Correlation analysis of cofilin-1 with renal prognosis in primary IgA nephropathy.

PURPOSE: The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN). METHODS: Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis. RESULTS: 133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803). CONCLUSION: Cofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN.

Optimization of sub-arc collimator angles in volumetric modulated arc therapy: a heatmap-based blocking index approach for multiple brain metastases.

To develop and assess an automated Sub-arc Collimator Angle Optimization (SACAO) algorithm and Cumulative Blocking Index Ratio (CBIR) metrics for single-isocenter coplanar volumetric modulated arc therapy (VMAT) to treat multiple brain metastases. This study included 31 patients with multiple brain metastases, each having 2 to 8 targets. Initially, for each control point, the MLC blocking index was calculated at different collimator angles, resulting in a two-dimensional heatmap. Optimal sub-arc segmentation and collimator angle optimization were achieved using an interval dynamic programming algorithm. Subsequently, VMAT plans were designed using two approaches: SACAO and the conventional Full-Arc Fixed Collimator Angle. CBIR was calculated as the ratio of the cumulative blocking index between the two plan approaches. Finally, dosimetric and planning parameters of both plans were compared. Normal brain tissue, brainstem, and eyes received better protection in the SACAO group (P < 0.05).Query Notable reductions in the SACAO group included 11.47% in gradient index (GI), 15.03% in monitor units (MU), 15.73% in mean control point Jaw area (AJaw,mean), and 19.14% in mean control point Jaw-X width (WJaw-X,mean), all statistically significant (P < 0.001). Furthermore, CBIR showed a strong negative correlation with the degree of plan improvement. The SACAO method enhanced protection of normal organs while improving transmission efficiency and optimization performance of VMAT. In particular, the CBIR metrics show promise in quantifying the differences specifically in the 'island blocking problem' between SACAO and conventional VMAT, and in guiding the enhanced application of the SACAO algorithm.

Early Acute Kidney Injury Recovery in Elderly Patients Undergoing Valve Replacement Surgery.

OBJECTIVES: This study was designed to determine the incidence, contributing factors, and prognostic implications of acute kidney injury (AKI) recovery patterns in patients who experienced AKI after valve replacement surgery (VRS). DESIGN: A retrospective cohort study was conducted. SETTING: The work took place in a postoperative care center in a single large-volume cardiovascular center. PARTICIPANTS: Patients undergoing VRS between January 2010 and December 2019 were enrolled. INTERVENTION: Patients were categorized into three groups based on their postoperative AKI status: non-AKI, AKI with early recovery (less than 48 hours), and persistent AKI. MEASUREMENT AND MAIN RESULTS: The primary outcome was in-hospital major adverse clinical events. The secondary outcomes included in-hospital and 1-year mortality. A total of 4,161 patients who developed AKI following VRS were included. Of these, 1,513 (36.4%) did not develop postoperative AKI, 1,875 (45.1%) experienced AKI with early recovery, and 773 (18.6%) had persistent AKI. Advanced age, diabetes, New York Heart Association III-IV heart failure, moderate-to-severe renal dysfunction, anemia, and AKI stages 2 and 3 were identified as independent risk factors for persistent AKI. In-hospital major adverse clinical events occurred in 59 (3.9%) patients without AKI, 88 (4.7%) with early AKI recovery, and 159 (20.6%) with persistent AKI (p < 0.001). Persistent AKI was independently associated with an increased risk of in-hospital adverse events and 1-year mortality. In contrast, AKI with early recovery did not pose additional risk compared with non-AKI patients. CONCLUSIONS: In patients who develop AKI following VRS, early AKI recovery does not pose additional risk compared with non-AKI. However, AKI lasting more than 48 hours is associated with an increased risk of in-hospital and long-term adverse outcomes.

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR.

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

A prospective, single-centre, randomized, double-blind controlled study protocol to study whether long-term oral metronidazole can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer.

INTRODUCTION: Fifteen to 25% of patients with colorectal cancer have combined liver metastases at the time of diagnosis, whereas an additional 15 to 25% will develop liver metastases after curative resection of primary colorectal cancer, with the vast majority (80-90%) of liver metastases unresponsive to curative resection at first. Colorectal cancer liver metastasis is also the leading cause of death in patients with colorectal cancer. In recent years, several studies have demonstrated that intestinal flora, especially Fusobacterium nucleatum, plays a crucial role in the development of colorectal cancer liver metastasis, so we hypothesized that long-term metronidazole use could effectively reduce the incidence of postoperative liver metastasis in colorectal cancer patients. METHODS/DESIGN: This study is a prospective, single-centre, randomized, double-blind controlled study in which 300 patients will be randomly assigned to the test group or the control group in a 1:1 allocation ratio. The aim of this trial is to demonstrate that long-term oral antibiotics can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee at the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20210229). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046201. Registered on July 05, 2021.

Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution.

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions: Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

Comparing intracorporeal mechanical anastomosis vs. hand-sewn esophagojejunostomy after total laparoscopic gastrectomy for esophagogastric junction cancer: a single-center study.

OBJECTIVE: This study aimed to compare the effects of continuous hand-sewn esophagojejunostomy with barbed suture and mechanical anastomosis in total laparoscopic gastrectomy for esophagogastric junction cancer. MATERIALS AND METHODS: The clinical data of 60 patients who underwent total laparoscopic total gastrectomy from January 2020 to October 2021 were collected retrospectively. Baseline data and short-term surgical results of patients in the hand-sewn anastomosis (n = 30) and mechanical anastomosis (n = 30) groups were analyzed. RESULTS: No significant differences were detected in the baseline data between groups. Meanwhile, the hand-sewn group had a shorter anastomosis time (21.2 ± 4.9 min vs. 27.9 ± 6.9 min, p < 0.001) and a decreased operation cost (CNY 70608.3 ± 8106.7 vs. CNY 76485.6 ± 3149.9, p = 0.001). The tumor margin distance in the hand-sewn group was longer than in the mechanical group (2.7 ± 0.4 cm vs. 2.2 ± 0.75 cm, p = 0.002). In esophagojejunostomy anastomosis, the distance between the jejunal opening and jejunal stump in the hand-sewn group was significantly shorter than that in the mechanical group (2.2 ± 0.54 cm vs. 5.7 ± 0.6 cm, p < 0.001). No significant difference was detected in the incidence of postoperative anastomotic complications. CONCLUSION: The continuous hand-sewn anastomosis with barbed suture in total laparoscopic gastrectomy for esophagogastric junction cancer is practical, safe, and cost-effective. It is also an effective supplementary technique for mechanical anastomosis.

Different 18F-FDG imaging: A rare case of liver multiple carcinomas.

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.

Study protocol for comparing the efficacy of left-open single-flap technique versus double-flap technique after proximal gastrectomy: A multicenter randomized controlled trial.

Background: Proximal gastrectomy has gradually gained more attention due to its superiority in retaining the function of part of the stomach. The inevitable loss of the antireflux barrier and postoperative complications resulting from proximal gastrectomy can severely affect the quality of life. Continuous improvements in digestive tract reconstruction after proximal gastrectomy have yielded the development of a variety of methods with antireflux functions. Recently, our center attempted the left-open single-flap technique and initiated a multicenter, prospective, randomized controlled trial for patients undergoing proximal gastrectomy to reduce the difficulty of surgical anastomosis and the incidence of perioperative complications compared with the double-flap technique. These findings will provide more evidence-based medical research for the development of clinical guidelines. Methods/design: This study is a prospective, multicenter, randomized controlled clinical trial. We plan to recruit 250 patients who are eligible for proximal gastrectomy. After informed consent is obtained, patients will be randomly assigned to the trial group (left-open single-flap technique) and the control group (double-flap technique) in a 1:1 allocation ratio. Discussion: Increasingly, clinical studies have focused on the improvement of reconstruction modalities after proximal gastrectomy. Among these methods, the double-flap technique is a clinically effective method. The purpose of this study is to establish a prospective randomized controlled trial to compare the efficacy of the left-open single-flap technique versus the double-flap technique after proximal gastrectomy, aiming to provide more evidence-based medical studies for digestive tract reconstruction in proximal gastrectomy. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT05418920].

[Effects of Dasatinib on the Maturation of Monocyte-Derived Dendritic Cells Derived from Healthy Donors and Chronic Myelogenous Leukemia Patients].

OBJECTIVE: To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. The generation of moDCs from PBMCs was completed after 7 days of incubation in DC I culture medium, and another 3 days of incubation in DC II culture medium with or without 25 nmol/L dasatinib. On the 10th day, cells were harvested and expression of molecules of maturation related marker were assessed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as DCs in the fluorescence-activated cell storting (FACS) analyzing system, then the expression of CD83, CD40 or HLA-DR in this population was analyzed respectively. RESULTS: The proportion of CD80+CD86+ cells in total cells didn't show a statistical difference between HD group and patient group (89.46%±9.70% vs 87.39%±9.34%, P=0.690). Dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.008) and HLA-DR (P=0.028) on moDCs derived from HDs compared with the control group, while the expression of CD83 on moDCs didn't show a significant difference between dasatinib group and the control group (P=0.428). Meanwhile, dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.023), CD83 (P=0.038) and HLA-DR (P=0.001) on moDCs derived from patients compared with the control group. CONCLUSION: For CML patients, the same high proportion of moDCs as HDs can be induced in vitro, which provides a basis for the application of DC-based immunotherapy strategy. Dasatinib at the concentration of 25 nmol/L can efficiently promote the maturation of moDCs derived from HDs and CML patients in vitro. Dasatinib shows potential as a DC adjuvant to be applied in DC-based immunotherapy strategies, such as DC vaccine and DC cell-therapy.

Protocol for Comparing the Efficacy of Three Reconstruction Methods of the Digestive Tract (Kamikawa Versus Double-Tract Reconstruction Versus Tube-Like Stomach) After Proximal Gastrectomy.

Background: Appropriate gastrointestinal reconstruction after proximal gastrectomy can effectively reduce the incidence of postoperative complications in patients with proximal early gastric cancer. However, there is still great controversy about the choice of digestive tract reconstruction after proximal gastrectomy, and there is no clinical consensus on the choice of digestive tract reconstruction after proximal gastrectomy. Currently, there is a lack of large-sample, prospective, randomized controlled studies to compare the efficacy of Kamikawa, double-tract reconstruction, and tube-like stomach reconstruction after proximal gastrectomy. Methods/design: This study will investigate the efficacy of three reconstruction methods after proximal gastrectomy in a prospective, multicenter, randomized controlled trial, which will enroll 180 patients with proximal early gastric cancer. Patients will be randomly divided into three groups: Group A (Kamikawa, n = 60), Group B (double-tract reconstruction, n = 60), and Group C (tube-like stomach, n = 60). The general information, past medical history, laboratory findings, imaging findings, and surgical procedures of the patients will be recorded and analyzed. The incidence of reflux esophagitis will be recorded as the primary endpoint. The incidence of anastomotic leakage, anastomotic stenosis, operative time and intraoperative blood loss will be recorded as secondary endpoints. Discussion: This study will establish a large-sample, prospective, randomized controlled trial to compare the efficacy of Kamikawa, double-tract reconstruction, and tube-like stomach reconstruction after proximal gastrectomy. Trial registration: This study was approved by the Chinese Clinical Trial Registry and registered on April 30, 2021. The registration number is ChiCTR2100045975.

A retrospective study of the role of preoperative ultrasonography in the detection of deep vein thrombosis in 1750 patients with gastric and colorectal cancers.

BACKGROUND: There has been a lack of research in the past on the prevalence and risk factors associated with deep vein thrombosis (DVT) in patients with resectable gastric and colorectal cancers. The purpose of this study was to review the anatomical distribution, prevalence and risk factors associated with lower limb DVT in 1750 patients with preoperative gastric and colorectal cancers and to evaluate the role of preoperative ultrasonography in the detection of DVT in preventing postoperative pulmonary thromboembolism (PTE) in patients with gastric and colorectal cancers. METHODS: A total of 1750 patients with gastric and colorectal cancers who underwent preoperative venous ultrasonography of the lower limbs were retrospectively reviewed. The risk factors associated with preoperative DVT were identified using univariate and multivariate logistic regression analysis. RESULTS: Seventy-three of the 1750 patients with gastric and colorectal cancers had DVT detected by preoperative venous ultrasonography of the lower limb and the incidence of lower limb DVT was 4.17 % in 1750 patients with gastric and colorectal cancers. Univariate analysis showed a higher risk of DVT in patients who met the following criteria: aged ≥80 years, female sex, the performance status ≥1, stage IV, ASA class ≥ III/IV, and hypertension. Multivariate logistic regression analysis showed that female sex, stage IV and ASA class ≥ III/IV were significantly associated with DVT before gastric and colorectal cancer surgery. CONCLUSIONS: Our study showed that female sex, stage IV and ASA class ≥ III/IV were significantly associated with DVT before gastric and colorectal cancer surgery. Routine venous ultrasonography for the lower limb can identify the risk of PTE, which is of great significance in the prevention and occurrence of PTE.

Low-Density Lipoprotein Cholesterol and Mortality Risk in Elderly Patients Undergoing Valve Replacement Surgery: A Propensity Score Matching Analysis.

Background: The prognostic value of low-density lipoprotein cholesterol (LDL-C) in elderly patients is controversial. This study aimed to elucidate the relationship between the preoperative LDL-C and adverse outcomes in elderly patients undergoing valve replacement surgery (VRS). Methods: A total of 2,552 aged patients (age ≥ 60 years) undergoing VRS were retrospectively recruited and divided into two groups according to LDL-C level on admission: low LDL-C (<70 mg/dL, n = 205) and high LDL-C groups (≥ 70 mg/dL, n = 2,347). The association between the preoperative LDL-C with in-hospital and one-year mortality was evaluated by propensity score matching analysis and multivariate analysis. Results: The mean age was 65 ± 4 years and 1,263 (49.5%) were men. Patients in the low LDL-C group were significantly older (65.9 ± 4.6 vs. 64.9 ± 4.1, p = 0.002), with more male (65.4 vs. 48.1%, p < 0.001), higher alanine transaminase (ALT) (21 vs. 19, p = 0.001), lower serum albumin (35.3 ± 4.6 vs. 37.1 ± 4.1, p < 0.001), higher serum creatinine (92.2 ± 38.2 vs.84.6 ± 26.1, p = 0.006), lower lymphocyte count (1.7 ± 0.7 vs. 1.9 ± 0.6, p < 0.001), lower hemoglobin (121.9 ± 22.3 vs. 130.2 ± 16.5, p < 0.001), lower platelet count (171.3 ± 64.3 vs. 187.7 ± 58.7, p < 0.001), lower prognostic nutrition index (44 ± 6.2 vs. 46.7 ± 5.8, p < 0.001), and more severe tricuspid regurgitation (33.7 vs. 25.1%, p = 0.008). The rates of in-hospital death (11.2 vs. 3.7%, p < 0.001) and major adverse clinical events (17.6 vs. 9.6%, p < 0.001) were significantly higher in the low LDL-C group. The cumulative one-year death rate was significantly higher in the low LDL-C group (Log-Rank = 16.6, p < 0.001). After matching analysis and multivariate analysis, no association between LDL-C level and adverse outcomes was detected (all p > 0.05). Conclusion: Our study did not support the negative relationship between LDL-C level and mortality risk in elderly patients undergoing VRS.

Are preoperative oral antibiotics effective in reducing the incidence of anastomotic leakage after colorectal cancer surgery? Study protocol for a prospective, multicentre, randomized controlled study.

INTRODUCTION: The optimal preoperative preparation for elective colorectal cancer surgery has been debated in academic circles for decades. Previously, several expert teams have conducted studies on whether preoperative mechanical bowel preparation and oral antibiotics can effectively reduce the incidence of postoperative complications, such as surgical site infections and anastomotic leakage. Most of the results of these studies have suggested that preoperative mechanical bowel preparation for elective colon surgery has no significant effect on the occurrence of surgical site infections and anastomotic leakage. METHODS/DESIGN: This study will examine whether oral antibiotic bowel preparation (OABP) influences the incidence of anastomotic leakage after surgery in a prospective, multicentre, randomized controlled trial that will enrol 1500 patients who require colon surgery. The primary endpoint, incidence of anastomotic leakage, is based on 2.3% in the OABP ± mechanical bowel preparation (MBP) group in the study by Morris et al. Patients will be randomized (1:1) into two groups: the test group will be given antibiotics (both neomycin 1 g and metronidazole 0.9 g) the day before surgery, and the control group will not receive any special intestinal preparation before surgery, including oral antibiotics or mechanical intestinal preparation. All study-related clinical data, such as general patient information, past medical history, laboratory examination, imaging results, and surgery details, will be recorded before surgery and during the time of hospitalization. The occurrence of postoperative fistulas, including anastomotic leakage, will be recorded as the main severe postoperative adverse event and will represent the primary endpoint. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200173). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. Protocol was revised on November 22, 2021, version 4.0. TRIAL REGISTRATION: ChiCTR2000035550 . Registered on 13 Aug 2020.

Biomechanics of extreme lateral interbody fusion with different internal fixation methods: a finite element analysis.

BACKGROUND: Establishing a normal L3-5 model and using finite element analysis to explore the biomechanical characteristics of extreme lateral interbody fusion (XLIF) with different internal fixation methods. METHOD: The L3-5 CT image data of a healthy adult male volunteer were selected to establish a normal lumbar finite element model (M0). The range of motion (ROM) of L3-4 and L4-5, under flexion, extension, left bending, right bending, left rotation, and right rotation, together with L3-4 disc pressure was analyzed. Then the L4-5 intervertebral disc was excised and implanted with a cage, supplemented by different types of internal fixation, including lateral two-hole plate model (M1), lateral four-hole plate model (M2), VerteBRIDGE plating model (M3), lateral pedicle model (M4), posterior unilateral pedicle screw model (M5) and posterior bilateral pedicle screw model (M6). The ROM,the maximum stress value of the cage, and the maximum stress value of the intervertebral disc of L3-4 were analyzed and studied . RESULTS: The ROM of L3-4 and L4-L5 segments in the validation model under various motion states was basically consistent with previous reports. The lumbar finite element model was validated effectively. After XLIF-assisted internal fixation, the range of activity in L3-4 segments of each internal fixation model was greater than that of the normal model under various working conditions, among which the M5、M6 model had the larger range of activity in flexion and extension. After the internal fixation of L4-5 segments, the mobility in M1-M6 was significantly reduced under various motion patterns. In terms of flexion and extension, the posterior pedicle fixation model (M5、M6) showed a significant reduction,followed by M2. The maximal von mises cage stress of M1 was obviously greater than that of other models (except the left bending). Compared with M0, the intervertebral disc stress of M1-M6 at L3-4 segments was increased. CONCLUSIONS: It is recommended that the posterior bilateral pedicle screw model is the first choice, followed by the lateral four-hole plate model for fixation during XLIF surgery. However, it is still necessary to be aware of the occurrence of adjacent segment degeneration (ASD) in the later stage.

The role of ferroptosis-related genes for overall survival prediction in breast cancer.

BACKGROUND: Ferroptosis is a novel iron-dependent form of cell death, which is implicated in various diseases including cancers. However, the influence of ferroptosis-related genes on the prognosis of breast cancer remains unclear. METHODS: RNA sequencing data of 1053 breast cancer tissue samples and 111 normal tissue samples from The Cancer Genome Atlas (TCGA) were analyzed. Expression levels of 259 ferroptosis-related genes were compared. Gene Ontology (GO) and the Kyoto Gene and Genomic Encyclopedia (KEGG) analyses were conducted on differentially expressed genes. Cox univariate analysis was conducted to explore the potential prognostic biomarkers of breast cancer. Infiltrating immune cell status was assessed. RESULTS: A total of 66 ferroptosis-related genes were differentially expressed in breast cancer tissues. The enriched GO terms included Biological Process (mainly included response to oxidative stress, cellular response to chemical stress, multicellular organismal homeostasis, cofactor metabolic process, response to metal ion, response to steroid hormone, cellular response to oxidative stress, transition metal ion homeostasis, iron ion homeostasis, and cellular iron ion homeostasis), Cellular Component (mainly included apical plasma membrane, early endosome, apical part of cell, lipid droplet, basolateral plasma membrane, blood microparticle, clathrin-coated pit, caveola, astrocyte projection, and pronucleus) and Molecular Function (mainly included iron ion binding, ubiquitin protein ligase binding, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor, ferric iron binding, aldo-keto reductase (NADP) activity, oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, steroid dehydrogenase activity, alditol:NADP+1-oxidoreductase activity, and alcohol dehydrogenase (NADP+) activity). The enriched KEGG pathway mainly included the HIF-1 signaling pathway, NOD-like receptor signaling pathway, ferroptosis, IL-17 signaling pathway, central carbon metabolism in cancer, PPAR signaling pathway, PD-L1 expression, and PD-1 checkpoint pathway in cancer. Among them, 38 ferroptosis-related genes were significantly associated with the prognosis of breast cancer. The prognostic model was constructed, and breast cancer patients in low-risk group had a better prognosis. In addition, risk score of ferroptosis prognostic model was negatively correlated with B cells (r = -0.063, p = 0.049), CD8+ T cells (r = -0.083, p = 0.010), CD4+ T cells (r = -0.097, p = 0.002), neutrophils (r = -0.068, p = 0.033), and dendritic cells (r = 0.088, p = 0.006). CONCLUSIONS: The ferroptosis pathway plays a key role in breast cancer. Some differentially expressed ferroptosis-related genes can be used as prognostic biomarkers for breast cancer.

Salidroside promoted osteogenic differentiation of adipose-derived stromal cells through Wnt/ß-catenin signaling pathway.

BACKGROUND: Bone disease causes short-term or long-term physical pain and disability. It is necessary to explore new drug for bone-related disease. This study aimed to explore the role and mechanism of Salidroside in promoting osteogenic differentiation of adipose-derived stromal cells (ADSCs). METHODS: ADSCs were isolated and treated with different dose of Salidroside. Cell count kit-8 (CCK-8) assay was performed to assess the cell viability of ADSCs. Then, ALP and ARS staining were conducted to assess the early and late osteogenic capacity of ADSCs, respectively. Then, differentially expressed genes were obtained by R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the differentially expressed genes were further analyzed. The expression of OCN, COL1A1, RUNX2, WNT3A, and ß-catenin were measured by real-time PCR and Western blot analysis. Last, ß-catenin was silenced by small interfering RNA. RESULTS: Salidroside significantly increased the ADSCs viability at a dose-response manner. Moreover, Salidroside enhanced osteogenic capacity of ADSCs, which are identified by enhanced ALP activity and calcium deposition. A total of 543 differentially expressed genes were identified between normal and Salidroside-treated ADSCs. Among these differentially expressed genes, 345 genes were upregulated and 198 genes were downregulated. Differentially expressed genes enriched in the Wnt/ß-catenin signaling pathway. Western blot assay indicated that Salidroside enhanced the WNT3A and ß-catenin expression. Silencing ß-catenin partially reversed the promotion effects of Salidroside. PCR and Western blot results further confirmed these results. CONCLUSION: Salidroside promoted osteogenic differentiation of ADSCs through Wnt/ß-catenin signaling pathway.

Identification of novel pleiotropic gene for bone mineral density and lean mass using the cFDR method.

Bone mineral density (BMD) and whole-body lean mass (WBLM) are two important phenotypes of osteoporosis and sarcopenia. Previous studies have shown that BMD and lean mass were phenotypically and genetically correlated. To identify the novel common genetic factors shared between BMD and WBLM, we performed the conditional false discovery rate (cFDR) analysis using summary data of the genome-wide association study of femoral neck BMD (n = 53,236) and WBLM (n = 38,292) from the Genetic Factors for Osteoporosis Consortium (GEFOS). We identified eight pleiotropic Single Nucleotide Polymorphism (SNPs) (PLCL1 rs11684176 and rs2880389, JAZF1 rs198, ADAMTSL3 rs10906982, RFTN2/MARS2 rs7340470, SH3GL3 rs1896797, ST7L rs10776755, ANKRD44/SF3B1 rs11888760) significantly associated with femoral neck BMD and WBLM (ccFDR < 0.05). Bayesian fine-mapping analysis showed that rs11888760, rs198, and rs1896797 were the possible functional variants in the ANKRD44/SF3B1, JAZF1i, and SH3GL3 loci, respectively. Functional annotation suggested that rs11888760 was likely to comprise a DNA regulatory element and linked to the expression of RFTN2 and PLCL1. PLCL1 showed differential expression in laryngeal posterior cricoarytenoid muscle between rats of 6 months and 30 months of age. Our findings, together with PLCL1's potential functional relevance to bone and skeletal muscle function, suggested that rs11888760 was the possible pleiotropic functional variants appearing to coregulate both bone and muscle metabolism through regulating the expression of PLCL1. The findings enhanced our knowledge of genetic associations between BMD and lean mass and provide a rationale for subsequent functional studies of the implicated genes in the pathophysiology of diseases, such as osteoporosis and sarcopenia.

Comparison of Outcomes of Totally Laparoscopic Total Gastrectomy (Overlap Reconstruction) versus Laparoscopic-Assisted Total Gastrectomy for Advanced Siewert III Esophagogastric Junction Cancer and Gastric Cancer of Upper and Middle Third of Stomach: Study Protocol for a Single-Center Randomized Controlled Trial.

BACKGROUND: Totally laparoscopic total gastrectomy (TLTG) using the overlap reconstruction method is associated with fewer postoperative complications and fast recovery than laparoscopic-assisted radical total gastrectomy (LATG). However, evidence on the safety and feasibility of TLTG (overlap reconstruction) in patients with advanced Siewert III esophagogastric junction cancer and gastric cancer of the upper and middle third of the stomach is scarce. METHODS: This study is a prospective, single-center, single-blind, two-arm randomized controlled trial designed to include 292 patients with advanced Siewert III esophagogastric junction cancer and gastric cancer of the upper and middle third of the stomach who will be randomly assigned to two groups: a TLTG overlap group (n=146) and an LATG group (n=146). The patients' demographics, pathological characteristics, intraoperative variables, postoperative complications, postoperative recovery variables, 3-year disease-free survival and 3-year overall survival will be collected and analyzed. The primary outcome is the postoperative complications within 30 days after surgery including intra-abdominal hemorrhage, anastomotic leakage, duodenal stump fistula, pancreatic fistula, chyle leakage, abdominal infection, intestinal obstruction, wound complications, pulmonary infection, pleural effusion, pulmonary embolism, cardiovascular and cerebrovascular complications, and deep vein thrombosis. The secondary outcomes are the 3-year disease-free survival and 3-year overall survival. DISCUSSION: This trial will provide high-level evidence for the safety and feasibility of TLTG (overlap reconstruction) compared with LATG in advanced Siewert III esophagogastric junction cancer and the upper and middle third of gastric cancer. TRIAL REGISTRATION: This trial has been registered at the Chinese Clinical Trial Registry: ChiCTR1900025667 (registration date: September 4, 2019).

Inflammatory indicator levels in patients undergoing aortic valve replacement via median sternotomy with preoperative anxiety and postoperative complications: a prospective cohort study.

OBJECTIVE: This study was performed to evaluate the association of preoperative anxiety with inflammatory indicators and postoperative complications in patients undergoing scheduled aortic valve replacement surgery. METHODS: A prospective cohort study was performed. The Hamilton Anxiety Scale was used to assess preoperative anxiety. The serum white blood cell (WBC) count and concentrations of C-reactive protein, interleukin (IL)-6, and IL-8 were measured 1 day preoperatively and 3 and 7 days postoperatively. Postoperative complications were also recorded. RESULTS: Seventy-three patients were included. The incidence of preoperative anxiety was 30.1% (22/73). The payment source was the only independent risk factor for preoperative anxiety. The incidence of postoperative complications was lowest in the mild anxiety group. The WBC count 3 days postoperatively was significantly lower in the mild than moderate-severe anxiety group. The IL-8 concentration 1 day preoperatively was highest in the no anxiety group. CONCLUSIONS: Mild preoperative anxiety might help to improve clinical outcomes. However, further investigations with more patients are warranted. Patients with different degrees of anxiety may have different levels of inflammatory cytokines.