ABSTRACT
Esophageal cancer (EC) is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis. The early diagnostic rate of EC is low, and most EC patients are diagnosed at an advanced stage. Multiple multimodality treatments have gradually evolved into the main treatment for advanced EC, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. And the emergence of targeted therapy and immunotherapy has greatly improved the survival of EC patients. This review highlights the latest advances in targeted therapy and immunotherapy for EC, discusses the efficacy and safety of relevant drugs, summarizes related important clinical trials, and tries to provide references for therapeutic strategy of EC.
Subject(s)
Humans , Immunotherapy , Combined Modality Therapy , Esophageal Neoplasms/pathologyABSTRACT
Objective:To investigate the static and dynamic trends of scientific research efficiency of the critical care medicine in hospitals affiliated S university during the 13th Five-Year Plan period.Methods:Based on the scientific research data of 16 hospitals affiliated to Beijing S University from 2014 to 2020, the scientific research investment funds and the number of physicians involved in scientific research were selected as input evaluation indexes, and the number of science citation index (SCI) papers, Chinese science citation database (CSCD) papers, and the number of masters and doctors trained were selected as output evaluation indexes, and the evaluation index system of scientific research efficiency of critical care medicine was constructed. SPSS version 23.0 software was used for descriptive data statistics, and data envelopment analysis (DEA)-BCC model and DEA-Malmquist index model of DEAP 2.1 software were used for static and dynamic evaluation of its scientific research efficiency from 2016 to 2020, respectively.Results:① The scientific research technical efficiency (TE) of critical care medicine in 16 hospitals affiliated with S universities varied greatly from 2016 to 2020, but pure technical efficiency (PTE) and scale efficiency (SE) were at a good level, and 6-11 affiliated hospitals in critical care medicine kept DEA effective for 5 consecutive years. ② Dynamic analysis of their total factor productivity (TFP) of scientific research from 2016 to 2020 showed a trend of rising and then falling and then rising again. The mean value was 0.985. The technical efficiency change (TEC) showed a decreasing and then increasing trend, and the technical progress change (TC) showed a slow increasing and then decreasing trend, with a mean value of 0.953. While the mean values of TEC, pure technical efficiency change (PTEC) and scale efficiency change (SEC) were above 1, which showed that the growth of total factor productivity index of research and innovation depended more on the technical efficiency index.Conclusions:The "gain effect" and "catch-up effect" of scientific research efficiency in the specialty of critical care medicine in hospitals affiliated S universities are obvious, but the "growth effect" is not obvious. "Although the research efficiency of the 13th Five-Year Plan period has been significantly improved, there is still much room for improvement in scientific and technological innovation and international academic influence.
ABSTRACT
BACKGROUND: Studies have shown that the osteogenic ability of 10% strontium-doped calcium hydrogen phosphate dihydrate is higher than that of calcium hydrogen phosphate dihydrate and 5% strontium-doped calcium hydrogen phosphate dihydrate, but also found that the pore structure of 10% strontium-doped calcium hydrogenphosphate dihydrate is not ideal, and the early osteogenic effect is not satisfactory. OBJECTIVE: To investigate the osteogenic effect of the composite of 10% strontium-doped calcium hydrogenphosphate dehydrate and gelatin and recombinant human bone morphogenetic protein 2/7 (rhBMP2/7). METHODS: Gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate and gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate material containing 0.04 g/L and 1 g/L rhBMP2/7 were prepared respectively. Forty-five rabbit models of bilateral mandibular defects were prepared and then divided into five groups. In the blank control group, no material was implanted. 10% strontium-doped calcium hydrogen phosphate dihydrate (control group) and gelatin-10% strontium-doped calcium hydrogen phosphate dihydrate (gelatin group), 0.04 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (0.04 g/L rhBMP2/7 group), and 1 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (1 g/L rhBMP2/7 group) were implanted in the remaining four groups, respectively. Bone defect specimens were taken at 4, 8 and 12 weeks after surgery, and were examined by cone beam CT and immunohistochemistry. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China. RESULTS AND CONCLUSION: Cone beam CT examination revealed that at 8 weeks after surgery, bone repair was basically completed and the new bone tissue was almost fused with the surrounding tissue in the 1 g/L rhBMP2/7 group. Most of defect area was repaired, and the edge of new bone was unsmooth in the 0.04 g/L rhBMP2/7 and gelatin groups. Bone defect in the control group partially repaired. At 12 weeks after surgery, bone repair was completed in the gelatin, 0.04 rhBMP2/7 and 1 g/L rhBMP2/7 groups. Immunohistochemistry revealed that at 4 and 8 weeks after surgery, type I collagen expression in the 1 g/L rhBMP2/7 group was significantly higher than that in the other four groups (P 0.05). These results suggest that the addition of gelatin and 1 g/L rhBMP2/7 to 10% strontium-doped calcium hydrogenphosphate dihydrate can promote the repair of bone defects.
ABSTRACT
Objective@#To investigate the relationship of PD-L1 protein expression and gene amplification in gastric cancer and their correlation with clinicopathologic factors.@*Methods@#The cohort included 247 gastric cancer specimens with follow-up data and clinicopathologic data obtained from Shanxi Cancer Hospital in 2011. PD-L1 expression was detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).@*Results@#PD-L1 protein was expressed in 25.9% (64/247) of the tumor cells and 26.7% (66/247) of the tumor infiltrating immune cells (IC). There was a correlation between the two (P<0.01). The expression of PD-L1 in tumor cells correlated with the degree of differentiation and tumor diameter(P<0.05). The PD-L1 expression in IC correlated with vascular tumor thrombi(P<0.05). The amplification rate of PD-L1 gene detected by FISH was 19.0% (47/247), and was associated with age, large/small curvature of the stomach, tumor location, tumor diameter, and lymph node metastasis(P<0.05). The positive coincidence rate of the two methods was 25.0% (16/64), negative coincidence rate was 83.0% (152/183), and total coincidence rate was 68.0% (168/247), suggesting that the coincidence of IHC and FISH was poor (P=0.157). There was a negative correlation between PD-L1 protein expression on tumor cells and prognosis in gastric cancer. There was no significant correlation between PD-L1 protein expression on IC and PD-L1 gene amplification with prognosis. Vascular tumor thrombi, tumor diameter, depth of invasion, and lymph node metastasis were all poor prognostic factors of gastric cancer(P<0.05). Multivariate Cox regression analysis showed that PD-L1 protein expression, depth of invasion and lymph node metastasis were all independent prognostic risk factors for gastric cancer.@*Conclusions@#Concordance between PD-L1 protein expression and gene amplification is poor. PD-L1 protein expression may signify poor prognosis. There is no significant correlation between PD-L1 gene amplification and prognosis of patients with gastric cancer.
ABSTRACT
Ouabain is used in the clinical treatment of the cardiovascular diseases and it can be extensively investigated due to its promising pharmacological, pathological, and physiological properties. The present study is aimed to assess the growth and apoptotic potential of ouabain in RAW 264.7 cells. Varying concentrations of ouabain were applied to cultured RAW 264.7 cells for different time. At 0.01 to 1.00mM doses, ouabain inhibited the proliferation and presented cytotoxicity in both dose- and time-dependent manner. The compound also increased apoptosis after 24 and 48 hours of exposing to 1.00mM dose. Furthermore, the expression of Bcl-2 mRNA significantly decreased following ouabain treatment while Bax mRNA expression increased significantly. In brief, ouabain inhibits cell growth, exerts cytotoxicity and induces apoptosis in RAW 264.7 cells by down-regulating the Bcl-2/Bax ratio at mRNA level
ABSTRACT
Objective@#The Notch signaling pathway is closely related to biliary fibrosis. Previous studies have shown that Astragaloside (AS) can prevent the progression of cholestatic liver fibrosis. The purpose of this study is to observe the effect of AS on the regulation of Notch signaling pathway in biliary fibrosis.@*Methods@#Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in rats. Two weeks after BDL, the rats were randomly divided into a model group (i.e., BDL), an Astragalosides group (AS), and a sorafenib (SORA) positive control group and treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Protein and gene expression were determined by immunostaining, immunoblotting and RT-PCR, respectively. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, -4, Jagged (JAG)1, Delta like (DLL)-1, -3, -4, Hes1, Numb and RBP-Jκ. Statistical analysis of variance analysis, q test, P < 0.05 showed that the difference was statistically significant.@*Results@#(1) AS significantly reduced the deposition of collagen and the Hyp content of liver tissue (500.15 ± 86.10 vs. 625.72 ± 105.62, P = 0.031), and inhibited the activation of hepatic stellate cells. (2) AS significantly decreased the protein and mRNA expressions of transforming growth factor (TGF)-β1 (1.02±0.15 vs. 1.89±0.36, P = 0.007; 1.17±0.18 vs. 1.68±0.29, P = 0.013, respectively) and α-smooth muscle actin (α-SMA, 0.41±0.11 vs. 0.72±0.16, P = 0.003; 1.71±0.57 vs. 2.68±0.46, P = 0.008, respectively) compared with BDL group. In contrast, AS significantly enhanced expression of the Smad 7 protein compared with the BDL group (0.72±0.008 vs. 0.33±0.001, P = 0.005). AS also reduced biliary epithelial cell proliferation. AS reduced the mRNA levels of CK7, CK8 and CK18 (1.31±0.39 vs. 2.63±0.82, P = 0.009; 0.71±0.09 vs. 0.87±0.08, P = 0.031; 2.56±0.32 vs. 3.41±0.39, P = 0.010, respectively) and reduced the positive areas of CK19 and OV6 (62 337.17±21 873.38 vs. 22 5472.67±26 933.63, P = 0.000; 92 237.43±15 894.11 vs. 171 298.13±61 761.37, P = 0.000, respectively). (3) The mRNA expression of Notch-2, -3, -4 and JAG1 were significantly reduced in the AS group compared to the BDL group (1.07±0.19 vs. 1.51±0.28, P = 0.044; 0.99±0.24 vs. 1.18±0.10, P = 0.043; 1.36±0.42 vs. 3.40±0.44, P = 0.048; 2.62±0.43 vs. 3.73±0.83, P = 0.046, respectively). In contrast, the mRNA level of Numb was clearly enhanced after AS treatment (0.90±0.05 vs. 0.75±0.11, P = 0.019). In addition, consistent with the mRNA levels, the protein expressions of Notch-2, -3, -4 and JAG1 were reduced significantly (1.27±0.18 vs. 1.71±0.26, P = 0.004; 0.99±0.11 vs. 4.38±0.60, P = 0.001; 1.76±0.32 vs. 4.01±0.74, P = 0.002; 1.62±0.33 vs. 2.74±0.63, P = 0.002) and the Numb protein level was increased significantly (1.50±0.15 vs. 0.85±0.11, P = 0.001) in AS group compared with BDL group.@*Conclusion@#AS may prevent cholestatic liver fibrosis via inhibition of the Notch signaling pathway, thereby inhibiting the abnormal proliferation of biliary epithelial cells. Results indicate that AS may be a potential treatment for cholestatic liver disease.
ABSTRACT
Objective@#To investigate differentiation direction of hepatic progenitor cells (HPCs) in cholestatic liver fibrosis (CLF), and the role of Notch signaling pathway in the differentiation of HPCs.@*Methods@#A CLF rat model was established by bile duct ligation (BDL) followed by monitoring changes of Notch signal pathway and the cellular origin of proliferating cholangiocytes. After intraperitoneal injection of DAPT (a Notch signaling inhibitor) after bile duct ligation, the progress of liver fibrosis and the proliferation of cholangiocytes after inhibition of the Notch pathway were analyzed.@*Results@#Data showed that bile duct proliferation gradually increased along with inflammatory cell infiltration and proliferating bile duct cells surrounded by abundant collagen in the BDL group. Immunostaining confirmed markedly increased expression of CK19, OV6, Sox9 and EpCAM. In addition, RT-PCR results showed that Notch signaling pathway was activated significantly. Once the Notch signaling pathway was inhibited by DAPT, bile duct proliferation markedly suppressed along with significantly decreased the mRNA expression of CK19, OV6, Sox9 and EpCAM, compared with BDL group [(10.2±0.7) vs. (22.3±0.8), (7.6±1.5) vs. (18.1±3.7), (1.4±0.4) vs. (4.1±1.1), (1.3±0.3) vs. (5.0±1.4), respectively, P<0.01]. Moreover, liver fibrosis was also reduced significantly.@*Conclusion@#Notch signaling activation is required for HPCs differentiation into cholangiocytes in CLF and inhibition of the Notch signaling pathway may offer a therapeutic option for treating CLF.
ABSTRACT
Objective To summarize the distribution of departments,conditions of diagnosis and treatment of the syphilis patients in the general hospitals,and thus to improve the level of diagnosis and treatment.Methods A retrospective analysis of epidemiology and clinical data of 282 cases with syphilis in recent 5 years were conducted. Results The ratio of male to female was about 1:1.9.Female showed a high incidence in the 21 -50 years old,aver-age (41.68 ±0.96)years old,but for male in the 41 -70 years old,average (53.25 ±1.59)years old.The cases combined with other infectious diseases accounted to 22.0 % (62/282).The cases from the department of obstetrics and gynecology were the most (106 cases),followed by surgery (86 cases)and internal medicine (49 cases).Only 23 cases showed the clinical manifestations of syphilis in the 79 cases,which must be treated.The test rate of TRUST was only 39.0% (110/282).Furthermore,it was very low for the rate of treatment and standard treatment. Conclusion Syphilis is the most in department of obstetrics and gynecology in general hospital,and it is also com-mon in the surgery and internal medicine.The most prominent problems are that the non-special doctors had weak awareness for definite diagnosis of syphilis,and the low rate of treatment and standard treatment.
ABSTRACT
Objective To explore the differences of memory functions and objective sleep parameters and their correlations in patients with insomnia disorder in different subtypes.Methods Eightynine patients with insomnia disorder,including 11 patients with difficulty initiating sleep(DIS),20 patients with early morning awakening(EMA),20 patients with difficulty maintaining sleep (DMS) and 38 patients with mixed sleep symptoms(MS) were enrolled between August 2012 and February 2014 in the Memory and Sleep Disorders Clinic of the First Affiliated Hospital of Anhui Medical University.Memory functions,including objective memory,spatial memory,working memory and reference memory were detected with nine boxes maze,and objective sleep profiles were assessed using polysomnography.Results The error numbers of spatial(H =15.404,P =0.002) and working (H =10.126,P =0.018) memories were significantly different among the 4 subtypes of patients,with more errors of spatial and working memory in the EMA (6.00 (5.00,8.00),5.00 (4.00,6.00)) and MS (5.00 (3.75,7.25),5.00 (2.75,7.00)) groups compared with the DMS (2.50 (2.00,4.00),2.00 (1.00,4.00)) group (tspstial =3.938,3.428;t =2.803,2.840;all P ＜ 0.05).Sleep efficiency(H =7.929,P =0.048),REM sleep time(F =2.840,P =0.043) and the percentage of REM sleep time on total sleep time (REM％;H =7.913,P =0.048) were also significantly different among the 4 subtypes of patients,with lower sleep efficiency in the MS(69.7％ (50.5％,78.7％)) group compared with the EMA (81.0％ (64.8％,86.4％)) and DMS (80.2％ (62.6％,88.9％)) groups (t =2.242,2.352;all P ＜ 0.05),less REM sleep time (min) and REM％ in the EMA(61.6 ±27.1,16.9％ (13.1％,21.9％)) and MS(56.9 ±31.4,16.9％ (11.5％,21.2％)) groups compared with the DMS (80.9 ± 32.7,22.3％ (18.5％,25.5％)) group (qREM time =3.791,5.397;tREM％ =2.513,2.612;all P ＜0.05).The error numbers of working memory and spatial memory negatively correlated with the REM sleep time (r =-0.387,-0.348;all P ＜ 0.05) and REM％ (r =-0.350,-0.354;all P ＜ 0.05).Conclusions There are discrepancies in the spatial and working memories and subtle differences in the objective sleep parameters among the patients with different subtypes of insomnia disorder.The worse memories in insomnia disorder patients might be associated with the decreased REM sleep.
ABSTRACT
The expression changes of genes associated with adipose metabolism and regulation of cell growth in backfat tissue at five growth stages (1, 2, 3, 4 and 5 months) of Landrace (a leaner Western breed) and Taihu pigs (a fatty indigenous Chinese breed) were measured by using pathway-focused Oligo microarray. The comparative results between two pig breeds of change ratios showed that the fold changes of 10, 6, 11, 8 and 19 genes were over two times at same month from 1 to 5 months respectively. Variance analysis (ANOVA) revealed that 25 genes in Landrace pigs showed significantly altered in expression among five growth stages (P < 0.05). Principal components analysis (PCA) revealed that angiopoietin-like 4 (ANGPTL4), cathepsin K (CTSK), isocitrate dehydrogenase 2(NADP+) (IDH2), lipoprotein lipase (LPL), malic enzyme 1 (ME1), stearoyl-CoA desaturase (SCD) and uncoupling protein 2 (UCP2) displayed distinctive expression patterns from other genes, which suggested that these genes may be subject to special regulation during the period from 1 to 5 months. K-means clustering analysis revealed that genes in Landrace pigs which showed up-regulation were mainly related to the positive regulation of fatty acid metabolism and genes in Taihu pigs which showed slight fluctuation were mainly related to the regulation of cell growth. Quantitative real-time RT-PCR was used to verify the microarray data for five modulated genes, and a good positive correlation between the two measures of expression was observed for both two pig breeds at different growth stages. These results highlight some possible candidate genes for porcine carcass and meat quality traits, reveal the expressional disciplinarian of correlative genes and provide some data on which to base further study of the dynamic balance process for fatty acid biogynthesis and hydrolyzation.