Volume 13, Issue 6

The mode of organ resection and reconstruction that has been used to treat digestive tract tumors (DTTs) can cure the disease. However, it involves the surgical resection of critical structures (such as the cardia, pylorus, and anus) and gastrointestinal reconstruction, which alter the physiological anatomy of the digestive system. These changes often lead to numerous postoperative complications and severely affect the patient’s quality of life ( e.g ., refractory gastroesophageal reflux following proximal gastrectomy, dumping syndrome after subtotal gastrectomy, loss of anal function after low rectal surgery). For the defect of this mode, professor Linghu Enqiang proposed the new mode that was “curing the disease and restoring normal function” in 2016, which was named as this new mode: Super Minimally Invasive Surgery (SMIS). To accomplish various types of SMIS, four operative channels were developed: the natural cavity channel, the tunnel channel, the puncture channel, and the multi-cavity channel. SMIS, with its advantages of minimal trauma and organ function preservation, has been recognized by authoritative domestic and international organizations and has developed rapidly. Based on its clinical value and the need for wider application, there is an urgent need to establish standardized guidelines to guide practice. This guideline was developed by leading organizations such as the SMIS committee of World Endoscopy Organization (WEO) and Chinese Society of Digestive Endoscopy (CSDE), in collaboration with multidisciplinary experts from gastroenterology, general surgery, and pathology. Systematic searches were conducted in nine major databases, including PubMed, Embase, and China National Knowledge Infrastructure (CNKI), for both Chinese and English literature published before 2025. Evidence from randomized controlled trials (RCTs), observational studies, and case series was included, with the quality of evidence and recommendation strength evaluated using the GRADE system (high-level evidence:RCTs; low-level evidence: observational studies). The recommendations were refined through several rounds of expert discussions and voting, and were reported following the AGREE II and RIGHT reporting standards. This guideline has been registered on the PREPARE (Practice Guideline REgistration for transPAREncy; registration number: PREPARE-2024CN1183). This guideline addresses 15 issues related to SMIS treatment for esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), their corresponding precancerous lesions, and precancerous lesions of the duodenal papilla. It provides corresponding recommendations in three main areas: (1) Definitions and principles: SMIS should meet ten core criteria, including organ preservation, complete resection (R0), and sterile procedures. It also standardizes naming conventions ( e.g ., “Super minimally invasive non-full-thickness resection of lower esophageal squamous carcinoma via the oral cavity”). (2) Surgical recommendations: EC: For early and precancerous lesions, SMIS of non-full-thickness resection (non-FTR) is preferred. For circumferential involvement ≥ 1/2, SMIS via tunnel channel for non-FTR is recommended. If the wound circumference is ≥ 75%, the use of corticosteroids or stents to prevent stenosis is advised. GC: For T1a-T1b stage and precancerous lesions, SMIS non-FTR or full-thickness resection (FTR) is preferred, with individualized plans based on the risk of lymph node metastasis (LNM). CRC: SMIS of non-FTR or FTR is recommended as the first-line treatment for T1a-T1b stage and precancerous lesions. For locally advanced rectal cancer (LARC) that achieves clinical remission after neoadjuvant therapy, SMIS of FTR can be considered to assess pathological remission. Duodenal papilla precancerous lesions: SMIS resection via the oral cavity is preferred. Postoperatively, whether to add pancreaticoduodenectomy and follow-up strategies should be determined based on pathology. (3) Postoperative management: A SMIS treatment cure evaluation system for early gastric cancer (EGC) was established, divided into SMIS-Cure A(cured), SMIS-Cure B (clinically cured), and SMIS-Cure C (surgical reassessment), which guides follow-up. For CRC or precancerous lesions, R0 resection is the standard for cure, and follow-up plans are developed according to risk stratification. This guideline systematically integrates the evidence from SMIS in the treatment of DTTs with expert consensus, establishing a standardized pathway centered on organ function preservation. It shifts the treatment model from “cure first” to “cure-function balance”. Its application is expected to reduce overtreatment, improve the patient’s quality of life, and provide a framework for future technological iterations and the expansion of indications. It should be continuously optimized with multicenter clinical data and long-term follow-up results to achieve more precise, individualized treatment.

Breast cancer accounts for the highest proportion of cancer cases among women worldwide. Despite remarkable advances in cancer diagnosis and treatment, novel precision therapy strategies for various subtypes of breast cancer are urgently needed. Ferroptosis, which is different from programmed cell death, such as apoptosis, necrosis, and pyroptosis, is considered an alternative method for cancer therapy. A comprehensive understanding of ferroptosis in breast cancer is lacking, including, but not limited to, ferroptotic inducers (small molecule drugs and natural products) and the interaction between ferroptosis and immunotherapy. Induction of ferroptosis is recognized as a novel and promising strategy for cancer pharmacotherapy, and a comprehensive understanding of the role of ferroptosis in breast cancer could help provide alternative treatment strategies for breast cancer. Furthermore, we highlight the signaling crosstalk bridging ferroptosis with the immune microenvironment and the feasibility of targeting their potential regulators ( e.g ., STAT3, AR, EZH2, and PRMT5) using small molecules to simultaneously achieve the induction of ferroptosis and inhibition of immune escape.

Background and objectives Catecholamine-dependent acute obstructive suppurative cholangitis (CD-AOSC) is a severe form of cholangitis characterized by refractory hypotension. This study aimed to investigate its underlying pathogenic mechanisms. Methods We conducted a retrospective case-control study involving 345 patients with biliary infections treated at Tongji Hospital, Tongji University, between 2012 and 2022. Patients were divided into three groups: chronic cholecystitis (CC; negative control), acute obstructive suppurative cholangitis (AOSC; positive control), and CD-AOSC (case group). Clinical and laboratory data were analyzed. Endotoxin levels in subcutaneous adipose tissue were measured, and transcriptomic analysis was performed to explore potential mechanisms. A rat model of cholangitis was used to validate findings related to hypotension in CD-AOSC. Results Patients with CD-AOSC exhibited slower endotoxin clearance from adipose tissue (1 st week vs . 2 nd week: 72.7 ± 4.0 EU/g vs . 23.3 ± 3.2 EU/g) and milder inflammation (Immune cell count: 665.4 ± 179.1, Immunodeconv analysis: 0.3 ± 0.1) compared to AOSC patients (1 st week vs . 2 nd week: 9.7 ± 2.6 EU/g vs . 2.6 ± 0.7 EU/g, Immune cell count: 1344.0 ± 599.3, Immunodeconv analysis: 0.6 ± 0.1). This slower clearance of endotoxin allowed adipose tissue to function as an endotoxin reservoir. Persistent endotoxin release resulted in prolonged activation of the interleukin-18 (IL-18)/IL-18 receptor accesary protein (IL-18RAP) pathway, thereby sustaining inflammation and contributing to extended hypotension. The rat model confirmed the role of the interleukin-1β (IL-1β) inhibitor in decelerating endotoxin release and maintaining activation of the IL-18/IL-18RAP/interferon-γ (IFN-γ) pathway. Conclusions Persistent hypotension in CD-AOSC appears to result from sustained activation of the IL-18/IL-18RAP pathway, driven by prolonged endotoxin release from adipose tissue. These findings highlight the potential of "Hours Exchanged Against (severity) Loss (HEAL)" strategy, in which early modulation of endotoxin release from adipose tissue by IL-1β inhibition during the initial phase of sepsis in cholangitis may improve patient survival.

Background Treatment for varicose veins has transitioned from invasive surgical interventions to minimally invasive, targeted, and personalized procedures. Limited data exist on the longterm outcomes of glue ablation (GA) as a new minimally invasive treatment. This study was conducted to evaluate the long-term safety and efficacy of GA for varicose veins. Methods Data were collected in a multicenter, prospective registry. Patients were randomly allocated to the experimental group (GA) or the control group (radiofrequency ablation [RFA]). The follow-up assessments were conducted at 7 days, 30 days, 3 months, 6 months, and 12 months after surgery. The non-inferiority of GA to RFA was assessed based on the primary outcome of the rate of complete great saphenous vein (GSV) closure at 3 months. Additional outcomes included the rate of complete GSV closure at 12 months, procedural duration, pain score, ecchymosis, and preoperative and postoperative Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire Score. Results Overall, 177 patients were treated (experimental group, n = 89; control group, n = 88). The mean age was 56.25 ± 12.23 years, and 61.58% were female. The mean target vessel diameter was 7.94 ± 2.09 mm, with a maximum diameter of 12 mm. The GA group did not experience any device-related adverse complications. Tumescent fluid was utilized in the RFA group but not in the GA group. GA was statistically non-inferior to RFA (lower boundary of the 95% confidence interval [CI] for the absolute difference in the mean rate of 3-month complete GSV closure did not reach the non-inferiority margin of -10%) (absolute difference -0.03%; one-sided 95% CI -3.19%; P < 0.001). The GSV closure rate at 12 months was higher in the GA group than in the RFA group (absolute difference 7.04%; one-sided 95% CI 1.09%). The GA group exhibited a significantly longer surgical duration than the RFA group ( P = 0.031). The comparisons of other secondary endpoints between the groups did not yield any significant findings. Conclusion The 3-month rate of complete GSV closure with GA was non-inferior to that with RFA in the treatment of varicosity, but the surgical duration was longer. The efficacy of GA therapy still requires validation through large-scale clinical trials with long-term follow-up periods.

Background and Objectives The relationship between falls and dementia risk remains unclear. This study aims to investigate this association and assess the impact of genetic risk on this relationship. Methods We included 265,416, 5,506, and 948 participants from the United Kingdom (UK) Biobank, China Health and Retirement Longitudinal Study (CHARLS), and Xuanwu cognitive cohort. A Cox model and logistic regression analysis were used to estimate the relationship between falls and dementia risk. Results Falls showed significant associations with an elevated risk of dementia in both UK Biobank (single falls: Hazard Ratio [HR] 1.22, 95% Confidence Interval [CI]: 1.13-1.31; multiple falls: HR 1.73, 95% CI: 1.58-1.89), CHARLS cohorts (falls: HR 1.29, 95% CI: 1.11-1.50) and Xuanwu cognitive cohort (single falls: OR 1.72, 95% CI: 1.18-2.50; multiple falls: OR 1.89, 95% CI: 1.17-3.02). In addition, the results showed that falls were associated with cognitive decline during follow-up. Those who experienced single falls demonstrated reduced whole-brain gray matter volume (β = −1276.031, P = 0.029) and parahippocampal gyrus volume (β left = −22.410, P = 0.011; β right = −31.570, P = 0.001), whereas those experienced multiple falls, in addition to these findings, demonstrated increased deep white matter hyperintensities (β = 123.146, P = 0.004) and decreased gray matter volume in the hippocampus (β left = −18.440, P = 0.002; β right = −20.599, P = 0.001) and parahippocampal gyrus volume (β left = −48.805, P < 0.001; β right = −58.263, P < 0.001). Furthermore, falls and polygenic risk scores (PRSs) showed a significant interaction ( P = 0.001), with higher dementia risk observed in individuals with multiple falls and high genetic risk. Conclusions Falls are an early sign of dementia risk, and genetic susceptibility facilitates this association. Falls indicate potential atrophy in cognition-related brain regions. Falls are a simple and easily observable sign for dementia screening.

Background and objectives Non-erosive reflux disease (NERD), a common gastrointestinal disorder, often responds poorly to acid suppressants. This study evaluated the efficacy and safety of Huoxue Tongjiang Decoction (HTD), a patented traditional Chinese medicine (TCM), for NERD with Qi stagnation-blood stasis syndrome, integrating network pharmacology and clinical trials. Methods Network pharmacology identified HTD's active components and targets using TCMSP and GeneCards databases. A "drug-component-target" network was constructed, followed by protein interaction analysis, Gene body analysis (GO), and KEGG pathway enrichment via DAVID. A randomized, double-blind, placebo-controlled trial enrolled 64 NERD patients with Qi stagnation-blood stasis syndrome, randomized to HTD ( n = 32) or placebo ( n = 32) for 4 weeks, with 2-week follow-up. Outcomes included reflux/heartburn severity (Visual Analog Scale [VAS], gastroesophageal reflux disease questionnaire [GERD-Q]), TCM syndrome scores, SF-36 quality-of-life, HAD scores, and recurrence rates. Results Network analysis revealed 20 core HTD components ( e.g ., quercetin, luteolin, baicalin) and 11 key targets (TNF, IL6, TP53), primarily modulating HIF-1 and TNF signaling pathways. Clinically, 30 HTD and 31 placebo patients completed the study. After 2/4 weeks and follow-up, HTD showed significantly higher overall symptom remission (43.3%, 73.3%, 73.3%) versus placebo (16.1% at all timepoints; P < 0.05). Reflux response rates for HTD were 30.0%, 66.7%, 66.7% vs . 12.9% (placebo; P < 0.0001). Heartburn response rates in HTD were 43.3%, 63.3%, 76.7% vs . 16.1% ( P < 0.05). VAS reflux scores decreased from 3.75 ± 1.599 to 1.98 ± 1.292 (HTD) vs . minimal changes in placebo; heartburn scores improved similarly (3.33 ± 1.724 to 1.81 ± 1.471; P < 0.05 post-2 weeks). GERD-Q scores were lower in HTD (7.9 ± 2.29, 6.2 ± 2.07, 6.8 ± 2.40) . placebo (9.4 ± 2.83, 8.9 ± 2.55, 8.9 ± 2.59; P < 0.05). TCM syndrome improvement rates in HTD were 56.7%, 86.7%, 76.7% vs . 16.1%, 25.8%, 41.9% ( P < 0.05). SF-36 physical pain, energy, and mental health scores improved in HTD ( P < 0.05). Recurrence rates were 27.3% (HTD) vs . 40.0% (placebo; P < 0.05). No adverse events occurred. Conclusions HTD significantly alleviates reflux, heartburn, and retrosternal pain in NERD, improves quality of life, reduces recurrence, and demonstrates duration-dependent efficacy. Its anti-inflammatory mechanisms may involve TNF and HIF-1 pathways, with no safety concerns observed.

Background and objectives Recent molecular landscape studies characterizing lung cancer mostly utilize single tumor regions, ignoring tumor heterogeneity and evolutionary patterns. To address this issue, the TRAcking NSCLC Evolution through therapy (TRACERx) Consortium established a multiregion sampling of Western lung cancer to investigate its longitudinal evolutionary dynamics. Due to ancestral differences, there are still major gaps in understanding oriental lung cancer. Methods We have established a prospective cohort of patients with non-small cell lung cancer (NSCLC) named Chinese lung cancer evolution and microenvironment tracking under therapy (CLEVER) study. Discussion By acquiring comprehensive genetic variation data and clonal events from multiple regions of the tumor, we aim to decipher the molecular evolution code of Chinese lung cancer. The analysis of cell composition and spatial structure further characterizes the remodeling effects of tumor evolution and neoadjuvant therapy on the tumor microenvironment, helping to identify important markers that influence treatment effectiveness and recurrence. By monitoring mutations using a personalized minimal residual disease (MRD) panel from tumors at baseline, we can trace evolutionary significance and clonality, aiding in therapy decisionmaking. The CLEVER study significantly contributes to the development of personalized treatment strategies for lung cancer patients, enhancing outcomes and tailoring interventions to individual patient profiles.