The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective:To investigate the status of frailty and activities of daily living (ADL) in maintenance hemodialysis (MHD) patients, and to explore the effect of frailty phenotype on ADL.Methods:The patients who underwent MHD in Kidney Disease Center of the First Affiliated Hospital from March 2019 to March 2020 were enrolled in this study. The demographic and laboratorial data were collected by cross-sectional survey method. Fried frailty phenotype scale and ADL scale were used to evaluate the frailty and ADL, respectively. The differences of basic data and different frailty phenotypes between the normal function group and the function decline group were compared in terms of ADL, physical self-maintenance ability and instrumental ADL ability. Pearson correlation analysis was used to analyze the correlation between frailty and ADL, and binary logistic regression analysis was used to analyze the influencing factors of ADL.Results:A total of 676 MHD patients were included in this study, including 434 males (64.2%) and 242 females (35.8%). The age was (59.2±19.4) years old, and the median dialysis age was 59.0 (25.3, 110.0) months. There were 159 frailty patients (23.5%), 230 pre-frailty patients (34.0%), and 287 non-frailty patients (42.5%). The ADL was decreased in 163 patients (24.1%), including 131 patients (19.4%) with decreased physical self-maintenance ability and 161 patients (23.8%) with decreased instrumental ADL ability. Pearson correlation analysis showed that the frailty score was positively correlated with total ADL score ( r=0.728, P<0.001), physical self-maintenance ability score ( r=0.669, P<0.001) and instrumental ADL ability score ( r=0.729, P<0.001). Binary logistic regression analysis results showed that older age and lower physical activity, fatigue, slowed steps and lower grip strength in the frailty phenotypes were the independent influencing factors of ADL, physical self-maintenance ability and instrumental ADL ability (all P<0.05). Conclusions:The prevalence of frailty is 23.5% in MHD patients, and 24.1% of MHD patients have decreased ADL. Elder age and lower physical activity, fatigue, reduced step counts, and lower grip strength in frailty phenotypes are the independent influencing factors for poor ADL, poor physical self-maintenance ability and poor instrumental ADL ability.

Objective: To evaluate the effect of the Thyroid Imaging Report and Data System proposed by American Radiological Society (ACR-TIRADS) for differential diagnosis in thyroid nodules, and compare ACR-TIRADS to the TIRADS proposed by Kwak et al.(K-TIRADS) and the ultrasound-based risk stratification system evaluated by American Thyroid Association (ATA-Risk Stratification). Methods: The clinical data of 1 760 patients with 1 912 thyroid nodules from 8 hospitals in Jiangsu province were retrospectively analysed. All of them were categorized based on ultrasound-based risk stratification systems. The ROC curve was established to assess and compare the diagnostic value of the systems. Results: The area under the ROC curve (AUC) of ACR-TIRADS was 0.830, with high sensitivity and negative predictive value (86.9% and 87.5%, respectively), and relatively low specificity and positive predictive value (64.1% and 62.9%, respectively). The sensitivity and specificity of K-TIRADS were up to 84.9% and 76.1%, respectively. The AUC of ATA-Risk Stratification was 0.852, with relatively high specificity (83.4%), and low sensitivity (79.4%). There were significant differences in the AUC among the three ultrasound-based risk stratification systems, of which K-TIRADS was the highest (P<0.001). There was no significant difference in sensitivity of ACR-TIRADS and K-TIRADS (P=0.137), but significantly higher than that of ATA-Risk Stratification (P<0.001). There were significant differences in the specificity among the three systems, of which ATA-Risk Stratification was the highest (P<0.001). In addition, there were 109 nodules (5.7%) couldn′t be classified based on ATA-Risk Stratification, with high malignancy rate of 31.2%. Conclusions The diagnostic efficiency of ACR-TIRADS is good, but lower than K-TIRADS and ATA-Risk Stratification. ACR-TIRADS has the highest sensitivity, and ATA-Risk Stratification has the highest specificity, while the overall diagnostic efficiency of K-TIRADS is the best.

Objective To explore the accuracy of Vitek 2 compact advanced expert system (AES) in indicating and analyze the carbapenemases-resisting Enterobacteriaceae phenotypes,and further investigate the methods to make up the AES.Methods 28 Enterobacteriaceae strains with Imipenem-Nonsusceptible by Vitek 2 compact,but AES suggested all production of carbapenemases were isolated.And imipenem susceptibility was determined by the disk diffusion method.Modified Hodge test (MHT) and the metallo-β-1actamase was detected by the double disk synergy method.Resistance genes were detected by the PCR amplification.Results ESBLs gene was amplified from all 28 selected strains,16 of which was detected KPC gene,and no strain of metallo-β-1actamases-producing bacteria.With carbapenemase gene detection as the gold standard,the accuracy of AES was 57.1％.Disc diffusion method detection accuracy rate of imipenem was 100％,and for 100％ of MHT accuracy.PCR amplification,MHT and the disk diffusion displayed the same result in detecting carbapenemases,but different with AES (x2 =10.08,P＜0.05).Conclusion The indications of the presence of carbapenemases using AES was not completely correct with a certain false-positive,and it is necessary to take other methods,such as disk diffusion or MHT methods,and improve the reliability of medicine-sensitivity tests.

To compare the diagnostic value between the thyroid imaging reporting and data system ( TIRADS) and ultrasound ( US ) patterns of 2015 American Thyroid Association ( ATA ) guidelines in the differentiation of benign and malignant thyroid nodules. 639 patients in Jiangsu province who were scheduled for ultrasound-guided fine-needle aspiration biopsy or thyroidectomy were recruited for the retrospective study. All of them were categorized based on TIRADS and ultrasound patterns of ATA ( 2015 ) guidelines. The receiver operating characteristic curve was established to assess and compare the diagnostic value of the two models. Results:( 1 ) 639 patients with 847 thyroid nodules were included in this study, 510 females and 129 males. The mean age was (46. 77 ±12.98)yearsold. (2)818nodulescouldbeclassifiedaccordingtoTIRADS. ThemalignancyratesofTIRADS2,3, 4A, 4B, 5 were 0, 15. 9%, 49. 1%, 78. 8% ,and 100%, respectively. (3) Ultrasound patterns of ATA could be assigned to 793 nodules. The malignancy rates of nodules with very low, low, intermediate, high suspicion for malignancy were 6. 2%, 10. 3%, 24. 9% and 70. 1%, respectively. (4) Ultrasound patterns of ATA had higher specificity (77. 9%) compared to TIRADS. The sensitivity and area under curve of ultrasound patterns of ATA were lower than those of TIRADS, though, not significant. Ultrasound patterns of ATA(2015) guidelines may yield higher specificity in the differential diagnosis of benign and malignant thyroid nodules, while TIRADS classification may offer a relatively higher sensitivity and area under curve.

Objective To investigate the application value of double-layer continuous suture in pancreatic jejunum anastomosis of pancreatoduodenectomy (PD).Methods A retrospective analysis of 114 consecutive patients (67 men and 47 women) who underwent PD from June 2012 to July 2013 were conducted. There were 79 patients who were treated by double-layer continuous suture technique and 35 patients by double-layer interrupted suture technique .The incidence of pancreatic fistula and other complications after PD with two different suture techniques were compared .Results The operation time of double-layer continuous suture group and double-layer interrupted suture group is respectively ( 284 ±5 ) and ( 288 ±7 ) mins, the intraoperative bleeding volume is respectively (236 ±29) and (282 ±49) ml, the differences between two groups were no statistical significance .The postoperative fasting time in two group was respectively (7.8 ± 0.5) and (9.7 ±0.5) days, the length of hospital stay time was respectively (14.0 ±1.0) and (17.2 ± 10.0) days, the incidence of postoperative pancreatic fistula ( POPF) was respectively 17.1%(6/35) and 39.2%(317/9 ), the differences between two groups were statistically significant (all P<0.05).Grade A POPF was found in 4 patients ( 11.4%) from the double-layer continuous suture group and in 5 patients (6.3%) from the double-layer interrupted suture group.Grade B POPF was identified only in 1 patients (2.9%) from the double-layer continuous suture group and in 23 patients (29.1%) from the double-layer interrupted suture group .The presence of Grade C POPF was only documented in 1 patient from the double-layer continuous suture group and in 3 patients from the interrupted suture group .Conclusions Continuous suture can be safely used in the duct-to-mucosa pancreatojejunostomy .The double-layer continuous suture can be more effective in reducing pancreatic fistula , improving the feeding time , and reducing the length of hospital stay, and it is worthy of clinical popularization and application .

Objective To explore the clinical characteristics of IgG4-related disease (IgG4-RD) in Chinese by detailed clinicopathological and laboratory assessments.Methods The baseline features of 36 patients with biopsy-proven disease were reviewed.The diagnosis was confirmed by pathology review according to consensus diagnostic criteria and clinicopathologic correlation.Disease activity and damage were assessed by the IgG4-RD responder index (RI).Results Thirty (83.3％) of the patients were male,while six were female,and the average age of onset was 65.1 years.All of the 36 patients had active disease,in which submandibular gland,lymph nodes,retroperitoneal tissue were the most common affected organs in this group of patients.Among 36 patients,77.7％ had elevated serum IgG4 concentrations and 44.4％ had hypocomplementemia.Patients with elevated serum IgG4 had a higher RI,a greater number of organs involved (P ＜ 0.01 for all comparisons).The correlation between serum IgG4 level and RI (r=0.737,P ＜ 0.01) was stronger than IgG,ESR,CRP and serum complement levels.The incidence of hypocomplementemia in IgG4-RD patients with renal involvement was higher than that in IgG4-RD patients with other organs involvement (P ＜ 0.01).Twenty-eight patients received glucocorticoids therapy,and had lower RI and serum IgG4 concentration after therapy (P ＜ 0.05).Conclusions Both IgG4-RD RI and IgG4 concentration may be regarded as assessment markers of disease activity and therapeutic effect of IgG4-RD.The diagnosis of IgG4-RD should be supported by histopathology and clinical features.

Objective To evaluate the awareness of primipara on self-care knowledge and explore its related factors. Methods 200 cases of pregnant women were surveyed through a self-designed questionnaire about their self-care knowledge, and analyze the influencing factors.Results The situation of awareness in 200 cases on self-care knowledge was in the middle level and related factors involving pregnant women education background, occupation, family income per capita, production inspection situation, etc. Most of the pregnant women were not enough to grasp the intrapartum and postpartum self-care knowledge. Conclusions The awareness of self-care knowledge in pregnant women is generally not enough, and was widespread demand. We should pay attention to the diversification and individuation of self-care education, cultivate pregnant women′s will to learn self-care knowledge actively. Multi-lateral cooperation, strengthen education, pay attention to prenatal examination, and do a good job of follow-up. Introduce the nursing mode “caring presence” to the obstetric nursing, focus on maternal active participation, in order to improve the ability of maternal self-care, and ensure the safety of mothers and children.

Objective Laboratory tests of yeast, with their disadvantages of long identification, complicated operation, and low positive rate, cannot meet the needsof rapid diagnosis and timely treatment.This studyinvestigated the feasibility ofapplying matrix-assisted laser desorption ionization-time of flight mass spectrometry ( MALDI-TOF-MS) in rapid identification and clinical isolationof yeast strains. Methods A total of 120 clinical non-repetitive isolates were collected from clinical culture samples and identified by MALDI-TOF-MS and VITEK 2-Compact/API, respectively.The discordant results were resolved by ITS gene sequencing. Results Of the 120 yeast isolates analyzed, 117 (97.5%) were correctly identified at the species level by MALDI-TOF-MS, 1(0.8%) misidenti-fied, and 2 ( 1.7%) unidentified.ITS gene sequencing of the 3 isolates showed the coincidence rate to be 0( 0/3) for MALDI-TOF-MS and Vitek 2-Compact/API. Conclusion MALDI-TOF-MScan be used as a rapid, accurate, and inexpensive tool for the identification of clinical yeast strains.

Objective To evaluate the diagnostic value of glycosylated hemoglobin A1c (HbA1c)and glycated albumin(GA) in hyperglycemia patients with liver cirrhosis (LCH).Methods One hundred LCH patients were divided into anemia and no-anemia group by Hb 110 g/L The no-anemia group was further divided into low albumin (serum albumin ＜ 30 g/L),and high albumin group (serum albumin 30-＜40 g/L).One hundred type 2 diabetes without liver cirrhosis were included as control group (T2DM).HbA1c,GA,fasting plasma glucose (FPG),postprandial 2h plasma glucose (2hPG) were collected for statistical analysis.Results (1) The HbA1c level in LCH with anemia tended lower than that in T2DM subjects [(6.76 ±2.20)％ vs (7.34 ± 1.23)％,P =0.06];though the level of GA [(19.10 ±7.47)％vs (16.68 ±2.90)％,P＜0.01] and 2hPG [(12.09 ±3.39) mmol/L vs (10.84 ±2.95) mmol/L,P＜0.05] were significantly higher than that in T2DM group.(2) No-anemia subjects in LCH group with albumin ＜ 30 g/L had obviously higher GA levels than those with albumin 30-＜ 40 g/L and T2DM (albumin≥40 g/L) [(18.79 ±2.28)％ vs (16.71 ±2.42)％ and (16.73 ±2.96)％,P＜0.01];though the level of HbA1c of three groups above has no significant difference.(3) The level of HbA1c between LCH without anemia group and T2DM group had no significant difference (P ＞ 0.05);and the level of GA between LCH without anemia group with albumin 30-＜ 40 g/L and T2DM group had no significant difference(P ＞0.05).(4) The HbA1c has a positive correlation with FPG and 2hPG in LCH (FPG∶r =0.45,P＜0.001;2hPG∶r =0.33,P=0.001) and T2DM subjects (FPG∶ r =0.76,P＜0.001;2hPG∶r =0.81,P ＜ 0.001).GA also has a positive correlation with FPG and 2hPG in LCH (FPG∶ r =0.48,P ＜0.001;2hPG:r=0.39,P ＜0.001) and T2DM subjects (FPG∶ r =0.74,P ＜0.001;2hPG∶ r =0.76,P ＜0.001).Conclusion It is unfavorable to use HbA1c to evaluate the blood glucose level in liver cirrhosis patients with Hb ＜ 110 g/L and to use GA in patients with serum albumin ＜ 30 g/L.