Influence of immunosuppressive drugs on natural killer cells in therapeutic drug exposure in liver transplantation.

Background: Natural killer (NK) cells are enriched in the liver and are the main regulators in liver transplantation regarding rejection or tolerance, viral infection, or tumor recurrence. Immunosuppression consists of a triple drug standard regimen comprising tacrolimus (TAC) and corticosteroids (CS) with either mycophenolate mofetil (MMF) or sirolimus (SIR)/everolimus (EVE). The aim of this study was to evaluate the impact of trough levels of these regimens under clinical conditions and exposure on human NK-cell activity and function in order to better understand the antiviral and anti-tumor effects of mammalian target of rapamycin inhibitor (mTORI). Methods: Peripheral blood mononuclear cells (PBMCs) were collected from liver transplant recipients and healthy controls. Number and phenotypes of NK cells in vivo were analyzed by flow cytometry. In this study we simulated the immunosuppressive microenvironment in vitro. PBMCs were cultured at the clinically effective plasma concentration of drugs for 3 d to detect the effect of immunosuppressants on NK cells. Drug type and concentration: single drug [EVE, 5 ng/mL; SIR, 5 ng/mL; TAC, 5 ng/mL; cyclosporine A (CSA), 125 ng/mL; MMF, 15 µg/mL; CS, 0.5 µg/mL] and combined immunosuppressants (Group 1: TAC, 5 ng/mL + MMF, 15 µg/mL + CS, 0.5 µg/mL; Group 2: TAC, 5 ng/mL + SIR, 5 ng/mL + CS, 0.5 µg/mL; Group 3: TAC, 5 ng/mL + EVE, 5 ng/mL + CS, 0.5 µg/mL). In addition, NK cells were sorted from PBMCs and treated under the above conditions to detect NK cell killing function and RNA transcription characteristics. Results: CS significantly impaired the cytolytic activity of NK cells, followed by MMF and SIR/EVE. CS and TAC/CSA significantly decreased the secretion of IFN-γ and CD107a. NK cell function in liver transplant recipients was most pronouncedly inhibited by a triple immunosuppressive regimen, with CS playing the most prominent role compared with the other drugs. The MMF-containing regimen demonstrated a significant increase in the expression of suppressive genes, especially of the Siglec7/9 family. The SIR group had stronger NK cell activity compared with that of the MMF group, although liver transplantation patients have lower NK cell activity and function. Conclusions: Despite an overall comparable immunosuppressive efficiency in terms of prevention of acute rejection, a mTORIs-including regimen might be considered as having less impact on NK cell function.

Entecavir Combined With Short-term Hepatitis B Immunoglobulin in Preventing Hepatitis B Virus Recurrence in Liver Transplant Recipients.

BACKGROUND: The combination of nucleoside analogs and long-term hepatitis B immunoglobulin (HBIG) is considered to be the standard regimen for preventing hepatitis B virus (HBV) recurrence after liver transplant (LT). However, long-term use of HBIG causes many adverse effects. The aim of this study was to evaluate the effect of nucleoside analogs entecavir combined with short-term HBIG in preventing HBV recurrence after LT. METHODS: This retrospective study assessed the effect a combination of entecavir and short-term HBIG in prophylaxis of HBV recurrence among 56 LT recipients who had undergone the procedure because of HBV-associated liver disease at our center between December 2017 and December 2021. All patients received entecavir treatment combined with HBIG for the prevention of hepatitis B recurrence, and HBIG treatment was withdrawn within 1 month. The patients were followed up to determine levels of hepatitis B surface antigen, antibody to hepatitis B surface antigen (HBsAb), and HBV-DNA and the recurrence rate of HBV. RESULTS: Only 1 patient appeared positive for hepatitis B surface antigen at 2 months post-LT. The overall HBV recurrence rate was 1.8%. The HBsAb titers of all patients gradually decreased over time, with a median of 376.6 IU/L at 1 month post-LT and a median of 13.47 IU/L at 12 months post-LT. During the follow-up period, the HBsAb titer of the preoperative HBV-DNA-positive patients remained at a lower level than that of HBV-DNA-negative patients. CONCLUSIONS: Entecavir combined with short-term HBIG can exert a good effect for the prevention of HBV reinfection post-LT.

An efficient sharding consensus algorithm for consortium chains.

The consensus algorithm is very critical in any blockchain system, because it directly affects the performance and security of the blockchain system. At present, the classic Practical Byzantine Fault Tolerance Algorithm (PBFT), which is mainly used in the consortium chain, will lead to system communication congestion and reduced throughput when the number of nodes increases, so the PBFT algorithm is not suitable for large-scale consortium chains. In response to the above problems, this paper proposes a new clustering-based sharding consensus algorithm (KBFT), which aims to ensure that the consortium chain takes into account decentralization, security and scalability. The KBFT algorithm first uses the K-prototype clustering algorithm to shard the nodes in the network according to mixed attributes, and second, disjoint transactions are used to reach consensus in parallel in different shards. Concurrently, the KBFT algorithm introduces a supervision mechanism and a node credit mechanism, which is used to supervise and score the behavior of the nodes and select the proxy nodes, which improves security. We discuss the choice of shard size with the help of the binomial probability distribution and analyze the probability that the system can successfully form a global block under different node failure probabilities. Finally, the proposed algorithm is evaluated through theoretical analysis and simulation experiments. Results show that the proposed algorithm achieves a marked improvement in scalability and throughput along with a marked reduction in communication complexity compared with the classic baseline algorithm PBFT in this field of study, which improves the operating efficiency of the system and simultaneously guarantees the security and robustness of the system.

Amphetamine-related intoxications in people living with HIV: An observational study in an emergency department in Barcelona (Spain) from 2018 to 2020.

BACKGROUND: Stimulant drugs, particularly amphetamines, are more commonly implicated in drug-related deaths in people living with HIV; however, the clinical characteristics of amphetamine-related intoxication in people living with HIV are poorly described. MATERIAL AND METHODS: We conducted a retrospective study in people living with HIV who were admitted for amphetamine-related intoxication to an emergency department of a teaching hospital between 2018 and 2021. Severe intoxication (SI) was arbitrarily defined as requiring admission to the emergency medical support unit and receiving medical treatment for ≥6 h. RESULTS: In total, 170 male patients with a median age of 36.2 + 7.5 years were included in the study. A total of 77 (45.3%) individuals had mental disorders, and 120 (85.7%) had HIV-1 RNA suppression, with a median CD4 cell count of 696 (interquartile range 490-905). In total, 61 (37.9%) individuals were on ritonavir/cobicistat-based regimens. Presenting clinical syndromes included agitation in 60 (35.3%) subjects, anxiety in 37 (21.7%), psychosis in 27 (15.8%), chest pain in 26 (15.3%) and altered level of consciousness in 20 (11.7%). SI was observed in 48 (28.2%) individuals, 12 (7.1%) required admission to the intensive care unit, and two (1.2%) died. Altered level of consciousness (odds ratio [OR] 6.5; 95% confidence interval [CI] 2.2-18.9; p < 0.01), psychosis (OR 5.8; 95% CI 2.2-15.1; p < 0.01) and suicide attempt (OR 4.6; 95% CI 1.8-11.6; p 0.01) were associated with SI in the adjusted analysis. CONCLUSIONS: Amphetamine-related intoxication causes high morbidity in people living with HIV. Healthcare providers serving these patients should consider incorporating harm-reduction measures in the prevention of amphetamine-related intoxication.

A Ranking Recommendation Algorithm Based on Dynamic User Preference.

In recent years, hybrid recommendation techniques based on feature fusion have gained extensive attention in the field of list ranking. Most of them fuse linear and nonlinear models to simultaneously learn the linear and nonlinear features of entities and jointly fit user-item interactions. These methods are based on implicit feedback, which can reduce the difficulty of data collection and the time of data preprocessing, but will lead to the lack of entity interaction depth information due to the lack of user satisfaction. This is equivalent to artificially reducing the entity interaction features, limiting the overall performance of the model. To address this problem, we propose a two-stage recommendation model named A-DNR, short for Attention-based Deep Neural Ranking. In the first stage, user short-term preferences are modeled through an attention mechanism network. Then the user short-term preferences and user long-term preferences are fused into dynamic user preferences. In the second stage, the high-order and low-order feature interactions are modeled by a matrix factorization (MF) model and a multi-layer perceptron (MLP) model, respectively. Then, the features are fused through a fully connected layer, and the vectors are mapped to scores. Finally, a ranking list is output through the scores. Experiments on three real-world datasets (Movielens100K, Movielens1M and Yahoo Movies) show that our proposed model achieves significant improvements compared to existing methods.

Incidence of Ischemia Reperfusion Injury Related Biliary Complications in Liver Transplantation: Effect of Different Types of Donors.

Liver transplantation from donors after circulatory death (DCD) is associated with considerable rates of primary nonfunction and ischemic-type biliary lesions. Compared with donation was after brain death (DBD), the biggest disadvantage of DCD is warm ischemia injury in the procurement stage. Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. Such donors should donate according to the DCD procedure, that is, remove life support and donate after cardiac arrest. We retrospectively analyzed donor and recipient characteristics with preoperative and postoperative parameters according to 3 donation types to comprehensively describe incidence of ischemia reperfusion injury (IRI) related biliary complications among different donor type adult liver transplantation recipients. A total of 50 patients were included in this study (DBD group n = 17, DCD group n = 26, DBCD group n = 7). Only 1 patient, whose donor type was DBCD was diagnosed with ischemic-type biliary lesions demonstrated cast and retrograde ascending cholangitis. Rates of primary graft non-function (DBD n = 1, 5.9%; DCD n = 2, 7.7%; DBCD, 0%; P = .546) were similar and total biliary complications (DBD n = 1, 5.9%; DCD n = 1, 3.8%; DBCD N = 2, 28.6%; P = .042) were different. No differences were found regarding development of postreperfusion syndrome or coagulopathy in 3 groups. Compared with standard DBD donor, the clinical outcome of DCD donor liver transplantation was satisfactory, with no increase in the incidence of IRI, and, no difference in the incidence of ischemic bile duct complications. This work was carried out in compliance with the Helsinki Congress and the Declaration of Istanbul.

Risk factors of perioperative complications and management with enhanced recovery after primary surgery in women with epithelial ovarian carcinoma in a single center.

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I-IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4-5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3-5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3-5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3-5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3-5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.

A List-Ranking Framework Based on Linear and Non-Linear Fusion for Recommendation from Implicit Feedback.

Although most list-ranking frameworks are based on multilayer perceptrons (MLP), they still face limitations within the method itself in the field of recommender systems in two respects: (1) MLP suffer from overfitting when dealing with sparse vectors. At the same time, the model itself tends to learn in-depth features of user-item interaction behavior but ignores some low-rank and shallow information present in the matrix. (2) Existing ranking methods cannot effectively deal with the problem of ranking between items with the same rating value and the problem of inconsistent independence in reality. We propose a list ranking framework based on linear and non-linear fusion for recommendation from implicit feedback, named RBLF. First, the model uses dense vectors to represent users and items through one-hot encoding and embedding. Second, to jointly learn shallow and deep user-item interaction, we use the interaction grabbing layer to capture the user-item interaction behavior through dense vectors of users and items. Finally, RBLF uses the Bayesian collaborative ranking to better fit the characteristics of implicit feedback. Eventually, the experiments show that the performance of RBLF obtains a significant improvement.

Fusing pre-trained convolutional neural networks features for multi-differentiated subtypes of liver cancer on histopathological images.

Liver cancer is a malignant tumor with high morbidity and mortality, which has a tremendous negative impact on human survival. However, it is a challenging task to recognize tens of thousands of histopathological images of liver cancer by naked eye, which poses numerous challenges to inexperienced clinicians. In addition, factors such as long time-consuming, tedious work and huge number of images impose a great burden on clinical diagnosis. Therefore, our study combines convolutional neural networks with histopathology images and adopts a feature fusion approach to help clinicians efficiently discriminate the differentiation types of primary hepatocellular carcinoma histopathology images, thus improving their diagnostic efficiency and relieving their work pressure. In this study, for the first time, 73 patients with different differentiation types of primary liver cancer tumors were classified. We performed an adequate classification evaluation of liver cancer differentiation types using four pre-trained deep convolutional neural networks and nine different machine learning (ML) classifiers on a dataset of liver cancer histopathology images with multiple differentiation types. And the test set accuracy, validation set accuracy, running time with different strategies, precision, recall and F1 value were used for adequate comparative evaluation. Proved by experimental results, fusion networks (FuNet) structure is a good choice, which covers both channel attention and spatial attention, and suppresses channel interference with less information. Meanwhile, it can clarify the importance of each spatial location by learning the weights of different locations in space, then apply it to the study of classification of multi-differentiated types of liver cancer. In addition, in most cases, the Stacking-based integrated learning classifier outperforms other ML classifiers in the classification task of multi-differentiation types of liver cancer with the FuNet fusion strategy after dimensionality reduction of the fused features by principle component analysis (PCA) features, and a satisfactory result of 72.46% is achieved in the test set, which has certain practicality.

Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation.

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.

Liver Transplantation Reverses Hepatic Myelopathy in Hepatitis B-Related Decompensated Liver Cirrhosis: Case Report and Review of the Literature.

Severe neurologic complications after chronic liver disease greatly affect the patient's quality of life. Hepatic myelopathy (HM) is a rare but devastating disease, in chronic liver disease. The limbs of patients with HM show slowly progressive symmetrical spastic paralysis without sensory loss. Management of this severe neurologic complication is challenging. These patients often require timely and effective clinical intervention. Although liver transplantation is one of the effective treatments for HM, the prognosis of these patients remains poor, many of them spend their lives in wheelchairs. Here, we report a patient with HM after hepatitis B virus related decompensated liver cirrhosis who recovered well after liver transplant. This work was carried out in compliance with the Helsinki Congress and the Declaration of Istanbul.

Successful, Combined Long-term Treatment of Cerebral Candidiasis and Aspergillosis in a Liver Transplant Recipient: A Case Report.

Invasive fungal infections, of which the most common are candidiasis and aspergillosis, are among the most important and fatal complications in solid organ transplantation. They continue to be a significant cause of morbidity and mortality in patients with involvement of the central nervous system (CNS) because of the poor CNS penetration of antifungal medications. Voriconazole yields fungicidal drug concentrations in the CNS, but its use is limited in solid organ transplant patients because of its metabolic interactions with immunosuppression. Here we report a case of invasive fungal infection in the CNS after an emergency liver transplantation due to hepatitis B virus-related acute liver failure. The patient was managed successfully with a long-term conservative medical treatment.

Sequential metastasis to the liver and pancreas 4 years after gestational trophoblastic neoplasia: a case report.

This case report describes a 43-year-old female initially diagnosed with gestational trophoblastic neoplasia that then experienced metastasis to the liver and then subsequently to the pancreas nearly 4 years after the primary diagnosis. After resection of the body and tail of the pancreas, the postoperative histopathological examination confirmed a placental site trophoblastic tumour that had developed after several cycles of chemotherapy for the original primary tumour and the liver metastases. This type of sequential recurrence of gestational trophoblastic neoplasia in the primary site or metastatic sites, such as the liver or pancreas, can be cured by a comprehensive treatment strategy involving surgery and/or salvage chemotherapy and continuous follow-up over a long period, especially for patients with a high-risk status.

Liver Transplantation in a Patient With Acute-on-Chronic Liver Failure Due to Traditional Chinese Medicine Intoxication Using Donation After Circulatory Death From a Renal Transplant Recipient: A Case Report.

Acute-on-chronic liver failure (ACLF) is a clinical manifestation of acute liver failure and decompensation on the basis of chronic liver disease. To date, hepatitis B virus-related ACLF is still the main cause of liver failure in China. Liver transplantation is currently the most likely treatment option to cure ACLF, but the shortage of donor livers is a barrier to its widespread use. The shortage of organs has led to increased use of expanded-criteria donors (ECDs), that is, donation after cardiac death (DCD) and its variant donation after brain and cardiac death (DBCD-China, DCBD-Switzerland). Here we report a case of liver transplantation, whose recipient was diagnosed with ACLF as a result of use of traditional Chinese medicine while the donor liver was retrieved from a renal transplant patient 4 years after transplantation. This transplant was carried out in accordance with the Helsinki Congress and the Declaration of Istanbul.

Extracting user influence from ratings and trust for rating prediction in recommendations.

The Collaborative Filtering (CF) algorithm based on trust has been the main method used to solve the cold start problem in Recommendation Systems (RSs) for the past few years. Nevertheless, the current trust-based CF algorithm ignores the implicit influence contained in the ratings and trust data. In this paper, we propose a new rating prediction model named the Rating-Trust-based Recommendation Model (RTRM) to explore the influence of internal factors among the users. The proposed user internal factors include the user reliability and popularity. The internal factors derived from the explicit behavior data (ratings and trust), which can help us understand the user better and model the user more accurately. In addition, we incorporate the proposed internal factors into the Singular Value Decomposition Plus Plus (SVD + +) model to perform the rating prediction task. Experimental studies on two common datasets show that utilizing ratings and trust data simultaneously to mine the factors that influence the relationships among different users can improve the accuracy of rating prediction and effectively relieve the cold start problem.

The IL-17A/IL-17RA Axis Is Not Related to Overall Survival and Cancer Stem Cell Modulation in Pancreatic Cancer.

(1) Background: IL-17A accelerates pancreatic intraepithelial neoplasia (PanIN) progression. In this study, we examined whether IL-17A/IL-17RA promotes pancreatic ductal adenocarcinoma (PDAC) aggressiveness in terms of survival and cancer stem cell modulation. (2) Methods: In vitro, the wound-healing assay, the sphere formation assay, and flow cytometry were applied to assess cancer stem cell features. In vivo, pancreatic tumors were induced in C57BL/6 mice using electroporation with oncogenic plasmids (P53-/- R172H; KrasG12V). Anti-IL-17 antibodies were administered as immunotherapy. We analyzed IL-17A/IL-17RA related survival using publicly available transcriptomic data (n = 903). (3) Results: IL-17A/IL-17RA expression was not related to survival in PDAC patients. IL-17A neither induces stem cell markers nor increases sphere formation and cell motility in vitro. Blocking the IL-17A/IL-17RA axis in a murine pancreatic cancer model did not improve the survival of mice, but reduced the tumor burden slightly. (4) Conclusions: IL-17A does not promote stem cell expansion in PDAC cell lines. Blocking IL-17A/IL-17RA signaling does not interfere with pancreatic cancer development and progression and may not be considered as a promising monotherapy for PDAC.

Incidence and potential predictors of thromboembolic events in epithelial ovarian carcinoma patients during perioperative period.

OBJECTIVE: To assess the incidence and the risk factors of venous thromboembolism (VTE) in patients with epithelial ovarian carcinoma (EOC) during the perioperative period. METHODS: A retrospective analysis was conducted on the patients with epithelial ovarian cancer treated in our hospital, between January 2017 and July 2019, and a comprehensive review of the medical documentation was performed to collect relevant data. We then analyzed the related factors of the thrombosis in the EOC patients, using univariate and multivariate analysis to identify significant risk factors for VTE, and bootstrap resampling method was used to verify the multivariate analysis results. The ROC curve methods were conducted to evaluate the diagnostic value for the prediction of VTE. RESULTS: We analyzed 233 cases of patients with EOC, of whom the incidence of VTE was 11.16%. According to multivariate and 5000 bootstrap samples analysis, preoperative D-dimer levels (>4.215 µg/ml, p = 0.041 and p = 0.032) and comorbid of cerebral infarction (p < 0.001 and p < 0.001) had statistical significance in predicting VTE events; bootstrap analysis also found the Alb, CA125, OCCC had statistical significance. While According to multivariate and 5000 bootstrap samples analysis, age (>50.5 years old, p = 0.019 and p = 0.002) and nonoptimal debulking surgery (p = 0.007 and p = 0.002) showed significance in predicting VTE after surgery; bootstrap analysis also found the D-dimer levels (>4.215 µg/ml) and tuberculosis had statistical significance. CONCLUSION: More effective thromboprophylaxis and pre-test assessment is necessary for EOC patients. For prediction VTE events, D-dimer levels (>4.215 µg/ml) were the independent predictors before operation. Age and debulking surgery were the independent predictors post operation.

Loss of the voltage-gated proton channel Hv1 decreases insulin secretion and leads to hyperglycemia and glucose intolerance in mice.

Insulin secretion by pancreatic islet ß-cells is regulated by glucose levels and is accompanied by proton generation. The voltage-gated proton channel Hv1 is present in pancreatic ß-cells and extremely selective for protons. However, whether Hv1 is involved in insulin secretion is unclear. Here we demonstrate that Hv1 promotes insulin secretion of pancreatic ß-cells and glucose homeostasis. Hv1-deficient mice displayed hyperglycemia and glucose intolerance because of reduced insulin secretion but retained normal peripheral insulin sensitivity. Moreover, Hv1 loss contributed much more to severe glucose intolerance as the mice got older. Islets of Hv1-deficient and heterozygous mice were markedly deficient in glucose- and K+-induced insulin secretion. In perifusion assays, Hv1 deletion dramatically reduced the first and second phase of glucose-stimulated insulin secretion. Islet insulin and proinsulin content was reduced, and histological analysis of pancreas slices revealed an accompanying modest reduction of ß-cell mass in Hv1 knockout mice. EM observations also indicated a reduction in insulin granule size, but not granule number or granule docking, in Hv1-deficient mice. Mechanistically, Hv1 loss limited the capacity for glucose-induced membrane depolarization, accompanied by a reduced ability of glucose to raise Ca2+ levels in islets, as evidenced by decreased durations of individual calcium oscillations. Moreover, Hv1 expression was significantly reduced in pancreatic ß-cells from streptozotocin-induced diabetic mice, indicating that Hv1 deficiency is associated with ß-cell dysfunction and diabetes. We conclude that Hv1 regulates insulin secretion and glucose homeostasis through a mechanism that depends on intracellular Ca2+ levels and membrane depolarization.

An updated systematic review and meta-analysis of the use of octreotide for the prevention of postoperative complications after pancreatic resection.

BACKGROUND: The use of octreotide prophylaxis following pancreatic surgery is controversial. We aimed to evaluate the effectiveness of octreotide for the prevention of postoperative complications after pancreatic surgery through this systematic review and meta-analysis. METHODS: Literature databases (including the MEDLINE, EMBASE, and Cochrane databases) were searched systematically for relevant articles. Only randomized controlled trials (RCTs) were eligible for inclusion in our research. We extracted the basic information regarding the patients, intervention procedures, and all complications after pancreatic surgery and then performed the meta-analysis. RESULTS: Thirteen RCTs involving 2006 patients were identified. There were no differences between the octreotide group and the placebo group with regard to pancreatic fistulas (PFs) (relative risk [RR] = 0.79, 95% confidence interval [CI] = 0.62-0.99, P = .05), clinically significant PFs (RR = 1.01, 95% CI = 0.68-1.50, P = .95), mortality (RR = 1.21, 95% CI = 0.78-1.88, P = .40), biliary leakage (RR 0.84, 95% CI = 0.39-1.82, P = .66), delayed gastric emptying (RR = 0.83, 95% CI = 0.54-1.27, P = .39), abdominal infection (RR = 1.00, 95% CI = 0.66-1.52, P = 1.00), bleeding (RR = 1.16, 95% CI = 0.78-1.72, P = .46), pulmonary complications (RR = 0.73, 95% CI = 0.45-1.18, P = .20), overall complications (RR = 0.80, 95% CI = 0.64-1.01, P = .06), and reoperation rates (RR = 1.18, 95% CI = 0.77-1.81, P = .45). In the high-risk group, octreotide was no more effective at reducing PF formation than placebo (RR = 0.81, 95% CI = 0.67-1.00, P = .05). In addition, octreotide had no influence on the incidence of PF (RR = 0.38, 95% CI = 0.14-1.05, P = .06) after distal pancreatic resection and local pancreatic resection. CONCLUSION: The present best evidence suggests that prophylactic use of octreotide has no effect on reducing complications after pancreatic resection.

Effects of LncRNA Lnc-LIF-AS on cell proliferation, migration and invasion in a human cervical cancer cell line.

This study explored the effect of LncRNA Lnc-LIF-AS on cell proliferation, migration and invasion in the human cervical cancer (HCC) cell line SiHa. SiHa cells had the lowest expression of Lnc-LIF-AS in the 4 human cervical cancer cell lines (SiHa, ME-180, C-33A and HeLa) and were transfected and divided into the SiHa/con (transfected with pMIGRI) cell group, SiHa/Lnc-LIF-AS (transfected with pMIGRI-Lnc-LIF-AS) cell group, and SiHa/Lnc-LIF-AS-DN (transfected with pMIGRI-Lnc-LIF-AS-DN, in which the sequences overlapping with LIF mRNA was deleted) cell group. Overexpression of Lnc-LIF-AS could promote the proliferation, colony formation, invasion and migration in SiHa and ME-180 cells. And the low expression of Lnc-LIF-AS suppress the proliferation, colony formation invasion and migration in HeLa cells when the Lnc-LIF-AS expression has been suppressed. In the SiHa/Lnc-LIF-AS cells group, the cell cycle was mainly halted in the S phase and overexpression of Lnc-LIF-AS had no effect on the apoptosis of SiHa cells. Overexpression of Lnc-LIF-AS could promote the secretion of LIF in SiHa cells, and the supernatant from SiHa/Lnc-LIF-AS cells could promote cell proliferation in the SiHa/con cells. The STAT3 inhibitor could inhibit cell proliferation in the SiHa/Lnc-LIF-AS cells. The expression level of Lnc-LIF-AS in cervical cancer tissues was higher than that in normal tissues and the expression level of Lnc-LIF-AS was positively correlated with the level of LIF. In the SiHa/con and SiHa/Lnc-LIF-AS-DN cell groups, there were no significant differences in cell proliferation, cell migration and cell invasion. The overexpression of Lnc-LIF-AS can promote cell proliferation, migration and invasion in cervical cancer cells, and the core function domain of this lncRNA was located in the overlapping a 3'-UTR base sequence of LIF mRNA.