Here we tell a 20-year long story. It began with an easily overlooked DNA degradation (Dnd) phenomenon during electrophoresis and eventually led to the discovery of an unprecedented DNA sulfur modification governed by five dnd genes. This unusual DNA modification, called phosphorothioation, is the first physiological modification identified on the DNA backbone, in which the nonbridging oxygen is replaced by sulfur in a sequence selective and stereo-specific manner. Homologous dnd gene clusters have been identified in diverse and distantly related bacteria and thus have drawn immediate attention of the entire microbial scientific community. Here, we summarize the progress in chemical, genetic, enzymatic, bioinformatical and analytical aspects of this novel postreplicative DNA modification. We also discuss perspectives on the physiological functions of the DNA phosphorothioate modification in bacteria and their implications.
Bacteria ; genetics ; metabolism ; DNA, Bacterial ; chemistry ; history ; metabolism ; Genes, Bacterial ; History, 20th Century ; History, 21st Century ; Multigene Family ; Streptomyces lividans ; genetics ; metabolism ; Sulfur ; chemistry ; history ; metabolism

Objective To explore the effects of massive open online courses (MOOC) teaching in new entry nurses standardized training of respiratory medicine. Methods A total of 33 new entry nurses of respiratory medicine at a hospital were selected as control group from 2013 to 2014 with the routine training method. A total of 34 new entry nurses were chosen as intervention group from 2015 to 2017. Nurses of intervention group accepted standardized training with the MOOC teaching method by formulating systematic online and offline training course. The training effects of two groups were evaluated. Results The specialized theoretical achievements and skill achievements of nurses were (72.68±9.44) and (75.78±10.32) in intervention group, and (67.33±8.89) and (62.64±5.8) in control group with significant differences (P< 0.05). After intervention, the degree of satisfaction of patients in intervention group was higher than that in control group with a significant difference (χ2=10.823, P< 0.05). Conclusions MOOC teaching can effectively improve the level of specialized skill in new entry nurses, contribute to linking theory with practice, fast role switching and improve the occupational satisfaction.

Objective To explore the value of multi-sequence MRI radiomics for predicting clinical stage of cervical squamous cell carcinoma(CSCC).Methods Totally 190 patients with single CSCC confirmed by pathology were retrospectively collected.Among them,67 cases with International Federation of Gynecology and Obstetrics(FIGO)stage ⅠB—ⅡA were classified into early stage group,while 123 cases with FIGO ⅡB—ⅢC were enrolled in middle-late stage group.The patients were divided into training set(n=114,including 40 cases in early stage subgroup and 74 cases in middle-late stage subgroup)and test set(n=76,including 27 cases in early stage subgroup and 49 cases in middle-late stage subgroup)at the ratio of 6∶4.Single factor and logistic analyses were used to screen clinical relevant factors,and a clinical model was constructed.The best radiomics features of lesions were extracted and selected based on pre-treatment pelvic MR T2WI,diffusion-weighted imaging(DWI),dynamic contrast enhancement(DCE)-T1WI and all the three,respectively,and the radiomics models were constructed,including T2WI,DWI,DCE-TWI and combined sequences models,then a clinical-radiomics model was established based on clinical model and combined sequences model.The predictive efficacy of each model was evaluated by receiver operating characteristic curves,and the area under the curves(AUC)were calculated.The integrated discrimination improvement(IDI)index was also calculated to compare the diagnostic efficacy of each model in training set,and decision curve analysis(DCA)was used to evaluate their clinical value.Results Squamous cell carcinoma associated antigen in middle-late stage subgroup was higher than that in early stage subgroup in both training and test sets(both P＜0.05),which was used to establish the clinical model.The AUC of clinical,T2WI,DWI,DCE-TWI,combined sequences and clinical-radiomics models for predicting clinical stage of CSCC was 0.66,0.71,0.78,0.81,0.88 and 0.89 in training set,respectively,which was 0.62,0.64,0.72,0.73,0.77 and 0.76 in test set,respectively.In training set,the predictive efficacy of clinical-radiomics model was higher than that of combined sequences model(IDI=0.19,P＜0.05),both higher than that of the rest models(IDI=0.19-0.47,all P＜0.05).When the thresholds were 0.02-1.00 and 0.05-1.00,combined sequences and clinical-radiomics models had higher clinical net benefits in training set.Conclusion Multi-sequence MRI radiomics could effectively predict clinical stage of CSCC,and combining clinical data could improve its diagnostic efficacy.

Objective:To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B.Methods:175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC).Results:The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion:HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.

ObjectiveTo compare the feasibility of establishing the rat model of acute coronary syndrome with combined blood stasis and poison by lipopolysacharide （LPS） injection， ligation of coronary artery and different combinations of the two methods. MethodA total of 225 male SD rats were randomly divided into sham operation group， simple coronary artery ligation group， first injected LPS group ［LPS（5 mg·kg）injection 24 h before coronary artery ligation］ and follow injected LPS group ［LPS（5 mg·kg）injection 10 min after coronary artery ligation］. The indexes of each group were detected at 3， 24， 72 h after modeling， and the model was comprehensively evaluated. The general state and macroscopic evaluation indexes of traditional Chinese medicine （TCM） syndrome （tongue and pulse） of rats in each group were observed. ECG and echocardiography were used to evaluate cardiac function， and the myocardial ischemia and infarction areas were measured by Evans blue/2，3，5-triphenyltetrazolium chloride （TTC） staining. The content of creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， creatine kinase （CK）， and troponin T （cTnT） in serum as well as interleukin-1 β （IL-1β） and IL-6 changes were determined by biochemical method or enzyme-linked immunosorbent assay （ELISA）. Hematology analyzer was adopted to determine the white blood cell （WBC） count， and the four coagulation indexes， platelet aggregation rate， hemorheology and other coagulation evaluation indexes were also detected. The myocardial tissue was observed by hematoxylin-eosin（HE）staining. ResultAfter 3 h of modeling， compared with the conditions in sham operation group， the R， G and B values of tongue of rats （P<0.01）， pulse amplitude （P<0.01）， and cardiac function in simple coronary artery ligation group were decreased， and the color of hypoglossal veins became purple（P<0.01）. The content of CK， LDH， cTnT， IL-1β and IL-6 in serum（P<0.05）， myocardial infarction area（P<0.01）， and total number of WBCs （P<0.05）were increased. Compared with simple coronary artery ligation group， first injected LPS group and follow injected LPS group had increased hypoglossal veins， decreased R value of tongue and elevated cTnT content （P<0.01）， while follow injected LPS group had reduced B value of tongue， decreased cardiac output （CO）（P<0.05）， increased IL-1β content， and thinned left ventricular anterior walls at end-systole （LVAWs）（P<0.01）. After 24 h of modeling， compared with sham operation group， simple coronary artery ligation group presented significantly decreased R， G and B values of tongue， lengthened purplish dark hypoglossal veins （P<0.01）， reduced pulse amplitude（P<0.01） and cardiac function， enlarged myocardial infarction area（P<0.01）， increased whole blood viscosity， platelet aggregation rate， fibrinogen （FIB）， shortened prothrombin time （PT） and thrombin time （TT）（P<0.01）， and elevated total number of WBCs （P<0.01）and content of CK， LDH， cTnT and IL-6 in serum（P<0.05）. Compared with the conditions in simple coronary artery ligation group， the pulse amplitude， R， G and B values of tongue （P<0.01）， and ejection fraction （EF） and fractional shortening （FS） scores （P<0.05）dropped， and hypoglossal veins were deepened and lengthened（P<0.05）， and cTnT content was increased（P<0.01）in first injected LPS group and follow injected LPS group. However， follow injected LPS group had thinned LVPWs， increased LDH content， platelet aggregation rate（P<0.05）， myocardial infarction area， and total number of WBC， level of IL-1β（P<0.05）， and shortened TT（P<0.01）. Additionally， 72 h after modeling， compared with sham operation group， simple coronary artery ligation group showed significantly reduced pulse amplitude， lowered R， G and B values of tongue， thickened and lengthened hypoglossal veins（P<0.01）， decreased cardiac function， and increased content of cTnT， FIB， whole blood viscosity（P<0.01），platelet aggregation rate， level of IL-6 and IL-1β（P<0.05）. Compared with the conditions in simple coronary artery ligation group， the hypoglossal veins of the first injected LPS group and the follow injected LPS group were more purple， and the content of cTnT was boosted（P<0.01）， whereas follow injected LPS group had decreased pulse amplitude， R， G and B values of tongue， EF and FS scores （P<0.05）， and enlarged myocardial infarction area（P<0.01）. ConclusionCompared with the other modeling methods and models at different modeling time， the established model by LPS injection 10 min after coronary artery ligation for 24 h was more consistent with the clinical characteristics of acute coronary syndrome with combined blood stasis and poison.

ObjectiveTo investigate the resistance to pyrethroids， beta-cyhalothrin and fenitrothion as well as the frequencies of kdr andace⁃1 alleles in Anopheles sinensis from three geographical populations in Chongming District， Shanghai. MethodsThe contact tube method recommended by WHO was used to determine mosquito resistance. The frequencies of kdr and ace⁃1 alleles in adult mosquitoes were determined by PCR amplification. The correlation between the frequencies of kdr alleles and insecticide resistance was analyzed by linear regression method. ResultsThe mosquito population near natural reserve （NF） was sensitive to deltamethrin， and the mortality rate was 100.00% at 24 h. The mosquito population with intensive breeding farms （HX） showed resistance to deltamethrin and beta-cyhalothrin， and the 24 h mortality was 48.00 % and 57.50 %， respectively. The 24 h mortality rate of the mosquito population with urban-rural integration area （AS） with suspected resistance to deltamethrin and beta-cyhalothrin was 84.40% and 86.00%. The 24 h mortality rate to Fenitrothion was 55.67%. There were 3 mutations in kdr gene locus 1014， and 7 mutated genotypes were detected， mainly L1014/L1014F and L1014F/L1014F. The mutation frequency of kdr allele in HX population was the highest （52.68%）. There was one mutation at site 119 of ace⁃1 gene， and three genotypes were detected， most of which were G119S mutation. There was a significant negative correlation between the frequency of kdr resistance allele and the mortality rate of beta-cypermethrin in An.sinensis populations （r²=0.930，P=0.036）. There was a significant negative correlation between the frequency of ace⁃1 resistance allele and the mortality rate of fenitrothion in An. sinensis populations from four habitats（r²=0.996，P=0.038）. ConclusionThe mutation frequency of insecticide resistance allele is associated with the development of mosquito resistance level. Therefore， comprehensive monitoring of resistance levels of An.sinensis in Chongming area should be continued to provide a basis for local mosquito resistance management.

BACKGROUND: Pneumonia-like primary pulmonary lymphoma (PPL) was commonly misdiagnosed as infectious pneumonia, leading to delayed treatment. The purpose of this study was to establish a computed tomography (CT)-based radiomics model to differentiate pneumonia-like PPL from infectious pneumonia. METHODS: In this retrospective study, 79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were enrolled. Patients from center 1 to center 7 were assigned to the training or validation cohort, and the remaining patients from other centers were used as the external test cohort. Radiomics features were extracted from CT images. A three-step procedure was applied for radiomics feature selection and radiomics signature building, including the inter- and intra-class correlation coefficients (ICCs), a one-way analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model. Two radiologists reviewed the CT images for the external test set. Performance of the radiomics model, clinical factor model, and each radiologist were assessed by receiver operating characteristic, and area under the curve (AUC) was compared. RESULTS: A total of 144 patients (44 with pneumonia-like PPL and 100 infectious pneumonia) were in the training cohort, 38 patients (12 with pneumonia-like PPL and 26 infectious pneumonia) were in the validation cohort, and 73 patients (23 with pneumonia-like PPL and 50 infectious pneumonia) were in the external test cohort. Twenty-three radiomics features were selected to build the radiomics model, which yielded AUCs of 0.95 (95% confidence interval [CI]: 0.94-0.99), 0.93 (95% CI: 0.85-0.98), and 0.94 (95% CI: 0.87-0.99) in the training, validation, and external test cohort, respectively. The AUCs for the two readers and clinical factor model were 0.74 (95% CI: 0.63-0.83), 0.72 (95% CI: 0.62-0.82), and 0.73 (95% CI: 0.62-0.84) in the external test cohort, respectively. The radiomics model outperformed both the readers' interpretation and clinical factor model ( P <0.05). CONCLUSIONS The CT-based radiomics model may provide an effective and non-invasive tool to differentiate pneumonia-like PPL from infectious pneumonia, which might provide assistance for clinicians in tailoring precise therapy.
Humans ; Retrospective Studies ; Pneumonia/diagnostic imaging* ; Analysis of Variance ; Tomography, X-Ray Computed ; Lymphoma/diagnostic imaging*