Malignant tumor is an individual disease that caused by gene mutation and disorder of protein expression.The abnormity of mammalian target of rapamycin (mTOR) signaling pathways is closely related to the tumors,and its main biological function is the regulation of protein synthesis and vascular endothelial cell proliferation.However,the activation of mTOR can increase the expression of hypoxia-inducible factor-1 (HIF-1),maintain the acid microenvironment of tumor,promote tumor cell invasion and metastasis,and affect prognosis of tumor.At present,targeted therapy with mTOR and HIF-1 for new targets and gene therapy have become hot points.

Objective To investigate the tissue remodeling and cell alignment of TDBM scaffolds seeded with rabbit tenocytes under the cycle dynamic tensile force or static tension-free culture in vitro. Methods TDBM were made by ourselves, and uniaxial cyclic tendon stretching device was designed and manufactured on our own. Primary tenocytes were isolated from the Achilles tendon of three-day-old New Zealand white rabbits and seeded into scaffolds, and were cultured collectively in DMEM in vitro. Samples were divided into two groups:dynamic tension-loaded group, and static tension-free group. Fresh natural tendons were used to be positive control. The experiment's time was six weeks. The scaffold-cell complexes were harvested at 3 and 7 days of culture for Inverted microscope and scanning electron micrograph (SEM) analysis. The morphological characters of the samples, including the general view, HE and Masson's dyeing, were observed at 2, 4 and 6 weeks. In addition, the gene expression of the I-type collagen and III-type collagen of the samples was detected by using Real time PCR at every week. Set fresh natural tendon as control. Results The inverted microscope and SEM showed that it was nice compatible condition between the tendon cells and TD-BM scaffold. In addition, the tendon of tension-loaded group revealed a structure of longitudinally aligned collagen fi bers and dense structure of collagen fibers arranged in orderly form a unique corrugated structure. Tenocytes layer located between the col-lagen fibers and aligned longitudinally along the force axis, with increased matrix deposition after the 3th week showed by RT-PCR. The cell/matrix ratio decreases. When cultured to 6 weeks, the tissue structure was very similar to that of fresh natural ten-don pattern. By contrast, HE and Masson's staining revealed the collagen fibro-tissue structure in tension-free groups with disorga-nized matrix structure and randomly distributed cells. Collagen fibers were gradually degraded with time. In tension-loaded group, Real-time PCR showed that gene expression of I-type collagen and III-type collagen gradually increase, but in tension-free group, the relative gene expression of I-type collagen and III-type collagen was highest at 3rd week, and from that time the relative expres-sion gradually decrease. Conclusion Under the dynamic stress, the TDBM scaffolds seeded with rabbit tenocytes can promote extra-cellular matrix biosynthesis and tendon structure remodeling, which is a promising method for tendon tissue engineering.

OBJECTIVE To assess the association of SLC12A3 and SCNN1B gene polymorphisms (rs11643718 and rs12447134) with essential hypertension among ethnic Koreans from Mudanjiang, China. METHODS For 204 patients with essential hypertension and 186 healthy controls, the genotypes of rs11643718 and rs12447134 loci were determined with an improved multiplex ligase detection reaction (iMLDR) method. RESULTS Allelic and genotypic frequencies of rs11643718 of SLC12A3 gene are associated with the onset of disease hypertension (P <0.05) as well as systolic blood pressure (P < 0.01, under a recessive model). No association was found between rs12447134 of SCNN1B gene with the onset of disease (P > 0.05) but diastolic blood pressure (P < 0.05, under a recessive model). CONCLUSION The polymorphisms of rs11643718 locus is associated with the susceptibility for essential hypertension among ethnic Koreans from Mudanjiang area and can be used as a predictor for the disease.

Objective To evaluate the clinical and pathological feature,as well as risk factors of lymph node metastasis (LNM) and high-volume LNM (hvLNM) in papillary thyroid microcarcinoma (PTMC) with di ameter ≤0.5 cm.Methods PTMC patients who received surgical treatments in Peking Union Medical College Hospital from Nov.2013 to Nov.2014 were reviewed.Patients were allocated into the ≤0.5 cm group and (0.5-1)cm group according to tumor diameter.Clinical and pathological features were assessed and compared.Risk factors of LNM and hvLNM were also assessed through univariate and multivariate analysis.Results 1414 patients were enrolled,of which 315 patients (22.3％) were in the ≤0.5 cm group.76 LNM (24.1％) and 9 hvLNM (2.9％) were detected in the ≤0.5 cm group.There was significantly less capsule invasion (14.3％ vs 25.0％,P＜0.05),LNM (24.1％ vs 39.8％,P＜0.05) and hvLNM (2.9％ vs 7.9％,P＜0.05) in ≤0.5 cm group than in (0.5-1)cm group.In univariate analysis,patients aging ＜40 years old were more likely to have LNM than those older than 40(38.0％ vs 20.1％,P＜0.05),while male patients tended to have more LNM than female (32.4％ vs 21.9％,P=0.073).No risk factors were identified for hvLNM.In multivariate analysis,multifocality and younger than 40 years old were the independent risk factors of LNM (OR=2.082 and 2.899,P＜0.05),while male tended to be the independent risk factors of LNM (OR=l.807,P=0.058).No independent risk factors was identified for hvLNM.Conclusions A certain proportion of PTMC patients are with tumor diameter ≤0.5 cm,who have lower risk of LNM and hvLNM.Dynamic observation may be an option,especially in older ≥40 years old),unifocal and female patients.

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.
Animals ; Bacillus ; Bacteria ; Chemokine CCL2 ; Flow Cytometry ; Injections, Intraperitoneal ; Interferon-gamma ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Lymph Nodes ; Mice* ; Mycobacterium bovis ; Mycobacterium* ; Pathology ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

Objective To predict the presence of MVI,the general clinicopathological of HCC patients' data of the preoperative neutrophil-lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR),altplatelet ratio (APRI) were evaluated.Methods 143 cases of HCC patients who underwent radical resection and ≤ 5 cm of tumor diameter in Chifeng Clinical Medical School of Inner Mongolia Medical University from January 2011 to December 2014 were analysed retrospectively and followed up.The relationship between NLR,PLR,APRI and other clinical parameters was evaluated.Results According to ROC Curve,the NLR truncation value was 2.00,PLR to 115.00,APRI 1.6.The single factor analysis of x2 test showed that NLR (x2=6.419;P＜0.05),APRI (x2=3.975;P＜0.05),AFP (x2=33.37;P＜0.05),Degree of differentiation (x2 =9.839;P＜0.05) were significant differences between MVI positive (MVI+) and negative (MVI-) groups,and the difference was statistically significant;Logistic regression multifactor analysis showed that NLR (OR 2.678;95％ CI 1.033～6.944;P＜0.05) and AFP (OR 1.724;95％CI 1.023～2.905;P＜0.05) are independent predictors of MVI.Conclusion Preoperative NLR and AFP are convenient,economical and reliable hematological indices for predicting the presence of MVI in HCC patients.

Objective To explore the risk factors of hemorrhagic transformation and prognosis of acute ischemic stroke (AIS) after intravenous thrombolysis. Methods From June 2017 to June 2019,211 patients with AIS undergoing intravenous thrombolysis were selected as the research object. Among them,34 patients with hemorrhagic tromsformation (HT) were recorded as HT group,and 177 patients without hemorrhagic transformation The patient was recorded as a non-HT group,with a bleeding conversion rate of 16.11%. The relationship between intensive blood pressure reduction and bleeding conversion and prognosis in patients with AIS intravenous thrombolysis was analyzed during intravenous thrombolysis. Results Univariate analysis revealed gender,age,time interval between onset to start of treatment (OTT),blood glucose at admission,baseline blood pressure,and baseline from the onset to start of treatment (reombinant tissue plasminogen activator,rt-PA) The National Institute of Health stroke scale (NIHSS) score,type 2 diabetes,atrial fibrillation,and venous thrombolysis have statistically significant differences (P<0.05 or P<0.01),which is a vein Risk factors related to HT after thrombolysis;binary logistic analysis showed that the baseline NIHSS score of 17.5 was divided into independent risk factors for the transformation of venous thrombolysis hemorrhage in AIS patients (OR=1.639,P=0.013). Atrial fibrillation (OR=9.129,P<0.01) is an independent risk factor for the prognosis of patients with intravenous thrombolysis. Conclusion The baseline NIHSS score of 17.5 is divided into independent risk factors for HT after intravenous thrombolysis in AIS patients,and intensive blood pressure reduction during intravenous thrombolysis is a related risk factor for HT;atrial fibrillation is an independent risk factor for the prognosis of patients with intravenous thrombolysis.

Objective To summarize clinicopathologic features of papillary thyroid carcinoma (PTC) coexistent with chronic lymphocytic thyroiditis (CLT) and investigate risk factors for lymph node metastasis.Methods The medical records of 4 264 consecutive papillary thyroid carcinoma patients who received surgical treatment from Oct 2013 to Oct 2015 in Peking Union Medical College Hospital were reviewed.The diagnoses was confirmed by histopathological tests.Univariate analysis was performed to identify specific clinicopathologic features of PTC with CLT.Univariate and multivariate analysis were performed to determine whether each clinicopathologic feature was an independent risk factor for lymph node metastasis.Results In all 4 265 cases,there were 3 059 papillary thyroid microcarcinoma (PTMC) (71.7％),1 010 PTC patients (23.7％) with CLT.909 female patients (90％),624 cases with multifocal lesions (61.8％),422 cases with extra-thyroid extension (41.8％),429 cases with lymph node metastasis (42.5％),and 133 cases with metastatic lymph nodes(LNs) ≥6 (13.2％).The median age was 43 years old and median tumor size was 0.8 cm.Patients with CLT were more females (90.0％ vs.70.2％;P ＜ 0.001),younger median age (43 vs.44 years;P =0.001),and lower incidence of lymph node metastasis (42.5％ vs.50.9％;P ＜0.001).CLT was not associated with tumor size,multifocal lesions,extra-thyroid extension and metastatic LNs≥6 (0.8 cm vs.0.7 cm,61.8％ vs.62.9％,41.8％ vs.42.1％ and 13.2％ vs.14.8％,respectively,all P ＞ 0.05).In multivariate analysis,CLT was an independent protective factor for lymph node metastasis (OR =0.713,95％ CI 0.609-0.835,P ＜0.001).In PTC patients with lymph node metastasis,CLT was not associated with lymph node metastasis number (3 vs.3,P =0.300).Conclusions Chronic lymphocytic thyroiditis was an independent protective factor for papillary thyroid carcinoma patients with lymph node metastasis.But in patients with lymph node metastasis,the metastatic number didn't decrease.

Objective: To investigate the related factors for lymph node metastasis (LNM), especially for high volume LNM (>5 metastatic lymph nodes) in papillary thyroid carcinoma (PTC). Methods: The medical records of 2 073 consecutive PTC patients who underwent lobectomy, near-total thyroidectomy or total thyroidectomy with ipsilateral or bilateral central lymph node dissection in Department of General Surgery, Peking Union Medical College Hospital from November 2013 to October 2014 were reviewed. Clinical and pathological features were collected. Univariate and multivariate analysis were performed to identify the related factors for LNM/high volume LNM. Results: In all 2 073 patients, LNM and high volume LNM were confirmed in 936 (45.15%) cases and 254 (12.25%) cases respectively. In univariate analysis, large tumor size, young patients (<40 years), male were associated with both LNM and high volume LNM. In multivariate analysis, tumor size >2.0 cm, young patients (<40 years), male were independent related factors of LNM (OR=5.262, 95% CI: 3.468 to 7.986; OR=2.447, 95% CI: 2.000 to 2.995; OR=1.988, 95% CI: 1.593 to 2.480, respectively, all P=0.000) and high volume LNM (OR=6.687, 95% CI: 4.477 to 9.986; OR=2.975, 95% CI: 2.224 to 3.980; OR=2.354, 95% CI: 1.737 to 3.191, respectively, all P=0.000). In 1 414 PTMC patients, a similar result was also demonstrated.Compared with young patients (<40 years), old patients (≥60 years) had lower incidence of LNM (25.47% vs. 52.24%, χ²=62.903, P=0.000) and high volume LNM (1.89% vs. 13.18%, χ²=37.341, P=0.000). Additionally, old patients also had lower risk of both LNM (OR=0.316, 95% CI: 0.194 to 0.517, P=0.000) and high volume LNM (OR=0.142, 95% CI: 0.034 to 0.599, P=0.000). Conclusions The tumor size was the main related factor for both LNM and high volume LNM in PTC. The treatment should be more active in patients with tumor size >2 cm with consideration of higher incidence and risk for LNM and high volume LNM. Young patient was another important related factor for LNM and high volume LNM. In PTMC, old patients had lower incidence and risk for both LNM and high volume LNM. Dynamic observation or less surgical extent could be an option for these patients.

【Objective】 To investigate the effect and mechanism of musk-containing serum on the migration of bone marrow mesenchymal stem cells (BMSCs). 【Methods】 Sixty SD rats were randomly divided into four groups: musk-high-, medium- and low-dose groups and blank control group; medicated serum was prepared. Fifteen SD rats were isolated and cultured with BMSCs, and the third generation of BMSCs were identified by morphology, phenotype, osteogenic and adipogenic induction. BMSCs received medicinal healing intervention with high-, medium- and low- (16.8, 8.4, and 4.2 μL/100 g) musk, and the cell proliferation rate was detected by MTT assay. Under the intervention of the protein kinase C (PKC) signaling pathway (GF109203X), the effect of musk with pharmacition on the migration of BMSCSs was detected with the Transwell test. 【Results】 The rat BMSCs were attached to the wall, with orderly arrangement and good cell viability. Phenotypic identification revealed that the expressions of CD44 and CD90 were positive, while the expressions of CD45 and CD34 were negative, and the cells could differentiate into osteoblasts and adipocytes. The proliferation rates of BMSCSs with different concentrations at different time periods were higher than those in the blank control group (P<0.05). The number of BMSCs in the low-concentration musk group (4.2 μL/100 g) was significantly increased at 24 h, 48 h and 72 h after the addition of the blocking agent GF109203X (P<0.05). The migration quantity of the low-concentration musk group + blocker group (GF109203X) significantly decreased at different time periods, and there was no significant difference between different time groups (P>0.05). 【Conclusion】 The mechanism of musk-containing serum in promoting BMSCs migration may be related to the activation of PKC signaling pathway.