The RPT2a-MET1 axis regulates TERMINAL FLOWER1 to control inflorescence meristem indeterminacy in Arabidopsis.

Plant inflorescence architecture is determined by inflorescence meristem (IM) activity and controlled by genetic mechanisms associated with environmental factors. In Arabidopsis (Arabidopsis thaliana), TERMINAL FLOWER1 (TFL1) is expressed in the IM and is required to maintain indeterminate growth, whereas LEAFY (LFY) is expressed in the floral meristems (FMs) formed at the periphery of the IM and is required to activate determinate floral development. Here, we address how Arabidopsis indeterminate inflorescence growth is determined. We show that the 26S proteasome subunit REGULATORY PARTICLE AAA-ATPASE 2a (RPT2a) is required to maintain the indeterminate inflorescence architecture in Arabidopsis. rpt2a mutants display reduced TFL1 expression levels and ectopic LFY expression in the IM and develop a determinate zigzag-shaped inflorescence. We further found that RPT2a promotes DNA METHYLTRANSFERASE1 degradation, leading to DNA hypomethylation upstream of TFL1 and high TFL1 expression levels in the wild-type IM. Overall, our work reveals that proteolytic input into the epigenetic regulation of TFL1 expression directs inflorescence architecture in Arabidopsis, adding an additional layer to stem cell regulation.

IMB-Guided Rehabilitation Nursing in Patients with Diabetic Nephropathy Undergoing Maintenance Hemodialysis.

Objective: This study aims to analyze the application effect of IMB (Information-Motivation-Behavioral skills) model rehabilitation nursing, which focuses on enhancing patient knowledge, motivation, and skills for disease management in patients with diabetes and end-stage renal disease receiving maintenance hemodialysis and its impact on the patient's nutritional status. Methods: Eighty-four patients with diabetes and end-stage renal disease undergoing maintenance hemodialysis were selected as study subjects at our hospital. All patients met the inclusion criteria and were divided into two groups based on the nursing interventions received. The control group (n=42) received routine rehabilitation nursing intervention, while the observation group (n=42) received IMB-guided rehabilitation nursing intervention. The effects of nursing intervention, psychological conditions, nutritional status, and quality of life were evaluated using standardized measurement tools. Psychological conditions were assessed using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Nutritional status was evaluated through measurements of albumin (ALB), body composition analysis (BBC), hemoglobin (Hb), triceps skinfold thickness (TSF), arm circumference (A.C.), and arm muscle circumference (AMC). Quality of life was assessed using the SF-36 Health Survey. Comparative analysis was conducted to examine the differences between the two groups in terms of the aforementioned outcomes. Results: The results of the study revealed compelling data showcasing the effectiveness of the nursing intervention. Notably, after the nursing intervention, ALB (albumin) levels in the observation group increased by 12%, indicating a significant improvement in nutritional status. This increase signifies enhanced protein synthesis and improved overall metabolic functioning among the patients. Additionally, the SF-36 scores, reflecting the quality of life, demonstrated a substantial improvement of 15 points in the observation group following the nursing intervention. This improvement indicates a significant enhancement in various aspects of health-related quality of life, such as physical functioning, mental health, social functioning, and overall well-being. Furthermore, the total nursing effective rate in the observation group was an impressive 97.62%, surpassing the 80.95% rate in the control group. This statistically significant difference (P < .05) emphasizes the superior outcomes achieved through the nursing intervention in the observation group. Moreover, when comparing psychological conditions, the SAS scores in the observation group after the nursing intervention were significantly lower than those in the control group by 8 points (P < .05). Similarly, the SDS scores in the observation group showed a significant decrease of 10 points compared to the control group (P < .05). These findings indicate a substantial reduction in anxiety and depression levels among patients in the observation group. Conclusion: The findings of this study have significant implications for patient care and highlight potential areas for future research. The results suggest that integrating IMB-guided approaches into hemodialysis care protocols could significantly enhance patient well-being. The notable improvements in nutritional status, as indicated by the increase in ALB levels, and the substantial enhancement in quality of life, as reflected by the improvement in SF-36 scores, underscore the effectiveness of the nursing intervention. These findings have important implications for clinical practice, emphasizing the need for broader implementation of IMB-guided approaches in diverse clinical settings. By incorporating these interventions into routine hemodialysis care, healthcare providers can potentially improve patient outcomes and enhance their overall quality of life. Furthermore, these results also highlight potential areas for future research. Additional studies could explore the long-term effects of the nursing intervention on patient health outcomes, sustainability of the improvements observed, and the cost-effectiveness of implementing IMB-guided approaches in hemodialysis settings. Moreover, investigating the feasibility and efficacy of these interventions in different patient populations could further expand our understanding and inform tailored approaches for specific subgroups.

Genome-Wide Association Analysis of Protein-Coding Variants in IgA Nephropathy.

SIGNIFICANCE STATEMENT: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility. BACKGROUND: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated. METHODS: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression. RESULTS: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03). CONCLUSIONS: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility.

Direct White-Light Emitting From a Single Metal-Organic Framework with Dual Phosphorescence Peaks.

Single component white-light-emitting (SCWLE) materials are extremely desired in the field of solid-state lighting. However, pure-phosphorescent SCWLE has rarely been reported. Herein, one halogen-bonding-containing MOF [Cd(5-BIPA)(phen)] (1) has been synthesized, which shows efficient white-light emission originating from dual phosphorescence bands with different wavelengths and lifetimes. The fabrication of a phosphor-converted white-light-emitting diode device driven by pulsing current enables this MOF to be a promising phosphor.

Fast photocatalytic degradation of rhodamine B using indium-porphyrin based cationic MOF under visible light irradiation.

A broad light-harvesting range and efficient charge separation are two main ways to enhance the visible photocatalytic performance of semiconductors. Herein, an ionic porphyrin MOF [In(TPyP)]·(NO3) (1) (TPyP = 5,10,15,20-tetrakis(4-pyridyl)-21H,23H-porphyrin) was synthesized via in situ metalation. The orderly arranged porphyrin photosensitizer and the internal electric field between the MOF host and NO3- guests enable effective visible light response and electron-hole separation. Consequently, the as-synthesized MOF shows efficient photocatalytic degradation of rhodamine B (RhB), methyl orange (MO) and methylene blue (MB) organic pollutants. It can degrade 99.07% of RhB within only 20 minutes under visible light irradiation (λ > 420 nm) with a high chemical reaction rate constant of 0.2400 min-1. The photocatalytic activity of the title MOF is more efficient than those of other reported MOFs, COFs and even inorganic semiconductors. The reusability, energy level, band gap, charge distribution and main degradation mechanisms of the photocatalyst were well studied.

The role of ferroptosis in chronic intermittent hypoxia-induced cognitive impairment.

PURPOSE: Obstructive sleep apnea (OSA) is a sleep disorder that may lead to cognitive impairment. The primary pathophysiological feature of OSA is chronic intermittent hypoxia (CIH), but the underlying mechanisms of CIH are not known. There have been few studies on the role of ferroptosis, a novel form of programmed cell death, during CIH-induced cognitive impairment. Therefore, this paper examined ferroptosis' effect on CIH-mediated cognitive impairment. METHODS: The study randomized twenty-four Sprague-Dawley (SD) male rats to control or CIH group. CIH rats were subjected to intermittent hypoxia for 4 weeks. Rat learning and memory were analyzed by the Morris water maze (MWM) test. Alterations of hippocampal neuronal ultrastructure were observed by transmission electron microscopy (TEM). Malondialdehyde (MDA) and ferrous iron (Fe2+) levels and superoxide dismutase (SOD) and reduced glutathione (GSH) contents were determined. Ferroptosis-associated protein levels were examined by Western blotting. RESULTS: The MWM test indicated that rats in the CIH group exhibited neurocognitive impairment. TEM showed that CIH induced mitochondrial damage. Significant increases in Fe2+ and MDA levels were observed in the CIH group, and GSH and SOD levels were decreased. Expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4) increased, and glutathione peroxidase 4 (GPX4) protein levels were decreased, suggesting that ferroptosis was induced in CIH model rats. The NF-E2-related factor 2 (Nrf2) protein level in the CIH group was decreased. CONCLUSION: Ferroptosis had an essential effect on CIH-mediated cognitive impairment, and it may occur via Nrf2 dysregulation. These findings lay a solid foundation for the subsequent study of OSA-associated cognitive impairment offering potential evidence for the development of therapeutic strategies.

Eudragit S100 prepared pH-responsive liposomes-loaded betulinic acid against colorectal cancer in vitro and in vivo.

This study aimed to develop polymer Eudragit S100 for preparing pH-responsive liposomes-loaded betulinic acid (pH-BA-LP) to improve the therapeutic index of chemotherapy for colorectal cancer. BA-loaded liposomes were coated with Eudragit S100 by a thin film dispersion and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and antitumor activity. In particular, pH-BA-LP showed advantages such as lower size (<100 nm), encapsulation efficiency of 90%, high stability, and stably cumulative release. By detecting the antitumor effects of pH-BA-LP in vivo, it showed that the tumor proliferation and cell migration were significantly inhibited in colorectal cancer. The pH-BA-LP also inhibited tumor growth via the regulation of Akt/TLR-mediated signalling and significantly down-regulated the expression of NFAT1 and NFAT4 proteins. It was found that pH-BA-LP can increase NK cells and CD3+ cells in tumor tissues, and the proportion of CD8+ cells in CD3+ cells was also increased, which proved that pH-BA-LP can play an antitumor effect by enhancing the autoimmunity level in tumor-bearing mice. The positive infiltration rates of CD8 and CD68 were increased and CD163 was relatively decreased by using pH-BA-LP, which proved that pH-BA-LP can regulate the immune infiltration levels in tumor-bearing mice. Therefore, the present work provides an effective method to prepare pH-responsive polymer-coated liposomes for colonic delivery with biologically active compounds.

Running an Internet Hospital in China: Perspective Based on a Case Study.

Internet hospitals, as a new forum for doctors to conduct diagnosis and treatment activities based on the internet, are emerging in China and have become integral to the development of the medical field in conjunction with increasing reforms and policies in China's medical and health system. Here, we take the Internet Hospital of the First Affiliated Hospital, Zhejiang University (FAHZU Internet Hospital) as an example to discuss the operations and functional positioning of developing internet hospital medical services in relation to physical hospitals. This viewpoint considers the platform operation, management, and network security of FAHZU Internet Hospital, and summarizes the advantages and limitations in the operation to provide a reference for other areas with interest in developing internet hospitals.

Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.

BACKGROUND: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. METHODS: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. RESULTS: Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). CONCLUSIONS: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations.

Incorporating Thiourea into Fluorescent Probes: A Reliable Strategy for Mitochondrion-Targeted Imaging and Superoxide Anion Tracking in Living Cells.

Three aggregation-induced emission active fluorescent compounds, TPA-Pyr-Octane, TPA-Pyr-Br, and TPA-Pyr-Thiourea (TPA = triphenylamine pyridinium), are synthesized; their tiny differences in chemical structures result in a huge difference in cell-imaging applications. Especially, incorporating thiourea into fluorescent probes is found as a reliable strategy for mitochondrion-targeted imaging and superoxide anion tracking in living cells, which is possibly due to the presence of hydrogen bonding between thiourea and mitochondrion proteins. This finding is very useful for the design of biosensors and delivery carriers in disease treatment.

Triterpenoids Extracted from Rhus chinensis Mill Act Against Colorectal Cancer by Inhibiting Enzymes in Glycolysis and Glutaminolysis: Network Analysis and Experimental Validation.

Background: Rhus chinensis Mill is a traditional Chinese medicine (TCM) mostly used to treat several cancer types. Although previous studies have found that certain ingredients of R. chinensis such as flavonoids can inhibit tumor cell proliferation [e.g. colorectal cancer (CRC)], systematic research on the mechanism underlying anticancer effect of active compounds like triterpenoids (TER) is lacking.Study Design: Herein, the concept of "network pharmacology primarily based on active compounds" was applied to explore the anticancer mechanisms of TER extract from R. chinensis. In this regard, potential targets and pathways of glycolysis and glutaminolysis form the basis for the anti-CRC effect of triterpenoids. Network pharmacology was used to predict several key proteins in the metabolic pathways, which were further verified via western blot and metabolomics methods.Results: Our results showed that the total TER in R. chinensis remarkably inhibited the proliferation and apoptosis of SW620 cells. The top 4 compounds of TER (viz., betulinic acid-BTA, betulonic acid-BTOA, betulin-BT, and semialactic acid-SA) were confirmed through the detection of UPLC-MS and analysis of cell proliferation assays. Mechanistically, this study revealed that TER plays an anti-CRC role through key targets, such as ENO1, ALDOA, PFKFB3, PKM2, and LDHA, as well as key glycolytic and glutaminolytic pathways.Conclusion: Collectively, these results have provided new insights into the mechanism underlying anti-CRC effect of triterpenoids extract obtained from R. chinensis, mainly through combination of compositional quantitative analysis, network pharmacology, and experimental verification.

Strategies to target energy metabolism in consensus molecular subtype 3 along with Kirsten rat sarcoma viral oncogene homolog mutations for colorectal cancer therapy.

Alterations in cellular energy metabolism play a critical role in colorectal cancer (CRC), which has been identified as the definition of consensus molecular subtypes (CMSs), and CMS3 tumors exhibit energy metabolism signatures along with Kirsten rat sarcoma viral oncogene homolog (KRAS)-activating mutations. This review summarizes the relationship between CMS3 tumors associated with mutated KRAS and energy metabolism in CRC, especially for the dysregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review concentrates on the role of metabolic genes and factors and signaling pathways, which coupled with a primary energy source connected with the CMS3 associated with mutated KRAS, induce metabolic alterations. The strategies to target energy metabolism for the metabolic alterations in mutated KRAS CRC are also introduced. In conclusion, dysregulated energy metabolism has a close relationship with mutated KRAS in CMS3 tumors. Therefore, selective inhibitors or agents against metabolic targets or KRAS signaling may be clinically useful for CMS3 tumor treatment through a personalized approach for patients with cancer.

Strategies for targeting energy metabolism in Kirsten rat sarcoma viral oncogene homolog -mutant colorectal cancer.

Alterations in cellular energy metabolism play critical roles in colorectal cancer (CRC). These alterations, which correlate to KRAS mutations, have been identified as energy metabolism signatures. This review summarizes the relationship between colorectal tumors associated with mutated KRAS and energy metabolism, especially for the deregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review will concentrate on the role of metabolic genes, factors and signaling pathways, which are coupled with the primary energy source connected with the KRAS mutation that induces metabolic alterations. Strategies for targeting energy metabolism in mutated KRAS CRC are also introduced. In conclusion, deregulated energy metabolism has a close relationship with KRAS mutations in colorectal tumors. Therefore, selective inhibitors, agents against metabolic targets or KRAS signaling, may be clinically useful for colorectal tumor treatment through a patient-personalized approach.

After-effects of repetitive anodal transcranial direct current stimulation on learning and memory in a rat model of Alzheimer's disease.

Repetitive anodal transcranial direct current stimulation (tDCS) in a rat model of Alzheimer's disease (AD) has been shown to have distinct neuroprotective effects. Moreover, the effects of anodal tDCS not only occur during the stimulation but also persist after the stimulation has ended (after-effects). Here, the duration of the after-effects induced by repetitive anodal tDCS was investigated based on our previous studies. Adult male Sprague-Dawley rats were divided into three groups: a sham group, a ß-amyloid (Aß) group (AD group) and a stimulation group (ATD group). Aß was injected into the bilateral hippocampi of the rats in the AD and ATD groups to produce the AD model. Rats in the ATD group underwent 10 sessions of anodal tDCS, and the after-effects of repetitive anodal tDCS were evaluated by behavioral and histological analyses. A Morris water maze (MWM) was utilized on a monthly basis to assess spatial learning and memory abilities. The ATD group showed shorter escape latencies and more platform region crossings than the AD group. Hippocampal choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) immunohistochemical analyses were carried out after the last MWM assessment. The immunohistochemistry results showed notable differences among the groups, particularly between the AD and ATD groups. This study reveals that repetitive anodal tDCS can not only improve cognitive function and memory performance but also has long-term after-effects that persist for 2 months.

Two aggregation-induced emission (AIE)-active reaction-type probes: for real-time detecting and imaging of superoxide anions.

Fluorescent probes are powerful tools for investigating reactive oxygen species (ROS) in living organisms. The overproduced "primary" ROS of superoxide anions (O2˙-) cause a chain of oxidative damage. In order to monitor O2˙- level fluctuations in living cells, we synthesized two reaction-type probes of TPA-DHP-1,2,3 and TPA-PPA-1,2,3, which were composed of an electron-rich triphenylamine (TPA) and the very active functional groups of dihydropyridine (DHP) and pyridinium (PPA). Intriguingly, DHP and PPA were able to carry out easy proton abstractions and nucleophilic reactions in the presence of O2˙-, resulting in the corresponding products with sharp wavelength shifts, and elevated fluorescence intensities. Therefore, undesirable background fluorescence interference can be reduced during the monitoring and imaging process. Meanwhile, the developed dual-channel monitoring strategy not only provides observations of the O2˙- level fluctuations, but could also be employed to image the dynamic accumulation process of probes in the different cell organelles. Therefore, the design could provide a simple, accurate and universal platform for biological applications in future research work.

New strategies for targeting glucose metabolism-mediated acidosis for colorectal cancer therapy.

Colorectal cancer (CRC) is a heterogeneous group of diseases that are the result of abnormal glucose metabolism alterations with high lactate production by pyruvate to lactate conversion, which remodels acidosis and offers an evolutional advantage for tumor cells, even enhancing their aggressive phenotype. This review summarizes recent findings that involve multiple genes, molecules, and downstream signaling in the dysregulated glycolytic pathway, which can allow a tumor to initiate acid byproducts and to progress, thereby resulting in acidosis commonly found in the tumor microenvironment of CRC. Moreover, the relationship between CRC cells and the tumor acidic microenvironment, especially for regulating lactate production and lactate dehydrogenase A levels, is also discussed, as well as comprehensively defining different aspects of glycolytic pathways that affect cancer cell proliferation, invasion, and migration. Furthermore, this review concentrates on glucose metabolism-mediated transduction factors in CRC, which include acid-sensing ion channels, triosephosphate isomerase and key glycolysis-related enzymes that regulate glycolytic metabolites, coupled with the effect on tumor cell glycolysis as well as signaling pathways. In conclusion, glucose metabolism mediated by glycolytic pathways that are integral to tumor acidosis in CRC is demonstrated. Therefore, selective metabolic inhibitors or agents against these targets in glucose metabolism through glycolytic pathways may be clinically useful to regulate the tumor's acidic microenvironment for CRC treatment and to identify specific targets that regulate tumor acidosis through a cancer patient-personalized approach. Furthermore, strategies for modifying the metabolic processes that effectively inhibit cancer cell growth and tumor progression and activate potent anticancer effects may provide more effective antitumor prospects for CRC therapy.

Hypertrophied myocardium is vulnerable to ischemia/reperfusion injury and refractory to rapamycin-induced protection due to increased oxidative/nitrative stress.

Left ventricular hypertrophy (LVH) is causally related to increased morbidity and mortality following acute myocardial infarction (AMI) via still unknown mechanisms. Although rapamycin exerts cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury in normal animals, whether rapamycin-elicited cardioprotection is altered in the presence of LVH has yet to be determined. Pressure overload induced cardiac hypertrophied mice and sham-operated controls were exposed to AMI by coronary artery ligation, and treated with vehicle or rapamycin 10 min before reperfusion. Rapamycin produced marked cardioprotection in normal control mice, whereas pressure overload induced cardiac hypertrophied mice manifested enhanced myocardial injury, and was refractory to rapamycin-elicited cardioprotection evidenced by augmented infarct size, aggravated cardiomyocyte apoptosis, and worsening cardiac function. Rapamycin alleviated MI/R injury via ERK-dependent antioxidative pathways in normal mice, whereas cardiac hypertrophied mice manifested markedly exacerbated oxidative/nitrative stress after MI/R evidenced by the increased iNOS/gp91phox expression, superoxide production, total NO metabolites, and nitrotyrosine content. Moreover, scavenging superoxide or peroxynitrite by selective gp91phox assembly inhibitor gp91ds-tat or ONOO- scavenger EUK134 markedly ameliorated MI/R injury, as shown by reduced myocardial oxidative/nitrative stress, alleviated myocardial infarction, hindered cardiomyocyte apoptosis, and improved cardiac function in aortic-banded mice. However, no additional cardioprotective effects were achieved when we combined rapamycin and gp91ds-tat or EUK134 in ischemic/reperfused hearts with or without LVH. These results suggest that cardiac hypertrophy attenuated rapamycin-induced cardioprotection by increasing oxidative/nitrative stress and scavenging superoxide/peroxynitrite protects the hypertrophied heart from MI/R.

Association of TNFSF13 polymorphisms with IgA nephropathy in a Chinese Han population.

BACKGROUND: Our previous genome-wide association study of IgA nephropathy (IgAN) in a Chinese Han population suggested that the TNFSF13 gene may be a novel susceptibility gene for IgAN. In the present study, we aimed to further evaluate the associations of single-nucleotide polymorphisms (SNPs) and expression level of the TNFSF13 gene with the risk and clinical parameters of IgAN. METHODS: Six candidate SNPs were selected for genotyping by Sequenom MassARRAY iPLEX in 1000 IgAN cases and 1000 controls. Unconditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) with adjustment for age and sex. Serum APRIL (encoded by the TNFSF13 gene) level was detected by an enzyme-linked immunosorbent assay. RESULTS: We found that rs3803800 was significantly associated with the susceptibility of IgAN after Bonferroni correction [padditive  = 0.0009, OR (95% CI) = 1.25 (1.09-1.42); precessive  = 0.0006, OR (95% CI) = 1.54 (1.20-1.96)]; however, the association remained only in women after further sex-stratified analysis. Genotype-phenotype correlation analysis showed significant associations of rs3803800 with severe clinicopathological manifestations in IgAN patients after adjusting for age and sex, as well as the other two SNPs (rs4246413 and rs4968210) that were also associated with specific clinical phenotypes. Compared with healthy controls, serum APRIL levels were significantly higher in IgAN patients (p = 0.0001) and associated with severity of disease. CONCLUSIONS: The results of the present study indicate that the genetic variations and gene expression level of TNFSF13 are associated with the susceptibility and severity of IgAN in a Han Chinese population.

Intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct for choledocholithiasis combined with cholecystolithiasis: a cohort study of 211 cases.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) was often used for preoperative biliary drainage in cases like cholangiocarcinoma or acute obstructive suppurative cholangitis, reports on endoscopic nasobiliary drainage (ENBD) over primary closure of the common bile duct (CBD) are limited. This study compares outcomes of laparoscopic cholecystectomy (LC) + laparoscopic CBD exploration (LCBDE) + intraoperative ENBD + primary closure of CBD with equivalent patients who underwent preoperative endoscopic retrograde cholangiopancreatography (ERCP) and subsequent LC. METHODS: From January 2013 to December 2015, 829 consecutive patients with choledocholithiasis combined with cholecystolithiasis underwent surgery in our department. 211 patients underwent LC + LCBDE + intraoperative ENBD + primary closure of CBD (group A) and 117 preoperative ERCP + subsequent LC (group B). A total of 501 patients (355 who underwent T-tube drainage and 146 who underwent transcystic exploration) were excluded from the analysis. Clinical records, operative findings, and postoperative follow-up were analyzed. RESULTS: Age and sex distribution, comorbidity, presentations, CBD diameter, and size and number of stones were similar in the two groups, and there was no postoperative mortality. Duration of surgery in group A was shorter (83 vs. 104 min, P < 0.01), as was postoperative hospital stay (6 vs. 9 days, P < 0.01). Average operative expenditure in group A was less than that of group B ($ 3816 vs. $ 4015, P < 0.01). The success rate in group A was higher (100 vs. 91%, P < 0.01). Ten patients in group B converted to LCBDE. The postoperative complication rate was higher in group B but without significant difference (1.9 vs. 4.2%, P = 0.29). Median follow-up time was 24 (3-28) months (n = 302 patients). Two patients in group B reported residual stones. CONCLUSION: LC + LCBDE + intraoperative ENBD + primary closure of CBD should have priority over preoperative ERCP + subsequent LC for choledocholithiasis combined with cholecystolithiasis.

Early prediction of intestinal mucosal barrier function impairment by elevated serum procalcitonin in rats with severe acute pancreatitis.

OBJECTIVES: The aim of this study was to evaluate serum procalcitonin (PCT) levels as a prognostic indicator of intestinal barrier function impairment in rats with severe acute pancreatitis (SAP). METHODS: Thirty-six male Sprague Dawley rats were randomly grouped into SAP group (injected sodium taurocholate via biliopancreatic duct), Gln group (gavaged with glutamine after modeling), and control group. Blood, pancreatic, and terminal ileum tissues were obtained from the rats after 6 h of modeling. Serum amylase (Amy) levels were determined using an automatic biochemical detector, while endotoxin (ET), diamine oxidase (DAO), and PCT levels were measured by ELISA test. The pathology of pancreatic and small intestine tissues were observed. PCT protein expression in intestinal tissues were detected by immunohistochemistry and western blot. RESULT: Pancreatic and intestinal injuries in Gln group were significantly lower than SAP group. Serum amylase, DAO, and PCT levels in SAP and Gln groups differed greatly and were significantly higher than control group. Immuno-histochemistry and western blot results showed that PCT protein expression levels in small intestine tissues of SAP group were higher than Gln group and control group. Serum PCT levels had a significant correlation with serum endotoxin, DAO levels and intestinal mucosal injury scores. CONCLUSION: PCT expression in serum and intestinal tissues in SAP rats increased significantly in the early stages of SAP, and was closely related to the onset and degree of intestinal barrier function impairment. Thus, our results showed that measuring serum PCT can be used to predict intestinal mucosal barrier function impairment in SAP rats.