Raloxifene-driven benzothiophene derivatives: Discovery, structural refinement, and biological evaluation as potent PPARγ modulators based on drug repurposing.

By virtue of the drug repurposing strategy, the anti-osteoporosis drug raloxifene was identified as a novel PPARγ ligand through structure-based virtual high throughput screening (SB-VHTS) of FDA-approved drugs and TR-FRET competitive binding assay. Subsequent structural refinement of raloxifene led to the synthesis of a benzothiophene derivative, YGL-12. This compound exhibited potent PPARγ modulation with partial agonism, uniquely promoting adiponectin expression and inhibiting PPARγ Ser273 phosphorylation by CDK5 without inducing the expression of adipongenesis associated genes, including PPARγ, aP2, CD36, FASN and C/EBPα. This specific activity profile resulted in effective hypoglycemic properties, avoiding major TZD-related adverse effects like weight gain and hepatomegaly, which were demonstrated in db/db mice. Molecular docking studies showed that YGL-12 established additional hydrogen bonds with Ile281 and enhanced hydrogen-bond interaction with Ser289 as well as PPARγ Ser273 phosphorylation-related residues Ser342 and Glu343. These findings suggested YGL-12 as a promising T2DM therapeutic candidate, thereby providing a molecular framework for the development of novel PPARγ modulators with an enhanced therapeutic index.

Comprehensive analysis of cuproptosis genes and cuproptosis-related genes as prognosis factors in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common invasive and pernicious cancer with a low five-year survival rate. To identify potential therapeutic targets, we first investigated the characteristics of cuproptosis genes (CUGs) in ESCC. The expression patterns of 10 CUGs (FDX1, LIPT1, LIAS, DLAT, DLD, PDHA1, PDHB, GLS, MTF1, and CDKN2A) were analyzed to identify ESCC-relevant targets. Weighted correlation network analysis (WGCNA) was performed to obtain CUG-related genes (CRGs). A total of seven differentially expressed genes were identified (FDX1, DLAT, LIAS, PDHB, MTF1, GLS, and CDKN2A). DLAT was upregulated in stage III, and LIPT1 was upregulated in N0 + N1 cancers. The high expression of CDKN2A, and PDHA1, was related to better overall survival, whereas the low expression of LIAS was related to better clinical outcomes. WGCNA was performed to get CUG-related genes (CRGs) and showed three key modules that related to FDX1, DLAT, and LIPT1. Moreover, CRGs (BTLA, CT47A1, and PRRX1) were selected to construct a risk score model in order to predict the survival and prognosis of patients with ESCC. Additionally, the cuproptosis score based on CUGs and a nomogram constructed based on it helped accurately predict the prognosis of patients with ESCC; thus, maybe it can be used for the clinical diagnosis of ESCC. The results also showed that milciclib might inhibit the proliferation and migration of KYSE150 and KYSE510 cells by targeting CDKN2A. In conclusion, the abovementioned CUGs and CRGs play a crucial role in tumorigenesis and cancer progression in ESCC, indicating their potential as therapeutic targets.

MoS2@N-doped graphitic carbon/TiO2 photocatalysts for photocatalytic H2 production from lignocellulosic biomass.

TiO2 nanoparticles grown on MoS2/N-doped graphitic carbon were demonstrated to be efficient noble-metal-free photocatalysts for H2 production from lignocellulosic biomass, and the H2 generation rate from wheat straw, corncob, polar wood chip, bamboo, rice hull, corn straw and rice straw aqueous solution respectively reaches 4.9, 6.7, 11.7, 14.5, 8.4, 7.3 and 6.2 µmol g-1 h-1.

Autophagy in the retinal neurovascular unit: New perspectives into diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most prevalent retinal disorders worldwide, and it is a major cause of vision impairment in individuals of productive age. Research has demonstrated the significance of autophagy in DR, which is a critical intracellular homeostasis mechanism required for the destruction and recovery of cytoplasmic components. Autophagy maintains the physiological function of senescent and impaired organelles under stress situations, thereby regulating cell fate via various signals. As the retina's functional and fundamental unit, the retinal neurovascular unit (NVU) is critical in keeping the retinal environment's stability and supporting the needs of retinal metabolism. However, autophagy is essential for the normal NVU structure and function. We discuss the strong association between DR and autophagy in this review, as well as the many kinds of autophagy and its crucial physiological activities in the retina. By evaluating the pathological changes of retinal NVU in DR and the latest advancements in the molecular mechanisms of autophagy that may be involved in the pathophysiology of DR in NVU, we seek to propose new ideas and methods for the prevention and treatment of DR.

Lactate Dehydrogenase and Risk of Readmission with Gastric Cancer: A Propensity Score Matching Analysis.

PURPOSE: Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer. METHODS: We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model. RESULTS: A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493-9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding. CONCLUSIONS: Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.

Toxoplasma gondii infection triggers ongoing inflammation mediated by increased intracellular Cl- concentration in airway epithelium.

Toxoplasma gondii is a widespread parasitic protozoan causing toxoplasmosis including pulmonary toxoplasmosis. As the first line of host defense, airway epithelial cells play critical roles in orchestrating pulmonary innate immunity. However, the mechanism underlying the airway inflammation induced by the T. gondii infection remains largely unclear. This study demonstrated that after infection with T. gondii, the major anion channel located in the apical membranes of airway epithelial cells, cystic fibrosis transmembrane conductance regulator (CFTR), was degraded by the parasite-secreted cysteine proteases. The intracellular Cl- concentration ([Cl-]i) was consequently elevated, leading to activation of nuclear factor-κB (NF-κB) signaling via serum/glucocorticoid regulated kinase 1. Furthermore, the heightened [Cl-]i and activated NF-κB signaling could be sustained in a positive feedback regulatory manner resulting from decreased intracellular cAMP level through NF-κB-mediated up-regulation of phosphodiesterase 4. Conversely, the sulfur-containing compound allicin conferred anti-inflammatory effects on pulmonary toxoplasmosis by decreasing [Cl-]i via activation of CFTR. These results suggest that the intracellular Cl- dynamically modulated by T. gondii mediates sustained airway inflammation, which provides a potential therapeutic target against pulmonary toxoplasmosis.

Predictive factors and nomogram to evaluate the risk of below-ankle re-amputation in patients with diabetic foot.

BACKGROUND: Diabetes mellitus, as the most common metabolic disease, is common worldwide and represents a crucial global health concern. The purpose of this research was to investigate the related risk factors and to develop a re-amputation risk nomogram in diabetic patients who have undergone an amputation. METHODS: A observational analysis was performed on 459 patients who have underwent amputation for diabetic foot from January 2014 through December 2019 at the First Affiliated Hospital of Wenzhou Medical University. The least absolute shrinkage and selection operator regression and stepwise regression methods were implemented to determine risk selection for the re-amputation risk model, and the predictive nomogram was established with these features. Calibration curve, receiver operating characteristic curve, and decision curve analysis of this re-amputation nomogram were assessed. RESULTS: Predictors contained in this predictive model included smoking, glycated hemoglobin A1c (HbA1c), ankle-brachial index (ABI) and C-reactive protein (CRP). Good discrimination with a C-index of 0.725 (95% CI, 0.6624-0.7876) and good calibration were displayed with this predictive model. The decision curve analysis showed that this re-amputation nomogram predicting risk adds more benefit than none strategy if the threshold probability of a patient was >6% and <59%. CONCLUSIONS: This novel re-amputation nomogram incorporating smoking, glycated hemoglobin A1c (HbA1c), ankle-brachial index (ABI), C-reactive protein (CRP), and smoking could be easily used to predict individual re-amputation risk prediction in diabetic foot patients who have undergone an amputation. In the future, further analysis and external testing will be needed as much as possible to reconfirm that this new Nomogram can accurately predict the risk of toe re-amputation.

Impact of time in range during hospitalization on clinical outcomes in diabetic patients with toe amputation: a propensity score matching analysis.

PURPOSE: In recent years, time in range (TIR), defined as a percentage within a target time range, has attracted much attention. This study was aimed to investigate the short-term effects of Time in Rang on diabetic patients undergoing toe amputation in a more specific and complete manner. METHODS: A retrospective analysis on patients with diabetic foot ulcer (DFU) treated by toe amputation or foot amputation at the First Affiliated Hospital of Wenzhou Medical University between January 2015 and December 2019 were evaluated. A 1:1 match was conducted between the TIR < 70% group and the TIR ≥ 70% group using the nearest neighbor matching algorithm. Data were analyzed using Chi-squared, Fisher's exact, and Mann-Whitney U tests. RESULTS: Compared with patients in the TIR ≥ 70% group, patients in the TIR < 70% had a higher rate of re-amputation, and a higher rate of postoperative infection. Multivariate analysis revealed that smoking, lower extremity arterial disease and TIR < 70% were risk factors for surgery of re-amputation. The results of subgroup analysis found that the TIR < 70% was associated with a greater risk of re-amputation in patients with HbA1c < 7.5%, lower extremity arterial disease, and non-smokers. CONCLUSIONS: TIR can be used as a short-term glycemic control indicator in patients with DFUs and should be widely accepted in clinical practice. However, a future multicenter prospective study is needed to determine the relationship between TIR and toe re-amputation in diabetic foot patients.

Establish a New Diagnosis of Sarcopenia Based on Extracted Radiomic Features to Predict Prognosis of Patients With Gastric Cancer.

Background: Preoperative sarcopenia is a prognostic risk factor for gastric cancer (GC). This study aimed to determine whether radiomic sarcopenia features on computed tomography (CT) could be used to diagnose sarcopenia preoperatively, and whether they could be used to accurately predict the postoperative survival and complication prognosis of patients with GC. Methods: We retrospectively analyzed data of 550 patients with GC who underwent radical gastrectomy. The patients were divided into training (2014-2016) and validation (2017-2019) cohorts. We established a radiomics-based diagnosis tool for sarcopenia. Thereafter, univariate and multivariate analyses of diagnostic factors were carried out. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were used to compare different diagnostic models. The Kaplan-Meier method was used to estimate the survival curve. Results: Radiomic sarcopenia correlated with complications and long-term survival. Skeletal muscle index, grip strength, and walking speed were correlated with postoperative complications in both cohorts (AUCs: 0.632, 0.577, and 0.614, respectively in the training cohort; 0.570, 0.605, 0.546, respectively, in the validation cohort), and original sarcopenia was more accurate than any of these indicators. However, radiomic sarcopenia has a higher AUC in predicting short-term complications than original sarcopenia in both groups (AUCs: 0.646 vs. 0.635 in the training cohort; 0.641 vs. 0.625 in the validation cohort). In the training cohort, the overall survival time of patients with original sarcopenia was shorter than normal patients (hazard ratio, HR = 1.741; 95% confidence interval [CI], 1.044-2.903; p = 0.031). While radiomic sarcopenia had a greater prognostic significance, the overall survival time of patients with radiomic sarcopenia was significantly worse than normal patients (HR, 1.880; 95% CI, 1.225-2.885, p = 0.003). Conclusion: Extracted sarcopenia features based on CT can predict long-term survival and short-term complications of GC patients after surgery, and its accuracy has been verified by training and validation groups. Compared with original sarcopenia, radiomic sarcopenia can effectively improve the accuracy of survival and complication prediction and also shorten the time and steps of traditional screening, thereby reducing the subjectivity effects of sarcopenia assessment.

SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl- accumulation in respiratory epithelium.

SARS-CoV-2, the culprit pathogen of COVID-19, elicits prominent immune responses and cytokine storms. Intracellular Cl- is a crucial regulator of host defense, whereas the role of Cl- signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear. By using human respiratory epithelial cell lines, primary cultured human airway epithelial cells, and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge, we demonstrated that SARS-CoV-2 nucleocapsid (N) protein could interact with Smad3, which downregulated cystic fibrosis transmembrane conductance regulator (CFTR) expression via microRNA-145. The intracellular Cl- concentration ([Cl-]i) was raised, resulting in phosphorylation of serum glucocorticoid regulated kinase 1 (SGK1) and robust inflammatory responses. Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation. Moreover, N protein promoted a sustained elevation of [Cl-]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4 (PDE4). Rolipram, a selective PDE4 inhibitor, countered airway inflammation by reducing [Cl-]i. Our findings suggested that Cl- acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection. Targeting the Cl- signaling pathway might be a novel therapeutic strategy for COVID-19.

Allicin Facilitates Airway Surface Liquid Hydration by Activation of CFTR.

Airway epithelium plays critical roles in regulating airway surface liquid (ASL), the alteration of which causes mucus stasis symptoms. Allicin is a compound released from garlic and harbors the capacity of lung-protection. However, the potential regulatory effects of allicin on airway epithelium remain elusive. This study aimed to investigate the effects of allicin on ion transport across airway epithelium and evaluate its potential as an expectorant. Application of allicin induced Cl- secretion across airway epithelium in a concentration-dependent manner. Blockade of cystic fibrosis transmembrane conductance regulator (CFTR) or inhibition of adenylate cyclase-cAMP signaling pathway attenuated allicin-induced Cl- secretion in airway epithelial cells. The in vivo study showed that inhaled allicin significantly increased the ASL secretion in mice. These results suggest that allicin induces Cl- and fluid secretion across airway epithelium via activation of CFTR, which might provide therapeutic strategies for the treatment of chronic pulmonary diseases associated with ASL dehydration.

Cellular mechanism underlying the facilitation of contractile response induced by IL-25 in mouse tracheal smooth muscle.

Asthma is a common heterogeneous respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR) which is associated with abnormality in smooth muscle contractility. The epithelial cell-derived cytokine IL-25 is implicated in type 2 immune pathology including asthma, whereas the underlying mechanisms have not been fully elucidated. This study aims to investigate the effects of IL-25 on mouse tracheal smooth muscle contractility and elucidate the cellular mechanisms. Incubation with IL-25 augmented the contraction of mouse tracheal smooth muscles, which could be suppressed by the L-type voltage-dependent Ca2+ channel (L-VDCC) blocker nifedipine. Furthermore, IL-25 enhanced the cytosolic Ca2+ signals and triggered the upregulation of α1C L-VDCC (CaV1.2) in primary cultured mouse tracheal smooth muscle cells. Knocking down IL-17RA/IL-17RB receptors or inhibiting the transforming growth factor-ß-activated kinase 1 (TAK1)-tumor progression locus 2 (TPL2)-MAPK kinase 1/2 (MEK1/2)-ERK1/2-activating protein-1 (AP-1) signaling pathways suppressed the IL-25-elicited upregulation of CaV1.2 and hyperreactivity in tracheal smooth muscles. Moreover, inhibition of TPL2, ERK1/2 or L-VDCC alleviated the AHR symptom induced by IL-25 in a murine model. This study revealed that IL-25 potentiated the contraction of tracheal smooth muscle and evoked AHR via activation of TPL2-ERK1/2-CaV1.2 signaling, providing novel targets for the treatment of asthma with a high-IL-25 phenotype.

Aerobic exercise combined with glucosamine hydrochloride capsules inhibited the apoptosis of chondrocytes in rabbit knee osteoarthritis by affecting TRPV5 expression.

OBJECTIVE: This study aimed to investigate the effect of aerobic exercise combined with glucosamine (OTL) on the apoptosis of chondrocytes of rabbit knee osteoarthritis (KOA) by affecting the expression of TRPV5. METHODS: After the KOA white rabbit model was established, aerobic training and OTL treatment were performed, then the model joints were evaluated by Mankin, HE staining was used to observe the pathological changes of articular cartilage, TUNEL and immunohistochemistry were used to detect chondrocyte apoptosis. Knee chondrocytes were isolated and identified by Alcian Blue and type II collagen fiber staining. The cells were treated with iodoacetic acid (MIA) to simulate osteoarthritis in vitro, and then the effect of TRPV5 on apoptosis was detected by flow cytometry, in addition, apoptosis-related proteins and TRPV5 were detected by western blotting and qRT-PCR. RESULTS: Both aerobic exercise and OTL treatment could significantly reduce the Mankin score of KOA model, and could effectively inhibit chondrocyte apoptosis in the KOA model, and inhibit the expression of caspase 3 and caspase 9 in the KOA model. TRPV5 expression was significantly increased in the model, while both aerobic exercise and OTL could reverse its expression. The low-expression of TRPV5 significantly reversed the role of MIA in promoting apoptosis and apoptosis-related proteins of knee chondrocytes, while overexpressing TRPV5 promoted MIA-induced apoptosis and apoptosis-related proteins. CONCLUSION: Aerobic exercise combined with glucosamine hydrochloride capsules inhibited the apoptosis of chondrocytes in rabbit KOA by affecting the expression of TRPV5.

[Research progress on the revision of Metal-on-Metal hip arthroplasty due to adverse reactions to metal debris].

The choice of friction interface has always been a controversial topic in hip arthroplasty. Although the metal-on-metal (MoM) interface has gradually faded out of our vision, its revision is a clinical difficulty. Adverse reactions to metal debris (ARMD) is the most common indication for MoM hip arthroplasty revision, and the clinical results of hip arthroplasty due to ARMD are not satisfactory. At present, the indications and suggestions for revision of ARMD are not uniform. In this article, the clinical diagnosis, indications of revision, risk factors of prognosis, intraoperative suggestions and reasons for revision of ARMD were summarized. This article briefly introduces the diagnosis and treatment strategies and precautions of hip arthroplasty due to ARMD, in order to provide reference for such patients in clinical practice.

Effect of Short-Term Preoperative Parenteral Nutrition Support for Gastric Cancer Patients with Sarcopenia: a Propensity Score Matching Analysis.

INTRODUCTION: Sarcopenia is well recognized as an unfavorable prognostic marker for gastric cancer (GC) patients. Currently, few nutritional interventions-such as parenteral nutrition-exist for the treatment of patients with sarcopenia. This study aimed to estimate the effectiveness of short-term preoperative parenteral nutrition (PN) in GC patients with sarcopenia. MATERIALS AND METHODS: We collected data on GC patients with sarcopenia who underwent radical gastrectomy at our hospital from 2010 to 2018. A 1:1 ratio propensity score matching (PSM) was applied to establish the PN and control groups. Data were analyzed using the chi-squared, Mann-Whitney U, and Fisher's exact tests. RESULTS: In total, 428 patients met the inclusion criteria, and the propensity scores identified 166 matched pairs of patients with sarcopenia. The overall incidence of postoperative complications between both groups was not significantly different (P = 0.728). The PN group had a lower rate of intra-abdominal infection (P = 0.032) and higher hospitalization costs (P < 0.001) than the control group. Multivariate analysis demonstrated that age, Charlson score, and TNM stage were independent risk factors for postoperative complications. Additionally, subgroup analysis revealed that short-term preoperative PN support is associated with decreased postoperative surgical complications in patients with albumin levels < 35 g/L (P = 0.025). CONCLUSION: Short-term preoperative PN support is not associated with reduction of overall complication rate in patients with GC and sarcopenia. However, those with sarcopenia and hypoalbuminemia benefited from preoperative PN support.

Association of time in range with postoperative wound healing in patients with diabetic foot ulcers.

Time in range (TIR) is a novel indicator of glycaemic control that has been reported to have an association with diabetic complications. The objective of the study was to explore the association of TIR with postoperative wound healing in patients with diabetic foot ulcers (DFUs). We retrospectively analysed the data of DFU patients who had undergone surgical treatment from 2015 to 2019. A 1:1 ratio in propensity score matching (PSM) was adopted to compare patients with TIR ≥50% with those <50%. Data were summarised using chi-squared, Fisher's exact, and Mann-Whitney U tests. Patients with TIR <50% underwent a higher rate of secondary surgery within a month (P = .032) and had a longer hospital stay (P = .045) with greater hospital charges (P < .001) than the TIR ≥50% group. Multivariate analysis revealed that TIR (P = .034), Wagner score (P = .009), diabetes treatment (P = .006), and type of surgery (P = .013) were independent risk factors for secondary surgery. Additionally, patient subgroups with TIR <50% and baseline HbA1c < 7.5% (P = .025), albumin level ≥ 30 g/L (P = .039), HDL < 1.16 (P = .021), or Wagner score ≥ 3 (P = .048) also experienced a higher incidence of secondary surgery. TIR was correlated with postoperative wound healing in patients with DFUs. Strict glycaemic targets should be established for surgical patients.

Cellular Mechanism Underlying the Facilitation of Contractile Response Induced by Tumor Necrosis Factor-α in Mouse Tracheal Smooth Muscle.

The proinflammatory cytokine tumor necrosis factor-α (TNF-α) augments intracellular Ca2+ signaling and contractile responses of airway smooth muscles, leading to airway hyperresponsiveness. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the cellular mechanism of the potentiated contraction of mouse tracheal smooth muscle induced by TNF-α. The results showed that TNF-α triggered facilitation of mouse tracheal smooth muscle contraction in an epithelium-independent manner. The TNF-α-induced hypercontractility could be suppressed by the protein kinase C inhibitor GF109203X, the tyrosine kinase inhibitor genistein, the Src inhibitor PP2, or the L-type voltage-dependent Ca2+ channel blocker nifedipine. Following TNF-α incubation, the α1C L-type Ca2+ channel (CaV1.2) was up-regulated in cultured primary mouse tracheal smooth muscle cells. Pronounced phosphotyrosine levels were observed in mouse tracheas. In conclusion, this study shows that TNF-α enhanced airway smooth muscle contraction via protein kinase C-Src-CaV1.2 pathways, which provides novel insights into the pathologic role of proinflammatory cytokines in mediating airway hyperresponsiveness.

Impact of malnutrition diagnosed using Global Leadership Initiative on Malnutrition criteria on clinical outcomes of patients with gastric cancer.

OBJECTIVE: Our objective is to validate the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) criteria in malnutrition diagnosis compared with Patient-Generated Subjective Global Assessment (PG-SGA) and assess the impact of malnutrition diagnosed using GLIM criteria on the clinical outcomes of patients with GC. METHODS: We retrospectively analyzed the data of 895 patients who underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Nutrition assessment was performed on all patients according to the GLIM criteria and PG-SGA. The κ statistic was used to evaluate the agreement between two methods. Multivariate logistic regression and Cox regression based on single-factor analysis were used to predict postoperative complications and overall survival rates. RESULTS: Based on the GLIM criteria, 38.3% of the patients were diagnosed as malnourished, including 21.7% Stage I (moderate malnutrition) and 16.6% Stage II (severe malnutrition). GLIM criteria had a moderate agreement with PG-SGA (κ = 0.548). Patients in the Stage II malnutrition group had a higher incidence of complications, a longer postoperative length of stay, and higher hospitalization costs. Logistic regression showed that Stage II malnutrition was an independent risk predictor of postoperative complications (odds ratio, 3.28; 95% confidence interval [CI], 2.18-4.94). Furthermore, Cox regression analysis showed that both Stage I (hazard ratio [HR], 1.52; 95% CI, 1.11-2.07; P = .009) and Stage II (HR, 1.85; 95% CI, 1.34-2.53; P < .001) malnutrition were independent risk predictors of overall survival. CONCLUSION: Diagnosis of malnutrition according to the GLIM criteria is useful in predicting the adverse postoperative clinical outcomes of patients with gastric cancer.

Application of Suspension Fixation with Button Plates for Patients with Distal Radioulnar Joint Dislocation: A Case Series.

OBJECTIVE: The aim of the present study was to assess the effect of suspension fixation with button plates on the reconstruction of the distal radioulnar joint dislocation (DRUJ). METHODS: This was a case series of six patients (two men and four women) who underwent suspension fixation with button plates for DRUJ dislocation between January 2015 and May 2017. Physical examination, radiography, MRI, functional activity of the wrist joint, grip strength of the wrist joint, Garland-Werley wrist score, Mayo wrist score, and visual analog scale (VAS) score were used to evaluate the effect of this procedure. All patients were followed up every 3 months. The evaluation time point was 12 months after the operation. Comparisons of the functional indexes of wrist function before and after the operation were performed using paired statistical tests. RESULTS: The mean range of motion of the affected limb was 70° at forearm pronation and 75° at forearm supination. The subjective assessments and tests of the motor function of the wrist showed improvement after surgery. The Garland-Werley wrist score was 13.50 ± 2.66 preoperatively, the Mayo wrist score was 56.67 ± 18.35, and the VAS score was 4.83 ± 1.17. The Garland-Werley wrist score was 2.83 ± 1.33 postoperatively at 12 months, the Mayo wrist score was 87.5 ± 6.89, and the VAS score was 0.50 ± 0.55. At 12 months, the Garland-Werley wrist score, the Mayo wrist score, and the VAS score showed significant improvements when compared with those before surgery (P = 0.000, P = 0.003, and P = 0.000, respectively). Radiographic examination revealed that the internal fixation device was in place, and no dislocation of the DRUJ could be observed. None of the patients had internal fixation device removal or re-dislocation of the DRUJ. None of the patients had re-dislocation of the DRUJ. No secondary ulnar or radial fractures and nerve injury were reported during and after surgery. No tumor recurrence was observed in patients with giant cell tumors of the tendon sheath. No loosening and displacement of screws were reported. CONCLUSION: The new method of suspension fixation with button plates for the surgical reconstruction of a DRUJ dislocation is simple, with minimal trauma, and maintains the stability of the DRUJ without the need for intra-articular or extra-articular reconstruction of the ligament. Furthermore, it allows early functional exercise and achieves satisfactory postoperative functional recovery.

Cytisine Exerts an Anti-Epileptic Effect via α7nAChRs in a Rat Model of Temporal Lobe Epilepsy.

Background and Purpose: Temporal lobe epilepsy (TLE) is a common chronic neurological disease that is often invulnerable to anti-epileptic drugs. Increasing data have demonstrated that acetylcholine (ACh) and cholinergic neurotransmission are involved in the pathophysiology of epilepsy. Cytisine, a full agonist of α7 nicotinic acetylcholine receptors (α7nAChRs) and a partial agonist of α4ß2nAChRs, has been widely applied for smoking cessation and has shown neuroprotection in neurological diseases. However, whether cytisine plays a role in treating TLE has not yet been determined. Experimental Approach: In this study, cytisine was injected intraperitoneally into pilocarpine-induced epileptic rats for three weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was used to evaluate the mechanism of action of cytisine. Rats were assayed for the occurrence of seizures and cognitive function by video surveillance and Morris water maze. Hippocampal injuries and synaptic structure were assessed by Nissl staining and Golgi staining. Furthermore, levels of glutamate, γ-aminobutyric acid (GABA), ACh, and α7nAChRs were measured. Results: Cytisine significantly reduced seizures and hippocampal damage while improving cognition and inhibiting synaptic remodeling in TLE rats. Additionally, cytisine decreased glutamate levels without altering GABA levels, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. α-bgt antagonized the above-mentioned effects of cytisine treatment. Conclusion and Implications: Taken together, these findings indicate that cytisine exerted an anti-epileptic and neuroprotective effect in TLE rats via activation of α7nAChRs, which was associated with a decrease in glutamate levels, inhibition of synaptic remodeling, and improvement of cholinergic transmission in the hippocampus. Hence, our findings not only suggest that cytisine represents a promising anti-epileptic drug, but provides evidence of α7nAChRs as a novel therapeutic target for TLE.