OBJECTIVE: To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis. METHODS: A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed. RESULTS: In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08). CONCLUSION The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Prognosis ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Myeloproliferative Disorders ; Mutation

Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan-Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple ( ⩾ 3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P < 0.001) and OS (68.5% vs. 85.8%, P = 0.001) than those without multiple abnormal immunologic markers. Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P = 0.008, P < 0.001) and OS (P = 0.003, P < 0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P = 0.001) and age > 60 years for OS (P = 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers ; China ; Disease Progression ; Female ; Humans ; Immunotherapy ; methods ; Lymphoma, Large B-Cell, Diffuse ; mortality ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Young Adult

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2–3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.
Adult ; Asian Continental Ancestry Group* ; China ; Comorbidity ; Developed Countries ; Developing Countries ; Diagnosis* ; Epidemiologic Studies ; Epidemiology ; Global Health ; Humans ; Hypersensitivity* ; Prevalence ; Rhinitis, Allergic*

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

Objective To provide experimental evidence for development of human cytomegalovirus (HCMV) nucleic acid vaccine,HCMV surface protein(gB),membrane protein(pplSO),and gB-pp150 fused gene eukaryotie expression vector were constructed.Methods gB and pp150 genes were amplified and fused into gB-pp150,then were cloned into pcDNA 3.1(+) to obtain recombinant expression plasmids pcDNA 3.1(+)-gB,pcDNA 3.1(+)-pp150 and pcDNA 3.1(+)-gB-pp150,which were encapsulated with chitosan.Mouse were vaccinated and the humoral and eell immune response were determined by ELISA,specific proliferative response of plenie lymphocytes.Results The gB,pp150 and gB-pp150 fusion gene eukaryotie expression vector were successfully constructed.The antibodies A value induced by peDNA3.1(+)-gB or peDNA3.1(+)-gB-pp150 were much higher than that of peDNA3.1(+)(P<0.01).The IFN-γ levels induced by pcDNA3.1(+)-pp150 and peDNA3.1(+)-gB-pp150 were significantly higher than that of pcDNA3.1(+).There are significant diferenee between the stimulating indexes of pcDNA3.1(+)-pp150 or peDNA3.1(+)-gB-pp150 immunized and normal mice.Conclusion The DNA vaccine pcDNA3.1(+)-gB can induce significant humeral immunity response.and pcDNA3.1 (+)-pp150 can induce high cellular immune response,whereas pcDNA3.1(+)-gB-pp150 can induce both humeral and cellar immune responses in BALB/c mice.

The aim of this study was to investigate the relationship between the plasma levels of chemokine CCL-2/MCP-1 and acute graft-versus-host disease (aGVHD) and/or idiopathic pneumonia syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ELISA assays were used to detect the plasma level of CCL-2/MCP-1 of 22 patients who received allo-HSCT, including 14 patients without or with grade I, 8 patients with grade II - IV aGVHD, respectively. 8 out of 22 patients were also diagnosed with IPS clinically. The dynamic changes of the plasma levels of CCL-2/MCP-1 chemokine and its correlation with aGVHD and/or IPS were analysized retrospectively. The results showed that the plasma levels of CCL-2/MCP-1 in the patients with moderate and serious aGVHD (grade II - IV) significantly increased, as compared with that prior to allo-HSCT (p < 0.05). The plasma levels of CCL-2/MCP-1 in the patients with aGVHD and/or IPS were higher significantly than those without any of these complications (p = 0.001). The retrospective analysis indicated that the plasma levels of CCL-2/MCP-1 in the patients with IPS significantly increased (p = 0.006). It is concluded that plasma level of CCL-2/MCP-1 correlates with aGVHD and/or IPS, and plays a role in the pathogenesis of these complications.
Adolescent ; Adult ; Chemokine CCL2 ; blood ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; blood ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Lung Diseases, Interstitial ; blood ; etiology ; Male ; Middle Aged ; Syndrome ; Young Adult

Objective To introduce the technique of interictal 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) examination and explore the value of 18F-FDG-PET in the localization of epileptogenic focus of temporal lobe epilepsy (TLE) confirmed by surgical result.Methods Clinical data were retrospectively analyzed in 82 TLE patients having received interictal 18F-FDG-PET preoperative evaluation and got EngleⅠ grade epileptic surgical outcome, and the sensitivity and specialty of interictal 18F-FDG-PET were compared with those of MRI and scalp video-EEG. Results Epileptogenic foci showed hypometabolism on 18F-FDG-PET, and the hypometabolism zones were localized in ipsilateral temporal lobe in 68 cases,beyond ipsilateral temporal lobe in 9 cases; the other 5 had no hypometabolism zone. Accuracy rate of localization of epileptogenic foci by interictal 18F-FDG-PET was 82.9% (68/82), significantly higher than that by MRI or EEG(P＜0.05).77.4%(41/53)epileptogenic foci where MRI showed negative and 75%(15/20)where EEG with imbedded electrode was applied were precisely localized by 18F-FDG-PET. The accuracy was higher in the cases with positive pathological result than in the ones with negative result. Conclusions Interictal 18F-FDG-PET possesses excellent sensitivity and specialty in preopemtive assessment for TLE, and is of good value in the localization of epileptogenic focus where MRI shows negative or invasive electrophysiologic monitoring is needed.Rational application may raise the accuracy rate.

OBJECTIVETo explore the mechanism of virulence regulation in group B streptococcus (BGS) by studying LuxS-related AI-2 quorum-sensing pathway in GBS.

METHODSluxS gene deletion mutants of GBS (Delta lusX) were characterized by reverse transcription (RT)-PCR, colony immunoblot analysis, growth curve measurement, and cAMP determination. Functional analysis of luxS in the deletion mutants was conducted by bioluminescence assay.

RESULTSGenetic analysis results showed that the luxS deletion in the mutant 515-Delta lusX caused upregulation of scpB gene expression. Phenotypic analysis revealed that, in comparison with the wild strain, 515-Delta lusX mutant grew slowly in DCM media but quickly in THY media. An approximately two-fold decrement in bioluminescence was detected in the luxS deletion mutants as compared with the wild strain.

CONCLUSIONThis study confirms the importance of LuxS molecule in the AI-2 quorum-sensing pathway in GBS and provides new insights into the virulence regulation mechanism of GBS.

Bacterial Proteins ; genetics ; Carbon-Sulfur Lyases ; genetics ; Gene Deletion ; Gene Expression Regulation, Bacterial ; Lighting ; Phenotype ; Streptococcus agalactiae ; genetics ; pathogenicity ; Virulence

BACKGROUND: The structural and functional impairment of endothelium cells were mainly presented by lowered endothelium activity, reduced nitrogen monoxide production, as well as increased endothelium vasoconstrictor peptide (EVCP).OBJECTIVE: To study the protective role of astragalus polysaccharide on atherosclerosis induced by eudothelium cell injury, which was compared with that of Captopril.DESIGN: Randomly controlled observation.SETTING: Department of Physiology, Hubei College of Traditional Chinese Medicine; Department of Pathophysiology, Medical College of Wuhan University;Department of Surgery,Hetang Hospital of Guangdong Province;Department of Endocrinopathic Sciences,Renmin Hospital,Wuhan University.MATERIALS: The study was carried out at the Organic Function Laboratory of Hubei College of Traditional Chinese Medicine and the Pathophysiological Department of Wuhan Medical University from July 2001 to December 2002. Forty healthy male rabbits provided by the experimental animal center of Wuhan medical university, weighed of 2.4-3.0 kg, were randomly divided into blank group,model control group,astragalus polysaccharide group and captopril group with 10 rabbits in each group.Astragalus polysaccharide was extracted from Shanxi produced astragalus root and made into injection powder that should be freshly composed with physical saline before usage.METHODS: Rabbits in blank group were raised with granular feed, while rabbits in other three groups were given hyperlipid feed (80％ basal feed mixed with 15％ yolk powder, 0.5％ cholesterin and 5％ lard), in addition with venous injection of bovine serum by 1 mL/kg once, atherosclerosis induced endothelium injury model was established on rabbit by hyperlipid feed combined with immune injury. Rabbits in astragalus polysaccharide group received intraperitoneal injection of polysaccharide of 500 mg/kg once a day; which replaced by 5 mg/kg captopril in captopril group that equals to 5 times clinical dosage; While rabbits in blank group and model control group were given the same volume physical saline of 4 mL/kg for totally 50 days. Blood were collected from SVC 24 after the last medication and then rabbits were put to death, the morphological changes of abdominal aorta were observed under optical microscope, meanwhile the changes of serum total cholesterol, triglycerides, nitrogen monoxide, EVCP, superoxide dismutase, malonaldehyde and total antioxidation activity were examined.MAIN OUTCOME MEASURES: ① Morphological changesof abdominal aorta. ② Changes of serum parameters.RESULTS: All 40 rabbits complete the experiment without loss. ① In contrast with model control group group, the total serum total cholesterol and triglycerides in astragalus polysaccharide group and captopril group obviously decreased [(9.33±1.13), (6.60±0.61), (7.09±0.74) mmol/L, P ＜ 0.05;(3.05±0.44), (1.26±0.16), (2.17±0.46) mmol/L, P ＜ 0.01, P＜ 0.05],malonaldehyde and EVCP markedly decreased [(9.98 ± 1.11 ), (7.10 ±0.68),(9.46±1.27) μmol/L, P ＜ 0.01; (741.90±34.98), (632.62±26.95),(600.74±32.59) ng/L, P ＜ 0.01]. ② Comparing to model control group group,the serum nitrogen monoxide and superoxide dismutase were obviously increased in astragalus polysaccharide group and captopril group ·[(11.04±1.68),(19.96±6.05), (18.35±3.52) μmol/L, P ＜ 0.01, P ＜ 0.05; (159.32±5.26),(207.54±16.98), (197.59±28.41) NU/mL, P ＜ 0.0l, P ＜ 0.05], the total antioxidation activity also increased [(23.8±3.5), (34.7±5.6), (30.7±6.8)％,P ＜ 0.01, P ＜ 0.05]. ③ Either the decrement of serum triglycerides, total cholesterol and malonaldehyde or the increment of nitrogen monoxide, superoxide dismutase and total antioxidation activity in astragalus polysaccharide group was greater than captopril group (P ＜ 0.01). ④ Morphological changes of abdominal aorta: The aorta intima was smooth and endothelium cells were continuous with small intervals between cells in blank control group,endothelium cells presented normal configuration without edema;while intima in model control group became thick and upheaved, part of endothelinm cells detached with widened intervals. The media became thickened with leiomyocyte displaying hyperplasic and infiltering into endothelium, foaming cells could also be observed; the aorta intima was smooth and endothelium was closely connected in astragalus polysaccharide group, the hyperplasia of leiomyocyte was not active and foaming cells seldom observed; while in captopril group, the aorta intima was smooth without obvious detachment of endothelium cells and infiltration of leiomyocyte, leiomyocytes were normal and ranked orderly.CONCLUSION:Astragalus polysaccharide could markedly eliminate serum triglycerides, total cholesterol, malonaldehyde and EVCP, thereby alleviate vascular impairment induced by EVCP, meanwhile markedly increased serum nitrogen monoxide, superoxide dismutase and total antioxidation activity, the intima surface of abdominal aorta could be smooth due to the administration of AP, endothelium configuration would be basically complete, implying that it has better antioxidation property and protective role for endothelium cells.

Objective To evaluate the value of diffusion tensor imaging(DTI)in cognitive impairment of patients with acute cerebral infarction.Methods Diffusion tensor images were obtained from 30 volunteers who underwent clinical MR imaging and were found to have no abnormalities on conventional MR images and 30 patients who were clinically diagnosed cerebral infarction and were found to have infarction lesions on conventional MR images.Color-coded FA images and three-dimensional color-coded tensor images were reconstructed.For volunteers,average apparent diffusion coefficient(ADC)and fractional anisotropy(FA)were measured in some main white matter structures of peripheral white matter, basal ganglia,and cerebral peduncle,etc.For infarction patients,ADC and FA were measured and compared between infarction lesions and corresponding contralateral normal regions.Pearson correlation analysis was used to determine correlation with cognitive impairment.Results In infarction patients group, FA and ADC of lesions unrecovered declined.Change in ADC and FA had positive correlation with cognitive impairment of patients with acute cerebral infarction.Conclusion DTI has positive correlation with cognitive impairment of patients with acute cerebral infarction.