The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly di-vided into five groups:the control group(Control group),model 1 group(ACLT group),adminis-tration 1 group(ACLT+GC group),model 2 group(MIA group),and administration 2 group(MIA+GC group.)The rats were euthanized after 4 weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemis-try was used to detect the expression levels of collagen Ⅱ and MMP-13 in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-α in the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural dam-age to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13 in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory me-diators COX-2,IL-1β,and TNF-α were significantly lower in the ACLT group than in the MIA group(P＜0.0l).GC intervention reduced the OARSI score(P＜0.05 or P＜0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-11,COMP),and inflammatory mediators(COX-2,INOS,IL-1β and TNF-α)ex-pression,and promoted collagen Ⅱ synthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint dam-age,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the rat OA model in both groups,thus exerting a cartilage-protective effect.

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Objective This study aimed to assess the clinical efficacy of Shenling Baizhu Granules in treating low anterior resection syndrome(LARS)in rectal cancer.Methods The study employed a randomized,double-blind,placebo-parallel controlled,single-center,validity-tested clinical trial design.December 2019 to June 2022,the Department of Gastrointestinal Surgery and Integrated Traditional Chinese and Western Medicine of Peking University First Hospital recruited 110 patients who had undergone low anterior resection(LAR)for rectal cancer and subsequently developed LARS.These patients,meeting the enrollment criteria,were randomly assigned into the treatment group(55)and the control group(55)using the double-blind method principle.The randomization table was generated by SAS 9.2 software employing the double-blind method.The treatment group received oral Shenling Baizhu Granules,while the control group received oral placebo granules.Both groups commenced treatment on the 10th day after-surgery for 30 consecutive days.Patients were evaluated using LARS score,traditional Chinese medicine(TCM)symptom grading,and XU Zhongfa score before treatment,on the 15th day of treatment,and on the 1st day after treatment cessation.Results Out of 110 patients,107 were included in the full analysis set for efficacy analysis:55 patients in the treatment group and 55 patients in the control group.One case in the treatment group was excluded(against protocol),and two cases in the control group were excluded(one lost to follow-up,one against protocol).Baseline data between the two groups were consistent,with no statistically significant difference.Before treatment,LARS scores for the treatment and control groups were 33.0(31.0,36.0)and 34.0(32.0,37.0)respectively.Patients with TCM symptom scores of grades 2 to 3 accounted for 92.73％and 90.57％in the treatment and control groups,respectively,with no statistically significant difference.After 30 days of treatment,LARS scores for the treatment and control groups were 21.0(19.8,23.0)and 26.0(22.0,28.0)respectively.The percentage of patients with TCM symptom scores of grades 2 to 3 decreased to 33.33％in the treatment group and 66.04％in the control group,with a statistically significant difference.Shenling Baizhu Granules showed rapid improvement in watery or loose stools in post-operative rectal cancer patients.After 30 days of treatment,Shenling Baizhu Granules significantly improved appetite,stool consistency,abdominal distension,abdominal pain,and eructation symptoms in postoperative rectal cancer patients.Before treatment,the XU Zhongfa scores for the treatment and control groups were 3.0(2.0,4.3)and 4.0(2.0,4.0)respectively,with no statistically significant difference.After 30 days of treatment,the XU Zhongfa scores for the treatment and control groups were 7.0(6.0,8.0)and 6.0(5.0,7.0)respectively,with the treatment group significantly higher than the control group(P＜0.01).Conclusion Shenling Baizhu Granules can effectively improve LARS symptoms in patients following LAR of rectal cancer within a short period of time.

Objective:By analyzing the clinical data of patients with primary duodenal adenocarcinoma (PDA), the risk factors affecting the postoperative prognosis of PDA patients were discussed.Methods:The clinical data of 191 patients diagnosed with PDA in Peking University First Hospital from Jan 2009 to Dec 2022 were collected. The survival rate was calculated and the survival curve was plotted by Kaplan-Meier method. Univariate analysis was performed by Log-Rank test, and multivariate analysis was performed by COX proportional hazards regression model to obtain independent risk factors.Results:The median age of onset in patients with PDA is 65 years old, and the most common symptoms are abdominal pain and abdominal distension. Prognostic analysis showed that the survival rates at 1, 3 and 5 years were 73.8%, 44.6%, and 23.0%. The analysis of Cox risk proportional regression model showed that preoperative CA19-9 level, depth of tumor invasion, degree of differentiation, TNM stage, and surgical mode were independent risk factors for the prognosis of PDA (all P<0.01). Conclusion:The overall incidence of PDA is low, but the prognosis is rather poor. Multvariable factors are associated with its prognosis and surgery is still the mainstay for hope of cure.

Objective:To evaluate CT and or MRI imaging in the diagnosis of lateral lymph node metastasis in patients of middle and low rectal cancer.Methods:In this study, 112 lateral lymph nodes were harvested in 79 patients with middle and low rectal cancer. The relationship between the preoperative imaging features of the lateral lymph nodes and the postoperative pathology was evaluated.Result:Thirty-eight cases (48%) were pathologically confirmed to have lateral lymph node metastasis. The diameter of metastasis-positive lateral lymph nodes was significantly larger than that of metastasis-negative lateral lymph nodes ( P<0.01). Multivariate analysis of clinical features and imaging features found that, tumors poorly differentiated, mucinous adenocarcinoma, signet ring cell carcinoma ( P=0.006), and the largest short diameter of the lateral lymph node ≥7 mm ( P=0.024), uneven density or signal ( P=0.022) were independent risk factors for lateral lymph node metastasis. Conclusion:Poor tumor differentiation, lateral lymph node maximum short diameter ≥7 mm, density or signal unevenness are independent risk factors for lateral lymph node metastasis in middle and low rectal carcinoma.

Objective:To investigate the risk factors of low anterior resection syndrome (LARS)after low anterior resection of rectal cancer (Dixon).Methods:This retrospective study was conducted in Peking University First Hospital and Traditional Chinese Medicine Hospital of Shanxi Provice from Jan 2012 to Jun 2019. A cohort of 504 patients with rectal cancer was enrolled in the study. All the patients underwent anterior resection. The relationship between clinical-pathological data were analyzed retrospectively. Univariate analysis using χ 2 test. Logistic regression analysis was used to screen the influencing factors of LARS, and the Nomogram method was used to score each factors. Results:Univariate analysis showed that BMI≥28 kg/m 2(χ 2=9.450, P=0.002), the distance from the lower edge of the tumors to the anus <6 cm (χ 2=12.070, P=0.001), high ligation of the inferior mesenteric artery (IMA) (χ 2=8.279, P=0.004), preoperative neoadjuvant therapy (χ 2=11.230, P=0.001), postoperative anastomotic leakage (χ 2=11.840, P=0.001) were associated with severe LARS.Multivariate analysis showed that the distance from the lower edge of the tumors to the anus <6 cm ( OR=1.861, 95% CI: 1.289-2.688, P=0.001), BMI≥28 kg/m 2 ( OR=1.747, 95% CI: 1.022-2.987, P=0.041), high IMA ligation ( OR=1.688, 95% CI: 1.157-2.463, P=0.007), preoperative neoadjuvant therapy ( OR=2.719, 95% CI: 1.343-5.505, P=0.005) were independent risk factors for LARS. Nomogram model showed that the total factor ranged from 2 to 212, and the corresponding risk rate ranged from 30% to 80%. The patients with higher score have greater risk for severe LARS. The area under the predictive power curve of Nomogram model (AUC) was 0.749 (95% CI: 0.705-0.793, P<0.001). Conclusion:Lower tumor location, obesity, preoperative neoadjuvant therapy, high IMA ligation and postoperative anastomotic leakage increase the risk of severe LARS.

Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer's disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.
Amyloid beta-Peptides/metabolism* ; Humans ; Neurodegenerative Diseases ; Neuroglia ; TRPM Cation Channels/genetics* ; Transient Receptor Potential Channels

Objective:To evaluate the factors affecting the degree of radical resection and the prognosis of patients with locally recurrent rectal cancer (LRRC).Methods:A retrospective case-control study was performed. Clinical data of 111 patients with LRRC undergoing operation at the General Surgery Department of Peking University First Hospital from January 2009 to August 2019 were analyzed retrospectively. The "Peking University First Hospital F typing" was performed according to the preoperative images of the pelvic involvement. The pelvis was assigned into four directions: the front wall, lateral sides of the pelvic wall and the sacrum. According to the degree of pelvic wall involvement, F typing included F0 type (no involvement of the pelvic wall, the cancer only involved the adjacent organs or invaded conteriorly the urinary tract, genital organs or small intestine), F1 type (cancer involved the pelvic wall in one direction, such as the sacrum, or one side of the pelvic wall), F2 type (cancer involved the pelvic wall in two directions) and F3 type (cancer involved the pelvic wall in three directions). Case inclusion criteria: (1) LRRC was confirmed by imaging and pathological examination of samples (puncture or endoscopic biopsy); (2) complete clinical and follow-up data; (3) informed consent of patient. Those with dysfunction of heart, lung, etc., intolerance of operation, F3 type indicated by image, and distant metastasis were excluded. The degree of radical resection was evaluated according to the postoperative pathological results. Patients were followed up every 12 months and related examinations were arranged. The univariate analysis of radical resection was performed by χ 2 test, and the multivariate analysis was performed by logistic methods. The survival rate was calculated by Kaplan-Meier method and the survival curve was drawn. The survival rate was compared by log-rank test. Cox proportional hazards model was used to analyze the factors affecting the prognosis of patients with LRRC. Results:A total of 111 patients were included in this study. Of 111 patients, 59 were male and 52 were female; recurrent age of 36 cases was ≥ 65 years old; CEA level of 48 cases was ≥15 μg/L. According to the "Peking University First Hospital F typing", 70 cases were F0 type, 38 F1 type and 3 F2 type. Surgical procedures were abdominoperineal resection ( n=28), posterior pelvic exenteration ( n=32), and total pelvic exenteration ( n=51, including 1 case of TPE combined with sacrectomy). According to the postoperative pathological results, R0, R1 and R2 resections were 83, 20 and 8 cases, respectively. Univariate analysis showed that the degree of radical resection was associated with the secondary surgical procedure, F typing and lymph node metastasis (all P<0.05). Multivariate analysis showed that F typing (F1-F2) was an independent risk factor for non- R0 resection (OR=37.256, 95%CI:8.572 to 161.912, P<0.001). The morbidity of operative complications was 22.5% (25/111); the perioperative mortality was 1.8% (2/111); the local recurrence rate after the second operation was 37.8% (42/111). The 3- and 5-year overall survival rates were 41.2% and 21.9% respectively. The 3-year survival rates of patients with and without postoperative chemotherapy were 52.7% and 32.4% respectively ( P=0.005). The 3-year survival rates of patients with lower (<15 μg/L) and higher CEA level (≥15 μg/L) were 52.9% and 24.3% respectively ( P<0.001). The 3-year survival rates of patients with R0, R1 and R2 resection were 49.8%, 21.3% and 8.5% respectively ( P=0.002). The 3-year survival rates of patients with F0, F1 and F2 type were 52.7%, 22.0% and 0 respectively ( P<0.001). Cox analysis confirmed that the degree of radical resection (HR=2.088, 95%CI:1.095 to 3.979, P=0.025), the CEA level before the secondary operation (HR=1.857, 95%CI:1.157 to 2.980, P=0.010) and postoperative chemotherapy (HR=1.826, 95%CI:1.137 to 2.934, P=0.013) were independent factors affecting the prognosis. Conclusions:The indication of LRRC surgical treatments must be strictly limited. Evaluation of the fixation site to the pelvic wall is helpful for improving the rate of R0 resection. Lower preoperative CEA level, radical resection and postoperative chemotherapy are protective factors of prolonged overall survival time of patients with LRRC.

Objective:To evaluate the factors affecting the degree of radical resection and the prognosis of patients with locally recurrent rectal cancer (LRRC).Methods:A retrospective case-control study was performed. Clinical data of 111 patients with LRRC undergoing operation at the General Surgery Department of Peking University First Hospital from January 2009 to August 2019 were analyzed retrospectively. The "Peking University First Hospital F typing" was performed according to the preoperative images of the pelvic involvement. The pelvis was assigned into four directions: the front wall, lateral sides of the pelvic wall and the sacrum. According to the degree of pelvic wall involvement, F typing included F0 type (no involvement of the pelvic wall, the cancer only involved the adjacent organs or invaded conteriorly the urinary tract, genital organs or small intestine), F1 type (cancer involved the pelvic wall in one direction, such as the sacrum, or one side of the pelvic wall), F2 type (cancer involved the pelvic wall in two directions) and F3 type (cancer involved the pelvic wall in three directions). Case inclusion criteria: (1) LRRC was confirmed by imaging and pathological examination of samples (puncture or endoscopic biopsy); (2) complete clinical and follow-up data; (3) informed consent of patient. Those with dysfunction of heart, lung, etc., intolerance of operation, F3 type indicated by image, and distant metastasis were excluded. The degree of radical resection was evaluated according to the postoperative pathological results. Patients were followed up every 12 months and related examinations were arranged. The univariate analysis of radical resection was performed by χ 2 test, and the multivariate analysis was performed by logistic methods. The survival rate was calculated by Kaplan-Meier method and the survival curve was drawn. The survival rate was compared by log-rank test. Cox proportional hazards model was used to analyze the factors affecting the prognosis of patients with LRRC. Results:A total of 111 patients were included in this study. Of 111 patients, 59 were male and 52 were female; recurrent age of 36 cases was ≥ 65 years old; CEA level of 48 cases was ≥15 μg/L. According to the "Peking University First Hospital F typing", 70 cases were F0 type, 38 F1 type and 3 F2 type. Surgical procedures were abdominoperineal resection ( n=28), posterior pelvic exenteration ( n=32), and total pelvic exenteration ( n=51, including 1 case of TPE combined with sacrectomy). According to the postoperative pathological results, R0, R1 and R2 resections were 83, 20 and 8 cases, respectively. Univariate analysis showed that the degree of radical resection was associated with the secondary surgical procedure, F typing and lymph node metastasis (all P<0.05). Multivariate analysis showed that F typing (F1-F2) was an independent risk factor for non- R0 resection (OR=37.256, 95%CI:8.572 to 161.912, P<0.001). The morbidity of operative complications was 22.5% (25/111); the perioperative mortality was 1.8% (2/111); the local recurrence rate after the second operation was 37.8% (42/111). The 3- and 5-year overall survival rates were 41.2% and 21.9% respectively. The 3-year survival rates of patients with and without postoperative chemotherapy were 52.7% and 32.4% respectively ( P=0.005). The 3-year survival rates of patients with lower (<15 μg/L) and higher CEA level (≥15 μg/L) were 52.9% and 24.3% respectively ( P<0.001). The 3-year survival rates of patients with R0, R1 and R2 resection were 49.8%, 21.3% and 8.5% respectively ( P=0.002). The 3-year survival rates of patients with F0, F1 and F2 type were 52.7%, 22.0% and 0 respectively ( P<0.001). Cox analysis confirmed that the degree of radical resection (HR=2.088, 95%CI:1.095 to 3.979, P=0.025), the CEA level before the secondary operation (HR=1.857, 95%CI:1.157 to 2.980, P=0.010) and postoperative chemotherapy (HR=1.826, 95%CI:1.137 to 2.934, P=0.013) were independent factors affecting the prognosis. Conclusions:The indication of LRRC surgical treatments must be strictly limited. Evaluation of the fixation site to the pelvic wall is helpful for improving the rate of R0 resection. Lower preoperative CEA level, radical resection and postoperative chemotherapy are protective factors of prolonged overall survival time of patients with LRRC.

OBJECTIVE: To investigate the value of neoadjuvant chemoradiotherapy (nCRT) combined with total pelvic exenteration (TPE) in the treatment of primary T4b rectal cancer. METHODS: A retrospective cohort study was conducted to analyze the clinicopathological data of 31 patients with primary T4b rectal cancer who underwent TPE from January 2008 to December 2015 at Peking University First Hospital. INCLUSION CRITERIA: preoperative clinical stage (cTNM) was defined as cT4b primary rectal cancer with only front wall Invasion; the lower edge of tumor was within 10 cm from the anal margin; TPE was performed; R0 resection was confirmed by pathology. Patients with recurrent rectal cancer, distant metastasis, and undergoing TPE for non-rectal tumors were excluded. Patients were divided into nCRT group and non-nCRT group according to whether receiving nCRT before surgery. The nCRT group received long course radiotherapy (total dose 50 Gy in 25 daily fractions) with concomitant chemotherapy (Capecitabine), and the surgery was performed 6-8 weeks after the neoadjuvant chemoradiation, while the non-nCRT group received surgery directly. The intraoperative, postoperative and pathological conditions and local recurrence were compared between the two groups. The survival curves were drawn by Kaplan-Meier method and the survival of two groups were compared. RESULTS: A total of 31 patients were enrolled, including 13 patients in the nCRT group and 18 patients in the non-nCRT group. The baseline data, such as age, duration of disease, preoperative basic disease, body mass index, smoking rate, and tumor distance from the anal margin, were not significantly different between the two groups (all P>0.05). In the nCRT group and non-nCRT group respectively, the ratio of anal preservation was 30.8%(4/13) and 38.9%(7/18) (P=0.468), the median intraoperative blood loss was 1 000 ml and 800 ml (P=0.644), the operation time was (531.7±137.2) minutes and (498.0±90.1) minutes (P=0.703), the median hospital stay was 18 days and 14 days (P=0.400), the morbidity of complications within 30 days after surgery was 23.1%(3/13) and 38.9%(7/18)(P=0.452), the incidence of postoperative abdominal abscess was 15.4%(2/13) and 0 (P=0.168), the proportion of secondary surgery was 7.7%(1/13) and 11.1%(2/18)(P=1.000), whose differences were not significantly different. The proportion of postoperative pathological pT4b in whole group was 58.1%(18/31), including 53.8%(7/13) in nCRT group and 61.1%(11/18) in non-nCRT group, which was not significantly different between the two groups (P=0.691). The number of harvested lymph node in nCRT group was 13.5±5.9, which was significantly less than 23.0±11.8 in non-nCRT group (P=0.013). There was no pathological complete remission (ypCR) case in nCRT group, and among 13 patients, tumor regression grade (TRG) of 2, 3, 4, and 5 was in 1 case (7.7%), 6 cases (46.2%), 5 cases(38.5%), and 1 case (7.7%), respectively. The median follow-up time was 33 (2 to 115) months, and the follow-up rate was 93.5%(29/31). One case was lost in both the nCRT group and non-nCRT group. The 3-year disease-free survival rate was 43.5% in pooled data, and was 43.6% and 43.3% in nCRT group and non-CRT group respectively without significant difference (P=0.833). The 3-year overall survival rate was 51.1% in pooled data, and was 45.7% and 54.7% in nCRT group and non-nCRT group respectively without significant difference (P=0.653).The local recurrence rate of nCRT and non-nCRT groups was 8.3%(1/12) and 5.9%(1/17) respectively, and the distant metastasis rate was 50.0%(6/12) and 41.2%(7/17) respectively, whose differences were not statistically significant as well (P=1.000 and P=0.865, respectively). CONCLUSION For primary T4b rectal cancer which can achieve R0 resection through total pelvic exenteration, neoadjuvant chemoradiotherapy has not been demonstrated any advantage in tumor regression, reducing local recurrence, or improving survival, and may increase postoperative complications.
Adenocarcinoma ; pathology ; therapy ; Antineoplastic Agents ; administration & dosage ; Chemoradiotherapy ; Combined Modality Therapy ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Pelvic Exenteration ; Rectal Neoplasms ; pathology ; therapy ; Retrospective Studies ; Treatment Outcome