Design, synthesis, and activity of 5-cyano-2-thiacetyl aromatic pyrimidinone as DENV NS5 RdRp inhibitors / 药学学报

To screen novel anti-dengue virus (DENV) NS5 RdRp enzyme inhibitors, a series of 5-cyano-2-thiacetoaryl pyrimidinone compounds were designed and synthesized by molecular hybridization method with HCV NS5B RdRp inhibitor 3jc and ZIKV NS5 RdRp inhibitor 4w as lead compounds. The anti-DENV activity of these compounds was evaluated by MTT assay and plaque assay and five compounds showed anti-DENV activity. The most active compound 7a'k showed better anti-DENV activity than that of the positive control ribavirin (EC50 = 7.86 μmol·L-1 vs EC50 = 18.07 μmol·L-1), and the other four compounds showed almost the same anti-DENV activity as ribavirin. Finally, the prediction and simulation of the binding mode through molecular provided new ideas for the further development of this new DENV NS5 RdRp inhibitor.

Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Lipid Accumulation and IL-6 Production in L02 Hepatocytes Induced by Sodium Oleate: Dose and Time Dependence / 生物医学与环境科学（英文）

To explore interleukin-6 (IL-6) production and characterize lipid accumulation in L02 hepatocytes induced by sodium oleate. L02 hepatocytes were incubated with 0, 37.5, 75, 150, 300, 600, or 1,200 μmol/L sodium oleate for 24 h, and the supernatant was collected to detect the concentration of IL-6. L02 hepatocytes were incubated with 300, 150, 75, or 0 μmol/L sodium oleate for 0-24 h. The supernatant was collected for detection of IL-6 and free fatty acids. L02 hepatocytes treated with 300 μmol/L sodium oleate for 0-24 h were stained with Oil Red O. With extended sodium oleate incubation time, IL-6 levels increased, and free fatty acids decreased. After 24 h incubation, IL-6 levels increased as sodium oleate increased from 37.5 to 300 μmol/L (

Characteristic of 8p11 Myeloproliferative Syndrome with Rare Phenotype / 中国实验血液学杂志

OBJECTIVE@#To deeply understand the clinical manifestation, laboratory examination characteristics, diagnosis and treatment of an eight p11 myeloproliferative syndrome (EMS) with rare phenotypes.@*METHODS@#The clinical and laboratory characteristics and the process of allogeneic hematopoietic stem cell transplantation (allo-HSCT) were summarized in 1 rare EMS case involving T/B/myeloid cells. Meanwhile, 2 similar cases in the previous literature were also discussed.@*RESULTS@#The bone marrow examination indicated that the patient with B-cell acute lymphocytic leukemia. The lymph node biopsy showed that the patient was T lymphoblastic/myeloid lymphoma. The 8p11 abnormality was found by the examination of bone marrow chromosomes. The RT-PCR examination showed that the BCR-ABL fused gene was negtive. The FGFR1 breakage was found by using the FISH with FGFR1 probe in lymph node. The Mutation of FMNL3, NBPF1 and RUNX1 genes was found by using the whole exome sequencing. The patient received allo-HSCT under CR2. By the follow-up till to September 2019, the patient survived without the above-mentioned disease.@*CONCLUSION@#EMS manifest as neoplasms involving T-lineage, B-lineage, and myeloid-lineage simultaneously is extremely rare. Although the FGFR1 gene-targeted therapy can be conducted, allo-HSCT should be actively considered.

Clinical Features and Prognosis of Patients with Hematological Disease Complicated with Mucor Infection / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features, treatment and prognosis of patients with hematological diseases complicated with mucor infection.@*METHODS@#The risk factors, clinical features, treatment regimen and prognosis of 18 hematological disease patients with mucor infection diagnosed by histopathology in our center from April 2014 to June 2020 were retrospectively analyzed.@*RESULTS@#Thirteen males and five females, with an average age of 30 (13－54) years old, were diagnosed as mucor infection by histopathological examination at the site of infection, including 16 cases of mucor infection alone and 2 cases of mucor + aspergillus mixed infection. There were 12 cases with malignant hematological disease and 6 cases with severe aplastic anemia, all of whom with long-term agranulocytosis, and their clinical manifestations and imaging findings were not specific. The common sites of infection were sinuses and lungs, and some patients showed multiple systemic manifestations. The remission status of hematological diseases and recovery of immune function showed an impact on the prognosis. All the patients were treated with amphotericin B liposome combined with posaconazole, and 15 patients were treated with surgery combined with antifungal drugs, 9 of whom were effective and 6 were ineffective, while intravenous administration in 3 cases was ineffective.@*CONCLUSION@#It is difficult to diagnose hematological disease complicated with mucor infection. After early diagnosis, prognosis can be improved by amelioration of primary state and combination of drugs and surgery.

Clinical and imaging features of thirty cases of paragonimiasis westermani / 中国血吸虫病防治杂志

Objective To analyze the clinical manifestations and imaging characteristics of pulmonary and extra pulmonary paragonimiasis westermani. Methods A retrospective analysis was performed of 30 patients diagnosed by clinical features, laboratory serological tests and surgical pathology. Results The symptoms of the lung included mainly chest distress, fever, chest pain, cough and expectoration, and dyspnea. The extra pulmonary symptoms included abdominal pain, vomiting, diarrhea, poor appetite, emaciation, both lower extremities asthenia, headache, dizziness, epileptic seizures, and subcutaneous migratory masses. The laboratory examination showed that the eosinophil numbers of serum and pleural effusion of all the thirty patients were increased, and the eggs of Paragonimus westermani were found by the stool tests in four cases. The chest CT tests found abnormal nodules, ground glass changes, insect damages, pleural effusion, "tunnel" signs, and "halo" signs. Cranial CT and MRI showed intracranial hemorrhage foci, and extensive "finger-like" edema. Abdominal CT showed serpentine deformation and “tunnel” signs in the hepatic and spleen capsules. Conclusions Paragonimiasis westermani is a multiple organ system involved infection, and it has complex and varied clinical manifestations. The "tunnel" sign and serpentine deformations in the intracranial part, lung, liver and spleen are important imaging manifestations of the disease.

Clinical and imaging features of thirty cases of paragonimiasis westermani / 中国血吸虫病防治杂志

Objective To analyze the clinical manifestations and imaging characteristics of pulmonary and extra pulmonary paragonimiasis westermani. Methods A retrospective analysis was performed of 30 patients diagnosed by clinical features, laboratory serological tests and surgical pathology. Results The symptoms of the lung included mainly chest distress, fever, chest pain, cough and expectoration, and dyspnea. The extra pulmonary symptoms included abdominal pain, vomiting, diarrhea, poor appetite, emaciation, both lower extremities asthenia, headache, dizziness, epileptic seizures, and subcutaneous migratory masses. The laboratory examination showed that the eosinophil numbers of serum and pleural effusion of all the thirty patients were increased, and the eggs of Paragonimus westermani were found by the stool tests in four cases. The chest CT tests found abnormal nodules, ground glass changes, insect damages, pleural effusion, "tunnel" signs, and "halo" signs. Cranial CT and MRI showed intracranial hemorrhage foci, and extensive "finger-like" edema. Abdominal CT showed serpentine deformation and “tunnel” signs in the hepatic and spleen capsules. Conclusions Paragonimiasis westermani is a multiple organ system involved infection, and it has complex and varied clinical manifestations. The "tunnel" sign and serpentine deformations in the intracranial part, lung, liver and spleen are important imaging manifestations of the disease.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study / 中华医学杂志(英文版)

Background@#Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT.@*Methods@#From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups.@*Results@#After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar–cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim).@*Conclusions@#Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Chimeric antigen receptors T cells for treatment of 48 relapsed or refractory acute lymphoblastic leukemia children: long term follow-up outcomes / 中华血液学杂志

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ2=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors. Conclusion: The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.

The efficacy analysis of allogeneic hematopoietic stem cell transplantation in 48 leukemia patients with central nervous system leukemia / 中华血液学杂志

Objective: To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of leukemia patients also suffering from central nervous system leukemia (CNSL) . Methods: A total of 48 leukemia patients with central nervous system leukemia admitted to our hospital from May 2012 to December 2017 were retrospectively analyzed. Results: ① Including 22 cases of acute lymphocytic leukemia (ALL) , 21 cases of acute myeloid leukemia (AML) , and 5 cases of chronic myelogenous leukemia (CML) . Before transplantation, 19 patients achieved complete remission (CR) , and the rest 29 ones without remission. ②The conditioning regimen used TBI as the main protocol, and 6 patients were combined with whole brain and total spinal cord radiotherapy, 2 with Cyber knife treatment, and children with modified IDA combined with BUCY. ③All 48 patients were successfully transplanted, the median time for leukocyte engraftment was 14 (10-23) days, the median time for platelet transplant 16 (6-78) days. ④Bone marrow was evaluated 28 days after transplantation, all 48 patients reached CR, and DNA testing confirmed that they were all full donor chimerism. ⑤The median follow-up was 14 (2-69) months. Of them, 28 cases survived, 10 relapsed and the rest 3 had recurrence of CNSL after transplantation. One year after allo-HSCT, the overall survival (OS) of CR and non-CR groups were (77.3±10.0) % and (57.6±9.3) % (P=0.409) , respectively, the disease-free survival rates (DFS) were (71.2±11.0) % and (53.9±9.5) % (P=0.386) , respectively. The 1-year OS rates of ALL and AML groups after transplantation were (54.2±10.7) %, (80.1±8.9) %, respectively (P=0.200) , and DFS rates were (49.2±10.8) %, (75.0±9.7) % (P=0.190) , respectively. Conclusion: Allo-HSCT was safe and effective for leukemia patients with CNSL.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study / 中华医学杂志(英文版)

BACKGROUND@#Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT.@*METHODS@#From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups.@*RESULTS@#After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim).@*CONCLUSIONS@#Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Observation on efficacy, pharmacokinetic behaviors and safety of new modified RNA oligonucleotide targeting Foxo-1 via two routes of administration / 药学学报

Foxo-1 plays an important role in development of muscle atrophy, serving as a potential target for therapeutic treatment of the disease. In this study, the Foxo-1 mRNA was targeted by a Foxo-1 specific RNA oligonucleotide modified by 2'-O-methyl and with a butanol tag at the 3'-end. To understand the in vivo significance of new modified RNA oligos, efficacy, pharmacokinetic and safety profiles of the new modified RNA oligonucleotide targeting Foxo-1 were evaluated in mice. All experimental protocols were approved by the Animal Ethics Committee of Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention. The results showed that different doses of the RNA oligonucleotide can reduce the expression of Foxo-1 in mice by two routes of administration, leading to an increase in skeletal muscle mass of the mice. The results of pharmacokinetic evaluation showed that the plasma disappearance curve for the RNA oligonucleotide could be described by a two-compartmental model. The results of safety evaluation showed that no obvious adverse effects on renal and hepatic functions, nor on hematological parameters by intravenous or oral administration of the RNA oligo with a maximum dose of 30 mg·kg-1. Histopathology also did not reveal any significant changes in the morphology of the organs studied. In conclusion, the new modified RNA oligo is safe and effective in mice, providing experimental evidence supporting the significance for its clinical application.

Clinical Study of Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Peripheral T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL).@*METHODS@#The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed.@*RESULTS@#All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months.@*CONCLUSION@#allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

Prognostic Analysis of Minimal Residual Disease from Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplant by Flow Cytometry / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the value of flow cytometry (FCM) detection in prognostic evaluation of minimal residual disease (MRD) of acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Eighty-two cases of AML (except M3) after allo-HSCT who accord to enrolled condition (no MRD positive after allo-HSCT confirmed by regular flow cytometry detection and followed-up for 2 years) from April 2012 to September 2016 in our department were selected. Among 82 cases males were 50 and females were 32 with average age of 27.27 (2-57) years old. According to FAB classification, 2 cases were classified as M0/M1, 51 cases as M2, 24 cases as M4/M5 and 5 cases as M6. The antibody panels were selected accordingly to the initial leukemia associated immunophentype(LAIP) of patients.</p><p><b>RESULTS</b>Twenty patients (24.39%) were identified as MRD(0.10%-4.91%, mean 1.64%) in 82 AML patients after allo-HSCT (all the patients were in complete remission phase based on bone marrow morphology). During follow-up, 16 cases relapsed (relapse rate 80%)in 20 MRDcases, including 1 case with extramedullary relapse; 4 out of 62 MRDcases relapsed (relapse rate 6.45%)in bone marrow, and 2 cases extramedullary relapsed. The average survival time of leukemia- free survival (LFS) in group MRDwas 15.19 ± 3.99 months, median LFS was 10± 3.84 months. The average LFS time was 53.50 ± 1.69 months in MRDgroup (P<0.001). The average overall survival (OS) of the MRDgroup was 22.52 ± 5.72 months, the median OS was 18 ± 3.27 months; the average OS time was 42.86 ± 2.83 months in MRDgroup(P=0.008).</p><p><b>CONCLUSION</b>For the patients with morphologically complete remission after allo-SCT, the FCM regular monitoring of bone marrow MRD closely relates with its relapse rate, LFS and OS. Compared with the MRDgroup, the relapse rate of MRDgroup is significantly increases, and the LFS and OS significantly decreases.</p>

Effects of CD34(+) selected stem cells for the treatment of poor graft function after allogeneic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the efficacy and safety of purified CD34(+) stem cell boost in the treatment of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HSCT) . Methods: 12 patients with poor graft function, reported in our hospital during January 2014 to March 2018, were retrospectively analyzed; The donors of 12 patients were HLA mismatched family members, and all treated with donor purified CD34(+) stem cell after G-CSF mobilization, calculating and statistical analyzing the purity of separation and the recovery rate of CD34(+) stem cells. The related complications and the recovery of blood cells after infusion were observed. Results: The purity of CD34(+) cells in the separation products was 92.0% (44.0%-97.0%) , and the recovery rate was 55.0% (45.0%-96.7%) . The median number of CD34(+) cells was 1.9 (0.9-4.4) ×10(6)/kg with CD3(+) cells as 0.6 (0.3-2.0) ×10(4)/kg. The median durations of white blood cells, platelet and red blood cells recoveries were 18 (14-39) , 29 (16-153) and 60 (9-124) days, respectively. All 12 patients didn't experience serious adverse reactions in the process of infusion, 10 patients achieved hematopoietic recovery, 1 case partial remission, 1 case no recovery, without occurrence of aggravated infection, graft versus host disease and other complications. Conclusion: The infusion of donor purified CD34(+) stem cell was a safe and effective method for PGF after allogeneic HSCT.

Combination of R848 and Poly（I:C）promotes antigen presentation by DC and enhances killing effect of CTL on lung adenocarcinoma A549 cells / 中国病理生理杂志

AIM: To investigate the effect of R848(a Toll-like receptor 7/8 agonist)combined with poly-inosinic:polycytidylic acid [Poly(I:C),a Toll-like receptor 3 agonist] on dendritic cell(DC)maturation,and the killing effect of DC-induced cytotoxic T-lymphocytes(CTL)on human lung adenocarcinoma A549 cells.METHODS:Mononu-clear cells were isolated from human peripheral blood and induced to differentiate into DC.The whole-cell lysate of A549 cells,namely tumor cell lysate(TCL), was used as antigen.R848 combined with Poly(I:C)was used as adjuvant to stimulate the DC.DC surface markers were analyzed by flow cytometry.The DC stimulated by antigen was co-cultured with T-lymphocytes for 7 d to induce CTL.The culture supernatant and CTL were collected.The levels of interleukin-12(IL-12)p70,interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)in the supernatant were measured by ELISA.The CTL and A549 cells were co-cultured for 16 h,and the cytotoxicity was observed by LDH assay.RESULTS:The expres-sion of CD83 and CD80 on the DC surface,and the secretion of IL-12 p70 in DC-R848+Poly(I:C)group were significant-ly increased compared with DC-TCL group(P<0.01).In addition,the cytotoxicity of CTL for A549 cells in DC-R848+Poly(I:C)group was significantly enhanced compared with DC-TCL group(P<0.01).The secretion levels of IFN-γand TNF-αin DC-R848+Poly(I:C)group were significantly elevated compared with DC-TCL group(P<0.01).CONCLU-SION:R848 combined with Poly(I:C)significantly promotes DC maturation and activation, and enhances the antigen-presenting effect of DC and the cytotoxicity of DC-induced CTL.

Four Cases of Wernicke's Encephalopathy Following Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To make through introduction of Wernicke's encephalopathy (WE) following hematopoietic stem cell transplantation (HSCT) in terms of clinical characteristics, diagnostic process and treatment.</p><p><b>METHODS</b>The clinical charactaristics, diagnostic and therapeutic process and prognostic follow-up in 4 patients diagnosed of WE following HSCT between January 2016 to January 2017 at Department of Hematology, Chinese Aerospace Center Hospital were retrospectively analyzed.</p><p><b>RESULTS</b>Four patients included 2 ALL and 2 AML, and 3 males and 1 female, their age ranged from 8 to 20 years old. 4 patients accouted for about 3% of all petients who received HSCT at that time. Typical triad syndrome consisting of ocular motility disorders, ataxia, global confusion was seen in only 1 patient. However, confusion and heterophthongia as onset of this complication were seen in all patients. Cerebral computed tomograph scan was universally unremarkable and useless. Cerebral MRI scan disclosed that typical involvement including thalamus, fourth ventricle, third ventricle, middle cerebral aqueduct was seen in 3, while untypical site including mamillary body was in the remaining 1 patient. All received vitamin B supplement therapy by intramuscular injection at a dose of 100 mg each day. Initial response was observed at 2, unknown, 3, 4 days after treatment and all obtained complete remission within 2 weeks without any event of relapse after median follow-up period of 8 (7-12) months.</p><p><b>CONCLUSION</b>Any recipient of HSCT with clinical signs or symptoms of central nervous system should receive vitamin B supplementary therapy immediately to decrease risk of mortality of WE even if the diagnosis of WE is uncertain.</p>

Clinical Analysis of Treating EBV Infection Accompanied with GVHD after Allon-HSCT by EBV-Specific Cytotoxic T Lymphocytes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficiency and safety of treating Epstein-Barr virus (EBV) infection of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by EBV specific cytotoxic T lymphocytes (EBV-CTL).</p><p><b>METHODS</b>The Clinical characteristics, therapeutic efficacy and safety of 12 patients with EBV infection treated by EBV-CTL infusion after allo-HSCT in Department of Hemahlogy of Aero Space Center Hospital between Jan 2015 and May 2017 were analyzed retrospectioely.</p><p><b>RESULTS</b>Our of 12 cases received EBV-CTL infusion after transplantation, 9 did not received Rituximab therapy due to the active infection, 4 cases including 3 received Ritaximab progressed into posttransplantation lymphoroliferetive disease (PTLD). The median time of EBV infection was 47 (22-71) days, median time of antivirus therapy before tramplantation was 10 (8-33) days, median time of first CTL infusion was 59(34-86) days after transplatation. The 43 cases-time CTL infusion was performed smoothly, no related harmful evnts occoured, no progression of GVHD was observed. After the first course of infusion, complete remission (CR), Partial remssion (PR) and no remssion (NR) were obtained in 9, 1 and 2 patients respectively, the relapse was observed in 4 patients who then received the socond course of infusion and all reached CR, the patient in PR did not reathed CR finally and died of GVGD at 5 months after transpplantation . Only 1 out of 2 cases of NR obtained CR, another 1 still was in NR, and died of transplantation related infection at 5 months after transplantation. 4 cases of PTLD were all cared.</p><p><b>CONCLUSION</b>Preliminary results of this study suggest that EBV-CTL infusion is safe for the EBV infection combined with acute GVHD after all-HSCT. However, a further larger scale clinical studies are needed to prove the efficiency.</p>

Alteration of choroidal thickness in patients with obstructive sleep apnea hyponea syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To analyze the choroidal thickness alteration in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). ·METHODS: Seventeen patients who were diagnosed with OSAHS initially and 31 healthy individuals were enrolled. Enhanced depth imaging choriodal scans were obtained by spectral - domain optical coherence tomography. Choroidal thickness of subfovea, 2mm superior,inferior,nasal and temporal to the fovea were measured and statistically analyzed. ·RESULTS:Subfoveal choroidal thickness of the control group and the OSAHS group was 323.58 ± 58.63μ m and 316.82 ± 46. 43μ m respectively, and the difference was unsignificant(t=0.409,P=0.684). Choroidal thickness at 2mm superior to the fovea of the control group and the OSAHS group was 318.29 ± 56.89μ m and 314.29 ± 59.8μ m respectively, and the difference was unsignificant (t=0.229,P=0.820). Choroidal thickness at 2mm inferior to the fovea of the control group and the OSAHS group was 308.42± 54.95μ m and 291.65 ± 55.37μ m respectively, and the difference was not significant (t=1.009, P=0.318). Choroidal thickness at 2mm temporal to the fovea of the control group and the OSAHS group was 308. 23 ± 54.62μ m and 302. 76 ± 46. 97μ m respectively, and the difference was not significant (t = 0. 347, P = 0. 730). Choroidal thickness at 2mm nasal to the fovea of the control group and the OSAHS group was 266. 23 ± 58.10μ m and 277. 12 ± 63. 99μ m respectively, and the difference was not significant (t= -0.599, P= 0.552). There were no significant differences among subgroups after grading based on the severity of sleep apnea hypopnea index and blood oxygen concentration. ·CONCLUSION: Compared with healthy individuals, choroidal thickness of patients with OSAHS decreases slightly (except for the location of 2mm nasal to the fovea),but the alteration is not significant. The severity of OSAHS has no effect on the choroidal thickness for the patients first diagnosis of OSAHS.

Effects of different antidiabetic therapies on the macular thickness in diabetes patients without fundus complication / 国际眼科杂志(Guoji Yanke Zazhi)

Abstract?AIM: To observe the effects of different antidiabetic therapies on macular thickness in diabetes patients without fundus complication.?METHODS: The macular thickness was measured by optical coherence tomography ( OCT) .The retina volume on the center of macula was scanned, and it generated automatically the average thickness data of three rings and nine areas of 1mm, 3mm and 6mm.The data were statistically analyzed.?RESULTS: Healthy control group, oral hypoglycemic drug group and insulin treatment group were enrolled. Each group included 22 cases 22 eyes.The macular retinal thickness of healthy control group is 268.09±17.97μm (the 1st ring), 340.41 ±22.25μm ( the 2nd ring) and 298.14 ± 12.90μm ( the 3 rd ring ) , respectively. The macular thickness of oral hypoglycemic drug group is 260.00 ± 18.17μm (the 1st ring), 335.44±21.12μm (the 2nd ring) and 295.63 ±15.92μm ( the 3rd ring), respectively.The macular thickness of insulin therapy group is 271.01 ± 26.09μm (the 1st ring), 340.86±17.10μm (the 2nd ring) and 298.57 ±12.14μm ( the 3rd ring ), respectively. Comparison of the macular thickness of the 1st ring among 3 groups was insignificant (F=1.21, P=0.31), neither the comparison of the 2nd ring (F=0.35, P=0.71), neither the comparison of the 3rd ring (F=0.22, P=0.81).? CONCLUSION: Compared with healthy individuals, both oral antidiabetic medicines and insulin therapy don't alter the macular thickness of patients with diabetes while without fundus complication.