ABSTRACT
Dihydrofolate reductase (DHFR), a housekeeping enzyme in primary metabolism, has been extensively studied as a model of acid-base catalysis and a clinic drug target. Herein, we investigated the enzymology of a DHFR-like protein SacH in safracin (SAC) biosynthesis, which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance. Furthermore, based on the crystal structure of SacH-NADPH-SAC-A ternary complexes and mutagenesis, we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore. These findings expand the functions of DHFR family proteins, reveal that the common reaction can be catalyzed by distinct family of enzymes, and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.
ABSTRACT
Objective:To investigate the epidemic trend and epidemiological characteristics of human brucellosis in Chengyang District of Qingdao City, and to provide a theoretical reference for formulating scientific prevention and control measures.Methods:The data of confirmed and clinically diagnosed brucellosis cases with current address in Chengyang District of Qingdao City reported by China Disease Control and Prevention Information System from January 2016 to December 2020 were collected, and the epidemic trend, three-dimensional distribution, clinical characteristics, case consultation and disease outcome and epidemiological history of human brucellosis were descriptively analyzed.Results:From 2016 to 2020, 23 cases of human brucellosis were reported in Chengyang District of Qingdao City, with an annual incidence of 0.52/100 000, and the incidence was decreasing year by year (χ 2trend = 7.83, P = 0.005). The onset time was mainly distributed in spring and summer, of which spring (1, 5 and 5 cases respectively from March to May) accounted for 47.83% (11/23), and summer (1, 4 and 1 cases respectively from June to August) accounted for 26.09% (6/23). There were 13 cases of males and 10 cases of females, the ratio of male to female was 1.30 ∶ 1.00; the age of onset was (52.52 ± 14.67) years old, mainly from 40 to 65 years old, accounted for 65.22% (15/23); farmers accounted for 69.57% (16/23). The largest number of reported cases was in Chengyang Street (6 cases), followed by Xiazhuang Street (4 cases) and Liuting Street (4 cases), accounted for 60.87% (14/23). The main clinical manifestations were fever (21 cases, 91.30%), followed by muscle and joint soreness (18 cases, 78.26%), fatigue (18 cases, 78.26%), and hyperhidrosis (15 cases, 65.22%). The median time interval from onset to diagnosis was 27 days, and 82.61% (19/23) of the cases were diagnosed as brucellosis at the acute stage. After follow-up, 21 cases (91.30%) reached the recovery standard, and 2 cases (8.70%) improved. Verified by the epidemiological investigation, 23 cases of human brucellosis had multiple routes of infection. The main mode of infection was direct contact, including feeding suspected sick animals (8 cases, 34.78%), contacting urine, feces and other excrement of suspected sick animals (8 cases, 34.78%), delivering suspected sick animals/disposing the apoblema (5 cases, 21.74%), and slaughtering/contacting raw lamb (4 cases, 17.39%). Conclusions:From 2016 to 2020, the incidence of human brucellosis in Chengyang District of Qingdao City has decreased year by year. It occurs frequently in spring and summer, mainly in middle-aged and elderly male farmers. The main clinical manifestation is fever and there are multiple ways of infection. It is recommended to take multiple measures to strengthen health education, behavioral intervention and regular monitoring.
ABSTRACT
Abstract Chimetic antigen receptor T cells (CAR-T) are a kind of novel killer cells derived from autogenous or allogeneic T cells targeting the tumor specific antigens by gene engineering transpormation. The CAR-T cells possess the advantages of high specificity, high efficiency and non-MHC restriction, thus achieving good therapeutic effects in relapsed/refractory hematological tumors and some solid tumors. The process of CAR-T cell preparation includes cell isolation and purification, activation and differentiation, gene modification, in vitro amplification, phenotypic quality control, preservation and reinfusion. In recent years, with the rapid development of flow cytometry, this technology has been widely used in all aspects of CAR-T cell therapy, including pre-treatment screening, in vitro preparation and post-transfusion monitoring, which plays an important role in its innovative optimization.
ABSTRACT
Objective@#To establish analytical method for the determination of vanadium ( V ), chromium ( Cr ), nickel ( Ni ), selenium ( Se ) and arsenic ( As ) in calcium based toothpastes by microwave digestion-inductively coupled plasma tandem mass spectrometry ( ICP-MS/MS ).@*Methods@#The 21 calcium based toothpaste samples from supermarkets and shops in the urban areas of Hangzhou were digested by 6 mL HNO3 and 1 mL H2O2 in microwave digestion system. Then He-SQ mode and O2-MS/MS mode of ICP-MS/MS were respectively used for the determination of Ni and V, Cr, Se, As. Indium ( In ) was used as internal standard for calibration. @*Results@# Good linear relationships were obtained for these five elements from 1.0 to 32.0 μg/L, with the correlation coefficients ranged from 0.999 3 to 1.000 0. The detection limits of the method ranged from 0.000 25 to 0.006 08 mg/kg. The recovery rates of standard spiking were 80.7%-105.7% when set at 0.4, 0.8 and 1.6 mg/kg, the recovery of standard reference material was 102.2%, and the relative standard deviations were 2.6%-4.8%. The concentrations of V, Cr, Ni, Se and As in 21 calcium based toothpaste samples were 0.024-1.935 mg/kg, 0.085-5.759 mg/kg, 0.090-3.673 mg/kg, <0.002 72-0.016 mg/kg and <0.006 08-0.321 mg/kg.@*Conclusion@#Microwave digestion-ICP-MS/MS can effectively reduce the interferences of polyatomic ions and doubly charged ions from the matrix, which is suitable for the determination of V, Cr, Ni, Se and As in calcium based toothpaste.
ABSTRACT
Obesity is a major risk factor for the progression of cardiovascular disease. Adipose tissue is considered to be an endocrine organ that produces various secretory molecules, also known as adipocytokines, which are involved in the pathogenesis of obesity complications, including metabolic dysfunction and cardiovascular disease. From the perspective of mechanism, diabetic cardiomyopathy is a typical metabolic cardiovascular disease. This article reviews the role of several adipokines in the pathogenesis of diabetic cardiomyopathy (DCM) from the aspects of insulin resistance, oxidative stress, myocardial fibrosis, myocardial apoptosis and inflammatory response.
ABSTRACT
OBJECTIVE: To report a modified transvaginal non-mesh repair surgery based on "double hammock" pelvic floor support theory,and to observe the perioperative characteristics and short-term follow-up effect.METHODS: We collected 72 patients who underwent modified transvaginal non-mesh repair surgery from October 2017 to July 2018 in the First People's Hospital of Yunnan Province.Data of perioperative,3-month,6-month and 12 month follow-up were analyzed.RESULTS: The procedures were performed successfully in 72 patients,the average operation time was(119±31)min,and the mean blood loss was(47.75±30.55)mL.No traumatic compliacations were found during the operation.The objective response rate evaluated postoperatively by POP-Q stage in short-term follow-up were 100%,and no subjective symptoms of recurrence were observed.CONCLUSION: Modified vaginal non-mesh pelvic floor repair based on the "double-layer hammock" pelvic floor support theory has the advantages of simple surgical procedure, fewer complications and good effect in the short-term. Further observation is needed to determine its long-term effectiveness.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical efficacy and possible influencing factors of autologous hematopoietic Stem cell transplantation (auto-HSCT) in the treatment of patients with multiple myeloma (MM).</p><p><b>METHODS</b>Clinical data of 40 MM patients received auto-HSCT in the Department of Hematology of Henan Cancer Hospital from September 2010 to November 2017 were retrospectively analyzed, the clinical curative efficiency was summarized and the related factors were analyzed.</p><p><b>RESULTS</b>The curative efficiency of the patients before transplantation was 9(22.5%) with complete remission(CR), 5(12.5%) with very good partial remission(VGPR), 26(65%) with partial remission(PR), respectively, one of them was PR after 3 recurrences. The curative efficiency after transplantation was 22(55%) with complete remission(CR), 12(30%) with very good partial remission(VGPR), 6(15%) with partial remission(PR), respectively. And 2 cases were CR after double transplantation. Median follow-up time was 28.4 (3.1 to 88) months,15 cases presented disease progression, 7 cases were dead, 3-year estimated progression-free survival(PFS) and overall survival(OS) rate were 45.1% and 82% respectively. Unvariate analysis showed that the OS was affected by ISS stage (P<0.05), CR and VGPR (P<0.05) after transplantation; PFS was affected by ISS stage (P<0.01), before transplantation induction therapy (27 cases with bortezomizomi or thalidomide) (P<0.05), disease risk stratification (6 cases in high risk group) (P<0.05) , CR and VGPR (P<0.05) before transplantation, CR and VGPR (P<0.01) after transplantation. Cox multivariate regression analysis showed that the independent prognostic factors for OS were ISS stage, CR and VGPR after transplantation; the independent prognostic factors for PFS were the CR, VGPR, ISS stage after transplantation and induction therapy before transplant.</p><p><b>CONCLUSION</b>Auto-HSCT can improve the clinical efficacy and survival rate of MM patients; ISS stage, CR and VGPR after transplantation are independent prognostic factors for OS and PFS, and induction therapy before transplantation is also an independent prognostic factor for PFS.</p>
ABSTRACT
Rapid discrimination of compounds with similar structures and properties is a hot topic in analytical chemistry. In this study, a cyclic chemiluminescence (CCL) system was designed by using nano-magnesium oxide as catalyst. The effects of reactant concentration, reaction temperature and detection wavelength on CCL analysis were studied. It was found that the CCL signal satisfied the first order exponential decay law. Each reaction had an exponential decay equation (EDE) describing its signal change law. The initial variable A was proportional to the reactant concentration. The decay-coefficient k was a characteristic constant that was independent of the reactant concentration. For iso-butanol, it's A-values versus concentration was linear in 0. 89-14. 24 mg / L, the average of k-value in this range was 32. 0 with a RSD of 2. 2% . Thus, qualitative and quantitative analysis could be conducted according to the A and k values. The system was used to analyze eight kinds of alcohol compounds, and it was found that there were significant differences in the k-values for different alcohols. For example, the k-values for n-butanol, iso-butanol and sec-butanol were 27. 2 ±0. 2, 32. 0±0. 8 and 19. 5±0. 1, respectively.
ABSTRACT
Graphene and silver nanoparticles showed good application potentials in electrochemistry due to their unique folded layered structure and good catalytic performance. In this work, reduced graphene oxide-Ag nanoparticles ( rGO/AgNPs ) composite material was prepared in situ by using hydrothermal reduction synthesis method with sodium citrate as reducing agent. The material was then used as modified electrodes to study the electrochemical behaviors of bisphenol A ( BPA) . The results of cyclic voltammetry and square wave voltammetry showed that the fast oxidation-reduction reaction of BPA could occur on the rGO/AgNPs modified glassy carbon electrode and lead to the sensitive determination of BPA. Under the optimal conditions, the oxidation current of BPA was linear to its concentration in the range of 0 . 1-40 . 0 μmol/L and the detection limit was 50 . 7 nmol/L ( S/N=3 ) . The presented method was also used for the determination of BPA in plastic samples with satisfactory results.
ABSTRACT
Objective To enhance the diagnosis of cerebral infarction of the hematopathy patient by analyzing its causes and MRI manifestations.Methods Totally 36 hematopathy patients with cerebral infarction from April 2010 to November 2015 had their data discussed retrospectively on involved vessel,anatomic distribution and MRI manifestations.Results Of the 36 patients,12 ones had only an artery involved in and 24 ones had multi arteries affected,31 ones had multi cerebral infarction foci and 5 ones had single focus.The foci had high or slighdy high signals in T2WI and very high signals in DWI,and there were no enhancement or only gyrus-like enhancement around the foci found by enhanced scan.Conchusion MRI gains advantages over CT when used to diagnose and find the hematopaty patient with cerebral infarction,when it has to be differentiated with cerebral early infection and parenchymal infiltration.It's suggested that the hematopathy patient has to undergo MRI examination in case central nervous system symptoms especially cerebral infarction occur.
ABSTRACT
Radiotherapy ( RT) is used as primary treatment for numerous cancers. Although it is usually described as an immunosuppressive modality,there are new preclinical evidences suggesting that RT could have also generated substantial changes in the tumor microenvironment, including triggering an inflammatory process. Some studies established the proof of concept that combining RT with strategies modifying immunology could enhance antitumor effects.
ABSTRACT
Objective To enhance the diagnosis of cerebral infarction of the hematopathy patient by analyzing its causes and MRI manifestations.Methods Totally 36 hematopathy patients with cerebral infarction from April 2010 to November 2015 had their data discussed retrospectively on involved vessel,anatomic distribution and MRI manifestations.Results Of the 36 patients,12 ones had only an artery involved in and 24 ones had multi arteries affected,31 ones had multi cerebral infarction foci and 5 ones had single focus.The foci had high or slighdy high signals in T2WI and very high signals in DWI,and there were no enhancement or only gyrus-like enhancement around the foci found by enhanced scan.Conchusion MRI gains advantages over CT when used to diagnose and find the hematopaty patient with cerebral infarction,when it has to be differentiated with cerebral early infection and parenchymal infiltration.It's suggested that the hematopathy patient has to undergo MRI examination in case central nervous system symptoms especially cerebral infarction occur.
ABSTRACT
Radiotherapy ( RT) is used as primary treatment for numerous cancers. Although it is usually described as an immunosuppressive modality,there are new preclinical evidences suggesting that RT could have also generated substantial changes in the tumor microenvironment, including triggering an inflammatory process. Some studies established the proof of concept that combining RT with strategies modifying immunology could enhance antitumor effects.
ABSTRACT
Objective: To evaluate therapeutic effect of aortic endovascular stent-graft exclusion (EVGE) combined percutaneous coronary intervention (PCI) on patients with descending thoracic aortic dissection (DTAD) complicated coronary heart disease (CHD).Methods: A total of 58 DTAD + CHD patients undergoing aortic EVGE combined PCI were regarded as EVGE group (received aortic EVGE at first, then PCI on 3d after operation).Another 60 DTAD+CHD patients undergoing open surgery combined PCI in our hospital were selected as open surgery group.Both groups were observed and followed up, and their therapeutic effects were compared.Results: Compared with open surgery group, there was significant rise in complete cut closure rate (78.33% vs.91.38%), and significant reductions in bleeding volume during operation [(919.83±242.12) ml vs.(58.17±9.53) ml], postoperative infection rate (15.0% vs.3.4%) and hospital stay [(16.40±0.96)d vs.(9.10±0.83)d] in EVGE group, P<0.05 or <0.01.Success rate of PCI was 100% in EVGE group, and there was no PCI-related severe complications.During follow-up, coronary restenosis rate within 12 months in EVGE group was significantly lower than that of open surgery group (5.20% vs.15.30%, P=0.04).Conclusion:It is safe and possesses significant effective to treat descending thoracic aortic dissection complicated coronary heart disease using aortic endovascular stent-graft exclusion combined percutaneous coronary intervention, which is worth extending.
ABSTRACT
With the deeper understanding of tumor , more and more evidence indicates that the occurrence and development of tumors are closely related to the body′s immune function .More and more researches focus on tumor immunology to find an effective way of enhancing anti-tumor immunity . Radiotherapy has played an important role in anti-tumor immunity recently though it was believed as a traditional treatment for cancer before .Radiotherapy could convert a cold tumor into a hot tumor, which might ameliorate immune suppressive microenvironment , improve tumor immunogenicity and activate the cellular immune response .However, the abscopal effectof single radiotherapy is very rare . Immunotherapy is capable of enhancing the immune response produced by radiotherapy .In this paper , the basic theory and clinical practice of radiotherapy and immunotherapy were reviewed and the related clinical strategies were summarized .
ABSTRACT
Objective@#To investigate the application of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) in the treatment of early-stage prostate cancer.@*METHODS@#We retrospectively analyzed the clinical data about 10 cases of early-stage prostate cancer treated by RS-RARP with the Da Vinci Robot Surgical System from September to October 2016.@*RESULTS@#All the operations were successfully completed without positive surgical margins. The operation time was 170－250 min (［196±25］ min), the intraoperative blood loss was 150－500 ml (［260±128］ ml), the postoperative hospital stay was 6－7 days, and the catheterization time was 14 days. Urinary continence occurred after catheter removal in 1 patient and was recovered 1 month later.@*CONCLUSIONS@#RS-RARP is a safe, effective and reliable method for the treatment of prostate cancer and conducive to the early recovery of urinary continence.
Subject(s)
Humans , Male , Middle Aged , Blood Loss, Surgical , Laparoscopy , Methods , Length of Stay , Margins of Excision , Operative Time , Postoperative Period , Prostatectomy , Methods , Prostatic Neoplasms , Pathology , General Surgery , Retrospective Studies , Robotic Surgical ProceduresABSTRACT
AIM:To compare the retinal nerve fiber layer (RNFL) thickness in patients with different severities of obstructive sleep apnea-hypopnea syndrome (OSAHS) versus normal controls.METHODS:This was an observational case-control study.Totally 79 patients presenting with snoring and daytime sleepiness who underwent overnight polysomnography (PSG) to determine OSAHS severity were recruited,and subsequently referred for ophthalmologic evaluation.The data including intraocular pressure (lOP),RNFL thickness etc was collected.RESULTS:A total of 73 subjects were recruited,including 53 patients with OSAHS and 20 normal control subjects.lOP was significantly higher for the moderate and severe OSAHS group than for the control group (both P＜0.05).The RNFL in the average and superior quadrants were significantly thinner for the moderate and severe OSAHS group than for the control group (both P＜0.05).AHI was negatively correlated with RNFL thickness in the superior quadrants,and with average RNFL thickness (r=-0.316,-0.205;both P＜0.01).Negative correlations were also identified between RNFL thickness in the superior quadrants and the ODI (r=-0.24,P =0.005).Positive correlations were identified between SaO2 on PSG and RNFL thickness in the superior quadrants (r=0.277,P=0.001).CONCLUSION:RNFL of the patients with OSAHS is thinned.Furthermore,it is observed that the greater severity of OSAHS,the greater the loss of RNFL.Among the four quadrants observed,the most affected quadrant was the superior quadrant.
ABSTRACT
In recent years, the immunotherapy based on the blocking of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has achieved encouraging progress in the treatment of malignant tumors such as melanoma and lung cancer. More and more studies have focused on its role in hepatocellular carcinoma (HCC). This article introduces the mechanism of action of PD-1/PD-L1, expression of PD-L1 in HCC tissues, and its basic and clinical research in the treatment of HCC, and points out that PD-L1 plays an important role in tumor immune escape and is expected to become an independent index for evaluating the prognosis of HCC. The discovery of PD-1/PD-L1 pathway provides a new target for immunotherapy for HCC.
ABSTRACT
ObjectiveTo determine the efficacy and prognostic factors of intensity-modulated radiotherapy (IMRT) for primary hepatocellular carcinoma (HCC) with portal vein and/or inferior vena cava tumor thrombus. MethodsTwenty-three HCC patients with portal vein and/or inferior vena cava tumor thrombus received IMRT with an 8 MV linear accelerator at the Cancer Center of General Hospital of Armed Police Forces, Anhui Medical University, from April 2008 to August 2011. A single dose of 3 to 6 Gy was delivered at five fractions per week, with a total dose of 56 to 96 Gy and a median dose of 60 Gy. Survival time was recorded, and adverse reactions were evaluated. Survival rate calculation and survival analysis were performed using the Kaplan-Meier method. Comparison of categorical between two groups was made by chi-square test. ResultsOne patient did not complete radiotherapy due to upper gastrointestinal bleeding. Of 22 patients who completed IMRT, 4 achieved complete remission and 10 achieved partial remission, with an overall response rate of 63.7%. Our analysis showed that the type of tumor thrombus and tumor size were associated with tumor response rate and were significant prognostic factors (P＜0.05). The median survival time was 13.4 months. The 1-, 2-, and 3-year survival rates were 59%, 27%, and 18%, respectively. The 22 patients who completed radiotherapy did not experience acute radiation injury or late adverse outcomes such as radiation-induced liver disease. ConclusionThis study suggests IMRT is a safe and effective treatment option for HCC patients with portal vein and/or inferior vena cava tumor thrombus.
ABSTRACT
ObjectiveTo investigate the efficacy of intensity-modulated radiotherapy (IMRT) in treating large primary hepatocellular carcinoma (LHCC) which is unsuitable for surgery or has poor response to radiofrequency ablation, interventional therapy, and other local treatments, and to identify the prognostic factors for survival. MethodsWe retrospectively analyzed the clinical data of 29 LHCC patients who received IMRT from April 2008 to August 2011. There were five fractions per week and the dose for each fraction was 2 to 6 Gy; the total dose was 50 to 70 Gy. The short-term efficacy and prognosis were observed and analyzed. The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis. Multivariate analysis was performed using the Cox regression model. ResultsThe complete remission, partial remission, stable disease, and disease progression rates were 3.57%, 32.14%, 53.57%, and 10.72%, respectively. The overall median progression-free survival (PFS) time was 6.43 months, and the median overall survival (OS) time was 11.43 months. The 1- and 2-year survival rates were 46.79% and 25.23%, respectively. Univariate analysis showed tumor response rate was an independent prognostic factor for PFS. The Cox proportional hazard model suggested the tumor response rate and prescribed dose were the independent prognostic factors for PFS. In addition, the independent prognostic factors for OS included tumor response rate, tumor diameter, and tumor volume. The common acute radiotherapy toxicities included gastrointestinal discomfort, radiation-induced liver damage, and myelosuppression. ConclusionIMRT is a safe and effective option for the LHCC patients who are unsuitable for surgery or in the cases that other local therapies fail.