Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Background and Aims:Studies have shown that the long non-coding RNA(lncRNA)FGD5-AS1 functions as an oncogene in gastric cancer(GC).Our previous bioinformatics analysis revealed potential binding sites between FGD5-AS1 and microRNA-142-3p(miR-142-3p),as well as between miR-142-3p and pyruvate dehydrogenase kinase 1(PDK1).Therefore,this study aimed to investigate the expression and functional role of the FGD5-AS1/miR-142-3p/PDK1 axis in GC cells.Methods:Dual-luciferase reporter assays were used to verify the targeting relationships between FGD5-AS1 and miR-142-3p,and between miR-142-3p and PDK1.qRT-PCR was conducted to measure the expression levels of FGD5-AS1,miR-142-3p,and PDK1 in GC tissues.A knockdown model of FGD5-AS1(sh-FGD5-AS1)and an miR-142-3p inhibitor were constructed and transfected,alone or in combination,into BGC823 GC cells.Cellular behaviors,including proliferation(CCK8,EdU),apoptosis(flow cytometry),migration,and invasion(Transwell assays),were assessed,along with related protein expression(Western blot).A subcutaneous xenograft model in nude mice was used to evaluate the effect of FGD5-AS1 on tumor growth in vivo.Results:The dual-luciferase assays demonstrated that miR-142-3p mimics significantly reduced the luciferase activity of wild-type(WT)FGD5-AS1 and PDK1 reporters(both P<0.05),but had no effect on mutant(MUT)reporters,confirming a direct binding relationship.Knockdown of FGD5-AS1 led to upregulation of miR-142-3p and downregulation of PDK1 in GC cells,with reduced proliferation,migration,and invasion,and enhanced apoptosis(all P<0.05);these effects were reversed by the miR-142-3p inhibitor.In vivo,FGD5-AS1 knockdown significantly inhibited tumor growth in nude mice and decreased Ki-67 and PDK1 expression in tumor tissues(all P<0.05).Conclusion:FGD5-AS1 may act as a ceRNA that sponges miR-142-3p,thereby relieving its suppression on PDK1,and promoting GC cell proliferation and invasion as well as tumor progression.The FGD5-AS1/miR-142-3p/PDK1 axis plays a critical role in the development of GC and may serve as a potential therapeutic target.

Objective:To develop and assess a deep learning-based model for automatic segmentation of organs at risk (OARs) in postoperative brachytherapy for endometrial carcinoma (EC).Methods:A retrospective study was conducted on the computed tomography (CT) images of 108 EC patients who received high-dose-rate (HDR) 192Ir intracavitary vaginal-cuff brachytherapy (VCB) at the Peking University Third Hospital from November 2021 to October 2022. Then, the rectum, colon, small intestine, and bladder in these images were manually segmented. These patients were randomly divided into two groups using a random number table: 90 cases for training the 3D no-new-U-Net (nnU-Net) segmentation model and 18 cases for model testing. The precision and clinical applicability of the automatic segmentation model were assessed using geometric indexes including Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean surface distance (MSD), as well as dose-volume parameters (DVPs) including the minimum dose to 0.1, 1.0, and 2.0 cm 3 of OARs that received the highest irradiation doses ( D0.1 cm 3, D1.0 cm 3, and D2.0 cm 3). Results:The 3D nnU-Net model yielded mean DSC values of 0.90, 0.85, 0.88, and 0.95, respectively for the segmentations of the rectum, colon, small bowel, and bladder, all of which were better than those of the 3D U-Net and V-Net models. The differences among the three models were statistically significant ( F = 21.78, 24.33, 36.00, 20.11, P < 0.001). The 3D nnU-Net exhibited statistically significant differences in HD values for the colon, small intestine, and bladder segmentations among the three method ( F = 17.33, 24.11, 6.33, P < 0.05). The 3D nnU-Net model yielded lower MSD values for the segmentations of all organs compared to the control model, with statistically significant differences ( F = 29.78, 27.11, 27.11, 14.78, P < 0.001). No statistically significant difference was found in all DVPs between the 3D nnU-Net model-based and manual segmentations ( P > 0.05). Bland-Altman analysis demonstrated great consistency between the 3D nnU-Net and manual segmentations. Conclusions:The 3D nnU-Net-based model exhibits high geometric accuracy and dosimetric consistency with manual segmentation of OARs in brachytherapy, holding potential to improve clinical efficiency.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

BACKGROUND:The occurrence of neuronal axonal injury can result in neurological dysfunction,and the facilitation of axonal elongation is anticipated to play a pivotal role in the treatment of diseases affecting the nervous system.OBJECTIVE:To investigate whether ectomesenchymal stem cells-derived extracellular vesicles can promote neuronal axonal elongation.METHODS:(1)Ectomesenchymal stem cells were obtained from nasal mucosa using the tissue adherence method,and the specific markers of were identified through immunofluorescence.Ectomesenchymal stem cells-derived extracellular vesicles were acquired via ultracentrifugation and identified.(2)Ectomesenchymal stem cells-derived extracellular vesicles(0,0.5,1.0,1.5 mg/mL)were incubated with PC12 cells for 72 hours.The cytotoxicity and proliferation of ectomesenchymal stem cells-derived extracellular vesicles on PC12 cells were assessed using the CCK-8 assay.(3)Ectomesenchymal stem cells-derived extracellular vesicles(1.0 mg/mL)were incubated with PC12 cells or neurons for 72 hours.The changes in axon length were observed using microscopic analysis.The expression levels of axon-related markers β3-tubulin(early stage),growth associated protein 43(middle stage),and neurofilament 200(mature stage)were analyzed through real-time fluorescence quantitative PCR and Western blotting.These investigations aimed to explore the potential of ectomesenchymal stem cells-derived extracellular vesicles in promoting neurite elongation within PC12 cells or neurons.RESULTS AND CONCLUSION:(1)The majority of the acquired ectomesenchymal stem cells exhibited a spindle-shaped morphology,while a minority displayed irregular shapes,and demonstrated high expression levels of mesenchymal stem cell-specific markers Nestin,CD44,and Vimentin.The obtained ectomesenchymal stem cells-derived extracellular vesicles fulfilled the biological criteria for extracellular vesicles.(2)Within the detected protein concentration range of 0.5 to 1.5 mg/mL,the proliferation of PC12 cells was promoted by ectomesenchymal stem cells-derived extracellular vesicles,and this effect was further enhanced with increasing concentrations.(3)Ectomesenchymal stem cells-derived extracellular vesicles increased the length of axons in PC12 cells and neurons and the expression of axon-related markers β3-tubulin,growth associated protein 43,and neurofilament 200.Above findings suggest that ectomesenchymal stem cells-derived extracellular vesicles have the potential to enhance neuronal axonal elongation.

In 2015,the International Ascites Club proposed a new definition of hepatorenal syndrome-acute kidney injury based on the progression of hepatorenal syndrome,and studies are still being conducted to explore the exact pathogenesis of hepatorenal syndrome-acute kidney injury.Intestinal barrier plays an important bridging role in liver-kidney connection,and intestinal flora disturbance,bacterial translocation,and endotoxins entering the blood cause damage to the kidneys by releasing proinflammatory cytokines and activating immune-related cells.The entrance of bile acid into the circulation system also directly or indirectly lead to the development and progression of hepatorenal syndrome-acute kidney injury.This article reviews the crosstalk mechanism of hepatorenal syndrome-acute kidney injury from the perspective of the intestinal barrier and further clarifies the key role of the liver-gut-kidney axis in the pathogenesis of this disease,in order to provide new treatment ideas.

Robot-assisted surgery with its advantages such as three-dimensional high-definition vision, dexterous robotic arms, and tremor filtration, is increasingly being applied to complex radical gastrectomy. However, the role of the surgical assistant remains crucial during the procedure. The assistant is responsible for tasks outside the console, including adjusting robotic arms, changing instruments, exposing the surgical field, and addressing unexpected situations. The technical proficiency of the assistant and their collaboration efficiency with the primary surgeon directly impact the smoothness of surgery and patients' outcomes. With the expansion of robot-assisted surgical indications, the establishment of a standardized training system and the optimization of team collaboration models have become urgent challenges to address. This article draws on the author's practical experience as an assistant in robot-assisted gastric cancer surgeries, conducting an in-depth analysis of the responsibilities and operational skills of surgical assistants in robot-assisted procedures. The aim is to develop a relatively comprehensive set of operational guidelines for surgical assistants in robot-assisted radical gastrectomy, providing valuable references for enhancing the overall efficiency of surgical teams and improving surgical outcomes.

Background and Aims:Studies have shown that the long non-coding RNA(lncRNA)FGD5-AS1 functions as an oncogene in gastric cancer(GC).Our previous bioinformatics analysis revealed potential binding sites between FGD5-AS1 and microRNA-142-3p(miR-142-3p),as well as between miR-142-3p and pyruvate dehydrogenase kinase 1(PDK1).Therefore,this study aimed to investigate the expression and functional role of the FGD5-AS1/miR-142-3p/PDK1 axis in GC cells.Methods:Dual-luciferase reporter assays were used to verify the targeting relationships between FGD5-AS1 and miR-142-3p,and between miR-142-3p and PDK1.qRT-PCR was conducted to measure the expression levels of FGD5-AS1,miR-142-3p,and PDK1 in GC tissues.A knockdown model of FGD5-AS1(sh-FGD5-AS1)and an miR-142-3p inhibitor were constructed and transfected,alone or in combination,into BGC823 GC cells.Cellular behaviors,including proliferation(CCK8,EdU),apoptosis(flow cytometry),migration,and invasion(Transwell assays),were assessed,along with related protein expression(Western blot).A subcutaneous xenograft model in nude mice was used to evaluate the effect of FGD5-AS1 on tumor growth in vivo.Results:The dual-luciferase assays demonstrated that miR-142-3p mimics significantly reduced the luciferase activity of wild-type(WT)FGD5-AS1 and PDK1 reporters(both P<0.05),but had no effect on mutant(MUT)reporters,confirming a direct binding relationship.Knockdown of FGD5-AS1 led to upregulation of miR-142-3p and downregulation of PDK1 in GC cells,with reduced proliferation,migration,and invasion,and enhanced apoptosis(all P<0.05);these effects were reversed by the miR-142-3p inhibitor.In vivo,FGD5-AS1 knockdown significantly inhibited tumor growth in nude mice and decreased Ki-67 and PDK1 expression in tumor tissues(all P<0.05).Conclusion:FGD5-AS1 may act as a ceRNA that sponges miR-142-3p,thereby relieving its suppression on PDK1,and promoting GC cell proliferation and invasion as well as tumor progression.The FGD5-AS1/miR-142-3p/PDK1 axis plays a critical role in the development of GC and may serve as a potential therapeutic target.

Objective:To develop and assess a deep learning-based model for automatic segmentation of organs at risk (OARs) in postoperative brachytherapy for endometrial carcinoma (EC).Methods:A retrospective study was conducted on the computed tomography (CT) images of 108 EC patients who received high-dose-rate (HDR) 192Ir intracavitary vaginal-cuff brachytherapy (VCB) at the Peking University Third Hospital from November 2021 to October 2022. Then, the rectum, colon, small intestine, and bladder in these images were manually segmented. These patients were randomly divided into two groups using a random number table: 90 cases for training the 3D no-new-U-Net (nnU-Net) segmentation model and 18 cases for model testing. The precision and clinical applicability of the automatic segmentation model were assessed using geometric indexes including Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean surface distance (MSD), as well as dose-volume parameters (DVPs) including the minimum dose to 0.1, 1.0, and 2.0 cm 3 of OARs that received the highest irradiation doses ( D0.1 cm 3, D1.0 cm 3, and D2.0 cm 3). Results:The 3D nnU-Net model yielded mean DSC values of 0.90, 0.85, 0.88, and 0.95, respectively for the segmentations of the rectum, colon, small bowel, and bladder, all of which were better than those of the 3D U-Net and V-Net models. The differences among the three models were statistically significant ( F = 21.78, 24.33, 36.00, 20.11, P < 0.001). The 3D nnU-Net exhibited statistically significant differences in HD values for the colon, small intestine, and bladder segmentations among the three method ( F = 17.33, 24.11, 6.33, P < 0.05). The 3D nnU-Net model yielded lower MSD values for the segmentations of all organs compared to the control model, with statistically significant differences ( F = 29.78, 27.11, 27.11, 14.78, P < 0.001). No statistically significant difference was found in all DVPs between the 3D nnU-Net model-based and manual segmentations ( P > 0.05). Bland-Altman analysis demonstrated great consistency between the 3D nnU-Net and manual segmentations. Conclusions:The 3D nnU-Net-based model exhibits high geometric accuracy and dosimetric consistency with manual segmentation of OARs in brachytherapy, holding potential to improve clinical efficiency.