Objective To investigate the feasibility,efficacy and safety of high dose chemotherapy (HDC)and autologous peripheral blood stem cell transplantation(PBSCT)with CD34~+ cell selection in patients with severe primary Sjgren's syndrome(pSS).Methods Three patients with persistent and severe pSS de- spite of glucocorticoid and immunosuppressive treatment were enrolled from 1999.All patients underwent high dose chemotherapy and peripheral blood stem cell infusion with CD34~+ cell selection.Autologous hematopoietic stem cells were mobilized with 2～3 g/m~2 CTX(total dosage,infused in two days)and 5?g/kg granulocyte colony stimulating factor(G-CSF),enriched with CD34~+ cell selection by CliniMACS,and reinfused after con- ditioning with 200 mg/kg CTX and 90 mg/kg swine antithymocyte globulin or 200 mg/kg CTX and total body irradiation of 4 Gy.Results One patient got complete remission after 2 times of mobilization,so no condi- tioning and transplantation were given.Other 2 patients completed the mobilization and leukapheresis proce dures successfully,and proceeded to receive conditioning and transplantation.All patients had rapid hematopoi- etic reconstitution.Three patients were followed up for 48 months,60 months and 18 months,respectively.All patients were free from abnormal activity of B lymphocytes.The titer of antibody decreased and anti-SSB anti- bodies of 2 patients turned to negative.Aggregation of focal lymphocytes in labial gland disappeared in 1 pa- tient after PBSCT.Improvement of pulmonary dysfunction and reversibility of interstitial pulmonary fibrosis fol- lowing hematopoietic stem cell transplantation were observed in 2 patients.Conclusion The abnormal activity of B lymphocytes in pSS patients can be controlled successfully with PBSCT.High close chemotherapy followed by peripheral blood stem cell transplantation with CD34~+ cell selection is feasible and safe.

OBJECTIVETo assess the value of fluorescent in situ hybridization (FISH) for detecting common chromosome aneuploidies in interphase nuclei of amniotic fluid cells.

METHODSEighty two uncultured amniotic fluid samples and supernatants from 2 successfully and 5 unsuccessfully cultured amniotic fluid samples were analyzed with FISH. Results from standard cytogenetic analysis of 79 uncultured amniotic fluid samples and 2 successfully cultured amniotic fluid samples were compared with FISH results.

RESULTSAll of the 89 samples were succeeded analyzed with FISH. Positive findings included 3 cases with trisomy 21, 1 case with 47, XYY and 1 case with 69, XXX, which were consistent with results of karyotype analysis.

CONCLUSIONFISH is a rapid and accurate method for prenatal diagnosis, and can also provide a remedy to failed amniotic fluid cells culture.

Adult ; Amniotic Fluid ; cytology ; Cell Culture Techniques ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Pregnancy

OBJECTIVETo evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy (HDIT) and autologous hemopoietic stem cell transplantation (HSCT) with CD34+ cell selection in patients with severe, refractory autoimmune diseases.

METHODSTwenty-six patients with persistent systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), or systemic sclerosis (SSc) who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease activity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored.

RESULTSOverall treatment related mortality was 7.7% (2/26) with 1 patient died of cytomegalovirus infection and another of severe pneumonia. Relapse occurred in 3 SLE patients (17.6%) in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index (SLEDAI) scores of SLE survivors decreased significantly (P < 0.01). RA patients recorded a drop of Disease Activity Score 28 (DAS 28). The pSS patient remained symptoms free up to now, more than 50 months after the transplantation.

CONCLUSIONHSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.

Adolescent ; Adult ; Antigens, CD34 ; analysis ; Arthritis, Rheumatoid ; immunology ; therapy ; Autoimmune Diseases ; immunology ; therapy ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lupus Erythematosus, Systemic ; immunology ; therapy ; Male ; Pilot Projects ; Recurrence ; Sjogren's Syndrome ; immunology ; therapy ; Transplantation Conditioning ; Transplantation, Autologous

Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4),following a 4-week observation period (week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score (range,0-52,with higher scores indicating more depression) over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.

The normal function of vascular endothelial cells is an important foundation for maintaining vascular permeability， restricting inflammatory activities of the vascular wall， and balancing the coagulation and fibrinolytic system. Endothelial dysfunction caused by persistent damage from pathological factors is considered as an early and prominent event of diabetic macroangiopathy. In traditional Chinese medicine， the classical theory of "restraining excessiveness to acquire harmony" was originally a condensed generalization of the rule of generation， restriction， replacement and evolution in the natural world， revealing the internal regulation mechanism of the stable operation of things. Then it gradually evolved into an important rule to explain the physiological phenomena and pathological mechanism of human body and guide the treatment. Corresponding to the nature， the body homeostasis also requires to achieve a state of strong viscera function and inexhaustible Qi and blood generation under the rule of restriction and generation. The pathogenesis of diabetic macroangiopathy is the process of "the predominant one failing to restrict and the hyperactive one becoming harmful". The loss of restriction and generation of the five organs leads to powerless Qi transformation and， as a result， the Qi， blood and body fluid cannot be dispersed. Therefore， the Qi， blood and body fluid turn into phlegm and blood stasis， such as glucose and lipid metabolism disorder， oxidative stress， inflammatory response and high blood viscosity， and finally block the veins. Excessive phlegm and blood stasis cannot be resolved， instead they become harmful and invade the blood vessel， causing endothelial dysfunction and further resulting in diabetic macroangiopathy. Under the guidance of the theory of "restraining excessiveness to acquire harmony"， the method of "harmonizing viscera， eliminating pathogen and removing turbidity" can effectively regulate the function of vascular endothelial cells， thus playing a positive role in preventing and treating diabetic macroangiopathy. The mechanism may be related to reducing oxidative stress， inhibiting inflammation， limiting vascular smooth muscle proliferation， and reducing platelet adhesion.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

: AbstractObjective: To identify the expression and methylation patterns of lncRNA CASC15 in bone marrow (BM) samples of acute myeloid leukemia (AML) patients, and further explore its clinical significance. METHODS: Eighty-two de novo AML patients and 18 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the expression and methylation data of CASC15. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML. The patients were divided into CASC15high group and CASC15low group by X-tile method, and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis. RESULTS: The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors (P<0.001). ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls. The expression of CASC15 was high at the early stage of hematopoiesis, and reached a peak at the stage of multipotent progenitors differentiation, then decreased rapidly, and was at a range of low level fluctuations in the subsequent process. Among FAB subtypes, CASC15 expression in M0 was significantly higher than that in M1-M7. Clinically, CASC15low patients were more likely to have NPM1 mutations than CASC15high patients (P=0.048), while CASC15high patients had a significantly higher frequency of IDH1 and RUNX1 mutations (P=0.021 and 0.014, respectively). Moreover, CASC15low group had a shorter overall survival (OS) in patients with NPM1 mutations. Furthermore, multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients. In addition, CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors. Patients with CASC15 high methylation had poor OS and disease-free survival. CONCLUSION The expression of CASC15 is decreased in AML, and low CASC15 expression may predict adverse prognosis in AML patients with NPM1 mutations. Moreover, CASC15 methylation level in AML is significantly decreased, and high CASC15 methylation may predict poor prognosis in AML.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Mutation ; Nuclear Proteins/genetics* ; Nucleophosmin/genetics* ; Prognosis ; RNA, Long Noncoding/genetics*

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health