Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

Objective:To explore the relationship between the expression of cerebellar zinc finger structure 5(ZIC5)protein in breast cancer and its clinicopathological characteristics,surgical prognosis.Methods:A total of 128 breast cancer patients,who were admitted to our hospital be-tween June 2016 and December 2017,were enrolled in this study.Immunohistochemistry was employed to assess the expression of ZIC5 protein.The positive expression rate of ZIC5 protein in breast cancer tissues was compared with that in normal surgical margin tissues.Additionally,an analysis was conducted to explore the association between the expression of ZIC5 protein and various clinical pathological characteristics of breast cancer patients,as well as its correlation with prognosis.Results:The positive expression rate of ZIC5 protein in breast cancer tissue was higher than that in normal tissue of resection margin.The postoperative survival rate of breast can-cer patients was 81.37％.TNM stage Ⅲ～Ⅳ,undifferentiated/poorly differentiated,tumor diam-eter ≥ 2 cm,invasion depth T3～T4,lymph node metastasis,ZIC5 protein positive expression were all risk factors for poor prognosis of breast cancer surgery.(RR=4.405,5.153,4.520,2.211,3.137,6.079,P＜0.05).The survival rate of patients with negative ZIC5 protein expression in breast cancer tissue was higher than that of patients with positive ZIC5 protein expression(P＜0.05).Conclu-sion:The positive expression rate of ZIC5 protein in breast cancer tissue is higher than that in nor-mal tissue of resection margin,and the expression of ZIC5 protein in cancer tissue is related to clinical stage,tumor differentiation,tumor size,invasion depth,and lymph node metastasis.The above indicators are risk factors for poor prognosis of breast cancer surgery.

Objective: In this study, we aimed to investigate the prevalence of low anterior resection syndrome (LARS) in patients who had survived for more than 5 years after sphincter-preserving surgery for rectal cancer and to analyze its relationship with postoperative time. Methods: This was a single-center, retrospective, cross-sectional study. The study cohort comprised patients who had survived for at least 5 years (60 months) after undergoing sphincter- preserving radical resection of pathologically diagnosed rectal adenocarcinoma within 15 cm of the anal verge in the Department of Gastrointestinal Surgery, Peking University People's Hospital from January 2005 to May 2016. Patients who had undergone local resection, had permanent stomas, recurrent intestinal infection, local recurrence, history of previous anorectal surgery, or long- term preoperative defecation disorders were excluded. A LARS questionnaire was administered by telephone interview, points being allocated for incontinence for flatus (0-7 points), incontinence for liquid stools (0-3 points), frequency of bowel movements (0-5 points), clustering of stools (0-11 points), and urgency (0-16 points). The patients were allocated to three groups based on these scores: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The prevalence of LARS and major LARS in patients who had survived more than 5 years after surgery, correlation between postoperative time and LARS score, and whether postoperative time was a risk factor for major LARS and LARS symptoms were analyzed. Results: The median follow-up time of the 160 patients who completed the telephone interview was 97 (60-193) months; 81 (50.6%) of them had LARS, comprising 34 (21.3%) with minor LARS and 47 (29.4%) with major LARS. Spearman correlation analysis showed no significant correlation between LARS score and postoperative time (correlation coefficient α=-0.016, P=0.832). Multivariate analysis identified anastomotic height (RR=0.850, P=0.022) and radiotherapy (RR=5.760, P<0.001) as independent risk factors for major LARS; whereas the postoperative time was not a significant risk factor (RR=1.003, P=0.598). The postoperative time was also not associated with LARS score rank and frequency of bowel movements, clustering, or urgency (P>0.05). However, the rates of incontinence for flatus (3/31, P=0.003) and incontinence for liquid stools (8/31, P=0.005) were lower in patients who had survived more than 10 years after surgery. Conclusions: Patients with rectal cancer who have survived more than 5 years after sphincter-preserving surgery still have a high prevalence of LARS. We found no evidence of major LARS symptoms resolving over time.
Humans ; Rectal Neoplasms/pathology* ; Cross-Sectional Studies ; Low Anterior Resection Syndrome ; Postoperative Complications/etiology* ; Retrospective Studies ; Flatulence/complications* ; Anal Canal/pathology* ; Diarrhea ; Quality of Life

Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K

Objective To investigate the contamination of Proteus mirabilis in cooked meat products sold in Zhongshan City from 2017 to 2020, and to analyze its drug resistance characteristics. Methods The detected positive strains of Proteus mirabilis were analyzed for drug resistance. The suspected strains of producing extended spectrum β-lactamases were detected by preliminary screening, then its genes were detected by using molecular biology methods and were finally sequenced. Results Among the 184 strains of Proteus mirabilis detected within 4 years, 117 strains were multi-drug resistant. 184 strains of Proteus mirabilis were highly resistant to tetracycline, polymyxin, minocycline, doxycycline and cefazolin, and they had a high sensitivity rate to ampicillin-sulbactam, cefotaxime, Ceftazidime, cefoxitin, gentamicin, ciprofloxacin, amoxicillin-clavulanic acid, and levofloxacin. In addition, all strains were sensitive to amikacin, meropenem and imipenem.Only one strain was isolated to produce extended spectrum β- Lactamase bacteria. Conclusion Comparing 2020 with 2017, the resistance rate of Proteus mirabilis in cooked meat to most antibiotics showed a downward trend, and the detection rate of multi-drug resistant bacteria decreased year by year. Compared with the clinically detected strains, the drug resistance rate of the detected strains in cooked meat is generally lower than that of the clinical strains. The monitoring of drug resistance of Proteus mirabilis should be continuously strengthened, which is of great significance for guiding the rational use of drugs in clinical practice and delaying the emergence of drug-resistant strains.

Aim To investigate the protective effect of mGluR5 activated by VU0360172 on germinal matrix hemorrhage in neonatal rats.Methods Seven day- old SD rats were randomly divided into Sham, GMH, and low-, medium-, and high-dose groups.The model was established by intracerebral injection of collagenase W-S.Then three doses of VU0360172 were injected intraperitoneal^ 3 h after surgery.Sham and GMH group were given the same amount of solvent.Neurobe- havioral tests were performed 24 h after surgery.Then the brain tissues were collected for evaluation of brain water content, brain hemoglobin content and HE stai¬ning.The expressions of Bcl-2 and cleaved-caspase-3 were determined by Western blot.Results Compared with Sham, GMH group had pooler behaviors in neuro- functional tests with increased brain water content and brain hemoglobin content (P < 0.01 ).And brain tis¬sues were destroyed significantly.WB results showed the expression level of Bcl-2 decreased ( P < 0.05 ) , while cleaved-caspase-3 being up-regulated ( P < 0.01).However, the administration of VU0360172 improved neurological function and ameliorated brain edema and hemorrhage ( P <0.01 ).Brain pathologi¬cal damage was reduced.Moreover, the stimulation of mGluR5 up-regulated Bcl-2 protein expression ( P < 0.05 ) and decreased the level of cleaved-caspase-3 ( P <0.01 ).Conclusion Activation of mGluR5 by VIJ0360172 protects against germinal matrix hemor¬rhage in neonatal rats.

The goal of rectal cancer treatment should be to better protect organ function and improve patients' quality of life on the basis of ensuring radical resection. The current evidence has proved the superiority of perioperative chemoradiotherapy in reducing local recurrence and improving long-term survival. From the perspective of organ function protection, however, perioperative chemoradiotherapy has both disadvantages and advantages. Despite the great help in improving long-term outcomes, adverse reactions of chemoradiotherapy can aggravate defecation, urination and sexual dysfunction. Also, for patients with significant or complete remission, if the treatment strategy of local resection or close follow-up is selected, organ function can be preserved to the greatest extent. The key to the choice of treatment is to evaluate preoperatively whether pathological complete response is achieved. It should be kept in mind that preserving organ itself is not the same as protecting organ function. For patients who need perioperative chemoradiation, the optimal treatment methods should be chosen based on the patient's condition. Surgeons should fully evaluate organ function before operation, select the appropriate treatment strategy, pay special attention to the protection of important organs and nerves during surgeries, and carry out close postoperative follow-up and organ function rehabilitation as soon as possible, so as to reduce the incidence of dysfunction and the impact on the quality of life.
Chemoradiotherapy ; Humans ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Quality of Life ; Rectal Neoplasms/surgery* ; Treatment Outcome ; Watchful Waiting

Objective: To understand the current status of diagnosis and treatment regarding the protection of defecation function in Chinese surgeons performing sphincter-preserving resections (SPR) for rectal cancer in order to discover the problems existing in the function protection during SPR and provide support and reference for the standardized clinical management of rectal cancer. Methods: A cross-sectional survey was performed. Colorectal surgeons who obtained the medical qualifications and volunteered to participate in this study were included, and respondents with incomplete information were excluded. From October 18 to 22, 2020, randomized sampling was conducted among Chinese colorectal surgeons from Chinese Association of Colorectal Surgeons, Chinese Colorectal Cancer Committee, Chinese Sexology Association Anal functional Surgery Committee and National Health Commission Capacity Building and Continuing Education Committee. The questionnaire included basic information of the respondents, assessment of defecation function before SPR, intraoperative details, postoperative follow-up, evaluation and intervention of patients with low anterior resection syndrome (LARS). Observation indicator: results of the questionnaire survey. Result: A total of 231 questionnaires were collected, and 230 were effective, with an effective rate of 99.6%. Among these participants, 217 (94.3%) were males; 107 (46.5%) had medical doctor degrees; 129 (56.1%) were national commission members in colorectal surgery; 137 (59.6%) performed more than 50 SPR operations per year; 211 (91.7%) assessed defection function by auxiliary examinations before SPR. Rigid sigmoidoscopy (n=116, 55.0%) and anorectal manometer (n=81, 38.4%) were the most commonly used method. Among the 230 respondents, 64.8% (n=149) of surgeons used 2D laparoscopy for SPR surgery most commonly, and 51.3% (n=118) of surgeons performed direct colorectal anastomosis for reconstruction, and 98.3% (n=226) used staplers during anastomosis. All the surgeons indicated that they would follow up patients after SPR, and outpatient clinic was the most common method (84.4%, 184/230). When LARS occurred, 50.0% (115/230) of surgeons chose defecation function scale and 78.7% (181/230) actively provided guidance and intervention for patients. Conclusions: Chinese colorectal surgeons still have shortcomings in the protection of defecation function during SPR for rectal cancer. They do not make enough preoperative functional evaluation and postoperative functional recovery estimate for patients. The knowledge and use of defecation function scales and interventions on LARS are expected to be standardized.
Anal Canal/surgery* ; China ; Cross-Sectional Studies ; Defecation ; Humans ; Male ; Postoperative Complications/prevention & control* ; Rectal Neoplasms/surgery* ; Surgeons ; Surveys and Questionnaires ; Syndrome

Sexual dysfunction with the incidence of 5%-90% is a common postoperative complication of rectal cancer and the ratio of men and women is similar. Sexual function is innervated by the abdominal-pelvic autonomic nerve. Different sexual dysfunctions can be caused by different parts and degrees of injury in autonomic nerve during operations of rectal cancer. With the development of pelvic autonomic nerves preservation in rectal cancer radical resection, postoperative sexual function can be protected. There may be many factors increasing the incidence of postoperative sexual dysfunction in rectal cancer, such as postoperative psychological factors, stoma, abdominal-perineal resection and radiotherapy. The effects of laparoscopic surgery, robotic surgery, transanal total mesorectal excision and lateral lymph node dissection on postoperative sexual function remain controversial. Based on the multidisciplinary cooperation model, attention should be paid to psychological intervention of patients and their partners. In clinical practice, for male using phosphodiesterase-5 inhibitors, vacuum erectile devices, injection of vasodilators through the penis or urethra, and for female local application of estrogen and lubricants in the vagina are effective treatment for postoperative sexual dysfunction of rectal cancer. In addition, stem cell therapy has a promising prospect for sexual dysfunction.
Female ; Humans ; Laparoscopy ; Lymph Node Excision ; Male ; Rectal Neoplasms/surgery* ; Rectum/surgery* ; Sexual Dysfunction, Physiological/etiology*

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.
China ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Quality Control