Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement is a procedure that can effectively treat complications of portal hypertension, such as variceal bleeding and refractory ascites. However, there have been no specific studies on predicting long-term survival after TIPS placement. AIM: To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS. METHODS: A retrospective analysis was conducted on a cohort of 224 patients who underwent TIPS implantation. Through univariate and multivariate Cox regression analyses, various factors were examined for their ability to predict survival at 6 years after TIPS. Consequently, a composite score was formulated, encompassing the indication, shunt reasonability, portal venous pressure gradient (PPG) after TIPS, percentage decrease in portal venous pressure (PVP), indocyanine green retention rate at 15 min (ICGR15) and total bilirubin (Tbil) level. Furthermore, the performance of the newly developed Cox (NDC) model was evaluated in an internal validation cohort and compared with that of a series of existing models. RESULTS: The indication (variceal bleeding or ascites), shunt reasonability (reasonable or unreasonable), ICGR15, postoperative PPG, percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement. The NDC model incorporated these parameters and successfully identified patients at high risk, exhibiting a notably elevated mortality rate following the TIPS procedure, as observed in both the training and validation cohorts. Additionally, in terms of predicting the long-term survival rate, the performance of the NDC model was significantly better than that of the other four models [Child-Pugh, model for end-stage liver disease (MELD), MELD-sodium and the Freiburg index of post-TIPS survival]. CONCLUSION: The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis, help identify high-risk patients and guide follow-up management after TIPS implantation.

Research on the relationship between CEO career variety, digital knowledge base extension, and digital transformation in the context of digital merger and acquisition: The case of China's new generation of information technology firms.

This study examines the relationship between CEO career variety, digital knowledge base extension, and digital transformation in a digital M&A context. An empirical test was conducted using regression analysis with the digital M&A events of the new generation of information technology firms in China as the research sample. The results reveal that CEO career variety has a positive effect on digital transformation in the digital M&A context and that digital knowledge-base extension plays a mediating role. Moreover, the heterogeneity impact analysis indicated that the moderating effects of geographical distance, knowledge disparity, and cultural difference between target and acquirer firms on the above relationships vary greatly: geographical distance has a negative moderating effect, cultural difference has a positive moderating effect, and the moderating effects of both geographical distance and cultural difference are realized through mediating effects, but none of the moderating effects of knowledge disparity are significant.

Evaluation and screening of technology start-ups based on PCA and GA-BPNN.

PURPOSE: Due to the existence of information opacity, there is a common problem of adverse selection in the process of screening alternative technology start-ups (TSs) and determining investment targets by venture capital institutions, which does not reveal the true value of enterprises and makes the market inefficient. The aim of this paper is to design an evaluation and screening system help venture capital institutions to select the qualified TSs as their investment objective. DESIGN: A research framework of four dimensions that include conception, technical innovation, business model and team structure, was built based on previous studies. Based on the research framework, 15 second-level indicators and 33 third-level indicators were extracted with literature research method. This paper proposes an evaluation model with back propagation neural network (BPNN) optimized by genetic algorithm (GA) to improve the rate of selecting and investing in qualified start-ups. FINDINGS: The results show that the evaluation accuracy of the evaluation model for qualified and unqualified enterprises can reach 80.33% and 93.67% respectively, which has verified the effectiveness of the model and algorithm. ORIGINALITY/VALUE: This paper established an effective evaluation system based on PCA and GA-BPNN to help venture capital institutions preliminarily screen potential technology start-ups, which provides the possibility for venture capital institutions to greatly reduce the screening time and cost, improve the screening efficiency of TSs, and scientifically assess the risk of investee projects or investee enterprises to obtain sustainable and stable excess profits.

A novel nomogram predicting overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in portal hypertension patients.

We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 min (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n = 207) and a validation cohort (n = 89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child-Pugh and MELD scoring model. Age (OR 1.036, 95% CI 1.002-1.070, p = 0.037), Creatinine (OR 1.011, 95% CI 1.003-1.019, p = 0.009), Blood ammonia (OR 1.025, 95% CI 1.006-1.044, p = 0.011), ICG-R15 (OR 1.030, 95% CI 1.009-1.052, p = 0.004) and Percentage decline in PPG (OR 1.068, 95% CI 1.029-1.109, p = 0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child-Pugh and MELD score, this new nomogram has a better predictive value (C-index = 0.828, 95% CI 0.761-0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

Development and validation of an online calculator to predict the pathological nature of colorectal tumors.

BACKGROUND: No single endoscopic feature can reliably predict the pathological nature of colorectal tumors (CRTs). AIM: To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy. METHODS: This was a single-center study. During the identification stage, 530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group. Logistic regression analysis was performed. A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally. During the validation stage, two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists [five highly experienced endoscopists and five less experienced endoscopists (LEEs)] for external validation before and after systematic training. RESULTS: A total of 750 patients were included, with an average age of 63.6 ± 10.4 years. Early colorectal cancer (ECRC) was detected in 351 (46.8%) patients. Tumor size, left semicolon site, rectal site, acanthosis, depression and an uneven surface were independent risk factors for ECRC. The C-index of the ECRC calculator prediction model was 0.906 (P = 0.225, Hosmer-Lemeshow test). For the LEEs, significant improvement was made in the sensitivity, specificity and accuracy (57.6% vs 75.5%; 72.3% vs 82.4%; 64.2% vs 80.2%; P < 0.05), respectively, after training with the ECRC online calculator prediction model. CONCLUSION: A novel online calculator including tumor size, location, acanthosis, depression, and uneven surface can accurately predict the pathological nature of ECRC.

Innovative angiography: a new approach to discover more hepatic vein collaterals in patients with cirrhotic portal hypertension.

BACKGROUND: The hemodynamics of patients with cirrhosis and portal hypertension are complex and variable. We aimed to investigate differences in venous pressures determined by innovative angiography and conventional angiography using balloon occlusion of the hepatic veins in patients with alcoholic cirrhosis and portal hypertension. METHODS: A total of 134 patients with alcoholic cirrhosis who fulfilled the inclusion criteria from June 2017 to June 2020 were included. During transjugular intrahepatic portosystemic shunt, conventional and innovative angiography were performed, and venous pressures were measured. A paired t-test and Pearson's correlation coefficient were used for analysis. RESULTS: Conventional and innovative hepatic angiography detected lateral branches of the hepatic vein in 26 (19.4%) and 65 (48.5%) cases, respectively (P < 0.001). Innovative angiography detected a total of 65 patients with lateral shunts, of whom 37 (56.9%) had initial shunts. The average wedged hepatic venous pressure and portal venous pressure of the initial lateral branches were 21.27 ± 6.66 and 35.84 ± 7.86 mmHg, respectively, with correlation and determination coefficients of 0.342 (P < 0.05) and 0.117, respectively. The mean hepatic venous pressure gradient and portal pressure gradient were 9.59 ± 7.64 and 26.86 ± 6.78 mmHg, respectively, with correlation and determination coefficients of 0.292 (P = 0.079) and 0.085, respectively. CONCLUSIONS: Innovative angiography reveals collateral branches of the hepatic veins more effectively than conventional angiography. Hepatic vein collateral branches are the primary factors leading to underestimation of wedged hepatic venous pressures and hepatic venous pressure gradients, with the initial hepatic vein collateral branches resulting in the most severe underestimations.

The impact of medical service on the return behavior: A city-level study in China.

Due to the constraints of the rural-urban household registration systems, the migrants of China currently receive varying degrees of medical services. The fact that many migrants choose to return to their hometowns due to the inequality in medical care has been a social phenomenon. Using data from the 2017 China Migrant Dynamic Survey (CMDS), this paper explores the effect of medical services on population migration. Probit regression analysis method was utilized to examine the relationship between medical service level (MSL) and medical service improvement (MSI) and return behavior (RB), as well as the interaction effect between MSL and MSI, and the moderating effect of health status (HS) and health education (HE). Multiple heterogeneity tests were performed. Grouping regressions were conducted using rural household registration (RHR), grouping regressions were conducted using new rural cooperative medical system (NRCMS), and multinomial Probit regressions were conducted using migration distance and age factors. The following findings were obtained. First, when MSL is low but MSI is high in the locality of household registration, the return probability of migrants will increase. MSL also has a positive interaction effect with MSI, and they jointly increase the return probability of migrants; Second, HS and HE have a positive moderating effect on the relationships between MSL and RB and between MSI and RB; Third, heterogeneity analysis indicates that the migrants with RHR or the migrants not covered by the NRCMS are more prone to return due to the reason of medical service. In addition, the analysis also shows that middle-aged and older people who return across provinces have the highest tendency to return due to medical services and young people have the lowest propensity to return across and within provinces. The study could help local governments change their public medical care policies and close the gap between medical services in different areas. As a result, it is necessary to understand population migration trends and promote New Urbanization Strategies.

Endoscopic classification and pathological features of primary intestinal lymphangiectasia.

BACKGROUND: The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL). AIM: To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes. METHODS: We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type. RESULTS: According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers. CONCLUSION: Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension.

BACKGROUND: Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis (mPVTT) and cirrhotic portal hypertension (CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm. AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with radioactive seed strand for the treatment of mPVTT patients with CPH. METHODS: The clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data (success rate, relief of portal vein pressure and CPH symptoms, and adverse events), PVTT response, and patient survival were assessed through a 2-year follow-up. RESULTS: The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure (22.25 ± 7.33 mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo (range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%, and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo (95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage, and PVTT response were independent prognostic factors (P < 0.05). CONCLUSION: TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.

Correlation between hepatic venous pressure gradient and portal venous pressure gradient in hepatitis B cirrhosis with different hepatic veins anatomy.

PURPOSE: The hepatic venous pressure gradient (HVPG) has been employed as the gold standard for indicating the portal venous pressure gradient (PPG) in the diagnosis of portal hypertension (PHT). However, little has been reported on whether the HVPG can accurately estimate the PPG in patients with hepatic vein collateral shunts. We aimed to explore the correlation between the HVPG and the PPG in hepatitis B cirrhosis patients with different hepatic vein anatomies. METHODS: A total of 461 hepatitis B cirrhosis patients with portal hypertension (PHT) who were treated with a transjugular intrahepatic portosystemic shunt (TIPS) between January 2016 and June 2020 were included. All patients underwent various venous pressure measurements and balloon-occluded compression hepatic venography during the TIPS operation. Agreements were evaluated by Pearson's correlation and the Bland-Altman method. Disagreements were assessed by paired t tests. RESULTS: The correlation coefficient (r) values (P < 0.001) between the HVPG and the PPG of the early (151 patients, 32.8 %), middle (73 patients, 15.8 %), late (46 patients, 10.0 %), portal vein (151 patients, 32.8 %), and no lateral branch development groups (40 patients, 8.7 %) were 0.373, 0.487, 0.569, 0.690, and 0.575, respectively; the determination coefficient (R2) values were 0.139, 0.238, 0.323, 0.475, and 0.330, respectively. According to the Bland-Altman method, agreement was the greatest in the portal vein development group, with the 95 % limits of agreement (95 % LoA, mean differences ± 1.96 SD) being the smallest. The differences were statistically significant (P < 0.05). CONCLUSION: The correlation between the HVPG and the PPG is the worst in early lateral branch development, followed by middle development, and the influence of lateral branches becomes significantly reduced in late development. Hepatic venous collateral formation is a vital factor for underestimation of the HVPG, which is the most accurate predictor of PPG in patients with portal vein development. Patients with no collateral channel development in the hepatic vein have a higher HVPG than PPG, which is an important reason for overestimation of the HVPG.

SFedChain: blockchain-based federated learning scheme for secure data sharing in distributed energy storage networks.

The intelligence of energy storage devices has led to a sharp increase in the amount of detection data generated. Data sharing among distributed energy storage networks can realize collaborative control and comprehensive analysis, which effectively improves the clustering and intelligence. However, data security problems have become the main obstacle for energy storage devices to share data for joint modeling and analysis. The security issues caused by information leakage far outweigh property losses. In this article, we first proposed a blockchain-based machine learning scheme for secure data sharing in distributed energy storage networks. Then, we formulated the data sharing problem into a machine-learning problem by incorporating secure federated learning. Innovative verification methods and consensus mechanisms were used to encourage participants to act honestly, and to use well-designed incentive mechanisms to ensure the sustainable and stable operation of the system. We implemented the scheme of SFedChain and experimented on real datasets with different settings. The numerical results show that SFedChain is promising.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient.

BACKGROUND: The liver is one of the most important organs in the human body, with functions such as detoxification, digestion, and blood coagulation. In terms of vascular anatomy, the liver is divided into the left and the right liver by the main portal vein, and there are three hepatic efferent veins (right, middle, and left) and two portal branches. Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation, which may lead to an increase in the portal pressure gradient (PPG) and cause portal hypertension (PHT). In order to measure the increased pressure gradient of portal vein, the hepatic venous pressure gradient (HVPG) can be measured to reflect it in clinical practice. The accuracy of PPG measurements is directly related to patient prognosis. AIM: To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT. METHODS: From January 2017 to December 2019, 102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed. RESULTS: The mean HVPG of the middle hepatic vein was 17.47 ± 10.25 mmHg, and the mean HVPG of the right and left hepatic veins was 16.34 ± 7.60 and 16.52 ± 8.15 mmHg, respectively. The average PPG was 26.03 ± 9.24 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.15 and 0.02 (P = 0.164); 0.25 and 0.05 (P = 0.013); and 0.14 and 0.02 (P = 0.013), respectively. The mean wedged hepatic vein/venous pressure (WHVP) of the middle and left hepatic veins was similar at 29.71 ± 12.48 and 29.1 ± 10.91 mmHg, respectively, and the mean WHVP of the right hepatic vein was slightly lower at 28.01 ± 8.95 mmHg. The mean portal vein pressure was 34.11 ± 8.56 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.26 and 0.07 (P = 0.009); 0.38 and 0.15 (P < 0.001); and 0.26 and 0.07 (P = 0.008), respectively. The average free hepatic venous pressure (FHVP) of the right hepatic vein was lowest at 11.67 ± 5.34 mmHg, and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19 ± 4.88 and 11.67 ± 5.34 mmHg, respectively. The average inferior vena cava pressure was 8.27 ± 4.04 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.30 and 0.09 (P = 0.002); 0.18 and 0.03 (P = 0.078); and 0.16 and 0.03 (P = 0.111), respectively. CONCLUSION: Measurement of the middle hepatic vein HVPG could better represent PPG. Considering the high success rate of clinical measurement of the right hepatic vein, it can be the second choice.

Cross Inhibition of MPK10 and WRKY10 Participating in the Growth of Endosperm in Arabidopsis thaliana.

The product of double fertilization produces seed, which contains three components: triploid endosperm, diploid embryo, and maternal seed coat. Amongst them, the endosperm plays a crucial role in coordinating seed growth. Mitogen-activated protein kinase (MAPK) cascades are conserved in eukaryotes and involved in signal transduction of plant development. MPK3, MPK6, and MPK10 form a small group of MPKs family in Arabidopsis thaliana. MPK3 and MPK6 are extensively studied and were found to be involved in diverse processes including plant reproduction. However, less is known about the function of MPK10. Here, we found WRKY10/MINI3, a member of HAIKU (IKU) pathway engaging in endosperm development, and MPK10 is high-specifically expressed in the early developmental endosperm but with opposite gradients. We further proved that MPK10 and WRKY10 cross-inhibit the expression of each other. The inhibition effect of MPK10 on gene expression of WRKY10 and the downstream targets is supported by the fact that MPK10 interacts with WRKY10 and suppresses the transcriptional activity of WRKY10. Constantly, mpk10 mutants produce big seeds while WRKY10/MINI3 positively regulate seed growth. Altogether, our data provides a model of WRKY10 and MPK10 regulating endosperm development with a unique cross inhibitory mechanism.

Cryptococcosis caused by cryptococcus gattii: 2 case reports and literature review.

Cryptococcosis caused by Cryptococcus gattii, is a life threatening fungal infection with recently increasing prevalence. C. gattii is a species complex comprising multiple independent species. However, many biological characteristics and clinical features of cryptococcosis due to C. gattii are relatively less well defined. In this paper, we identify two cases of C. gattii infection, and laboratory findings of genotype VGI and VGII in two groups of apparently immunocompetent Chinese individuals respectively. Upon detailed review of all 35 cases of C. gattii infections, it was observed that C. gattii can cause debilitating illness in both immunocompetent and immunocompromised individuals. Cryptococcosis due to C. gattii is a serious systemic fungal infection, with pulmonary central nervous system tropism. Epidemiologically, C. gattii infection is not only restricted in tropical and subtropical regions, but also in other geographical settings.

Mass spectrum analysis of membrane proteins reveals that CASK, CD36 and EPB42 are differentially expressed in pancreatic adenocarcinoma.

Pancreatic cancer is one of the most life-threatening malignancies worldwide. Despite advances in checkpoint immunotherapy for patients with cancer, the current immunotherapies have demonstrated limited benefits for the treatment of pancreatic cancer. Apart from the intricate microenvironments that restrict T-cell function, membrane proteins other than programmed death-ligand 1 may also facilitate immune escape of tumor cells. The present study investigated the membrane proteins of seven paired pancreatic adenocarcinoma (PAAD) and adjacent normal tissues with mass spectrometry, and identified 10 up-and eight downregulated membrane proteins in PAAD. Together with the online database analysis, the results showed that the CASK protein was upregulated in PAAD samples and cell lines, and predicts poor outcomes in patients with PAAD. Furthermore, the results exhibited downregulated CD36 and EPB42 in PAAD samples and cell lines, and higher levels of CD36. EPB42 was shown to predict improved survival outcomes in patients with PAAD. Overall, the results of the present study revealed PAAD-specific membrane proteins as potential diagnostic markers and drug-targets for the immunotherapy of pancreatic cancer.

Catalog of Lung Cancer Gene Mutations Among Chinese Patients.

Background: Detailed catalog of lung cancer-associated gene mutations provides valuable information for lung cancer diagnosis and treatment. In China, there has never been a wide-ranging study cataloging lung cancer-associated gene mutations. This study aims to reveal a comprehensive catalog of lung cancer gene mutations in china, focusing on EGFR, ALK, KRAS, HER2, PIK3CA, MET, BRAF, HRAS, and CTNNB1 as major targets. Additionally, we also aim to correlate smoking history, gender, and age distribution and pathological types with various types of gene mutations. Patients and Methods: A retrospective data acquisition was conducted spanning 6 years (2013-2018) among all patients who underwent lung cancer surgeries not bronchial or percutaneous lung biopsy at three major tertiary hospitals. Finally, we identified 1,729 patients who matched our inclusion criteria. Results: 1081 patients (62.49%) harbored EGFR mutation. ALK (n = 42, 2.43%), KRAS (n = 201, 11.62%), CTNNB1 (n = 28, 1.62%), BRAF (n = 31, 1.79%), PIK3CA (n = 51, 2.95%), MET (n = 14, 0.81%), HER2 (n = 47, 2.72%), HRAS (n = 3, 0.17%), and other genes(n = 232, 13.4%). Females expressed 55.38% vs. males 44.62% mutations. Among subjects with known smoking histories, 32.82% smokers, 67.15% non-smokers were observed. Generally, 51.80% patients were above 60 years vs. 48.20% in younger patients. Pathological types found includes LUADs 71.11%, SQCCs 1.68%, ASC 0.75%, LCC 0.58%, SCC 0.35%, ACC 0.17%, and SC 0.06%, unclear 25.19%. Conclusion: We offer a detailed catalog of the distribution of lung cancer mutations. Showing how gender, smoking history, age, and pathological types are significantly related to the prevalence of lung cancer in China.

Global liver disease burdens and research trends: Analysis from a Chinese perspective.

Liver diseases affect millions of people worldwide. In most developed countries, the incidence of viral hepatitis is waning as a result of modern advances in disease prevention, diagnosis, and therapies. Expanded programmes for systematic immunisation against hepatitis B virus have also significantly brought down the number of new cases in many countries, including China. In contrast, with the improvement in living standards, the prevalence of metabolic liver diseases including non-alcoholic fatty liver disease and alcohol-related liver disease is set to rise, ultimately leading to more cases of end-stage liver diseases (liver failure, cirrhosis, and liver cancer). Over the past 30 years, visionary governments of major nations have provided strong incentives for basic/clinical research, vaccination programmes, and drug discovery and development in the field of hepatology. To get rid of her unflattering title as the "leader in liver diseases", China has also made a serious effort to initiate nationwide preventive measures for liver diseases, global partnerships, and mentoring programmes for young hepatologists. Instrumental to such progress is the continuous support of the National Natural Science Foundation of China (NSFC), which has helped hepatology to thrive in virtually all research directions within the country. In this article, we seek to provide stimulating glimpses into the evolving liver disease epidemiology, institutional research profiles, funding landscape, and drug development trends in China, with an attempt to compare her status and achievements with those of the United States, European countries, and Japan.

MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN.

Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.

Bone marrow stromal cells induced activation of nuclear factor κB signaling protects non-Hodgkin's B lymphoma cells from apoptosis.

The microenvironment encompassing a variety of non-malignant cells in close proximity with malignant tumor cells has been well known to significantly affect the behavior of tumor cells. In this study, we therefore studied the mechanism of bone marrow stromal cells in protection of lymphoma cells from spontaneous apoptosis. We demonstrated that adhesion of the freshly isolated lymphoma B cells to bone marrow stromal cells or freshly isolated lymphoma stromal cells inhibited B cell spontaneous apoptosis in culture. This inhibition of apoptosis correlated with decreased cleavage of caspase-3/8 and increased activation of canonical and non-canonical NF-κB signaling pathway. In addition to BAFF signaling which has been reported as a functional determinant for B lymphoma cell survival in the bone marrow environment, we demonstrated RANKL from BMSCs works synergistically with BAFF to activate NF-κB signaling pathway and thus protects lymphoma B cells from spontaneous apoptosis.