Objective: To investigate the effect of moxibustion at Shenque (CV 8) on fatigue in rats with chronic exercise-induced exhaustion. Methods: Thirty male Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group and a moxibustion group, 10 rats in each group. Except rats in the blank group, the remaining rats were subjected to create long-term exhaustion models by repeated swimming. After successful modeling, rats in the moxibustion group received mild moxibustion at Shenque (CV 8) for 15 min, once every other day with a total of 10 times. Rats in the model group and the blank group did not receive moxibustion. At the end of the treatment, the exhausted times, and the body weight of rats before and after the experiment were compared among groups. The levels of blood malondialdehyde (MDA) and urea nitrogen (BUN), as well as the activities of aspartate transarninase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were also measured by the automatic biochemical analyzer, 24 h after the exhausting excise. Results: The 10th swimming time was significantly longer in the moxibustion group than that in the model group (P<0.01). The increase rate of the body weight was lower in the rats of the moxibustion group than that in the model group before the 7th and the 10th exhausting excise (P<0.05, P<0.01). The levels of serum MDA and BUN, as well as the activities of AST, ALT and LDH in the model group were higher than those in the blank group (all P<0.01). The levels of serum MDA and BUN, as well as the activities of AST, ALT and LDH in the moxibustion group were lower than those in the model group (P<0.01). Conclusion: Moxibustion at Shenque (CV 8) can decrease the serum levels of MDA and BUN, as well as activities of AST, ALT and LDH in the long-term fatigue rats, thus to improve the symptoms of fatigue.

OBJECTIVETo explore the relationship between electrocardiographic (ECG) and genetic mutations of patients with hypertrophic cardiomyopathy (HCM), and early ECG changes in HCM patients.

METHODSClinical, 12-lead ECG and echocardiographic examination as well as genetic examinations were made in a three-generation Chinses HCM pedigree with 8 family members (4 males). The clinical characterization and ECG parameters were analyzed and their relationship with genotypes in the family was explored.

RESULTSFour missense mutations (MYH7-H1717Q, MYLK2-K324E, KCNQ1-R190W, TMEM70-I147T) were detected in this pedigree. The proband carried all 4 mutations and 5 members carried 2 mutations. Corrected QTc interval of KCNQ1-H1717Q carriers was significantly prolonged and was consistent with the ECG characterization of long QT syndrome. MYLK2-K324E and KCNQ1-R190W carriers presented with Q wave and(or) depressed ST segment, as well as flatted or reversed T waves in leads from anterolateral and inferior ventricular walls. ECG results showed ST segment depression, flat and inverted T wave in the gene mutation carriers with normal echocardiographic examination results. ECG and echocardiographic results were normal in TMEM70-I147T mutation carrier.

CONCLUSIONSThe combined mutations of the genes associated with cardiac ion channels and HCM are linked with the ECG phenotype changes in this HCM pedigree. The variations in ECG parameters due to the genetic mutation appear earlier than the echocardiography and clinical manifestations. Variation in ECG may become one of the indexes for early diagnostic screening and disease progression of the HCM gene mutation carriers.

Brugada Syndrome ; Cardiac Conduction System Disease ; Cardiac Myosins ; Cardiomyopathy, Hypertrophic ; Echocardiography ; Electrocardiography ; Exons ; Genetic Testing ; Genotype ; Humans ; KCNQ1 Potassium Channel ; Long QT Syndrome ; Mutation ; Mutation, Missense ; Myosin Heavy Chains ; Myosin-Light-Chain Kinase ; Pedigree ; Phenotype

OBJECTIVETo explore the expression of serine protease Omi/HtrA2 in gastric carcinoma tissue and its association with clinicopathological features and prognosis.

METHODSOmi/HtrA2 protein expression levels were detected by immunohistochemistry method in resected gastric carcinomas(n=68), adjacent noncancerous tissues(n=15), and normal tissues(n=15), and its association with clinicopathological features and prognosis were analyzed.

RESULTSOmi/HtrA2 expression was positive in 73.5%(50/68) of gastric cancer tissues, which was significantly higher than that in adjacent noncancerous tissues and normal tissues(P<0.05). There were no significant differences in Omi/HtrA2 expression with respect to sex, age, tumor size, and depth of invasion(all P>0.05). Omi/HtrA2 expression level was significantly associated with tumor differentiation, extent of lymph node metastasis, and tumor stage(all P<0.05). Overall 5-year survival rate of patients with gastric carcinoma was 63.3%. Five-year survival rate was higher in Omi/HtrA2 positive cases than Omi/HtrA2 negative cases(72.0% vs. 61.1%), however the difference was not statistically significant.

CONCLUSIONSOmi/HtrA2 expression is more common in gastric carcinoma. Omi/HtrA2 expression is associated with tumor differentiation, extent of lymph node metastasis, and tumor stage.

Adult ; Aged ; Aged, 80 and over ; Female ; High-Temperature Requirement A Serine Peptidase 2 ; Humans ; Male ; Middle Aged ; Mitochondrial Proteins ; genetics ; metabolism ; Neoplasm Staging ; Prognosis ; Serine Endopeptidases ; genetics ; metabolism ; Stomach ; metabolism ; pathology ; Stomach Neoplasms ; metabolism ; pathology ; Young Adult

OBJECTIVETo investigate the clinicopathologic features, diagnosis and treatment of neuroendocrine carcinoma (NEC) in the digestive system.

METHODSThirty-eight patients with NEC from Jan 1985 to Mar 2008 were analyzed retrospectively and the related literatures were reviewed.

RESULTSThere were 29 males and 9 females. Common symptoms were melena or hematochezia (n=21, 55%), abdominal pain (n=19, 50%), abdominal mass (n=15, 39%), constipation (n=14, 37%), rectal mass (n=12, 32%), abdominal distention (n=11,29%) and diarrhea (n=7,18%). All the patients received surgical treatment including 1 esophagectomy, 5 radical total gastrectomies, 1 palliation proximal gastric resection, 2 local gastric resections, 6 pancreaticoduodenectomies, 1 distal pancreatectomies, 3 partial small intestine resections, 7 radical right hemicolectomies, 5 Dixon operations, 3 Miles operations, and 4 local resections of rectal tumor. Thirty-six patients received follow-up. The follow-up time ranged from 3 months to 144 months (median, 70 months). The 1-, 3- and 5-year survival rates were 94.7%, 86.8%, and 57.9% respectively. The median survival time was 62 months. The survival time of the patients with carcinoma infiltration exceeding bowel muscularis propria was (36+/-5) months, significantly shorter than that of patients without carcinoma infiltration exceeding the bowel muscularis propria [(73+/-5) months, P<0.05]. The survival time of the patients with positive lymph node metastasis was (34+/-7) months, significantly shorter than that of patients with negative lymph node metastasis [(74+/-5) months, P<0.05].

CONCLUSIONSClinical symptoms, signs of neuroendocrine carcinoma in the digestive system are nonspecific. The correct diagnosis should depend on histopathologic examination. Systematic treatments including radical resection of NEC are the preferable treatment.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Neuroendocrine ; diagnosis ; surgery ; Digestive System Neoplasms ; diagnosis ; surgery ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Young Adult

Objective To evaluate the characteristics of left ventricular structure ,function ,myocardial mechanics ,hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy ( HCM ) using state‐of‐the‐art echocardiography . Methods A consecutive series of 85 adult HCM patients w ho were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected . According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography ,the patients were divided into three groups :patients with non‐obstructive HCM ( n ＝28) ,those with labile‐obstructive HCM ( n ＝27) ,and those with obstructive HCM ( n ＝ 30 ) . In addition ,16 normal family members of HCM patients were included as control group . T wo‐dimensional speckle tracking imaging ,tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states . Results ① As compared with the control group ,left ventricular end‐diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups ( all P ＜ 0 .05 ) . Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM , followed by labile‐obstructive and non‐obstructive HCM ,and the lowest in the control group ( all P ＜0 .05) . ②A t rest ,the left ventricular global longitudinal ,circumferential and radial strain ( GLS ,GCS and GRS) ,as well as the twist of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . As compared with the control group ,the GLS and twist decreased in the labile‐obstructive and non‐obstructive HCM ( all P ＜0 .05 ) ,but there were no significant changes of GCS and GRS ( all P ＞ 0 .05 ) . T he obstructive HCM had the lowest mitral annular plane systolic excursion ( M APSE ) and s′,and the longest systolic peaking time standard deviation( T s‐SD) and early diastolic peaking time standard deviation ( Te‐SD) ( all P ＜0 .05) . T he left ventricular diastolic function of obstructive HCM ( e′,the E/e′ratio and the left atrial volume index ) was the worst ,labile‐obstruction and non‐obstructive HCM were better ,and the control group was the best ( all P ＜ 0 .001 ) . ③ During exercise ,the GLS ,GCS ,GRS ,twist of the left ventricle and the M APSE were the lowest in the obstructive HCM ,which increased in the labile‐obstructive and non‐obstructive HCM ,and were best in the control group . T he T s‐SD and Te‐SD were the shortest in the control group ,were prolonged in non‐obstructive and labile‐obstruction HCM ,and were longest in obstructive HCM ( all P ＜ 0 .05 ) . Additionally ,the exercise time of the control group was the longest , followed by non‐obstructive and labile‐obstruction HCM ,and the shortest in the obstructive HCM ( all P ＜0 .05) . T he M ET s of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . Conclusions In obstructive HCM ,the left ventricular systolic strain and synchronization ,as well as the M APSE ,are significantly impaired in patients both at rest and during exercise . T he patients with labile‐obstructive and non‐obstructive HCM have reduced left ventricular GLS , twist ,and e′,but normal left ventricular GCS ,GRS ,synchrony ,and M APSE at rest ,which are all impaired during exercise .

BACKGROUNDIn vivo quantification of choroidal neovascularization (CNV) based on noninvasive optical coherence tomography (OCT) examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD) both in human and animal studies. This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection.

METHODSCNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1), as reported previously. After 4 weeks, CNV was imaged by OCT and fluorescence angiography. The scaling factors for each dimension, x, y, and z (μm/pixel) were recorded, and the corneal curvature standard was adjusted from human (7.7) to mice (1.4). The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute, available at http://www.sci.utah.edu/cibc-software/seg3d.html). Eighteen mice were prepared for choroidal flatmounts and stained by CD31. The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining. Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology.

RESULTSThe CNV volume calculated using OCT was, on average, 2.6 times larger than the volume calculated using the laser confocal microscopy. The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R 2 =0.448, P = 0.001, n = 18). The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n = 18, P = 0.001).

CONCLUSIONSThere is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal injection. The result might provide a useful evaluation of CNV both for the studies using CNV models induced by subretinal injection and human AMD studies.

Animals ; Choroidal Neovascularization ; pathology ; physiopathology ; Disease Models, Animal ; Fluorescein Angiography ; Humans ; Mice ; Mice, Inbred C57BL ; Tomography, Optical Coherence

Animals ; Apoptosis ; Brain/metabolism* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Thyroxine/pharmacology*

Objective: To evaluate the characteristics of left ventricular structure, function, myocardial mechanics, hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy (HCM) using state-of-the-art echocardiography. Methods: A consecutive series of 85 adult HCM patients who were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected. According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography, the patients were divided into three groups: patients with non-obstructive HCM (n=28), those with labile-obstructive HCM (n=27), and those with obstructive HCM (n=30). In addition, 16 normal family members of HCM patients were included as control group. Two-dimensional speckle tracking imaging, tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states. Results: ①As compared with the control group, left ventricular end-diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups(all P<0.05). Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM, followed by labile-obstructive and non-obstructive HCM, and the lowest in the control group (all P<0.05). ②At rest, the left ventricular global longitudinal, circumferential and radial strain (GLS, GCS and GRS), as well as the twist of obstructive HCM were significantly lower than the other three groups (all P<0.05). As compared with the control group, the GLS and twist decreased in the labile-obstructive and non-obstructive HCM(all P<0.05), but there were no significant changes of GCS and GRS (all P>0.05). The obstructive HCM had the lowest mitral annular plane systolic excursion (MAPSE) and s′, and the longest systolic peaking time standard deviation(Ts-SD) and early diastolic peaking time standard deviation(Te-SD) (all P<0.05). The left ventricular diastolic function of obstructive HCM (e′, the E/e′ ratio and the left atrial volume index) was the worst, labile-obstruction and non-obstructive HCM were better, and the control group was the best (all P<0.001). ③During exercise, the GLS, GCS, GRS, twist of the left ventricle and the MAPSE were the lowest in the obstructive HCM, which increased in the labile-obstructive and non-obstructive HCM, and were best in the control group. The Ts-SD and Te-SD were the shortest in the control group, were prolonged in non-obstructive and labile-obstruction HCM, and were longest in obstructive HCM (all P<0.05). Additionally, the exercise time of the control group was the longest, followed by non-obstructive and labile-obstruction HCM, and the shortest in the obstructive HCM (all P<0.05). The METs of obstructive HCM were significantly lower than the other three groups (all P<0.05). Conclusions In obstructive HCM, the left ventricular systolic strain and synchronization, as well as the MAPSE, are significantly impaired in patients both at rest and during exercise. The patients with labile-obstructive and non-obstructive HCM have reduced left ventricular GLS, twist, and e′, but normal left ventricular GCS, GRS, synchrony, and MAPSE at rest, which are all impaired during exercise.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

OBJECTIVETo observe the morphology of hypertrophic scar tissue and explore the expressions and distribution of vascular endothelial growth factor (VEGF) and transforming growth factor beta activated kinase 1(TAK1 )in these tissues.

METHODHematoxylin-eosin staining, Masson staining,immunofluorescence,and real-time polymerase chain reaction were used to detect the localization and expression of VEGF and TAK1 in 15 hypertrophic scar tissues and 10 normal skin tissues.

RESULTSMorphological observation showed that the dermal fibroblasts in hypertrophic scar were disorderly and densely arranged (compared to the normal skin). Immunofluorescence displayed that the expressions of VEGF and TAK1 in hypertrophic scar tissue were higher than in normal skin tissues. Real-time polymerase chain reaction showed the mRNA expressions of both VEGF and TAK1 were significantly higher in hypertrophic scar tissue than in normal tissue (P<0.01, P<0.05,respectively).

CONCLUSIONSHypertrophic scar tissue has higher collagen fibrosis degree and higher TAK1 and VEGF expressions than the normal skin. VEGF and TAK1 can be used as the reference indicators for the diagnosis and differential diagnosis of hypertrophic scar and serve as new therapeutic targets.

Cell Shape ; Cicatrix, Hypertrophic ; Collagen ; Fibroblasts ; Humans ; MAP Kinase Kinase Kinases ; Transforming Growth Factor beta ; Vascular Endothelial Growth Factor A