Objective To investigate the therapeutic effect and mechanism of MCC950 on benzalkonium chloride-in-duced dry eye(DED)in rats.Methods Among 60 male SD rats,50 rats were treated with 20 g·L-1 benzalkonium chlo-ride solution 3 times a day in both eyes to induce DED model,and a significant decrease in tear secretion was regarded as a successful modeling,and the remaining 10 rats were regarded as the control group.DED rats were randomly divided into 5 groups:DED,DED+10MCC950,DED+50MCC950,DED+100MCC950,and DED+500MCC950 groups,and were given 0.2 mL of 0,10,50,100,and 500 μmol·L-1 MCC950 in both eyes for two weeks,and then examined the amount of tear secretion,corneal histopathology(HE staining),reactive oxygen species(ROS),and inflammation factors(NLRP3,Caspase-1,IL-1β,IL-6).Results The tear secretion of rats in the DED group was significantly lower than that of the control group(P＜0.05).Except for the DED+10MCC950 group,the tear secretion of rats in different concentrations of MCC950 treatment groups was increased and positively correlated with the MCC950 dose(all P＜0.05).HE staining of the cornea showed that compared with the control group,the cornea of the DED group was significantly thinner,the arrange-ment of surface cells was disorganized,the number of cells was significantly reduced,and a large number of"vacuole"-like structures appeared;the corneal stroma was disorganized and sparsely structured.The degree of histopathological changes in the cornea of rats treated with different concentrations of MCC950 decreased with the increase of the concentration of MCC950.Compared with the control group,the relative expression level of ROS in the DED group of rats was significantly increased(P＜0.05).In each MCC950 treatment group,as the concentration of MCC950 increased,the relative expression level of corneal ROS staining in rats gradually decreased,showing a concentration-dependent effect(all P＜0.05).Com-pared with the control group,the levels of NLRP3,IL-1 β,Caspase-1 and IL-6 were significantly increased in the DED group(all P＜0.05).The levels of various inflammatory factors were dose-dependently reduced in the MCC950 treatment groups(all P＜0.05).Conclusion MCC950 can reduce oxidative stress and inflammation and improve the symptoms of benza-lkonium chloride-induced DED in rats by inhibiting the activation of NLRP3 inflammatory vesicles.

A minimum of 12 lymph nodes examined is a requirement for the pathological specimens of radical colon cancer surgery according to the NCCN guidelines. However, the increase in the number of lymph nodes examined by expanding the range of lymph node dissection is not the fundamental factor. Addressing whether the range of lymph node dissection brings benefits requires evidence from researches. In recent years, high-level evidence brought by the RELARC trial has defined the indications for central lymph node dissection in the right hemicolectomy. Clinical research on indications for infrapyloric and gastroepiploic lymph nodes and non-regional/non-feeding vessel lymph node dissection has also been carried out. This article provides strategic references in the era of precision medicine by clarifying the research evidence about controversial issues related to lymph node dissection in right hemicolectomy.

Objective:To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors.Methods:A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups.Results:All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436–34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220–36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017–12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive ( n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion:In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.

As high-quality, evidence-based medical research continues to update, the diag-nosis and treatment of mid and low rectal cancer presents complex patterns, adapting to the require-ments of real-world study. In the process of building real-world database and data collection, the selection of database fields, the structured design of imaging reports, as well as quality control during and after data collection, will significantly impact the quality of real-world data and its generated evidence. The authors hope to provide references for subsequent real-world database construction through the experience of constructing a national multicenter database for mid and low rectal cancer.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To compare the prognostic impact of complete mesocolic excision (CME) versus D2 lymphadenectomy in patients with stage III right-sided colon cancer.Methods:A retrospective cohort study was conducted. Clinical data of 263 patients with stage III colon cancer undergoing right hemicolectomy in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital (January 1, 2016 to August 8, 2023) were included. Of the 263 patients, 152 underwent CME and 111 received D2 dissection. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Continuous variables were compared using the Mann-Whitney U test or Student's t-test; categorical variables were compared using the χ2 test or Fisher exact test. Survival curves were constructed using the Kaplan-Meier method, and the Log-Rank test was used to compare disease-free survival (DFS) and overall survival (OS) between groups. Cox proportional hazards models were utilized to analyze prognostic factors, with subgroup analyses performed.Results:Patients undergoing CME surgery were younger (proportion >75 years: 4.6% vs. 25.2%, P<0.001), had a lower burden of comorbidities (Charlson comorbidity index ≥ 1: 25.0% vs. 36.9%, P=0.045), The rates of open surgery and converted open surgery were lower [0.6% (1/152) vs. 4.5% (5/111) and 0.6% (1/152) vs. 2.7% (3/111), respectively; P=0.040].They also had a higher rate of receiving adjuvant therapy (92.7% vs. 76.0%, P<0.001). In terms of short-term postoperative outcomes, the CME group had a greater number of harvested lymph nodes (median: 30 vs. 25, P<0.001) and less blood loss (median: 20 ml vs. 20 ml, P=0.041). There were no significant differences between the groups in terms of the number of metastatic lymph nodes, operation time, and the incidence of postoperative complications. Survival analysis demonstrated significantly longer DFS in the CME group both before and after PSM. CME was an independent favorable prognostic factor for DFS (pre-PSM: HR=0.53, 95%CI: 0.31-0.91, P=0.022; post-PSM: HR=0.50, 95%CI: 0.26-0.97, P=0.042). No significant difference in OS was detected between the two groups across models. The subgroup analysis based on clinicopathological features revealed DFS benefits associated with CME in patients with tumor deposits (HR=0.41, 95%CI: 0.18-0.94, P=0.035), moderately-to-well-differentiated adenocarcinoma(HR=0.48, 95%CI: 0.26-0.90, P=0.023), proficient mismatch repair tumors (HR=0.55, 95%CI: 0.32-0.94, P=0.030), and pN2 stage disease (HR=0.43, 95%CI: 0.19-0.95, P=0.036). Conclusion:An extended lymph node dissection, as exemplified by CME, may confer a DFS advantage in patients with stage III right-sided colon cancer, especially those exhibiting a substantial burden of lymph node metastases.

A minimum of 12 lymph nodes examined is a requirement for the pathological specimens of radical colon cancer surgery according to the NCCN guidelines. However, the increase in the number of lymph nodes examined by expanding the range of lymph node dissection is not the fundamental factor. Addressing whether the range of lymph node dissection brings benefits requires evidence from researches. In recent years, high-level evidence brought by the RELARC trial has defined the indications for central lymph node dissection in the right hemicolectomy. Clinical research on indications for infrapyloric and gastroepiploic lymph nodes and non-regional/non-feeding vessel lymph node dissection has also been carried out. This article provides strategic references in the era of precision medicine by clarifying the research evidence about controversial issues related to lymph node dissection in right hemicolectomy.

Objective:To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors.Methods:A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups.Results:All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436–34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220–36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017–12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive ( n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion:In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.

As high-quality, evidence-based medical research continues to update, the diag-nosis and treatment of mid and low rectal cancer presents complex patterns, adapting to the require-ments of real-world study. In the process of building real-world database and data collection, the selection of database fields, the structured design of imaging reports, as well as quality control during and after data collection, will significantly impact the quality of real-world data and its generated evidence. The authors hope to provide references for subsequent real-world database construction through the experience of constructing a national multicenter database for mid and low rectal cancer.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.