Colorectal cancer (CRC) remains a formidable threat to human health, with considerable challenges persisting in its diagnosis, particularly during the early stages of the malignancy. In this study, we elucidated that fecal extracellular vesicle microRNA signatures (FEVOR) could serve as potent noninvasive CRC biomarkers. FEVOR was first revealed by miRNA sequencing, followed by the construction of a CRISPR/Cas13a-based detection platform to interrogate FEVOR expression across a diverse spectrum of clinical cohorts. Machine learning-driven models were subsequently developed within the realms of CRC diagnostics, prognostics, and early warning systems. In a cohort of 38 CRC patients, our diagnostic model achieved an outstanding accuracy of 97.4% (37/38), successfully identifying 37 of 38 CRC cases. This performance significantly outpaced the diagnostic efficacy of two clinically established biomarkers, CEA and CA19-9, which showed accuracies of mere 26.3% (10/38) and 7.9% (3/38), respectively. We also examined the expression levels of FEVOR in several CRC patients both before and after surgery, as well as in patients with colorectal adenomas (CA). Impressively, the results showed that FEVOR could serve as a robust prognostic indicator for CRC and a potential predictor for CA. This endeavor aimed to harness the predictive power of FEVOR for enhancing the precision and efficacy of CRC management paradigms. We envision that these findings will propel both foundational and preclinical research on CRC, as well as clinical studies.

Liver metastasis is a leading cause of mortality from malignant tumors and significantly impairs the efficacy of therapeutic interventions. In recent years, both preclinical and clinical research have made significant progress in understanding the molecular mechanisms and therapeutic strategies of liver metastasis. Metastatic tumor cells from different primary sites undergo highly similar biological processes, ultimately achieving ectopic colonization and growth in the liver. In this review, we begin by introducing the inherent metastatic-friendly features of the liver. We then explore the panorama of liver metastasis and conclude the three continuous, yet distinct phases based on the liver's response to metastasis. This includes metastatic sensing stage, metastatic stress stage, and metastasis support stage. We discuss the intricate interactions between metastatic tumor cells and various resident and recruited cells. In addition, we emphasize the critical role of spatial remodeling of immune cells in liver metastasis. Finally, we review the recent advancements and the challenges faced in the clinical management of liver metastasis. Future precise antimetastatic treatments should fully consider individual heterogeneity and implement different targeted interventions based on stages of liver metastasis.

Lymph nodes (LNs) are critical peripheral immune organs extensively innervated by both sympathetic and sensory nerves. During tumor metastasis, LNs undergo significant structural remodeling and enlargement; however, the role of neural innervation in this process remains unclear. Here, using whole-organ three-dimensional (3D) imaging, we observed pronounced elongation and increased branching specifically in sympathetic nerve fibers, but not sensory nerves, during tumor-induced LN enlargement (TLNE), suggesting adaptive neural remodeling. Single-nucleus RNA sequencing further revealed activation of fibroblastic reticular cells (FRCs) during TLNE, characterized by enriched neuro-related signaling pathways and substantial secretion of hepatocyte growth factor (HGF). Functional validation using targeted HGF inhibitors and adeno-associated virus (AAV)-mediated HGF silencing confirmed that FRC-derived HGF critically drives sympathetic nerve growth. Additionally, both HGF inhibition and sympathetic nerve denervation significantly reduced TLNE and tumor-induced LN metastasis, highlighting the importance of adaptive sympathetic innervation in tumor-associated LN remodeling. These findings identify a previously unrecognized FRC-HGF-sympathetic nerve axis and propose neural regulation as a potential therapeutic strategy for tumor-induced LN metastasis.

Lymph node (LN) metastasis of gastric cancer (GC) is one of the important pathways of GC metastasis, indicating the clinical staging and prognosis of patients. To investigate the underlying mechanism during the process of GC-induced LN metastasis, 7 pairs of GC tissues, paracancerous (PC) tissues, GC-positive LN (LN.P) and GC-negative LN (LN.N) tissues from GC patients with homogeneity were selected for RNA sequencing (RNA-seq) analysis. Tensin 4 (TNS4) was screened out and found to be significantly upregulated in LN.P tissues and closely related with the characteristics of GC. In vitro and in vivo experiments demonstrated that knockdown of TNS4 could significantly inhibit LN metastasis of GC cells and activation of fibroblastic reticular cells (FRCs) in LNs, thus inhibiting LN expansion induced by tumor cell invasion. Moreover, TNS4 was found to be interacted with integrin beta 1 (ITGB1) on FRCs, thereby affecting the binding of transforming growth factor β1 (TGF-β1) to ITGB1 and subsequently regulating downstream signaling molecules, and supporting the GC cell-induced LN metastasis.

Statins, commonly used to lower cholesterol, are associated with improved prognosis in colorectal cancer (CRC), though their effectiveness varies. This study investigates the anti-cancer effects of atorvastatin in CRC using patient-derived organoids (PDOs) and PDO-derived xenograft (PDOX) models. Our findings reveal that atorvastatin induces mitochondrial dysfunction, leading to apoptosis in cancer cells. In response, cancer cells induce mitophagy to clear damaged mitochondria, enhancing survival and reducing statin efficacy. Analysis of a clinical cohort confirms mitophagy's role in diminishing statin effectiveness. Importantly, inhibiting mitophagy significantly enhances the anti-cancer effects of atorvastatin in CRC PDOs, xenograft models, and azoxymethane (AOM)-dextran sulfate sodium (DSS) mouse models. These findings identify mitophagy as a critical pro-survival mechanism in CRC during statin treatment, providing insights into the variable responses observed in epidemiological studies. Targeting this vulnerability through combination therapy can elicit potent therapeutic responses.

The microbiome-gut-brain-axis plays a critical role in mental health. However, research linking the microbiome to brain function is limited, particularly during development, when tremendous plasticity occurs and many mental health issues, like depression and anxiety, initially manifest. Further complicating attempts to understand interactions between the brain and microbiome is the complex and multidimensional nature of both systems. In the current observational study (N = 55), we use sparse partial least squares to identify linear combinations of brain networks (brain signatures) derived from resting state fMRI scans at age 6 years that maximally covary with internalizing symptoms at age 7.5 years, before identifying microbe abundances (microbial profiles) derived from 16S rRNA sequencing of stool samples at age 2 years that maximally covary with those brain signatures. Finally, we test whether any early microbial profiles are indirectly associated with later internalizing symptoms via the brain signatures, highlighting potential microbial programming effects. We find that microbes in the Clostridiales order and Lachnospiraceae family are associated with internalizing symptoms in middle childhood through connectivity alterations within emotion-related brain networks.

Cancer development is intricately linked with metabolic dysregulation, including lactic acid metabolism, which plays a pivotal role in tumor progression and immune evasion. However, its specific implications in gastric adenocarcinoma (STAD) remain unclear. This study introduces a novel methodology to evaluate lactic acid metabolism comprehensively in STAD, aiming to elucidate its prognostic significance and impact on immunotherapy efficacy. Targeted therapies directed at key lactic acid metabolism genes (LMGs) identified within the tumor microenvironment (TME) hold promise for personalized treatment strategies. Lactic acid metabolism patterns were assessed in 415 STAD patients using a panel of 21 LMGs. Cox regression and Lasso regression analyses were employed to develop a predictive risk model based on differentially expressed genes (DEGs). Validation of the model was conducted using independent cohorts from the GEO and TCGA databases, as well as additional datasets focused on immunotherapy responses. Further investigations into TME dynamics of lactic acid metabolism included functional assays targeting SLC16A3, a pivotal gene identified through our analyses. Patients were stratified into distinct risk groups based on their lactic acid metabolism profiles. Low-risk patients exhibited attenuated lactic acid metabolism, correlating with favorable clinical outcomes characterized by prolonged survival and enhanced responsiveness to immunotherapy. Notably, tumor cells within the TME demonstrated heightened levels of active lactic acid metabolism, particularly impacting tumor-infiltrating lymphocytes such as CD8 + T cells and regulatory T cells. Mechanistically, SLC16A3 emerged as a critical regulator promoting STAD cell proliferation, invasion, and migration while modulating the metabolic landscape. This study underscores the prognostic value of a lactic acid metabolism-based model in STAD, providing insights into its potential as a predictive biomarker for patient stratification and therapeutic targeting. The findings highlight SLC16A3 as a promising candidate for therapeutic intervention aimed at modulating lactic acid metabolism in the TME, thereby advancing personalized treatment strategies in gastric cancer management.

Background:Gastric cancer (GC) is a gastric malignant tumor with over 1 million new cases globally each year. There are many diagnostic methods for GC, but due to the hidden early symptoms of GC, early GC is easy to be missed and misdiagnosed, which affects the follow-up treatment of patients. The early and accurate diagnosis of GC is of great significance for the treatment and survival of GC patients. Our laboratory study found that gamma-glutamyl transferase (GGT) was highly expressed in GC patients, but the mechanism of GGT family genes in the occurrence and development of GC remained to be further studied. Therefore, this study aimed to explore the mechanism of GGT family functional gene GGT5 regulating the proliferation and migration of GC cells, and provide a possible new biomarker for the early diagnosis of GC. Methods:The value of serum GGT in GC patients was first statistically analyzed. Then, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the mRNA expression of GGT5 in GC, and its clinical relationship and function. Furthermore, expression of GGT5 was reduced by lentivirus RNA interference and verified by polymerase chain reaction (PCR), Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation after GGT5 knockdown. Scratch and Transwell assays were applied to observe cell migration after knockdown of GGT5. Finally, Western blot assays were observed to demonstrate PI3K/AKT-MAPK and MMPs expression levels after knockdown of GGT5. Results:Serum GGT was expressed at a high level in GC patients. GGT5 was highly expressed in GC tissues, and was associated with poor prognosis and clinical stage of GC. GGT5 might be involved in the regulation of vascular development and angiogenesis, as well as in the mechanisms of cell motility and migration, and it was positively correlated with the PI3K/AKT pathway. The proliferation and migration capacity of GC cells was dampened by downregulation of GGT5. GGT5 mediated proliferation and migration of GC cells by directly targeting PI3K/AKT-MAPK-MMPs pathways. Conclusions:Low expression of GGT5 reduced proliferation and migration in GC cells by modulating the PI3K/AKT-MAPK-MMPs pathway, and GGT5 might be a new target for GC.

The prognosis for osteosarcoma patients, a devastating malignancy affecting young individuals, remains grim despite multimodal therapeutic advances. Recently, the advent of cuproptosis, a novel programmed cell death, offers hope in fighting osteosarcoma. In this study, we introduce SAHAm@{[Cu(HA-Cys)2]Cl2}n, an injectable hyaluronate-L-cysteine hydrogel that integrates both copper ions (Cu2+) and vorinostat (SAHA) for the possible therapeutic effect. The Cu2+ targets the TCA cycle, inducing cuproptosis in osteosarcoma cells. While SAHA acts as both a histone deacetylase inhibitor and an ROS generator for eliminating tumor cells. The mechanism involves amplifying FDX-1 expression via SAHA modulation of the TCA cycle, which was an original discovery. Critically, the combined mechanisms and localized injection enables the hydrogel partially eradicating osteosarcoma without metastasis in rats. Therefore, this study advances cuproptosis induced photothermal therapy for promising clinical translations, shedding light on favorable prognosis for osteosarcoma.

Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging. PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age. Phenotypic age acceleration (PhenoAgeAccel), an aging biomarker, represents PhenoAge after adjusting for CA. This study conducts an in-depth association analysis of PhenoAgeAccel with clinical, nutritional, lipidomic, gut microbiome, and genetic factors. Higher adiposity, glycaemia, plasma saturated fatty acids, kynurenine pathway metabolites, GlycA, riboflavin, nicotinamide, and insulin-like growth factor binding proteins were positively associated with PhenoAgeAccel. Conversely, a healthier diet and higher levels of pyridoxal phosphate, all-trans retinol, betaine, tryptophan, glutamine, histidine, apolipoprotein B, and insulin-like growth factors were inversely associated with PhenoAgeAccel. Lipidomic analysis found 132 lipid species linked to PhenoAgeAccel, with PC(O-36:0) showing the strongest positive association and CE(24:5) demonstrating the strongest inverse association. A genome-wide association study identified rs9864994 as the top genetic variant (P = 5.69E-07) from the ZDHHC19 gene. Gut microbiome analysis revealed that Erysipelotrichaceae UCG-003 and Bacteroides vulgatus were inversely associated with PhenoAgeAccel. Integrative network analysis of aging-related factors underscored the intricate links among clinical, nutritional and lipidomic variables, such as positive associations between kynurenine pathway metabolites, amino acids, adiposity, and insulin resistance. Furthermore, potential mediation effects of blood biomarkers related to inflammation, immune response, and nutritional and energy metabolism were observed in the associations of diet, adiposity, genetic variants, and gut microbial species with PhenoAgeAccel. Our findings provide a comprehensive analysis of aging-related factors across multiple platforms, delineating their complex interconnections. This study is the first to report novel signatures in lipidomics, gut microbiome and blood biomarkers specifically associated with PhenoAgeAccel. These insights are invaluable in understanding the molecular and metabolic mechanisms underlying biological aging and shed light on potential interventions to mitigate accelerated biological aging by targeting modifiable factors.

Introduction Liver transplantation is a risk factor for premalignant and malignant changes of the duodenum. De novo duodenal malignancy is seldom reported after liver transplantation. Case Report The present study reports a case of an asymptomatic 67-year-old male patient who underwent liver transplantation more than 10 years ago and subsequently developed duodenal malignancy. Endoscopic biopsy of the de novo duodenal malignancy indicated duodenal carcinoma and pancreatoduodenectomy (PD) was performed. The patient was successfully discharged 12 days after the surgery. A metastatic lesion occurred at the right seventh rib 14 months after the pancreatoduodenectomy. Postoperative pathological examination indicated hepatocellular carcinoma metastasis. Conclusions To the best of our knowledge, this case type has not been previously reported. The present study sheds light on the development, the treatment, the prognosis, and the management of a new type of de novo duodenal malignancy.

BackgroundCerebral amyloid angiopathy (CAA) is the most common cause of lobar intracerebral hemorrhage (ICH) in the elderly, and its multifocal and recurrent nature leads to high rates of disability and mortality. Therefore, this study aimed to summarize the evidence regarding the recurrence rate and risk factors for CAA-related ICH (CAA-ICH).MethodsWe performed a systematic literature search of all English studies published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, and CINAHL from inception to June 10, 2023. Studies reporting CAA-ICH recurrence rates and risk factors for CAA-ICH recurrence were included. We calculated pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) using a random/fixed-effects model based on the I2 assessment of heterogeneity between studies. Publication bias was assessed using Egger's test.ResultsThirty studies were included in the final analysis. Meta-analysis showed that the recurrence rate of CAA-ICH was 23% (95% CI: 18–28%, I2 = 96.7%). The risk factors significantly associated with CAA-ICH recurrence were: previous ICH (OR = 2.03; 95% CI: 1.50–2.75; I2 = 36.8%; N = 8), baseline ICH volume (OR = 1.01; 95% CI: 1–1.02; I2 = 0%; N = 4), subarachnoid hemorrhage (cSAH) (OR = 3.05; 95% CI: 1.86–4.99; I2 = 0%; N = 3), the presence of cortical superficial siderosis (cSS) (OR = 2.04; 95% CI: 1.46–2.83; I2 = 0%; N = 5), disseminated cSS (OR = 3.21; 95% CI: 2.25–4.58; I2 = 16.0%; N = 6), and centrum semiovale-perivascular spaces (CSO-PVS) severity (OR = 1.67; 95% CI: 1.14–2.45; I2 = 0%; N = 4).ConclusionCAA-ICH has a high recurrence rate. cSAH, cSS (especially if disseminated), and CSO-PVS were significant markers for recurrent CAA-ICH. The onset of ICH in patients with CAA is usually repeated several times, and recurrence is partly related to the index ICH volume. Identifying clinical and neuroimaging predictors of CAA-ICH recurrence is of great significance for evaluating outcomes and improving the prognosis of patients with CAA-ICH.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=400240, identifier [CRD42023400240].

目的 回顾我科收治的严重意面腕损伤急诊修复手术的开展情况及临床疗效,总结此类损伤的临床特征和诊治要点.方法 本研究回顾2020年1月1日至2021年12月31日于我院急诊骨科治疗的意面腕损伤患者27例,按受伤场所将患者分为工伤组13例和生活组14例,其中男性24例,女性3例,年龄15至70岁,平均年龄(45±14)岁,其中左侧14例,右侧13例.损伤结构均予一期修复,术后随访观察患肢功能及并发症,并比较两组患者损伤结构数量、损伤机制、Noaman功能评价和DASH评分.结果 工伤组掌侧肌腱损伤(9.1±2.9)条,背侧肌腱损伤(2.2±0.5)条,17例动脉断裂,23例神经断裂,9例骨折,平均随访(17.8±5.8)月,1例出现局部感染,Noaman评价各分项优良率达61.5％以上,DASH评分(17.2±4.7)分.生活组掌侧肌腱损伤(9.1±2.3)条,背侧肌腱损伤(1.9±0.6)条,20例动脉断裂,25例神经,未及骨折,平均随访(16.0±4.9)月,未及严重并发症,Noaman评价各分项优良率达57.1％以上,DASH评分(13.9±6.9)分.两组仅在损伤方位(c2=23.280,P<0.05)、损伤机制(c2=27.000,P<0.05)和固定方式(c2=6.608,P<0.05)上差异存在统计学意义,在肌腱、血管、神经损伤数量、Noaman评价各分项及DASH评分等方面差异均无统计学意义,但生活组仍呈现出桡侧较尺侧更易损伤的趋势.结论 伴有主要神经和血管断裂的意面腕损伤可存在多处屈、伸肌腱断裂,损伤方位与损伤发生的场所有关,修复策略也应据此进行灵活调整.尽管经过及时修复与系统康复后的患肢功能明显改善,严重意面腕损伤的诊治仍是骨科医生面临的严峻挑战.高效的团队配合、娴熟的修复技巧和系统的康复训练能够保存功能、改善预后.

Facial prostheses have developed significantly in the last 10 years, especially between 2016 and 2021. This development is mainly due to the great progress made in the fields of biocompatible materials, digital technology, and three-dimensional printing technology, which provides guarantee for low allergy, high biosimulation, comfort, and satisfactory usability. Treatment teams typically consist of plastic surgeons, material experts, engineers, and computer scientists who have extensive clinical experience. These teams successfully implement an integrated, multidisciplinary model by prioritizing the reasonable expectations of both the physician and patient, leading to improved patient satisfaction and compliance with prosthetic constraints. This study aimed to review the concept, development status, existing problems, and future of facial prosthesis.

Objective:To explore the clinical outcomes of combination of Ilizarov technique and composite surgeries for treatment of congenital fibula hemimelia, and to summarize the key points of limb reconstruction management for such deformity.Method:Twenty patients with congenital fibula hemimelia were treated surgically and retrospectively studied in Department of Orthopedics, Shanghai Jiao Tong University affiliated Sixth People's Hospital since 2014. Patients included 12 males and 8 females, with an age of (17.5 ± 7.0) y (4 to 26 y). According to Achterman classification, there were 14 cases of type IA and 6 cases of type IB. Single Ilizarov technique or combined intramedullary assistance was applied for limb length deficiency; For genu valgus or valgus ankle deformities, close-wedge osteotomy and internal fixation were applied for adult patients, and hemiepiphysiodesis for pediatric patients; Contracted iliotibial band, fibular tendons and Achilles' tendon were released and elongated; Overlapping toes were corrected by tendon transfer.Results:Twenty patients were followed up for (36.1±8.7) months. The limb was lengthened for (7.2±1.0) cm, with average EFI (15.9±6.3) d/cm and average HI (21.7±2.8) d/cm. All obvious limb length discrepancy, genu valgus [GVA: (14.9±3.4)° and (2.1±1.7)° preoperatively and at last follow-up, t=13.510, P<0.05], tibial angulation [TBA: (3.3±3.3)° and (0.8±0.7)° preoperatively and at last follow-up, t=3.490, P<0.05] and ankle and foot deformities [VAA: (9.2±3.4)° and (1.2±1.3)° preoperatively and at last follow-up, t=9.785, P<0.05] were corrected at the final follow-up. Clinical outcomes indicated significantly improved limb function compared with preoperative grading. [LLRS AIM: (10.1±1.2) points and (2.0±1.4) points preoperatively and at last follow-up, t=21.140, P<0.05].Conclusion:Congeinital fibular hemimelia is a rare and complicated syndrome with co-exist limb length deficiency, abnormal alignment of lower-limb and foot and ankle deformities. Combination of Ilizarov technique and composite surgeries can bring satisfying outcomes for treatment of congenital fibula hemimelia and improve the quality of life of the patients.

Gastric cancer (GC) is a malignant tumour with high mortality, and liver metastasis is one of the main causes of poor prognosis. SLIT- and NTRK-like family member 4 (SLITRK4) plays an important role in the nervous system, such as synapse formation. Our study aimed to explore the functional role of SLITRK4 in GC and liver metastasis. The mRNA level of SLITRK4 was evaluated using publicly available transcriptome GEO datasets and Renji cohort. The protein level of SLITRK4 in the tissue microarray of GC was observed using immunohistochemistry. Cell Counting Kit-8, colony formation, transwell migration assays in vitro and mouse model of liver metastasis in vivo was performed to investigate the functional roles of SLITRK4 in GC. Bioinformatics predictions and Co-IP experiments were applied to screen and identify SLITRK4-binding proteins. Western blot was performed to detect Tyrosine Kinase receptor B (TrkB)-related signaling molecules. By comparing primary and liver metastases from GC, SLITRK4 was found to be upregulated in tissues of GC with liver metastasis and to be closely related to poor clinical prognosis. SLITRK4 knockdown significantly abrogated the growth, invasion, and metastasis of GC in vitro and in vivo. Further study revealed that SLITRK4 could interact with Canopy FGF Signalling Regulator 3 (CNPY3), thus enhancing TrkB- related signaling by promoting the endocytosis and recycling of the TrkB receptor. In conclusion, the CNPY3-SLITRK4 axis contributes to liver metastasis of GC according to the TrkB-related signaling pathway. which may be a therapeutic target for the treatment of GC with liver metastasis.

骨组织再生修复一直是骨科学领域的热点话题.先天、创伤或肿瘤造成的骨缺损、骨不连的有效治疗手段仍待优化.纳米材料的发展为骨组织修复重建带来了新的机遇和挑战.脂质体、水凝胶、金属等纳米材料不仅可以单独促进骨组织愈合,而且可以构建成为复合支架,对骨缺损部位进行精准、个体化治疗.金属纳米材料还可与其他材料如水凝胶、生物陶瓷、生物合金、石墨烯等复合构建成为运载体,为机体靶向精准控释药物、生长因子、基因片段等.同时,金属纳米材料作为纳米材料家族中的重要成员,具备优良的物理、化学和生物特性,在促进骨再生修复中具备巨大潜力.该文就金属纳米材料在骨组织再生修复中的应用进行综述.

Objective Previous studies have indicated that neurotransmitters play important roles in the occurrence and development of gastric cancer. MAOA is an important catecholamine neurotransmitter-degrading enzyme involved in the degradation of norepinephrine, epinephrine and serotonin. To find a potential therapeutic target for the treatment of gastric cancer, the biological functions of MAOA and the underlying mechanism in gastric cancer need to be explored. Methods The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets, Kaplan‒Meier (KM) plotter were used to identify the differentially expressed genes, which mainly involved the degradation and synthesis enzymes of neurotransmitters in gastric cancer. We also investigated the expression pattern of MAOA in human and mouse tissues and cell lines by immunohistochemistry and Western blotting analysis. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and a Seahorse experiment were used to identify the molecular mechanism of cancer cell glycolysis. MAOA expression and patient survival were analysed in the Ren Ji cohort, and univariate and multivariate analyses were performed based on the clinicopathological characteristics of the above samples. Results MAOA expression was significantly downregulated in gastric cancer tissue and associated with poor patient prognosis. Moreover, the expression level of MAOA in gastric cancer tissue had a close negative correlation with the SUXmax value of PET-CT in patients. MAOA suppressed tumour growth and glycolysis and promoted cancer cell apoptosis. We also reported that MAOA can interact with NDRG1 and regulate glycolysis through suppression of the PI3K/Akt/mTOR pathway. MAOA expression may serve as an independent prognostic factor in gastric cancer patients. Conclusions MAOA attenuated glycolysis and inhibited the progression of gastric cancer through the PI3K/Akt/mTOR pathway. Loss of function or downregulation of MAOA can facilitate gastric cancer progression. Overexpression of MAOA and inhibition of the PI3K/Akt/mTOR pathway may provide a potential method for gastric cancer treatment in clinical therapeutic regimens.

Objective:To investigate the short-term efficacy of laparoscopic total gastrec-tomy with hand-sewn esophagojejunostomy versus Roux-en-Y anastomosis.Methods:The propen-sity score matching and retrospective cohort study was conducted. The clinicopathological data of 159 patients who underwent laparoscopic total gastrectomy in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to July 2021 were collected. There were 107 males and 52 females, aged 63(range, 28?79)years. Of 159 patients, 71 cases undergoing totally laparoscopic total gastrectomy with hand-sewn esophagojejunostomy were allocated into totally laparoscopic group and 88 cases undergoing laparoscopic-assisted total gastrectomy with Roux-en-Y anastomosis were allocated into laparoscopic-assisted group, respectively. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability method. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 159 patients, 112 cases were successfully matched, including 56 cases in the totally laparoscopic group and 56 cases in the laparoscopic-assisted group. Before propensity score matching, age, cases with tumor located in cardia or gastric body in the totally laparoscopic group were 61(range, 30?76)years, 26, 45, respectively. The above indicators in the laparoscopic-assisted group were 65(range, 28?79)years, 50, 38, respectively. There were significant differences in the above indicators between the two groups ( Z=?2.89, χ2=6.43, P<0.05). After propensity score matching, the males and females, age, body mass index, cases of American Society of Anesthesiologists classification Ⅰ, Ⅱ, Ⅲ and Ⅳ, tumor diameter, cases with tumor located in cardia or gastric body, cases in TNM stage Ⅰ, Ⅱ and Ⅲ of patients in the totally laparoscopic group were 40, 16, (62±9)years, (22.7±2.8)kg/m 2, 22, 26, 7, 1, 3.5(range, 0.6?17.0)cm, 24, 32, 22, 9, 25. The above indicators of patients in the laparoscopic-assisted group were 38, 18, (62±10)years, (22.7±3.2)kg/m 2, 19, 32, 5, 0, 4.0(range, 0.6?15.0)cm, 23, 33, 21, 7, 28, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.17, t=?0.09, ?0.04, Z=?0.12, ?0.82, χ2=0.04, Z=?0.42, P>0.05). The elimination of age and tumor location confounding bias ensured comparability between the two groups. (2) Intraoperative and postoperative conditions: after propensity score matching, the total operation time, time of esophagojejunostomy, postopera-tive 24-hour pain numerical score and time to first out-off bed activities were (310±49)minutes, (37±10)minutes, 2.3±0.8 and (2.4±0.7)days for patients in the totally laparoscopic group, versus (344±77)minutes, (44±12)minutes, 3.1±1.2 and (2.9±1.0)days in the laparoscopic-assisted group, showing significant differences between the two groups ( t=?2.85, ?3.05, ?4.20, ?3.10, P<0.05). (3) Perioperative complications: after propensity score matching, 6 cases of the patients in the totally laparoscopic group had Clavien-Dindo grade 2 or higher complications, including 2 cases of anas-tomotic leak, 1 case of anastomotic stenosis, 1 case of pleural effusion, 1 case of abdominal infection and 1 case of intestinal obstruction. The incidence of Clavien-Dindo grade 2 or higher complications was 10.7%(6/56). In the laparoscopic-assisted group, 5 patients had Clavien-Dindo grade 2 or higher complications, including 2 cases of anastomotic leak, 1 case of abdominal infection, 1 case of intestinal obstruction and 1 case of cholangitis. The incidence of Clavien-Dindo grade 2 or higher complications was 8.9%(5/56). There was no significant difference in the incidence of Clavien-Dindo grade 2 or higher complications between the two groups ( χ2=0.10, P>0.05). Patients with anas-tomotic leak were improved after puncture and drainage, secondary surgery and conservative treat-ment, and other complications were improved after symptomatic treatment. Conclusions:Com-pared with Roux-en-Y anastomosis in laparoscopic total gastrectomy, the time of hand-sewn esophagojejunostomy and esophago-jejunal anastomosis are shorter, patients have less postopera-tive pain and faster postoperative recovery. Both methods have good peri-operative safety.