In the heart, stimulation of beta-adrenergic receptors (betaAR) serves as the most powerful means to increase cardiac contractility and relaxation in response to stress or a "fight-or-flight" situation. However, sustained beta-adrenergic stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy, apoptosis and necrosis, thus contributing to the pathogenesis of chronic heart failure. Over the past decade, compelling evidence has demonstrated that coexisting cardiac betaAR subtypes, mainly beta(1)AR and beta (2)AR, activate markedly different signaling cascades. As a result, acute beta(1)AR stimulation activates the G(s) -adenylyl cyclase-cAMP-PKA signaling that can broadcast throughout the cell, whereas beta(2)AR-evoked cAMP signaling is spatially and functionally compartmentalized, due to concurrent G(i) activation. Chronic stimulation of beta(1)AR and beta(2)AR elicits opposing effects on the fate of cardiomyocytes: beta(1)AR induces hypertrophy and apoptosis; but beta(2)AR promotes cell survival. The cardiac protective effect of beta(2)AR is mediated by a signaling pathway sequentially involving G(i), G(betagamma), PI3K and Akt. Unexpectedly, beta(1)AR-induced myocyte hypertrophy and apoptosis are independent of the classic cAMP/PKA pathway, but require activation of Ca(2+)/calmodulin-dependent kinase II (CaMK II). The outcomes of cardiac-specific transgenic overexpression of either beta AR subtype in mice have reinforced the fundamentally different functional roles of these betaAR subtypes in governing cardiac remodeling and performance. These new insights regarding betaAR subtype stimulation not only provide clues as to cellular and molecular mechanisms underlying the beneficial effects of beta AR blockers in patients with chronic heart failure, but also delineate rationale for combining selective beta(1)AR blockade with moderate beta(2)AR activation as a potential novel therapy for the treatment of chronic heart failure.
Adenylyl Cyclases ; metabolism ; Animals ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; GTP-Binding Proteins ; metabolism ; Heart ; physiology ; Heart Failure ; physiopathology ; Humans ; Myocardium ; metabolism ; Receptors, Adrenergic, beta ; classification ; physiology ; Receptors, Adrenergic, beta-1 ; physiology ; Receptors, Adrenergic, beta-2 ; physiology ; Signal Transduction

The course of estahlishing coronary collateral circulation has been studied after ligating the anterior descending branch of the left coronary artery (L. A. D.) of the heart in 20 rabbits. Another 5 rabbits were studied as control group. The experimental results were as follows: (1) The rabbit electrocardiograms EGG were made before and after the ligation of the L. A. D. The EGG of control group was made only before killing. In these experiments, the pathological changes of No. 28 were observed immediately after ligating the L. A.D. It was found that the T wave was inverted in standard lead I, and that the volts of the QRS complex in lead Vc fell apparently. This phenomenon may be interpreted as myocardial ischemia in the anterior wall of the heart. After ligating the L. A. D. the S-T segment of No. 27 in AVL lead elevated and exceeded I mm, and the depressive Q wave in Vc lead was greater than the one-fourth of the R wave before killing. All of the phenomenen observed in the rabbit entirely confirmed the myocardial infarction and myocardial ischemia. In No. 25, the T wave was inverted in standard lead I, and the QRS complex in lead Vc was not only shallow in depth but also very little. The conditions accounted probably for myocardial ishcmia. During 4 to 21 days after ligating the L. A. D.,the pathological changes in the EGG occurred frequently.The rabbit ECG gradually became normal from 21 st day on. (2) The coronary arteries of the rabbit hearts were injected with X-ray contrast medium and were examined. The X-ray film thus obtained were compared with the specimen after they were cleared. At the same time, sections of the heart walls (the infarcted area and its surrounding areas) of fifteen rabbits were studied carefully under microscope. Our primary impression was that only a few newly formed vessels in the central part of the infarct till the fourth day after ligating the L. A. D. The vessels surrounding of the infarct show a slight winding and distension. During 10 to 28 days, the number of the newly formed vessels in the infarct increased gradually day by day. The vessels surroundings the infarct were also highly crooked and distended, especially in the anterior wall of the right ventricle. This is possibly the most active period in the establishment of coronary collateral circulation. During 28 to 49 days, the morphology of the vessels in the infarct area became similar to that of the corresponding area of the control group. (3) The significance of the coronary collateral circulation on the heart wall was discussed.

A Study of one hundred hearts (adults 56, children 44) has been made. The S-A mode arteries and A-V node arteries are measured and analysed. The chief results are as fo11ows: (1) 67% of S-A node arteries originated from the right coronary artery; 33% arose from the left coronary artery. A number of the S-A node arteries arising from the right coronary artery were the continuation from the anterior right atrial branch. Occasionally, they may be come from the intermediate right atrial branch or intermediate left atrial branch. (2) The distance between the right S-A node artery origin and the aortic root was about 1.28?0.12 cm in adults, and 0.85?0.09 cm in children, while between the left S-A node artery origin and the bifurcation of the left coronary artery, it was about 0.84?0.19 cm in adults and 0.41?0.03 cm in children. The external diameters of the S-A node arteries were measured. The mean value was as follows: 0.17?0.01 cm (adults); 0.12?0.01 cm (children). (3) The relation between the origins of S-A node artery and A-V node artery may be divided into six types. ①The S-A node artery and A-V node artery which originated from the right coronary artery were about 58.06%. ②The S-A node artery arising from the left coronary artery and the A-V node artery originating from the right coronary artery occurred in 30.11% ③The S-A node artery originated from the right coronary attery, while the A-V node artery arose from the left. This condition was about 6.45%.④The type that the S-A node artery arose from both coronary arteries, and the A-V node artery originated from the right was about 3.22%.⑤Both the S-A node artery and A-V node artery arising from left coronary artery occurred in 1.08%.⑥The A-V node artery originating from the left and right coronary arteries, and the S-A node artery arising from the right coronary artery were about 1.08%.

Observations on the coronary arteries of 100 embalmed hearts from 56 adults and 44 children, have been made. The results are as follows: (1) The point of origin of coronary arteries was found vertically on the margin of the aortic sinus in 69.4% of the left and 52.8% of the right respectively and horizontally at the middle third of the aortic sinus in 79.7% of the left and 67.5% of the right respectively. (2) The external diameter at the opening of the left coronary artery is greater than the right in both adults and children. The mean value of the external diameter at the opening of the left coronary arteries was 0.41?0.14 cm and of the right 0.31?0.02 cm, in children, while in adult, the figures were 0.53?0.02 cm and 0.45?0.02 cm respectively. (3) The accessory coronary artery occurred in 10%.The percentage is lower than other reports in China. (4) The branch and distribution of the left coronary artery were studied thoroughly; its diagonal branch occurred in 38.4%.The mean value of the angle between the left anterior descending branch and the left circumflex artery was about 80?. In one the left circumflex artery was absent. (5) The branch and distribution of the right coronary artery were also investigated carefully. Fifty six percent of the right coronary arteries terminate in the heart, diaphragmatic surface between the crux of the heart and the obtuse margin. The posterior descending branch of right coronary artery ended in the middle-lower third of the posterior longitudinal sulcus of the heart. The occurrence of desending septum artery is 6.1%. (6) An investigation on the posterior superior septum artery and Kugel’s artery has been made: the former, 45.5% of which originated from the right coronary artery, possessed only one branch while the latter, which has been seen in three cases, occurred in 30%. (7) The common type of distribution, in which the posterior wall of the left ventricle was supplied by the right circumflex branch, occurred in 80.2%.

The coronary arteries of 80 rabbit hearts were studied.Suspension of red lead oxide (Pb_3O_4)in turpentine was injected into the coronary artery.With clearing method and angiographic technique,we studied the branches of the left and right coronary artery, the angle between the anterior descending branch and the left circumflex branch of the left coronary artery,the relationship between the anterior descending artery and the great cardiac vein,the origin of the sinoatrial nodal artery and the atrioventricular nodal artery as well as the type of branch in coronary artery.The results were outlined as follows: 1.The angle between the anterior descending branch and the left circumflex branch is 35～45?in more than one half of the cases(54.5%). 2.The anterior descending branch is often small and short and accompanies the great cardiac vein.It may exist in four forms:1)Both branches run closely to each other. 2)Both run along with each other but leaving a distance in between.3)Both are over- lapping each other.4)Both are crossing each other between the inferior margin of the left auricle and pulmonary artery cone.Ligation of the anterior descending branch in animal experiments should be appropriately made between the right inferior margin of the auricle and the pulmonary artery cone. 3.The left ventricular branch is a direct continuation of the circumflex branch and gives off branches to anterior and posterior wall of the left ventricle. 4.There is an independent ventricular septal artery in the rabbit heart. 5.The sinoatrial nodal artery of the rabbit heart arises frequently from the right coronary artery(86.6%)and the atrioventricular nodal artery from the left coronary artery(72.5%). 6.Commonly the distribution of the coronary blood supply from the left and right coronary arteries to rabbit heart is nearly a balanced circultion(67.5%).Next frequent is the preponderance of the left coronary artery(28.8%),and the preponderance of the right coronary artery occurs only in 3.7%.

Objective:To establish the HPLC fingerprint of dry ginger to provide experimental evidence for the quality control. Methods:An Agilent TC-C18 column (250 mm × 4. 6 mm,5 μm) was used, the flow phase was acetonitrile-water with gradient elu-tion, the flow rate was 1. 0 ml·min-1 , the column temperature was 30℃, and the detection wavelength was 240 nm. The data were e-valuated by the similarity evaluation software for TCM fingerprint. Results:There were 10 common peaks in HPLC chromatogram of 10 batches of dry ginger at 240 nm, and the chemical similar coefficient was 99%. Conclusion: The fingerprint of ginger at 240 nm is highly specific and typical with a rich fund of information, which can provide useful references for the quality control and evaluation of dry ginger.

Objective To evaluate the clinical application of automated urine formed elements analyzer and/or urine dipstick analyzer for examination of urinary formed elements in screening urinary tract infection (UTI). Methods 148 fresh midstream clear-catch urine samples from the UTI patients and 284 fresh midstream clear-catch urine samples from non-UTI subjects were selected. Bacteria culture was performed for bacterial colony counting and identification. Bacteria counts ( BACT), yeast-like fungus and WBC were performed by UF-looOi automated urine formed elements analyzer. Leukocyte esterase test (LEU) and nitrite test (NIT) were performed by URISYS 2400 urine dipstick analyzer. We evaluated data obtained from urine dipstick analyzer, UF-1000i and combination of UF-1000i with urine dipstick analyzer and the results was compared with those obtained from quantitative bacterial culture. Then we evaluated the sensibility, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. Results Among the 148 patients with UTI, the positive rate of the quantitative bacterial culture was 73.6% (109/148), the positive rate of LEU and NIT detected by dipstick test 26. 4% (39/148).There was significantly statistical difference between bacterial culture and strip test(χ2 = 55.68 ,P < 0. 05 ). The positive rate of urine flow cytometry by UF-1000i with either positive of BACT and WBC was 91.2%(135/148), which was higher than the positive rate of the quantitative bacterial culture. There was significant difference between two methods (χ2 = 14. 70, P < 0. 05 ). The positive rate of anyone positive among BACT, WBC, LEU and NIT was 94. 6% (140/148) when detected with combination of dipstick test and UF-1000i, which was higher than the positive rate of the quantitative bacterial culture. And there was significant difference between two methods (χ2 = 20. 45, P < 0. 05 ). The sensitivity of dipstick test was low (26. 4% ,39/148 ), and specificity was high ( 99. 3%, 282/284 ) . The sensitivity, specificity, positive predictive value, negative predictive value of BACT detected by UF-1000i in diagnosing urinary tract infection were 92. 6% ( 137/148 ), 39. 8% ( 113/284 ). 44. 5% ( 137/308 ) and 91.1% ( 113/124 ), respectively. If the dipstick test was combined with UF-1000i, the sensitivity, negative predictive value, specificity, positive predictive value and accuracy were 98.0% ( 145/148 ), 97.1% ( 100/103 ). 35.2% (100/284) ,44. 1% (145/329) and 56. 7% (245/432), respectively. Conclusions The combination of urine dipstick test and automated urine formed elements analyzer UF-1000i plays an important role in early diagnosis of UTI. And it has significant value in diagnosis of UTI, especially for the patients with negative bacterial cultures of urine sample.

Objective To compare the effects of non-steroidal anti-inflammatory drugs (NSAIDs) and free radical scavengers (FRS) on formation of traumatic heterotopic ossification (HO) in rabbits. Methods 48 New Zealand rabbits were randomly divided into control group (n=12), NSAIDs group (n=12), FRS group (n=12) and combination group (n=12). The model of traumatic HO was established, and the NSAIDs group, FRS group and combination group were administered indometacin intragastrically, edaravone intravenously and both, respectively, while the control group was administered normal saline for 4 weeks. The incidence and severity of HO were observed with X-ray 8 and 12 weeks after modeling. Results 8 and 12 weeks after operation, the incidence of HO was 33.3% and 41.7% in the NSAIDs group, 43.0% and 45.8% in the FRS group, 29.2% and 37.5% in the combination group, and 70.8% and 75.0% in the control group, respectively. The incidence and severity of HO in all the treatment groups were significantly less than those in the control group (P<0.05), and there was no significant difference among the treatment groups (P>0.05). Conclusion The systemic application of FRS may prevent the formation of HO effectively, similar with the NSAIDs. There is no synergistic effect between them.

The voltage-gated sodium channel subtype Nav1.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes. In recent years, a large number of studies have shown that Nav1.7 plays an important role in inflammatory, neuropathic, and nociceptive pain. Therefore, targeting Nav1.7 is a new strategy and hotspot for the development of novel analgesics. This review introduces the structure and function of Nav1.7, its regulatory role in pain, highlights the development progress of small-molecule Nav1.7 inhibitors in clinical trials, and analyzes the preclinical development of highly specific Nav1.7 inhibitors, with a view to providing reference for the development of Nav1.7 analgesic drugs.

The dry seeds of Cassia obtusifolia were carried by the "ShenZhou 8" satellite and sowed after landing. Based on our pri- or study on SP1, the characteristics of plants growth, physiological index and content of effective components were examined. The results showed that the QC10, QC29 strains matured 5 d earlier compared with control. The plant height, across diameter and ground diameter of QC10, QC29, QC46 strains was superior to the control at whole growth period. The branch number increased ranging from 4 to 11 and the number of pods reached 321, 313,281, respectively, which was dramatically higher than the control (246). The yield of QC10, QC29, QC46 strains increased noticeably from 31.4 to 63.2 g. The 1000-seed-weight of QC10, QC29, QC46 strains was 25.86, 25.88, 24.06 g, while the control was 23.69 g. Compared to the control, the mass fraction of chlorophyll was enhanced 1.098, 1.016, 0.297 mg. There was no significant difference in aurantio-obtusin and chrysophanol content of seeds. Through two years research, three high-yield mutant strains were obtained. This study indicates that spaceflight-induced mutants could provide new germplasm for C. obtusifolia breeding and offers the theoretical basis for further utilization of spaceflight-induced mutation to breed high-quality C. obtusifolia strains.
Cassia ; chemistry ; genetics ; growth & development ; Mutation ; Space Flight