Objective:To observe the interventative effect of Ziyin-Huatan Decoction by regulating exosomes on subcutaneous tumor of mice with gastric cancer. Methods:MGC-803 cells were randomly divided into exosome control group, low-dose group and high-dose group. The low-dose group and high-dose group were intervened with Ziyin-Huatan Decoction of 25 μg/ml and 100 μg/ml respectively. After 48 hours, the exosomes secreted by MGC-803 cells in each group were extracted. Twenty BALB/c male mice were randomly divided into exosome control group, low-dose Ziyin-Huatan Decoction group, high-dose Ziyin-Huatan Decoction group and blank control group, with 5 mice in each group. Except for the blank control group, the mice in the other groups were injected with exosomes extracted from the cells of the corresponding group through the orbit, 10 μg/time for each mouse, once every other day, a total of 15 times; the blank control group was injected with the same amount of PBS. Then SGC-7901 cells were inoculated into mice to establish a tumor model. The tumorigenic rate and body weight of mice were observed. The levels of CD31, VEGF and bFGF in tumor tissues were detected by immunohistochemistry. Results:Compared with the blank control group, the tumor weight [(170.00 ± 10.00) mg vs. (343.33 ± 20.82) mg] and the expression of CD31 (37.43 ± 0.55 vs. 63.30 ± 0.85), VEGF (11.37 ± 1.19 vs. 70.30 ± 0.72) and bFGF (43.77 ± 1.53 vs. 84.97 ± 1.86) in the high-dose Ziyin-Huatan Decoction group significantly decreased ( P<0.05). Compared with exosome control group, the expressions of CD31, VEGF and bFGF in low and high dose Ziyin-Huatan Decoction groups were decreased ( P<0.05). Conclusion:Ziyin-Huatan Decoction can significantly inhibit the growth of subcutaneous tumor of gastric cancer in mice by regulating exudation, which may be related to the inhibition of tumor angiogenesis.

Objective To investigate the significance of metastasis associated lung adenocarcinoma transcript 1 ( MALAT1 ),cyclooxygerase-2 ( COX-2 ),beta catenin ( β-catenin )、matrix metalloproteinase (MMP)-3 and MMP-9 in the occurrence and development of colorectal carcinoma.Methods Real-time PCR was used to detect MALAT1,COX-2,β-catenin,MMP-3 and MMP-9 rnRNA expression in samples from 30 fresh colorectal carcinomas and 30 corresponding adjacent tissues.And the correlation analysis of the gender and age of patients,CEA,immune cellular factors ( CD4 and CD8 ),clinical stages,and the degree of differentiation was undertaken.Results The expression levels of MALAT1,COX-2,β-catenin and MMP-9 were significantly different between colorectal carcinoma tissues and adjacent colorectal tissues (P ＜ 0.05 ).MMP-3 showed no significant difference (P ＞ 0.05).MALAT1,COX-2,β-catenin and MMP-9 expression levels showed an average 2.22-fold,1.86-fold,2.16-fold,0.58-fold ( P ＜ 0.01 ) increase in colorectal carcinoma tissues when compared with adjacent colorectal tissues respectively.There were negative correlation between MALAT1 and β-cateuin ( colorectal carcinoma tissues vs adjacent colorectal tissues) ( r =- 0.346,P =0.030).While there were positive correlation between MMP-9 and β-catenin ( colorectal carcinoma tissues vs adjacent colorectal tissues) ( r =0.312,P =0.047 ).There were significant difference between male patients and female patients in terms of COX-2 and MMP-9 (colorectal carcinoma tissues vs adjacent colorectal tissues) (P =0.047; P =0.018).There were significant difference between patients with tumor marker CEA increase and patients without CEA increase in terms of COX-2 ( colorectal carcinoma tissues vs adjacent colorectal tissues) ( P =0.021 ).Conclusion MALAT1,COX-2,MMP-9 and β-catenin have significance in the occurrence and development of colorectal carcinoma,while MMP-3 has no significant reference value. The negative correlation between MAL(A)T-1 and β-catenin and the positive correlation between MMP-9 and β-catenin might show some interaction relationship in the development of colorectal carcinoma.The expression differences of COX-2 and MMP-9 (colorectal carcinoma tissues vs adjacent colorectal tissues) in male and female patients suggest that above two genes may affect the occurrence ratio of colorectal carcinoma.Detecting of COX-2 maybe helpful to the tumor marker CEA during the diagnosis of colorectal carcinoma.

Objective To study adrenomedullin (AM) mRNA and protein expression level in myocardium of autoimmune myocarditis animal models induced by immunization of mice with lactobacillus casei cell wall element(LCWE). Methods Forty-five Balb/c male mice were randomly divided into experimental group (n = 30) and control group (n = 15), which were intraperitoneally injected with LCWE and phosphate buffered solution(PBS) at day 0,3,5 and 10,respectively. Sera and myocardium samples were gained 14,21 and 28 days after the first immunization. AM expression levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction(RT- PCR) and immunchistochemistry,and mycardial histopathological lesions were observed. The anti- myosin antibodies in different stages were examined by an ELISA. Results There were myocardial necrosis or inflammatory infiltration in the experimental group, but myocardial lesions were not found in the control group. Anti - myosin antibodies were detected in sera of experimental mice,but not in control group. Immunchistochemistry findings demonstrated that AM expression level was higher in the experimental group than in the control group( P

BACKGROUNDLocal hypothermia induced by intravascular infusion of cold saline solution effectively reduces brain damage in stroke. We further determined the optimal temperature of local hypothermia in our study.

METHODSSeventy-eight adult male Sprague Dawley rats (260 - 300 g) were randomly divided into 3 groups: group A, ischemia/reperfusion without cold saline infusion (n = 26) (control group); group B, infusion with 20 degrees C saline before reperfusion (n = 26); group C: infusion with 10 degrees C saline before reperfusion (n = 26). In each group, we chose 15 rats for monitoring physical indexes and the temperature of the brain (cortex and striatum) and body (anus), measurement of brain infarction volume, assessment of neurological deficits and the survival rate of reperfusion at 48 hours. Another 8 rats from each group was chosen for examining brain edema, another 3 from each group for histological observation by electron microscopy (EM) and light microscopy (LM) at 48 hours after reperfusion.

RESULTSThere was no significant difference among the 3 groups for physical indexes during the examination (F((2, 45)) = 0.577, P = 0.568; F((2, 45)) = 0.42, P = 0.78 for blood pressure and blood gas analysis, respectively). The brain temperature was significantly reduced in the group C compared to the other groups (F((2, 45)) = 37.074, P = 0.000; F((2, 45)) = 32.983, P = 0.000, for cortex and striatum temperature respectively), while the difference in rectal temperature between group A and B or C after reperfusion was not significant (F((2, 45)) = 0.17115, P = 0.637). And the brain infarct volume was significantly reduced in group C (from 40% +/- 10% in group A, 26% +/- 8% in group B, to 12% +/- 6% in group C, F((2, 45)) = 43.465, P = 0.000) with the neurological deficits improving in group C (chi(2) = 27.626, P = 0.000). The survival rate at 48 hours after 10 degrees C and 20 degrees C saline reperfusion was increased by 132.5% and 150%, respectively, as compared to the control group (chi(2) = 10.489, P = 0.005). The extent of the brain edema showed no significant difference (F((2, 21)) = 0.547, P = 0.587) after cold saline infusion compared to the control group. No obvious vascular injury was found by electron or light microscopy in either infusion group.

CONCLUSIONSRegional hypothermia with 10 degrees C cold saline infusion can significantly decrease the infarction volume, improve the neurological deficits, and 10 degrees C seems to be the optimal temperature in inducing a cerebral protection effect during stroke. This procedure could be adopted as a further treatment for acute stroke patients.

Animals ; Body Temperature ; Brain ; pathology ; Cerebral Infarction ; pathology ; Hypothermia, Induced ; Male ; Rats ; Rats, Sprague-Dawley ; Stroke ; mortality ; pathology ; physiopathology ; therapy ; Survival Rate ; Temperature

PURPOSETo determine the effect of the posterior condylar offset (PCO) on clinical results after total knee arthroplasty (TKA) using a high-flex posterior-stabilized (PS) fixed-bearing prosthesis.

METHODSWe prospectively studied the clinical and radiographic materials of 89 consecutive female patients (89 knees), who had undergone primary TKAs for end-stage osteoarthritis. All operations were performed by a single senior surgeon or under his supervision using the same operative technique. Based on the corrected PCO change, we divided all cases into two groups: group A (corrected PCO change ≥0 mm, 58 knees) and group B (corrected PCO change<0 mm, 31 knees). One-year postoperatively, clinical and radiographic variables from the two groups were compared by independent t-test. The associations between the corrected PCO changes and the improvements of clinical variables in all patients were analyzed by Pearson linear correlation.

RESULTSOne-year postoperatively, the Knee Society Scores, the Western Ontario and McMaster Universities Osteoarthritis Index, non-weight-bearing active and passive range of knee flexion, flexion contracture, extensor lag, and their improvements had no statistical differences between the two groups (all p>0.05). The corrected PCO change was not significantly correlated with the improvement of any clinical variable (all p>0.05). Group A demonstrated greater flexion than group B during active weight bearing (p<0.05).

CONCLUSIONSRestoration of PCO plays an important role in the optimization of active knee flexion during weight-bearing conditions after posterior-stabilized TKA, while it has no benefit to non-weight-bearing knee flexion or any other clinical result.

Aged ; Arthroplasty, Replacement, Knee ; methods ; Biomechanical Phenomena ; Female ; Humans ; Knee Joint ; physiopathology ; Knee Prosthesis ; Middle Aged ; Osteoarthritis ; physiopathology ; surgery ; Prospective Studies ; Range of Motion, Articular

Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.

BACKGROUNDRecombinant human parathyroid hormone (1-34) (rhPTH (1-34)) given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique. rhPTH (1-34) is mainly used to treat osteoporosis, especially for postmenopausal women. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.

METHODSTwo hundred and five women with osteoporosis were enrolled in a 6-month, multicenter, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 microg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), as well as biochemical markers of bone turnover were measured. Adverse events were recorded.

RESULTSrhPTH (1-34) increased lumbar BMD significantly more than did elcatonin at 3 months and 6 months (2.38% vs 0.59%, P < 0.05; 5.51% vs 1.55%, P < 0.01), but there were no significant increases of BMD in these two groups at femoral neck. There were larger mean increases in bone markers in the rhPTH (1-34) group than in the elcatonin group at 3 months and 6 months (serum bone-specific alkaline phosphatase (BSAP) 36.79% vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine (NTX/Cr) 48.91% vs -5.32%; 68.82% vs -10.86%). Both treatments were well tolerated and there were no significant differences detected between the two groups in the proportion of any adverse events and any serious adverse events (67.0% vs 59.0%; 0 vs 0).

CONCLUSIONSrhPTH (1-34) has more positive effects on bone formation, as shown by the larger increments of lumbar BMD and bone formation markers, than elcatonin, with only mild adverse events and no significant change in the liver, kidney or hematological indices.

Aged ; Calcitonin ; analogs & derivatives ; pharmacology ; therapeutic use ; Female ; Humans ; Middle Aged ; Osteogenesis ; drug effects ; Osteoporosis, Postmenopausal ; drug therapy ; Parathyroid Hormone ; pharmacology ; therapeutic use ; Recombinant Proteins ; pharmacology ; therapeutic use

OBJECTIVETo evaluate the clinical features in Chinese patients with apical hypertrophic cardiomyopathy (AHCM) and typical hypertrophic cardiomyopathy (HCM).

METHODSThis retrospective analysis included 160 patients hospitalized in Fuwai hospital. Patients were divided into three groups: apical hypertrophic cardiomyopathy (AHCM, n = 41) group, non-obstructive typical hypertrophic cardiomyopathy group [NOHCM, LVOT < 30 mm Hg (1 mm Hg = 0.133 kPa) at rest, n = 52] and obstructive typical hypertrophic cardiomyopathy (OHCM, LVOT ≥ 30 mm Hg at rest, n = 67). Clinical features, diagnosis, therapy, and plasma levels of biomarkers of these three groups were analyzed.

RESULTS(1) The age at disease onset was older in AHCM group than in OHCM group [(49.9 ± 13.6) years vs. (41.4 ± 14.6) years, P < 0.01]. Exertional dyspnea appeared more often in HCM patients than in AHCM patients, NT-proBNP level was significantly lower in AHCM patients than in OHCM patients (P = 0.001). Plasma CK-MB, LDH, TnI and MYO levels were similar among the three groups. (2) Thirty-three AHCM patients were first hospitalized for suspected coronary heart disease (CHD) and CHD was excluded in 18 cases (43.9%). (3) The frequency of giant negative T waves (depth ≥ 10 mm) on ECG was 43.9%, 13.5% and 4.4% (P < 0.01) in AHCM, NOHCM and OHCM respectively. Half of AHCM patients showed left ventricular high voltage on ECG. (4) Cardiac magnetic resonance imaging is superior to echocardiography on correctly diagnosing AHCM.

CONCLUSIONAHCM patients differ from typical OHCM patients in clinical characteristics. There were significant differences on echocardiography and electrocardiography features among three groups. Cardiac magnetic resonance imaging and giant negative T waves on ECG are helpful for the diagnosis of AHCM.

Adult ; Aged ; Asian Continental Ancestry Group ; Cardiomyopathy, Hypertrophic ; classification ; diagnosis ; physiopathology ; Echocardiography ; Electrocardiography ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies

BACKGROUNDRecombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.

METHODSA total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded.

RESULTSrhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group.

CONCLUSIONSrhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.

Aged ; Bone Density ; drug effects ; Calcitonin ; analogs & derivatives ; therapeutic use ; China ; Female ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; Parathyroid Hormone ; therapeutic use ; Treatment Outcome

OBJECTIVE: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study. METHODS: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA. RESULTS: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors. CONCLUSIONS The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.
Animals ; Cattle ; China ; Female ; Humans ; Infant ; Milk Hypersensitivity ; Milk Proteins ; Pregnancy ; Risk Factors ; Surveys and Questionnaires