Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective To explore the mechanism of Xinkang Prescription (Descurainiae Semen Lepidii Semen,Armeniacae Semen Amarum,Poria,Astragali Radix,Citri Reticulatae Pericarpium,Sparanii Rhizoma) for purging the lung and promoting diuresis in treating heart failure by regulating phosphorylation of phospholamban (PLN). Methods Forty-eight C57BL/6J mice were randomly divided into sham-operation group,model group,low-,medium-and high-dose Xinkang Prescription groups(0.455,0.91,1.82 g·kg-1),as well as Entresto group (25 mg·kg-1),with eight mice in each group. The model of ischemic heart failure was established by ligating the left anterior descending coronary artery in mice. After the model was successfully replicated,mice were orally administered with the above-mentioned dosages of Xinkang Prescription and Entresto once a day for four weeks,while sham-operation group and model group were given 0.9％ sodium chloride solution by gavage at the same time. Echocardiography was used to detect the cardiac function of the mice in each group,including left ventricular ejection fraction (LVEF),left ventricular fractional shortening (LVFS),left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in cardiac tissue of mice. qRT-PCR was used to detect the mRNA expression of BNP. Western Blot and Jess were used to detect the expression of PLN,p-Thr17-PLN,p-Ser16-PLN,sarcoplasmic reticulum calcium ATPase 2a (SERCA2a),protein kinase A (PKA),p-PKA,Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ) and p-CaMKⅡ in cardiac tissue,and to calculate the ratio of SERCA2a/PLN. The SERCA2a activity was determined by the inorganic phosphorus method.Results Compared with the sham-operation group,the model group showed a significant decrease in LVEF and LVFS(P<0.01) and a significant increase in LVEDD and LVESD (P<0.01). HE staining showed the fibril of cardiac muscle broke and disarranged,accompanied by inflammatory cell infiltration. The mRNA expression of BNP was significantly up-regulated (P<0.01),and the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly down-regulated (P<0.01),while the expression of p-CaMKⅡ was up-regulated (P<0.01). Compared with the model group,LVEF and LVFS in medium-,high-dose Xinkang Prescription groups were significantly increased(P<0.01),while LVEDD and LVESD were significantly decreased (P<0.01). HE staining showed significant improvement in the pathological damage of cardiac tissue. The expression level of BNP was significantly decreased (P<0.01),while the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly increased (P<0.01). The protein expression of p-CaMKⅡ was remarkably decreased(P<0.05). Conclusion Xinkang Prescription can effectively improve cardiac function of mice with heart failure,which may be related to enhance phosphorylation levels of phospholamban.

Modafinil can be used to treat narcolepsy and depression, but there are few reports of mental disorders caused by modafinil at home and abroad. This artical reported a case of mental disorder following high-dose combined use of modafinil and Armodafinil in the hope of attracting attention of the clinicians.

Modafinil can be used to treat narcolepsy and depression, but there are few reports of mental disorders caused by modafinil at home and abroad. This artical reported a case of mental disorder following high-dose combined use of modafinil and Armodafinil in the hope of attracting attention of the clinicians.

Objective To test reliability and validity on the scale of hurting factors participation for mental disorders (SHFP-MD).Methods 402 cases were retrospectively evaluated by SHFP-MD from 13 forensic psychiatric appraisal agencies in China,and all cases were involved causal relationships in mental injury from July 2010 to June 2012.42 cases were evaluated a month later again.13 raters evaluated respectively for five cases.52 cases involved causal relationship of mental impairment were evaluated prospectively in January 2013 to June 2014.The validity of the scale was tested by experts assessed as a criterion level of relationship.Results ①The retest correlation coefficient on all items of SHFP-MD were between 0.746-0.989,and the time reliability of test-retest on the full scale score was 0.970 interval of one month.Raters reliability between 0.57 to 1.00; overall average reliability was 0.84 (P＜0.01).②The total coincidence rate was 90.4％-91.0％ between the demarcation scores of SHFP-MD and the grade identification of forensic psychiatrists respectively and prospectively(P＞0.05).Conclusion SHFP-MD has good reliability and validity,and met the basic requirements of scale assessment.

Objective To observe the clinical effect of magnesium isoglycyrrhizinate on moderate and severe nonalcoholic steatohepatitis(NASH) and analyse its mechanism. Methods 42 cases with moderate and severe nonalcoholic steatohepatitis were selected in our study. All patients were divided into observation group and control group randomly. Control group were received simvastatin while the observation group were received simvastatin combined with magnesium isoglycyrrhizinate treatment. The course was 6 weeks.The changes of NASH classiifcation, clinical symptom, liver function, lipid levels and liver ifbrosis items in two groups before and after treatment were observed and recorded. Results All patients were received 6 week treatment, none of them dropped out. The clinical symptoms were improved in both two groups. There were 5 severe NASH improved to moderate NASH, 8 moderate NASH improved to mild NASH in observation group while only 3 severe NASH improved to moderate NASH in control group. The difference of NASH classiifcation between two groups was signiifcant(P<0.05). Compared to pre-treatment, the AST, ALT, TBIL,γ-GT were decreased in both two groups. But the liver function items in observation were lower than control group(P<0.05). The lipid level were decreased in both two group and there were no signiifcant differences between two groups after treatment. The level of PC III, HA, C-IV were decreased in observation group while had no changes in control group. Conclusion The magnesium isoglycyrrhizinate could decrease the AST, ALT and lipid level, improve the classiifcation of liver ifbrosis, and had low rate of side effect during treatment.

Objective To examine the relationship between renal vascular lesions and clinical prognosis in lupus nephritis patients. Methods Renal biopsy specimens and clinical data of 451 patients with lupus nephritis in our hospital from January 1998 to February 2006 were enrolled in this study. According to renal vascular lesions, those patients were classified into six groups: no renal vascular lesion (NVL), immune complex deposits (ICD), lupus vasculopathy (LV),thrombotic microangiopathy (TMA), vasculitis (VAS) and arteriosclerosis (AS). The relationship of renal vascular lesions and the clinical features was retrospectively analyzed. Results (1) In 451 lupus nephritis patients, 247 eases (54.8%) had renal vascular lesion. The incidence of the ICD, LV, TMA, AS and VAS were 8.4%, 9.8%, 6.7%, 29.3% and 0.7%, respectively. (2) The incidence of vascular lesions in IV type lupus nephritis was 69.7%, which was higher than others.(3) Except ICD group, the incidences of renal insufficiency and hypertension were significantlyhigher in vascular lesion groups than those in NVL group (P<0.05). TMA group showed the most severe clinical manifestation, including anemia and depression of platelet. (4) The prognosis of TMAgroup was the worst. The prognosis among other groups was not significantly different.Conclusions Vascular lesions are common in lupus nephritis. TMA patients present not only the most severe clinical manifestation with the poorest prognosis. Other vascular lesions also indicate an elevation of blood pressure and Scr level, but without significant difference in prognosis.