Bounding the Amount of Entanglement from Witness Operators.

We present an approach to estimate the operational distinguishability between an entangled state and any separable state directly from measuring an entanglement witness. We show that this estimation also implies bounds on a variety of other well-known entanglement quantifiers. This approach for entanglement estimation is then extended to both the measurement-device-independent scenario and the fully device-independent scenario, where we obtain nontrivial but suboptimal bounds. The procedure requires no numerical optimization and is easy to compute. It offers ways for experimenters to not only detect, but also quantify, entanglement from the standard entanglement witness procedure.

Involvement of reactive oxygen species in lanthanum-induced inhibition of primary root growth.

Although lanthanum (La) has been used as an agricultural plant growth stimulant for approximately 50 years, high concentrations are toxic to plants. Despite significant advances in recent years, the mechanisms underlying the effects of La on root system development remain unclear. Here, we report that a high concentration of La inhibits primary root (PR) elongation and induces lateral root (LR) development. La results in cell death in PR tips, thereby leading to the loss of meristematic cell division potential, stem cell niche activity, and auxin distribution in PR tips. Further analysis indicated that La induces reactive oxygen species (ROS) over-accumulation in PR tips. Reduction in ROS accumulation partially alleviated the inhibitory effects of La on PR elongation by improving cell survival in PR tips and thereby improving meristematic cell division potential and auxin distribution in PR tips. We also found ROS to be involved in La-induced endocytosis. Genetic analyses supported the described phenotype. Overall, our results indicate that La affects root growth, at least partially, by modulating ROS levels in roots to induce cell death in PR tips and subsequent auxin redistribution in roots, leading to remodeling of the root system architecture.

Design, synthesis and preliminary evaluation of the anti-inflammatory of the specific selective targeting druggable enzymome cyclooxygenase-2 (COX-2) small molecule.

CONTEXT: Development of a reliable and selective anti-inflammatory agent of cyclooxygenase-2 (COX-2), induced or up-regulated by inflammatory/injury stimulus such as IL-1ß, TNF-α and LPS in the various types of organs, tissues and cells, with low side effects is a long-standing medicinal chemistry problem with significant social implications. OBJECTIVE: To target druggable enzymome COX-2 by exploiting NSAIDs and genipin (GEP) in anti-inflammatory infection. MATERIALS AND METHODS: The compound aspirin GEP ester (AGE) was designed by computer-assisted screening, synthesized in the esterification of the acylate derivative and the methylate derivative with Et3N, and evaluated with 20, 40 and 60 mg/kg from days 18 to 24 after immunization in collagen-induced arthritis (CIA) rats by the sequential enzymatic experiments, western-blot analysis and pathological observation methods. RESULTS: AGE exhibited higher binding affinity with COX-1 and displayed the lowest estimated free energy with COX-2 than other ligands built by hanging NSAIDs with GEP, and was characterized by 1H NMR, 13C NMR and HRMS. AGE was competed against COX-2 with molecule-dependent potencies and selectivity (IC50: 0.36 mM; selectivity index: 275) in the sequential enzymatic experiments and decreased the expression of COX-2 in peripheral blood lymphocytes of CIA rats. AGE (40 and 60 mg/kg) could significantly relieve the secondary hind paw swelling and arthritis index, along with observing AGE attenuated histopathological changes of fibroblast like synovial tissue (FLST) and mesenteric lymph node lymphocytes (MLNL) in CIA rats. DISCUSSION AND CONCLUSION: AGE pharmacophore reported herein may be an effective strategy to develop a novel anti-inflammatory agent and potential inhibitor of COX-2.

Effects of Fluid Shear Stress on Expression of Smac/DIABLO in Human Umbilical Vein Endothelial Cells.

OBJECTIVE: To investigate the molecular mechanisms of laminar shear stress on inhibition of apoptosis in endothelial cells, human umbilical vein endothelial cells (HUVECs) were starved in medium containing 2% fetal bovine serum and 20 dyne/cm(2) shear stress. METHODS: HUVECs were subjected to shear stress or incubated in a static condition and then Smac/DIABLO expression was quantified by reverse-transcription polymerase chain reaction, real-time PCR, and western blot. The effect of shear stress on the migration of Smac/DIABLO proteins was detected by immunofluorescence microscopy. RESULTS: Results demonstrated that 20 dyne/cm(2) shear stress inhibited the expression of Smac/DIABLO at both the mRNA and protein levels in cultured HUVECs. Furthermore, release of Smac/DIABLO from mitochondria was induced by removal of basic fibroblast growth factor and decrease of fetal bovine serum in the medium, whereas shear stress inhibited its release under the same conditions. CONCLUSIONS: These results suggest that down-regulation of Smac/DIABLO may contribute to the potent antiatherosclerotic effect of shear stress by preventing endothelial cells from entering apoptosis.

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus.

Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1α) is widely expressed in pancreatic ß cells, the liver, the intestines, and other organs. HNF1α is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1α gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1α by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1α mutation.

Treatment of patients with Covid-19 with a high dose of ulinastatin.

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

15-Month Health Outcomes and the Related Risk Factors of Hospitalized COVID-19 Patients From Onset: A Cohort Study.

Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored. Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients' health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed. Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from post-traumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females to males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity. Conclusions: 15-month follow-up in this study demonstrated the need of extended rehabilitation intervention for complete recovery in COVID-19 patients.

Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma.

BACKGROUND: Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision. OBJECTIVE: To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration. METHODS: Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration. RESULTS: Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level greater than 37 U/mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, respectively. CONCLUSIONS: The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.

Symptomatic features and prognosis of 932 hospitalized patients with coronavirus disease 2019 in Wuhan.

OBJECTIVE: To discern the symptomatic features of coronavirus disease 2019 (COVID-19) and to evaluate the severity and prognosis of the disease. METHODS: In this retrospective cohort study, 932 hospitalized patients with COVID-19 in Wuhan were enrolled, including 52 severe and 880 non-severe cases. All patients were followed up for 3 months after discharge. The symptomatic features and follow-up data of the patients in both groups were analyzed and compared. RESULTS: Of the 932 patients, fever (60.0%), cough (50.8%) and fatigue (36.4%) were the most common symptoms. In total, 32.7% of the severe cases presented with gastrointestinal symptoms at disease onset, including anorexia, nausea, vomiting or diarrhea, which was significantly higher than that of the non-severe group (P = 0.0015). The incidence of olfactory disturbance and dysgeusia was only 3.1% and 6.2%, respectively. After adjusting for age and sex, multivariate regression analysis showed that fever lasting for over 5 days (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.00-3.62, P = 0.0498), anorexia at onset (OR 2.61, 95% CI 1.26-5.40, P = 0.0096), and modified Medical Research Council level above grade 2 when dyspnea occurred (OR 14.19, 95% CI 7.01-28.71, P < 0.0001) were symptomatic risk factors for severe COVID-19. During the follow-up, cough (6.2%), dyspnea (7.2%), fatigue (1.8%), olfactory disturbance and dysgeusia (1.5%) were the significant remaining symptoms. CONCLUSIONS: COVID-19 causes clusters of symptoms with multiple systems involved. Certain symptomatic characteristics have predictive value for severe COVID-19. Short-term follow-up data reveal that most patients have a good prognosis.

[Exogenous NO application effectively alleviates the allelochemical stress on cucumber root border cells caused by Eupatorium adenophorum extracts.] / 外源NOç¼“è§£ç´«èŒŽæ³½å °æå–ç‰©å¯¹é»„ç“œæ ¹è¾¹ç¼˜ç»†èƒžçš„åŒ–æ„Ÿèƒè¿«.

Using suspension cultures of cucumber (Cucumis sativus) cultivar Jinyou 35, we investigated the effects of allelochemical stresses induced by Eupatorium adenophorum extracts on root border cells (RBC), and the role of exogenous NO application in alleviation of the damage of root tips exposed to E. adenophorum extracts. The results showed that, 1000 mg·L-1 E. adenophorum extracts had significant damage to the cucumber root tip, resulting in severe tissue damage, exfoliated surface cells and irregular arrangement of inner cells, while those damages could be effectively alleviated by spraying exogenous NO. Compared with the control, E. adenophorum extracts (ZL) markedly reduced RBC numbers and survival rates by 54.5% and 97.2%, respectively, the RBC apoptosis rates were 12.3 times higher, the thicknesses of RBC adhesive layers were increased by 31.4%, and the root cap PME activities were markedly increased. Compared with the ZL treatment, exogenous NO application (ZN) significantly increased RBC numbers and survival rates by 72.4% and 146.0%, respectively, reduced the corresponding RBC apoptosis rates and the thicknesses of RBC adhesive layers by 30.7% and 15.0%, respectively, and inhibited the PME activities by 14.3% upon treatment for 72 hours. Our findings revealed that E. adenophorum extracts showed toxic effects on the cucumber RBC, resulting in cell apoptosis, abolishment of the RBC protection on root tips, and the destruction of root tip structure. Exogenous NO application, to some extent, could prevent the root tip and RBC from cell damage caused by E. adenophorum extracts.

Quantitative Analysis of Multi-components by Single Marker and Fingerprint Analysis of Achyranthes bidentata Blume.

A simple and effective method of high performance liquid chromatography (HPLC) with diode array detection was established to identify the origin of Achyranthes bidentata Blume and evaluate its quality, based on chromatographic fingerprint combined with the similarity analysis, hierarchical cluster analysis and the quantitative analysis of multi-components by single marker (QAMS). In the chromatographic fingerprint, 16 peaks were selected as the common model to evaluate the similarities among 18 batches (S1-S18) of A. bidentata Blume samples collected from different origins in China. The similarities values for 18 batches of samples were more than 0.75, which compared with control fingerprint. Furthermore, 18 batches of A. bidentata Blume samples were categorized into two groups for quantitative analysis, the quantification of three bioactive constituents (ß-ecdysterone, cyasterone and 5-hydroxymethyl furfural) between QAMS and external standard method proved the consistency of the two methods, the three constituents showed good regression (R > 0.9995) within linear ranges, and their recoveries were within the range of 97.6-101.5%. This study demonstrated that the quality of A. bidentata Blume can be successfully evaluated by means of a combination of HPLC chromatographic fingerprint and QAMS approach.

Tumor SOCS3 methylation status predicts the treatment response to TACE and prognosis in HCC patients.

BACKGROUND: Suppressor of cytokine signaling (SOCS) 1 and 3 methylation have been associated with clinical features and outcomes of cancer patients. However, their roles in determining the treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) remain unknown. RESULTS: We found that presence of SOCS3 methylation is significantly associated with the major clinical features of HCC patients, including tumor stage, lymph node and vascular invasion. Of note, we observed that the presence of SOCS3 methylation is closely related to TACE response. In prognosis analyses, HCC patients with SOCS3 methylation presence have a poorer prognosis indicated by lower 3-, and 5-year survival rates and shorter mean survival period, than those without. Multivariate COX analysis confirms the prognostic role of the presence of SOCS3 methylation in HCC patients receiving TACE treatment. MATERIALS AND METHODS: A total of 246 HCC patients receiving TACE were enrolled in this study. Tumor samples was obtained from echo-guided fine needle aspiration and genomic DNA from tumor samples was purified. SOCS1 and SOCS3 methylation status were detected using methylation-specific polymerase chain reaction. The treatment responses to TACE of patients were evaluated after procedure and all patients were followed for prognosis analysis. CONCLUSIONS: This finding suggests that the presence of SOCS3 methylation is a marker to predict treatment response and prognosis in HCC patients receiving TACE therapy.

Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces ß-cell proliferation in diabetic mice.

Recent progress in regenerative medicine has suggested that mesenchymal stem cell (MSC)-based therapy is a novel potential cure for diabetes. Betatrophin is a newly identified hormone that can increase the production and expansion of insulin-secreting ß-cells when administered to mice. In this study, we evaluated the effect of betatrophin overexpression by human adipose-derived MSCs (ADMSCs) by in vitro experiments, as well as following their transplantation into a mice with streptozotocin (STZ)-induced diabetes. The overexpression of betatrophin did not affect the ADMSCs in terms of proliferation, differentiation and morphology. However, the co-culture of human islets with ADMSCs overexpressing betatrophin (ADMSCs-BET) induced islet proliferation, ß-cell specific transcription factor expression, and the islet production of insulin under the stimulation of glucose or KCl and Arg. In addition, ADMSCs-BET enhanced the anti-inflammatory and anti-apoptotic effects of the co-cultured islets compared with ADMSCs cultured alone. In mice with STZ-induced diabetes, the transplantation of ADMSCs-BET ameliorated the hyperglycemia and weight loss associated with STZ-induced diabetes; ADMSCs-BET also significantly enhanced the ratio of ß-cells per islet compared to the transplantation of ADMSCs alone. Thus, our study demonstrates a novel strategy for inducing ß-cell regeneration. ADMSCs-BET may replace insulin injections by increasing the number of endogenous insulin-producing cells in patients with diabetes. This combined strategy of ADMSC transplantation and gene therapy may prove to be a useful therapy for the treatment of diabetes.

Determination of geniposide in adjuvant arthritis rat plasma by ultra-high performance liquid chromatography tandem mass spectrometry method and its application to oral bioavailability and plasma protein binding ability studies.

A specific, sensitive and high throughput ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometric method (UHPLC-ESI-MS/MS) was established and validated to assay geniposide (GE), a promising anti-inflammatory drug, in adjuvant arthritis rat plasma: application to pharmacokinetic and oral bioavailability studies and plasma protein binding ability. Plasma samples were processed by de-proteinised with ice-cold methanol and separated on an ACQUITY UPLC™ HSS C18 column (100 mm × 2.1mm i.d., 1.8 µm particle size) at a gradient flow rate of 0.2 mL/min using acetonitrile-0.1% formic acid in water as mobile phase, and the total run time was 9 min. Mass detection was performed in selected reaction monitoring (SRM) mode with negative electro-spray ionization includes the addition of paeoniflorin (Pae) as an internal standard (IS). The mass transition ion-pair was followed as m/z 387.4 → 122.4 for GE and m/z 479.4 → 449.0 for IS. The calibration curves were linear over the concentration range of 2-50,000 ng/mL with lower limit of quantification of 2 ng/mL. The intra-day and inter-day precisions (RSD, %) of the assay were less than 8.4%, and the accuracy was within ± 6.4% in terms of relative error (RE). Extraction recovery, matrix effect and stability were satisfactory in adjuvant arthritis rat plasma. The UHPLC-ESI-MS/MS method was successfully applied to a pharmacokinetic study of GE after oral administration of depurated GE at 33, 66, 132 mg/kg and intravenous injection at 33, 66, 132 mg/kg in adjuvant arthritis (AA) rats. In addition, it was found that GE has rapid absorption and elimination, low absolute bioavailability, high plasma protein binding ability in AA rats after oral administration within the tested dosage range. It suggested that GE showed slow distribution into the intra- and extracellular space, and the binding rate was not proportionally dependent on plasma concentration of GE when the concentration of GE was below 5.0 µg/mL.

Effects of fluid shear stress on the expression of Omi/HtrA2 in human umbilical vein endothelial cells.

To investigate the molecular mechanisms of laminar shear stress on the inhibition of apoptosis in endothelial cells, human umbilical vein endothelial cells (HUVECs) were starved in medium containing 2% fetal bovine serum (FBS) and treated with 15 dyne/cm2 shear stress. We confirmed that 15 dyne/cm2 shear stress inhibited the expression of Omi/HtrA2 at the mRNA and protein levels in cultured HUVECs. Furthermore, the release of Omi/HtrA2 from the mitochondria was induced by removal of basic fibroblast growth factor and decrease of FBS in the medium, while shear stress inhibited its release under the same conditions. These results suggest that downregulation of Omi/HtrA2 may contribute to the potent anti-atherosclerotic effect of shear stress by preventing endothelial cells from entering apoptosis.

Regulation of C-type natriuretic peptides and natriuretic peptide receptor-B expression in diabetic rats renal treated by Tongluo Recipe.

OBJECTIVE: To investigate the expression of C-type natriuretic peptides (CNP) and natriuretic peptide receptor-B (NPR-B) receptor in diabetic rats renal cortex, and the regulation by Tongluo Recipe (TLR). METHODS: Sixty male SD rats were divided into 3 groups: the normal control group, diabetic model group and diabetic TLR group. Each group was further divided into two subgroups of ten in each, according to 4-week or 12-week observation period. Streptozotocin (STZ)-induced diabetic rats were treated with TLR (1.0 g·kg(-1)·d(-1)) for 4 and 12 weeks, respectively. (1) The essential information was collected for comparing renal mass, serum creatinine and 24 h urine albumen on each group was calculated. (2) CNP mRNA and NPR-B mRNA were detected by realtime-polymerase chain reaction (PCR) on rats renal cortex. (3) Concentration of CNP on renal cortex or serum were analyzed by enzyme-linked immunosorbent assay (ELISA). (4) Pathological evaluation and NPR-B immunostaining for renal tissue were also performed. RESULTS: (1) CNP and NPR-B mRNA levels were detected in each treated or untreated group, with slight elevated in untreated diabetes rats administrated with STZ after 4-week and CNP mRNA level remarkable elevated at 39.21 times higher than normal control group after 12 weeks, but NPR-B mRNA level showed a remarkably down-regulation at 98.07% after 12 weeks. CNP mRNA of TLR-treated group was also elevated after 12-week treatment, but less than untreated group. (2) Concentrations of CNP in renal cortex were obviously increased in treated or untreated diabetes rats, within these groups the treatment of TLR was found more significantly on prompting CNP concentration. Comparing to normal group, serum concentrations of CNP were also increased in treated or untreated diabetic groups, but there was no difference between these diabetic groups. (3) Renal lesions like glomerular volume increased are observed mostly in the relative early stage after 4 weeks. Although TLR treated group had no significant difference in their glomerular volume, the degrees of injury of glomerulus were ameliorated, as well as the NPR-B immunostaining enhanced in glomerulus. Weakly positive immunostaining of NPR-B are observed in glomerulus of normal control, and negative in glomerulus of untreated diabetes rats administrated with STZ after 12 weeks, whereas TLR-treatment groups showed a little enhancement. CONCLUSION: CNP and NPR-B showed different characteristic on renal cortex at different pathological period in diabetes rats, and TLR regulated their expression.

MicroRNA-15a positively regulates insulin synthesis by inhibiting uncoupling protein-2 expression.

MicroRNAs are small noncoding RNAs that have been highly conserved during evolution and have been implicated to play an important role in many diseases, including diabetes. Several reports indicated the function of miRNAs in insulin production. However, the mechanisms by which miRNAs regulate this process remain poorly understood. Here we found that the expression of miR-15a was up-regulated in the presence of high glucose for 1h, whereas prolonged periods of high glucose exposure resulted in depressed expression of miR-15a, and the change in expression levels of miR-15a coincided with insulin biosynthesis. Moreover, ectopic expression of miR-15a promoted insulin biosynthesis in MIN6 cells, whereas its repression was sufficient to inhibit insulin biosynthesis. Further, we verified that miR-15a directly targeted and inhibited uncoupling protein-2 (UCP-2) gene expression. miR-15a mimics inhibited UCP-2 3'UTR luciferase reporter activity. Western blot analysis showed that miR-15a inhibited endogenous UCP-2 protein levels, and resulted in the increase in oxygen consumption and reduced ATP generation. This study suggests miR-15a is a mediator of ß cell function and insulin biosynthesis, thus offering a new target for the development of preventive or therapeutic agents against diabetes.

Retrospective analysis of histopathologic prognostic factors after hepatectomy for intrahepatic cholangiocarcinoma.

BACKGROUND: The aim of this study was to investigate histopathologic prognostic factors in patients with intrahepatic cholangiocarcinoma (ICC) whose tumors were resected to determine the optimal surgical strategies. METHODS: One hundred and two ICC patients who underwent laparotomy from July 1998 to December 2000 were followed up successfully. Histopathologic variables were selected for univariate and multivariate analyses to evaluate their influence on the outcome. RESULTS: The 1-, 3-, and 5-year survival rates after surgery were 56.9%, 25.5%, and 16.9%, respectively. The average survival duration was 21.91 +/- 20.17 months. In univariate analysis, the presence of lymph node (LN) metastasis, number of LNs with metastases, presence of intrahepatic metastasis, curative resection, and TNM stage were significant risk factors for survival. Multivariate analysis revealed that intrahepatic metastasis, noncurative resection, and TNM stage IVa were independent prognostic factors. CONCLUSIONS: The histopathologic characteristics of intrahepatic metastasis were closely related to poor prognosis in ICC patients. Extensive hepatectomy with LN dissection may offer the only chance for long-term survival in patients with ICC.