[Analysis of the therapeutic efficacy and factors influencing sequential combination of nucleos(t)ide analogues with pegylated interferon alpha for 48~96 weeks in the treatment of patients with chronic hepatitis B].

Objective: To explore the therapeutic efficacy and factors influencing the sequential combination of nucleos(t)ide analogues (NAs) with pegylated interferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB). Methods: 144 CHB cases with NAs treatment for more than 1 year, HBV DNA < 20 IU/ml, hepatitis B surface antigen (HBsAg) quantification < 3 000 IU/ml, treated with a sequential combination of Peg-IFN-α treatment for 48 to 96 weeks, and followed up were selected from the Fifth Medical Center of the PLA General Hospital between May 2018 and May 2020. Intention-to-treat analysis was used to measure the HBsAg clearance rate at 96 weeks. The Kaplan-Meier method was used to compute the cumulative HBsAg clearance rate at 96 weeks. Univariate and multivariate logistic regression were used to analyze the factors influencing HBsAg clearance at 48 weeks of sequential combination therapy. Univariate and multifactorial COX proportional hazard models were used to analyze the factors influencing HBsAg clearance following 96 weeks of prolonged PEG-IFN-α treatment. The receiver operating characteristic curve was used to assess the predictive value of factors influencing HBsAg clearance. A Mann-Whitney U test was used to compare the measurement data between groups. The count data was compared using the χ(2) test between groups. Results: 41 (28.47%) cases achieved HBsAg clearance at 48 weeks of sequential combination therapy. The HBsAg clearance rate at 96 weeks was 40.28% (58/144) by intention-to-treat analysis. The Kaplan-Meier method computed that the cumulative HBsAg clearance rate at 96 weeks was 68.90%. Multivariate logistic regression analysis showed that HBsAg quantification at baseline (OR = 0.090, 95%CI: 0.034-0.240, P < 0.001) and a 24-week drop in HBsAg level (OR = 7.788, 95%CI: 3.408-17.798, P < 0.001) were independent predictors of HBsAg clearance in CHB patients treated sequentially in combination with NAs and Peg-IFN-α for 48 weeks. Receiver operating characteristic curve analysis showed that the baseline HBsAg quantification [area under the receiver operating characteristic curve (AUC), 0.911, 95% CI: 0.852-0.952)] and 24-week drop in HBsAg level (AUC = 0.881, 95%CI: 0.814-0.930) had equally good predictive value for 48-week HBsAg clearance, but there was no statistically significant difference between the two (Z = 0.638, P = 0.523). The value of the combination of baseline HBsAg quantification and 24-week drop in HBsAg level (AUC = 0.981, 95%CI: 0.941-0.997) was superior to that of single baseline HBsAg quantification (Z = 3.017, P = 0.003) and 24-week drop in HBsAg level (Z = 3.214, P = 0.001) in predicting HBsAg clearance rate at 48 weeks. Multivariate COX proportional hazards model analysis showed that HBsAg quantification at 48 weeks (HR = 0.364, 95%CI: 0.176-0.752, P = 0.006) was an independent predictor of HBsAg clearance with a prolonged course to 96 weeks of Peg-IFN-α treatment. Conclusion: The HBsAg clearance rate can be accurately predicted with baseline HBsAg quantification combined with a 24-week drop in HBsAg level in patients with CHB who are treated with a sequential combination of NAs and Peg-IFN-α therapy for 48 weeks. Prolonging the course of Peg-IFN-α treatment can enhance the HBsAg clearance rate's capability. An independent predictor of HBsAg clearance is HBsAg quantification at 48 weeks of sequential combination therapy with a prolonged course of 96 weeks of Peg-IFN-α treatment.

[Investigation on medical security and quality of life of migrant workers with pneumoconiosis].

Objective: To investigate and understand the medical security and quality of life of migrant workers with pneumoconiosis, so as to provide scientific basis for the prevention and control countermeasures of migrant workers with pneumoconiosis and targeted poverty alleviation. Methods: Using a stratified random sampling method, 200 migrant workers diagnosed with pneumoconiosis at the Shandong Academy of Occupational Health and Occupational Medicine from January 2016 to December 2021 were selected as the observation group, while 200 non migrant workers diagnosed with pneumoconiosis were selected as the control group. St. George's Respiratory Questionnaire (SGRQ) and Pneumoconiosis Questionnaire were used to collect and compare information on the age, working age of dust exposure, economic sources, employment status, income, medical security and quality of life of two groups of patients. Results: The age of migrant worker pneumoconiosis patients in the observation group was (58.1±8.1) years old, and the working age of dust exposure was (19.3±10.1) years. The main source of income was children support (85.5%, 171/200), employment status was mainly wait for employment or unemployed (69.0%, 138/200), personal monthly income was mainly non income (90.0%, 180/200), and family annual income was mainly less than 10000 yuan (48.0%, 96/200). The average personal annual medical expenditure of 5000-<10000 yuan accounted for 42.0% (84/200). The age of pneumoconiosis patients in the control group was (59.2±8.9) years old, and the working age of dust exposure was (20.2±10.5) years. The main source of income was retirement pension or salary (99.0%, 198/200), with retirement as the main employment status (66.0%, 132/200), the main personal monthly income was 2000-<4000 yuan (61.5%, 123/200), the main family annual income was 20000-<40000 yuan (44.0%, 88/200), and the average personal annual medical expenditure was mostly non-expenditure (92.0%, 184/200). There were statistically significant differences in the distribution of economic sources, employment status, personal monthly income, family annual income and average personal annual medical expenditure between the two groups (P<0.001). The main type of insurance for the observation group was rural cooperative medical care (68.5%, 137/200), and 87.0% (174/200) had no medical reimbursement and a proportion less than 50%. There were statistically significant differences in insurance type and medical reimbursement proportion between the two groups (P<0.001). The respiratory symptoms, activity ability, daily life influence and total quality of life scores of pneumoconiosis patients in the observation group were significantly higher than those in the control group, the differences were statistically significant (P<0.001) . Conclusion: Migrant workers with pneumoconiosis have low income, high medical expenditure, low medical reimbursement proportion and poor quality of life. Therefore, it is necessary to draw high attention from relevant departments and provide timely attention and assistance to improve the quality of life of migrant workers with pneumoconiosis.

[A single-center retrospective analysis of 100 consecutive cases treated with lenalidomide/bortezomib/dexamethasone in newly diagnosed multiple myeloma].

Objective: To investigate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: A total of 100 consecutive NDMM patients treated with RVD from August 2016 to September 2020 at Peking University People's Hospital were retrospectively analyzed, including response, drug toxicity, follow-up and survival, and subgroup analysis. Results: The median follow-up time was 19.5 (2.0-57.0) months. For patients undergoing autologous stem cell transplantation (ASCT) after RVD regimen, the objective response rate (ORR)/complete response+stringent complete response (CR+sCR)/≥very good partial response (VGPR) rates were 100%, 73.3% (33/45), 95.6% (43/45) respectively. For 54 patients not receiving transplantation, the ORR/CR+sCR/≥VGPR rates were 79.6% (43/54), 18.5% (10/54), 51.9% (28/54) respectively. As to the survival analysis, 2-year progression free survival (PFS) rates were 84.5% and 70.9% in transplant and non-transplant patients respectively (P=0.102). Two-year overall survival (OS) rates were 100% and 80.8% in transplant and non-transplant patients respectively (P=0.003). The common hematologic adverse events (AEs) were thrombocytopenia (33%) and neutropenia (25%). Abnormal liver function (43%) and peripheral neuropathy (24%) were recognized more as non-hematologic AEs. Conclusion: RVD as front-line regimen has high efficient response rate and acceptable safety in Chinese NDMM patients.

[Characteristics and research progress on the role of intestinal fungi in chronic liver disease].

At present, a large number of studies have revealed that intestinal bacteria play a very complex role in benign liver diseases, while there is relatively little research on intestinal fungi. As part of the gut microbiome, intestinal fungi are insignificant in numbers compared with intestinal bacteria, but the impact of intestinal fungi on human health and diseases cannot be ignored. This paper summarizes the characteristics and research progress of intestinal fungi in patients with alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis and liver cirrhosis, so as to provide basis of reference and ideas for the further research on the diagnosis and treatment of intestinal fungi in benign liver diseases.

[The multi-dimensional molecular characteristics of the indolent pulmonary ground-glass nodules].

With the dramatically increasing detection rate of ground-glass nodules (GGN), exact understanding and treatment strategy of them has become the hottest issue currently. More and more studies have begun to explore the underlying mechanisms of their indolent characteristics and favorable prognosis from the perspectives of molecular evolution and immune microenvironment. GGN has different dominating gene mutations at different evolutional stages. The pure GGN has a lower tumor mutation burden and genomic instability, while a gradually evolutionary feature of genomic mutation along with the pathological progression can be observed. GGN has less infiltration of immune cells, and they are under the pressure of immune surveillance with weakened immune escape. With the increase of solid components, an inhibitory immune microenvironment is gradually established and immune escape is gradually enhanced, leading to rapid tumor growth. Further exploration of the molecular characteristics of GGN will help to more precisely distinguish these highly heterogeneous lesions, which could be helpful to make personalized treatment plans.

[Influencing factors for postoperative survival of patients with pneumoconiosis treated by lung transplantation].

Objective: To explore the influencing factors for postoperative survival of patients with pneumoconiosis (silicosis) after lung transplantation in order to improve their clinical outcomes. Methods: In August 2021, retrospective alalysis from December 2015 to July 2021, 29 patients with end-stage pneumoconiosis underwent lung transplantation at Department of Thoracic Surgery, Affiliated Henan Provincial People's Hospital, Zhengzhou University. The survival, postoperative complications, and causes of death were analyzed. Life table and Kaplan-Meier method were used to draw survival curves, the log-rank test was used to compare the influence of each factor on survival rates, and the multivariate Cox proportional hazards regression model was used to evaluate the influence of each factor on survival. Results: All the patients underwent successful lung transplantation, with survival rates of 75% at 6 months, 70% at 1 year, 65% at 2 years, 50% at 3 years and 50% at 5 years. The Kaplan-Meier survival analysis showed that BMI, age and preoperative albumin level were influencing factors for postoperative survival rates (P<0.05) . The multivariate COX regression model showed that BMI≥18.5 kg/m(2) and the albumin level≥35 g/L were the protective factors (P<0.05) . Conclusion: Aging older, preoperative BMI<18.5 kg/m(2) and hypoalbuminemia are independent risk factors for death after lung transplantation. Survival rates are affected by preoperative BMI index, albumin level and age. Early intervention should be made before lung transplantation to promote the BMI index and albumin level to reach the standard.

[Vincristine inhibits the proliferation of ovarian cancer cells by regulating the demethylation of RASSF2A].

Objective: To investigate the effect of vincristine on the proliferation of ovarian cancer cells by regulating RASSF2A demethylation. Methods: SKOV3 cells were infected with control (LV-NC) and RASSF2A lentivirus (LV-RASSF2A) and treated with or without vincristine. Cell counting kit-8 (CCK-8) was used to detect the activity of ovarian cancer cells (SKOV3) treated with different doses of vincristine. Colony formation assay was used to detect the proliferation of SKOV3 cells. Flow cytometry was used to detect the apoptosis of SKOV3 cells. Real time polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of RASSF2A in IOSE-29 and SKOV3 cells. Western blot was used to examine the protein expression of RASSF2A in IOSE-29 and SKOV3 cells. Methylation-specific PCR was used to detect methylation and demethylation levels of RASSF2A gene in IOSE-29 and SKOV3 cells. Results: The cell viabilities of SKOV3 cell treated with 6.25 nmol/L, 12.5 nmol/L, 25 nmol/L, 50 nmol/L and 100 nmol/L vincristine were (87.19±4.49)%, (73.67±8.62)%, (66.35±6.04)%, (50.32±6.00)% and (34.92±6.11)%, respectively, lower than (100.46±4.69)% of control group (P<0.05). The half maximal inhibitory concentration of vincristine at 48 hours was 50.02 nmol/L. The proliferation abilities of SKOV3 cells in vincristine 12.5 nmol/L group, 25 nmol/L group and 50 nmol/L group were (41.70±2.21)%, (32.15±1.80)% and (23.00±2.01)%, respectively, significantly lower than (100.78±5.66)% in the control group (all P<0.05). The apoptotic rates of SKOV3 cells in vincristine 12.5 nmol/L group, 25 nmol/L group and 50 nmol/L group were (3.65±0.27)%, (5.21±0.76)% and (10.46±1.00)%, respectively, significantly higher than (2.12±0.23)% in the control group (all P<0.05). Compared with the IOSE-29 group (1.00±0.07 and 0.68±0.04), the mRNA expression (0.32±0.04) and protein expression (0.24±0.02) of RASSF2A were down-regulated in SKOV3 cells (P<0.05). Compared with the LV-NC group [(101.60±4.39)%, (100.73±3.29)%, (4.06±0.30)%], over-expression of RASSF2A down-requlated cell viability (68.92±3.94)%, inhibited proliferation (16.38±2.16)%, and promoted apoptosis (8.65±0.56)%, (P<0.05). Conclusion: Vincristine can increase RASSF2A expression and inhibit ovarian cancer cell proliferation by promoting the demethylation of RASSF2A promoter.

[Early reduction of serum RANTES can predict HBsAg clearance in patients with chronic hepatitis B treated with nucleos(t)ide analogues combined with peginterferon alpha].

Objective: To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B. Methods: 98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks. Results: During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log(10)IU/ml vs. (0.73 ± 0.81) log(10)IU/ml, P = 0.017; (1.54 ± 1.27) log(10)IU/ml vs. (0.57 ± 0.56) log(10)IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion: Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

Imaging mass spectrometry allows for neuroanatomic-specific detection of gangliosides in the healthy and diseased brain.

Gangliosides have a wide variety of biological functions due to their location on the outer leaflet of plasma membranes. They form a critical component of membrane rafts, or ganglioside-enriched microdomains, where they influence the physical properties of the membrane as well as its function. Gangliosides can change their structure to meet their external and internal environmental demands. This ability to change structure makes gangliosides both fascinating and technologically challenging targets to identify and understand. A full understanding on how gangliosides are regulated within the central nervous system (CNS) is critical, as ganglioside dysregulation is observed in the aging brain as well as in several neurodegenerative injuries and diseases such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease and several lysosomal storage disorders diseases, including Tay Sach's disease. Mass spectrometry (MS) has become a useful means to better understand ganglioside composition and function. Imaging mass spectrometry (IMS) provides the added benefit of placing analytical information within an anatomical context. This review article will discuss recent advances in MS-based detection methods, with a focus on IMS-based approaches to help understand the spatial-specific role gangliosides in the healthy brain as in CNS injuries and disease.

[Cardiovascular toxicities associated with immune checkpoint inhibitors].

With the continuous development of cancer treatment, the immune checkpoint inhibitors have been applied to the treatment of a variety of malignant tumors, which improved the patient's survival time and quality of life. However, immune-related adverse reactions occur inevitably. Like chemotherapeutics and targeted drugs, immunosuppressants can also cause cardiovascular events that affect the mortality of cancer patients. With the extension of the survival time of cancer patients, it will increasingly become a key factor which affects the prognoses of these diseases. This review focuses on the cardiotoxic mechanism, clinical manifestation, and future direction of immune checkpoint inhibitors during cancer treatment.

[Study on the quality of life and influencing factors of pneumoconiosis in migrant workers].

Objective: To investigate and understand the general situation and quality of life of migrant workers with pneumoconiosis, and analyze the influencing factors, so as to provide scientific basis for effective countermeasures to improve the quality of life of migrant workers with pneumoconiosis. Methods: In June 2019, 79 cases of migrant workers' pneumoconiosis diagnosed by Shandong Occupational Disease Hospital from March 2017 to August 2018 were selected as the study object by cluster random sampling method. Questionnaires and on-site visits were used to investigate the quality of life and its influencing factors. The questionnaire was administered by self-designed questionnaire and WHO quality of life questionnaire. Results: The farmer's pneumoconiosis patients are generally lower in culture. High school or above is only 6.33% (5/79) . Their economic income is low. The monthly income of less than 1000 RMB is 49.37% (39/79) . The disease was heavy and pneumoconiosis was 58.23% (46/79) . Pneumoconiosis patients without systematic treatment accounted for 69.62% (55/79) . Only 11.39% of rural workers with pneumoconiosis can timely increase or decrease clothing and wear masks to avoid respiratory irritation. Pneumoconiosis patients who smoked accounted for 77.22% (61/79) . The quality of life of the pneumoconiosis patients in the physiological, psychological, social and environmental fields were (10.40±2.31) , (11.40±2.82) , (11.46±3.03) and (8.38±3.37) respectively. The influencing factors of quality of life were pneumoconiosis stage, education level, economic income and smoking (P< 0.05) . Conclusion: The quality of life of migrant workers with pneumoconiosis is generally low. The main factors that affect the quality of life of patients are disease severity (pneumoconiosis stage) , education level, economic income and smoking.

LncRNA SNHG16 promotes cell proliferation through miR-302a-3p/FGF19 axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth common malignancies worldwide and the leading cause of death in Asian and African countries. Aberrant accumulation of lncRNAs is one of major causes of tumorigenesis in HCC. Small nucleolar RNA host gene 16 (SNHG16) is identified as an oncogene in multiple types of tumor. However, the role of SNHG16 in HCC is poor understood. Here, we showed that SNG16 was up-regulated and associated with poor prognosis in HCC. Then, we demonstrated that SNHG16 interacted with miR-302a-3p and depressed its expression. Moreover, our result indicated that SNHG16/miR-302a-3p axis regulated the expression of FGF19 in liver cancer cells. Finally, we investigated the biological function of SNHG16 in HCC and showed that SNHG16 promoted liver cancer cells proliferation via the SNHG16/miR-302a-3p/FGF19 axis. Collectively, these data suggest that SNHG16 might be a predictive biomarker and a potential therapeutic target of liver cancer.

Experimental demonstration of high sensitivity refractive index sensing based on magnetic plasmons in a simple metallic deep nanogroove array.

A high-performance wide-angle refractive index sensor based on a simple one-dimensional (1D) metallic deep nanogroove array with a high aspect ratio is experimentally fabricated and demonstrated. The 1D deep groove array is featured by the excitation of magnetic plasmon (MP), referring to an effective coupling of incident electromagnetic waves with a strong magnetic response induced inside the deep grooves. Utilizing the MP resonances that are extremely sensitive to the surrounding dielectric medium, we successfully achieve a refractive index sensitivity (RIS) up to ∼1300 nm/RIU, which is higher than that of most experimentally designed plasmonic sensors in the infrared region. Importantly, benefiting from angle-independent MP resonances with strong confinement of the magnetic field inside the deep grooves and strong electric field localization at the groove openings, we demonstrate wide-angle sensing capability valid in a broadband infrared region with an excellent linear dependence on the change of refractive index. Such a MP-based sensor, together with its simple 1D flat nature and ease of fabrication, has great potential for the practical design of high sensitive, cost-effective and compact sensing devices.

[Relationship between FGF23/FGFR4 expression in atrial tissue and atrial fibrosis in patients with atrial fibrillation].

Objective: To observe the expression of fibroblast growth factor 23 (FGF23) and FGFR4 in patients with atrial fibrillation (AF) and its relationship with atrial fibrosis. Methods: Fifty-one patients with rheumatic heart disease undergoing cardiac surgery at the Second Affiliated Hospital of Nanchang University from October 2016 to April 2017 were divided into two groups according to whether they were complicated with atrial fibrillation: 39 patients with persistent AF(AF group), and 12 patients with sinus rhythm (SR group). The right atrial appendage was cut out during cardiac surgery. The expression of FGF23 and FGFR4 mRNA was detected by quantitative real-time PCR. The expression of FGFR4 protein was detected by Western blot. Atrial structure was evaluated by echocardiography. Masson staining was used to evaluate the degree of atrial fibrosis. The expression of FGF23 and FGFR4 was compared between the two groups.Additionally, the relationship between FGF23 and FGFR4 expression and atrial fibrosis was evaluated. Results: AF group had significantly higher right and left atrial diameter than SR group((40.1±1.6 )mm vs (34.1±1.5)mm, (52.4±2.9)mm vs (41.3±2.4)mm, all P<0.05) . There were no statistically significant differences in age, gender, ejection fraction between the two groups. The expression of FGF23 and FGFR4 mRNA in AF group were significantly higher than those in SR group (1.93±0.32 vs 0.93±0.14, 1.89±0.17 vs 0.91±0.11, both P<0.05). Compared with the SR group, the protein expression of FGFR4 in the AF group was significantly higher(1.76±0.21 vs 0.84±0.12). In AF group, there was no correlation between FGF23 mRNA and atrial diameter (r=0.274 (left atrial), r=0.238 (right atrium), both P>0.05). Meanwhile, FGFR4 mRNA and protein expression had no correlation with atrial diameter either. There was positive correlation between FGF23 mRNA and atrial collagen volume fraction in AF group (r=0.42, P<0.05). The expression of FGFR4 mRNA and protein were positively correlated with the atrial collagen volume fraction (r=0.573, r=0.478, all P<0.05). Conclusion: The expression of FGF23 and FGFR4 in atrial fibrillation patients is increased, which is positively correlated with atrial fibrosis, suggesting that FGF23/FGFR4 pathway may play an important role in atrial fibrillation by promoting atrial fibrosis.

Main-Ion Intrinsic Toroidal Rotation Profile Driven by Residual Stress Torque from Ion Temperature Gradient Turbulence in the DIII-D Tokamak.

Intrinsic toroidal rotation of the deuterium main ions in the core of the DIII-D tokamak is observed to transition from flat to hollow, forming an off-axis peak, above a threshold level of direct electron heating. Nonlinear gyrokinetic simulations show that the residual stress associated with electrostatic ion temperature gradient turbulence possesses the correct radial location and stress structure to cause the observed hollow rotation profile. Residual stress momentum flux in the gyrokinetic simulations is balanced by turbulent momentum diffusion, with negligible contributions from turbulent pinch. The prediction of the velocity profile by integrating the momentum balance equation produces a rotation profile that qualitatively and quantitatively agrees with the measured main-ion profile, demonstrating that fluctuation-induced residual stress can drive the observed intrinsic velocity profile.

TRIM59 is a key regulator of growth and migration inrenal cell carcinoma.

Renal cell carcinoma (RCC) is the most common renal neoplasms and metastatic is common. Previous data have shown that the tripartite motif (TRIM) family proteinswere implicated in human tumoriogenesis. In this study, we aimed to investigate the role of TRIM59 in the cell growth and migration in RCC. The expression of TRIM59 in human RCC tissues was initially examined by qRT-PCR. Alentivirus-based shRNA against TRIM59 (Lv-shTRIM59) was constructed. The effects of TRIM59 knockdown on cell proliferation were examined by in vitro MTT assay, colony formation assay and in vivo a mouse xenograft model of RCC. Cell migration and invasion after knockdown of TRIM59 were also examined by transwell assay. Our data showed that the mRNA level of TRIM59 in cancerous tissues was 2-fold increased as compared with non-cancerous tissues. Knockdown of TRIM59 in a RCC cell line 786-O significantly slowed down cell proliferative rate and decreased both the colony number and sizes. In the mouse model, knockdown of TRIM59 consistently inhibited tumor growth in vivo. Moreover, it was shown that cell migration and invasion were suppressed by 68% and 50%, respectively in TRIM59-depleted 786-O cells. Our data suggest that TRIM59 may serve as a pro-oncogenic protein in promoting the progression of RCC. Knockdown of TRIM59 may be a promising strategy concerning the early detection and treatment of RCC.

Molecular characterization, expression analysis and RNAi knock-down of elongation factor 1α and 1γ from Nilaparvata lugens and its yeast-like symbiont.

In the present paper, four cDNAs encoding the alpha and gamma subunits of elongation factor 1 (EF-1) were cloned and sequenced from Nilaparvata lugens, named NlEF-1α, NlEF-1γ, and its yeast-like symbiont (YLS), named YsEF-1α and YsEF-1γ, respectively. Comparisons with sequences from other species indicated a greater conservation for EF-1α than for EF-1γ. NlEF-1α has two identical copies. The deduced amino acid sequence homology of NlEF-1α and NlEF-1γ is 96 and 64%, respectively, compared with Homalodisca vitripennis and Locusta migratoria. The deduced amino acid sequence homology of YsEF-1α and YsEF-1γ is 96 and 74%, respectively, compared with Metarhizium anisopliae and Ophiocordyceps sinensis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the expression level of NlEF-1α and NlEF-1γ mRNA in hemolymph, ovary, fat body and salivary glands were higher than the midgut and leg tissue. YsEF-1α and YsEF-1γ was highly expressed in fat body. The expression level of NlEF-1α was higher than that of NlEF-1γ. Through RNA interference (RNAi) of the two genes, the mortality of nymph reached 92.2% at the 11th day after treatment and the ovarian development was severely hindered. The RT-qPCR analysis verified the correlation between mortality, sterility and the down-regulation of the target genes. The expression and synthesis of vitellogenin (Vg) protein in insects injected with NlEF-1α and NlEF-1γ double-stranded RNA (dsRNA) was significantly lower than control groups. Attempts to knockdown the YsEF-1 genes in the YLS was unsuccessful. However, the phenotype of N. lugens injected with YsEF-1α dsRNA was the same as that injected with NlEF-1α dsRNA, possibly due to the high similarity (up to 71.9%) in the nucleotide sequences between NlEF-1α and YsEF-1α. We demonstrated that partial silencing of NlEF-1α and NlEF-1γ genes caused lethal and sterility effect on N. lugens. NlEF-1γ shares low identity with that of other insects and therefore it could be a potential target for RNAi-based pest management.

The effect of continuous perfusion of esmolol on cardiovascular risk in elderly patients undergoing noncardiac surgery.

We evaluated the effect of continuous perfusion of esmolol on cardiovascular risk during curative laparoscopic surgery for gastrointestinal cancer in elderly patients. Sixty patients with gastrointestinal cancer, aged from 60 to 80 years, were divided into an esmolol group (ES, n = 30) and a control group (NS, n = 30). ES patients were treated with esmolol at a dose of 0.3 mg/kg 3 min before tracheal intubation, and received continuous perfusion of esmolol at a dose of 50 µg/kg/min during operation. In NS, esmolol was replaced by saline. SBP/DBP, MAP, HR, SPO2, PETCO2, the depth of anesthesia and the value of RPP were recorded before anesthesia (T0), during intubation (T1), 10 min before pneumoperitoneum (T2), during pneumoperitoneum (T3), 30 min after incision (T4), at the end of surgery (T5), during extubation (T6) and 30 min after extubation (T7). The serum levels of cTnI, CK, CK-MB and LDH were measured before anesthesia, 6 and 30 h after surgery. HR, MAP, RPP at T1, T3, T6 in ES were obviously decreased compared with NS (P < 0.05). There were no significant differences between both groups at different time points with respects to the serum levels of cTnI, CK, CK-MB and LDH. No major adverse cardiocerebral event was observed in both groups in three postoperative months. The present study indicated that the application of esmolol during curative laparoscopic surgery for gastrointestinal cancer can effectively reduce the cardiovascular responses in intubation, operation and extubation, sustain hemodynamic stable, reduce myocardial oxygen consumption, and prevent perioperative adverse cardiovascular events, but had no significant myocardial protective effect.