Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

OBJECTIVEMacrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China.

METHODSFour macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23S rRNA and erm, were analyzed with nucleotide sequence analysis.

RESULTSVaried effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191A and T2221C on rrl were specific for the M. abscessus complex (MABC). Seven sites, G2140A, G2210C, C2217G, T2238C, T2322C, T2404C, and A2406G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192G, T2358G, and A2636G, were observed only in M. fortuitum and one site G2152A was specific for M. gordonae. The genes erm(39) and erm(41) were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar.

CONCLUSIONThe susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23S rRNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.

Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; China ; Drug Resistance, Bacterial ; Gene Expression Regulation, Bacterial ; Humans ; Macrolides ; pharmacology ; Mycobacterium ; drug effects ; genetics ; Polymorphism, Genetic

Objective To analyze the status of quality indicators(QI) on specimen acceptability and establish preliminary qual ity specification.Methods Web based External Quality Assessment system was used to collect data of laboratories partici pated in "Medical quality control indicators in clinical laboratory" from 2015 to 2017,including once in 2015 and 2017 and twice in 2016.Rate and sigma scales were used to evaluate incorrect sample type,incorrect sample container,incorrect fill level and anticoagulant sample clotted.The 25th percentile (P25) and 75th percentile (P75) of the distribution of each QI were employed to establish the high,medium and low specification.Results 5 346,7 593,5 950 and 6 874 laboratories sub mitted the survey results respectively.The P50 of biochemistry (except incorrect fill level),immunology and microbiology reach to 6σ.The P50 of clinical laboratory is 4 to 6σ except for incorrect sample container.There is no significant change of the continuous survey results.Based on results in 2017 to establish the quality specification,the P25 and P75 of the four QIs is 0 and 0.084 4 ％,0 and 0.047 6 ％,0 and 0.114 2 ％,0 and 0.078 4 ％,respectively.Conclusion According to the results of the survey,most laboratories had a faire performance in biochemistry,immunology and microbiology,and clinical laboratory needs to be strengthened.Laboratories should strengthen the laboratory information system construction to ensure the actual and reliable data collection,and make a long time monitoring to achieve a better quality.

Objective To explore the effect of ambroxol hydrochloride combined with budesonide on the airway inflammation and lung oxidative stress in allergized rats.Methods Forty cases of clean health level SD male rats were randomly divided into blank control group,model group,positive control group and test group,10 rats in each group.Except blank control group,the rats of other groups were treated with ovalbumin to build the asthma model.Model group was intraperitoneally injected 10％ ovalbumin 1 mL on 1,8 d,and 1％ ovalbumin was inhaled on 15 d,once a day for 0.5 h,till the rats appear abdominal muscle contraction,nodding and so on.Positive control group was inhaled 0.02％ budesonide 30 min before nebulization for 1 h before nebulization.The test group was intraperitoneal injected ambroxol hydrochloride 60 mg · kg-1 at 25 min before inhalation of budesonide on the basis of positive control group.Each group were intervention for 10 weeks.The numbers of lymphocytes and eosinophils in bronchoalveolar lavage fluid of rats in each group were measured by cell counting method.The airway histopathological and morphological changes were observed by hematoxylin-eosin (HE) staining.Colorimetric method was used to detect the levels of oxidative stress in lungs of each group.Results The percentages of eosinophils in blank control group,model group,positive control group and test group were (1.29 ±0.41)％,(81.44 ±5.15)％,(37.51 ±5.38)％,(20.14±4.65)％,the percentages of lymphocytes were (4.01 ± 0.87) ％,(17.38-± 2.99) ％,(11.59 ± 2.01) ％,(7.96 ± 1.43) ％.The difference betweent test group and model group and positive control group was statistically significant (P ＜0.01).HE staining showed that the most obvious pathological changes in model group,followed by positive control group.The levels of glutathione (GSH) in lung tissue of blank control group,model group,positive control group and test group were (1.54±0.15),(0.53 ±0.18),(0.79 ±0.09),(1.15 ±0.11) μmol · L-1,and reactive oxygen species (ROS) were (1643 ±163),(4986 ±195),(3619 ± 184) and (2348 ± 171) U mg-1 pro.The GSH,ROS in test group and positive control group had significant difference (P ＜ 0.01).Conclusion Ambroxol hydrochloride combined with budesonide can relieve the airway inflammation and lung oxidative stress in rats with asthma,which can be used for the treatment of acute asthma attacks.

Objective To help the medical student to master the principle and operation of magnetic resonance imaging instrument.Methods The imaging principle,structure and functions of HT-3DNMR-25 magnetic resonance imaging instrument were described,and its application to experiment teaching was introduced including one-dimension imaging,two-dimension imaging,free induction decay signal observation and etc.Results The instrument facilitated the student to master technical principle,imaging method as well as parameters setup and regulation,and could be a supplement to clinical practical teaching.Conclusion The instrument plays an irreplaceable role in teaching,and thus is worthy promoting in colleges.

Clinical breakpoints are used in phaseⅡorⅢclinical trials to categorize microorganisms if susceptibility to new tested antibacterial agents that means the patient infected by the pathogen will be enrolled the study or not.The role of this consensus is to define procedure and required data to setting breakpoints and how to revaluate it in clinical trials.

OBJECTIVETo observe the clinical effect of electric stimulation of long-term retaining needle on analgesia after laparoscopic cholecystectomy (LC) and the impacts on the post-surgical flatus time.

METHODSUnder static absorptive composite general anesthesia, 90 cases of LC were randomized into three groups, 30 cases in each one. In the control group, the analgesia was not applied after LC. In the analgesia-pumper group, the patient controlled intravenous analgesia (PCIA) was used. In the needle-retaining group, the electric acupuncture stimulator was used. The needles were inserted transversely at Riyue (GB 24), Qichong (ST 30) and Yanglingquan (GB 34) and fixed with sterile sticker. Separately, in 8 h and 24 h after surgery, the electric acupuncture stimulation with disperse-dense wave, 2 Hz/100 Hz frequency was applied continuously for 30 min. Visual analogue scale (VAS), adverse reactions such as vomiting and nausea and the postoperative flatus time in 2, 4, 8, 12, 24 and 36 h after surgery were observed and recorded in the three groups.

RESULTSIn 2, 4, 8, 12 and 24 h after surgery, VAS scores in the needle-retaining group and the analgesia-pumper group were all lower than those in the control group (P < 0.05, P < 0.01). The analgesia effect at the above time points in the needle-retaining group was better than that in the analgesia-pumper group (all P < 0.05). There was not adverse reaction in the needle-retaining group. But there were 3 cases of somnolence, 6 cases of nausea and 3 cases of vomiting in the analgesia-pumper group, and 2 cases of nausea and 1 case of vomiting in the control group. The flatus time was quite earlier in the needle-retaining group as compared with the other two groups [(14.77 +/- 4.99) h vs (18.50 +/- 4.22) h, P < 0.01; (14.77 +/- 4.99) h vs (18.17 +/- 4.69) h, P < 0.05].

CONCLUSIONThe electric stimulation of long-term retaining needle is safe and effective in analgesia after LC. It avoids the adverse reactions of analgesics and promotes postoperative flatus.

Acupuncture Analgesia ; instrumentation ; Adult ; Aged ; Cholecystectomy, Laparoscopic ; adverse effects ; Electroacupuncture ; instrumentation ; Female ; Humans ; Male ; Middle Aged ; Pain Management ; Pain, Postoperative ; etiology ; therapy

OBJECTIVETo evaluate the efficacy and safety of colonoscopy-guided placement of self-expandable metallic stent without fluoroscopic monitoring in the emergence management for acute malignant colorectal obstruction.

METHODSClinical data of 42 patients (24 males and 18 females with a mean age of 64.3 years) undergoing colonoscopy-guided placement of self-expandable metallic stents without fluoroscopic monitoring for acute malignant colorectal obstruction between January 2010 and June 2012 were reviewed retrospectively.

RESULTSThe obstruction was located in the rectum (n=19), sigmoid (n=9), descending colon (n=8), splenic flexure (n=1), hepatic flexure (n=3), and ascending colon (n=2). Technical success was achieved in all the 42 patients (100%). The mean time of operation was (11.8±10.4) min (range 1.1-51.0 min). No serious procedure-related complication occurred. Minor bleeding occurred in 3 cases (7.1%). One patient died on the second day after surgery because of heart failure.

CONCLUSIONSColonoscopy-guided placement of self-expandable metallic stents without fluoroscopic monitoring in emergence management for acute malignant colorectal obstruction is effective and safe with shorter operative time.

Adult ; Aged ; Aged, 80 and over ; Colonoscopy ; Colorectal Neoplasms ; complications ; Female ; Humans ; Intestinal Obstruction ; etiology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Stents