Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort. Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM). Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China.

INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

Objective: To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Methods: Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. Results: In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Conclusion: Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.

Tislelizumab induced dual organs dysfunction in a patient with advanced esophageal squamous cell carcinoma: a case report.

Background: Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody has been approved in China and Europe. According to the published clinical research, tislelizumab shows satisfactory safety profile. No severe hepatotoxicity or acute kidney injury were reported. Case presentation: We presented a case study of a 74-year-old man who developed acute kidney injury (grade 3) and acute liver injury (grade 4) after being administered tislelizumab for the treatment of esophageal squamous cell carcinoma. We reviewed the patient's history, physical examination, and laboratory findings and provided comprehensive differentials of the possible causes of the toxicities. Immune Checkpoint Inhibitors (ICI) hepatotoxicity and nephrotoxicity were confirmed clinically. We also discussed the management of toxicities associated with ICIs and the need for a multidisciplinary approach to care. Conclusions: The case highlights the importance of close monitoring and prompt management of toxicities associated with ICIs and the need for further research to better understand the risk factors for these toxicities and to identify effective treatments for them.

Effects of Liver Fibrosis on Islet Function in Patients with Chronic Hepatitis B Complicated with Impaired Fasting Glucose.

Background: Patients with chronic hepatitis B (CHB) and cirrhosis often have impaired fasting glucose (IFG). This study sought to investigate the impact of liver fibrosis on islet function in individuals diagnosed with CHB and IFG. Material and Methods: Patients with chronic hepatitis B (CHB) and impaired fasting glucose (IFG) were selected for this study. They were divided into low-risk (L-R), intermediate-risk (M-R), and high-risk (H-R) liver fibrosis groups based on the FIB-4 score. The study compared islet function among different risk groups of liver fibrosis and analyze the correlation between liver fibrosis and islet function. Additionally, the patients were divided into a diabetes mellitus (DM) group and a non-DM (NDM) group based on the development of DM. The cumulative risk of progression to DM in patients with L-R, M-R, and H-R liver fibrosis was analyzed using the Kaplan-Meier method. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for DM development through Cox regression analysis. Results: In this study of 228 individuals, higher FIB-4 scores were observed in the DM group compared to the NDM group. Patients with H-R liver fibrosis displayed lower islet function and had a significantly higher risk of developing DM. The FIB-4 score and fasting plasma glucose (FPG) were identified as independent risk factors for DM progression in CHB patients with IFG. Conclusion: Among patients with CHB and IFG, the severity of liver fibrosis is associated with islet function, and the FIB-4 score is a significant risk factor for DM development.

Correlation of TNF-α, Cys C, and NLRP3 inflammasomes with venous ulcers in patients with lower extremity varicose veins.

OBJECTIVE: To explore the correlation of tumor necrosis factor α (TNF-α), cystatin C (Cys C), and NLR family pyrin domain containing 3 (NLRP3) inflammasomes with venous ulcers from lower extremity varicose veins. METHODS: In this retrospective analysis, 135 patients with primary varicose veins of lower extremities were selected and divided into a varicose ulcer group (n=32) and a non-varicose ulcer group (n=103) according to clinical ulcer presence. Healthy adults with similar general information during the same period were included as a healthy controls (n=30). The levels of TNF-α, interleukin-1ß (IL-1ß), Cys C, and NLRP3 inflammasomes were statistically analyzed among the three groups. Logistic regression was used for analyzing the risk factors for venous ulcers in patients with varicose veins of the lower extremities. Spearman correlation was applied for correlation analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was found to disclose the predictive value of TNF-α, Cys C, and NLRP3 inflammasomes for venous ulcers. RESULTS: (1) Logistic regression analysis showed that TNF-α, IL-1ß, and NLRP3 inflammasomes were risk factors for venous ulcers in patients with varicose veins of the lower extremity, and Cys C in ulcer wound tissue was a protective factor. (2) TNF-α was significantly correlated with IL-1ß and Cys C in ulcer wound tissue, and NLRP3 in plasma (r=0.256, -0.290, 0.305; P=0.003, 0.001, <0.001). IL-1ß was significantly correlated with CysC in ulcer wound tissue and plasma (r=-0.251, -0.193; P=0.003, 0.025). (3) The AUC, sensitivity, and specificity of TNF-α and NLRP3 inflammasomes for predicting varicose veins were high, with AUC of 0.881 and 0.712, sensitivity of 0.875% and 0.875%, and specificity of 0.893% and 0.738%, respectively. CONCLUSION: TNF-α in plasma, Cys C in ulcer wound tissue and plasma, and NLRP3 inflammasomes in plasma were closely related to the occurrence of venous ulcers in patients with varicose veins of the lower and may serve as new targets for treatment.

Validation and analysis of the geographical origin of Angelica sinensis (Oliv.) Diels using multi-element and stable isotopes.

BACKGROUND: Place of origin is an important factor when determining the quality and authenticity of Angelica sinensis for medicinal use. It is important to trace the origin and confirm the regional characteristics of medicinal products for sustainable industrial development. Effectively tracing and confirming the material's origin may be accomplished by detecting stable isotopes and mineral elements. METHODS: We studied 25 A. sinensis samples collected from three main producing areas (Linxia, Gannan, and Dingxi) in southeastern Gansu Province, China, to better identify its origin. We used inductively coupled plasma mass spectrometry (ICP-MS) and stable isotope ratio mass spectrometry (IRMS) to determine eight mineral elements (K, Mg, Ca, Zn, Cu, Mn, Cr, Al) and three stable isotopes (δ13C, δ15N, δ18O). Principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and linear discriminant analysis (LDA) were used to verify the validity of its geographical origin. RESULTS: K, Ca/Al, δ13C, δ15N and δ18O are important elements to distinguish A. sinensis sampled from Linxia, Gannan and Dingxi. We used an unsupervised PCA model to determine the dimensionality reduction of mineral elements and stable isotopes, which could distinguish the A. sinensis from Linxia. However, it could not easily distinguish A. sinensis sampled from Gannan and Dingxi. The supervised PLS-DA and LDA models could effectively distinguish samples taken from all three regions and perform cross-validation. The cross-validation accuracy of PLS-DA using mineral elements and stable isotopes was 84%, which was higher than LDA using mineral elements and stable isotopes. CONCLUSIONS: The PLS-DA and LDA models provide a theoretical basis for tracing the origin of A. sinensis in three regions (Linxia, Gannan and Dingxi). This is significant for protecting consumers' health, rights and interests.

New insights into the phylogeny of Sinocarum (Apiaceae, Apioideae) based on morphological and molecular data.

Sinocarum is a Sino-Himalayan endemic genus of Apiaceae and distributed in high-elevations from Nepal to SW China. In this study, morphological characteristics were combined with nuclear internal transcribed spacer (ITS) and two chloroplast DNA (cpDNA) intron sequences (rpl16 and rps16) to determine the phylogenetic placement of Sinocarum and the infrageneric relationships between five Sinocarum species. The results confirmed that Sinocarum was a polyphyletic group separated into two clades, Acronema and East Asia clades. S. coloratum, the generic type of Sinocarum, S. cruciatum, S. vaginatum and S. filicinum are in the Acronema clade. Among them, the first three species are clustered into a subclade and are closely related to the genus Acronema. While S. filicinum has a close affinity with Meeboldia. S. schizopetalum did not ally with its congeners we collected and is allied closely with members of the distantly related East Asia clade. In addition, the fruit of the Acronema clade Sinocarum species is usually oblong-ovoid or ovoid, and the pollen is super-rectangular, while the Sinocarum species in the East Asia clade have broad-ovoid fruit and sub-rhomboidal pollen. This study has furnished cumulative evidence to reduce phylogenetic uncertainty and provide a more comprehensive description of the plant morphology, fruit morphology and anatomy, and pollen morphology of these five Chinese Sinocarum species.

Complete Plastid Genome Sequencing of Eight Species from Hansenia, Haplosphaera and Sinodielsia (Apiaceae): Comparative Analyses and Phylogenetic Implications.

Hansenia Turcz., Haplosphaera Hand.-Mazz. and Sinodielsia H.Wolff are three Apiaceae genera endemic to the Hengduan Mountains and the Himalayas, which usually inhabit elevations greater than 2000 m. The phylogenetic relationships between and within the genera were uncertain, especially the placement of Hap. himalayensis and S. microloba. Therefore, we aimed to conduct comparative (simple sequence repeat (SSR) structure, codon usage bias, nucleotide diversity (Pi) and inverted repeat (IR) boundaries) and phylogenetic analyses of Hansenia, Haplosphaera and Sinodielsia (also compared with Chamaesium and Bupleurum) to reduce uncertainties in intergeneric and interspecific relationships. We newly assembled eight plastid genomes from Hansenia, Haplosphaera and Sinodielsia species, and analyzed them with two plastid genomes from GenBank of Hap. phaea,S. yunnanensis. Phylogenetic analyses used these ten genomes and another 22 plastid genome sequences of Apiaceae. We found that the newly assembled eight genomes ranged from 155,435 bp to 157,797 bp in length and all had a typical quadripartite structure. Fifty-five to 75 SSRs were found in Hansenia, Haplosphaera and Sinodielsia species, and the most abundant SSR was mononucleotide, which accounted for 58.47% of Hansenia, 60.21% of Haplosphaera and 48.01% of Sinodielsia. There was no evident divergence of codon usage frequency between the three genera, where codons ranged from 21,134 to 21,254. The Pi analysis showed that trnE(UUC)-trnT(GGU), trnH(GUG)-psbA and trnE(UUC)-trnT(GGU) spacer regions had the highest Pi values in the plastid genomes of Hansenia (0.01889), Haplosphaera (0.04333) and Sinodielsia (0.01222), respectively. The ndhG-ndhI spacer regions were found in all three genera to have higher diversity values (Pi values: 0.01028-0.2), and thus may provide potential DNA barcodes in phylogenetic analysis. IR boundary analysis showed that the length of rps19 and ycf1 genes entering IRs were usually stable in the same genus. Our phylogenetic tree demonstrated that Hap. himalayensis is sister to Han. weberbaueriana; meanwhile, Haplosphaera and Hansenia are nested together in the East Asia clade, and S. microloba is nested within individuals of S. yunnanensis in the Acronema clade. This study will enrich the complete plastid genome dataset of the Apiaceae genera and has provided a new insight into phylogeny reconstruction using complete plastid genomes of Hansenia, Haplosphaera and Sinodielsia.

Impact of tenofovir antiviral treatment on survival of chronic hepatitis B related hepatocellular carcinoma after hepatectomy in Chinese individuals from Qingdao municipality.

The impact of different antiviral regimen on prognosis of chronic hepatitis B (CHB) related hepatocellular carcinoma (HCC) remains to be explored.A total of 479 CHB-related HCC patients after curative liver resection were enrolled receiving tenofovir (TDF, TDF group) or lamivudine, telbivudine, and entecavir (non-TDF group). Both the overall survival and diseases-free survival were analyzed and compared.A total of 242 patients received TDF treatment and 237 patients received other antiviral regimen. Child-Pugh score, serum α-fetoprotein (AFP) level, total bilirubin level, status of hepatitis B e antigen (HBeAg), and cirrhosis were compared between groups. Kaplan-Meier analysis revealed that patients with TDF treatment had significantly longer overall survival than those of patients with other regimen (P = .015). Similarly, compared with patients with non-TDF treatment, disease-free survival time was longer (P = .042) in those with TDF treatment. Multivariate analysis showed that TDF treatment (P = .04), AFP level (P = .03) were significant independent factors associated with overall survival of CHB-related HCC patients. While TDF treatment (P = .04) and serum AFP level (P = .03) were independent factors associated with disease-free survival.Anti-virus treatment with TDF benefits for both overall survival and disease-free survival of CHB-related patients than other Nucleos(t)ide analogues.

Tunable Nonreciprocal Quantum Transport through a Dissipative Aharonov-Bohm Ring in Ultracold Atoms.

We report the experimental observation of tunable, nonreciprocal quantum transport of a Bose-Einstein condensate in a momentum lattice. By implementing a dissipative Aharonov-Bohm (AB) ring in momentum space and sending atoms through it, we demonstrate a directional atom flow by measuring the momentum distribution of the condensate at different times. While the dissipative AB ring is characterized by the synthetic magnetic flux through the ring and the laser-induced loss on it, both the propagation direction and transport rate of the atom flow sensitively depend on these highly tunable parameters. We demonstrate that the nonreciprocity originates from the interplay of the synthetic magnetic flux and the laser-induced loss, which simultaneously breaks the inversion and the time-reversal symmetries. Our results open up the avenue for investigating nonreciprocal dynamics in cold atoms, and highlight the dissipative AB ring as a flexible building element for applications in quantum simulation and quantum information.

Topological Quantum Walks in Momentum Space with a Bose-Einstein Condensate.

We report the experimental implementation of discrete-time topological quantum walks of a Bose-Einstein condensate in momentum space. Introducing stroboscopic driving sequences to the generation of a momentum lattice, we show that the dynamics of atoms along the lattice is effectively governed by a periodically driven Su-Schrieffer-Heeger model, which is equivalent to a discrete-time topological quantum walk. We directly measure the underlying topological invariants through time-averaged mean chiral displacements, which are consistent with our experimental observation of topological phase transitions. We then observe interaction-induced localization in the quantum-walk dynamics, where atoms tend to populate a single momentum-lattice site under interactions that are nonlocal in momentum space. Our experiment opens up the avenue of investigating discrete-time topological quantum walks using cold atoms, where the many-body environment and tunable interactions offer exciting new possibilities.

Myricitrin inhibits vascular endothelial growth factor-induced angiogenesis of human umbilical vein endothelial cells and mice.

In the present study, the protective effects of myricitrin against vascular endothelial growth factor (VEGF)-induced angiogenesis of vascular endothelial cells were characterized. Cells were induced with 50 ng/mL VEGF in the presence or absence of various concentrations of myricitrin for 24 h. Myricitrin treatment significantly reduced cell proliferation by more than 50 %. Cells treated with myricitrin showed significantly increased caspase 3/7 activity and apoptosis in a dose-dependent manner. Treatment with 1, 10, or 100 µM myricitrin significantly reduced matrix metalloproteinase (MMP) activity by 23.3 %, 46.2 %, or 64.3 %, respectively. Myricitrin significantly reduced MMP1 and MMP2 mRNA expression. Similarly, treatment with 1, 10, or 100 µM myricitrin reduced MMP1 protein expression by 10.5 %, 31.6 %, or 52.6 %, respectively, and MMP2 protein expression by 10.9 %, 28.2 %, or 43.5 %, respectively. Cells treated with myricitrin showed significant inhibition of cell migration as well as capillary tube and sprouting formation. Myricitrin treatment significantly reduced the VEGF level. Immune-deficient nude mice bearing U251 xenograft tumors were used to investigate the antiangiogenic effects of myricitrin in vivo. The results demonstrated that myricitrin treatment in vivo significantly inhibited U251 cell xenograft tumor growth, as confirmed by the decreases in tumor volume and tumor weight. VEGF expression is a key proangiogenic factor. Myricitrin treatment significantly reduced mRNA and protein VEGF expression. Taken together, these results indicate that myricitrin is a potential inhibitor of VEGF-induced angiogenesis.

KCa3.1 channel mediates inflammatory signaling of pancreatic ß cells and progression of type 2 diabetes mellitus.

Chronic islet inflammation is associated with development of type 2 diabetes mellitus (T2DM). Intermediate-conductance calcium-activated K+ (KCa3.1) channel plays an important role in inflammatory diseases. However, the role and regulation of KCa3.1 in pancreatic ß cells in progression of T2DM remain unclarified. In the present study, we evaluated the effect of the specific KCa3.1 channel blocker 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) on diabetic phenotype in the db/db model. In diabetic mice, blockade of KCa3.1 significantly improved glucose tolerance, enhanced secretion of postprandial insulin level, and reduced loss of ß-cell mass through attenuating the expression and secretion of inflammatory mediators. Furthermore, in cultured pancreatic ß cells, exposure to high levels of glucose or palmitic acid significantly increased expression and current density of the KCa3.1 channel as well as secretion of proinflammatory chemokines, and the effects were similarly reversed by preincubation with TRAM-34 or a NF-κB inhibitor pyrrolidinedithiocarbamate. Additionally, expression of KCa3.1 in pancreas islet cells was up-regulated by activation of NF-κB with IL-1ß stimulation. In summary, up-regulated KCa3.1 due to activation of NF-κB pathway leads to pancreatic inflammation via expression and secretion of chemokines and cytokines by pancreatic ß cells, thereby facilitating progression of T2DM.-Pang, Z.-D., Wang, Y., Wang, X.-J., She, G., Ma, X.-Z., Song, Z., Zhao, L.-M., Wang, H.-F., Lai, B.-C., Gou, W., Du, X.-J., Deng, X.-L. KCa3.1 channel mediates inflammatory signaling of pancreatic ß cells and progression of type 2 diabetes mellitus.

Effects of exercise on pregnant women's quality of life: A systematic review.

OBJECTIVES: Exercise is a promising approach to improve the health of pregnant women. However, data from studies investigating exercise and the quality of life of pregnant women are inconsistent and, to date, no systematic review on this topic has been published. The aim of this review was to comprehensively assess the effects of exercise on pregnant women's quality of life, and to determine whether exercise positively affects quality of life in this population. STUDY DESIGN: Literature was retrieved from electronic databases, namely PubMed, EMBASE, Web of Science and the Cochrane Library, from inception to 30 October 2018. Clinical trials published in English evaluating the effects of exercise on pregnant women's quality of life were included. The authors assessed the risk of bias in all eligible studies using the Effective Public Health Practice Project, and used a qualitative synthesis method to identify the effects of exercise on pregnant women's quality of life. RESULTS: Thirteen studies were included. Exercise was divided into the following four modes: aerobic exercise, resistance exercise, a combination (aerobic and resistance exercises), and yoga or physical activity. Aerobic and resistance training had a mixed effect on pregnant women's quality of life, while the combination of aerobic and resistance exercises and yoga or physical activity resulted in significant improvements. CONCLUSIONS: This systematic review is the first to suggest that group-based combined exercise and yoga or physical activity are associated with significant benefits related to improvements in pregnant women's quality of life. Furthermore, aerobic or resistance exercise could potentially improve pregnant women's quality of life. Therefore, it is recommended that medical service providers should pay more attention to the importance of exercise, and develop tailored exercise programmes to promote improvements in pregnant women's quality of life.

MiR-552 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells by inhibiting AJAP1 expression.

Our goal was to explore the function of miR-552 and its potential target AJAP1 in hepatocellular carcinoma (HCC) oncogenesis and progression. In this study, bioinformatics analysis was performed to detect abnormally expressed miRNAs. The relationship between miR-552 and AJAP1 was validated using luciferase reporter assays. RT-qPCR and Western blot assays were applied to explore the expression level of miR-552, AJAP1 and epithelial-mesenchymal transition (EMT) markers. HCC cell proliferation was examined using CCK8 assays, while migration and invasion were investigated using Transwell assays. Nude mouse tumourigenesis models were established to facilitate observation of HCC progression in vivo. Finally, prognostic analysis was performed to discover how the prognosis of HCC patients correlated with miR-552 and AJAP1 expression. MiR-552 overexpression in HCC cells promoted HCC cell migration, invasion and EMT by targeting/suppressing AJAP1. Poorer prognosis appeared in HCC patients with higher miR-552 expression or lower AJAP1 levels. Our findings suggested that miR-552 promotes HCC oncogenesis and progression by inhibiting AJAP1 expression.

The complete chloroplast genome of Meeboldia yunnanensis (Apiaceae).

Meeboldia yunnanensis Wolff (Apiaceae) is a perennial species naturally distributed in Yunnan and Xizang. The complete chloroplast genome sequence of M. yunnanensis was generated by de novo assembly using whole-genome next-generation sequencing data. The complete chloroplast genome of M. yunnanensis was 154,865 bp in total sequence length and divided into four distinct regions: small single-copy region (17,370 bp), large single-copy region (84,641 bp), and a pair of inverted repeat regions (26,427 bp). The genome annotation displayed a total of 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis with the reported chloroplast genomes revealed that M. yunnanensis has close relationship to Pterygopleurum neurophyllum.

KCa3.1 Channels Promote Cardiac Fibrosis Through Mediating Inflammation and Differentiation of Monocytes Into Myofibroblasts in Angiotensin II -Treated Rats.

Background Cardiac fibrosis is a core pathological process associated with heart failure. The recruitment and differentiation of primitive fibroblast precursor cells of bone marrow origin play a critical role in pathological interstitial cardiac fibrosis. The KCa3.1 channels are expressed in both ventricular fibroblasts and circulating mononuclear cells in rats and are upregulated by angiotensin II . We hypothesized that KCa3.1 channels mediate the inflammatory microenvironment in the heart, promoting the infiltrated bone marrow-derived circulating mononuclear cells to differentiate into myofibroblasts, leading to myocardial fibrosis. Methods and Results We established a cardiac fibrosis model in rats by infusing angiotensin II to evaluate the impact of the specific KCa3.1 channel blocker TRAM -34 on cardiac fibrosis. At the same time, mouse CD 4+ T cells and rat circulating mononuclear cells were separated to investigate the underlying mechanism of the TRAM -34 anti-cardiac fibrosis effect. TRAM -34 significantly attenuated cardiac fibrosis and the inflammatory reaction and reduced the number of fibroblast precursor cells and myofibroblasts. Inhibition of KCa3.1 channels suppressed angiotensin II -stimulated expression and secretion of interleukin-4 and interleukin-13 in CD 4+ T cells and interleukin-4- or interleukin-13-induced differentiation of monocytes into fibrocytes. Conclusions KCa3.1 channels facilitate myocardial inflammation and the differentiation of bone marrow-derived monocytes into myofibroblasts in cardiac fibrosis caused by angiotensin II infusion.

Effectiveness of telbivudine antiviral treatment in patients with hepatitis B virus-associated glomerulonephritis: A 104-week pilot study.

The aim of this study was to evaluate clinical efficacy of telbivudine in treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN).A total of 43 HBV-GN patients combined with chronic hepatitis B were treated with telbivudine for 104 weeks. Serum levels of HBV DNA viral load, HBeAg, HBeAb, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), and 24-hour urinary protein were evaluated after telbivudine treatment of 12, 24, 52, 76, and 104 weeks. Estimated glomerular filtration rate (eGFR) was calculated at baseline, 24 weeks, 52 weeks, and 104 weeks of treatment, respectively. Complete remission (CR) was defined as urinary protein <0.3 g/day, with normal ALT, AST, Cr, and eGFR. Criteria for partial remission include: 24-hour urinary protein excretion decreased by >50% compared with baseline level, and ALT and AST decreased >50%.Proteinuria level gradually decreased in patients with HBV-GN after telbivudine treatment. The percentages of PR + CR were 90.7% and 95.3%, respectively, at 52 and 104 weeks. Compared to baseline, eGFR were significantly increased from 69.2 ±â€Š23.1 mL/min/1.73 m to 116.2 ±â€Š26.3 mL/min/1.73 m at 104 weeks of treatment. Multivariate analysis indicated that baseline HBV DNA viral load (odds ratio [OR] = 1.19, 95% confidence interval [CI] 1.11-2.19, P = .02) and baseline urinary protein (OR = 1.08, 95% CI 1.04-2.44, P = .03) were independent risk factors associated with CR after telbivudine treatment among patients with HBV-GN.Our study demonstrates that telbivudine can be used to treat HBV-GN and effectively improve eGFR in these patients.

Study of Staphylococcus aureus N315 Pathogenic Genes by Text Mining and Enrichment Analysis of Pathways and Operons.

BACKGROUND: Staphylococcus aureus (S. aureus) is a versatile pathogen found in many environments and can cause nosocomial infections in the community and hospitals. S. aureus infection is an increasingly serious threat to global public health that requires action across many government bodies, medical and health sectors, and scientific research institutions. METHODS: In the present study, S. aureus N315 genes that have been shown in the literature to be pathogenic were extracted using a bibliometric method for functional enrichment analysis of pathways and operons to statistically discover novel pathogenic genes associated with S. aureus N315. RESULTS: A total of 383 pathogenic genes were mined from the literature using bibliometrics, and subsequently a few new pathogenic genes of S. aureus N315 were identified by functional enrichment analysis of pathways and operons. CONCLUSIONS: The discovery of these novel S. aureus N315 pathogenic genes is of great significance to treat S. aureus induced diseases and identify potential diagnostic markers, thus providing theoretical fundamentals for epidemiological prevention.