Objective Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and network pharmacology technology combined with pharmacodynamic experiments were used to analyze the quality markers(Q-markers)in Saorilao Qingfei Zhike Capsules.Methods Using UPLC-Q-TOF-MS technology,the chemical components in different polar extracts of Saorilao Qingfei Zhike Capsules was analyzed.Potential pharmacological components were screened by using antitussive and expectorant models.The"components-targets-diseases"network was constructed and potential Q-markers were screened by network pharmacology technology.Then we conducted pharmacodynamic validation to confirm the Q-markers,which have antitussive and expectorant effects in Saorilao Qingfei Zhike Capsules.Results A total of 120 compounds were obtained from the Saorilao Qingfei Zhike Capsules through qualitative analysis.Among the extracts of different polarity,44 compounds were derived from petroleum ether extract,85 compounds were derived from ethyl acetate extract,79 compounds were derived from n-butanol extract,and 71 compounds were derived from water extract.The results of pharmacological experiments showed that among extracts of different polarity,petroleum ether extract had the best antitussive effect,while n-butanol extract had the best expectorant effect.Three core components for eliminating phlegm and relieving cough were screened through network pharmacology techniques:farcalinol,farcalinediol,and rubimaillin.Pharmacodynamic studies verified that all core components mentioned above have certain antitussive and expectorant effects.Conclusion Based on the above research,farcalinol,farcalindiol,and rubimaillin can be used as Q-markers for the antitussive and expectorant effects of Saorilao Qingfei Zhike Capsules.This paper provides reference for the quality standard of Saorilao Qingfei Zhike Capsules.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Transanal total mesorectal excision (TaTME) is a hot topic in the field of colorectal surgery.After nearly ten years of development,it has entered a period of rapid development.Due to the difference between the traditional surgical approach and the previous one,more sufficient preconditions are needed to carry out TaTME cautiously.Therefore,systematic and stan-dardized training is indispensable.Compared with the mature foreign cadaver training courses,the domestic cadaver training is limited,while the traditional laparoscopic animal training model has limited effects on the training of transanal endoscopic surgery.Therefore,how to use the existing domestic conditions to build a training system suitable for Chinese national conditions,so as to standardize the implementation of transanal total mesorectal excision,improve the safety of new technologies,has become an urgent problem to be solved.This article has reviewed deve-lopment history of TaTME training and investigated establishment of TaTME training system,intending to provide references for standardization of TaTME.

Objective To investigate the long-term efficacy of pure transanal total mesorectal excision (PtaTME) for middle-low rectal cancer.Methods The retrospective descriptive study was conducted.The clinicopathological data of 18 patients with middle-low rectal cancer who were admitted to the Sixth Affiliated Hospital of Sun Yat-sen University from July 2014 to August 2016 were collected.There were 7 males and 11 females,aged (58±13) years,with a range from 40 to 84 years.The body mass index was (22±3) kg/m2.All the 18 patients underwent PtaTME.Observation indicators:(1) surgical and postoperative conditions;(2) postoperative pathological examination;(3) follow-up and survival.Follow-up using inpatient reexamination,outpatient examination,and telephone interview were performed to detect anastomotic complications,anal function,urinary retention,sexual dysfunction,survival and tumor recurrence and metastasis once every 3 months within postoperative 6 months,once every 6 months from 6 months to 3 years,and once a year after 3 years up to June 2019.The measurement data with normal distribution were represented as Mean±SD,and the measurement data with skewed distribution were represented as M (range).Count data were expressed as percentages.Survival rates were calculated by the Kaplan-Meier method.Results (1) Surgical and postoperative conditions:18 patients successfully underwent PtaTME,without conversion to open surgery.The operation time,volume of intraoperative blood loss,distance between anastomosis and anal verge,time to first flatus,time to urinary catheter removal,and duration of postoperative hospital stay were (202±68) minutes,50 mL (range,20-400 mL),(4.5± 2.0)cm,2 days (range,2-7 days),3 days (range,2-5 days),and 7 days (range,5-10 days) in the 18 patients,respectively.There was no perioperative complication.Among 18 patients,4 underwent preventive ileostomy.(2) Postoperative pathological examinations:the length of surgical specimens,the number of lymph node dissection,distance from tumor to the distal margin were (11.0±3.0)cm,12±6,and 1.0 cm (range,0.8-3.7 cm),respectively.The 18 patients had complete mesorectal membrane excision,with negative proximal margin,distal margin,and circumferential margin.Tumor pathological staging:there were 2 cases in Tis stage,4 in T1 stage,7 in T2 stage,and 5 in T3 stage;16 in N0 stage,1 in N1 stage,and 1 in N2 stage.Tumor histological classification:2 patients had carcinoma in situ,9 had moderately differentiated adenocarcinoma,and 7 had high-differentiated adenocarcinoma.(3) Follow-up and survival:18 patients were followed up for 34.0-59.0 months,with a median follow-up time of 57.5 months.During the follow-up,4 patients developed grade B anastomotic leakage and were cured after conservative treatment.One patient developed anastomotic recurrence at 2 years after surgery,and no recurrence was found after surgical resection of the recurrent lesion.Four patients with prophylactic ileostomy had the stoma closured,and the anus function was satisfactory after surgery.There was no urinary retention or sexual dysfunction in the 18 patients.Of the 18 patients,17 had tumor free survival after surgery.The 3-year disease-free survival rate was 94.4％,and the 3-year overall survival rate was 100.0％ in 18 patients.Conclusion PtaTME can achieve high quality of specimen,which is safe and feasible for the treatment of rectal cancer.

Objective: To evaluate the feasibility and safety of transanal lateral lymph node dissection for mid-low rectal cancer. Methods: A descriptive case series research method was used. Clinical and pathological data of 5 mid-low rectal cancer patients who underwent transanal lateral lymph node dissection at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from November 2018 to May 2019 were retrospectively collected and analyzed. Of 5 cases, 4 were male and 1 was female with mean age of (43.2±13.2) years and mean body mass index of (21.2±2.6) kg/m²; the mean diameter of tumor was (3.2±2.4) cm; the mean distance between tumor and anus was (6.3±2.5) cm; 3 received preoperative neoadjuvant chemotherapy. In preoperative TNM staging, 2 cases were T3N1M0, 1 was T3cN2aM0, 1 was T3cN2bM0, and 1 was T2N1M0. All the patients had no intestinal obstruction before operation. Surgical methods: (1) total mesorectal excision: using general transanal and transabdominal methods to mobilize and resect total mesorectum, and dissect No.252, No.253 lymph nodes; (2) transanal lateral lymph node dissection: dissect the adipose lymphoid tissue on the surface of the iliococcygeal muscle, the coccygeal muscle, and the obturator muscle (the No.283 lymph nodes) upward, and dissect No.263d and No.263p lymph nodes with fat tissue sequentially till the bifurcation of the internal and external iliac artery; (3) take out the specimen from anus, and make anastomosis between proximal colon and anal canal. Intraoperative and postoperative variables was observed. Results: All the 5 patients completed surgery successfully, and no patient needed to convert to open approach. The mean operative time was (295.6±97.7) minutes, and the median intraoperative blood loss was 70 (50-500) ml. The mean length of specimen was (12.9±3.0) cm, and the mean number of harvested lymph node was 30.4±9.9. The positive lateral lymph nodes were founder in 4 patients. The median distance between tumor and distal resection margin was 1.5 (1.2-8.0) cm. The resection margin in all the patients was negative. The mean time to postoperative flatus was (4.2±1.6) days, the mean postoperative spontaneous urination was (3.0±1.9) days, time to drainage tube removal was (5.6±1.9) days, and the mean postoperative hospital stay was (9.4±2.1) days. The postoperative TNM staging by pathology was 1 case with T1N0M0, 1 with T2N1M0, 1 with T3N2bM0, and 2 with T3N2M0. Five patients were moderately differentiated adenocarcinoma. Only 1 patient developed postoperative abdominal bleeding, who was healed after conservative treatment. The other 4 patients did not develop any perioperative complications, such as incision infection, presacral abscess, pelvic abscess, anastomotic leakage, or anastomotic stricture. Four patients underwent postoperative chemotherapy. All the patients were followed up for 2 to 28 weeks after surgery and they all felt well. The patients with stoma had fluent bowel. Conclusions Transanal lateral lymph node dissection is feasible and safe in the treatment of mid-low rectal cancer, which can achieve the purpose of extended radical resection of mid-low movement rectal cancer. Moreover, this procedure is a new method to treat rectal cancer patients with lateral lymph node metastasis.

OBJECTIVE: To compare the effects of transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laparoscopic TME) on patients' postoperative long-term bowel function. METHODS: A retrospective cohort study was used in this study. We analyzed the clinical data of 134 patients with locally advanced mid-low rectal cancer, who underwent transanal TME or laparoscopic TME in the TaLaR randomized controlled trial at the Sixth Affiliated Hospital, Sun Yat-sen University from April 2016 to November 2017. Inclusion criteria included age of 18 to 80 years old, distance from tumor low margin to anal edge ≤10 cm, preoperative staging of T1-3NxM0, and single rectal adenocarcinoma. Exclusion criteria included local recurrence, distant metastases, abdominoperineal resection, unreduced stoma, new stoma, less than 1 year after protectomy or stoma reduction, or preoperative poor anal function or incontinence. Patients were divided into taTME group and laparoscopic TME group. The taTME group received hybrid transanal and transabdominal approach performed simultaneously. The effects of surgical procedures on postoperative bowel function were evaluated with LARS (low anterior resection syndrome) scale, where 0-20 was defined as " no LARS" , 21-29 as " minor LARS" , and 30-42 as " major LARS" . Univariate and multivariate logistic regression analyses were performed to determine the risk factors associated with major LARS, with surgical approach as a pre-selected variate. RESULTS: A total of 107 patients were included. Of the 54 patients in the taTME group, 35 were male, median age was 57.2 (26.0-77.0) years old, and 22 cases had a tumor less than 5 cm from anal verge. Of the 53 patients in the laparoscopic TME group, 35 were male, median age was 62.0 (33.0-73.0) years old, and 25 cases had a tumor less than 5 cm from anal verge. All baseline clinical data including age, gender, preoperative staging, and tumor height were comparable between the two groups (all P>0.05). All operations in both groups were performed successfully. The operation time, intra-operative blood loss, postoperative anastomotic complication, postoperative hospital stay were comparable between the two groups (all P>0.05), except for a lower diverting stoma rate in the taTME group [37.0% (20/54) vs. 64.2% (34/53), χ²=7.866, P=0.005]. Of the 107 patients, 27 (25.2%) had no LARS, 32 (29.9%) had minor LARS, and 48 (44.9%) had major LARS, after a median follow-up of 17.2 (12.1-30.4) months. No significant difference was found between the two groups in overall bowel function [major LARS: 48.1% (26/54) vs. 41.5% (22/53), Z=-0.994, P=0.320]. Compared with the laparoscopic TME group, the taTME group experienced worse clustering of stools [68.5% (37/54) vs. 45.3% (24/53), Z=-2.354, P=0.019]. However, there were no significant differences between the two groups in terms of gas incontinence, liquid stool incontinence, frequency of defecation, and urgency (all P>0.05). Multivariate analysis identified preoperative radiotherapy (OR=5.073, 95% CI: 1.336 to 19.259, P=0.017) and anastomotic height (OR=3.633, 95% CI: 1.501 to 8.802, P=0.004) as independent risk factors for major LARS, but no impact of taTME on LARS (OR=1.442, 95% CI: 0.638 to 3.261, P=0.379). CONCLUSIONS Compared with laparoscopic TME, taTME has similar outcomes of postoperative long-term bowel function. Preoperative radiotherapy and anastomotic height, but not surgical approach, are independent risk factors for postoperative bowel function.
Adult ; Aged ; Defecation ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Postoperative Complications ; Rectal Neoplasms ; surgery ; Rectum ; Retrospective Studies ; Syndrome ; Transanal Endoscopic Surgery ; Young Adult

Transanal total mesorectal excision (taTME) for rectal cancer is a hot spot in the field of colorectal surgery in recent years, because this technique has the advantages of clear distal margin, early separation of tumor leision, in the treatment of low rectal cancer. However, this technique is not popularized yet, and there are only a few colorectal surgeons who have enough experience. This article shares the experience of taTME in our hospital, including the details of purse string suture, spiral dissection of rectum, and the anatomic markers of anterior and posterior of rectum, conjoined longitudinal muscle and capillary of pelvic nerves locating in pelvic fascia. We sum up the crucial techniques as transanal operation, single port endoscopic technique and mucosal surgical principle (from inside to outside and from bottom to top), aiming to help colorectal surgeons to grasp the essentials of the techniques with initial cases as soon as possible, and to shorten the learning curve, so that more and more patients can benefit.
Anal Canal ; Colorectal Surgery ; Humans ; Rectal Neoplasms ; surgery ; Rectum ; Transanal Endoscopic Surgery

Objective To evaluate the feasibility and safety of transanal lateral lymph node dissection for mid?low rectal cancer. Methods A descriptive case series research method was used. Clinical and pathological data of 5 mid?low rectal cancer patients who underwent transanal lateral lymph node dissection at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat?sen University from November 2018 to May 2019 were retrospectively collected and analyzed. Of 5 cases, 4 were male and 1 was female with mean age of (43.2±13.2) years and mean body mass index of (21.2± 2.6) kg/m2; the mean diameter of tumor was (3.2±2.4) cm; the mean distance between tumor and anus was (6.3 ± 2.5) cm; 3 received preoperative neoadjuvant chemotherapy. In preoperative TNM staging, 2 cases were T3N1M0, 1 was T3cN2aM0, 1 was T3cN2bM0, and 1 was T2N1M0. All the patients had no intestinal obstruction before operation. Surgical methods: (1) total mesorectal excision: using general transanal and transabdominal methods to mobilize and resect total mesorectum, and dissect No.252, No.253 lymph nodes;(2) transanal lateral lymph node dissection: dissect the adipose lymphoid tissue on the surface of the iliococcygeal muscle, the coccygeal muscle, and the obturator muscle (the No. 283 lymph nodes) upward, and dissect No. 263d and No. 263p lymph nodes with fat tissue sequentially till the bifurcation of the internal and external iliac artery; (3) take out the specimen from anus, and make anastomosis between proximal colon and anal canal. Intraoperative and postoperative variables was observed. Results All the 5 patients completed surgery successfully, and no patient needed to convert to open approach. The mean operative time was (295.6±97.7) minutes, and the median intraoperative blood loss was 70 (50?500) ml. The mean length of specimen was (12.9±3.0) cm, and the mean number of harvested lymph node was 30.4±9.9. The positive lateral lymph nodes were founder in 4 patients. The median distance between tumor and distal resection margin was 1.5 (1.2?8.0) cm. The resection margin in all the patients was negative. The mean time to postoperative flatus was (4.2±1.6) days, the mean postoperative spontaneous urination was (3.0±1.9) days, time to drainage tube removal was (5.6±1.9) days, and the mean postoperative hospital stay was (9.4± 2.1) days. The postoperative TNM staging by pathology was 1 case with T1N0M0, 1 with T2N1M0, 1 with T3N2bM0, and 2 with T3N2M0. Five patients were moderately differentiated adenocarcinoma. Only 1 patient developed postoperative abdominal bleeding, who was healed after conservative treatment. The other 4 patients did not develop any perioperative complications, such as incision infection, presacral abscess, pelvic abscess, anastomotic leakage, or anastomotic stricture. Four patients underwent postoperative chemotherapy. All the patients were followed up for 2 to 28 weeks after surgery and they all felt well. The patients with stoma had fluent bowel. Conclusions Transanal lateral lymph node dissection is feasible and safe in the treatment of mid?low rectal cancer, which can achieve the purpose of extended radical resection of mid?low movement rectal cancer. Moreover, this procedure is a new method to treat rectal cancer patients with lateral lymph node metastasis.

Objective To evaluate the feasibility and safety of transanal lateral lymph node dissection for mid?low rectal cancer. Methods A descriptive case series research method was used. Clinical and pathological data of 5 mid?low rectal cancer patients who underwent transanal lateral lymph node dissection at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat?sen University from November 2018 to May 2019 were retrospectively collected and analyzed. Of 5 cases, 4 were male and 1 was female with mean age of (43.2±13.2) years and mean body mass index of (21.2± 2.6) kg/m2; the mean diameter of tumor was (3.2±2.4) cm; the mean distance between tumor and anus was (6.3 ± 2.5) cm; 3 received preoperative neoadjuvant chemotherapy. In preoperative TNM staging, 2 cases were T3N1M0, 1 was T3cN2aM0, 1 was T3cN2bM0, and 1 was T2N1M0. All the patients had no intestinal obstruction before operation. Surgical methods: (1) total mesorectal excision: using general transanal and transabdominal methods to mobilize and resect total mesorectum, and dissect No.252, No.253 lymph nodes;(2) transanal lateral lymph node dissection: dissect the adipose lymphoid tissue on the surface of the iliococcygeal muscle, the coccygeal muscle, and the obturator muscle (the No. 283 lymph nodes) upward, and dissect No. 263d and No. 263p lymph nodes with fat tissue sequentially till the bifurcation of the internal and external iliac artery; (3) take out the specimen from anus, and make anastomosis between proximal colon and anal canal. Intraoperative and postoperative variables was observed. Results All the 5 patients completed surgery successfully, and no patient needed to convert to open approach. The mean operative time was (295.6±97.7) minutes, and the median intraoperative blood loss was 70 (50?500) ml. The mean length of specimen was (12.9±3.0) cm, and the mean number of harvested lymph node was 30.4±9.9. The positive lateral lymph nodes were founder in 4 patients. The median distance between tumor and distal resection margin was 1.5 (1.2?8.0) cm. The resection margin in all the patients was negative. The mean time to postoperative flatus was (4.2±1.6) days, the mean postoperative spontaneous urination was (3.0±1.9) days, time to drainage tube removal was (5.6±1.9) days, and the mean postoperative hospital stay was (9.4± 2.1) days. The postoperative TNM staging by pathology was 1 case with T1N0M0, 1 with T2N1M0, 1 with T3N2bM0, and 2 with T3N2M0. Five patients were moderately differentiated adenocarcinoma. Only 1 patient developed postoperative abdominal bleeding, who was healed after conservative treatment. The other 4 patients did not develop any perioperative complications, such as incision infection, presacral abscess, pelvic abscess, anastomotic leakage, or anastomotic stricture. Four patients underwent postoperative chemotherapy. All the patients were followed up for 2 to 28 weeks after surgery and they all felt well. The patients with stoma had fluent bowel. Conclusions Transanal lateral lymph node dissection is feasible and safe in the treatment of mid?low rectal cancer, which can achieve the purpose of extended radical resection of mid?low movement rectal cancer. Moreover, this procedure is a new method to treat rectal cancer patients with lateral lymph node metastasis.

Objective To explore the diagnostic value of HR -HPV combined with TCT in the diagnosis of cervical cancer and precancerous lesion.Methods 1 198 cervical specimens were selected for the study.The results of HR -HPV detection and TCT detection were analyzed,with the pathological results as the gold standard,the diag-nostic value of HR -HPV and TCT in the diagnosis of cervical cancer and precancerous lesion were discussed. Results With increasing pathological grade,TCT positive rate increased gradually,there was a correlation between them(r =0.629,P <0.05).With increasing pathological grade,HR -HPV positive rate increased gradually,there was a correlation between them(r =0.684,P <0.05).The sensitivity of HR -HPV combined with TCT in the differ-ential diagnosis of cervical cancer,precancerous lesions was 100.00%,specificity was 79.64%,missed diagnosis rate was 0.00%,the misdiagnosis rate was 20.36%.Conclusion HR -HPV combined with TCT examination has high clinical value in the diagnosis of cervical cancer and precancerous lesions.