cyclic nucleotide-gated channel (HCN) isoforms HCN2 and HCN4 were measured by quantitative RT-PCR.

RESULTSET-1 increased the expression of HCN2 and HCN4 mRNA in a dose- and time-dependent manner. These effects were blocked by specific ETA receptor antagonist BQ-123 but not the ETB receptor antagonist BQ-788. The effects of ET-1 on HCN2 and HCN4 mRNA expression were not affected by the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB-203580).

CONCLUSIONThese findings indicate that ET-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes via ETA receptor through a p38 MAPK-independent signaling pathway, which might be linked to the intrinsic arrhythmogenic potential of ET-1.

Animals ; Animals, Newborn ; Cyclic Nucleotide-Gated Cation Channels ; drug effects ; Endothelin-1 ; metabolism ; Imidazoles ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Oligopeptides ; pharmacology ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

Acute myeloid leukemia(AML)is one of the most common acute leukemias in adults. Those patients with FLT3 mutations have a particularly poor prognosis. Recently, the emergence of a variety of targeted inhibitors has shown the capability of suppressing FLT3 signaling in vivo, which provided a new way to treat AML. In this paper, we reviewed those inhibitors based on their structures, which include indolone-related inhibitors, indolocarbazo-related inhibitors, benzimidazole/benzopyrazole-related inhibitors, quinoline/quinoxaline/quinazoline-related inhibitors, tricyclic inhibitors, pyrimidine-related inhibitors and others.

Objective To discuss the diagnosis effect and clinical significance of thrombelastography in chronic kidney disease. Methods From June 2016 to February 2017, two hundred and seventy non-dialysis patients with chronic kidney disease ( CKD) treated in the Fourth Hospital of Hebei Medical University were divided into non-hypercoagulable group and hypercoagulable group according to TEG comprehensive coagulation index. The changes of related clinical indexes between the two groups were analyzed and the related factors affecting the differences between the two groups were studied. Results The correlation between the two groups showed that the coagulation reaction time ( R ) , coagulation formation time ( K ) and albumin in the hypercoagulable group were significantly lower than those in the non-hypercoagulable group ((4. 69±0. 94) min vs. (6. 29±1. 63) min,(0. 93±0. 13) min vs. (1. 51±0. 58) min,(27. 54±7. 81) g/L vs. (34. 26±8. 39) g/L, P= 0. 000 ) Angle angle, maximum thrombus strength ( MA ) , fibrinogen, D-dimer, platelet count, protein/creatinine and protein content in hypercoagulable group were significantly higher than those in non-hypercoagulable group((76. 76±2. 23)°vs. (68. 19±7. 65)°;(75. 13±3. 81)mm vs. (66. 35±7. 81)mm;(4. 28 ±0. 93) g/L vs. (3. 56±1. 10) g/L ;0. 4(0. 15,0. 91) mg/L vs. 0. 22(0. 12,0. 52) mg/L;(276. 03±127. 15) ×109/L vs. (198. 18±78. 46)×109/L;5430(2579,9634) mg vs. 2620(692,5286) mg;4864(2341,7712) mg/g vs. 2557(840,5805) mg/g,P<0. 05). The differences were statistically significant. There was no significant difference in prothrombin, thromboplastin time, thrombin time, total cholesterol, triglyceride, low density lipoprotein,high density lipoprotein,creatinine between the two groups ( P>0. 05) . Correlation analysis of common clinical indicators showed that the comprehensive coagulation index ( CI) was positively correlated with Angle angle,maximum thrombus strength,fibrinogen,platelet count,protein/creatinine and protein quantification (r=0. 532,0. 522,0. 307,0. 354,0. 293,0. 216,P<0. 05),was negatively correlated with coagulation reaction time,coagulation formation time and albumin (r=- 0. 462,- 0. 496,- 0. 360,P<0. 05). Logistic regression analysis showed that platelet count, albumin and fibrinogen were the influencing factors for the grouping of comprehensive coagulation index ( OR ( 95％CI ) :1. 007 ( 1. 002-1. 013 ) , 0. 868 ( 0. 827-0. 912 ) , 1. 510 (1. 042-2. 187),P<0. 05). Conclusion TEG is a more sensitive indicator to reflect the coagulation status of patients with CKD, and has a certain guiding significance for anticoagulation treatment of patients with CKD;platelet count,albumin,fibrinogen are the factors affecting coagulation function of patients.

Pain is a prevalent symptom in both cancer and non-cancer end-stage diseases, often being the most feared by patients and significantly impacting their quality of life.Hospice care aims to address physical, psychological, spiritual, and other needs of patients and their families during this stage, with a focus on alleviating pain and discomfort.Effective pain management is a crucial component of hospice care, particularly given the increasing prevalence of cancer and chronic diseases in China and the growing elderly population.To provide analgesic management for hospice patients, a thorough assessment of pain is essential to identify its type and characteristics.Treatment approaches may include etiological interventions, pharmacotherapy, interventional therapy, physiotherapy, psychotherapy, and comfort care, all aimed at achieving comprehensive pain management.The use of opioid should be carefully guided by scientific principles to minimize adverse effects and optimize pain relief, ultimately enhancing patients' end-of-life quality of life.

OBJECTIVES: To explore the prescribing habits of doctors, and to provide basis for rational use of antibiotics in clinical practice via investigating and analyzing the applications of antibiotics in treatment of coronavirus disease 2019 (COVID-19) in the designated hospital. METHODS: Specification, quantity, amount, defined daily dose system (DDDs), defined daily dose consumption (DDDc), antibiotics use density (AUD), composition, frequency of use, combined use of antibacterial drugs used in the hospital were analyzed between Feb. 2020 and Mar. 2020. RESULTS: A total of 25 antibiotic drugs in 12 categories were used. The total cost for antibiotic drugs was 1 million 238 thousand yuan, in which quinolone accounts for 48%, the third generation cephalosporin/lactamase inhibitors accounts for 15.86%, antifungals accounts for 14.17%, oxazolidone accounts for 13.46%, and carbapenms account for 12.73%. The top three drugs of DDDs and AUD were moxifloxacin hydrochloride tablets, moxifloxacin hydrochloride and sodium chloride injection, cefoperazone sodium and sulbactam sodium for injection. The proportion of patients who had been used more than two kinds of antibiotics was 22.36%. CONCLUSIONS Broad-spectrum, high-potency antibiotics are used at the beginning of COVID-19 treatment. The varieties of antibiotics meet the requirements of the management of antibiotics, and the utilization rate of antibiotics and the cost proportion of antibiotics in COVID-19 patients are within a reasonable range.In the future, for the treatment of COVID-19, we should continue to summarize the experience, improve the strategies, and rationally apply antibiotics on the basis of guidelines.
Anti-Bacterial Agents ; classification ; therapeutic use ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy