The application of ERAS in pilonidal sinus: comparison of postoperative recovery between primary suture and Limberg flap procedure in a multicenter prospective randomized trial.

Purpose: We evaluated the clinical effect of utilizing a Limberg rhomboid flap graft in conjunction with Enhanced Recovery After Surgery (ERAS) protocols for the management of pilonidal sinus in the sacrococcygeal region to demonstrate the feasibility of applying ERAS to the treatment of pilonidal sinus. Methods: Between January 2010 and August 2018, prospective data analysis was undertaken on 109 patients who received surgical treatment for pilonidal sinus in the sacrococcygeal region at the Department of Colorectal and Anal Surgery, Jingzhou Hospital affiliated to Yangtze University, and Taizhou Affiliated Hospital of Nanjing University of Chinese Medicine. The patients were randomly separated into two groups based onoperation technique: the control group (pilonidal sinus resection with primary suture) and the observation group (pilonidal sinus resection with Limberg flap graft). Some patients in the above two groups received ERAS after surgery, which included early feeding and early ambulation, etc. Therefore, we further subdivided each group into group A (without ERAS) and group B (with ERAS) according to whether they received ERAS. Comparative analysis was conducted to assess differences in pertinent data before and after surgery across the respective groups. Results: The length of postoperative hospitalization was shorter and wound dehiscence was more common in control group B than in control group A [(9.00 ± 1.20) vs. (11.07 ± 1.78), 26.7% (8/30) vs. 7.1% (2/28), P < 0.05]. Observation group B exhibited significantly shorter wound recovery periods and postoperative hospital stays compared to observation group A [(8.08 ± 1.20) vs. (9.16 ± 2.21), (26.23 ± 3.97) vs. (29.08 ± 4.74), P < 0.05]. The hospitalization duration and wound healing time in observation group B were notably shorter than those observed in control group B [(8.08 ± 1.20) vs. (9.00 ± 1.20), [26.23 ± 3.97 vs. (43.67 ± 7.26), P < 0.05], but the operation time was longer and scar acceptance was lower [(78.85 ± 10.16) vs. (43.30 ± 6.06), (4.00 ± 0.69) vs. (7.53 ± 0.86), P < 0.05]. The VAS score, infection rate, wound dehiscence rate, subcutaneous hematoma rate and 5-year recurrence rate in observation group B were lower than those in control group B [(5.00 ± 1.39) vs. (7.13 ± 0.78), 3.8% (1/26) vs. 23.3% (7/30), 3.8% (1/26) vs. 26.7% (8/30), 3.8% (1/26) vs. 26.7%(8/30), 7.7% (2/26) vs. 30.0% (9/30), P < 0.05], but the rate of flap ischemia or necrosis was higher [15.4% (4/26) vs. 0(0/30), P < 0.05]. Conclusion: The combination of ERAS with pilonidal sinus resection using Limberg flap graft demonstrated a reduction in infection rates, wound dehiscence, subcutaneous hematoma occurrence, and recurrence rates, along with alleviation of postoperative pain and acceleration of healing time. Comparatively, this approach offers superior advantages over pilonidal sinus resection with primary suture in the management of sacrococcygeal pilonidal sinus.

Node-Aligned Graph-to-Graph: Elevating Template-free Deep Learning Approaches in Single-Step Retrosynthesis.

Single-step retrosynthesis in organic chemistry increasingly benefits from deep learning (DL) techniques in computer-aided synthesis design. While template-free DL models are flexible and promising for retrosynthesis prediction, they often ignore vital 2D molecular information and struggle with atom alignment for node generation, resulting in lower performance compared to the template-based and semi-template-based methods. To address these issues, we introduce node-aligned graph-to-graph (NAG2G), a transformer-based template-free DL model. NAG2G combines 2D molecular graphs and 3D conformations to retain comprehensive molecular details and incorporates product-reactant atom mapping through node alignment, which determines the order of the node-by-node graph outputs process in an autoregressive manner. Through rigorous benchmarking and detailed case studies, we have demonstrated that NAG2G stands out with its remarkable predictive accuracy on the expansive data sets of USPTO-50k and USPTO-FULL. Moreover, the model's practical utility is underscored by its successful prediction of synthesis pathways for multiple drug candidate molecules. This proves not only NAG2G's robustness but also its potential to revolutionize the prediction of complex chemical synthesis processes for future synthetic route design tasks.

Feasibility and safety of specimen extraction via an enlarged (U-Plus) skin bridge loop ileostomy: a single-center retrospective comparative study.

Objective: To investigate the feasibility and safety of specimen extraction via an enlarged (U-Plus) skin bridge loop ileostomy. Methods: A retrospective analysis of 95 patients with rectal cancer who underwent laparoscopic low anterior rectal resection and skin bridge loop ileostomy between August 2018 and August 2022, including 44 patients with specimen extraction via an enlarged (U-Plus) skin bridge loop ileostomy (experimental group) and 51 patients with specimen extraction via an abdominal incision (control group). Following the application of propensity score matching (PSM), 34 pairs of data were successfully matched. Subsequently, a comparative analysis was conducted on the clinical data of the two groups. Results: The experimental group exhibited significantly better outcomes than the control group in various aspects. Specifically, the experimental group had lower values for average operative time (P < 0.001), estimated blood loss (P < 0.001), median length of visible incision after surgery (P < 0.001), median VAS pain score on the first day after surgery (P = 0.015), and average postoperative hospitalization (P = 0.001). There was no statistical significance observed in the incidence of stoma-related complications in both groups (P > 0.05). Within each group, the stoma-QOL scores before stoma closure surgery were significantly higher than those at one month and two months after the surgery, with statistical significance (P < 0.05). Conclusion: Specimen extraction via a U-Plus skin bridge loop ileostomy is a safe and feasible method that shortens operation time and postoperative visual incision length, decreases estimated blood loss, and reduces patient postoperative pain compared with specimen extraction via an abdominal incision.

Application of laparoscopic modified Bacon operation in patients with low rectal cancer and analysis of the changes in anal function: A retrospective single-center study.

Purpose: To investigate the value of modified Bacon operation in patients with low rectal cancer. Methods: Retrospective analysis of 60 patients treated with laparoscopic surgery for low rectal cancer in the Department of Colorectal and Anal Surgery, Jingzhou Hospital affiliated to Yangtze University, from 2019 to 2022, divided into observation and control groups based on the method of the operation (laparoscopic modified Bacon operation group and laparoscopic Dixon operation with prophylactic ileostomy group). We compared the variations between the two groups. Results: The length of the abdominal surgical incision was shorter in the observation group than in the control group(P<0.05). In the observation group, the length of hospital stay after the first operation was shorter(P<0.05), the both operations time and the second intraoperative bleeding were less(P<0.05), the DET score at one week after the first operation and the VAS after both operations were fewer than in the control group(P<0.05), the postoperative rate of ischemic necrosis of the exposed bowel was higher(P<0.05), and the anal function was poorer in the short term after the second operation compared with the control group(P<0.05), but there was no significant difference between the anal function at 6 months after the second operation compared with the control group(P>0.05).12 months after the second operation, the anal function has recovered to the preoperative level in the observation group(P>0.05). Conclusion: The laparoscopic modified Bacon operation has smaller abdominal wounds, which reduces postoperative pain; it does not require the use of staplers, which reduces the patient's financial burden; no postoperative anastomotic leakage occurs, and a more satisfactory anal function can be obtained.

Increased mitophagy protects cochlear hair cells from aminoglycoside-induced damage.

Aminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. In the current study, we found that PINK1-PRKN-mediated mitophagy was impaired in neomycin-treated hair cells. Our data suggested that mitochondrial recruitment of PRKN and phagophore recognition of damaged mitochondria during mitophagy were blocked following neomycin treatment. In addition, the degradation of damaged mitochondria by lysosomes was significantly decreased as indicated by the mitophagic flux reporter mt-mKeima. Moreover, we demonstrated that neomycin disrupted mitophagy through transcriptional inhibition of Pink1 expression, the key initiator of mitophagy. Moreover, we found that neomycin impaired mitophagy by inducing ATF3 expression. Importantly, treatment with a mitophagy activator could rescue neomycin-treated hair cells by increasing mitophagy, indicating that genetic modulation or drug intervention in mitophagy may have therapeutic potential for aminoglycoside-induced hearing loss.Abbreviations: AAV: adeno-associated virus; ABR: auditory brainstem response; ATF3: activating transcription factor 3; ATOH1/MATH1: atonal bHLH transcription factor 1; BafA1: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; COX4I1/COXIV: cytochrome c oxidase subunit 4I1; CTBP2/RIBEYE: C-terminal binding protein 2; DFP: deferiprone; EGFP: enhanced green fluorescent protein; FOXO3: forkhead box O3; GRIA2/GLUR2: glutamate receptor, ionotropic, AMPA2 (alpha 2); HC: hair cell; HSPD1/HSP60: heat shock protein 1 (chaperonin); IHC: inner hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MYO7A: myosin VIIA; OPTN: optineurin; OMM: outer mitochondrial membrane; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; RT-qPCR: real-time quantitative polymerase chain reaction; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling; USP30: ubiquitin specific peptidase 30; XBP1: X-box binding protein 1.

Immunoglobulin G4-related disease in the sigmoid colon in patient with severe colonic fibrosis and obstruction: A case report.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition characterized by abundant IgG4 positive plasma cells and fibrosis in the affected tissues. It affects most parts of the body; however, there are not many reports on IgG4-RD involving the colon. CASE SUMMARY: A 50-year-old man complaining of intermittent fever for more than two years was referred to our hospital. Based on various investigations before surgery, we diagnosed him with chronic perforation of the sigmoid colon caused by inflammatory change or tumor. IgG blood tests before the operation suggested IgG4-RD, and postoperative pathology confirmed this prediction. CONCLUSION: We present a patient with IgG4-RD with colon involvement, which is an uncommon site. This report will expand the understanding of IgG4-RD in unknown tissues.

CT psoas calculations on the prognosis prediction of emergency laparotomy: a single-center, retrospective cohort study in eastern Asian population.

BACKGROUND: Emergency laparotomy (EL) has a high mortality rate. Clinically, frail patients have a poor tolerance for EL. In recent years, sarcopenia has been used as an important indicator of frailty and has received much attention. There have been five different calculation methods of psoas for computed tomography (CT) to measure sarcopenia, but lack of assessment of these calculation methods in Eastern Asian EL patients. METHODS: We conducted a 2-year retrospective cohort study of patients over 18 years of age who underwent EL in our institution. Five CT measurement values (PMI: psoas muscle index, PML3: psoas muscle to L3 vertebral body ratio, PMD: psoas muscle density, TPG: total psoas gauge, PBSA: psoas muscle to body face area ratio) were calculated to define sarcopenia. Patients with sarcopenia defined by the sex-specific lowest quartile of each measurement were compared with the rest of the cohort. The primary outcome was "ideal outcome", defined as: (1) No postoperative complications of Clavien-Dindo Grade ≥ 4; (2) No mortality within 30 days; (3) When discharged, no need for fluid resuscitation and assisted ventilation, semi-liquid diet tolerated, and able to mobilize independently. The second outcome was mortality at 30-days. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were used. RESULTS: Two hundred and twenty-eight patients underwent EL met the inclusion criteria, 192 (84.2%) patients had an ideal outcome after surgery; 32 (14%) patients died within 30 days. Multivariate analysis showed that, except PMD, each calculation method of psoas was independently related to clinical outcome (ideal outcome: PML3, P < 0.001; PMI, P = 0.001; PMD, P = 0.157; TPG, P = 0.006; PBSA, P < 0.001; mortality at 30-days: PML3, P < 0.001; PMI, P = 0.002; PMD, P = 0.088; TPG, P = 0.002; PBSA, P = 0.001). In ROC analysis, the prediction model containing PML3 had the largest area under the curve (AUC) value (AUC value = 0.922 and 0.920, respectively). CONCLUSION: The sarcopenia determined by CT psoas measurements is significantly related to the clinical outcome of EL. The calculation of CT psoas measurement is suitable for application in outcome prediction of EL. In the future, it is necessary to develop a scoring tool that includes sarcopenia to evaluate the risk of EL better.

Isoquercitrin Upregulates Aldolase C Through Nrf2 to Ameliorate OGD/R-Induced Damage in SH-SY5Y Cells.

Isoquercitrin (ISO), an extract from Chinese traditional herb, exhibits potent neuroprotective roles in various disease models. However, its role in stroke is not fully understood. We established oxygen-glucose deprivation and reoxygenation (OGD/R) model in SH-SY5Y cell to study the roles of ISO in stroke. In the experiment, the changes of LDH level and cell viability (MTT) were analyzed. Apoptotic cells stained with anti-Annexin V antibody and propidium iodide (PI) were detected by flow cytometry. The mRNA and protein level of aldolase C (ALDOC) and nuclear factor erythroid 2-related factor (Nrf2) was determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting assay, respectively. The localization of Nrf2 was investigated by immunofluorescent assay. OGD/R reduced cell viability via inducing cell apoptosis, while ISO treatment reduced the level of apoptosis in OGD/R-treated SH-SY5Y cells ISO rescued OGD/R-treated cells. Mechanistically, the expression of Nrf2 and ALDOC was upregulated upon ISO treatment, while knockdown of ALDOC diminished the activation of autophagy and hence inhibited ISO-mediated protective activity. We further demonstrated that ISO enhanced ALDOC transcription by promoting nuclear translocation of Nrf2, and suppression of Nrf2 decreased the expression of ALDOC. Our data revealed that ISO exhibited neuroprotective activity in OGD/R model through Nrf2-ALDOC-autopagy axis and highlighted the potential application of ISO in stroke treatment.

Black Bamboo Rhizome Extract Improves Cognitive Dysfunction by Upregulating the Expression of Hippocampal BDNF and CREB in Rats with Cerebral Ischaemia-Reperfusion Injury.

INTRODUCTION: The study aimed to explore the effects of treatment with black bamboo rhizome extracts on learning and memory and determine the underlying mechanisms in rats with cerebral ischaemia-reperfusion injury. METHODS: Sprague-Dawley rats were randomly divided into the following four groups: control, middle cerebral artery occlusion (MCAO), low-dose drug, and high-dose drug groups. Rats underwent MCAO using a suture method before drug treatment. Then, neurological impairment was assessed using the Longa scoring method, and triphenyl tetrazolium chloride staining was used to analyse the cerebral infarction area. The Elliott formula was used to calculate water content in the brain tissue. A Morris water maze (MWM) was used to assess changes in learning and memory abilities, and Western blotting was used to detect cyclic adenosine phosphate response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of MCAO rats. RESULTS: After treatment with black bamboo rhizome extracts, the neurological dysfunction score was lower in the drug groups than in the MCAO group, and a significant difference was observed between the high-dose drug and MCAO groups (P<0.05). Additionally, the cerebral infarction area was significantly smaller in the drug groups than in the MCAO group (P<0.01), and the effect was more obvious in the high-dose drug group than in the low-dose drug group. There was also a significant difference in water content between the high-dose drug and MCAO groups, and cerebral oedema was significantly reduced in the high-dose drug group (P<0.05). In the MWM, the incubation period was significantly reduced, the number of platform crossings was significantly increased, and the search time was prolonged in the drug groups compared with those in the MCAO group (P<0.05). Moreover, the expression of BDNF and CREB was significantly increased in the drug groups compared to that in the MCAO group, and the increase was more obvious in the high-dose group than in the low-dose group (P<0.05). DISCUSSION: Black bamboo rhizome extracts significantly improved cognitive dysfunction, reduced cerebral oedema, decreased the cerebral infarction area, and improved the neurological function score and learning and memory abilities in rats with cerebral ischaemia-reperfusion injury.

Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression.

Ischaemic stroke is a common condition leading to human disability and death. Previous studies have shown that oleanolic acid (OA) ameliorates oxidative injury and cerebral ischaemic damage, and miR-186-5p is verified to be elevated in serum from ischaemic stroke patients. Herein, we investigated whether OA regulates miR-186-5p expression to control neuroglobin (Ngb) levels, thereby inhibiting neuronal pyroptosis in ischaemic stroke. Three concentrations of OA (0.5, 2, or 8 µM) were added to primary hippocampal neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R), a cell model of ischaemic stroke. We found that OA treatment markedly inhibited pyroptosis. qRT-PCR and western blot revealed that OA suppressed the expression of pyroptosis-associated genes. Furthermore, OA inhibited LDH and proinflammatory cytokine release. In addition, miR-186-5p was downregulated while Ngb was upregulated in OA-treated OGD/R neurons. MiR-186-5p knockdown repressed OGD/R-induced pyroptosis and suppressed LDH and inflammatory cytokine release. In addition, a dual luciferase reporter assay confirmed that miR-186-5p directly targeted Ngb. OA reduced miR-186-5p to regulate Ngb levels, thereby inhibiting pyroptosis in both OGD/R-treated neurons and MCAO mice. In conclusion, OA alleviates pyroptosis in vivo and in vitro by downregulating miR-186-5p and upregulating Ngb expression, which provides a novel theoretical basis illustrating that OA can be considered a drug for ischaemic stroke.

Lnc-ATG9B-4 aggravates progress of hepatocellular carcinoma through cell proliferation and migration by upregulating CDK5.

Long noncoding RNAs play an important role in the occurrence, invasion, as well as metastasis of various human cancers, including hepatocellular carcinoma. Long noncoding RNAs can affect the biological functions of hepatocellular carcinoma cells by regulating various genes; however, only a small fraction of molecular mechanisms of long noncoding RNAs have been elucidated. In the present study, lnc AC010973.1 (lnc-ATG9B-4) was first identified by microarray analysis from 8 patients with hepatocellular carcinoma and confirmed by quantitative PCR in 176 patients with hepatocellular carcinoma. We demonstrated that lnc-ATG9B-4 was tightly relative to the tumorous size, TNM stages, portal vein tumor thrombus (PVTT), the tumor capsule, metastasis, degree of differentiation, and poor prognosis of hepatocellular carcinoma according to long-term follow-up data. In hepatocellular carcinoma cells, overexpression of lnc-ATG9B-4 promoted proliferation, invasion, as well as migration, while inhibiting lnc-ATG9B-4 by siRNA significantly attenuated the proliferation, invasion, as well as migration. Interestingly, lnc-ATG9B-4 increased the expression of cyclin-dependent kinase 5 (CDK5), which was closely related to the development and chemotherapy sensitivity of hepatocellular carcinoma. In summary, our results revealed that lnc-ATG9B-4 suggests an unfavorable prognosis of hepatocellular carcinoma and facilitates the proliferation, invasion, as well as migration of hepatocellular carcinoma cells by upregulating CDK5. This research suggests that lnc-ATG9B-4 may be a new biomarker for predicting the prognosis of hepatocellular carcinoma; meanwhile, targeting lnc-ATG9B-4 might serve as a potential strategy for the treatment hepatocellular carcinoma.

Preoperative Nutritional Status Contributes to the Development of Neutropenia Event in Patients With Gastric Cancer Receiving CAPEOX Adjuvant Chemotherapy.

Purpose: The aim of this study is to evaluate the risk factors for ≥ grade 3 neutropenia in gastric cancer patients receiving postoperative adjuvant chemotherapy. Methods: This is a retrospective study from a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in this study. Baseline and clinicopathological characteristics of the patients were collected. Patients were followed-up for 12 months and the incidence of neutropenia were recorded. Factors associated with neutropenia of chemotherapy in cycle 1 were investigated. Results: A total of 202 patients with gastric cancer were included. All patients received oxaliplatin plus oral capecitabine (CAPEOX) as the adjuvant chemotherapy. The incidence of ≥ grade 3 neutropenia is 11.9% (24/202) in cycle 1 among all patients. In multivariate analysis, independent risk factors for ≥ grade 3 neutropenia were serum prealbumin level (p = 0.041), prognostic nutritional index (PNI) (p = 0.049) and pre-cycle neutrophil count (p = 0.007). Conclusions: Our findings for the first time showed that nutritional parameter as prealbumin level and PNI are independent risk factors for neutropenia in gastric cancer patients receiving adjuvant chemotherapy. This may provide evidence for further investigation on prophylaxis use of granulocyte colony-stimulating factor in selected high-risk patients to prevent sever neutropenia in cycle 1 of adjuvant chemotherapy.

Effect of Pd loading on ZrO2 support resulting from pyrolysis of UiO-66: Application to CO oxidation.

The effect of Pd loading (0.25, 0.5 and 1.0 wt%) and ZrO2 support calcined at diverse temperatures (600, 700 and 800 °C) by pyrolysis of UiO-66 was investigated for CO oxidation in this work, respectively. The physicochemical properties of the samples were characterized by various characterization methods. The XRD results exhibited that all ZrO2 support possessed mixed crystalline phase, the monoclinic ZrO2 and tetragonal ZrO2. And the calcination temperature had a big impact on the composition of ZrO2 supports. Pyrolysis of UiO-66 at high temperature was favorable for the formation of monoclinic ZrO2. Additionally, the introduction of Pd was induced the phase conversion from tetragonal to monoclinic of ZrO2. The order of catalytic efficiency was as follows: 0.5Pd/Zr-700 > 0.5Pd/Zr-600 > 0.5Pd/Zr-800. Moreover, 0.5Pd/Zr-700 presented high stability and great reusability. The good catalytic performance of 0.5Pd/Zr-700 was ascribed to the better reduction ability at low temperature and high Oads/Olat and Pd0/Pd2+ on the surface. Importantly, the reaction pathway of CO oxidation over the 0.5Pd/Zr-700 was exposed.

High level of unmet needs and anxiety are associated with delayed initiation of adjuvant chemotherapy for colorectal cancer patients.

AIMS: Adjuvant chemotherapy is recommended for patients with curatively resected colorectal cancer. The aim of this study is to evaluate the impact of unmet supportive care needs and anxiety on the initiation of postoperative adjuvant chemotherapy in colorectal cancer patients. METHODS: This is a retrospective study from a single tertiary referral hospital. Patients diagnosed with colorectal cancer who met the inclusion criteria were included. The Hospital Anxiety and Depression Scale (HADS) and modified 34-item Supportive Care Needs Survey (SCNS-SF34) were applied to assess patient's anxiety level and unmet needs. The time intervals between initiation of adjuvant chemotherapy and operation were recorded. Factors associated with delayed initiation of chemotherapy were investigated in univariate and multivariate analysis. RESULTS: A total of 135 patients with colorectal cancer were included. In total, 16.3% (22/135) and 5.2% (7/135) reported symptoms of anxiety and depression. In multivariate analysis, low to moderate income status, postoperative complications, anxiety, and high level of unmet needs are independent risk factors for late initiation of chemotherapy. CONCLUSIONS: Our findings showed that psychological problems such as anxiety and high unmet supportive needs are correlated with delayed initiation of adjuvant chemotherapy in colorectal cancer patients.

Comparison of therapeutic interventions for recurrent pregnancy loss in association with antiphospholipid syndrome: A systematic review and network meta-analysis.

Antiphospholipid syndrome (APS) is one of the treatable causes for pregnant women with recurrent pregnancy loss (RPL). This review compares the efficacy of a few treatment interventions (low-dose aspirin (LDA), aspirin plus low molecular weight heparin (LMWH), or unfractionated heparin (UFH)) in preventing complications during pregnancy and miscarriages for women with RPL and APS, and the potential differences in therapeutic effects of UFH and LMWH when combined with aspirin. We searched randomized controlled trials (RCTs) in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials and performed a systematic review and a Bayesian network meta-analysis (NMA). Finally, we found aspirin alone had a lower live birth rate compared to LMWH plus aspirin (OR = 0.37; 95% CrI, 0.17, 0.71), and UFH plus aspirin showed a higher live birth rate than aspirin alone (OR = 2.63; 95% CrI, 1.04, 5.39) in NMA, treating with UFH plus aspirin or LMWH plus aspirin did not have difference on live birth. Furthermore, LDA alone resulted in a lower birthweight compared to heparin plus aspirin, while higher birthweight was found when compared UFH plus aspirin to LMWH plus aspirin (MD = 895.40; 95% CrI, 817.40, 988.57) in NMA. Additionally, in women with RPL and APS and without a prior thrombosis, heparin plus aspirin improved birthweight but could not promote live birth rate compared to aspirin alone. In conclusion, heparin plus aspirin is recommended for women with RPL and APS. Notably UFH plus aspirin demonstrates the most significant therapeutic efficacy among these interventions in improving birthweight.

A novel and validated nomogram to predict overall survival for gastric neuroendocrine neoplasms.

BACKGROUND: This study aims to develop and validate an effective nomogram to estimate the individual outcome of patients with Gastric neuroendocrine neoplasms (G-NENs). METHODS: A total of 260 patients diagnosed with G-NENs at two medical centers were included, with 156 patients allocated as training set and 104 patients as validation. Predictive nomogram was constructed based on multivariate analyses using RMS package in R version. The predictive accuracy and discriminative ability were analyzed by C-index, risk group stratification and calibration curve, which was compared with other predictive systems for G-NENs. RESULTS: In multivariate analysis, age, Ki-67, mitoses, neutrophil to lymphocyte ratio, serum tumor marker and distant metastasis were significantly associated with overall survival. The constructed prognostic nomogram demonstrated a good calibration and discrimination value with 0.884 and 0.852 C-indices in training and validation dataset. Compare to World Health Organization (WHO) grading system (C-indices=0.760 and 0.732) and American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (C-indices=0.747 and 0.811), the nomogram displayed a better predictive accuracy. CONCLUSIONS: The novel prognostic nomogram showed superior predictive value in overall survival of G-NENs. It might be a useful tool for clinicians in estimating individual survival in G-NENs patients.

[Effect of attenuated expression of neuraminidase 3 via RNA interference on the proliferation and apoptosis of osteosarcoma MG-63 cells].

Objective: To investigate the effect of attenuated expression of neuraminidase 3 (NEU3) via RNA interference on the proliferation and apoptosis in human osteosarcoma MG-63 cells. Methods: MG-63 cells were immunostained to observe the expression of NEU3. The cells were then divided into 5 groups: MG-63 cells in normal control group (group A) were not treated; MG-63 cells in 30, 50, and 100 nmol/L NEU3 RNA interference groups (groups B, C, and D) were transfected with 30, 50, and 100 nmol/L of NEU3 small interfering RNA (siRNA); negative control group (group E), MG-63 cells were transfected with different species negative siRNA (actin siRNA of mice, 50 nmol/L). The expression level of NEU3 mRNA was measured with real-time fluorescence quantitative PCR (qPCR). The proliferation of the cells was measured by cell counting kit 8 (CCK-8). The cell apoptosis rate was detected by flowcytometry (FCM). The expressions of cell apoptosis related proteins (Ras and Bcl-2) were detected by Western blot assay. Results: NEU3 expressed in the cytoplasm of MG-63 cells under fluorescence microscope. The qPCR results showed that NEU3 mRNA levels were significantly lower in groups B, C, D than that in groups A and E ( P<0.05) after 24 hours of transfection; meanwhile, with the increase of siRNA concentration, NEU3 mRNA levels were significantly decreased ( P<0.05). The CCK-8 results showed that with the increase of siRNA concentration, the survival rate of MG-63 cells was significantly suppressed ( P<0.05) and the apoptosis rate of MG-63 cells was significantly accelerated ( P<0.05) after 48 hours of transfection. FCM results showed that after 24 hours of transfection, the number of live MG-63 cells decreased as that of the dead cells increased in groups B, C, D, and showing significant differences between 3 groups ( P<0.05). While the apoptosis rate in groups B, C, and D showed significant difference when compared with that of group A ( P<0.05); and when compared with group E, the apoptosis rate in groups C and D were significantly reduced ( P<0.05), but there was no significant difference between groups B and E ( P>0.05). The results of Western bolt assay showed that the protein levels of Ras and Bcl-2 in groups B and C were not significantly different from groups A and E ( P>0.05), while the protein levels of Ras and Bcl-2 were significantly decreased in group D ( P<0.05). Conclusion: Attenuated expression of NEU3 could inhibit the survival of MG-63 cells and accelerate its apoptosis. The results suggest that NEU3 could be a possible target for treating osteosarcoma.

The prognostic role of Gas6/Axl axis in solid malignancies: a meta-analysis and literature review.

BACKGROUND: Axl is a receptor tyrosine kinase that is involved in many pathological conditions and carcinogenesis. Gas6 is the major ligand of Axl. Activation of Gas6/Axl pathway is essential for cancer development. However, its prognostic significance in solid tumors remains unclear. Therefore, we performed this meta-analysis to elucidate the prognostic impact of Axl. METHODS: Published studies on Axl or Gas6 expression and overall survival (OS) and/or disease-free survival (DFS) were searched from databases. The outcome measurement is hazard ratio (HR) for OS or DFS related to Axl/Gas6 expression. Meta-analysis was performed using RevMan. The pooled HR was calculated by fixed-/random-effect models. RESULTS: A total of 3,344 patients from 25 studies were included. The results of meta-analysis showed that Axl overexpression was correlated with shorter OS (HR: 2.03, p<0.0001) and DFS (HR: 1.85, p<0.0001). In subgroup analysis, Axl expression was significantly correlated with poor prognosis in hepatocellular, esophageal and lung cancer. Axl expression was associated with differentiation grade, TNM stage, lymph node and distant metastasis. CONCLUSION: These results suggest that Axl overexpression is correlated with poor prognosis in solid tumors. This correlation varies among different types of cancers. More studies are needed to further investigate the prognostic value of Axl.

Prognostic significance of SATB1 in gastrointestinal cancer: a meta-analysis and literature review.

BACKGROUND: The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic regulator. The clinical and prognostic significance of SATB1 in gastrointestinal cancer remains controversial. The purpose of this study is to conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in gastrointestinal cancer. RESULTS: A total of 3174 gastrointestinal cancer patients from 15 studies were included. The correlation between SATB1 expression and OS or RFS was investigated in 12 and 5 studies respectively. The results of meta-analysis showed that SATB1 overexpression is inversely correlated with OS (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In subgroup analysis, SATB1 expression is significantly correlated with poor prognosis in gastrointestinal cancer in Asian population. SATB1 expression is associated with stage, invasion depth, lymph node metastasis and distant metastasis. METHODOLOGY: Published studies with data on overall survival (OS) and/or relapse free survival (RFS) and SATB1 expression were searched from Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers independently screened the literatures, extracted the data and performed meta-analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed- or random-effect models. CONCLUSIONS: The results of this meta-analysis suggest that SATB1 overexpression is related to advanced stage, lymph node metastasis and distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in gastrointestinal cancer.

Platelet secretion in inflammatory and infectious diseases.

Platelets are small, anucleate circulating cells that possess a dynamic repertoire of functions spanning the hemostatic, inflammatory, and immune continuum. Once thought to be merely cell fragments with responses limited primarily to acute hemostasis and vascular wall repair, platelets are now increasingly recognized as key sentinels and effector cells regulating host responses to many inflammatory and infectious cues. Platelet granules, including α-granules and dense-granules, store hundreds of factors and secrete these mediators in response to activating signals. The cargo packaged and stored within platelet granules orchestrates communication between platelets and other circulating cells, augments host defense mechanisms to invading pathogens and tumor cells, and - in some settings - drives dysregulated and injurious responses. This focused review will highlight several of the established and emerging mechanisms and roles of platelet secretion in inflammatory and infectious diseases.