Lysyl hydroxylase LH1 promotes confined migration and metastasis of cancer cells by stabilizing Septin2 to enhance actin network.

BACKGROUND: Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors such as hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). These conditions create confined spaces for tumor cell migration and metastasis. The regulatory mechanism of confined migration remains unclear. METHODS: LC-MS was applied to determine the differentially expressed proteins between HCC tissues and corresponding adjacent tissue. Collective migration and single cell migration microfluidic devices with 6 µm-high confined channels were designed and fabricated to mimic the in vivo confined space. 3D invasion assay was created by Matrigel and Collagen I mixture treat to adherent cells. 3D spheroid formation under various stiffness environment was developed by different substitution percentage GelMA. Immunoprecipitation was performed to pull down the LH1-binding proteins, which were identified by LC-MS. Immunofluorescent staining, FRET, RT-PCR, Western blotting, FRAP, CCK-8, transwell cell migration, wound healing, orthotopic liver injection mouse model and in vivo imaging were used to evaluate the target expression and cellular phenotype. RESULTS: Lysyl hydroxylase 1 (LH1) promoted the confined migration of cancer cells at both collective and single cell levels. In addition, LH1 enhanced cell invasion in a 3D biomimetic model and spheroid formation in stiffer environments. High LH1 expression correlated with poor prognosis of both HCC and PDAC patients, while it also promoted in vivo metastasis. Mechanistically, LH1 bound and stabilized Septin2 (SEPT2) to enhance actin polymerization, depending on the hydroxylase domain. Finally, the subpopulation with high expression of both LH1 and SEPT2 had the poorest prognosis. CONCLUSIONS: LH1 promotes the confined migration and metastasis of cancer cells by stabilizing SEPT2 and thus facilitating actin polymerization.

Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma.

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.

Classification and survival prediction in early-stage cirrhosis by gene expression profiling.

Liver cirrhosis has been increasingly diagnosed at an early stage owing to the non-invasive diagnostic techniques. However, it is difficult to identify patients at high risk of disease progression. Screening cirrhotic patients with poor prognosis who are most in need of surveillance is still challenging. Gene expression data GSE15654 and GSE14520 were downloaded for performing unsupervised clustering analysis. The prognostic differences between the different clusters were explored by Cox regression. Integrative analysis of gene expression signature, immune cell enrichments and clinical characterization was performed for different clusters. Two distinctive subclasses were identified in HCV-related GSE15654, and Kaplan-Meier analysis indicated that subtype 2 had lower survival rates than subtype 1 (p = 0.0399). Further analysis revealed subtype 2 had a higher density of follicular T helper cells, resting natural killer cells and M0, M2 macrophages while subtype 1 with a higher fraction of naive B cells, memory B cells, resting memory CD 4 T cells, activated natural killer cells and monocytes. 226 differentially expressed genes were identified between the two subtypes, and Reactome analysis showed the mainly enriched pathways were biological oxidations and fatty acid metabolism. Five hub genes (AKT1, RPS16, CDC42, CCND1 and PCBP2) and three significant modules were extracted from the PPI network. The results were validated in HBV-related GSE14520 cohort. We identified two subtypes of patients with different prognosis for hepatitis C-related early-stage liver cirrhosis. Bioinformatics analysis of the gene expression and immune cell profile may provide fresh insight into understanding the prognosis difference.

Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a malignant renal tumor that is highly prone to metastasis and recurrence. The exact pathogenesis of this cancer is still not well understood. This study aimed to identify novel hub genes in renal clear cell carcinoma and determine their diagnostic and prognostic value. METHODS: Intersection genes were obtained from multiple databases, and protein-protein interaction analysis and functional enrichment analysis were performed to identify key pathways related to the intersection genes. Hub genes were identified using the cytoHubba plugin in Cytoscape. GEPIA and UALCAN were utilized to observe differences in mRNA and protein expression of hub genes between KIRC and adjacent normal tissues. The Wilcoxon rank sum test was used to analyze hub gene levels between paired KIRC and matched non-cancer samples. IHC results were obtained from the HPA online database, and according to the median gene expression level, they were divided into a high-expression group and a low-expression group. The correlation of these groups with the prognosis of KIRC patients was analyzed. Logistic regression and the Wilcoxon rank sum test were used to test the relationship between SLC34A1 level and clinicopathological features. The diagnostic value of SLC34A1 was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Cox regression analysis was used to analyze the relationship between clinicopathological features, SLC34A1 expression, and KIRC survival rate. LinkedOmics was used to obtain the genes most related to SLC34A1 and their functional enrichment. Genetic mutations and methylation levels of SLC34A1 in KIRC were obtained from the cBioPortal website and the MethSurv website, respectively. RESULTS: Fifty-eight ccRCC differential genes were identified from six datasets, and they were mainly enriched in 10 functional items and 4 pathways. A total of 5 hub genes were identified. According to the GEPIA database analysis, low expression of SLC34A1, CASR, and ALDOB in tumors led to poor prognosis. Low expression of SLC34A1 mRNA was found to be related to clinicopathological features of patients. SLC34A1 expression in normal tissues could accurately identify tumors (AUC 0.776). SLC34A1 was also found to be an independent predictor of ccRCC in univariate and multivariate Cox analyses. The mutation rate of the SLC34A1 gene was 13%. Eight of the 10 DNA methylated CpG sites were associated with the prognosis of ccRCC. SLC34A1 expression in ccRCC was positively correlated with B cells, eosinophils, neutrophils, T cells, TFH, and Th17 cells, and negatively correlated with Tem, Tgd, and Th2 cells. CONCLUSION: The expression level of SLC34A1 in KIRC samples was found to be decreased, which predicted a decreased survival rate of KIRC. SLC34A1 may serve as a molecular prognostic marker and therapeutic target for KIRC patients.

New prediction equations for knee isokinetic strength in young and middle-aged non-athletes.

BACKGROUND: This study aimed to develop alternative prediction equations to predict isokinetic muscle strength at 60°/s based on anthropometric characteristics, including body mass, height, age, and sex for young and middle-aged non-athlete populations. METHODS: Three hundred and thirty-two healthy non-athletic participants (174 females, 158 males) between 20 and 59 years underwent a 60°/s isokinetic knee joint concentric contraction test. Forty people were randomly selected for retesting to assess the reliability of the isokinetic instrument. Multivariate linear regression was used to establish extension peak torque (EPT) and flexion peak torque (FPT) prediction equations. Sixty extra participants were used individually to validate the prediction equations, and Bland Altman plots were constructed to assess the agreement of predicted values with actual measurements. RESULTS: The result demonstrated that the instrument we used has excellent reliability. The multivariable linear regression model showed that body mass, age, and sex were significant predictors of PT (EPT: Adjusted R2 = 0.804, p < 0.001; FPT: Adjusted R2 = 0.705, p < 0.001). Furthermore, the equations we established had higher prediction accuracy than those of Gross et al. and Harbo et al. CONCLUSION: The equations developed in this study provided relatively low bias, thus providing a more suitable reference value for the knee isokinetic strength of young and middle-aged non-athletes.

Rapid oxidative removal of Fe2+ and Mn2+ from acidic mining wastewater by a new-type biofilter system: application and mechanism.

Aimed at the problem of excessive concentration of Fe2+ and Mn2+ in acidic mining wastewater during mining and utilization, a new rapid oxidative removal technology of Fe2+ and Mn2+ by a new-type biofilter system was designed and tested. The new-type biofilter system was constructed using a bioreactor filled with special mature bioceramic pellets after continuous biofilm cultivation as the filter layers. The results indicated that the biofilter system could efficiently treat five times its volume of wastewater per hour. The Fe2+ concentration of the influent wastewater was about 500 mg/L, and its Mn2+ concentration was about 20 mg/L. The average Fe2+ and Mn2+ removal rates could reach 99.7% and 90.8%, respectively. In addition, scanning electron microscopy and energy dispersive spectroscopy-energy dispersive spectroscopy and X-ray photoelectron spectroscopy were applied to analyze the migration distribution and valence change of Fe and Mn ions to clarify the removal mechanism of Fe2+ and Mn2+ using the biofilter system. The results showed that iron oxidation products were mainly coated at the surface of the mature bioceramic pellets and could be easily washed out from the filter layer with flowing water, while manganese oxidation products tended to accumulate between the pores of the mature bioceramic pellets. Furthermore, the final filtration products were multivalent complex oxides, indicating that the high-valent oxidation products could adsorb Fe and Mn ions, which were mainly removed by the oxidation effect.

New Class of Radially Adjustable Stentrievers for Acute Ischemic Stroke: Primary Results of the Multicenter TIGER Trial.

[Figure: see text].

Analysis of Differentially Expressed Novel MicroRNAs as Potential Biomarkers in Dengue Virus Type 1 Infection.

BACKGROUND: Host-derived miRNAs are reported to play diverse roles in dengue virus (DENV) infection, but DENV-derived miRNAs have been rarely studied. METHODS: Here, we used serum samples from three patients infected with dengue virus type 1 (DENV1) and three healthy volunteers to detect and profile novel microRNAs in dengue virus-infected human serum. MicroRNAs in serum samples were sequenced using an Illumina HiSeq 2000 system, and clean reads were trimmed, aligned, normalized, and analyzed to identify differentially expressed and novel microRNAs. Four microRNAs were selected as DENV1 infection biomarkers and verified through 1:2 paired case-control study, using serum from 15 DENV1-infected patients and 30 healthy volunteers. RESULTS: We identified 182 potential novel miRNAs, with 20 novel miRNAs found to have miRDeep2 score ≥ 4.0. Fifty-eight known and 11 novel miRNAs were upregulated at least 2-fold in DENV1-infected serum. Twenty-two known and 4 novel miRNAs were downregulated at least 0.5-fold. The AUCs of four selected miRNAs, hsa-miR-106b-3p, hsa-miR-122-5p, hsa-miR-novel-chr17_35150, and hsa-miR-novel-chr10_24390, were respectively: 0.962 (95% CI: 0.913 - 1.000, p > 0.05), 0.924 (95% CI: 0.851 - 0.998, p < 0.05), 0.941 (95% CI:0.877 - 1.000, p > 0.05), and 0.991 (95% CI: 0.973 - 1.000, p > 0.05). CONCLUSIONS: In summary, our study demonstrates that serum miRNA levels are affected by DENV1 infection, identifies novel DENV1-associated miRNAs, and suggests that Hsa-miR-122-5p may be a potential biomarker for DENV1 infection.

Intracranial Hemorrhage in COVID-19 Patients.

OBJECTIVE: To describe the clinical, laboratory, temporal, radiographic, and outcome features of acute Intracranial Hemorrhage (ICH) in COVID-19 patients. METHODS: Retrospective, observational, consecutive case series of patients admitted with ICH to Maimonides Medical Center from March 1 through July 31, 2020, who had confirmed or highly suspected COVID-19. Demographic, clinical, laboratory, imaging, and outcome data were analyzed. ICH rates among all strokes were compared to the same time period in 2019 in two-week time intervals. Correlation of systolic blood pressure variability (SBPV) and neutrophil-to-lymphocyte ratio (NLR) to clinical outcomes were performed. RESULTS: Of 324 patients who presented with stroke, 65 (20%) were diagnosed with non-traumatic ICH: 8 had confirmed and 3 had highly suspected COVID-19. Nine (82%) had at least one associated risk factor for ICH. Three ICHs occurred during inpatient anticoagulation. More than half (6) suffered either deep or cerebellar hemorrhages; only 2 were lobar hemorrhages. Two of 8 patients with severe pneumonia survived. During the NYC COVID-19 peak period in April, ICH comprised the highest percentage of all strokes (40%), and then steadily decreased week-after-week (p = 0.02). SBPV and NLR were moderately and weakly positively correlated to discharge modified Rankin Scale, respectively. CONCLUSIONS: COVID-19 associated ICH is often associated with at least one known ICH risk factor and severe pneumonia. There was a suggestive relative surge in ICH among all stroke types during the first peak of the NYC pandemic. It is important to be vigilant of ICH as a possible and important manifestation of COVID-19.

Environmental impact and health risk assessment of volatile organic compound emissions during different seasons in Beijing.

Volatile organic compounds (VOCs) are major contributors to air pollution. Based on the emission characteristics of 99 VOCs that daily measured at 10 am in winter from 15 December 2015 to 17 January 2016 and in summer from 21 July to 25 August 2016 in Beijing, the environmental impact and health risk of VOC were assessed. In the winter polluted days, the secondary organic aerosol formation potential (SOAP) of VOC (199.70 ± 15.05 µg/m3) was significantly higher than that on other days. And aromatics were the primary contributor (98.03%) to the SOAP during the observation period. Additionally, the result of the ozone formation potential (OFP) showed that ethylene contributed the most to OFP in winter (26.00% and 27.64% on the normal and polluted days). In summer, however, acetaldehyde was the primary contributor to OFP (22.00% and 21.61% on the normal and polluted days). Simultaneously, study showed that hazard ratios and lifetime cancer risk values of acrolein, chloroform, benzene, 1,2-dichloroethane, acetaldehyde and 1,3-butadiene exceeded the thresholds established by USEPA, thereby presenting a health risk to the residents. Besides, the ratio of toluene-to-benzene indicated that vehicle exhausts were the main source of VOC pollution in Beijing. The ratio of m-/p-xylene-to-ethylbenzene demonstrated that there were more prominent atmospheric photochemical reactions in summer than that in winter. Finally, according to the potential source contribution function (PSCF) results, compared with local pollution sources, the spread of pollution from long-distance VOCs had a greater impact on Beijing.

Rare Meningitis and Epileptic Seizure Infected with Brucella melitensis: a Case Report.

BACKGROUND: Although brucellosis is the most common zoonotic disease worldwide, human meningitis infected with Brucella melitensis is rare and difficult to diagnosis. Herein we describe the clinical aspects of a rare case of Brucella melitensis meningitis accompanied by epileptic seizure. METHODS: Bacterial culture of CSF was utilized to find the pathogen. Serum and CSF agglutination tests were used to detect the capacity of Brucella antigen. Bacterial clone was identified by the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). Magnetic resonance imaging (MRI) was used to monitor the recovery changes for meningitis. RESULTS: The bacterial culture was positive for Brucella app. Antigen-antibody agglutination test was also positive with a titer more than 1/200. A reliable identification score of 2.8 for Brucella melitensis was obtained by MALDI-TOF. MRI showed obviously improved meningitis after therapy. CONCLUSIONS: The results of this study suggest the treatments for Brucella meningitis must be planned depending on the patient's clinical conditions and the laboratory identification of pathogen infection as early as possible.

Emission characteristics of 99 NMVOCs in different seasonal days and the relationship with air quality parameters in Beijing, China.

In recent years, the haze incidents have occurred frequently in China. Therefore, more attention should be taken in comprehensively determination and analysis of the extended-ranges of volatile organic compounds (VOCs). Here, up to 99 non-methane VOCs (NMVOCs), including not frequently reported partial halocarbons and oxygenated VOC (OVOC) species, were monitored in atmosphere of Beijing. The mean concentration of total NMVOC (TNMVOC) decreased in the order of winter polluted days (216.05 µg m-3) > summer polluted days (127.01 µg m-3) > summer normal days (95.63 µg m-3) > winter normal days (50.25 µg m-3). The ethane to n-butane, ethylene to 1-butene, BTEX, acetaldehyde, acetone, n-hexanal, dichloromethane, chloroform and 1,2-dichloroethane, were determined to be the main composition in their respective alkane, alkene, aromatic, OVOC and halocarbon classes. The minor propylbenzene, diethylbenzene, ethyltoluene, and trimethylbenzene isomer ratios were within the narrow range of 1.3-3.21. Generally, the most abundant NMVOCs were alkanes in winter but OVOCs in summer. TNMVOC significantly positively correlated with PM10, PM2.5, CO, RH, SO2 (winter), NO2 (winter), but negatively with windspeed, SSD and PRS (winter). The opposite correlation was observed between TNMVOC and O3 in winter and summer. There was no meaningful correlation between TNMVOC and T, PRS (summer), SO2 (summer) and NO2 (summer). 3D surface graphs, built by MATLAB, were drawn to investigate the relationship between PM2.5 and NMVOC taking air quality parameters into account. The PM2.5 concentration increased non-linearly as TNMVOC concentration increased, with various surface graphs. Unlike other air quality parameters, O3 affected the relationship differently between winter and summer. The findings presented herein may provide a new train of thought for occurrence of haze.

Cell-free lncRNA expression signatures in urine serve as novel non-invasive biomarkers for diagnosis and recurrence prediction of bladder cancer.

Cell-free long non-coding RNAs (lncRNAs) are stably present in urine and can serve as non-invasive biomarkers for cancer. We aimed to identify signatures of lncRNAs in urine for diagnosis and prognosis of bladder cancer (BC). Screening of lncRNAs by microarray analysis was performed using urine samples of 10 BC patients and 10 controls. Expressions of candidate lncRNAs were evaluated in the training and validation set including 230 BC patients and 230 controls by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A two-lncRNA panel (uc004cox.4 and GAS5) was constructed and provided high diagnostic accuracy of BC with an area under the curve (AUC) of 0.885 (95% CI, 0.836-0.924). The AUCs of the lncRNA panel for Ta, T1 and T2-T4 were 0.843, 0.867 and 0.923, respectively, significantly higher than those of urine cytology (all P < .05). Kaplan-Meier analysis revealed that higher level of uc004cox.4 was associated with poor recurrence-free survival (RFS) of non-muscle invasive BC (NMIBC) (P = .008). Additionally, Cox regression analysis indicated that uc004cox.4 was an independent prognostic factor for RFS of NMIBC (P = .018). Taken together, our findings indicated that urinary lncRNA signatures possessed potential clinical value for BC diagnosis. Moreover, uc004cox.4 could provide prognostic information for NMIBC.

Clinicopathological features and prognosis of familial papillary thyroid carcinoma--a large-scale, matched, case-control study.

OBJECTIVE: It remains controversial whether or not the aggressiveness of familial nonmedullary thyroid cancer (FNMTC) differs from sporadic carcinoma. The aim of this study was to determine the clinicopathological features and prognosis of FNMTC. DESIGN: A matched-case comparative study. METHODS: Three hundred and seventy-two patients with familial papillary thyroid carcinoma (FPTC) were enrolled as the study group, and another 372 patients with sporadic PTC were enrolled as controls and matched for gender, age, tumour/node/metastasis (TNM) staging and approximate duration of follow-up. We compared the differences in the clinicopathological features and prognosis between the subgroups. RESULTS: Compared with sporadic PTC, patients with FPTC were more likely to present tumour multicentricity, bilateral growth and a concomitant nodular goitre (P < 0·05). In papillary thyroid microcarcinoma (PTMC), a higher recurrence rate was noted in patients with a family history of PTC, and this remained independently predictive on multivariate analysis. The patients with FPTC in the second generation showed an earlier age of onset, more frequent Hashimoto's thyroiditis and a higher recurrence rate than the first generation, while the first-generation offspring of patients had a higher incidence of nodular goitre than the second generation. CONCLUSIONS: The presence of familial history in PTC indicates an increase in biological aggressiveness, and patients in the second generation may exhibit the 'genetic anticipation' phenomenon. At present, the available data are not sufficient to support a more aggressive approach for FPTC. However, a family history of PTC is an independent risk factor for recurrence in patients with PTMC.

Optimal staging system for predicting the prognosis of patients with hepatocellular carcinoma in China: a retrospective study.

BACKGROUND: Several staging systems have been developed to evaluate patients with hepatocellular carcinoma (HCC), including the China Staging System (CS), the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, and seventh edition; the Barcelona Clinic Liver Cancer (BCLC) staging system, and Cancer of the Liver Italian Program (CLIP) staging system. The optimal staging system for to evaluate patients in China with HCC has not been determined. This study was designed to determine the optimal staging system for predicting patient prognosis by comparing the performances of these four staging systems in a cohort of Chinese patients with HCC. METHODS: This study enrolled 307 consecutive Chinese patients with HCC in Shandong Province. The performances of the CS, TNM, BCLC, and CLIP staging systems were compared and ranked using a concordance index. Predictors of survival were identified using univariate and multivariate Cox model analyses. RESULTS: The mean overall survival of the patient cohort was 12.08 ± 11.87 months. Independent predictors of survival included tumor size, number of lesions, tumor thromboses, cirrhosis, serum albumin level and serum total bilirubin level. Compared with the other three staging systems, the CS staging system showed optimal performance as an independent predictor of patient survival. The BCLC staging system showed the poorest performance; its treatment algorithm was not suitable for patients in this study. CONCLUSIONS: CS was the most suitable staging system for predicting survival of patients with HCC in China.

Laparoscopic RFA with splenectomy for hepatocellular carcinoma.

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) is complicated and challenging because of the frequent presence of cirrhosis. Therefore, we propose a novel surgical approach to minimize the invasiveness and risk in patients with HCC, hypersplenism, and esophagogastric varices. METHODS: This was a retrospective study carried out in 25 patients with HCC and hypersplenism and who underwent simultaneous laparoscopic-guided radio-frequency ablation and laparoscopic splenectomy with endoscopic variceal ligation. Tumor size was restricted to a single nodule of <3 cm. Characteristics of the patients (cirrhosis etiology, liver function, tumor size, spleen size), surgery (complications, blood loss, time of stay), and follow-up (recurrence and survival) were examined. RESULTS: Mean operative time was 128 ± 18 min. Mean blood loss was 206 ± 57 mL. Length of stay was 7.0 ± 1.5 days. Mean total costs were 8064 USD. Cytopenia and thrombocytopenia recovered quickly after surgery. No procedure was converted to open surgery. Two patients showed worsening liver function after surgery, three patients showed worsening of ascites, and five patients suffered from portal vein thrombosis. The 1-year tumor-free survival was 78.8 %, and the 21-month tumor-free survival was 61.4 %. According to a literature review, these outcomes were comparable to those of simultaneous open hepatic resection and splenectomy. CONCLUSIONS: Laparoscopic-guided radio-frequency ablation with laparoscopic splenectomy and endoscopic variceal ligation could be an available technique for patients with HCC <3 cm, hypersplenism, and esophagogastric varices. This approach may help to minimize the surgical risks and results in a fast increase in platelet counts with an acceptable rate of complications.

Antitumor Effect of C21 Steroidal Glycosides on Adenoid Cystic Carcinoma Cell Line SACC83.

BACKGROUND: To observe the anti-tumor effects and possible mechanism of C21 steroidal glycoside (17-ß-Marsdenia tenacissima glycoside B (17-ß-tenacigenin B)) and Xiaoaiping injection in the adenoid cystic carcinoma cell line SACC83. METHODS: We used the salivary adenoid cystic carcinoma cell line SACC83 for the study and used MTT, flow cytometry, and Western-blot (WB) to study the anti-tumor efficacy and mechanism of 17-ß-tenacigenin B and Xiaoaiping injection. Three groups were divided as follows: group 1: control group (without drug treatment), group 2: SACC83 treated with 17-ß-Marsdenia tenacissima glycoside B, group 3: SACC83 treated with Xiaoaiping injec- tion. RESULTS: The 17-ß-tenacigenin B had no significant anti-tumor effect while the Xiaoaiping injection had a dosage-dependent growth inhibition effect on the adenoid cystic carcinoma cell line SACC83. According to WB, after the administration of the 17-p-tenacigenin B, the expression of apoptosis-related protein was not very significant; however, after the administration of the Xiaoaiping injection, the expression of apoptosis inhibition protein bcl-2 decreased while the expression of apoptosis promotion protein bax increased. CONCLUSIONS: The 17-ß-tenacigenin B had no obvious anti-tumor effects while the Xiaoaiping injection had good anti-tumor effects. Even though the 17-ß-tenacigenin B is an important component of the Xiaoaiping injection, in the in vitro experiment, compared with the Xiaoaiping injection, the 17-ß-tenacigenin B showed no good anti-tumor effects. However, we need further studies on in vivo experiments of 17-ß-tenacigenin B and the anti-tumor effect of other C21 steroidal glycoside monomers in the Xiaoaiping injection.

Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA.

The mRNA export complex TREX (TREX) is known to contain Aly, UAP56, Tex1 and the THO complex, among which UAP56 is required for TREX assembly. Here, we systematically investigated the role of each human TREX component in TREX assembly and its association with the mRNA. We found that Tex1 is essentially a subunit of the THO complex. Aly, THO and UAP56 are all required for assembly of TREX, in which Aly directly interacts with THO subunits Thoc2 and Thoc5. Both Aly and THO function in linking UAP56 to the cap-binding protein CBP80. Interestingly, association of UAP56 with the spliced mRNA, but not with the pre-mRNA, requires Aly and THO. Unexpectedly, we found that Aly and THO require each other to associate with the spliced mRNA. Consistent with these biochemical results, similar to Aly and UAP56, THO plays critical roles in mRNA export. Together, we propose that Aly, THO and UAP56 form a highly integrated unit to associate with the spliced mRNA and function in mRNA export.

[Logistic regression model of noninvasive prediction for portal hypertensive gastropathy in patients with hepatitis B associated cirrhosis].

OBJECTIVE: To explore the risk factors of portal hypertensive gastropathy (PHG) in patients with hepatitis B associated cirrhosis and establish a Logistic regression model of noninvasive prediction. METHODS: The clinical data of 234 hospitalized patients with hepatitis B associated cirrhosis from March 2012 to March 2014 were analyzed retrospectively. The dependent variable was the occurrence of PHG while the independent variables were screened by binary Logistic analysis. Multivariate Logistic regression was used for further analysis of significant noninvasive independent variables. Logistic regression model was established and odds ratio was calculated for each factor. The accuracy, sensitivity and specificity of model were evaluated by the curve of receiver operating characteristic (ROC). RESULTS: According to univariate Logistic regression, the risk factors included hepatic dysfunction, albumin (ALB), bilirubin (TB), prothrombin time (PT), platelet (PLT), white blood cell (WBC), portal vein diameter, spleen index, splenic vein diameter, diameter ratio, PLT to spleen volume ratio, esophageal varices (EV) and gastric varices (GV). Multivariate analysis showed that hepatic dysfunction (X1), TB (X2), PLT (X3) and splenic vein diameter (X4) were the major occurring factors for PHG. The established regression model was Logit P=-2.667+2.186X1-2.167X2+0.725X3+0.976X4. The accuracy of model for PHG was 79.1% with a sensitivity of 77.2% and a specificity of 80.8%. CONCLUSION: Hepatic dysfunction, TB, PLT and splenic vein diameter are risk factors for PHG and the noninvasive predicted Logistic regression model was Logit P=-2.667+2.186X1-2.167X2+0.725X3+0.976X4.