Treatment delivered before surgery in colorectal cancer now encompasses several clinically distinct strategies rather than one uniform pathway. These include selective neoadjuvant chemotherapy for radiologically high-risk colon cancer, total neoadjuvant therapy (TNT) and response-adapted organ preservation in rectal cancer, immunotherapy for mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) disease, and perioperative or conversion treatment for colorectal liver metastases (CRLM). This Review separates these settings by treatment intent, expected endpoint, likelihood of surgery, and evidence maturity. MMR/MSI has direct treatment relevance in localized disease; RAS/BRAF status and primary tumor sidedness mainly inform metastatic and conversion strategies; HER2-directed treatment remains supported principally by advanced-disease data; and circulating tumor DNA (ctDNA), radiomics, and other dynamic tools remain adjunctive or investigational for most preoperative decisions. Quantitative results from pivotal trials are summarized alongside practical decision boundaries, including clinical complete response assessment, watch-and-wait surveillance, CRLM resectability reassessment, and stopping rules. The central message is deliberately cautious: moving treatment earlier is useful only when the clinical scenario, therapeutic aim, evidence level, reassessment plan, and salvage pathway are defined before treatment begins.

Colorectal cancer (CRC) is accompanied by complex metabolic alterations, but the diagnostic value and biological relevance of circulating metabolites require further clarification. In this study, untargeted serum metabolomics was performed in 90 individuals, including 45 patients with CRC and 45 healthy controls. Differential metabolites were screened and further prioritized using LASSO regression and random forest modelling, yielding an 11-metabolite panel. The random forest model showed AUCs of 0.989 in the training set and 0.906 in the testing set. To evaluate whether this panel provided information beyond common clinical variables, we compared a clinical-covariate model, the metabolite model, and a combined model in the testing set. The clinical-covariate model showed limited discrimination (AUC = 0.4089), whereas the metabolite and combined models showed higher AUCs of 0.9911 and 0.9956, respectively, with sensitivity of 1.0000 and specificity of 0.8000 at the training-set Youden cutoff. Pathway and cell-based analyses further linked phenylalanine and L-valine with mTOR-associated proliferative and migratory phenotypes, and L-carnitine with fatty-acid-oxidation-related metabolic activity in CRC cells. These findings suggest that serum metabolic profiling may provide candidate markers for CRC classification and biological stratification, although larger prospective and externally validated studies are needed before clinical translation.

Objective: To investigate the effect and possible mechanism of Huanghou Zhixie dropping pills in ulcerative colitis treatment. Method: The study was conducted at the Inner Mongolia Medical University, Hohhot, China, between March and November 2022, and comprised specific pathogen-free Bagg albino (C57BL6) adult female mice. Ulcerative colitis was induced using dextran sulfate sodium. The mice were divided randomly into control group, model group, low-dose Huanghou Zhixie dropping pills HZDP-L group, medium-dose Huanghou Zhixie dropping pills HZDP-M group, high-dose Huanghou Zhixie dropping pills HZDP-H group, and mesalazine group. The quality of the model was verified through Disease Activity Index, Colonic Mucosal Damage Index, and Histopathological) analysis. Enzyme-linked immunosorbent assay was used to measure inflammatory factors related to ulcerative colitis, including Interleukin-1 beta (IL-1beta), Transforming Growth Factor-beta (TGF- beta), Interleukin-4 (IL-4), Tumour Necrosis Factor-alpha (TNF-alpha), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). Western blot analysis was conducted to examine the relevant factors, such as cyclooxygenase-2, inducible nitric oxide synthase, Protein 65 (P65), Mitogen-Activated Protein Kinase (MAPK), Phosphorylated Mitogen-Activated Protein Kinase (p-MAPK) and Phosphorylated Protein 65 (p-P65). Data was analysed using SPSS 20. Results: Of the 36 female mice aged 8 weeks and having mean weight 18±2g, 6(16.66%) were in each of the 6 groups. Huanghou Zhixie dropping pills significantly reduced dextran sulfate sodium-induced ulcerative colitis symptoms, weightloss and colon damage (p<0.05). Huanghou Zhixie dropping pills decreased the expression of pro-inflammatory TNF-alpha, IL-1beta, TGF-beta, and IL-6 factors, and increased the expression of anti-inflammatory IL-4 and IL-10 factors in the colon tissue of the mice (p<0.05). Additionally, Huanghou Zhixie dropping pills reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase, P-MAPK and P-P65 in the colon tissue (p<0.05). Conclusion: Huanghou Zhixie dropping pills alleviated colitis by modulating inflammatory factors through the Mitogen- Activated Protein Kinase/Nuclear Factor kappa-light-chain-enhancer of activated B cells (MAPK/NF-kB) signalling pathway. The Huanghou Zhixie dropping pills could be a potential therapeutic option for ulcerative colitis treatment, offering a novel approach to managing the disease by targeting specific inflammatory pathways. Keywords: HZDP, Ulcerative colitis, MAPK/NF-kB signaling pathway, Inflammatory factors.

Gastric cancer still is a severe threat to human health, often presenting with a poor prognosis, effective biomarkers for early detection and targeted treatment are urgently needed. This study performed a comprehensive bioinformatics and machine learning approach to identify key protein biomarkers for gastric cancer and elucidate their potential functions. Gastric cancer-related datasets were obtained from the NCBI Gene Expression Omnibus database. Differential expression analysis identified 171 genes with noticeable differences between control and tumor samples. Utilizing LASSO, SVM-RFE, and RF algorithms, five genes—INHBA, DPT, ADH7, FBP2 and GPR155—were identified as potential biomarkers. A logistic regression model demonstrated the highest performance among ten machine learning models constructed using these five genes. Shapley additive explanations (SHAP) were employed to illustrate the detailed contribution of the pivotal genes to the logstics model. Gene set enrichment analysis and gene set variation analysis were then used to find out the functional roles of these genes in gastric cancer cells. At length, we revealed the distinctive effects of signature genes on immune cell infiltration and patient diagnosis. In conclusion, the identified proteins have the potential to serve as diagnostic biomarkers and provide treatment value for gastric cancer. This study offers a comprehensive, data-driven approach to uncover critical molecular targets for improved detection and management of this deadly disease.

ETHNOPHARMACOLOGICAL RELEVANCE:Batri-7 (BT-7) is a compound herbal remedy rooted in traditional Mongolian medicine (TMM), composed of seven medicinal plants. Historically, it has been prescribed to treat various gastrointestinal conditions, including chronic enteritis and ulcerative colitis. However, despite this long-standing use in managing inflammatory disorders of the gut, the preventive effects of BT-7 on colitis-associated colorectal cancer (CAC), as well as its underlying molecular mechanisms, remains incompletely elucidated. AIM OF THE STUDY:This study aimed to assess the therapeutic efficacy of BT-7 in an AOM/DSS-induced murine model of CAC, while also investigating its modulatory effects on systemic inflammation, intestinal barrier function, gut microbiota dynamics, and inflammation-related molecular signaling pathways. MATERIALS AND METHODS:A chemically induced CAC model was established in C57BL/6 mice using azoxymethane (AOM) and dextran sodium sulfate (DSS). BT-7 was then administered orally at three dosage levels, and therapeutic outcomes were evaluated through a range of methods:clinical scoring, serum biochemical analysis, histological analysis, immunohistochemistry, and gut microbial profiling via 16S rRNA sequencing. To explore the underlying mechanistic pathways, with a particular focus on inflammasome regulation, transcriptome sequencing, quantitative PCR, and Western blotting were employed. RESULTS:BT-7 treatment was well-tolerated, with no evidence of liver or kidney toxicity. Mice receiving BT-7 exhibited improved body weight maintenance, lower disease activity scores, and preserved colon length. Histologically, there was substantial restoration of mucosal architecture and reduced epithelial hyperplasia, alongside significant suppression of tumor formation. Systemically, BT-7 reduced levels of key pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and KC/GRO) and enhanced intestinal barrier integrity, as evidenced by the elevation of Occludin and ZO-1. Additionally, BT-7 decreased the abundance of pro-inflammatory taxa, such as Bacteroidota, and enriched beneficial genera like Lactobacillus and Dubosiella. The increased relative abundance of Lactobacillus_johnsonii and decreased Lactobacillus _murinus highlighted the probiotic effects of BT-7. Functional pathway prediction revealed that BT-7's microbiota was enriched in pathways related to carbohydrate and amino acid metabolism, as well as digestive system and immune-related functions. Transcriptomic analysis revealed downregulation of inflammatory signaling, particularly within the NOD-like receptor pathway, with reduced NLRP3 expression at both mRNA and protein levels confirming this effect. CONCLUSIONS:This work demonstrates that BT-7 exerts protective effects against CAC by suppressing inflammation, improving epithelial integrity, and restoring microbial homeostasis. Mechanistically, the NLRP3 inflammasome is identified as BT-7's primary target in this context, which aligns with its traditional use in treating gastrointestinal disorders. Collectively, these findings highlight BT-7's therapeutic potential as a chemopreventive agent, supporting its utility in aiding inflammation-associated colorectal cancer treatment.

Gastric cancer still is a severe threat to human health, often presenting with a poor prognosis, effective biomarkers for early detection and targeted treatment are urgently needed. This study performed a comprehensive bioinformatics and machine learning approach to identify key protein biomarkers for gastric cancer and elucidate their potential functions. Gastric cancer-related datasets were obtained from the NCBI Gene Expression Omnibus database. Differential expression analysis identified 171 genes with noticeable differences between control and tumor samples. Utilizing LASSO, SVM-RFE, and RF algorithms, five genes—DPT, FBP2, ADH7, INHBA, and GPR155—were identified as potential biomarkers. A support vector machine (SVM) model demonstrated the highest performance among ten machine learning models constructed using these five genes. Shapley additive explanations (SHAP) were employed to illustrate the detailed contribution of the pivotal genes to the SVM model. Gene set enrichment analysis and gene set variation analysis were then used to find out the functional roles of these genes in gastric cancer cells. At length, we revealed the distinctive effects of signature genes on immune cell infiltration and patient prognosis. In conclusion, the identified proteins have the potential to serve as diagnostic biomarkers and provide prognostic value for gastric cancer. This study offers a comprehensive, data-driven approach to uncover critical molecular targets for improved detection and management of this deadly disease.

ObjectiveTo evaluate the efficacy and further analyze the application prospects of the combined multitarget fecal FIT-DNA assay in the early screening of colorectal cancer. MethodsSubjects were selected from a population attending the Inner Mongolia Medical University Hospital. Each subject underwent a combined multi-target fecal FIT-DNA test (experimental group), a serum tumor marker test and enteroscopy (control group). The pathological results were used as the gold standard to evaluate the efficacy of novel fecal molecular testing techniques for colorectal cancer screening with timely intervention given to screen positive individuals. ResultsThe data of 115 individuals were analyzed. Serum tumor markers test had a sensitivity of 63.2% (43/68) and a specificity of 74.5% (35/47). The enteroscopy had a sensitivity of 97.1% (66/68) and a specificity of 80.7% (38/47); the combined multitarget fecal FIT-DNA test had a sensitivity of 89.7% (61/68) and a specificity of 87.2% (41/47). ConclusionThe sensitivity and specificity of multitarget fecal FIT-DNA combined detection are better than those of serum tumor marker detection. Although its sensitivity is lower than enteroscopy, its operation is simpler and can be tested at home.

Objective To undertake a comprehensive assay of PDCD11 expression in colorectal cancer (CRC) and its association with prognosis and immune cell infiltration (ICIN) utilizing bioinformatics tools. Methods The PDCD11 expression in CRC and pan-cancer was quantified through datasets from TCGA and GEO databases, and the assay was conducted through R software and the GEPIA database. Moreover, mRNA and protein expression data of PDCD11 were attained from the HPA database. It was attempted to establish protein-protein interaction networks of PDCD11 via the STRING and GeneMANIA databases. The association of PDCD11 expression with CRC staging was evaluated through R software, while its association with CRC and pan-cancer prognosis was figured out via the GEPIA database. Furthermore, the relationship of PDCD11 expression with ICIN was assayed using R software and the TIMER database. Additionally, the influences of PDCD11 knockdown on the proliferation, apoptosis, and migration of colon cancer RKO cell lines was evaluated. Results PDCD11 exhibited elevated expression in CRC and various other malignancies, potentially indicating a promotive role in cancer progression. Overexpression of PDCD11 was found to correlate with attenuated overall survival in CRC and other malignancies. Moreover, PDCD11 demonstrated promising predictive capabilities for distinguishing between tumor and non-tumor tissues. The positive association of high PDCD11 expression with the infiltration of neutrophils, dendritic cells, CD8+ T cells, CD4+ T cells, and macrophages, as well as with the expression of immune checkpoint molecules CTLA4 and PD-1 was noteworthy. Lentivirus-mediated PDCD11 knockdown suppressed RKO cell proliferation, colony formation, and migration, while triggered apoptosis in these cells. Conclusion The outcomes unveiled the noticeable function of PDCD11 in CRC and various other malignancies, emphasizing its potential as a prognostic biomarker and therapeutic target.

BACKGROUND:Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1.METHODS:Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway.RESULTS:YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1's inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP.CONCLUSIONS:This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.

Colorectal cancer (CRC) is a significant global health burden, with high morbidity and mortality rates. It is often diagnosed at middle to advanced stage, affecting approximately 35% of patients at the time of diagnosis. Currently, chemotherapy has been used to improve patient prognosis and increase overall survival. However, chemotherapy can also have cytotoxic effects and lead to adverse reactions, such as inhibiting bone marrow hematopoiesis, causing digestive dysfunction, hand-foot syndrome, and even life-threatening conditions. In response to these adverse effects, researchers have proposed using Traditional Chinese Medicine (TCM) as an option to treat cancer. TCM research focuses on prescriptions, herbs, and components, which form essential components of the current research in Chinese medicine. The study and implementation of TCM prescriptions and herbs demonstrate its distinctive holistic approach to therapy, characterized by applying multi-component and multi-target treatment. TMC components have advantages in developing new drugs as they consist of single ingredients, require smaller medication dosages, have a precise measure of pharmacodynamic effects, and have a clear mechanism of action compared to TCM prescriptions and herbs. However, further research is still needed to determine whether TMC components can fully substitute the therapeutic efficacy of TCM prescriptions. This paper presents a comprehensive analysis of the research advancements made in TCM prescriptions, herbs, and components. The findings of this study can serve as a theoretical basis for researchers who are interested in exploring the potential of TCM for the treatment of colorectal cancer.

N-cadherin又被称为神经钙黏蛋白,属于钙黏蛋白家族,主要存在于人体神经组织、晶状体、横纹肌、心肌等组织细胞,其通过瞬时表达和永久表达,在胚胎发育、突触功能、血管稳定性和骨内稳态等正常生理功能中发挥重要作用.N-cadherin表达异常时,可通过多种途径影响肿瘤侵袭转移过程.近年来,随着对N-cadherin研究的不断深入,其作为肿瘤治疗靶点的潜力日益凸显.该文就N-cadherin的结构功能、在生理病理中的作用及其作为肿瘤治疗靶点等方面作一综述.

Mongolian medicine prescriptions are recognized as promising gastroprotective agents. This study is to explore the effects and mechanisms of Liuwei Anxiao San (LAS) in gastric ulcer (GU). GU rat models were established using acetic acid, followed by treatment with LAS at different doses and/or the JAK2 agonist Coumermycin A1 (CA1). The ulcerous area and inhibition rates were calculated. The mucosal damage and cell apoptosis in gastric tissues were assessed by H&E and TUNEL staining. The activities of SOD, GSH-Px, and CAT, and MDA levels were measured. The levels of pro-inflammatory and anti-inflammatory factors were determined by ELISA. The activation of the JAK2/STAT3 pathway was determined by Western blot. As the results suggested, LAS dose-dependently ameliorated gastric mucosal damage and inhibited oxidative stress and inflammatory response, evidenced by increased activities of SOD, GSH-Px, and CAT, decreased MDA level, increment of anti-inflammatory factors and decrement of pro-inflammatory factors, and inhibited the activation of the JAK2/STAT3 pathway in GU rats. CA1 partly abolished the function of LAS on gastric mucosal injury, oxidative stress, and inflammation in GU rats. In conclusion, LAS protects against gastric mucosal injury in GU rats through inhibition of oxidative stress and inflammation by suppressing the JAK2/STAT3 pathway.

ObjectiveGastric cancer (GC) remains a prevailing threat to life. Baicalein exhibits anti-cancer properties. This study estimated the mechanism of baicalein in GC cell apoptosis by mediating endoplasmic reticulum stress (ERS) through the PI3K/AKT pathway.MethodsAfter treatment with different concentrations of baicalein, GC cell (HGC-27 and AGS) viability was detected by MTT assay. AGS cells more sensitive to baicalein treatment were selected as study subjects. The IC50 of baicalein on AGS cells was determined. Colony formation, cell cycle, and apoptosis were detected using crystal violet staining and flow cytometry. Levels of ERS-related and BTG3/PI3K/AKT pathway-related proteins were determined by Western blot. Intracellular Ca2+ level was measured using Fluo-3 AM fluorescence working solution. GC mouse models were established by subcutaneously injecting AGS cells into the right rib and were intragastrically administrated with baicalein. Tumor volume and weight were recorded. Expression of Ki67 in tumor tissues and positive expression of apoptotic cells were detected by immunohistochemistry and TUNEL staining.ResultsBaicalein inhibited cell proliferation and induced G0/G1 arrest and apoptosis by regulating the cell cycle, and triggered ERS in GC cells. Baicalein impeded the PI3K/AKT pathway by activating BTG3, thereby triggering ERS and inducing apoptosis. BTG3 inhibition reversed baicalein-induced apoptosis and ERS. Baicalein regulated GC cells in a concentration-dependent manner. Moreover, in xenograft mice, baicalein prevented tumor growth, decreased Ki67-positive cells, activated BTG3, and inhibited the PI3K/AKT pathway, thus activating ERS and increasing apoptotic cells.ConclusionBaicalein facilitates GC cell apoptosis by triggering ERS via repression of the PI3K/AKT pathway.

核糖体蛋白(ribosomal protein,RP)是参与构成核糖体所有蛋白质的统称,其在细胞内蛋白质生物合成中发挥重要作用,已经在多个生物中被发现,它在人体的不同器官和组织中均存在表达.

达芬奇机器人具有三维高清视野、操作精准灵活、震颤过滤、远程操控等特点,已在腹部外科中得到广泛应用,尤其结直肠癌的手术治疗方面,与传统手术相比,减少了术中出血量、缩短了住院时间、降低了并发症发生率,更利于术后康复.本文现就达芬奇机器人在结直肠癌治疗中的应用进展作一综述.

A hiatal hernia (HH) is usually associated with gastroesophageal reflux disease (GERD). An HH can increase the incidence of GERD.[1] The coexistence of these diseases increases the difficulty of treatment and can be challenging for endoscopic treatment. Therapeutic methods for small HHs (≤2 cm) combined with refractory GERD have recently been emerging. However, there are still knowledge gaps in the endoscopic treatment of large HHs (≥3 cm) combined with refractory GERD. We developed a new endoscopic method called hiatal hernia-endoscopic submucosal dissection (HH-ESD) and performed the present study to clarify the efficacy and safety of HH-ESD. This clinical trial was approved by the Ethics Committee of the Affiliated People's Hospital of Inner Mongolia Medical University (No. KY201801) and registered at the China Clinical Trial Registry (clinical trial number: ChiCTR2000034032). The inclusion criteria were (1) an age of 18 to 75 years; (2) symptoms of acid regurgitation and heartburn that were not significantly relieved or that relapsed after >2 months of daily proton pump inhibitor (PPI) therapy; (3) diagnosis of a sliding HH (≥3 cm) by gastroscopy, radiography, and esophageal manometry before the procedure; and (4) 24 h pH monitoring results in accordance with a DeMeester score of >30.0.[2] The exclusion criteria were (1) a history of surgery around the gastroesophageal junction (GEJ) that destroyed the normal anatomical structure and (2) any esophageal motility disorders affecting esophageal contractile function. All patients provided informed consent. In total, 14 patients underwent HH-ESD at the Affiliated Hospital of Inner Mongolia Medical University and Affiliated People's Hospital of Inner Mongolia Medical University from December 2018 to December 2019. All operations were performed by one experienced endoscopist (HQ Hu). All patients underwent assessment using the Gastroesophageal Reflux Disease-Health-Related Quality of Life scale, Gastroesophageal Reflux Disease Questionnaire, gastroscopy (Los Angeles classification was used to grade the severity of esophagitis), upper gastrointestinal radiography, 24 h pH monitoring, esophageal manometry, and gastroesophageal radionuclide imaging. All examinations were repeated at the 6-month post-operative follow-up visit. The procedure was performed as follows [Figure 1]. When the patient was awake, routine gastroscopy was performed to observe any esophageal mucosal lesions, the looseness of the cardia, and the size of the HH. The HH removal range was then marked by electrocoagulation. After induction of general anesthesia, methylene blue was submucosally injected 0.5 cm outside the mark to elevate the lesion away from the muscle layer; this injection was repeated three to five times. A circumferential incision was then performed using a Golden knife from Micro-Tech (Nanjing) Co., Ltd (Jiangsu, China). Next, during submucosal dissection, 1/2 to 2/3 of the mucosas of the circumference of the GEJ and hernia sac were removed to prevent post-operative stenosis. The actual extent of resection depended on the size of the hernia sac and the severity of the mucosal lesions. The wound was observed for submucosal hemorrhage and deep damage, and exposed blood vessels on the wound were treated with argon plasma coagulation or hemostatic forceps. Finally, the specimen was collected, its length and width were measured, its resection area was calculated, and it was sent out for pathologic examination. The operative procedure is shown in the Supplementary Video [https://links.lww.com/CM9/A817].Figure 1: HH-ESD procedure and post-operative follow-up. (A) Mucosal erosion at the GEJ. (B) The endoscope was flipped to observe a large sliding HH. (C) Electrocoagulation mark in forward view. (D) Electrocoagulation mark in retroflexed view. (E) Submucosal dissection in forward view. (F) Submucosal peeling in retroflexed view. (G) Six months after the operation, the scar had healed well and the surface mucosa was smooth. (H) The cardia had tightened, the hernia sac had shrunk, and the anti-regurgitation valve had formed 6 months after the operation. GEJ: Gastroesophageal junction; HH: Hiatal hernia; HH-ESD: Hiatal hernia (HH)-endoscopic submucosal dissection.After HH-ESD, PPIs and mucosal protective agents were taken orally from day 3 to week 4 postoperatively. Statistical analysis was performed using SPSS 22.0 (IBM Corp, Armonk, NY, USA). The Wilcoxon signed-rank test was used for evaluation of continuous variables. A P value of <0.05 was considered statistically significant. All 14 patients successfully underwent HH-ESD. Their baseline characteristics are summarized in Supplementary Table 1 [https://links.lww.com/CM9/A816]. Six months after HH-ESD, all relevant evaluation indices were significantly improved with the exception of the gastroesophageal reflux index (GERI) [Supplementary Table 2, https://links.lww.com/CM9/A816]. The GERI decreased in 4/5 of the patients, although the decrease was not statistically significant; this was considered to be related to the small sample size. Gastroscopy showed that the severity of esophagitis improved in all 14 patients (100%), and Los Angeles grade A/B/C/D was present in 1/6/7/0 patients before treatment and in 6/0/2/0 patients after treatment; the remaining six patients showed no manifestations of esophagitis. The gastroscopy results six months after HH-ESD are shown in Figure 1G and H. Radiography showed smooth passage of barium in all patients and no stenosis or obstruction was observed in any of the patients. No intra-operative adverse events occurred. After HH- ESD, delayed hemorrhage occurred in one patient (7.1%) and dysphagia occurred in seven patients (50.0%); in six of these seven patients, the dysphagia was spontaneously resolved without any treatment within 3 months. Twelve patients (85.7%) stopped using PPIs completely 6 months later. Dysphagia is a major complication after treatment of HHs. Fortunately, none of the patients required surgery or dilatation. The four main causes of dysphagia can be summarized as follows: (1) Development of dysphagia may be related to the normal healing of local tissues. (2) Dysphagia may also be related to the scope of resection. In our study, “crescentic resection” was performed in 13 patients; that is, 1/2 to 2/3 of the mucosa of the circumference of the GEJ and hernia sac were removed. All patients who underwent crescentic resection showed good therapeutic effects, and six patients had mild dysphagia that improved spontaneously. Only one patient who had severe reflux lesions and a sliding HH with a paraesophageal hernia was treated by circumferential resection. The resection area was 30 cm2. The patient developed severe dysphagia that lasted for >6 months post-operatively. Therefore, we consider that circumferential resection may significantly increase the incidence of stenosis and that the presence of a paraesophageal hernia may greatly weaken the therapeutic effect of HH-ESD. (3) Dysphagia may also be related to reflux stimulation. After treatment, patients should take oral PPIs for 4 weeks, and are advised to maintain good living habits. (4) Finally, we cannot rule out the presence of differences in individual responses to HH-ESD. The contractile function of the esophagus and the constitution of scars will also affect the therapeutic outcome. Endoscopic treatment of GERD is being constantly updated, and anti-reflux mucosectomy (ARMS) has attracted our attention.[3–5] The mechanism of both HH- ESD and ARMS is the same. However, the two procedures are different in three respects: (1) The indications are different. ARMS is used to treat refractory GERD with a small HH (≤2 cm), whereas HH-ESD is used to treat a large HH (≥3 cm) in patients with refractory GERD. (2) The excision techniques are different. ARMS mostly uses endoscopic mucosal resection, whereas HH-ESD uses endoscopic submucosal dissection. (3) The excision area is different. The excision areas vary during ARMS; that is, clinicians may remove 1/2 to 4/5 of the mucosa of the circumference of the GEJ. HH-ESD involves removal of not only the mucosa around the GEJ but also part of the mucosa of the hernia sac; that is, 1/2 to 2/3 of the mucosa of the circumference of the GEJ and hernia sac are removed. The main limitation of this technique is that an experienced endoscopist is needed for performance of all procedures; thus, the learning curve may be a potential limiting factor. Compared with endoscopic mucosal resection and radiofrequency ablation, HH-ESD is difficult and time-consuming. In this study, we conducted a preliminary exploration of HH-ESD. Verification of the therapeutic effect of HH- ESD still requires further data and long-term follow-up. In conclusion, HH-ESD is a possible endoscopic treatment for large HHs with refractory GERD. It is safe and feasible with promising short-term results. Funding This study was supported by the China's Inner Mongolia Autonomous Region Applied Technology Research and Development Funding Plan (No. 201802160). Conflicts of interest None.

BACKGROUND:Colorectal cancer (CRC) is one of the most commonly diagnosed human malignancies. Ribosomal protein L31 (RPL31, aka eL31) is a component of the 60S large ribosomal subunit, and its expression pattern and functional role in CRC have not been reported.METHODS:Herein, we identified that eL31 protein level was dramatically increased in CRC tissues through using IHC analysis. More notably, elevated eL31 was associated with larger tumor size and shorter overall survival. Besides, we evaluated the effects of eL31 depletion on CRC cell phenotypes in vitro.RESULTS:The data indicated that eL31 knockdown restricted CRC cell proliferation, migration and colony formation whilst enhancing cell apoptosis. Importantly, eL31 was also essential for CRC tumor growth in vivo, as demonstrated by impaired tumor growth markers and reduced Ki67 levels in xenografts from eL31-depleted cells. In addition, our evidence indicated that DEP domain containing 1 (DEPDC1) was a potential downstream target of eL31 in regulating CRC. Consistently, DEPDC1 depletion restrained CRC cell proliferation and migration, as well as facilitated cell apoptosis. More interestingly, DEPDC1 depletion could reverse the promotion effects of eL31 elevation on CRC cells.CONCLUSIONS:Identification of eL31's function in CRC may pave the way for future development of more specific and more effective targeted therapy strategies against CRC.

Gastric cancer (GC) is one of the most prevalent malignancies of the digestive tract. Ginsenoside Rh1 was reported to exert effects on GC. The current study set out to explore the mechanism underlying Ginsenoside Rh1 effects on GC. With oxaliplatin (OXA) serving as the positive control, human GC cells AGS were treated with 0, 10, 25, 50, 74, or 100 μM of ginsenoside Rh1 for 48 h. Proliferation, migration, invasion, and apoptosis were subsequently assessed by means of MTT, scratch test, Transwell, and TUNEL, respectively. AGS cells were further jointly treated with Rh1 and the TGF-β/Smad pathway activator Kartogenin, followed by detection of TGF-β/Smad pathway effects on AGS biological behaviours. Moreover, TGF-β/Smad pathway activation was detected with a Western blot assay. Furthermore, xenograft tumour models were established and tumour growth was recorded. Ki-67 expression patterns and apoptosis were detected with immunohistochemistry and TUNEL, respectively. In vitro, Ginsenoside Rh1 repressed AGS cell proliferation, migration, and invasion, and further promoted apoptosis, with a concentration of 50 μM Rh1 exerting the equivalent effects as OXA. In vivo, Ginsenoside Rh1 inhibited GC proliferation and induced tumour cell apoptosis. Mechanistically, Ginsenoside Rh1 reduced TGF-β1 and TGF-β2 levels and Smad2 and Smad3 phosphorylation levels. Collectively, our findings highlighted that ginsenoside Rh1 inhibited GC cell growth and tumour growth in xenograft tumour models via inhibition of the TGF-β/Smad pathway.