Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

OBJECTIVETo explore the value of spinal canal and dural sac dimensions for the treatment of lumbar disc herniation in MRI.

METHODSThe clinical data of 144 patients with single-level lumbar disc herniation underwent nonsurgical or surgical treatment from January 2010 to December 2012 were retrospectively analyzed. There were 91 patients in the nonsurgical group, including 55 males and 36 females, ranging in age from 20 to 68 years old with an average of (43.37±12.48) years; and there were 53 patients in the surgical group, including 28 males and 25 females, ranging in age from 20 to 64 years old with an average of (42.98±12.95) years. JOA scores (29 scores) were used to evaluate clinical manifestation (including subjective symptoms, objective findings, limitation of daily activities and bladder function) and outcomes. The parameters related to spinal canal and dural sac dimensions (including spinal canal midsagittal diameter and available diameter, lateral recess width, spinal canal and dural sac cross-sectional area) in the initial axial T2-weighted MRI were measured, and odds ratio of available diameter to midsagittal diameter, odds ratio of lateral recess width to midsagittal diameter and area ratio of dural sac to spinal canal were calculated. Then, the differences of all parameters between two groups, and the correlations with initial JOA scores were analyzed.

RESULTS(1) All patients were followed up from 1 to 3 years with an average of 2.1 years. JOA scores before treatment were 16.27±2.96 in nonsurgical group and 12.64±3.30 in surgical group, there was statistically significant difference (t=6.319, P<0.01). At final follow-up time, there was no statistically significant difference in JOA scores (25.41±2.22 vs 25.76±2.29), improvement rate [(72.95±12.54)% vs (76.80±9.45)%], and the excellent and good rate (84.91% vs 78.02%) between two groups (P>0.05). But, the relapse rate of nonsurgical group was higher than surgical group (14.29% vs 5.67%). (2) Spinal canal midsagittal diameter and available diameter, lateral recess width, spinal canal and dural sac area, the ratio of available diameter to midsagittal diameter, and the ratio of lateral recess width to midsagittal diameter in surgical group were smaller than that of nonsurgical group, but the area ratio of dural sac to spinal canal was larger, and there were statistically significant differences between two groups (P<0.01). (3) The initial JOA scores showed significantly positive correlation with spinal canal midsagittal diameter and available diameter, lateral recess width, and canal and dural sac area (P<0.01); also presented positive correlation with the ratio of available diameter to midsagittal diameter and the ratio of lateral recess width to midsagittal diameter (P<0.05); but there was a significantly negative correlation between initial JOA scores and the area ratio of dural sac to spinal canal.

CONCLUSIONBoth nonsurgical and surgical treatment of lumbar disc herniation can obtain good effect, but the recurrence rate of non-surgical treatment is higher. Preoperative MRI measurement parameters of spinal canal and dural sac dimensions has certain value for the treatment selection of lumbar disc herniation, but further refinement and validation is still required.

Adult ; Aged ; Dura Mater ; pathology ; Female ; Humans ; Intervertebral Disc Displacement ; pathology ; therapy ; Lumbar Vertebrae ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Spinal Canal ; pathology

To make a preliminary study on the mechanism of Coptidis Rhizoma(CR) and Rehmanniae Radix(RR) before and after the combined administration in treating type II diabetes mellitus. The type I diabetes animal model in rats was established by fat emulsion and intraperitoneal injection with streptozotocin, in order to compare the hpyerglycemic and hypolipidemic effects of CR, RR and their combined administration of different ratio. The urinary metabolic profiling in rats of Coptidis Rhizoma and Rehmanniae Radix before and after the combined administration was analyzed by using the gas chromatography-mass spectrometry. The differences among groups in metabolome were analyzed by the principal component analysis (PCA). The biochemical index results indicated that both CR and RR before and after the combined administration could lower high blood glucose, hypertriglyceride and high cholesterol. According to the analytical results of PCA of the rats' urine samples, the CR group was the most close to the normal group, with no significant difference in CR and RR group of different combination ratios. Twelve differentiated metabolites were identified to be related to type II diabetes. Compared with the normal group, the CR-treated group showed significant increase in seven differentiated metabolites. Among CR and RR drugs with different combination ratios, CR played a major role and thus acted as the monarch drug. Whereas RR served as the ministerial drug and assisted CR to show the efficacy. This study laid a foundation for the explanation of the combination mechanism of traditional Chinese medicines.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; urine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Rehmannia ; chemistry

Objective To study the the feasibility of real-time 3D transesophageal echocardiography (RT-3D TEE) in measuring the distance between the coronary artery ostia and the aortic annulus.Methods RT-3D TEE image of aortic root was collected intraoperatively in 18 cases who were refered to our center for transcatheter aortic valve implantation.The aortic annulus was reconstructed and the height of the annulus (H) was generated.Meanwhile RT-3D TEE and MDCT was used to determine the left coronary artery ostia-aortic annulus distance (E-LAA,C-LAA) and the right coronary artery ostia-aortic annulus distance (E-RAA,C-RAA).Results The display rate of right coronary artery was 94.4％ (17/18),with the left coronary artery 88.9％ (16/18) on the RT-3D TEE imaging.The height of the annulus(H) was lower than the distance between the coronary artery ostia and the aortic annulus(P ＜0.05).No statistically significant differences was found in the parameters of the distance between the coronary artery ostia and the aortic annulus between RT-3D TEE and MDCT (P ＞0.05).Conclusions RT-3D TEE imaging can display and measure the distance between the coronary artery ostia and the aortic annulus.

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Objective:To stablish of chemiluminescent Southern blot detection system for examining HBV DNA replication intermediates in HepG2.2.15,and analyse the inhibition of HBV replication with three kind of drugs with different targets.Methods:The HBV DNA replication intermediates were extracted and analyzed by Southern blot with HBV probe,which(pTHBV1047) was labelling with digoxigenin.The results of the hybridization were detected by chemiluminescent,and the condition of hybridization was optimized.After treated with lamivudine,Bay41-4109,?-Galcer in different concentration,the HBV DNA from the HepG2215 cells were detected with the system.Results:the sensitivity of the system was 1pg of pTHBV1047,and HBV specific positive signals was detected with the DNA from HepG2.2.15.The three kinds of drugs can inhibit the HBV replication obviously with chemiluminescent Southern blot detection system,the IC50 were 1.53?mol/L,0.41?mol/L,0.01?mol/L.Conclusion:The HBV replication intermediates from the cell of HepG2.2.15 can reflect the antiviral effect accurately with different targets drugs and this mothod would be used in the study of Chinese-midicine.

OBJECTIVETo investigate the effects of different thickness of foam on the postural control of standing in healthy subjects.

METHODSThirty healthy adult subjects (11 males, 19 females) were taken into examination of computerized posturography measurement under different surface conditions such as the firm surface and 1 to 5 layer foams of medium density with 4.7 cm high respectively in stance of feet together with eye open and eye closed for 30 s. The following time-dominated parameters regarding to the center of pressure (COP) movement were used for the analysis: whole path length (WPL), unit path length (UPL) which means the sway velocity of the COP movement, unit area path length (UAPL), circumference area (CA), effective value area (EVA) and rectangle areas (RA).

RESULTSAll parameters had the increased tendency when the layer of foam was added with both eye open and closed conditions except the UAPL, which had a decreased tendency. The parameters on different layer of foam were significance (P < 0.05) except the following conditions: (1) WPL and UPL on layer 4 and 5 with eyes opened and eyes closed; (2) UAPL on layer 2 and 3, layer 3 and 4, layer 4 and 5 with eyes opened, layer 3 and 4, layer 3 and 5 and layer 4 and 5 with eyes closed, (3) CA on layer 2 and 3, layer 3 and 4, layer 4 and 5 with eyes opened, layer 3 and 4, layer 3 and 5, layer 4 and 5 with eyes closed; (4) RA and EVA on layer 2 and 3, layer 4 and 5 with eyes opened, layer 3 and 4, layer 4 and 5, layer 3 and 5 with eyes closed.

CONCLUSIONSThe postural stability of normal subjects decreased when the foam thickness was added in some extent. It was important that the thickness of foam should be considered for interrupting the proprioception of feet in clinical. The whole path length and average velocity of movement of COP can be considered as the stable and sensitivity parameters in the foam posturography.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Musculoskeletal System ; Postural Balance ; Proprioception ; Young Adult

Elastic Tissue ; pathology ; Humans ; Lung Neoplasms ; diagnosis ; Pleura ; pathology ; Staining and Labeling

BACKGROUNDThe Borg scale is most commonly used to measure dyspnea in China. However, many patients that find it is difficult to distinguish the labeled numbers corresponding to different dyspnea scores. We developed a new method to rate dyspnea, which we call the count scale (CS). It includes the count scale number (CSN) and count scale time (CST). The aims of the present study were to determine the reproducibility and sensitivity of the CS during exercise in patients with chronic obstructive pulmonary disease (COPD).

METHODSFourteen male patients with COPD (aged 58.00 ± 7.72 years) participated in this study. A progressive incremental exercise and a 6-minute constant work exercise test were performed every 2 to 3 days for a total of 3 times. The CS results were evaluated at rest and at 30% and 70% of maximal workload (Wmax) and Wmax. The Borg scales were obtained during exercise.

RESULTSNo significant differences occurred across the three trials during exercise for the CS and Borg scores. The CSN and CST were more varied at Wmax (coefficient of variation (CV) = (22.28 ± 16.96)% for CSN, CV = (23.08 ± 19.11)% for CST) compared to 30% of Wmax (CV = (11.92 ± 8.78)% for CSN, CV = (11.16 ± 9.96)% for CST) and 70% of Wmax (CV = (9.08 ± 7.09)% for CSN, CV = (12.19 ± 12.32)% for CST). Dyspnea ratings with either CSN or CST tended to decrease at the higher workload compared to the lower workload. CSN and CST scores were highly correlated (r = 0.861, P < 0.001). CSN was negatively correlated with Borg scores (r = -0.363, P = 0.001). Similar results were obtained for the relationship between CST and Borg scores (r = -0.345, P = 0.003).

CONCLUSIONWe concluded that the CS is simple and reproducible when measuring dyspnea during exercise in patients with COPD.

Aged ; Dyspnea ; diagnosis ; Exercise ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; physiopathology ; Reproducibility of Results

The expression plasmid pET32CPS harboring SmCPS gene was transformed into E. coli BL21 trxB (DE3) resulting in recombinant strain E. coli [pET32CPS]. The induction of E. coli [pET32CPS] in different temperatures, induction time, IPTG concentrations and A600 values of E. coli were performed. The optimal expression conditions of SmCPS were characterized according to the orthogonal analysis, and the ratio of the interest protein to total proteins reached to 35.6%. The recombinant SmCPS protein purified by Ni2+ affinity chromatography column was identified by SDS-PAGE and Western blotting, and then used for rabbit immunization. The titer of the rabbit antiserum against SmCPS was about 1:24 300 after the third immunization, and could specifically recognize the antigen of SmCPS protein by Western blotting analysis. The successful preparation of polyclonal antibody against SmCPS laid a foundation for further correlative study between expression of SmCPS and the production of tanshinones in protein level.
Alkyl and Aryl Transferases ; genetics ; isolation & purification ; metabolism ; Animals ; Antibody Formation ; Escherichia coli ; metabolism ; Gene Expression ; Immune Sera ; biosynthesis ; immunology ; Isopropyl Thiogalactoside ; chemistry ; Male ; Plant Proteins ; genetics ; isolation & purification ; metabolism ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Plasmids ; Rabbits ; Recombinant Proteins ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; Temperature ; Time Factors ; Transformation, Genetic