Gender and race disparities in the prevalence of chronic kidney disease among individuals with hypertension in the United States, 2001-2016.

Background: Chronic kidney disease (CKD) is a common complication among individuals with hypertension. We aimed to identify the prevalence of CKD and the sex and race disparities within the hypertensive population in the United States from 2001-2016. Methods: A total of 16,148 participants with hypertension were included, representing 561,909,480 individuals from the U.S. population between 2001 and 2016, as documented in the National Health and Nutrition Examination Survey. The prevalence of albuminuria and CKD stage were assessed using survey-weighted general linear regression analysis. Heterogeneity in the CKD stage among the hypertensive population, stratified by sex and race, was identified through survey-weighted logistic regression analysis. Results: Overall, the prevalence of albuminuria remained stable (p for trend = 0.3196), and changes in the CKD stage were minimal (p for trend > 0.05) from 2001-2016. In the analysis of CKD stage heterogeneity by sex and race, the prevalence of CKD was higher among women than men and higher among individuals of other races combined than non-Hispanic Whites, but the differences were not statistically significant. Conclusion: The overall CKD stage within the hypertensive population plateaued between 2001 and 2016. Our findings highlight the importance of continuous monitoring and potential refinement of renoprotection strategies in individuals with hypertension to mitigate the persistent burden of CKD and address health disparities among different demographic groups.

Comparison of drug-eluting bead with conventional transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: A randomized clinical trial.

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.

Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis.

BACKGROUND: The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis. METHODS: Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value. RESULTS: We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously. CONCLUSIONS: Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.

Identification and extraction of cementation patterns in sand modified by MICP: New insights at the pore scale.

Microbially induced calcium carbonate precipitation (MICP) is an environmentally friendly technology that improves soil permeability resistance through biocementation. In this study, 2D microscopic analysis and 3D volume reconstruction were performed on river sand after 24 cycles of bio-treatment based on stacked images and computed tomography (CT) scanning data, respectively, to extract biocementation patterns between particles. Based on the mutual validation findings of the two techniques, three patterns in the biocemented sand were identified as G-C-G, G-C, and G-G. Specifically, 2D microscopic analysis showed that G-C-G featured multi-particle encapsulation and bridging, with a pore filling ratio of 81.2%; G-C was characterized by locally coated particle layers, with a pore filling ratio of 19.7%; and the G-G was marked by sporadic filling of interparticle pores, with a pore filling ratio of 11.7%. G-C-G had the best cementation effect and permeability resistance (effective sealing rate of 68.5%), whereas G-C (effective sealing rate of 2.4%) had a relatively minor contribution to pore-filling and flow sealing. 3D volume reconstruction showed that G-C-G had the highest pore filling rate, followed by G-G and G-C. The average filling ratios of area and volume for G-C-G were 83.979% and 77.257%, respectively; for G-G 20.360% and 23.600%; and for G-C 11.545% and 11.250%. The analysis of the representative element volume (REV) was conducted, and the feasibility and reliability of the micro-scale pattern extraction results were confirmed to guide the analysis of macro-scale characteristics. The exploration of the effectiveness of cementation patterns in fluid sealing provides valuable insights into effective biocementation at the pore scale of porous media, which may inspire future research.

Analysis of postoperative quality of life and prognosis of patients with intracranial aneurysm after nursing based on concept of time.

OBJECTIVE: To assess the postoperative quality of life and prognosis of patients with intracranial aneurysm (IA) after nursing based on a time-based concept. METHODS: Data of 84 patients with IA who underwent treatment at the Shengjing Hospital Affiliated to China Medical University from February 2019 to February 2021 were analyzed retrospectively. Among them, the control group (n=41) received conventional nursing. On this basis, the observation group (n=43) received nursing based on the concept of time. Patients' limb motor function and quality of life before and after treatment, postoperative complications and prognosis, and nursing satisfaction were evaluated. Also, risk factors for poor prognosis were analyzed through multifactorial analysis. RESULTS: One month after surgery, the scores of Fugl-Meyer Assessment (FMA) and Quality-of-Life Questionnaire Core in both groups were higher than those before nursing, and both scores were dramatically higher in the observation group than in the control group (P<0.05). The overall postoperative complication rate was markedly higher in the control group than in the observation group (P<0.05). Patients in the observation group were more satisfied with the nursing than those in the control group (P<0.05). The postoperative prognosis in the observation group was dramatically better than that in the control group (P<0.05). There were statistical differences in age, timing of intervention, hypertension, aneurysm diameter, Hunt-Hess classification, Fisher grade, FMA score and nursing regimen at one month postoperatively between the good prognosis group and the poor prognosis group (P<0.05). Older age, delayed timing of intervention, aneurysm ≥15 mm and Fisher grade ≥3 were independent risk factors for poor prognosis. CONCLUSION: In summary, a nursing model based on the concept of time can effectively improve the rehabilitation outcome, improve the prognosis, and enhance the quality of life in IA patients.

Coil and n-butyl-2-cyanoacrylate migration into the stomach after TIPS for gastroesophageal variceal bleeding: a case report and literature review.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established therapeutic option for the management of variceal hemorrhage in patients with cirrhosis. The simultaneous migration of the coil and n-butyl-2-cyanoacrylate (NBCA) is an extremely rare but significant complication after TIPS. Because of its rare presentation, there are currently no definitive recommendations for the management of this condition. CASE PRESENTATION: A 46-year-old man with hepatitis B cirrhosis underwent TIPS placement for uncontrolled gastroesophageal varix (GEV) bleeding secondary to portal hypertension in August 2018. During the procedure, large GEVs were embolized using a coil and NBCA. After a year, coil and NBCA migration into the stomach was observed. Attempts to remove the coil using biopsy forceps during esophagogastroduodenoscopy failed. The patient refused further intervention on the coil to prevent further complications and received conservative therapy instead. Close surveillance with endoscopy is recommended for detecting coils and varices. CONCLUSIONS: The present case reports an extremely rare but significant complication after TIPS, which highlights the management and follow-up recommendation for such rare complications. Our experience may provide guidance for the management of future similar cases and stimulate discussion about treatment methods of similar patients.

A Comprehensive Analysis of the DUF4228 Gene Family in Gossypium Reveals the Role of GhDUF4228-67 in Salt Tolerance.

Soil salinization conditions seriously restrict cotton yield and quality. Related studies have shown that the DUF4228 proteins are pivotal in plant resistance to abiotic stress. However, there has been no systematic identification and analysis of the DUF4228 gene family in cotton and their role in abiotic stress. In this study, a total of 308 DUF4228 genes were identified in four Gossypium species, which were divided into five subfamilies. Gene structure and protein motifs analysis showed that the GhDUF4228 proteins were conserved in each subfamily. In addition, whole genome duplication (WGD) events and allopolyploidization might play an essential role in the expansion of the DUF4228 genes. Besides, many stress-responsive (MYB, MYC) and hormone-responsive (ABA, MeJA) related cis-elements were detected in the promoters of the DUF4228 genes. The qRT-PCR results showed that GhDUF4228 genes might be involved in the response to abiotic stress. VIGS assays and the measurement of relative water content (RWC), Proline content, POD activity, and malondialdehyde (MDA) content indicated that GhDUF4228-67 might be a positive regulator of cotton response to salt stress. The results in this study systematically characterized the DUF4228s in Gossypium species and will provide helpful information to further research the role of DUF4228s in salt tolerance.

A Comprehensive Gene Co-Expression Network Analysis Reveals a Role of GhWRKY46 in Responding to Drought and Salt Stresses.

Abiotic stress, such as drought and salinity stress, seriously inhibit the growth and development of plants. Therefore, it is vital to understand the drought and salinity resistance mechanisms to enable cotton to provide more production under drought and salt conditions. In this study, we identified 8806 and 9108 differentially expressed genes (DEGs) through a comprehensive analysis of transcriptomic data related to the PEG-induced osmotic and salt stress in cotton. By performing weighted gene co-expression network analysis (WGCNA), we identified four co-expression modules in PEG treatment and five co-expression modules in salinity stress, which included 346 and 324 predicted transcription factors (TFs) in these modules, respectively. Correspondingly, whole genome duplication (WGD) events mainly contribute to the expansion of those TFs. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses revealed those different modules were associated with stress resistance, including regulating macromolecule metabolic process, peptidase activity, transporter activity, lipid metabolic process, and responses to stimulus. Quantitative RT-PCR analysis was used to confirm the expression levels of 15 hub TFs in PEG6000 and salinity treatments. We found that the hub gene GhWRKY46 could alter salt and PEG-induced drought resistance in cotton through the virus-induced gene silencing (VIGS) method. Our results provide a preliminary framework for further investigation of the cotton response to salt and drought stress, which is significant to breeding salt- and drought-tolerant cotton varieties.

Six Genes Associated with Lymphatic Metastasis in Colon Adenocarcinoma Linked to Prognostic Value and Tumor Immune Cell Infiltration.

Objective: The aim of the study is to explore the relationship between lymphatic metastasis genes, prognosis, and immune cell infiltration in patients with colon cancer. Methods: Based on the Cancer Genome Atlas Program (TCGA) database, differentially expressed genes and prognostic genes related to colon adenocarcinoma (COAD) lymphatic metastasis were screened and intersected. We used lasso and univariate Cox regression analysis to screen core genes and establish a preliminary prediction model. GO and KEGG enrichment analysis was used for lymphatic metastasis-related genes, and single GSEA was used for the final screening results. Finally, we evaluated the relationship between identified genes and immune cell infiltration. Results: A total of 1727 genes were differentially expressed between COAD patients with TNM stages of N0 and N1. After further screening, six core genes (RNU4-2, ZNF556, RNVU1-15, NSA2P6, RN7SL767P, and RN7SL473P) were obtained, and a preliminary prediction model was established, in which ZNF556 was a risk factor, and the rest were protective factors. Single GSEA showed that pathways such as systemic lupus erythematosus might play an important role in the initial lymphatic metastasis of COAD. GO and KEGG enrichment analysis of 1727 genes supported this result. Immune infiltration analysis showed that six genes were significantly correlated with T cell and NK cell families. Conclusion: Six core genes may affect COAD initial lymphatic metastasis through the systemic lupus erythematosus pathway and immune cell infiltration.

Integrated Analyses of Transcriptome and Chlorophyll Fluorescence Characteristics Reveal the Mechanism Underlying Saline-Alkali Stress Tolerance in Kosteletzkya pentacarpos.

In recent years, soil salinization has become increasingly severe, and the ecological functions of saline-alkali soils have deteriorated because of the lack of plants. Therefore, understanding the tolerance mechanisms of saline-alkali-tolerant plants has become crucial to restore the ecological functions of saline-alkali soils. In this study, we evaluated the molecular mechanism underlying the tolerance of Kosteletzkya pentacarpos L. (seashore mallow) seedlings treated with 0.05 or 0.5% saline-alkali solution (NaCl: NaHCO3 = 4:1 mass ratio) for 1 and 7 days. We identified the key genes involved in tolerance to saline-alkali stress using orthogonal partial least squares regression analysis (OPLS-RA) based on both chlorophyll fluorescence indexes and stress-responsive genes using transcriptome analysis, and, finally, validated their expression using qRT-PCR. We observed minor changes in the maximum photochemical efficiency of the stressed seedlings, whose photosynthetic performance remained stable. Moreover, compared to the control, other indicators varied more evidently on day 7 of 0.5% saline-alkali treatment, but no variations were observed in other treatments. Transcriptome analysis revealed a total of 54,601 full-length sequences, with predominantly downregulated differentially expressed gene (DEG) expression. In the high concentration treatment, the expression of 89.11 and 88.38% of DEGs was downregulated on days 1 and 7, respectively. Furthermore, nine key genes, including KpAGO4, KpLARP1C, and KpPUB33, were involved in negative regulatory pathways, such as siRNA-mediated DNA methylation, inhibition of 5'-terminal oligopyrimidine mRNA translation, ubiquitin/proteasome degradation, and other pathways, including programmed cell death. Finally, quantitative analysis suggested that the expression of key genes was essentially downregulated. Thus, these genes can be used in plant molecular breeding in the future to generate efficient saline-alkali-tolerant plant germplasm resources to improve the ecological functions of saline-alkali landscapes.

Scanning of Bridge Surface Roughness from Two-Axle Vehicle Response by EKF-UI and Contact Residual: Theoretical Study.

The scanning of bridge surface roughness by the test vehicle is a coupled and non-stationary problem since the bridge deflection caused by vehicles will inevitably enter into the vehicle response. To this end, a two-step procedure is proposed to retrieve the bridge surface profile from the noise-contaminated responses of a two-axle vehicle moving over bridges. Central to this is the elimination of the bridge deflection from the estimated unknown input to the test vehicle system. First, the extended Kalman filter with unknown inputs (EKF-UI) algorithm is extended to formulating the state-space equations for the moving vehicle over the bridge. Analytical recursive solutions are derived for the improved vehicle states and the unknown input vector consisting of the vehicle-bridge contact displacement and surface profile. Second, the correlation between the cumulated contact residuals and contact displacements for the two axles is approximately defined by using the vehicle's parameters and location on the bridge. Then, the surface profile is retrieved from the unknown input by removing the roughness-free contact (bridge) displacement, calculated with no prior knowledge of bridge properties. The efficacy of the proposed procedure was validated by the finite element method and demonstrated in the parametric study for various properties of the system. It is confirmed that the retrieved bridge surface profile is in excellent agreement with the original (assumed). For practical use, the vehicle is suggested to run at a not-too-high speed or in a too noisy environment. The proposed technique is robust with regard to vehicle mass and bridge damping.

Association of preserved vegetable consumption and prevalence of colorectal polyps: results from the Lanxi Pre-colorectal Cancer Cohort (LP3C).

PURPOSE: Although fresh vegetable consumption has been linked with a lower risk of colorectal polyps, a precursor lesion for colorectal cancer (CRC), the association between preserved vegetable consumption and colorectal polyps is unknown. We aimed to assess the association of preserved vegetable intake with the prevalence of colorectal polyps with the consideration of subsites, sizes and multiplicity of polyps. METHODS: We analyzed the cross-sectional data from 40-80 years Chinese at a high risk of CRC from the Lanxi Pre-colorectal Cancer Cohort (LP3C) baseline survey, which was conducted between March 2018 and December 2019. Dietary information was obtained via a validated food frequency questionnaire. Multivariate logistic regression was employed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of preserved vegetable consumption and the prevalence of colorectal polyps. RESULTS: Of 6783 eligible participants in 2018-2019 survey of LP3C, 2064 prevalent colorectal polyp cases were identified. In the multivariable-adjusted model, preserved vegetable consumption was positively associated with the prevalence of colorectal polyps (OR for fourth vs. first quartile: 1.18; 95% CI 1.01-1.36; P trend = 0.02). The similar association was also detected for small polyps [ORQ4 vs Q1 (95% CI): 1.17 (1.00-1.37); P trend = 0.03]. The similar trend was detected for multiple polyps [OR Q4 vs Q1 (95% CI):1.27 (0.98-1.64); P trend = 0.04], proximal colon polyps [ORQ4 vs Q1 (95% CI): 1.12 (0.90-1.38); P trend = 0.07], and single polyp [ORQ4 vs Q1 (95% CI) for 1.15 (0.98-1.35); P trend = 0.06]. No significant association was observed for distal colon [ORQ4 vs Q1 (95% CI) 1.19 (0.98-1.45); P trend = 0.09]. Replacing one serving per day of preserved vegetables with fresh vegetables was related to 20%, 23%, and 37% lower prevalence of overall, small, and multiple polyps, respectively. CONCLUSIONS: Preserved vegetable consumption was associated with a higher prevalence of colorectal polyps in a Chinese population at a high risk of CRC. Replacing preserved vegetables with fresh vegetables may be conducive to lower prevalent colorectal polyps.

Modulatory effect of euxanthone in liver cancer-bearing obese mice: crosstalk between PPARγ and TIMP3 signalling axes.

Liver cancer is one of the prominent cancer-associated fatal diseases with > 80% of cases befall in low-middle resource nations worldwide. In the current study, we studied the effect of euxanthone (EUX) on obesity-associated liver cancer using a high-fat diet-fed mouse model of diethylnitrosamine (DEN)-provoked hepatocellular carcinoma. Mice with 2 weeks of age were intraperitoneally injected with diethylnitrosamine (DEN) 25 mg/kg b.w. After 4 weeks, the mice were divided into four groups with low-fat diet (LFD), high-fat diet (HFD), and EUX treatment groups with or without PPARγ inhibitor (GW9662). We observed that TIMP3, E-cadherin, and Klotho expressions were downmodulated, while MMP9, ADAM17, and Wnt signalling biofactors (Wnt5a, Wnt3a and ß-catenin) were upmodulated in the HFD groups. Nevertheless, these aberrations were reciprocated by the treatment with EUX; at the same time, co-administration of PPARγ inhibitor ablated the anti-cancer effects of EUX, indicating that PPARγ activation is a pivotal mechanism underpinning the negative regulation of oncogenic factors by EUX. Together, these results imply that EUX might be a viable therapeutic option in the treatment of obesity-associated hepatocarcinogenesis.

Analysis of the efficacy of transcatheter arterial infusion chemotherapy in the treatment of pancreatic carcinoma.

OBJECTIVE: To evaluate the clinical efficacy of infusion of gemcitabine (GEM) and fluorouracil (5-FU)through the celiac artery and superior mesenteric artery in the treatment of pancreatic carcinoma (PC). METHODS: We analyzed 20 patients diagnosed clinically or pathologically with PC, without metastases, who had an estimated survival duration of >3 months in our department from May 2009 to December 2014. Nine patients were treated directly without surgical resection of the tumor, while the other 11 patients were treated after surgery. In all patients, the femoral artery was punctured using the Seldinger technique, and a catheter was placed in the opening of the celiac artery or the superior mesenteric artery. We administered 500 â€‹mg/m2 GEM and 500 â€‹mg/m2 5-FU. Observational data included data on clinical efficacy and survival rates during the follow-up period of 3-72 months. RESULTS: Twenty patients were treated 85 times with transcatheter arterial infusion chemotherapy (TAI). The survival rates were 80%, 40%, 35%, 20%, 10%, and 5% at 3, 6, 12, 24, and 72 months, respectively. CONCLUSION: TAI chemotherapy with GEM and 5-FU may be a therapeutic option for the treatment of PC.

Comparison of Transjugular Intrahepatic Portosystemic Shunt in the Treatment of Cirrhosis With or Without Portal Vein Thrombosis: A Retrospective Study.

Aim: The purpose of our study was to conduct a retrospective analysis to compare the effectiveness of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of patients with cirrhosis with or without portal vein thrombosis (PVT). Methods: We included a total of 203 cirrhosis patients successfully treated with TIPS between January 2015 and January 2018, including 72 cirrhosis patients with PVT (35.5%) and 131 without PVT (64.5%). Our subjects were followed for at least 1 year after treatment with TIPS. Data were collected to estimate the mortality, shunt dysfunction, and complication rates after TIPS creation. Results: During the mean follow-up time of 19.5 ± 12.8 months, 21 (10.3%) patients died, 15 (7.4%) developed shunt dysfunction, and 44 (21.6%) experienced overt hepatic encephalopathy (OHE). No significant differences in mortality (P = 0.134), shunt dysfunction (P = 0.214), or OHE (P = 0.632) were noted between the groups. Age, model for end-stage liver disease (MELD) score, and refractory ascites requiring TIPS were risk factors for mortality. A history of diabetes, percutaneous transhepatic variceal embolization (PTVE), 8-mm diameter stent, and platelet (PLT) increased the risk of shunt dysfunction. The prevalence of variceal bleeding and recurrent ascites was comparable between the two groups (16.7 vs. 16.7% P = 0.998 and 2.7 vs. 3.8% P = 0.678, respectively). Conclusions: Transjugular intrahepatic portosystemic shunts are feasible in the management of cirrhosis with PVT. No significant differences in survival or shunt dysfunction were noted between the PVT and no-PVT groups. The risk of recurrent variceal bleeding, recurrent ascites, and OHE in the PVT group was generally similar to that in the no-PVT group. TIPS represents a potentially feasible treatment option in cirrhosis patients with PVT.

Protopine triggers apoptosis via the intrinsic pathway and regulation of ROS/PI3K/Akt signalling pathway in liver carcinoma.

BACKGROUND: Protopine is an isoquinoline alkaloid that possesses various biological activities including the anti-tumour activity. However, the effects of protopine on liver carcinoma cells are still elusive. The aim of this study is to examine the effects of protopine on liver carcinoma cells both in vitro and in vivo. METHODS: MTT assay was performed to measure the cell viability. Wound healing and transwell assays were conducted to assess the motility of cells. Cellular apoptosis and ROS levels were measured by the flow cytometry. Western blotting assay was used to measure the change of proteins. The cytotoxicity of protopine was also evaluated in xenograft mice. RESULTS: Protopine inhibited viabilities and triggered apoptosis via the intrinsic pathway in a caspase-dependent manner in liver carcinoma cells. Furthermore, protopine also induced accumulation of intracellular ROS which further led to the inhibition of PI3K/Akt signalling pathway. Finally, in vivo study showed that protopine also repressed tumour growth in xenograft mice without noticeable toxicity. CONCLUSIONS: Protopine might be used as a potential therapeutic agent for the treatment of liver carcinoma.

Complete Response of Hepatocellular Carcinoma with Macroscopic Vascular Invasion and Pulmonary Metastasis to the Combination of Drug-Eluting Beads Transarterial Chemoembolization and Huaier Granule: A Case Report.

BACKGROUND: Hepatocellular carcinoma (HCC) associated with macroscopic vascular invasion and distant metastasis is an advanced-stage disease with an extremely poor prognosis and low survival rate. Therefore, there is an urgent need to develop novel therapeutic strategies to extend the lives of patients with advanced HCC. CASE PRESENTATION: We represent a case of HCC with macroscopic vascular invasion and pulmonary metastasis responding dramatically to the combination treatment with drug-eluting beads transarterial chemoembolization (DEB-TACE) and Huaier granule. A 64-year-old man with hepatitis B virus (HBV)-induced liver cirrhosis was diagnosed with advanced HCC involved renal vein and inferior vena cava accompanied by pulmonary metastasis. The patient received three cycles of on-demand DEB-TACE from 9th September 2016 to 22nd August 2017 and combined with Huaier granule 20 g three times a day orally. Eight months following the treatment, complete response occurred with regression of HCC and vascular thrombus and disappearance of pulmonary metastasis. The levels of AFP had decreased from 8165.8ng/mL to within the normal range (1.7 ng/mL). This is the first case report of complete response of HCC to the combination treatment with DEB-TACE and Huaier granule. At the most recent follow-up, he remained in remission 36 months after cessation of treatment without clinical or imaging evidence of disease recurrence. The current overall survival is 54 months since the initial treatment. CONCLUSION: Data from this clinical case report suggest that the combination treatment with DEB-TACE and Huaier granule is a promising therapeutic option for advanced HCC with macroscopic vascular invasion and distant metastasis.

Safety and efficacy of drug-eluting bead transarterial chemoembolization with CalliSpheres® microsphere for hepatocellular carcinoma with portal vein tumor thrombus: a preliminary study.

Objective: To prospectively evaluate the safety and therapeutic effectiveness of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) with CalliSpheres® microsphere (CSM) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to analyze the prognostic factors. Method: Between November 2015 and November 2017, consecutive 58 HCC patients with PVTT who received DEB-TACE with CSM treatment were prospectively enrolled in this study. The demographic characteristics, adverse events (AEs) and treatment response were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the independent factors correlated with OS. Results: The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh classification (HR=2.279; 95%CI, 1.042-4.985, p = 0.039) and tumor burden (p = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. The most common clinical AEs were postembolization syndrome (PES) and the most prevalent laboratory toxicity was transient liver function damage. Conclusion: DEB-TACE with CSM is safe and well-tolerated in HCC patients with PVTT, and reveals a favorable preliminary clinical outcome. The higher Child-Pugh classification and liver tumor burden are independent prognostic factors associated with poor survival for HCC patients with PVTT treated by DEB-TACE with CSM.

Evolution and Stress Responses of CLO Genes and Potential Function of the GhCLO06 Gene in Salt Resistance of Cotton.

The caleosin (CLO) protein family displays calcium-binding properties and plays an important role in the abiotic stress response. Here, a total of 107 CLO genes were identified in 15 plant species, while no CLO genes were detected in two green algal species. Evolutionary analysis revealed that the CLO gene family may have evolved mainly in terrestrial plants and that biological functional differentiation between species and functional expansion within species have occurred. Of these, 56 CLO genes were identified in four cotton species. Collinearity analysis showed that CLO gene family expansion mainly occurred through segmental duplication and whole-genome duplication in cotton. Sequence alignment and phylogenetic analysis showed that the CLO proteins of the four cotton species were mainly divided into two types: H-caleosins (class I) and L-caleosins (class II). Cis-acting element analysis and quantitative RT-PCR (qRT-PCR) suggested that GhCLOs might be regulated by abscisic acid (ABA) and methyl jasmonate (MeJA). Moreover, transcriptome data and qRT-PCR results revealed that GhCLO genes responded to salt and drought stresses. Under salt stress, gene-silenced plants (TRV: GhCLO06) showed obvious yellowing and wilting, higher malondialdehyde (MDA) content accumulation, and significantly lower activities of superoxide dismutase (SOD) and peroxidase (POD), indicating that GhCLO06 plays a positive regulatory role in cotton salt tolerance. In gene-silenced plants (TRV: GhCLO06), ABA-related genes (GhABF2, GhABI5, and GhNAC4) were significantly upregulated after salt stress, suggesting that the regulation of salt tolerance may be related to the ABA signaling pathway. This research provides an important reference for further understanding and analyzing the molecular regulatory mechanism of CLOs for salt tolerance.

Integrative Analysis of HNF1B mRNA in Human Cancers Based on Data Mining.

Cancer incidence is rapidly growing, and cancer is the leading cause of death worldwide in the 21st century. Hepatocyte nuclear factor 1B (HNF1B) is a transcription factor that involves the growth and development of multiple organs. The aim of this study was to explore the significance of HNF1B in human cancer by an integrative analysis of online databases. The UALCAN database, cBio cancer genomics portal, Cancer Regulome tools, Kaplan-Meier plotter and Tumor IMmune Estimation Resource (TIMER) website were used to perform the corresponding analysis. The results showed that HNF1B is dysregulated in various cancers and associated with the differential overall survival of cancer patients. HNF1B showed many mutation forms and high mutation levels in different cancer types. In addition, we found that HNF1B interacted with different genes in multiple aspects. Moreover, HNF1B expression is associated with many immune cell infiltration levels and influences the prognostic prediction of immune cells in some kinds of cancers. In conclusion, HNF1B plays a significant role in cancer and may be a potential target for cancer immunotherapy.