Background: Studies showed that aberrant activation of JAK/STAT3 signaling pathway promoted the tumorigenesis and progression of hepatocellular carcinoma (HCC), and transforming growth factor-β1 (TGF-β1) has either tumor-suppressing or tumor-promoting effect in regulation of tumor progression.Aims: To investigate the effect of specific inhibition of JAK/STAT3 signaling pathway on HCC and whether TGF-β1 signaling pathway is involved in this process or not.Methods: Thirty Wistar rats were randomly divided into three groups: control group, HCC group, and HCC+AG490 group.In the latter two groups, diethylnitrosamine was administered in drinking water to induce HCC model, and in HCC+AG490 group, AG490, a specific inhibitor of JAK was injected intraperitoneally in the first week of model establishment.At the end of the 16th week, all rats were sacrificed.The maximum diameter of tumor nodules in the liver was recorded and the number of tumors with maximum diameter greater than 1 cm was counted.Expression and distribution of STAT3 and TGF-β1 in liver tissue were determined by real-time PCR, immunohistochemistry, and immunofluorescence.Results: Compared with the control group, expressions of STAT3 and TGF-β1 mRNA in liver tissue were significantly increased in HCC group (P<0.05).Phosphorylated STAT3 (p-STAT3) and TGF-β1 proteins were absent in liver tissue in control group, and both were up-regulated and co-expressed in HCC group.While in HCC+AG490 group, expressions of STAT3 and TGF-β1 mRNA were significantly lower than those in HCC group (P<0.05);the liver tissue was weakly positive for p-STAT3 and TGF-β1 proteins, and the number of tumor nodules greater than 1 cm and the maximum diameter were markedly reduced when compared with the HCC group [1.20±1.03 and (1.14±0.18) cm vs.4.30±1.06 and (1.78±0.27) cm, P all<0.05].Conclusions: Specific inhibition of JAK/STAT3 signaling pathway may restrain the tumorigenesis and progression of HCC partially by interfering TGF-β1 signaling pathway.

OBJECTIVE:To analyze the utilization status and developing trend of drugs in Chengdu area. METHODS:Data regarding the drug variety,consumption quantity and sum of money in 16 hospitals of Chengdu area between 2001 and 2006 were analyzed retrospectively. RESULTS:The drug consumption sum in 16 Hospitals of Chengdu area from 2001 to 2006 increased by 19.56%,27.19%,17.84%,15.08% and 10.40%,respectively,assuming an downtrend. Among the top 14 chief drug categories on the list of consumption sum,the sequence of anti-infective agents,cardiovascular agents,antineoplastic agents and nervous system agents experienced no obvious changes. CONCLUSION:The drug utilization in Chengdu area tends to be rational and standard.

At present, antibacterial drugs are widely used in the clinical treatment of infectious diseases. It is particularly impor-tant to focus on the safety of antibacterial drugs for the application improvement in the clinical treatment. The paper reviewed and sys-tematically analyzed the relative literatures in order to explain the pathomechanism of drug-induced renal injury caused by antibacterial drugs and propose some preventive measures. The study suggested that attention should be paid to the distribution and characteristics of the adverse drug reaction of antibacterial drugs to ensure the safe and proper administration of the drugs.

Objective To explore the splenic macrophages phenotype and secretory function of mice with periodontitis, so as to explore effects of periodontitis on macrophages. Methods 22 mice were randomly divided into periodental ligation group (group P10d ) and pseudo periodental ligation control group (group C), with 11 mice in each group. The experimental periodental ligation on mice lasted for 10 days before they were sacrificed. Flow cytometry was applied to detect the expression of M1 and M2 in mononuclear macrophages. Real-time PCR was applied to detect the relative expression of pro-inflammatory cytokines IL-1β and anti inflammatory cytokines IL-10. Results Compared with the control group C, the proportion of M1 macrophages in the periodontitis group decreased, and the ratio of M1/M2 was also decreased significantly, and IL-1β mRNA also down-regulated. Conclusions Chronic periodontal infection could down regulate the proportion of M1 macrophages , decrease ratio of M1/M2 and the expression of inflammatory cytokines IL-1βmRNA.

Objective: To observe the therapeutic effect of sinew-regulating bone-setting manipulations for knee osteoarthritis (KOA) model rabbits and its impacts on the chondrocyte apoptosis rate and the levels of interleukin (IL)-1β and nitric oxide (NO). Methods: According to the random number table method, 30 New Zealand white rabbits were divided into a normal group (n=9) and a modeling group (n=21). Rabbits in the modeling group were used to establish KOA models with the modified Hulth method. At the 8th week, three rabbits were sacrificed to verify the model and the remaining 18 rabbits were randomly divided into a model group (n=9) and an intervention group (n=9). Rabbits in the normal group and model group were bred routinely without any intervention. Rabbits in the intervention group were treated with the sinew-regulating bone-setting manipulations, 10 min/time, once every other day for a total of 20 times. The Lequesne MG knee function rating was used to evaluate the behavioral differences of the rabbits in each group. The Pelletier score was used to evaluate the general changes of the rabbits. The Mankin score was used to evaluate the pathology of knee cartilages. The enzyme-linked immunosorbent assay and nitrate reductase methods were used to determine the levels of IL-1β and NO in serum and synovial fluid of each group, respectively. In situ terminal deoxynucleotidyl transferase-mediated nick and labeling method was used to determine the apoptosis of chondrocytes in each group. Results: Compared with the normal group, the scores of Lequesne MG, Pelletier and Mankin, and the levels of IL-1β and NO in the model group were increased (P<0.05), which indirectly indicated the success of the model. Compared with the model group, the scores of Lequesne MG, Pelletier and Mankin, IL-1β and NO levels, and chondrocyte apoptosis rate of the intervention group were decreased, and the differences were statistically significant (P<0.05). Conclusion: The sinew-regulating bone-setting manipulations can reduce the levels of IL-1β, NO, and chondrocyte apoptosis rate, and delay the articular cartilage degeneration, therefore, having a good therapeutic effect on KOA.

Aged ; Coal Mining ; Electrocardiography ; Heart Rate ; Humans ; Male ; Middle Aged ; Pneumoconiosis ; complications ; physiopathology ; Tachycardia ; etiology

Objective To investigate the mechanism of tumor necrosis factor-α (TNF)-α inhibiting osteo blastdifferentiation of mesenchymal stem cells (BMMSCs) in the pathogenesis of osteoporosis in the mouse model of systemic lupus erythematosus (MRL/lpr). Methods The femurs of MRL / lpr and C3He/HeJ mice were isolated, the bone structure were examined by hematoxylin-eosin (HE) staining. The proteins of TNF-α, NF-κB P50, bone morphogenetic protein -2 (BMP-2) and PSmad1/5/8 were measured by immunohistochemical stain. Bone marrow mesenchymal stem cells (BMMSCs) were isolated. After BMMSCs grew on the cover slips, the proteins on top of it were evaluated by immunohistochemistry stain. Moreover, the alkaline phosphatase (ALP) staining was employed for the measurement of the early osteogenic differentiation. BMMSCs together with hydroxyapatite were embedded subcutaneously in the nude mice and eight weeks later, the ectopic bone formation was evaluated. The recombinant human tumor necrosis factor receptor type Ⅱantibody fusion protein (etanercept) or normal saline was subcutaneous injected to the mice with lupus. After four weeks, the expression of these proteins was observed and the ectopic bone formation was investigated. Image-Pro plus 6.0 software was employed for imagine analysis, and Studentˊs t-test was used to test the differences between 2 independent groups. Results MRL/lpr mice showed decreased volume of cortex and the percentage of cortex to the volume of bone of MRL/lpr mice was significantly lower compared to control groups and with C3He/HeJ mice (13.96±0.25 vs 23.61±0.71, n=3, P<0.01). The protein levels of both TNF-αand NF-κB P50 on the femur of MRL/lprl mice were higher than those of the control group (0.643±0.051 vs 0.405±0.022, 0.917±0.023 vs 0.650±0.032, n=3, P<0.01). The expressions of BMP-2 on the femur of MRL/lpr mice were lower than those of the C3He/HeJ mice (0.52 ±0.03 vs 0.72 ±0.03, n=3, P<0.01). There was no difference in the expression of PSmad1/5/8 on the femur between the two groups by immunohistochemistry detection (1.264 ±0.021 vs 1.301± 0.044, n=3, P>0.05). The expressions of TNF-α and NF-κB P50 in BMMSCs of MRL/lprl mice were higher than those of the C3He/HeJ (0.184±0.021 vs 0.136±0.013, 0.132±0.021 vs 0.097± 0.014, n=3, P<0.01), while BMP-2 and PSmad were lower than those of the control group (0.128±0.013 vs 0.216±0.221, 0.115±0.023 vs 0.196±0.034, n=3, P<0.01). After 7 days of BMP-2 stimulation, the activities of ALP of BMMSCs from MRL/lprl mice were reduced detected by ALP staining and the osteoblast differentiation of these cells were decreased than BMMSCs from the control mice by HE and Masson staining. The percentage of the cortex to the volume of bone of the etanercept injection MRL/lpr mice was higher than that of the control group (21.8±1.0 vs 14.3 ±0.6, n=3, P<0.01). Moreover, the proteins of TNF-α and NF-κB P50 on the femurs of such injected mice were lower than those of the control group (0.540±0.024 vs 0.682±0.031, 0.857±0.023 vs 1.098±0.044, n=3, P<0.05), while the expressions of BMP-2 were higher than the control group (0.99±0.04 vs 0.85±0.04, n=3, P<0.05). There was no difference in the PSmad1/5/8 expression on the bone of the two group of lupus mice (0.88 ±0.08 vs 0.84 ±0.04, n=3, P>0.05). The ectopic bone formation of BMMSCs of the etanercept injected MRL/lpr mice was higher than that of the normal saline injected mice, however, it was lower than that of the C3He/HeJ mice. Conclusion TNF-α inhibits osteoblast differentiation of mesenchymal stem cells by depressing Smad signaling which may contribute to the osteoporosis of the lupus mice.

BACKGROUND: Strontium-doped calcium polyphosphate (SCPP) is a new type of bone repair materials with good biocompatibility and controlled degradation. The preliminary studies of our group indicate their role in promoting angiogenesis,but its mechanism is unclear.OBJECTIVE: By co-culturing osteoblasts ROS17/2.8 with SCPP in vitro to observe cell proliferation and the secretion of vascular endothelial growth factor (VEGF).DESIGN, TIME AND SETTING: A contrast study was performed at the Laboratory of Tissue Engineering of Sichuan University from October 2008 to June 2009.MATERIALS: A series of calcium polyphosphate (CPP) respectively containing 0%, 1 %, 2%, 5%, 8%, and 10% Sr~(2+) were prepared. ROS17/2.8 osteoblastic cell strain was provided by Laboratory of Transplantation Immunity and Transplantation Engineering, West China Hospital, Sichuan University.METHODS: ①Preparation of cell scaffold complexes: The materials were placed in 24-well plates, then 300 μL cell suspension with a concentration of 2×10~7 cells/Lwas inoculated into each hole. These complexes were cultured for 14 days and the liquid was changed every two days. ②These complexes were measured by MTT assay to observe the proliferation of osteoblasts on the 1~(st), 3~(rd), 5~(th), 7~(th), 10~(th) and 14~(th) days, respectively. ③ The centrifugal supernatant of the complex cultured for seven days was measured by ELISA assay to check the secretion of VEGF.MAIN OUTCOME MEASURES: The proliferation of osteoblastic cells on SCPP and CPP was observed. The amount of VEGF protein secreting from osteoblastic cells was detected.RESULTS: The results of MTT showed that, compared with the CPP group, SCPP groups could promote the proliferation of osteoblasts, and 8% SCPP group was the best; ELISA results showed that, compared with the CPP group, SCPP groups could increase the amount of VEGF protein secretion, of which the promoting role of 8% SCPP was the most obvious (P < 0.05).CONCLUSION: When cultured with osteoblasts, SCPP can promote cell proliferation, and can significantly increase the secretion of VEGF; moreover, 8% SCPP is the best, which reveals a certain mechanism of its promoting angiogenesis.

Objective To evaluate the feasibility of Mycobacteria growth indicator tube ( MGIT ) liquid culture combined with rifampin resistance test real-time PCR ( Xpert MTB/RIF test) in the diagnosis of tuberculosis.Methods 652 cases of suspected pulmonary tuberculosis from October 2014 to March 2015 in Quzhou People′s Hospital were enrolled. The morning sputum samples were collected for acid-fast staining, L?wenstein-Jensen ( L-J) culture, BACTEC MGIT culture and Xpert MTB/RIF test.Samples with positive results of MGIT liquid culture were subjected to strain identification and drug sensitivity test with fluid method.Methodological comparison between four methods was made and the performance of MGIT liquid culture combined with Xpert MTB/RIF test in the rapid diagnosis and drug resistance detection in Mycobacterium tuberculosis was evaluated by chi-square test. Results Among the samples from 399 confirmed tuberculosis patients, the diagnostic sensitivity of the 4 methods ( acid-fast staining, L-J culture, MGIT culture and Xpert MTB/RIF test) were 17.0%(68/399), 23.8%(95/399), 37.8% (151/399) and 37.3%(149/399) respectively.The sensitivity and specificity of MGIT culture combined with Xpert MTB/RIF test was 39.8%(159/399) and 94.8%(240/253).The sensitivity of MGIT culture combined with Xpert MTB/RIF test was significantly higher than acid-fast staining (χ2 =50.9, P<0.01 ) and L-J culture (χ2 =23.7,P<0.01).The average detection time of MGIT culture was 7.5 days ( smear positive and Xpert MTB/RIF positive), 13.4 days (smear negative and Xpert MTB/RIF positive) and 16.9 days ( smear negative and Xpert MTB/RIF negative) .The sensitivity and specificity of Xpert MTB/RIF test in rifampin resistance detection were 9/9 and 97.3% ( 129/132 ) respectively.The average detection time of fluid method for drug sensitivity test was 8.3 days.Conclusions MGIT liquid culture combined with Xpert MTB/RIF test can detect Mycobacterium tuberculosis and the drug sensitivity rapidly.The method is highly sensitive and specific.It is important for clinical diagnosis and treatment of tuberculosis.

Objective To analyze the changes of clinical and pathological features in the patients of IgA nephropathy with anemia.Methods Four hundred and nine patients of IgA nephropathy diagnosed by renal biopsy were classified into two groups:IgA nephropathy with nonanemia (group 1) and IgA nephropathy with anemia (group 2).Changes were studied retrospectively between the groups.Results Serum hemoglobin level was correlated with the clinical parameters of IgA nephropathy.Companed to group 1,changes in group 2 were as followed:serum creatinine increased,eGFR decreased,proteinuria increased; the global sclerosis,segmental sclerosis,crescents and tubulointerstitial lesions worsened.The glomerular and tubulointerstitial lesions were negatively correlated with serum hemoglobin and eGFR,but positively correlated with serum uric acid and proteinuria (P＜0.05).Multivariate Logistic regression analysis revealed that anemia was an independent risk factor for the tubulointerstitial lesion.Conclusion Clinical feature and pathological damages in the patients of IgA nephropathy with anemia are more serious than those with non-anemia.