Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg^-1) and high dose (10 mg·kg^-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.

Objective:To study effects of balance and motor function of walking stability training guided by mirror neuron theory for stroke patients with hemiplegia.Methods:A total of 67 stroke with hemiplegia from January 2019 to June 2020 in Heze Municipal Hospital were divided into experimental group (34 cases) and control group (33 cases). All patients were given conventional rehabilitation training, the control group was given body weight support treadmill training, the experimental group was given mirror visual feedback therapy combined with body weight support treadmill training. The training time was 8 weeks. The body balance function, body motor function and life quality were evaluated by Fugl-Meyer Balance scale(FM-B), Berg Balance Scale(BBS), Tinetti Gait Analysis(TGA), Functional Ambulation Category scale(FAC), Stroke-Specific Quality of Life scale (SS-QOL) and compared before and after training between the two groups.Results:There was no significant difference in the score (classification) of FM-B, BBS, TGA, SS-QOL, FAC before training between the two groups( P>0.05). The score (classification) of FM-B, BBS, TGA, FAC after training were (11.35±1.32), (47.33±6.20), (9.32±1.12) points and (3.54±0.61)grades in the experimental group and (9.86±1.25), (42.14±6.35), (8.25±1.32) points and (3.15±0.54) grades in the control group. There were statistically significant of differences( t values were 2.768-4.741, P<0.05). The score of energy, activity ability, emotion, self-care ability, thinking, upper limb function and life quality total score of SS-QOL were (10.31±1.43), (21.46±4.45), (17.64±3.36), (17.32±3.15), (16.23±2.21), (159.11±16.34) points in the experimental group and (8.46±1.21), (17.32±3.24), (15.35±3.11), (14.78±2.32), (8.45±1.25), (13.45±1.54), (141.65±17.24) points in the control group. There were statistically significant of differences( t values were 2.893-7.096, P<0.05). Conclusions:Walking stability training based on mirror neuron theory help to restore limb balance and motor function, and improve life quality in stroke patients with Hemiplegia.

Objective To investigate the distribution and changing resistance proifle ofSalmonella isolates in hospitals across China during the period from January 2005 to December 2014.Methods Seventeen general hospitals and two children’s hospitals were involved in this program. Antimicrobial susceptibility testing was carried out by means of a unified protocol using Kirby-Bauer method or MIC determination. The results were analyzed according to CLSI 2014 breakpoints.Results The proportion ofSalmonella isolates increased with time from 0.2% in 2005 to 0.7% in 2014. A total of 3 478Salmonella strains were collected from 19 hospitals. The proportion ofSalmonella typhimurium andSalmonella enteritidis was 27.4% and 24.4%, respectively. During the 10-year period, theSalmonella strains showed highest resistance rate to ampicillin (33.3%-64.8%), but low resistance to cefoperazone-sulbactam (0-5.3%) and ciprofloxacin (2.4%-14.3%).S. typhimurium showed higher resistance rate thanS. typhi,S. paratyphi andS. enteritidis. About 76.8% and 50.5% ofS. typhimurium were resistant to ampicillin and trimethoprim-sulfamethoxazole. The average prevalence of multi-drug resistantSalmonellawas 3.9% in the ten-year period, the highest (7.5%) was in 2005, the lowest (1.5%) in 2013.Conclusions During the period from 2004 to 2015, majority of theSalmonella isolates in hospitals across China wasS. typhimurium andS. enteritidis. Ampicillin and trimethoprim-sulfamethoxazole are no longer appropriate for empirical treatment ofS. typhimurium infection due to high resistance rate.Salmonella isolates are relatively more susceptible to third-generation cephalosporins and quinolones. Ongoing monitoring is necessary to identify multi-drug resistant strains ofSalmonella.

OBJECTIVETo study the inhibition of berberine (BBR) against ECV-304 apoptosis induced by Staphylococcus aureus (S. aureus).

METHODSECV-304 cells were pre-treated with 128 microg/mL BBR for 2 h and then S. aureus was added (1:100). The viability of cells was detected by MTT (3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The morphological changes were observed by Hoechst 33258 staining. The protection of BBR for infected cells was detected by DNA Ladder.

RESULTSECV-304 cells' viability were not obviously affected by berberine. But S. aureus induced ECV-304 cells' viability could be significantly inhibited by pre-treatment of BBR (P < 0.05). Besides S. aureus-induced ECV-304 apoptosis could be reduced, with significantly lessened apoptotic body and unobvious DNA degradation.

CONCLUSIONBBR could significantly inhibit S. aureus induced ECV-304 apoptosis.

Apoptosis ; drug effects ; Berberine ; pharmacology ; Cell Line ; Human Umbilical Vein Endothelial Cells ; drug effects ; microbiology ; pathology ; Humans ; Staphylococcus aureus

Objective To investigate the antimicrobial resistance in the A cinetobacter baumannii strains in different parts of China during 2012 .Methods A total of 8 739 clinical isolates of Acinetobacter were collected from 13 general hospitals and two children’s hospitals ,of which most were A . baumannii (89 .6% , 7 827/8 739 ) . Antimicrobial susceptibility testing was carried out by means of Kirby-Bauer method according to the unified protocol . The susceptibility testing data were analyzed by WHONET 5 .6 software according to CLSI 2013 breakpoints .Results Majority (85 .4% ) of the Acinetobacter strains were isolated from inpatients .The remaining 14 .6% were from outpatients and emergency room patients .Of the 7 827 strains of A .baumannii , 10 .9% ,35 .2% ,35 .7% and 43 .4% were resistant to tigecycline ,minocycline ,cefoperazone-sulbactam and amikacin , respectively .The percentage of A .baumannii resistant to imipenem and meropenem was 63 .5% and 68 .2% ,respectively . The antimicrobial resistant pattern varied in different hospitals . The resistance of A . baumannii varied between different clinical departments .A number of pandrug resistant (PDR) (20 .0% ,1 567/7 827) and multidrug-resistant (MDR) (45 .0% , 3 521/7 827 ) A . baumannii were identified . Conclusions A . baumannii is the most popular pathogenic bacteria among Acinetobacter .The antibiotic resistance of A .baumannii is still increasing .Cefoperazone-sulbactam and minocycline has good in vitro antibacterial activity against A .baumannii .The antibiotic resistance of A .baumannii varies greatly with hospital and department .

OBJECTIVETo explore the risk factors for pulmonary metastasis after curative resection of colorectal cancer in order to improve the effectiveness of follow-up and the rate of early diagnosis for the high-risk patients.

METHODSThe clinicopathological and follow-up data of 268 patients with colorectal cancer undergoing radical resection from January 2004 to December 2006 in the Beijing Cancer Hospital were analyzed retrospectively. Patients were divided into study group including 16(6.0%) patients who developed lung metastasis and control group without lung metastasis. The high-risk variables associated with lung metastasis were reviewed by univariate analysis and multivariate analysis.

RESULTSLung metastasis developed in 16 patients, including 10 cases with unilateral lung metastasis and 6 with bilateral. The median duration from colorectal surgery to identification of lung metastasis was 13.9 months. The diagnosis rate of pulmonary metastasis by enhanced chest CT was 81.3%(13/16). Univariate analysis identified the following associated with significant factors associated with pulmonary metastasis: primary tumor location(P=0.003), adjuvant chemotherapy(P=0.034), TNM stage(P=0.005) and preoperative serum carcinoembryonic antigen(CEA) level (P=0.001). Multivariate analysis revealed that primary tumor location(rectum) and preoperative serum CEA level(≥5 μg/L) were independent risk factors for pulmonary metastasis(both P<0.05).

CONCLUSIONSPrimary tumor location and elevated preoperative CEA level are independent risk factors for pulmonary metastasis. Strict postoperative follow-up and routine chest enhanced CT examination is necessary for this particular patient population.

Carcinoembryonic Antigen ; blood ; Colorectal Neoplasms ; Humans ; Lung Neoplasms ; diagnosis ; Prognosis ; Risk Factors

OBJECTIVETo observe the short term effect of argon plasma coagulation (APC) combined with cryotherapy via bronchoscopy for treatment of severe post-intubation tracheal stenosis in a child.

METHODA 3-year old boy was admitted for cephalothorax abdominal compound trauma and dyspnea, who had severe post-incubation tracheal stenosis. The agreement about the operation risk was signed by the parents. Endotracheal APC procedure was performed with a bronchoscope under general anesthesia. The APC probe was put into the working channel of the bronchoscope. The stenotic lesion was endoscopically visualized and then coagulated by argon plasma. Such coagulation was carried out several times at the stenotic site until it gradually became dilated. The devitalized tissue was mechanically removed with grasping forceps. Thereafter, bronchoscopic cryosurgery was repeatedly performed at the stenotic site. Clinical symptoms, signs and bronchoscopic manifestations were observed right after operation, after 1 day, 10 days, 1 month and 6 months separately.

RESULTTracheal tissue hyperplasia and cyanosis disappeared, laryngeal stridor and dyspnea improved obviously right after the operation. General condition of the patient was well, there was no laryngeal stridor and dyspnea 10 days after operation. The mucosa of the surgical site was smooth and no tracheostenosis was seen under bronchoscope at 1 month and 6 months after the operation.

CONCLUSIONArgon plasma coagulation combined with cryotherapy via bronchoscope is an effective method to treat tracheal stenosis of children, which needs further exploration for the application.

Argon Plasma Coagulation ; methods ; Bronchoscopy ; Child, Preschool ; Cryotherapy ; Humans ; Intubation, Intratracheal ; adverse effects ; Laryngeal Diseases ; etiology ; surgery ; Male ; Trachea ; surgery ; Tracheal Stenosis ; etiology ; surgery ; Treatment Outcome ; Wounds and Injuries ; surgery

Objective To construct the recombinant baculovirus with NA gene of Influenza H1N1 virus.Methods Full-length NA gene of Influenza virus H1N1 (A/PR/8/34) was amplified by PCR and inserted into pFastBacdual vector to construct the recombinant baculovirus transfer vector pFBD-NA.Recombinant shuttle vectors rBacmid-NA was then obtained after transforming DH10B competent cells containing bacmid plasmids.After transfecting into sf9 cells,recombinant baculovirus rBac-NA was obtained.The rBac-NA genome was extracted and identified by PCR.NA protein expressed by recombinant baculovirus-infected sf9 cells was determined by IFA,Western Bolt and ELISA.Results PCR results proved that recombinant shuttle vectors rBacmid-NA was successfully constructed.NA protein was detected by IFA and showed strong specific green fluorescence on the surface of infected cells.NA protein was recognized by two polyclonal antibodies specific for NA in Western Blot.ELISA showed specific reaction of recombinant NA protein with mouse polyclonal antibody against influenza virus (PR8),indicating high antigenicity.Conclusion Recombinant baculovirus rBac-NA that expresse NA protein of influenza virus was successfully constructed.This work provides a basis for further study on NA protein function and novel influenza vaccine development.

Adolescent ; Adult ; Antibody Formation ; DNA, Recombinant ; Hepatitis B Antibodies ; blood ; Hepatitis B Vaccines ; immunology ; Humans ; Immunization ; Middle Aged ; Pichia ; genetics ; Saccharomyces ; genetics ; Young Adult