1.Clinical Analysis of Dasatinib and Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia.
Yuan LI ; Bing-Jie WANG ; Wei LIU ; Ze-Yin LIANG ; Yue YIN ; Yu-Jun DONG ; Qian WANG ; Yu-Hua SUN ; Wei-Lin XU ; Han-Yun REN
Journal of Experimental Hematology 2020;28(1):18-23
OBJECTIVE:
To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
Clinical data of 19 newly diagnosed as Ph ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed.
RESULTS:
There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively.
CONCLUSION
First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of PhALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.
2.Clinical features of influenza with plastic bronchitis in children.
Qin YANG ; Yan-Min BAO ; Qiu-Wei YI ; Wei WANG ; Yue-Jie ZHENG
Chinese Journal of Contemporary Pediatrics 2020;22(2):106-111
OBJECTIVE:
To study the clinical features of influenza with plastic bronchitis (PB) in children, and to improve the awareness of the diagnosis and treatment of PB caused by influenza virus.
METHODS:
A retrospective analysis was performed for the clinical data of 70 children with lower respiratory influenza virus infection from October 2018 to October 2019. According to the presence or absence of PB, they were divided into an influenza+PB group with 12 children and a non-PB influenza group with 58 children. Related clinical data were collected for the retrospective analysis, including general information, clinical manifestations, laboratory examination, imaging findings, treatment, and prognosis.
RESULTS:
In the influenza+PB group, most children experienced disease onset at the age of 1-5 years, with the peak months of January, February, July, and September. Major clinical manifestations in the influenza+PB group included fever, cough, and shortness of breath. The influenza+PB group had significantly higher incidence rates of shortness of breath and allergic diseases such as asthma than the non-PB influenza group (P<0.05). Of the 12 children in the influenza+PB group, 7(58%) had influenza A virus infection and 5 (42%) had influenza B virus infection, among whom 1 had nephrotic syndrome. For the children in the influenza+PB group, major imaging findings included pulmonary consolidation with atelectasis, high-density infiltration, pleural effusion, and mediastinal emphysema. Compared with the non-PB influenza group, the influenza+PB group had a significantly higher proportion of children who were admitted to the pediatric intensive care unit (P<0.05). Bronchoscopic lavage was performed within 1 week after admission, and all children were improved and discharged after anti-infective therapy and symptomatic/supportive treatment.
CONCLUSIONS
Influenza with PB tends to have acute onset and rapid progression, and it is important to perform bronchoscopy as early as possible. The possibility of PB should be considered when the presence of shortness of breath, allergic diseases such as asthma or nephrotic syndrome in children with influenza.
3.Network pharmacology study on anti-stroke of Xiaoshuan Tongluo formula based on systematic compound-target interaction prediction models
Yi-fu ZHENG ; Ling-lei KONG ; Hao JIA ; Bao-yue ZHANG ; Zhe WANG ; Lü-jie XU ; Ai-liu LIU ; Guan-hua DU
Acta Pharmaceutica Sinica 2020;55(2):256-264
Xiaoshuan Tongluo formula is effective in treating mental retardation and speech astringency caused by cerebral thrombosis, but its mechanism remains unclear. In this investigation, by collecting the chemical constituents from Xiaoshuan Tongluo formula and the targets related to stroke, we obtained 1 251 constituents from the formula and 10 drug targets related with stroke. We established 18 prediction models of compound-target interaction for 10 stroke-related targets, using molecular docking method and machine learning methods includes Naive Bayesian and recursive partitioning based on the input of molecular fingerprints and molecular descriptors. Using these models, we predicted the active chemical constituents from Xiaoshuan Tongluo formula and their drug targets, 153 potential active constituents were discovered, 22 among them could interact with at least two drug targets related with stroke. On this basis, the chemical constituent-target network was constructed using network construction software, and then the important metabolic pathways of the targets were identified by using Gene-Ontology (GO) enrichment analysis, such as blood coagulation, positive regulation of angiogenesis, positive regulation of ion transport and so on. On this basis, a target-pathway network was constructed. In conclusion, using machine learning, molecular docking, virtual screening, data mining and network construction, this study explored and partially revealed the active chemical constituents and chemical constituent-target-pathway network action mechanism of Xiaoshuan Tongluo formula against stroke, which will provide important information for its further study.
4.Sexual behavior characteristics and influencing factors of gonorrhea patients in Yunnan Province
Nan WANG ; Wan-yue ZHANG ; Yan GUO ; Xiu-jie ZHANG ; Xiao-bin ZHANG ; Qing-yan FANG ; Zhi-fang YANG ; Wen-qing CUI ; Yi HU ; Xing-fang SU ; Man-hong JIA
Chinese Journal of Disease Control & Prevention 2020;24(1):101-104
Objective To investigate the sexual behavior types, condom use and influencing factors of gonorrhea patients in Yunnan Province, and to provide evidence for the adjustment of sexually transmitted disease (STD) prevention and control strategy. Methods A cross-sectional study was carried out to investigate gonorrhea patients in 14 STD clinics in 7 more prevalent prefectures (cities) of Yunnan Province. A questionnaire survey was conducted to investigate the socio-demographic and sexual characteristics of the patients in a one-to-one way. Multiple Logistic regression model was used to analyze the influencing factors of sexual behavior. Results A total of 179 cases of gonorrhea were investigated. The average age was (29.01±8.93) years old. 95.53% (171/179) patients were 40 years old and 88.27% were male patients (158/179). Unmarried patients accounted for 55.31% (99/179). Service and self-employed patients accounted for 34.64% (62/179) and 23.46% (42/179) respectively. The rate of sexual intercourse with opposite sex was 98.32% (176/179), the rate of men who have sex with men was 1.68% (3/179) and the rate of having more than two sexual partners was 27.93% (50/179). The rate of sexual intercourse between temporary partners, spouses/fixed partners and commercial partners were 53.07% (95/179), 37.99% (68/179) and 8.94% (16/179) respectively. Recent sexual activity had lower condom use rate, 17.89% (17/95), 19.12% (13/68) and 18.75% (3/16) respectively. The main ways for gonorrhea patients to make temporary partners were friend introductions or gatherings, accounting for 66.32% (63/95). Condom use in male patients was worse than that in female patients (OR=0.234, 95% CI: 0.084-0.656, P=0.006). Conclusions The patients with gonorrhea were mainly unmarried young adults. The main risk behaviors were unprotected behaviors between heterosexual temporary and spouse/fixed sexual partners. The condom use consciousness was generally low. The promotion of safe sex education for young adults should be further strengthened, with special attention to the use of condoms for temporary sexual behavior and spouse/fixed sexual intercourse.
5. Progress on clinical trials of cancer drugs in China, 2019
Huiyao HUANG ; Dawei WU ; Haixue WANG ; Jun WANG ; Qi FAN ; Shuhang WANG ; Ying BAI ; Yue YU ; Yuan FANG ; Chao SUN ; Hong FANG ; Hua BAI ; Xin WANG ; Zeyuan LIU ; Min JIANG ; Zhe LIU ; Xinghe WANG ; Haiyan LI ; Ning LI ; Cai CAO ; Binghe XU ; Yan SUN ; Jie HE
Chinese Journal of Oncology 2020;42(2):127-132
Objective:
To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019.
Methods:
The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted.
Results:
There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%,
6.Correlations of quality of life with optimisms and sense of coherence in adult kidney transplant recipients
Han WANG ; Hongxia LIU ; Chunyan DU ; Yingxin FU ; Jie ZHAO ; Mengxi HAN ; Shasha WANG ; Sisi WU ; Yue HU ; Jiaqi LI
Modern Clinical Nursing 2019;18(1):16-22
Objective To explore the relationship of quality of life with optimisms and sense of coherence in adult kidney transplant recipients. Method A total of 295 kidney transplant recipients participated in the study by a self-designed general questionnaire, revised life orientation test (LOT-R), sense of coherence (SOC-13) and the MOS 36-item short form health survey (MOS SF-36). Results The mean score of mental health scale (PCS) was 47.02±7.30, which differed with different age, employment status and transplant vintage (P <0.01). The mean score of phyical health scale (MCS) was 46.87 ±11.14, which differed with education, economic burden and transplant vintage (P <0.05). PCS and MCS were positively correlated with the total score of sense of coherence (52.05%) and optimism (23.45%) (P<0.001). Optimism played a partially mediating role in the relationship between sense of coherence and quality of life. Conclusions The quality of life of kidney transplant recipients needs to be improved, which was at a low level.Optimism (medium to high level) and sense of coherence (medium to low level) are influencing factors of the quality of life. Improving accessment of mental state of patients with kidney transplant receients, paying more atentent and support to their mental change can improve their optimism and sense of coheherce and then life quiality.
7.Imaging findings of hepatic hemangioendothelioma with arteriovenous shunt and evaluation of interventional therapy
Chinese Journal of General Surgery 2019;34(8):689-692
Objective To observe the efficacy of arteriosclerosis embolization in the treatment of hepatic hemangio endothelioma (HHE) and the imaging manifestations of HHE.Methods Eight HHE children admitted to our hospital from Oct 2016 to Jan 2019 were enrolled to evaluate the efficacy of interventional therapy and the differentiation from other liver tumors.Results Eight patients underwent 10 interventional operations.The first embolization materials were gelatin sponge particles (2 000 μm).After the second embolization,microspheres (300-500 μm) were used for embolization materials.After superselective embolization,all 8 patients were weaned from the auxiliary ventilation.There was no hepatic venous development during the arterial phase after re-angiography.Tumor volume decreased or disappeared after chemoembolization.Tumors disappeared completely in 3 patients,shrank significantly in the remaining 5 cases.Conclusion Contrast-enhanced scanning is of great significance in the diagnosis of hepatic vascular endothelial cell tumor.Arteriosclerosis embolization has significant effect on children with hepatic vascular endothelial cell tumor.
8.Preclinical microPET imaging in tumor-bearing nude mice and pharmacokinetic studies of 18F-Alfatide II
Deliang ZHANG ; Yesen LI ; Zuoquan ZHAO ; Jie LU ; Yue WANG ; Qian YU ; Zijing LI ; Pu ZHANG ; Ruiqin CHEN ; Hua WU ; Wei FANG ; Xianzhong ZHANG ; Xiaoyuan CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(4):201-206
Objective To assess the imaging characteristics of 18F-Alfalide II in different tumorbearing mice and pharmacokinetics in Beagle dogs.Methods BALB/c nude mice(n-24)were used for subcutaneous tumor models(A549 and U87MG),orthotopic lung cancer models(A549)and orthotopic breast cancer models(MDA-MB-231)(n=6 in each group).18F-Alfatide II and 18F-fluorodeoxyglucose(FDG)microPET/CT images were compared in the 4 types of tumor-bearing nude mice models.18F-Alfatide II blocking experiment,biodistribution experiment and imaging studies in tumors of different growth cycles were performed in A549 subcutaneous tumor-bearing nude mice models.Pharmacokinetic experiments were carried out in Beagle dogs(n = 6)and CD-1 mice(n = 9).Two-sample t test was used to analyze the data.Results Compared with 18F-FDG,18F-Alfatide II microPET/CT images showed better imaging quality and contrast in subcutaneous A549,U87MG tumors and orthotopic A549(tumor/heart:4.50±1.17 vs 0.95±0.31;t = 4.125,P<0.01),orthotopic MDA-MB-231(tumor/muscle:6.60±1.53 vs 0.92±0.43;t = 3.984,P<0.01)transplantation nude mice models.18F-Alfatide II could specifically target A549 tumors,and the tumor uptake of 18F-Alfatide II was reduced by about 75% after pre-injection with cyclo(Arg-Gly-Asp-D-Tyr-Lys)(c(RGDyk)).18F-Alfatide II was rapidly cleared from the blood of Beagle dogs(T1/2 was(57.34±11.69)min).It was cleared in the form of prototype drug and(69.24±6.82)% of cumulative dose was excreted through the urine within 4 h after administration.Conclusions 18F-Alfatide II shows a higher target/non-target ratio than,18F-FDG in the imaging of A549,MDA-MB-231 and U87MG tumor-bearing nude mice models,which is more conducive to the diagnosis of tumor.18F-Alfatide II has excellent pharmacokinetic properties.
9.Effects of intraoperative goal-directed fluid therapy on postoperative outcomes in patients undergoing thoracoscopic lobectomy: a comparison with restrictive fluid therapy
Liyuan ZHAO ; Yue YUE ; Lulu WANG ; Jie ZHANG
Chinese Journal of Anesthesiology 2019;39(1):84-88
Objective To investigate the effects of different fluid therapies on postoperative outcomes in patients undergoing thoracoscopic lobectomy and to evaluate the advantages of intraoperative goaldirected fluid therapy when compared with restrictive fluid therapy.Methods Fifty-four patients,aged 18-64 yr,with body mass index of 18.5-24.9 kg/m2,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,scheduled for elective thoracoscopic lobectomy under general anesthesia,were divided into goal-directed fluid therapy group (group G) and restrictive fluid therapy group (group R) using a random number table method,with 27 patients in each group.In group G,fluid management was guided by an oesophageal Doppler monitoring,Ringer's solution was continuously infused at a rate of 4 ml · kg-1 · h-1,with corrected flow time (FTc) ≥350 ms and change in stroke volume (SV) < 10% of the pre-rehydration level as the goal.In group R,restrictive fluid management was performed,and blood loss was replaced with hydroxyethyl starch 130/0.4 at a 1 ∶ 1 ratio.Compound sodium chloride injection was continuously infused at a rate of 4 ml · kg-1 · h-1 until the end of surgery in both groups.Mean arterial pressure,heart rate,SpO2,FTc,SV and cardiac index were recorded at 5 min before intubation,immediately after lateral position,at the start of one-lung ventilation,at the end of one-lung ventilation and at the end of surgery.The amount of fluid intake and output during surgery was recorded.The complications on 1st,3rd,5th and 8th days after surgery were evaluated using POMS scale.The length of hospital stay,admission to intensive care unit and in-hospital death were also recorded.Results Compared with group R,FTc,SV and cardiac index were significantly increased at the end of one-lung ventilation and at the end of surgery in group G (P<0.05).There were no significant differences in the incidence of postoperative complications or length of hospital stay between two groups (P>0.05).No patients were admitted to intensive care unit after surgery,and no in-hospital death occurred in two groups.Conclusion GDFT and restrictive fluid therapy applied during surgery produce similar postoperative outcomes in patients undergoing thoracoscopic lobectomy.
10.cGAS recognizes HTLV-1 RTI and induces STING-dependent innate immune responses
Yue LIU ; Yuhan CUI ; Di SONG ; Yuhe GUAN ; Fan CHEN ; Mengmeng CHEN ; Bo YANG ; Jie WANG
Chinese Journal of Microbiology and Immunology 2019;39(3):168-173
Objective To investigate whether cyclic GMP-AMP synthase ( cGAS ) , a cytosolic DNA sensor, could recognize the reverse transcription intermediate and induce the subsequent signaling path-way during the infection of human T cell leukemia virus type 1 ( HTLV-1 ) . Methods Biotin-labeled ssDNA90, a reverse transcription intermediate of HTLV-1, was transfected into HeLa cells and the interac-tion between it and cGAS was detected by co-immunoprecipitation experiments. HeLa cells were co-cultured with HTLV-1-positive MT2 cells and the interaction between cGAS and stimulator of interferon genes ( STING) was analyzed by co-immunoprecipitation experiments. The expression of STING in HeLa cells was silenced by siRNA. cGAS was transfected into the HeLa cells 24 h after the silencing and after 24 h, these cells were co-cultured with MT2 cells for another 24 h. Real-time PCR assay was used to measure the ex-pression of IFN-β, RANTES ( regulated upon activation, normal T-cell expressed, and secreted) , TNF-α, HTLV-1 protein Tax, p19 and HBZ. Immunoblot assay was performed to evaluate the phosphorylation of IRF3 and p65 in HeLa cells. Results cGAS interacted with ssDNA90. cGAS interacted with STING in the cytoplasm. In STING-silenced HeLa cells, cGAS transfection had no influence on the expression of IFN-β, RANTES , TNF-α, Tax , p19 or HBZ , nor did it affect the phosphorylation of IRF3 or p65 . Conclusions cGAS interacted with HTLV-1 RTI ssDNA90 and activated STING-dependent innate immune responses.

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