BACKGROUND:The long-term survival outcomes for patients with clinical stage I gastric cancer who undergo laparoscopic total gastrectomy (LTG) are still uncertain due to the limited high-level clinical evidence. MATERIAL AND METHODS:The CLASS02 study was designed as a prospective, multicenter, open-label, randomized, non-inferiority clinical trial carried out across 14 gastroenterology centers in China. Patients diagnosed with clinical stage I gastric adenocarcinoma located in the middle and/or upper third of the stomach were randomly assigned to receive either LTG or open total gastrectomy (OTG) accompanied by D1+/D2 lymphadenectomy performed by skilled surgeons. Building on the primary analysis of safety results at 30 days, published in 2020, this extended analysis aimed to evaluate 5-year overall survival (OS) and disease-free survival (DFS) rates between LTG and OTG. RESULTS:Of the 227 patients who were enrolled between January 2017 and September 2018, 214 patients underwent total gastrectomy: 105 (49.0%) in the LTG group and 109 (51.0%) in the OTG group. The 5-year OS rate was 93.3% in the LTG group compared to 94.5% in the OTG group, and the 5-year DFS rate was 92.4% in the LTG group compared to 93.6% in the OTG group. There were no significant differences between the groups. CONCLUSION:Given the current underpowered long-term follow-up findings, LTG with D1 +/D2 lymphadenectomy performed by experienced surgeons showed numerically similar 5-year overall survival and disease-free survival rates to OTG in patients with clinical stage I gastric cancer.

BACKGROUND:The multicentre RESOLVE trial examined the efficacy of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in gastric or gastro-oesophageal junction cancer. Initial analyses did not encompass overall survival owing to the immature data. This paper provides an updated analysis of the survival data from the RESOLVE trial. METHODS:In this randomised, open-label, phase 3 study, participants aged 18 years or older with cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma who were feasible for D2 lymphadenectomy and had a Karnofsky performance score of 70 or higher were enrolled. Participants were randomly assigned in a 1:1:1 ratio via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral capecitabine 1000 mg/m2 twice a day on days 1-14, adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day on days 1-14), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy. The primary endpoint, assessed in the modified intention-to-treat population, was 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-CapOx and the non-inferiority (hazard ratio [HR] non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx, and has been reported previously. This final report focuses on the secondary endpoint of 5-year overall survival, also assessed in the modified intention-to-treat population. Other secondary endpoints-R0 resection rate and safety-were not updated in this analysis. The study is registered at ClinicalTrials.gov, NCT01534546, and is complete. FINDINGS:Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were enrolled and randomly assigned, of whom 1022 participants were included in the modified intention-to-treat population: 345 (259 male, 86 female) in the adjuvant-CapOx group, 340 (238 male, 102 female) in the adjuvant-SOX group, and 337 (271 male, 66 female) in the perioperative-SOX group. As of April 7, 2022, the median duration of follow-up was 62·8 months (IQR 52·0-75·1). The 5-year overall survival rates were 52·1% (95% CI 46·3-57·5) for the adjuvant-CapOx group, 61·0% (55·3-66·2) for the adjuvant-SOX group, and 60·0% (54·2-65·3), for the perioperative-SOX group. Overall survival was significantly prolonged with perioperative-SOX (HR 0·79; 95% CI 0·62-1·00, p=0·049) and adjuvant-SOX (HR 0·77, 0·61-0·98, p=0·033), compared with adjuvant-CapOx. INTERPRETATION:Consistent with the initial analysis of 3-year disease-free survival, the extended 5-year overall survival analysis from the RESOLVE trial confirmed the survival advantage of perioperative-SOX and adjuvant-SOX compared with the standard adjuvant-CapOx regimen. The SOX regimen, given perioperatively or as an adjuvant treatment, emerges as a potential standard treatment modality for locally advanced gastric or gastro-oesophageal junction cancer management in Asian patients. FUNDING:The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, the Beijing Natural Science Foundation, National Natural Science Foundation of China, the Beijing Natural Science Foundation, Taiho, Hengrui Pharmaceutical and Sanofi-Aventis. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

Objective:Laparoscopic distal gastrectomy (LDG) has potential as a surgical treatment option for locally advanced gastric cancer (LAGC). However, there is uncertainty regarding the generalizability of LDG efficacy across diverse patient populations and treatment settings. This study aimed to assess the outcomes of LDG vs. open distal gastrectomy (ODG) in patients with LAGC despite differences in clinical trial populations and treatment environments. Methods:The KLASS-02 and CLASS-01 trials are multicenter, non-inferiority, open-label, randomized controlled trials for patients with LAGC eligible for distal subtotal gastrectomy in Korea and China, respectively. Some 1,050 patients were enrolled in KLASS-02, and 1,056 patients were enrolled in CLASS-01. Individual patient data (IPD) from KLASS-02 and CLASS-01 were pooled and analyzed. Results:There were 900 patients in the LDG group and 920 in the ODG group. Baseline characteristics were well balanced between groups. The LDG group had better short-term and recovery outcomes than the ODG group, although anastomotic leakage was more frequent. For patients who underwent LDG vs. ODG, 5-year overall survival (OS) was 82.7% [95% confidence interval (95% CI), 80.2%-85.2%] vs. 83.3% (95% CI, 80.9%-85.8%) (P=0.706) and 5-year recurrence-free survival (RFS) was 76.9% (95% CI, 74.1%-79.7%) vs. 77.9% (95% CI, 75.2%-80.6%) (P=0.666), respectively, with a median follow-up of 70 months. In the multivariable prognostic IPD meta-analysis, the operative approach was not independently associated with OS [hazard ratio (HR)=1.045, 95% CI, 0.833-1.311; P=0.706] or RFS (HR=1.044, 95% CI, 0.859-1.269; P=0.667) for LDG vs. ODG. In the subgroup analysis, LDG demonstrated a significant association with poorer RFS in the pT4 subgroup (HR=1.377, 95% CI, 1.022-1.760; P=0.034). Conclusions:Despite differences in patient populations, surgical practices, and postoperative treatments between trials, LDG is oncologically safe with the benefit of being minimally invasive for patients with LAGC, except for the pT4 patients. Therefore, LDG could be a good treatment alternative for patients with LAGC; however, caution should be warranted in its application for patients classified as T4.

PURPOSE Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. METHODS This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942 ) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). RESULTS Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). CONCLUSION This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

There has been a major increase in Type 2 diabetes and obesity in many countries, and this will lead to a global public health crisis, which not only impacts on the quality of life of individuals well but also places a substantial burden on healthcare systems and economies. Obesity is linked to not only to type 2 diabetes but also cardiovascular diseases, musculoskeletal disorders, and certain cancers, also resulting in increased medical costs and diminished quality of life. A number of studies have linked changes in gut in obesity development. Dysbiosis, a deleterious change in gut microbiota composition, leads to altered intestinal permeability, associated with obesity and Type 2 diabetes. Many factors affect the homeostasis of gut microbiota, including diet, genetics, circadian rhythms, medication, probiotics, and antibiotics. In addition, bariatric surgery induces changes in gut microbiota that contributes to the metabolic benefits observed post-surgery. Current obesity management strategies encompass dietary interventions, exercise, pharmacotherapy, and bariatric surgery, with emerging treatments including microbiota-altering approaches showing promising efficacy. While pharmacotherapy has demonstrated significant advancements in recent years, bariatric surgery remains one of the most effective treatments for sustainable weight loss. However, access to this is generally limited to those living with severe obesity. This underscores the need for non-surgical interventions, particularly for adolescents and mildly obese patients. In this comprehensive review, we assess longitudinal alterations in gut microbiota composition and functionality resulting from the two currently most effective anti-obesity treatments: pharmacotherapy and bariatric surgery. Additionally, we highlight the functions of gut microbiota, focusing on specific bacteria, their metabolites, and strategies for modulating gut microbiota to prevent and treat obesity. This review aims to provide insights into the evolving landscape of obesity management and the potential of microbiota-based approaches in addressing this pressing global health challenge.

Rationale: Malignant gastric glomus tumor (GGT) is an extremely rare malignant tumor of mesenchymal origin, it affects the patient's health and even threatens life. Malignant GGT with vascular invasion is even more rarely reported in the available literature without a prognostic study. So, in this case, we report a malignant GGT with vascular invasion and performed a 5-year postoperative follow-up. To the best of our knowledge, we report the first case of malignant GGT with vascular invasion without recurrence 5 years after surgery. This provides examples and lessons for the treatment of malignant GGT with vascular invasion. Patient concerns: A 49-year-old male was admitted to the hospital with gallbladder stones found on health check. After completing abdominal CT and ultrasound gastroscopy, a mass in the gastric antrum was found. Diagnoses: The diagnosis of malignant GGT was confirmed by combination of postoperative pathology with positive immunohistochemistry for SMA, vimentin, synaptophysin, H-caldesmon, and calponin, mitosis > 10/50 HPF and moderate-to-severe nuclear atypia. Interventions: On the 6th day of hospitalization, the patient underwent laparoscopic distal gastrectomy and cholecystectomy. Outcomes: The patient was discharged successfully 1 week after surgery and was followed up for 5 years without recurrence. Conclusion: Malignant GGT can be asymptomatic. For malignant GGT without distant metastasis, despite the presence of vascular invasion, negative margin surgery can still be the standard surgical radical treatment.

Intermittent urethral catheter clamping is widely used to reduce secondary catheterization in patients after proctectomy; however, its effectiveness is unclear. This study investigated the effects of intermittent catheter clamping combined with active urination training (ICCAUT) on postoperative urinary dysfunction in patients after proctectomy. This retrospective cohort study analyzed data on patients who underwent laparoscopic/robotic-assisted proctectomy at a single medical center in China between July 2023 and January 2024. Patients received ICCAUT or free urinary drainage during the indwelling urethral catheter period after surgery. Data from the ICCAUT and free-drainage groups were compared. The primary outcome measure was urinary dysfunction. The secondary outcomes were urinary tract infections, time to first void after catheter removal, and urine volume during first voiding. Propensity-score matching (PSM), inverse probability-of-treatment weighting (IPTW), and multivariable logistic regression analyses were used to identify factors associated with urinary dysfunction. Among 360 eligible patients, 173 received a free-drainage strategy and 187 received ICCAUT. The incidence of urinary dysfunction was 52.5

3575 Background: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. Methods: This randomized, controlled, unblinded, phase 3, superiority trial involved 17 hospitals in China. Totally 1,072 patients diagnosed with stage T2-T4aNanyM0 or TanyN+M0 right-sided colon cancer were enrolled from January 11, 2016, through December 26, 2019. Participants were randomly assigned (1:1 ratio) to undergo either CME (n=536) or D2 dissection (n=536) during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). Results: Among 1072 patients, 77 were excluded after randomization. The remaining 995 patients (median age 61years, 59% male) were included in the primary analysis (CME [n=495] vs. D2 dissection [n=500]). The 3-year primary outcome assessment was completed for 97% patients. No significant differences were found between the groups in 3-year DFS (86.1% in CME group vs. 81.9% in D2 group; HR = 0.74; 95% confidence interval [CI]: 0.54-1.02; P = 0.06) or in 3-year OS (94.7% in CME group vs. 92.6% in D2 group; HR = 0.70; 95% CI: 0.43-1.16; P = 0.17). Conclusions: For primary surgical excision of right-sided colon cancer, complete mesocolic excision did not improve disease free survival, compared to standard D2 lymph node dissection. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement. Trial Registration: ClinicalTrials.gov Identifier: NCT02619942. Clinical trial information: NCT02619942 .

目的 探讨经食管裂孔下纵隔淋巴结清扫在SiewertⅡ型食管胃结合部腺癌(AEG)根治术中的应用价值.方法 回顾性分析吉林大学第一医院胃肠外科2018年11月至2019年12月间收治的32例经手术治疗的SiewertⅡ型AEG病人的临床资料,均采用腹腔镜下经食管裂孔途径,"以食管为中心按腹侧→背侧→两侧的清扫次序"清扫No.110、No.111、No.112淋巴结.记录病人的手术时间、术中出血量、收获淋巴结数量、术后肠蠕动恢复时间、术后排气时间、术后并发症等.结果 通过经食管裂孔途径,"以食管为中心按腹侧→背侧→两侧的清扫次序"实现了No.110、No.111、No.112淋巴结的确切清扫,淋巴结转移发生率No.110为6.25％ (2/32),No.111为9.38％(3/32),No.112为9.38％(3/32).无术中副损伤发生.术后出现胸腔积液21例,胰瘘7例,腹腔感染1例以及吻合口漏1例.结论 通过经食管裂孔途径,"以食管为中心按腹侧→背侧→两侧的清扫次序"对AGE病人进行下纵隔淋巴结清扫是安全可行的.

Efficient molecular targeting therapies for most gastric cancers (GCs) are currently lacking, despite GC being one of the most frequent and often devastating malignancies worldwide. Thus, identification of novel therapeutic targets for GC is in high demand. Recent advancements of high‐throughput nucleic acid synthesis methods combined with next‐generation sequencing (NGS) platforms have made it feasible to conduct functional genomics screening using large‐scale pooled lentiviral libraries aimed at discovering novel cancer therapeutic targets. In this study, we performed NGS‐based functional genomics screening for human GC cell lines using an originally constructed 6,399 shRNA library targeting all 2,096 human metabolism genes. Our screening identified aspartyl‐tRNA synthetase (DARS) as a possible candidate for a therapeutic target for GC. In‐house tissue microarrays containing 346 cases of GC combined with public datasets showed that patients with high expression levels of DARS protein exhibited more advanced clinicopathologic parameters and a worse prognosis, specifically among diffuse‐type GC patients. Both in vitro and in vivo experiments concretely evidenced that DARS inhibition achieved robust growth suppression of GC cells. Moreover, RNA sequencing of GC cell lines under shRNA‐mediated DARS knockdown suggested that DARS inhibition exerts its effect through the inactivation of multiple p‐ERK pathways. This MAPK‐related growth suppression by DARS inhibition would also be applicable to other cancers; thus, it is warranted to investigate the expression and clinical significance of DARS in a wide spectrum of malignancies. Taken together, NGS‐based high‐throughput pooled lentiviral screening showed DARS as a novel prognostic marker and a promising therapeutic target for GC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

日本大肠癌研究会编撰的《大肠癌治疗指南(2022年版)》于2022-01-25出版发行.2022年版在2019年版指南基础上进行了部分修订.在外科治疗方面修订较少,主要体现在Ⅳ期大肠癌的治疗方针.但是在大肠癌的药物疗法方面,随着日本及国际相关Ⅲ期临床试验结果的发布,主要变更了免疫检查点抑制剂和BRAF抑制剂等药物疗法方面内容.了解最新版本日本《大肠癌治疗指南》的内容,对于推动我国大肠癌的规范化诊治具有重要意义.

Malignant tumors pose a serious threat to human health and have high fatality rates. Conventional clinical anti-tumor treatment is mainly based on traditional surgery, chemotherapy, radiotherapy, and interventional therapy, and even though these treatment methods are constantly updated, a satisfactory efficacy is yet to be obtained. Therefore, research on novel cancer treatments is being actively pursued. We review the classification of gene therapies of malignant tumors and their advantages, as well as the development of gene editing techniques. We further reveal the nano-drug delivery carrier effect in improving the efficiency of gene editing. Finally, we summarize the progress in recent years of gene editing techniques based on nano-drug delivery carriers in the treatment of various malignant tumors, and analyze the prospects of the technique and its restricting factors.

Importance It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes among patients with locally advanced gastric cancer. Data from a multicenter, randomized clinical trial (Chinese Laparoscopic Gastrointestinal Surgical Study [CLASS]-01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy. Objective To report 5-year overall survival data from the CLASS-01 trial of laparoscopic vs open distal gastrectomy among patients with locally advanced gastric cancer. Design, Setting, and Patients This was a noninferiority, open-label, randomized clinical trial conducted at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 12, 2012, to December 3, 2014. Final follow-up was on December 31, 2019. Interventions Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histologic features to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main Outcomes and Measures The 5-year overall survival rates were updated to compare laparoscopic distal gastrectomy with open distal gastrectomy. All analyses were performed on an intention-to-treat basis. In addition, per-protocol and as-treated analyses were performed for overall survival. Results Data from 1039 patients (726 men [69.9%]; mean [SD] age, 56.2 [10.7] years) who received curative therapy were analyzed. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P = .19; hazard ratio, 1.17; 95% CI, 0.93-1.48; P = .19). After comparison for competing risk events, gastric cancer-related deaths (hazard ratio, 1.14; 95% CI, 0.87-1.49; P = .34) and deaths from other causes (hazard ratio, 1.23; 95% CI, 0.74-2.05; P = .42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage. Conclusions and Relevance This study found that laparoscopic distal gastrectomy with D2 lymphadenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar 5-year overall survival compared with open distal gastrectomy among patients with locally advanced gastric cancer. Trial Registration ClinicalTrials.gov Identifier: NCT01609309.

DEK is known to be a potential proto-oncogene and is highly expressed in gastric cancer (GC); thus, DEK is considered to contribute to the malignant progression of GC. DEK is an RNA-binding protein involved in transcription, DNA repair, and selection of splicing sites during mRNA processing; however, its precise function remains elusive due to the lack of clarification of the overall profiles of gene transcription and post-transcriptional splicing that are regulated by DEK. We performed our original whole-genomic RNA-Seq data to analyze the global transcription and alternative splicing profiles in a human GC cell line by comparing DEK siRNA-treated and control conditions, dissecting both differential gene expression and potential alternative splicing events regulated by DEK. The siRNA-mediated knockdown of DEK in a GC cell line led to significant changes in gene expression of multiple cancer-related genes including both oncogenes and tumor suppressors. Moreover, it was revealed that DEK regulated a number of alternative splicing in genes which were significantly enriched in various cancer-related pathways including apoptosis and cell cycle processes. This study clarified for the first time that DEK has a regulatory effect on the alternative splicing, as well as on the expression, of numerous cancer-related genes, which is consistent with the role of DEK as a possible oncogene. Our results further expand the importance and feasibility of DEK as a clinical therapeutic target for human malignancies including GC.

Background Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial. Methods This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18–75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes—intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only—are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing. Findings Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, −2·2% [95% CI −7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I–II complications were similar between groups (91 [18%] vs 92 [18%], difference, −0·0% [95% CI −4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III−IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], −2·2% [−4·1 to −0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes. Interpretation Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons. Funding The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences.

Background Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. Methods RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. Discussion This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. Trial registration Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.

Mesenchymal stem cells (MSCs) can sense and convert mechanical stimuli signals into a chemical response. Integrins are involved in the mechanotransduction from inside to outside and from outside to inside, and ultimately affect the fate of MSCs responding to different mechanical signals. Different integrins participate in different signaling pathways to regulate MSCs multi-differentiation. In this review, we summarize the latest advances in the effects of mechanical signals on the differentiation of MSCs, the importance of integrins in mechanotransduction, the relationship between integrin heterodimers and different mechanical signals, and the interaction among mechanical signals. We put forward our views on the prospect and challenges of developing mechanical biology in tissue engineering and regenerative medicine.

IntroductionGastric cancer is one of the most common gastrointestinal tumors, ranking forth in incidence and second in mortality worldwide. Discovering molecular biomarkers for early gastric cancer diagnosis is of great importance. MethodsUrine and related clinical data of 40 patients with gastric cancer (20 in advanced stage and 20 in early stage) and 20 healthy volunteers from Jilin University First Hospital were collected. Liquid chromatography-mass spectrometry (LC-MS) was used to detect urine samples and the metabolic differences between the three groups of urine samples were analyzed. The principal component analysis was performed after data processing, and different metabolites were found using analysis of variance. Partial least square discriminant analysis was performed to further narrow the range of different metabolites. The precise mass to charge ratios of different metabolites were imported into the Human Metabolomics Database (HMDB). Finally, the identified different metabolites were further screened by cluster analysis and ROC curve. ResultsUrine samples of the healthy group (NOR), the early gastric cancer group (EGC), and the advanced gastric cancer group (AGC) were different metabolites. 324 statistically significant metabolites are screened out. The cluster analysis showed 7-Methylguanine, vinylacetylglycine, butyric acid, 4-Vinylphenol sulf,
5`-biotinyl-AMP, and 3-Amino-2-piperido in EGC, AGC and NGO were similar. 7-Methylguanine, vinylacetylglycine and 4-Vinylphenolsulfate had good diagnostic ability in EGC and NOR (p<0.05), and gastric cancer and NOR (p<0.05). ConclusionDifferences in the metabolites in urine between the early gastric cancer group and the healthy group were found. 7-Methylguanine, Vinylacetylglycine, and 4-Vinylphenolsulfate have good diagnostic ability and may be potential biomarkers of early gastric cancer.