OBJECTIVE To investigate the activation of xanthine oxidase(XO)from the human liver by vitamin K3 and the mechanism.METHODS Using human liver S9(0.1 g·L-1)as the source,XO was incubated with substrate xanthine of 0,2,4,8,and 16 μmol·L-1 at 37℃ for 90 min.The Michaelis constant(Km)of the reaction of xanthine oxidation was determined using the liquid chromatography diode array method.At the concentration of Km,the three-point method(1,10 and 100 μmol·L-1)was used to detect the activity of vitamin K3 activators.The multi-point method(vitamin K3 1,2,5,10,20,50,100,200 and 400 μmol·L-1)was adopted to determine the half effective concentration(EC50)of activated XO.Kinetic parameters(Km and Vmax)and the fit of double reciprocal curves were determined via vitamin K3 of 1/2EC50,EC50 and 2EC50.The changes in kinetic behavior at different concentrations of vitamin K3 were observed and their types of activation were analyzed.The interactions between XO and activator vitamin K3 were explored via molecular docking.RESULTS The Km of XO-mediated xanthine oxidation reac-tion was 4.71 μmol·L-1.As an activator of this reaction,vitamin K3 activated XO in a concentration-dependent manner(according to the logistic fitting formula y=A2+(A1-A2)/(1+(x/x0)^p),with an EC50 of 32.0 μmol·L-1.The kinetic parameters also changed after the addition of vitamin K3.The Km value decreased(4.71-1.34 μmol·L-1)with the increase of vitamin K3 concentrations,while the Vmax value increased(0.08-1.31 μmol·min-1·g-1),leading to an increase in Vmax/Km(17.0-977.6 mL·min·g-1).In addition,the double reciprocal curve fitting found that the activation type of vitamin K3 on XO was mixed.The molecular docking results showed that vitamin K3 bound to the molybdopterin domain of XO and maintained hydrogen bonding interactions with Arg599 and Ser605.CONCLUSION Vitamin K3 is an activator of XO,which can form hydrogen bonds with Arg599 and Ser605 in the XO domain,regu-late its affinity with the substrate xanthine,activate XO and increase the uric acid level.

Objective To investigate the inhibitory effects of pyruvate-ferredoxin oxidoreductase(PFOR)by luteolin and its anti-Clostridium difficile effect.Methods The PFOR encoding sequence of Clostridium difficile was cloned into the expression vector pET-2a and transformed into competent Escherichia coli.The crude enzyme was prepared after induction with IPTG(Isopropyl β-D-Thiogalactoside).The inhibitory rate of the test compounds on PFOR was determined after an 8-hour anaerobic reaction between PFOR and 40 μmol·L-1 of test compounds at 25℃.The minimum inhibitory concentration(MIC)of PFOR inhibitors against C.difficile strains(ATCC BAA 1382 and ATCC BAA 1870)was determined by monitoring the OD600 of the bacterial culture.Molecular docking was performed to investigate the possible interaction mechanisms between PFOR and inhibitors.Results Among the tested compounds,the luteolin showed the strongest inhibitory activity against PFOR,with a single-point inhibition rate of approximately 33%,which is comparable to that observed with the positive inhibitor nitazoxanide(40%).Molecular docking revealed that luteolin could form hydrogen bonds with Asp428,Val431,Gly429,Asp456,Lys458,Lys459,and other residues in the PFOR domain.The MIC of luteolin against C.difficile was approximately 32 μg·mL-1.Conclusion Luteolin exhibits good activity against C.difficile,and PFOR may be a target for its antibacterial action.

Objective To investigate the therapeutic effect and prognostic significance of lateral lymph node dissection (LPLND) in patients with lateral lymph node (LPLN) metastasis. Methods The clinicopathological data of rectal cancer patients who underwent total mesorectal excision (TME) combined with LPLND and pathologically confirmed as LPLN metastasis after operation were retrospectively analyzed. The clinicopathological characteristics and metastasis rules of patients with LPLN metastasis were discussed, and the survival prognosis after LPLND was analyzed. Results A total of 102 rectal cancer patients with pathologically confirmed LPLN metastasis were included. The common sites of LPLN metastasis were internal iliac vessels lymph nodes (n=68, 66.7%), followed by obturator lymph nodes (n=44, 43.1%), and common iliac vessels or external iliac vessels lymph nodes (n=12, 11.8%). There were 10 patients (9.8%) with bilateral LPLN metastases, and the mean number of LPLN metastases was 2.2±2.4, among which 16 patients (15.7%) had LPLN metastases number≥2. The 3-year OS (66.8% vs. 7.7%, P < 0.001) and DFS (39.1% vs. 10.5%, P=0.012) of patients with LPLN metastases to the external iliac or common iliac lymph node were significantly lower than those with metastases to the internal iliac or obturator lymph node. The multivariate analysis showed that LPLN metastasis to external iliac or common iliac lymph node was an independent risk factor both for OS (HR=3.53; 95%CI: 1.50-8.31; P=0.004) and DFS (HR=2.40; 95%CI: 1.05-5.47; P=0.037). Conclusion LPLN mainly metastasizes to the internal iliac or obturator lymph node areas. The survival of patients with metastasis to the external iliac or common iliac lymph node cannot be improved by LPLND, and thus systemic comprehensive treatment is often the optimal treatment option.

The treatment of locally advanced rectal cancer (LARC) is extremely challenging, and it is difficult to achieve satisfactory results with surgical resection alone. In recent years, the diagnosis and treatment of LARC tends to be multi-disciplinary (MDT) mode. The emerging neoadjuvant treatment strategy is a milestone. At present, the preferred treatment for LARC is neoadjuvant chemoradiotherapy combined with total mesorectal excision. This article summarizes the main treatments of LARC neoadjuvant therapy, hoping to provide reference for clinical diagnosis and treatment.

Uridine diphosphate glucuronic acid transferase (UDP-glucuronosyltransferases, UGT) is an important Ⅱmetabolic enzymes in the body. It is invovled in the metabolism of exogenous compounds, and also in endogenous substances such as bile acid metabolism and regulation. Parsing uridine diphosphate glucuronic acid transferase mediated bile acid metabolism and its influence factors can help enhance related disease treatment and prevention. Studies have shown that the interaction between UGT and bile acids is influenced by many endogenous and exogenous factors. This paper will focus on the effects of internal and exogenous factors such as nuclear receptors, genetic factors, xenobiotics and liver-related diseases on the action of UGT enzyme, and discuss the potential mechanism of bile acid balance intervention.

Methods:Two thousand standard sections images werre collected from 2 000 clinical retrospective pediatric hip ultrasound videos from January 2019 to January 2021. All standard sections were annotated by the annotation team through the self-designed software based on Python 3.6 environment for image cross-media data annotation and manual review standardization process with unified standards. Among them, 1 753 were randomly selected for training the deep learning system, and the remaining 247 were used for testing the system. Further, 200 standard sections were randomly selected from the test set, and 8 clinicians independently completed the film reading annotation. The 8 independent results were then compared with the AI results.Results:The testing set consists of 247 patients. Compared with the clinician's measurements, the area under the receiver operating characteristic curve (AUC) of diagnosing hip joint maturity was 0.865, the sensitivity was 76.19%, and the specificity was 96.9%. The AUC of AI system interpretation under Graf detailed typing was 0.575, the sensitivity was 25.90%, the specificity was 89.10%. The 95% LoA of α-angle determined by Bland-Altman method, of -4.7051° to 6.5948° ( Bias -0.94, P<0.001), compared with clinicians' measurements. The 95% LoA of β-angle, of -7.7191 to 6.8777 ( Bias -0.42, P=0.077). Compared with those from 8 clinicians, the results of AI system interpretation were more stable, and the β-angle effect was more prominent. Conclusion:The AI system can quickly and accurately measure the Graf correlation index of standard DDH ultrasonic standard diagnosis plane.

Objective:To evaluate the safety and feasibility of radical surgery and explore prognostic factors affecting cancer-specific survival (CSS) in elderly patients with colorectal cancer (CRC).Methods:From Jan 2010 to Dec 2020, a total of 372 elderly (aged over 80 years) CRC patients who underwent curative resection at the National Cancer Center were enrolled. Preoperative clinical features, perioperative outcomes and postoperative pathological characteristics were collected.Results:In the multivariable COX regression analysis, BMI ≥30 kg/m 2 ( HR:2.30, 95% CI: 1.27-4.17, P=0.006) and N1-N2 stage ( HR: 2.97,95% CI:1.48-5.97, P=0.002) correlated with worse CCS. Conclusions:The results of this study demonstrated that radical resection for CRC is safe and feasible for patients over 80 years of age. BMI and N stage were independent prognostic factors for elderly CRC patients after radical resection.

Objective: To evaluate the risk factors of perineal incision complications after abdominal abdominoperineal resection (APR) in elderly patients with rectal cancer. Methods: From January 2007 to September 2018, the clinical data of 72 elderly rectal cancer patients (age≥80 years) underwent abdominoperineal resection at Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were collected and retrospectively analyzed. Univariate and multivariate analyses were performed to determine the risk factors of perineal incision complications in elderly patients with rectal cancer after APR. Results: Of the 76 patients, 47 were male and 25 were female, with an average age of (81.8±1.8) years. The incidence of postoperative perineal incision complications was 23.6% (17/72), including 5 cases of wound infection, 4 cases of incision fat liquefaction, and 8 cases of delayed wound healing. All of the patients were well recovered and discharged without death. The result of univariate analysis showed that, the occurrence of perineal incision complications was associated with serum albumin level < 35g/L (χ²=4.860, P=0.027), intraperitoneal chemotherapy with fluorouracil sustained release/lobaplatin rinse (χ²=8.827, P=0.003), pelvic restoration (χ²=9.062, P=0.003), diabetes (χ²=6.387, P=0.011) and coronary heart disease (χ²=7.688, P=0.006). Multivariable logistic regression analysis showed that the intraoperative pelvic restoration (OR=0.17, 95% CI: 0.04~0.82, P=0.027) and diabetes (OR=4.32, 95% CI: 1.05~17.81, P=0.043) were independent risk factors for perineal incision complications. Conclusions Elderly patients with rectal cancer who undergo APR should preserve and restore the pelvic peritoneum as much as possible. Moreover, perioperative blood glucose monitoring is a powerful guarantee for preventing complications of perineal incision.

Objective:To investigate the risk factors of severe postoperative complications in elderly patients with colorectal cancer aged over 80 years old.Methods:A retrospective case-control study was conducted to collect and analyze the clinicopathological data of patients (≥80 years old) who underwent radical colorectal cancer surgery at department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2010 to December 2018. A total of 269 patients were included in the study, including 160 males and 109 females. The average age was 83 (80-94) years. Among them, the pathological TNM stage was 16 in stage I, 76 in stage II, 167 in stage III, and 10 in stage IV. According to Clavien-Dindo classification, the postoperative complications of grade III and above were defined as serious complications. To analyze the relationship between the patient's clinical data, such as general information, the surgeon's experience (whether to complete more than 500 radical colorectal cancer surgery), intraoperative conditions and the occurrence of severe complications. Univariate analysis was conducted with the chi-squared test. Multivariate logistic regression analysis was used for statistically significant variables in univariate analysis.Results:Of the 269 patients, 34 (12.6%) had severe complications after surgery. The incidence of postoperative complications ranged from high to low, respectively, for pulmonary infection (8/269,3.0%), intestinal obstruction (8/269, 3.0%) and anastomotic leakage (7/269, 2.6%). One patient died of pulmonary embolism and one patient died of multiple organ failure, with a perioperative mortality rate of 0.7% (2/269). On univariate analysis, the occurrence of severe postoperative complications was associated with age (χ 2=8.181, P=0.004), American society of anesthesiologists grade (χ 2=7.945, P=0.005), preoperative albumin level (χ 2=9.088, P=0.003), operation experience (χ 2=9.395, P=0.002). Multivariable logistic regression analysis showed that age ≥85 years old (OR=4.415, 95% CI: 1.702-11.453, P=0.080), preoperative albumin <35 g/L (OR=2.544, 95%CI: 1.083-5.974, P=0.032), and less-experieced group (OR=2.475, 95% CI:1.082-5.661, P=0.032) was independent risk factor for severe postoperative complications. The incidence of serious postoperative complications was similar in patients undergoing laparoscopy and laparotomy [10.1% (17/169) vs. 17.0% (17/100), χ 2=2.741, P=0.098]. Conclusion:Adequate preoperative evaluation, appropriate perioperative nutritional support and experienced specialists are the key factors to ensure the successful perioperative period of elderly patients with colorectal cancer aged over 80 years old. In addition, more attention should be paid to the elderly patients aged ≥85 years.

Objective:To investigate the risk factors of severe postoperative complications in elderly patients with colorectal cancer aged over 80 years old.Methods:A retrospective case-control study was conducted to collect and analyze the clinicopathological data of patients (≥80 years old) who underwent radical colorectal cancer surgery at department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2010 to December 2018. A total of 269 patients were included in the study, including 160 males and 109 females. The average age was 83 (80-94) years. Among them, the pathological TNM stage was 16 in stage I, 76 in stage II, 167 in stage III, and 10 in stage IV. According to Clavien-Dindo classification, the postoperative complications of grade III and above were defined as serious complications. To analyze the relationship between the patient's clinical data, such as general information, the surgeon's experience (whether to complete more than 500 radical colorectal cancer surgery), intraoperative conditions and the occurrence of severe complications. Univariate analysis was conducted with the chi-squared test. Multivariate logistic regression analysis was used for statistically significant variables in univariate analysis.Results:Of the 269 patients, 34 (12.6%) had severe complications after surgery. The incidence of postoperative complications ranged from high to low, respectively, for pulmonary infection (8/269,3.0%), intestinal obstruction (8/269, 3.0%) and anastomotic leakage (7/269, 2.6%). One patient died of pulmonary embolism and one patient died of multiple organ failure, with a perioperative mortality rate of 0.7% (2/269). On univariate analysis, the occurrence of severe postoperative complications was associated with age (χ 2=8.181, P=0.004), American society of anesthesiologists grade (χ 2=7.945, P=0.005), preoperative albumin level (χ 2=9.088, P=0.003), operation experience (χ 2=9.395, P=0.002). Multivariable logistic regression analysis showed that age ≥85 years old (OR=4.415, 95% CI: 1.702-11.453, P=0.080), preoperative albumin <35 g/L (OR=2.544, 95%CI: 1.083-5.974, P=0.032), and less-experieced group (OR=2.475, 95% CI:1.082-5.661, P=0.032) was independent risk factor for severe postoperative complications. The incidence of serious postoperative complications was similar in patients undergoing laparoscopy and laparotomy [10.1% (17/169) vs. 17.0% (17/100), χ 2=2.741, P=0.098]. Conclusion:Adequate preoperative evaluation, appropriate perioperative nutritional support and experienced specialists are the key factors to ensure the successful perioperative period of elderly patients with colorectal cancer aged over 80 years old. In addition, more attention should be paid to the elderly patients aged ≥85 years.