Objectives: To investigate the factors influencing the height of anterior peritoneal reflection (APR) for patients with rectal cancer, and to analyze the relationship between the APR and the lateral lymph node metastasis. Methods: Clinical data of 432 patients with tumor located within and below APR were retrospectively collected from the rectal cancer database at the Department of General Surgery, Peking Union Medical College Hospital from August 2020 to September 2022. Ninty-eight non-rectal cancer patients were also enrolled as a control group. There were 308 males and 124 females in the tumor group, aged (M(IQR)) 62 (16) years (range: 24 to 85 years) and 53 males and 45 females in the control group, aged 60 (22) years (range: 27 to 87 years). The APR height, pelvis, and tumor-related parameters were measured by MRI. A multifactor linear regression model was established to analyze the dependent correlation factors of APR height. These factors of the two groups were matched by propensity score matching and their APR heights were compared after matching. An ordinal Logistic regression model was established to explore the relationship between APR-related parameters and radiographic lateral lymph node metastasis. Results: The APR height of the tumor group was (98.7±14.4) mm (range: 43.3 to 154.0 mm) and the control group was (95.1±12.7) mm (range: 68.0 to 137.9 mm). Multivariable linear regression revealed that the greater the weight (B=0.519, 95%CI: 0.399 to 0.640, P<0.01), the anterior pelvic depth (B=0.109, 95%CI: 0.005 to 0.213, P=0.039) and the smaller the bi-ischial diameter (B=-0.172, 95%CI:-0.294 to -0.049, P=0.006), the higher the APR height. The tumor group had a higher APR height than the control group after propensity score matching ((98.3±14.2) mm vs. (95.1±12.7) mm, t=-1.992, P=0.047). Ordinal Logistic regression indicated that the longer segment of the tumor invade the nonperitoneal rectum was an independent influencing factor of radiographic lateral lymph node metastasis (OR=1.016, 95%CI: 1.002 to 1.030, P=0.021), while the distance between the anal verge and the tumor was not (OR=0.986, 95%CI: 0.972 to 1.000, P=0.058). Conclusions: The higher the weight, the deeper and narrower the pelvis, the higher the APR height. There is a certain relationship between APR and lateral lymph node metastasis on imaging.

ObjectiveTo explore and establish the liver injury risk prediction model of indirect toxicity of Chinese medicinals under the condition of compound formulas， and provide new ideas and methods for the study of evaluation of liver injury of Chinese medicinals based on indirect toxicity. MethodsTaking Buguzhi （Fructus Psoraleae） pre-parations as model drug， the combined Chinese medicinals with Buguzhi （Fructus Psoraleae） of high frequency are screened out， and their components and action targets were obtained through TCMSP， TCMIP and PharmMapper databases. The association strength value and risk value of Chinese medicinals that acted on the nuclear factor κB （NF-κB） pathway were analyzed. For those having greater values than the median association strength value and risk value were regarded as indirect Chinese medicinals of liver injury risk. In this way， a prediction model of liver injury risk of Chinese medicinals was constructed based on immune activation-related indirect liver injury process （taking NF-κB pathway as an example）. And verification of the prediction model was performed using Heshouwu （Radix Polygoni Multiflori） preparations. ResultsThe prediction model of liver injury risk based on important immunoactivated pathway （taking NF-κB pathway as an example） found that Yinyanghuo （Herba Epimedii） （association strength value = 0.18， risk value = 0.25） was a Chinese medicinal with potential risk of indirect liver injury within Buguzhi （Fructus Psoraleae） prepartions， which may increase the risk of liver injury by positively regulating Bruton's tyrosine kinase （Btk） and protein kinase C theta （PKCθ） on NF-κB pathway. Further verification of prediction model by Heshouwu （Radix Polygoni Multiflori） preparations showed that Buguzhi （Fructus Psoraleae） （association strength value = 0.25， risk value = 0.33） and Tusizi （Semen Cuscutae） （Semen Cuscutae， association strength value = 0.34， risk value = 0.33） may increase the liver injury risk of Heshouzu. ConclusionThe liver injury risk prediction model of indirect toxicity of Chinese medicinals has been constructed in this study， providing metho-dological reference for the identification of Chinese medicinals of indirect liver injury risk under the condition of compound formulas.

Objective: To compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.
Anastomotic Leak/etiology* ; Humans ; Laparoscopy/methods* ; Postoperative Complications/epidemiology* ; Prognosis ; Prospective Studies ; Rectal Neoplasms/pathology* ; Rectum/surgery* ; Retrospective Studies ; Transanal Endoscopic Surgery/methods* ; Treatment Outcome

Objective: To explore the incidence and risk factors of postoperative surgical site infection (SSI) after colon cancer surgery. Methods: A retrospective case-control study was performed. Patients diagnosed with colon cancer who underwent radical surgery between January 2016 and May 2021 were included, and demographic characteristics, comorbidities, laboratory tests, surgical data and postoperative complications were extracted from the specialized prospective database at Department of General Surgery, Peking Union Medical College Hospital. Case exclusion criteria: (1) simultaneously multiple primary colon cancer; (2) segmental resection, subtotal colectomy, or total colectomy; (3) patients undergoing colostomy/ileostomy during the operation or in the state of colostomy/ileostomy before the operation; (4) patients receiving natural orifice specimen extraction surgery or transvaginal colon surgery; (5) patients with the history of colectomy; (6) emergency operation due to intestinal obstruction, perforation and acute bleeding; (7) intestinal diversion operation; (8) benign lesions confirmed by postoperative pathology; (9) patients not following the colorectal clinical pathway of our department for intestinal preparation and antibiotic application. Univariate analysis and multivariate analysis were used to determine the risk factors of SSI after colon cancer surgery. Results: A total of 1291 patients were enrolled in the study. 94.3% (1217/1291) of cases received laparoscopic surgery. The incidence of overall SSI was 5.3% (69/1291). According to tumor location, the incidence of SSI in the right colon, transverse colon, left colon and sigmoid colon was 8.6% (40/465), 5.2% (11/213), 7.1% (7/98) and 2.1% (11/515) respectively. According to resection range, the incidence of SSI after right hemicolectomy, transverse colectomy, left hemicolectomy and sigmoid colectomy was 8.2% (48/588), 4.5% (2/44), 4.8% (8 /167) and 2.2% (11/492) respectively. Univariate analysis showed that preoperative BUN≥7.14 mmol/L, tumor site, resection range, intestinal anastomotic approach, postoperative diarrhea, anastomotic leakage, postoperative pneumonia, and anastomotic technique were related to SSI (all P<0.05). Multivariate analysis revealed that anastomotic leakage (OR=22.074, 95%CI: 6.172-78.953, P<0.001), pneumonia (OR=4.100, 95%CI: 1.546-10.869, P=0.005), intracorporeal anastomosis (OR=5.288, 95%CI: 2.919-9.577,P<0.001) were independent risk factors of SSI. Subgroup analysis showed that in right hemicolectomy, the incidence of SSI in intracorporeal anastomosis was 19.8% (32/162), which was significantly higher than that in extracorporeal anastomosis (3.8%, 16/426, χ(2)=40.064, P<0.001). In transverse colectomy [5.0% (2/40) vs. 0, χ(2)=0.210, P=1.000], left hemicolectomy [5.4% (8/148) vs. 0, χ(2)=1.079, P=0.599] and sigmoid colectomy [2.1% (10/482) vs. 10.0% (1/10), χ(2)=2.815, P=0.204], no significant differences of SSI incidence were found between intracorporeal anastomosis and extracorporeal anastomosis (all P>0.05). Conclusions: The incidence of SSI increases with the resection range from sigmoid colectomy to right hemicolectomy. Intracorporeal anastomosis and postoperative anastomotic leakage are independent risk factors of SSI. Attentions should be paid to the possibility of postoperative pneumonia and actively effective treatment measures should be carried out.
Case-Control Studies ; Colonic Neoplasms/surgery* ; Humans ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection/etiology*

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

BACKGROUND: We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice. METHODS: Intestinal epithelial CCL7 overexpression (CCL7) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: We found that the CCL7 mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7 mice compared to WT. Furthermore, HFD-fed CCL7 mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis. CONCLUSIONS Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.
Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology* ; Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; Peptidyl-Dipeptidase A/chemistry* ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry* ; COVID-19 Drug Treatment

Objective To detect the molecular characterization of polysaccharide purified from Amusium pleuronectes, so as to investigate its role of intervention to the formation of hepatic fibrosis caused by Schistosoma japonicum infection. Methods The crude polysaccharide from A. pleuronectes was extracted and further purified, and the molecular weight and monosaccharide composition were determined by the high pressure size exclusion chromatography and PMP pre-column derivatization method, respectively. A total of 50 female BALB/c mice were randomly divided into five groups：A (normal group), B (experimental group), C (polysaccharide group), D (praziquantel), and E (polysaccharide + praziquantel group). The mice in B, C, D, or E groups were attacked on the abdominal skin by using the cercariae of S. japonicum (30 ± 2 for each mouse) respectively. After 8 weeks, the mice in C, D, and E groups were administrated by polysaccharide and/or praziquantel, and the mice in B group were instead of saline. All the livers and sera were collected after 16 weeks. HE staining was employed for the livers, and serum IFN-γ and IL-13 were measured by using ELISA kits. Results The molecular weight of purified polysaccharide from A. pleuronectes was 11.7 kDa. Compared with A and B groups, the serum levels of IFN-γ in C, D, and E groups were significantly increased (F = 63.525, P < 0.01). However, the serum levels of IL-13 in C, D, and E groups were significantly decreased (F = 99.788, P < 0.01) compared with that in B group. HE staining showed that the egg nodules and hepatic fibrosis were observed in B, C, D, and E groups. The number of egg nodules and fibrosis degree in E group were milder than those in B group (χ² = 7.875, P < 0.05). Conclusions The polysaccharide from A. pleuronectes has an obvious effect in preventing hepatic fibrosis process induced by S. japonicum infection, particularly combining with the administration of praziquantel.

Objective To investigate the clinical efficacy and long-term outcomes of laparoscopic radical re-section for stageⅢcolon cancer.Methods A total of 169 stageⅢcolon cancer patients treated with laparoscopic surgery (n=75) or open surgery (n=94) between January 2007 and December 2012 in Department of General Sur-gery, Peking Union Medical College Hospital were included.The clinicopathologic features, as well as long-term outcomes including 5-year local recurrence rate, overall survival, and disease-free survival, were compared between the two groups.Results Compared with the open surgery group, the laparoscopic surgery group had significantly longer operation time [ (171.3 ±43.2) minutes vs.(132.7 ±60.4) minutes, P<0.001], significantly less blood loss [ (86.3 ±61.7) ml vs.(109.8 ±74.6) ml, P=0.030], and significantly more invaded lymph nodes detec-ted (23.3 ±12.2 vs.19.3 ±9.6, P=0.022).No significant difference was found between the laparoscopic surgery group and open surgery group in cumulative local recurrence rate (6.7%vs.8.5%, P=0.876), 5-year overall survival (73.6% vs.58.8%, P=0.317), and 5-year disease-free survival (61.6% vs.56.3%, P=0.544). Conclusion Laparoscopic colectomy is safe and effective for stageⅢcolon cancer, comparable with the conven-tional open colectomy in terms of long-term oncological outcomes.

Objective To investigate the feasibility of extralevator abdominoperineal excision ( ELAPE) under laparoscope .Methods We retrospectively analyzed 12 patients with distal rectal cancer who underwent ELAPE in our center from June 2012 to August 2013 .During the procedures , the levator ani muscles were cut off laparoscopically at its origin at both sides on the pelvic wall , and its attachment on coccyx was removed posterior-ly.The dissection plane was taken along the Denonvillier fascia anteriorly as far as possible to the perineal body . The adjacent organs were removed if invaded by the tumors .The anus and its surrounding tissue were removed by perineal approach without changing patients'positions .The pelvic perinium was closed laparoscopically to prevent the intestine dropping .The operation time , blood loss , retrieval of lymph nodes , radial margin , and postoperative complications were recorded .Results The patients aged ( 65.2 ±12.5 ) years and their body mass index was 21.6 ±3.1.The distance from lower edge of tumor to anal verge was (3.3 ±0.7) cm.The procedure lasted (176.1 ±27.5) minutes, with a blood loss of (49.6 ±38.2) ml.The average number of node retrieval was 18.3 ±7.8 , and no positive radial margin was identified .The postoperative complications included urinary reten-tion in 2 patients.The perineal incision appeared to be class A healing in 9 patients.Conclusion By extensive-ly removing the levator ani muscles laterally and posteriorly , ELAPE procedure can be accomplished under lapa-roscope without changing operative position or flap repair of the pelvic floor .