Colorectal cancer(CRC),a common malignant tumor of the digestive system,poses a significant threat to patients'quality of life and prognosis.In recent years,immune checkpoint inhibitor(ICI)therapy has brought breakthroughs for patients with deficient mismatch re-pair(dMMR)or microsatellite instability-high(MSI-H)types of CRC.However,the efficacy of ICI therapy in patients with microsatellite stabil-ity(MSS)CRC,who account for more than 85%of all CRCs,is significantly limited,which is a clinical dilemma that highlights the importance of in-depth investigation of immunotherapy resistance mechanisms.Existing studies have demonstrated that the microenvironment of MSS-type CRC is characterized by unique immunosuppression,including multidimensional factors,such as defective antigen presentation,infiltra-tion of suppressive immune cells,and dysregulation of the cytokine network.These factors collectively constitute a response barrier to im-munotherapy.This review systematically analyzes the key molecular mechanisms of immunoresistance in MSS-type CRC,focusing on the im-munosuppressive characteristics of the tumor microenvironment,epigenetic regulatory abnormalities,immune-metabolic reprogramming,gut microbiota imbalance,and other core aspects.The study aims to provide a theoretical basis for breaking through the immunothera-peutic bottleneck of MSS-type intestinal cancer at the mechanistic level and pointing to the potential direction of research on combined therapeutic strategies.

Objective:To evaluate the impact of surgical margin status and pathological subtypes on the prognosis of patients with adenoid cystic carcinoma of the head and neck (ACCHN) who underwent postoperative radiotherapy.Methods:A retrospective analysis was conducted on 309 patients with initially treated, non-metastatic ACCHN who completed postoperative radiotherapy at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. All patients underwent curative (non-palliative) surgery followed by postoperative radiotherapy, with a median dose of 66 Gy (range: 54-70 Gy). The Kaplan-Meier method was used to compare 5-year local recurrence-free survival (LRFS) between R0 (negative margin) and non-R0 resections in patients with initially resectable (T 1-T 4a stage) and initially unresectable (T 4b stage) disease. Univariate and multivariate Cox proportional hazards models were employed to analyze risk factors for local recurrence, with a focus on surgical margin status and pathological subtypes. Results:The median follow-up was 48 months. Of the 309 patients included in the study, 133 were males and 176 were females, with a median age of 51 years (range: 18-77 years). Primary tumors were located in the major salivary glands in 135 cases (including 42 in the parotid gland, 65 in the submandibular gland, and 28 in the sublingual gland) and in the minor salivary glands in 174 cases. The 5-year overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and progression-free survival rates were 91.5%, 90.8%, 66.1%, and 63.9%, respectively. Non-R0 resection was achieved in 177 patients (57.3%). Among initially resectable patients ( n=253), the non-R0 resection rate was 49.0% ( n=124), with only 6 cases (2.4%) experiencing local recurrence (all non-R0 resections). In initially unresectable patients ( n=56), the non-R0 resection rate was as high as 95% ( n=53), with 13 cases (23%) experiencing local recurrence (2 cases in non-R0 resection and 1 case in R0 resection). For initially resectable patients, non-R0 resection significantly reduced the 5-year LRFS rate to 95.2%, compared to 100% in R0 resection patients ( P=0.014). However, multivariate analysis revealed that the solid pathological subtype was an independent risk factor for 5-year LRFS ( HR=7.40, 95% CI: 2.81-19.52, P<0.001), while the surgical margin status was not an independent factor. Conclusions:The combined strategy of surgery and postoperative radiotherapy provides high local control rates for ACCHN patients. Achieving R0 resection is crucial for initially resectable patients, while a comprehensive treatment strategy involving surgery and postoperative radiotherapy remains essential for initially unresectable patients. The solid pathological subtype is the most significant risk factor for local recurrence.

Colorectal cancer(CRC),a common malignant tumor of the digestive system,poses a significant threat to patients'quality of life and prognosis.In recent years,immune checkpoint inhibitor(ICI)therapy has brought breakthroughs for patients with deficient mismatch re-pair(dMMR)or microsatellite instability-high(MSI-H)types of CRC.However,the efficacy of ICI therapy in patients with microsatellite stabil-ity(MSS)CRC,who account for more than 85%of all CRCs,is significantly limited,which is a clinical dilemma that highlights the importance of in-depth investigation of immunotherapy resistance mechanisms.Existing studies have demonstrated that the microenvironment of MSS-type CRC is characterized by unique immunosuppression,including multidimensional factors,such as defective antigen presentation,infiltra-tion of suppressive immune cells,and dysregulation of the cytokine network.These factors collectively constitute a response barrier to im-munotherapy.This review systematically analyzes the key molecular mechanisms of immunoresistance in MSS-type CRC,focusing on the im-munosuppressive characteristics of the tumor microenvironment,epigenetic regulatory abnormalities,immune-metabolic reprogramming,gut microbiota imbalance,and other core aspects.The study aims to provide a theoretical basis for breaking through the immunothera-peutic bottleneck of MSS-type intestinal cancer at the mechanistic level and pointing to the potential direction of research on combined therapeutic strategies.

Objective:To evaluate the impact of surgical margin status and pathological subtypes on the prognosis of patients with adenoid cystic carcinoma of the head and neck (ACCHN) who underwent postoperative radiotherapy.Methods:A retrospective analysis was conducted on 309 patients with initially treated, non-metastatic ACCHN who completed postoperative radiotherapy at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. All patients underwent curative (non-palliative) surgery followed by postoperative radiotherapy, with a median dose of 66 Gy (range: 54-70 Gy). The Kaplan-Meier method was used to compare 5-year local recurrence-free survival (LRFS) between R0 (negative margin) and non-R0 resections in patients with initially resectable (T 1-T 4a stage) and initially unresectable (T 4b stage) disease. Univariate and multivariate Cox proportional hazards models were employed to analyze risk factors for local recurrence, with a focus on surgical margin status and pathological subtypes. Results:The median follow-up was 48 months. Of the 309 patients included in the study, 133 were males and 176 were females, with a median age of 51 years (range: 18-77 years). Primary tumors were located in the major salivary glands in 135 cases (including 42 in the parotid gland, 65 in the submandibular gland, and 28 in the sublingual gland) and in the minor salivary glands in 174 cases. The 5-year overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and progression-free survival rates were 91.5%, 90.8%, 66.1%, and 63.9%, respectively. Non-R0 resection was achieved in 177 patients (57.3%). Among initially resectable patients ( n=253), the non-R0 resection rate was 49.0% ( n=124), with only 6 cases (2.4%) experiencing local recurrence (all non-R0 resections). In initially unresectable patients ( n=56), the non-R0 resection rate was as high as 95% ( n=53), with 13 cases (23%) experiencing local recurrence (2 cases in non-R0 resection and 1 case in R0 resection). For initially resectable patients, non-R0 resection significantly reduced the 5-year LRFS rate to 95.2%, compared to 100% in R0 resection patients ( P=0.014). However, multivariate analysis revealed that the solid pathological subtype was an independent risk factor for 5-year LRFS ( HR=7.40, 95% CI: 2.81-19.52, P<0.001), while the surgical margin status was not an independent factor. Conclusions:The combined strategy of surgery and postoperative radiotherapy provides high local control rates for ACCHN patients. Achieving R0 resection is crucial for initially resectable patients, while a comprehensive treatment strategy involving surgery and postoperative radiotherapy remains essential for initially unresectable patients. The solid pathological subtype is the most significant risk factor for local recurrence.

Objective To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. Methods Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low-and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-α, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutin-treated LX-2 cells were detected with Western blotting. Results Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P<0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-α mRNA levels in mice (P<0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. Conclusion Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.

Objective To analyze the long-term outcome of modified Morrow surgery (interventricular septal cardiomyectomy) in the treatment of hypertrophic obstructive cardiomyopathy (HOCM) in children. Methods The clinical data of the children with HOCM (aged≤14 years) who underwent modified Morrow surgery from January 2010 to August 2022 in Guangdong Provincial People's Hospital were retrospectively analyzed, including changes in hospitalization status, perioperative period, and long-term 15-lead electrocardiogram and echocardiography. Results A total of 29 patients were collected, including 22 males and 7 females, aged 10.00 (5.00, 12.00) years. Five (17.9%) patients had New York Heart Association (NYHA) heart function grade Ⅲ or Ⅳ. Ventricular septal cardiomyectomy was performed in all patients. All 29 patients survived and their cardiac function recovered after operation. Before discharge, right bundle branch block was observed in 2 patients and left bundle branch block in 6 patients. After surgery, in the left ventricular septal cardiomyectomy, the left atrial diameter decreased (P＜0.001), left ventricular end-systolic diameter increased (P=0.009), the peak pressure gradient of left ventricular outflow tract decreased (P＜0.001), and the thickness of ventricular septum decreased (P＜0.001). The systolic anterior motion of mitral valve disappeared and mitral regurgitent jet area decreased (P＜0.001). The flow velocity and peak pressure gradient of right ventricular outflow tract also decreased in the patients who underwent right ventricular septal cardiomyectomy. The average follow-up of the patients was 69.03±10.60 months. All the patients survived with their NYHA cardiac function grading Ⅰ or Ⅱ. No new-onset arrythmia event was found. Echocardiography indicated that the peak pressure gradient of the left ventricular outflow tract remained low (P<0.001). Moderate mitral regurgitation occurred in 2 patients, and left ventricular outflow tract obstruction with moderate mitral regurgitation occurred in 1 patient after simple right ventricular septal cardiomyectomy. Conclusion Right ventricular or biventricular obstruction is frequent in the children with HOCM and they usually have more symptoms before surgery. Modified Morrow surgery can effectively relieve outflow tract obstruction and improve their cardiac function. The long-term outcome is satisfactory. However, the posterior wall of the left ventricle remains hypertrophic. Also, there is an increased risk of a conduction block.

Objective To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. Methods Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low-and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-α, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutin-treated LX-2 cells were detected with Western blotting. Results Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P<0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-α mRNA levels in mice (P<0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. Conclusion Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.

Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.

This project starts with the teaching of clinical anatomy for eight-year medical students, selects specialists to enter the courses according to the content of clinical anatomy, and explores the deep integration of basic and clinical education. This study used the self-made questionnaire to evaluate the effect of the integrated teaching model, and Likert scale was used to score. Meanwhile, the correlation between the scores of each question and total points was analyzed with the item analysis. Moreover, we assessed the principal components through the exploratory factor analysis. The results showed that more than 95% questioned students thought the preclinical education integrated with clinical medicine teaching model is necessary and practical, which can assist medical students in the anatomical structure learning combined with clinical disease, and meanwhile cultivate students' clinical thinking. Only fewer than 10% thought it can connect the basic knowledge and clinical cases effectively, and over 35% thought there are difficulties. Additionally, more than half students (54%) hold the negative attitude which clinicians can't completely replace basic teachers in teaching. Our finding suggests that the integrated teaching model is attractive and feasible. Nonetheless, clinicians can’t replace preclinical teachers completely in the clinical anatomy education yet.

Objective:To illustrate a relatively complete knowledge system (e.g., research outputs, current hotspots, and future trends) in the sepsis field and to help scholars grasp the scientific research direction or clinical focus of treatment.Methods:The relevant literatures of sepsis during the time from 1985 to 2019 in Web of Science database were collected. Sepsis-related research contents were generated using softwares (CiteSpace 5.6.R2 and VOSviewer 1.6.13), which using data mining, information processing and knowledge map methods, to analyze the historical evolution and predict the development trend.Results:A total of 8 189 papers on sepsis were published. The volume of publications were increasing yearly from 1985 to 2019, and reached the top list of 1 276 in 2019. For research contents of sepsis, it has formed the basic characteristics of sepsis which focusing on epidemiological studies and animal experiments. Through cluster analysis, the researches mainly focused on six aspects: septic rat, necrotizingenterocolitis, sepsis-associated encephalopathy, acute kidney injury (AKI), gut-derived sepsis, and inflammatory mediator. And it presented the literature characteristics that related to the injury or dysfunction of intestines, brain, liver, kidney or other organs, but the heart and lung researches were more marginal. Additionally, based on the top key words with the strongest citation bursts, it reflected that the development trend of the continuous attention hotspots with "endotoxin" or "endotoxin shock", the significant attention hotspots with "inflammation", "immunity" and "multiple organ dysfunction syndrome" (MODS), and the novel burst attention hotspots with sepsis management including "diagnosis" and "chemotherapy".Conclusions:Through the hotspots and trends visualization of sepsis, the current researches are prefer to animal experiments, epidemiology, or other basic scientific aspects. Meanwhile, the researches are mostly focusing on inflammatory reaction, immune function or organ dysfunctions. Integrating the knowledge maps of hotspots and trends, based on researches of epidemiology, diagnosis, risk factors, pathogenesis, or treatment, we predict that the future scientific topics will concentrating on childhood sepsis, organ injury mechanism or intervention relating to MODS, and integrated management of sepsis by combining traditional Chinese medicine and Western medicine.