S-methyl-L-cysteine sulfoxide (SMCO) is a non-protein sulfur-containing amino acid with a variety of functions. There are few reports on the enzymes catalyzing the biosynthesis of SMCO from S-methyl-L-cysteine (SMC). In this study, the flavin-containing monooxygenase gene derived from Schizosaccharomyces pombe (spfmo) was heterologously expressed in Escherichia coli BL21(DE3) and the enzymatic properties of the expressed protein were analyzed. The optimum catalytic conditions of the recombinant SpFMO were 30 ℃ and pH 8.0, under which the enzyme activity reached 72.77 U/g. An appropriate amount of Mg²⁺ improved the enzyme activity. The enzyme kinetic analysis showed that the K_m and k_cat/K_m of SpFMO on the substrate SMC were 23.89 μmol/L and 61.71 L/(min·mmol), respectively. Under the optimal reaction conditions, the yield of SMCO synthesized from SMC catalyzed by SpFMO was 12.31% within 9 h. This study provides reference for the enzymatic synthesis of SMCO.
Schizosaccharomyces/genetics* ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Cysteine/biosynthesis* ; Mixed Function Oxygenases/metabolism* ; Schizosaccharomyces pombe Proteins/metabolism* ; Oxygenases/metabolism* ; Kinetics

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Objective:To investigate the regression of regional lymph nodes after administering neoadjuvant short-course chemoradiother-apy combined with immunotherapy in patients with locally advanced rectal cancer(LARC).Methods:This retrospective study analyzed the clinical data of 40 patients with LARC admitted to Zhongshan Hospital Affiliated to Xiamen University(32 cases)and the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology(8 cases)between January 2021 and December 2022.The control and experimental groups consisted of 20 patients who underwent direct laparoscopic surgery and neoadjuvant short-course chemoradio-therapy combined with immunotherapy prior to the laparoscopic surgery,respectively.The detection of the postoperative lymph node was compared between the two groups.In addition,the pathologic complete response(pCR)rate of the primary tumor and regional lymph nodes in the experimental group was assessed.Results:The number of patients with N downstaging(18 vs.7,P<0.001)significantly in-creased,whereas the positive lymph node metastasis rate(1.4%vs.19.1%,P<0.001)and number of patients with positive lymph nodes(4 vs.16,P<0.001)significantly decreased in the experimental group compared to those in the control group.Although the number of detected lymph nodes in the experimental group was slightly lower compared to that in the control group(18.3±8.7 vs.20.4±6.5,P=0.392),it was not statistically different.Furthermore,the pCR rate of the regional lymph nodes was significantly higher than that of the primary tumor in the experimental group(80%vs.30%,P=0.001).Conclusions:Neoadjuvant short-course chemoradiotherapy combined with immunotherapy caused significant pathological remission of positive lymph nodes in patients with LARC.This study hypothesizes that a"spatial effect"con-tributes to the pathological remission of regional lymph nodes in rectal tumors.

Objective:To investigate the predictive value of inflammatory markers for the risk of stroke-associated infection (SAI) in patients with anterior circulation large vessel occlusive stroke who received endovascular therapy.Methods:Patients with anterior circulation large vessel occlusive stroke received endovascular treatment in Nanjing First Hospital, Nanjing Medical University from 2016 to 2020 were retrospectively enrolled. The clinical data of SAI group and non-SAI group were compared. Multivariate logistic regression analysis was used to screen the independent influencing factors of SAI, and then the predictive nomogram was established according to these influencing factors to verify its clinical application efficiency. Results:A total of 409 patients were enrolled during the study. Their age was 71.3±11.7 years, and 250 were male (61.1%). The median baseline Naitonal Institutes of Health Stroke Scale (NIHSS) score was 16. One hundred and nineteen patients (29.1%) received intravenous thrombolysis, 376 (91.9%) were successfully recanalized after endovascular therapy, and 293 (71.6%) developed SAI. Univariate analysis showed that age, atrial fibrillation ratio, NIHSS score at admission, fasting blood glucose, triglyceride, high sensitivity C reactive protein (hs-CRP), leukocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were significantly higher than those in the non-SAI group (all P<0.05). Multivariate logistic regression analysis showed that age, NIHSS score at admission, fasting blood glucose, hs-CRP, leukocyte count, neutrophil count and NLR were the independent influencing factors of SAI ( P<0.05). Receiver operating characteristics curve analysis showed that the predictive value of multiple inflammatory markers (hs-CRP, leukocyte count, neutrophil count and NLR) for SAI was significantly better than that of the single inflammatory marker ( P<0.01). The area under the curve was 0.782 (95% confidence interval 0.719-0.846), and the predictive sensitivity and specificity were 80.6% and 64.5% respectively. Decision curve analysis showed that compared with the traditional indicators, the predictive nomogram based on inflammation related indicators (hs-CRP, leukocyte count and NLR) had a higher net profitability for predicting SAI. Conclusion:The hs-CRP, leukocyte count and NLR can be used to predict the risks of SAI in patients with acute ischemic stroke receiving endovascular therapy.

Objective:To investigate the predictive values of serum hypersensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A 2 (Lp-PLA 2) for early neurological deterioration (END) and parenchymal hematoma (PH)-type 2 hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke. Methods:Patients with acute ischemic stroke treated with intravenous thrombolysis in the Department of Neurology, Nanjing First Hospital, Nanjing Medical University from January 2018 to January 2021 were enrolled retrospectively. END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score at 24 h after thrombolysis compared with the baseline. PH-2 type HT was defined as parenchymal hematoma with obvious space occupying effect or hemorrhage at the distant site of infarct. Multivariate logistic regression analysis was used to determine the independent influencing factors of END and PH-2 type HT. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of hs-CRP and Lp-PLA 2 levels for END and PH-2 type HT. Results:A total of 804 patients with acute ischemic stroke treated with intravenous thrombolysis were included, of which 63 (7.8%) developed END within 24 h after intravenous thrombolysis; 41 (5.1%) developed HT, of which 38 were PH-2 type HT. Univariate analysis showed that the levels of serum hs-CRP and Lp-PLA 2 in the END group were significantly higher than those in the non-END group (all P<0.05), and the levels of serum hs-CRP and Lp-PLA 2 in the PH-2 HT group were significantly higher than those in the non-PH-2 HT group ( P<0.05). Multivariate logistic analysis showed that hs-CRP (odds ratio [ OR] 1.017, 95% confidence interval [ CI] 1.001-1.034; P=0.043) and Lp-PLA 2 ( OR 1.002, 95% CI 1.000-1.003; P=0.020) were the independent risk factors for END after intravenous thrombolysis. In addition, hs-CRP ( OR 1.019, 95% CI 1.002-1.036; P=0.027) and Lp-PLA 2 ( OR 1.002, 95% CI 1.000-1.003; P=0.018) were also the independent risk factors for PH-2 HT after intravenous thrombolysis. The ROC curve analysis showed that the areas under the curve of hs-CRP and Lp-PLA 2 for predicting END were 0.675 (95% CI 0.609-0.741; P<0.001) and 0.606 (95% CI 0.528-0.683; P=0.005) respectively, and the areas under the curve for predicting PH-2 HT were 0.641 (95% CI 0.545-0.737; P=0.003) and 0.600 (95% CI 0.500-0.699; P= 0.051) respectively. Conclusion:Higher baseline serum hs-CRP and Lp-PLA 2 are the independent predictors of END and PH-2 type HT after intravenous thrombolysis in patients with acute ischemic stroke.

Background: Endoscopic submucosal dissection has become the preferred treatment for early gastric cancer without lymph node metastasis (LNM). The risk of LNM is different among different pathological types of early gastric cancer. Aims: To investigate the risk factors of LNM in patients with early gastric cancer. Methods: The clinicopathological features of 1 093 early gastric cancer patients underwent radical gastrectomy and diagnosed by pathology from January 2005 to December 2019 at Nanjing Drum Tower Hospital and Nanjing Gaochun People's Hospital were retrospectively analyzed. Risk factors of LNM in patients with early gastric cancer were analyzed by univariate analysis and logistic regression model analysis. Results: A total of 1 093 patients with early gastric cancer were enrolled, and positive LNM was found in 154 patients (14.1%). Univariate analysis showed that gender, age, tumor size, tumor location, gross classification, depth of tumor invasion, vascular and nerve invasion, differentiation type, ulcers were related with LNM (P<0.05). Multivariate analysis showed that age (OR=1.654, 95% CI: 1.102-2.480, P=0.015), tumor location (OR=1.617, 95% CI: 1.227-2.131, P=0.001), differentiation type (OR=1.664, 95% CI: 1.205-2.298, P=0.002), depth of invasion (OR=1.569, 95% CI: 1.212-2.030, P=0.001), vascular invasion (OR=10.514, 95% CI: 6.353-17.401, P=0.000) were the independent risk factors of LNM in early gastric cancer. Conclusions: Age, tumor location, differentiation type, depth of invasion, and vascular invasion are the independent risk factors of LNM in early gastric cancer, especially vascular invasion. For patients with vascular invasion, if there are no contraindications, surgical intervention is recommended.

Objective: To investigate the correlations of serum uric acid with outcomes and symptomatic intracranial hemorrhage (sICH) after intravascular mechanical thrombectomy bridged with intravenous thrombolysis in patients with ischemic stroke. Methods: From January 2015 to January 2019, patients with acute ischemic stroke admitted to Nanjing First Hospital, Nanjing Medical University and underwent intravascular mechanical thrombectomy bridged with intravenous thrombolysis were analyzed retrospectively. Demographic characteristics, vascular risk factors, laboratory findings, National Institutes of Health Stroke Scale (NIHSS) scores, onset to treatment time, and whether sICH occurred were recorded. The modified Rankin Scale was used to evaluate the outcomes at 90 d after onset, and 0 to 2 was defined as good outcome. Multivariate logistic regression models were used to determine the independent factors for outcomes and sICH. Results: A total of 144 patients were included, 54 (37.5%) had a good outcome, 90 (62.5%) had a poor outcome (including 28 deaths), and 29 (20.1%) had sICH. Serum uric acid was significantly higher in the good outcome group than in the poor outcome group (P<0.05). Serum uric acid was significantly higher in the non-sICH group than in the sICH group (P<0.05). Multivariate logistic regression analysis showed that higher serum uric acid were the independent protective factors of good outcome (odds ratio 0.82, 95% confidence interval 0.66-0.93; P<0.001) and sICH (odds ratio 0.97, 95% confidence interval 0.93-0.99; P=0.004). Conclusion High serum uric acid level is independently associated with good outcome after intravascular mechanical thrombectomybridged with intravenous thrombolysis in patients with acute ischemic stroke.

BACKGROUNDAn zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resource-limited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT-substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource-limited settings.

METHODSThis prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZT-substitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96.

RESULTSIn terms of hematological adverse effects, AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT-substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81-39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19-2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT-substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences.

CONCLUSIONAZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; HIV Infections ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stavudine ; administration & dosage ; adverse effects ; therapeutic use ; Zidovudine ; administration & dosage ; adverse effects ; therapeutic use

Space breeding in medicinal plants is special characteristics in China. Compared with other plants, in spite of a relatively small number, Medicinal plants have more obvious characteristics and advantages. Research on medicinal plants has also been carried into all aspects, such as biological traits, physiology and biochemistry, genomics, as well as differences in chemical composition, and chemical composition analysis is also involved. However, compared with other plants, especially crops and vegetables, biological research is an obvious deficiency, that is mainly reflected in the insufficient genetics and breeding researches, the stability of genetic traits from generation to generation were not followed up and in-depth study in breeding areas was not carried out. If medicinal plants resources from space with the genetic stability good quality were selected, it would address the problem of lack of resources and ease the pressure on wild resources of medicinal plants. It would at the same time play an important role in promoting the development of medicinal botany space breeding and the implementation of modernization of traditional Chinese medicine.
Breeding ; methods ; Plants, Medicinal ; growth & development ; physiology ; Space Flight ; Weightlessness