Pediatric femoral shaft fractures: the American Academy of Orthopaedic Surgeons clinical practice guidelines versus actual management in a teaching hospital.

Background: In 2009, the clinical practice guidelines (CPG) were released by the American Academy of Orthopaedic Surgeons (AAOS), which outline an age-based approach for treating pediatric femoral shaft fractures (PFSF), both nonoperatively and operatively. The aim of the current study was to investigate potential disparities between the recommended treatments for PFSF based on the AAOS-CPG and the actual treatments administered in The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Methods: A retrospective review was conducted on the medical charts and radiographs of all PFSF treated at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2014 to January 2022. We identified 445 children who met our inclusion criteria and evaluated their treatments according to the AAOS-CPG. Actual treatments were then compared with the treatments recommended by the AAOS-CPG. Binomial and multivariate logistic regression was used to examine whether different factors could predict the choice between operative and nonoperative management. Results: Operative treatments were undertaken in 102 of 215 (47.4%) fractures in children younger than 6 years, in 102 of 122 (83.6%) fractures in those between 6 and 12 years of age, and in 107 of 108 (99.1%) fractures in those older than 12 years. Nonoperative management was conducted in 113 of 215 (52.6%) fractures in children younger than 6 years, in 20 of 122 (16.4%) fractures in those between 6 and 12 years of age, and in 1 of 108 (0.9%) fractures in those older than 12 years of age. Surgeon decisions for non-surgery were in agreement with the CPG 52.6% of the time, whereas agreement reached 90.9% for surgical choices. Predictors of actual operative management were age (P=0.01), patient weight (P<0.001), fracture pattern (P<0.001), presence of other orthopedic injuries requiring surgery (P=0.002), and polytrauma (P=0.02). Conclusions: There was limited concordance between actual treatments and CPG recommendations, particularly for the nonoperative management of fractures in children under 6 years old. Age, patient weight, fracture pattern, presence of other orthopedic injuries requiring surgery, and polytrauma were the main predictors of our operative decision-making process.

FERMT1 suppression induces anti-tumor effects and reduces stemness in glioma cancer cells.

OBJECTIVE: Glioma is a leading cause of mortality worldwide, its recurrence poses a major challenge in achieving effective treatment outcomes. Cancer stem cells (CSCs) have emerged as key contributors to tumor relapse and chemotherapy resistance, making them attractive targets for glioma cancer therapy. This study investigated the potential of FERMT1 as a prognostic biomarker and its role in regulating stemness through cell cycle in glioma. METHODS: Using data from TCGA-GBM, GSE4290, GSE50161 and GSE147352 for analysis of FERMT1 expression in glioma tissues. Then, the effects of FERMT1 knockdown on cell cycle, proliferation, sphere formation ability, invasion and migration were investigated. The influences of FERMT1 on expression of glycolysis-related proteins and levels of ATP, glucose, lactate and G6PDH were also explored. Furthermore, the effects of FERMT1 knockdown on cellular metabolism were evidenced. RESULTS: Significant upregulation of FERMT1 in glioma tissues was observed. Silencing FERMT1 not only affected the cell cycle but also led to a notable reduction in proliferation, invasion and migration. The expression of glycolysis-associated proteins including GLUT1, GLUT3, GLUT4, and SCO2 were reduced by FERMT1 knockdown, resulted in increased ATP and glucose as well as decreased lactic acid and G6PDH levels. FERMT1 knockdown also inhibited cellular metabolism. Moreover, FERMT1 knockdown significantly reduced sphere diameter, along with inhibiting the expression of transcription factors associated with stemness in glioma cells. CONCLUSION: These findings demonstrated that FERMT1 could be an ideal target for the advancement of innovative strategies against glioma treatment via modulating cellular process involved in stemness regulation and metabolism.

PGAM5 interacts with and maintains BNIP3 to license cancer-associated muscle wasting.

Regressing the accelerated degradation of skeletal muscle protein is a significant goal for cancer cachexia management. Here, we show that genetic deletion of Pgam5 ameliorates skeletal muscle atrophy in various tumor-bearing mice. pgam5 ablation represses excessive myoblast mitophagy and effectively suppresses mitochondria meltdown and muscle wastage. Next, we define BNIP3 as a mitophagy receptor constitutively associating with PGAM5. bnip3 deletion restricts body weight loss and enhances the gastrocnemius mass index in the age- and tumor size-matched experiments. The NH2-terminal region of PGAM5 binds to the PEST motif-containing region of BNIP3 to dampen the ubiquitination and degradation of BNIP3 to maintain continuous mitophagy. Finally, we identify S100A9 as a pro-cachectic chemokine via activating AGER/RAGE. AGER deficiency or S100A9 inhibition restrains skeletal muscle loss by weakening the interaction between PGAM5 and BNIP3. In conclusion, the AGER-PGAM5-BNIP3 axis is a novel but common pathway in cancer-associated muscle wasting that can be targetable. Abbreviation: AGER/RAGE: advanced glycation end-product specific receptor; BA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ckm-Cre: creatinine kinase, muscle-specific Cre; CM: conditioned medium; CON/CTRL: control; CRC: colorectal cancer; FUNDC1: FUN14 domain containing 1; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; S100A9: S100 calcium binding protein A9; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TIMM23: translocase of inner mitochondrial membrane 23; TSKO: tissue-specific knockout; VDAC1: voltage dependent anion channel 1.

ß-hydroxybutyrate restrains colitis-associated tumorigenesis by inhibiting HIF-1α-mediated angiogenesis.

Decreased levels of ß-hydroxybutyrate (BHB), a lipid metabolic intermediate known to slow the progression of colorectal cancer (CRC), have been observed in the colon mucosa of patients with inflammatory bowel diseases (IBD). In particular, patients with recurrent IBD present an increased risk of developing colitis-associated colorectal cancer (CAC). The role and molecular mechanism of BHB in the inflammatory and carcinogenic process of CAC remains unclear. Here, the anti-tumor effect of BHB was investigated in the Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-induced CAC model and tumor organoids derivatives. The underlying mechanisms were studied using transcriptome and non-target metabolomic assay and further validated in colon tumor cell lineage CT26 in vitro. The tumor tissues and the nearby non-malignant tissues from colon cancer patients were collected to measure the expression levels of ketogenic enzymes. The exogenous BHB supplement lightened tumor burden and angiogenesis in the CAC model. Notably, transcriptome analysis revealed that BHB effectively decreased the expression of VEGFA in the CAC tumor mucosa. In vitro, BHB directly reduced VEGFA expression in hypoxic-treated CT26 cells by targeting transcriptional factor HIF-1α. Conversely, the deletion of HIF-1α largely reversed the inhibitory effect of BHB on CAC tumorigenesis. Additionally, decreased expression of ketogenesis-related enzymes in tumor tissues were associated with poor survival outcomes in patients with colon cancer. In summary, BHB carries out anti-angiogenic activity in CAC by regulating HIF-1α/VEGFA signaling. These findings emphasize the role of BHB in CAC and may provide novel perspectives for the prevention and treatment of colonic tumors.

Thoracolumbar fractures patients undergoing posterior pedicle screw fixation can benefit from drainage.

PURPOSE: To explore whether it is necessary to put drain tubes after posterior pedicle screw fixation of thoracolumbar fractures. METHODS: From April 2020 to January 2023, a total of 291 patients with recent thoracolumbar fractures (AO type-A or type-B) who received the pedicle screw fixation operation were enrolled retrospectively. In 77 patients, drain tubes were used in the pedicle screw fixation surgery, while no drain tubes were placed in the other group. After gleaning demographic information and results of lab examination and imageology examination, all data were put into a database. Independent-sample t-tests, Pearson Chi-Square tests, Linear regression analysis, and correlation analysis were then performed. RESULTS: Compared to the control group, the drainage group had significantly lower postoperative CRP levels (P = 0.047), less use of antipyretics (P = 0.035), higher ADL scores (P = 0.001), and lower NRS scores (P < 0.001) on the 6th day after surgery. Other investigation items, such as demographic information, operation time, intraoperative blood loss, body temperature, and other preoperative and postoperative lab results, showed no significant differences. CONCLUSIONS: The use of a drain tube in the pedicle screw fixation of thoracolumbar fractures is correlated with the improvement of patients' living and activity ability and the reduction of inflammation, postoperative fever and pain.

Comparison of young femoral neck fractures treated by femoral neck system, multiple cancellous screws and dynamic hip screws: a retrospectively comparison study.

BACKGROUND: Implant choice for the fixation of femoral neck fracture is one of the most important management controversies. This study aims to evaluate and compare the short-term outcomes associated with the use of the Femoral Neck System (FNS), Multiple Cancellous Screws (MCS), and Dynamic Hip Screws (DHS) in treating femoral neck fractures in a young patient population. METHODS: From June 2018 to June 2021, a total of 120 surgeries for a primary femoral neck fracture were retrospectively analyzed. This review encompassed demographic details of the patients and the mechanisms behind the injuries. Key surgical parameters such as operation duration, intraoperative blood loss, fluoroscopy duration, and hospital stay were meticulously documented. The employed surgical technique was described. All patients were followed up at 6 weeks, 3 months, 6 months, and 12 months postoperatively. Avascular necrosis of the femoral head (AVN), nonunion, malreduction, implant failure or other complications were noted. The functional status at the last follow-up was assessed using the Harris functional scoring criteria. RESULTS: There were 90 males and 30 females, with a mean age of 40.4 years. As to patient characteristics, there were no significant differences between the three groups. DHS group showed longer operation time(52.15 ± 4.80 min), more blood loss(59.05 ± 5.87 ml) and longer time of hospitalization(7.6 ± 0.90 d) than FNS group (39.65 ± 2.84 min, 45.33 ± 9.63 ml and 4.87 ± 0.48 d) and MCS group (39.45 ± 3.10 min, 48.15 ± 7.88 ml and 5.04 ± 0.49 d) (p < 0.05). In addition, the time of fluoroscopy in FNS group (15.45 ± 3.67) was less than that in MCS group (26.3 ± 4.76) and DHS group (27.1 ± 5.67) (p < 0.05). The cost of FNS group(44.51 ± 2.99 thousand RMB) was significantly higher than the MCS and DHS groups. The FNS, MCS and DHS groups showed a similar mean length of femoral neck shortening (LFNS) and Harris score. The FNS, MCS and DHS groups showed a similar mean rate of AVN and internal fixation failure. CONCLUSIONS: Following successful fracture reduction, FNS, MCS, and DHS are effective for in the young femoral neck fractures. No difference was found in complications between the three groups. However, the reduced fluoroscopy time associated with FNS contributes to shorter operation durations. The adoption of minimally invasive techniques correlates with decreased blood loss and shorter hospital stays. Nevertheless, these advantages may be offset by the potential economic burden they impose.

Efficacy and safety of stem cells in the treatment of ischemic stroke: A meta-analysis.

BACKGROUND: Stem cell therapy on ischemic stroke has long been studied using animal experiments. The efficacy and safety of this treatment in ischemic stroke patients remain uncertain. METHODS: We searched for all clinical randomized controlled trials published before October 2023, on PubMed, EMBASE, and the Cochrane Library using predetermined search terms, and performed a meta-analysis of the efficacy of stem cell therapy in ischemic stroke patients. RESULTS: 13 studies that included 592 ischemic stroke patients were reviewed. The mRS (MD -0.32, 95% CI -0.64 to 0.00, I2 = 63%, P = .05), NIHSS (MD -1.63, 95% CI -2.69 to -0.57, I2 = 58%, P = .003), and BI (MD 14.22, 95% CI 3.95-24.48, I2 = 43%, P = .007) showed effective stem cell therapy. The mortality (OR 0.42, 95% CI 0.23-0.79, I2 = 0%, P = .007) showed improved prognosis and reduce mortality with stem cell therapy. CONCLUSION: Stem cell therapy reduces mortality and improves the neurological prognosis of ischemic stroke patients. However, due to the different types of stem cells used and the limited data in the reported studies, the safety of clinical applications of stem cells in patients with ischemic stroke must be carefully evaluated. Future randomized controlled trials with large sample sizes from controlled cell sources are warranted to validate this finding.

PGAM5 knockout causes depressive-like behaviors in mice via ATP deficiency in the prefrontal cortex.

INTRODUCTION: Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated. AIMS: Our study aimed to investigate how deficiency of PGAM5-mediated depressive behavior. RESULTS: We firstly discovered that PGAM5 knockout (PGAM5-/- ) mice generated depressive-like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)-induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex (PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in PGAM5-/- mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F1 F0 synthase without influencing the interaction between ATP F1 F0 synthase and Bcl-xl. We then conducted ATP administration to PGAM5-/- mice and found that ATP could rescue the behavioral and neuronal phenotypes of PGAM5-/- mice. CONCLUSIONS: Our findings provide convincing evidence that PGAM5 ablation generates depressive-like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC.

Whole-transcriptome defines novel glucose metabolic subtypes in colorectal cancer.

Colorectal cancer (CRC) is the most prevalent malignancy of the digestive system. Glucose metabolism plays a crucial role in CRC development. However, the heterogeneity of glucose metabolic patterns in CRC is not well characterized. Here, we classified CRC into specific glucose metabolic subtypes and identified the key regulators. 2228 carbohydrate metabolism-related genes were screened out from the GeneCards database, 202 of them were identified as prognosis genes in the TCGA database. Based on the expression patterns of the 202 genes, three metabolic subtypes were obtained by the non-negative matrix factorization clustering method. The C1 subtype had the worst survival outcome and was characterized with higher immune cell infiltration and more activation in extracellular matrix pathways than the other two subtypes. The C2 subtype was the most prevalent in CRC and was characterized by low immune cell infiltration. The C3 subtype had the smallest number of individuals and had a better prognosis, with higher levels of NRF2 and TP53 pathway expression. Secreted frizzled-related protein 2 (SFRP2) and thrombospondin-2 (THBS2) were confirmed as biomarkers for the C1 subtype. Their expression levels were elevated in high glucose condition, while their knockdown inhibited migration and invasion of HCT 116 cells. The analysis of therapeutic potential found that the C1 subtype was more sensitive to immune and PI3K-Akt pathway inhibitors than the other subtypes. To sum up, this study revealed a novel glucose-related CRC subtype, characterized by SFRP2 and THBS2, with poor prognosis but possible therapeutic benefits from immune and targeted therapies.

Migration-inducing gene-7 promotes glioma cell proliferation and invasiveness via activating the MAPK signaling pathway.

Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.

Prognostic impact of lymphovascular and perineural invasion in squamous cell carcinoma of the tongue.

This study aimed to investigate the prognostic impact of lymphovascular and perineural invasions in patients with squamous cell carcinoma of the tongue who received surgery-based treatment at our institution between January 2013 and December 2020. Patients were divided into four groups based on the presence of perineural (P-/P +) and lymphovascular invasions (V-/V +): P-V-, P-V + , P + V-, and P + V + . Log-rank and Cox proportional hazard models were used to evaluate the association between perineural /lymphovascular invasion and overall survival (OS). Altogether, 127 patients were included, and 95 (74.8%), 8 (6.3%), 18 (14.2%), and 6 (4.7%) cases were classified as P-V-, P-V + , P + V-, and P + V + , respectively. Pathologic N stage (pN stage), tumor stage, histological grade, lymphovascular invasion, perineural invasion, and postoperative radiotherapy were significantly associated with OS (p < 0.05). OS was significantly different among the four groups (p < 0.05). Significant between-group differences in OS were detected for node-positive (p < 0.05) and stage III-IV (p < 0.05) cases. OS was the worst in the P + V + group. Lymphovascular and perineural invasions are independent negative prognostic factors for squamous cell carcinoma of the tongue. Patients with lymphovascular and/or perineural invasion may have significantly poorer overall survival than those without neurovascular involvement.

Dahuang Fuzi Baijiang decoction restricts progenitor to terminally exhausted T cell differentiation in colorectal cancer.

Obesity increases the risk of colorectal cancer (CRC) by 30%. The obese tumor microenvironment compromises antitumor immunity by eliciting exhausted T cells (Tex). Hypothesizing that Dahuang Fuzi Baijiang decoction (DFB) is a combined classical prescription from the "Synopsis of Prescriptions of the Golden Chamber". We first determined that DFB regresses tumor growth in high-fat diet-induced obese mice by expanding the TIM3- subset with intermediate expression of programmed cell death-1 (PD-1int TIM3- ) and restricting the PD-1hi TIM3+ subset. Transcription factor 1 (TCF1) is highly expressed in the PD-1int TIM3- subset but is absent in PD-1hi TIM3+ cells. We next confirmed that progenitor PD-1int TCF+ cells robustly produce tumor necrosis factor-α (TNFα) and interferon-γ, whereas terminally differentiated PD-1int TCF+ cells have defects in generating TNFα. With transgenic ob/ob mice, we found that DFB produces cooperative efficacy with anti-PD-1 (αPD-1) by limiting the PD-1hi Tim3+ subset and amplifying the PD-1int TCF+ population. Finally, we defined the recombinant chemokine C-C-motif receptor 2 (CCR2)+ CD8+ subset as terminal Tex and identified that the differentiation from progenitor to terminal Tex is driven, at least in part, by the chemokine (C-C motif) ligand 2 (CCL2)/CCR2 axis. The CCR2 inhibitor enhances the response to αPD-1 by promoting the counts of progenitor Tex. Altogether, DFB dampens CCL2 and preserves progenitor Tex in the obese microenvironment to restrain CRC progression. These findings provide unambiguous evidence that the traditional Chinese formula DFB can prevent tumor progression by modulating adaptive immunity and establish a strong rationale for further clinical verification.

Clinical Analysis of the Treatment of Primary Trigeminal Neuralgia by Percutaneous Balloon Compression.

PURPOSE: To summarize the technical points and clinical effects of percutaneous balloon compression (PBC) in the treatment of primary trigeminal neuralgia. METHODS: The clinical data of 13 patients with trigeminal neuralgia who received PBC from April 2020 to July 2021 were retrospectively analyzed. VAS, VRS-4 and PPI were used to evaluate the postoperative pain relief. Different postoperative complications were analyzed. RESULTS: All patients had a smooth operation, the inflation volume of the balloon was 0.7 ml, the average compression time was 120 s, and there was no balloon rupture during the operation. On the day after operation, 12 patients (92.3%) had complete pain relief, and 1 patient (7.7%) was not satisfied with pain relief, but the pain disappeared 2 weeks after the operation. After operation, there were 12 patients with facial numbness in the affected side (92.3%), 3 patients with masseter muscle weakness (23.0%), 1 patient with herpes around the mouth (7.6%), and 1 patient with diplopia (7.6%). CONCLUSION: PBC is an effective minimally invasive surgical method for the treatment of primary trigeminal neuralgia. It is suitable for the elderly and infirm people, those who cannot tolerate general anesthesia or are afraid of surgery, and patients who had undergone surgery but relapsed after surgery. However, it is necessary to pay attention to the serious facial numbness and postoperative masticatory weakness. These discomforts are generally relieved after half a year.

Comparison of vacuum sealing drainage and conventional drainage for postoperative drainage in closed calcaneal fracture: A randomized controlled trial.

BACKGROUND: The objective of this study was to compare the outcomes of vacuum sealing drainage (VSD) and conventional drainage after surgery in the treatment of closed calcaneal fracture. We hypothesize that VSD is superior to conventional drainage in reducing volume of drainage, time of wound drying, time of skin fold, time of wound healing, VAS at day 3 postoperatively, wound complications and increasing wound healing grade. METHODS: 120 patients with closed calcaneal fractures from January 2016 to December 2018 were enrolled in our study. They were divided randomly into VSD group (n = 60) and conventional (n = 60). The volume of drainage, duration of drainage, time of wound drying, time of skin fold, time of wound healing and VAS at day 3 postoperatively were recorded. Furthermore, the wound complications of the two groups were also evaluated. Besides, wound healing grade was used to assess the degree of wound healing. The functional outcome American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores and visual analog scale (VAS) pain scores was also evaluated. RESULTS: A total of 10 patients were lost to follow-up for various reasons, VSD group remained 55 cases while conventional group remained 53 cases. Our results showed that VSD group exhibited significantly more volume of drainage (P< 0.0001), longer duration of drainage (P< 0.0001), shorter time of wound drying (P = 0.0086), shorter time of skin fold (P = 0.0158), shorter time of wound healing (P = 0.0240) and lower VAS at day 3 postoperatively (P = 0.0019) compared with conventional group. Moreover, VSD group was demonstrated to have significantly lower wound complications (P = 0.025) and higher rate grade A of wound healing (P = 0.031). However, no significant difference was noted in time of fracture union (P = 0.754), VAS (P = 0.407) and AOFAS score (P = 0.512) at final follow-up between the two groups. CONCLUSIONS: Our hypothesis was confirmed that VSD was superior in terms of some aspects than conventional drainage. Therefore, VSD is a safe and effective postoperative wound drainage method in the treatment of closed calcaneal fracture. However, more and higher evidence needs to be carried to demonstrate the results.

Prognostic value of nicotinamide adenine dinucleotide (NAD+) metabolic genes in patients with stomach adenocarcinoma based on bioinformatics analysis.

Background: Because stomach adenocarcinoma (STAD) has a poor prognosis, it is necessary to explore new prognostic genes to stratify patients to guide existing individualized treatments. Methods: Survival and clinical information, RNA-seq data and mutation data of STAD were acquired from The Cancer Genome Atlas (TCGA) database. Fifty-one nicotinamide adenine dinucleotide (NAD+) metabolism-related genes (NMRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Differentially expressed NMRGs (DE-NMRGs) between STAD and normal samples were screened, and consistent clustering analysis of STAD patients was performed based on the DE-NMRGs. Survival analysis, Gene Set Enrichment Analysis (GSEA), mutation frequency analysis, immune microenvironment analysis and drug prediction were performed among different clusters. Additionally, the differentially expressed genes (DEGs) among different clusters were selected, and the intersections of DEGs and DE-NMRGs were selected as the prognostic genes. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed on a human gastric mucosa epithelial cell line and cancer cell line to verify the expression of the prognostic genes. Results: A total of 27 DE-NMRGs and two clusters were selected. There was a difference in survival between clusters 1 and 2. Furthermore, 18 DE-NMRGs were significantly different between clusters 1 and 2. The different Gene Ontology (GO) biological processes and KEGG pathways between clusters 1 and 2 were mainly enriched in cyclic nucleotide mediated signaling, synaptic signaling and hedgehog signaling pathway, etc. The somatic mutation frequencies were different between the two clusters, and TTN was the highest mutated gene in the patients of the clusters 1 and 2. Additionally, eight immune cells, immune score, stromal score, and estimate score were different between clusters 1 and 2. The patients in cluster 2 were sensitive to CTLA4 inhibitor treatment. Furthermore, the top five drugs (AP.24534, BX.795, Midostaurin, WO2009093927 and CCT007093) were significantly higher in cluster 1 than in cluster 2. Finally, three genes (AOX1, NNMT and PTGIS) were acquired as prognostic, and their expressions were consistent with the results of bioinformatics analysis. Conclusions: Three prognostic genes related to NAD+ metabolism in STAD were screened out, which provides a theoretical basis and reference value for future treatment and prognosis of STAD.

Tiaochang Xiaoliu Decoction Granules prevent the recurrence of colorectal adenoma: a study protocol for a randomized controlled trial.

BACKGROUND: With the changes in lifestyle and diet, the incidence and mortality of colorectal cancer (CRC) is increasing in China. CRC mainly develops from colorectal adenomas (CRAs). There is a lack of chemopreventative drugs with definite efficacy for CRAs. Tiaochang Xiaoliu Decoction (TXD) was developed by Professor Yunjian Luo and has been used clinically over the last ten years for the prevention of CRA recurrence. To facilitate its clinical use, TXD was further standardized and produced as "Tiaochang Xiaoliu Decoction Granules (TXDG)". A study was designed to investigate the preventive effects of TXDG on the recurrence of CRA. METHODS: A randomized, double-blinded, controlled, and multi-center experiment is proposed to assess the effectiveness and safety of TXDG. Patients with CRAs (after complete polypectomy under colonoscopy) will be randomly divided into two groups, one will be treated with TXDG (the TXDG group) and the other will be treated with a TXDG mimetic agent (the TXDG mimetic group). The patients will be treated for 6 months and followed up for 3 years. Follow-up colonoscopy is expected to be carried out within 1 to 3 years after the baseline examinations. The primary outcome measure is adenoma detection rate within 1 to 3 years. The secondary outcome measures are the number, location, and pathology of the adenomas, and the polyp detection rate. DISCUSSION: Reliable objective evidence will be provided to evaluate the efficacy and safety of TXDG as an accessorial therapy for CRA occurrence in post-polypectomy patients. TRIAL REGISTRATION: ChiCTR2000035257.

Molecular Surgery at Microporous MOF for Mesopore Generation and Renovation.

Hierarchically porous MOFs (HP-MOFs) present advantageous synergism of micro- and mesopore but challenging in synthetic control at molecular scale. Herein, we present the first example of reversible and controllable mesopore generation and renovation in a microporous MOF of HKUST-1 via synthetic manipulation at molecular scale. An ammonia-gas etching strategy is proposed to create mesopores in carboxylate-based microporous MOFs and thus produce HP-MOFs. Gas-phase etching ensures uniform mesopore formation inside the MOF crystals via plane-oriented cutting the carboxylate-metal bonds off without affecting the crystal size and morphology. The mesopore size is controlled by the etching temperature, while the mesopore volume could be tuned by adjusting etchant pressure. The generated mesopores could be renovated using MOF precursors solutions so that to achieve controllable mesopore generation/closure, and encapsulation of the adsorbed molecules. This work demonstrates a powerful protocol for precisely tailoring and tuning the properties of MOF materials at molecular scale.

Superhydrophobic Fe3O4/OA Magnetorheological Fluid for Removing Oil Slick from Water Surfaces Effectively and Quickly.

Considering the severe impacts on the economic losses caused by oil spills, it is of great significance to develop an oil-absorbent material for removing the oil slick from the water surface effectively. As a new oil-absorbent material, magnetorheological fluid (MRF) has unsinkability, hydrophobicity, and lipophilicity, which could effectively remove the oil slick on the water surface while repelling water. Particularly, the prepared MRF shows a good response to external magnetic field. MRFs show high oil removal capacity in fresh water, deionized water, and salt water with efficiencies up to 94.39, 93.65, and 92.71%, respectively. Besides, Fe3O4/OA magnetic nanoparticles (MPs) could be reprepared into MRF by simple treatments. After the fifth cycle, the MRF prepared by the recovered Fe3O4/OA MPs still has high oil removal efficiency, and that means the Fe3O4/OA MPs has excellent reusability and stability. The method for preparing MRFs provided in this work is simple and effective, and the MRFs have a promising potential for cleaning oil slick.

The efficacy and safety of tranexamic acid in the treatment of intertrochanteric fracture: an updated meta-analysis of 11 randomized controlled trials.

This meta-analysis was performed to investigate the efficacy and safety of tranexamic acid (TXA) in the elderly patients undergoing intertrochanteric fracture surgery from the current literatures. The electronic literature database of PubMed, Embase and Cochrane library were searched in October 2019. The intraoperative blood loss, hidden blood loss, postoperative drainage and total blood loss, postoperative hemoglobin, length of stay, transfusion rate, mortality rate, thromboembolic events and wound complications were extracted. Stata 14.0 software was used for our meta-analysis. A total of 11 RCTs (3 new RCTs in 2019) with 1202 patients met our inclusion criteria. This meta-analysis showed that administration of TXA can reduce intraoperative blood loss (P = 0.009), hidden blood loss (P = 0.000), total blood loss (P = 0.000), length of stay (P = 0.003), transfusion rate (P = 0.000) and the occurrence of wound complications (P = 0.006). Furthermore, administration of TXA was associated with an increase in the postoperative Hb level at day 1, 2 and 3 (P = 0.000, P = 0.000 and P = 0.000, respectively) after surgery. However, no significant difference was found between the TXA group and control group regarding the occurrence of thromboembolic events (P = 0.978, including deep vein thrombosis, P = 0.850; pulmonary embolism, P = 0.788; cerebrovascular accident, P = 0.549; myocardial infarction, P = 0.395) and mortality rate (P = 0. 338). Our meta-analysis suggested that administration of TXA is effective in reducing intraoperative blood loss, hidden blood loss, total blood loss, length of stay, transfusion rate, wound complications and enhancing postoperative Hb without increasing the risk of thromboembolic events and mortality rate in intertrochanteric fracture surgery. More large multi-center and high-quality RCTs are required for further research.

Artificial Total Disc Replacement Versus Fusion for Lumbar Degenerative Disc Disease: An Update Systematic Review and Meta-Analysis.

AIM: To conduct an updated systematic review and meta-analysis to compare the efficacy and safety between total disc replacement (TDR) and fusion surgery for lumbar degenerative disc disease (LDDD). MATERIAL AND METHODS: We comprehensively searched meta-analyses comparing TDR with fusion through the PubMed, Embase, and Cochrane Library databases. Only randomized controlled trials (RCTs) were selected and collected. The end of the retrieval time was June 2017. Two authors independently extracted the data from the studies after assessing their quality. The statistical software STATA version 12.0 was used to analyze the data. RESULTS: A total of seven RCTs (1706 patients) were included in our analysis. The patients in the TDR group had significantly improved. A greater percentage of these patients were satisfied with the surgery concerning Oswestry disability index, visual analog scale score, and complication rate. In addition, the clinical success in the TDR group was greater than that in the fusion group. Meanwhile, the TDR group had shorter operative time and hospital stay. However, there was no clinical significance regarding blood loss, work status, and reoperation rate between the two groups. CONCLUSION: Our current updated meta-analysis suggests that TDR could be an alternative treatment for LDDD, since it yielded better clinical success and patient satisfaction, shorter hospital stay and operative time, less pain, and lower complication rates than lumbar fusion.