Challenges of maintaining malaria elimination in China: Cross-border malaria / 中国血吸虫病防治杂志

China was certificated malaria-free by WHO in 2021 and has continued to maintain malaria elimination. However, there are still huge challenges in malaria control in the border regions between Yunnan Province, China and Myanmar due to lack of geographic barriers and frequent cross-border travel. Hereby, we review the direction contributions of the Global Fund Malaria Program implemented by Health Poverty Action (HPA), an international non-governmental organization (NGO), to malaria elimination in China, and analyze the challenges of malaria control caused by external environmental factors, such as COVID-19, in regions where the Global Fund Malaria Program is implemented. In addition, some suggestions are proposed for cross-border collaboration on malaria control.

Interferon-regulatory factors regulate macrophage polarization and its role in diseases / 药学学报

Macrophages are highly plastic and heterogeneous. In different types of inflammatory diseases, or at different stages of the same disease, macrophages can undergo phenotypic transformation to elicit different functions. Hence, exploring new regulatory mechanism of macrophage polarization and seeking for new key mediators will lay the foundation for the diagnosis and treatment of macrophage-related diseases, such as inflammatory diseases, autoimmune diseases, and cancer. Interferon regulatory factors (IRFs) have been reported to play an important role in the maturation and differentiation of macrophages. In this review, we will describe the structure and modulation pattern of IRFs, and then further summarize the molecular mechanism and signal regulation network of IRFs in pathological processes of related diseases through controlling macrophage polarization. Our review will explore the new therapeutic strategy and potential drug targets for related diseases.

Histopathological Diagnosis System for Gastritis Using Deep Learning Algorithm / 中国医学科学杂志(英文版)

Objective To develope a deep learning algorithm for pathological classification of chronic gastritis and assess its performance using whole-slide images (WSIs). Methods We retrospectively collected 1,250 gastric biopsy specimens (1,128 gastritis, 122 normal mucosa) from PLA General Hospital. The deep learning algorithm based on DeepLab v3 (ResNet-50) architecture was trained and validated using 1,008 WSIs and 100 WSIs, respectively. The diagnostic performance of the algorithm was tested on an independent test set of 142 WSIs, with the pathologists' consensus diagnosis as the gold standard. Results The receiver operating characteristic (ROC) curves were generated for chronic superficial gastritis (CSuG), chronic active gastritis (CAcG), and chronic atrophic gastritis (CAtG) in the test set, respectively.The areas under the ROC curves (AUCs) of the algorithm for CSuG, CAcG, and CAtG were 0.882, 0.905 and 0.910, respectively. The sensitivity and specificity of the deep learning algorithm for the classification of CSuG, CAcG, and CAtG were 0.790 and 1.000 (accuracy 0.880), 0.985 and 0.829 (accuracy 0.901), 0.952 and 0.992 (accuracy 0.986), respectively. The overall predicted accuracy for three different types of gastritis was 0.867. By flagging the suspicious regions identified by the algorithm in WSI, a more transparent and interpretable diagnosis can be generated. Conclusion The deep learning algorithm achieved high accuracy for chronic gastritis classification using WSIs. By pre-highlighting the different gastritis regions, it might be used as an auxiliary diagnostic tool to improve the work efficiency of pathologists.

RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. @*Materials and Methods@#We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. @*Results@#Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. @*Conclusion@#RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.

Effects of apple polyphenols on monocrotaline-induced pulmonary vascular remodeling in rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of apple polyphenols on pulmonary vascular remodeling in rats with pulmonary arterial hypertension and its mechanism.@*METHODS@#Rats were randomly divided into 4 groups:control (Con) group, monocrotaline (MCT) group, apple polyphenol (APP) group,monocrotaline + apple polyphenol (MCT+APP) group. In Con group, rats received a subcutaneous injection of physical saline. In APP group, rats received intraperitoneal injection of 20 mg/kg APP, every other day. In MCT group, rats received a single subcutaneous injection of MCT(60 mg/kg). In MCT+APP group, rats received subcutaneous injection of 60 mg/kg MCT followed by an intraperitoneal injection of 20 mg/kg APP every other day. All the disposal lasted 3 weeks. Then the PAH-relevant indicators, such as mean pulmonary artery pressure(mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index (RVHI) ,wall thickness (WT%) and wall area (WA%) were tested. After that, the inflammatory pathway related indicators, such as interleukin1(IL-1),interleukin1(IL-6), tumor necrosis factor α(TNF-α), cyclooxygenase 2(COX-2) and myeloperoxidase(MPO) in pulmonary tissue and free intracellular Ca in pulmonary smooth muscle cell(PASMC), content of eNOS and NO in endothelial cells were determined.@*RESULTS@#Compared with the control group, the levels of mPAP, PVR, RVHI, WA%, WT%, and IL-1, IL-6, TNF-α, COX-2, MPO in tissue and the expression of Ca in PASMC of MCT group were increased significantly, while the contents of eNOS and NO in endothelial cells were decreased significantly (P＜0.05). Compared with the MCT group, the apple polyphenol treatment could improve the above mentioned situation, and the COX-2 and Ca indicators of the apple polyphenol treatment group were decreased significantly (P＜0.05).@*CONCLUSION@#MCT can increase COX-2 expression and intracellular Ca in pulmonary artery smooth muscle cells, decrease the contents of eNOS and NO in endothelial cells, while apple polyphenols can significantly inhibit these effects.

Observation of Addition and Subtraction Therapy of Liuwei Dihuangwan Combined with Huanglian Ejiaotang to Primary Insomnia in Elderly Liver and Kidney Yin Deficiency Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of addition and subtraction therapy of Liuwei Dihuangwan combined with Huanglian Ejiaotang to primary insomnia in the elderly (liver and kidney Yin deficiency syndrome), and to investigate its regulation effect on neurotransmitter. Method:Randomly 136 patients were divided into control group (68 cases) and observation group (68 cases) by number table. Patients in control group got Estazolam tablets by oral administration before going to bed, 1-2 mg/time, 1 time/day. Patients in observation group got addition and subtraction therapy of Liuwei Dihuangwan combined with Huanglian Ejiao tang, 1 dose/day. Both groups of patients received sleep guidance and cognitive behavior guidance, with treatment course of 8 weeks. During the observation period, physical therapy and acupuncture could not been used. Before and after treatment, pittsburgh sleep quality index (PSQI), whole night polysomnography, sleep latency (SL), awakening times (AT), sleep efficiency (SE), rapid eye movement (REM), latency (RL), total actual sleep time (TST) and proportion of N1, N2, N3 and REM in the whole sleep stage were recorded. Scores of self-rating depression scale (SDS), self-rating anxiety scale (SAS), kidney Yin deficiency syndrome score and treatment emergent symptom scale (TESS) were graded, and levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid(5-HIAA), gamma-aminobutyric acid (GABA), norepinephrine (NE) and dopamine (DA) were detected. Result:In rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.115, PPPPPPPPχ2=9.945, PConclusion:Addition and subtraction therapy of Liuwei Dihuangwan combined with Huanglian Ejiaotang can improve sleep quality, prolong sleep time, alleviate depression, anxiety, and can also regulate neurotransmitters to improve sleep effect. The efficacy of PSQI is better than that of Estazolam tablets.

Faster R-CNN-based artificial intelligence image-aided diagnosis platform in identifying EMVI of rectal cancer: A multicenter clinical study / 中国实用外科杂志

OBJECTIVE: To explore the clinical application value of artificial intelligence image aided diagnosis platformbased on Faster R-CNN in identifying EMVI of rectal cancer.METHODS: In the multicenter retrospective study,500 patients with rectal cancer who underwent high-resolution MRI examination between July 2016 and February 2019 wereselected from seven hospitals in China. They were divided into 174 positive and 326 negative patients. Patients wererandomized to a training group(400 patients,including 133 positive and 267 negative) and a validation group(100 patients,including 41 positive and 59 negative) using a random number method. Using the Faster R-CNN to learn and train 20 430 high-resolution MRI images of thetraining group,an artificial intelligence image-aided diagnosis platform was established. The5107 high-resolution MRI images of thevalidation group were clinically validated.Receiver operating characteristic(ROC) curveand area under the curve(AUC) were used tocompare the diagnostic results of the artificialintelligence image-aided diagnosis platform andthe senior image expert.RESULTS: The accuracy,sensitivity,specificity,positive predictive valueand negative predictive value of EMVI forartificial intelligence image-aided diagnosis platform were 93.4%, 97.3%, 89.5%, 0.90 and 0.97,respectively. The area under the receiver operating characteristiccurve(AUC) was 0.98. The time required to automatically recognize a single image was 0.2 seconds,which had clearadvantages compared to radiologists(estimated to be about 10 seconds).CONCLUSION: The artificial intelligence image-assisted diagnosis platform based on Faster R-CNN has high efficiency and feasibility for identifying rectal cancerEMVI,and can assist imaging diagnosis.

Deep neural network-assisted computed tomography diagnosis of metastatic lymph nodes from gastric cancer / 中华医学杂志(英文版)

BACKGROUND@#Artificial intelligence-assisted image recognition technology is currently able to detect the target area of an image and fetch information to make classifications according to target features. This study aimed to use deep neural networks for computed tomography (CT) diagnosis of perigastric metastatic lymph nodes (PGMLNs) to simulate the recognition of lymph nodes by radiologists, and to acquire more accurate identification results.@*METHODS@#A total of 1371 images of suspected lymph node metastasis from enhanced abdominal CT scans were identified and labeled by radiologists and were used with 18,780 original images for faster region-based convolutional neural networks (FR-CNN) deep learning. The identification results of 6000 random CT images from 100 gastric cancer patients by the FR-CNN were compared with results obtained from radiologists in terms of their identification accuracy. Similarly, 1004 CT images with metastatic lymph nodes that had been post-operatively confirmed by pathological examination and 11,340 original images were used in the identification and learning processes described above. The same 6000 gastric cancer CT images were used for the verification, according to which the diagnosis results were analyzed.@*RESULTS@#In the initial group, precision-recall curves were generated based on the precision rates, the recall rates of nodule classes of the training set and the validation set; the mean average precision (mAP) value was 0.5019. To verify the results of the initial learning group, the receiver operating characteristic curves was generated, and the corresponding area under the curve (AUC) value was calculated as 0.8995. After the second phase of precise learning, all the indicators were improved, and the mAP and AUC values were 0.7801 and 0.9541, respectively.@*CONCLUSION@#Through deep learning, FR-CNN achieved high judgment effectiveness and recognition accuracy for CT diagnosis of PGMLNs.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry, No. ChiCTR1800016787; http://www.chictr.org.cn/showproj.aspx?proj=28515.

Treatment of aseptic ulnar diaphyseal nonunion with locking compression plate and autogenous iliac bone graft / 中国骨伤

OBJECTIVE@#To investigate the clinical results of locking compression plate combined with autologous iliac bone graft in the treatment of aseptic ulnar nonunion.@*METHODS@#From March 2009 to July 2017, 22 patients with aseptic ulnar diaphyseal nonunion with complete follow-up data were treated with surgery, including 12 males and 10 females, aged from 16 to 58 (39.7±9.9) years old and ranging in course of disease from 10 to 192 (39.4±55.7) months. There were 15 atrophic nonunions, 5 hypertrophic nonunions and 2 synovial pseudo-articular nonunions. After debridement of the nonunion, locking compression plate was used to fix the nonunion and autogenous iliac bone graft was given. Bone healing rate, surgical complications and clinical results were evaluated.@*RESULTS@#All the patients were followed up, and the duration ranged from 13 to 42 months, with a mean of (22.5±8.2) months, and 1 patient did not heal. Visual analogue pain scores ranged from 0 to 3 (0.9±0.9). Pronation of forearm was 47 to 86 (69.0±14.7) degrees, supination was 35 to 85 (63.0±9.4) degrees, wrist flexion was 20 to 80 (51.0±10.2) degrees, wrist flexion was 32 to 88 (71.0±11.7) degrees, elbow flexion contracture was 0 to 25 (9.0±5.6) degrees, further flexion was 105 to 150 (134.0±13.9) degrees, and grip strength was 87% on the opposite side. According to the Anderson scoring system, 8 cases were excellent, 11 were satisfied, 2 were not satisfied, and 1 was failed.@*CONCLUSIONS@#LCP combined with autologous iliac bone graft can effectively treat aseptic ulna diaphyseal nonunion.

A novel calcium phosphate cement pre-loaded with chitosan and small molecule adenosine for repairing large cranial defects in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of a novel biomaterial in repairing large cranial defects in rats.</p><p><b>METHODS</b>Eighteen SD rats were used to establish rat modes of large cranial defect (8 mm in diameter). The rat models were randomized into 3 groups and the cranial defects were repaired using different scaffold materials, namely CPC paste prepared with distilled water (CPC control group), CPC paste mixed with 10% chitosan (CPC/CN group), or CPC paste with 10% chitosan and 300 mg adenosine (CPC/CN/AD group). The defects were examined 12 weeks after the surgery with X-ray, CT, HE staining and quantitative assessments.</p><p><b>RESULTS</b>X-ray showed that the defect was repaired in all the groups. The fracture line became obscure and the defects were almost fully repaired by regenerated bone tissues in CPC/CN/AD group, which was consistent with CT findings. In all the 3 groups, HE staining revealed the presence of new bones in the defects and new vessels in and around the new bones without inflammatory cells. The new bone area was significantly greater in CPC/CN/AD group than in CPC/CN group and CPC control group (P<0.05). The new vessel density was the highest in CPC/CN/AD group (P>0.05) but similar between CPC/CN group and CPC control group (P>0.05).</p><p><b>CONCLUSION</b>This novel calcium phosphate cement pre-loaded with chitosan and small molecule adenosine can better promote bone regeneration than calcium phosphate cement for repairing large bone defects to serve as a good replacement material for bone regeneration.</p>

Effects and Safety of Metformin Combined with Vildagliptin on the Glycemic Control for Patients with Newly Diagnosed Type 2 Diabetes Mellitus / 现代生物医学进展

Objective:To study the effects and safety of metformin combined with vildagliptin on the glycemic control for patients with newly diagnosed type 2 diabetes mellitus.Methods:60 patients with type 2 diabetes mellitus who were treated from February 2015 to April 2016 were selected and divided into the control group and the observation group according to different treatment methods.The control group was treated with routine treatment.The observation group was treated with vildagliptin based on the control group.The blood glucose,glycosylated hemoglobin,two-hour postprandial blood glucose and serum as well as urinal amylase were measured before and after treatment,and the clinical curative effect of the two groups and the levels of interleukin-6,tumor necrosis factor and C-reactive protein were compared.Results:After treatment,the total effective rate of observation group was 90％,which was significantly higher than that of the control group(66.7％,P＜0.05).After treatment,the serum interleukin-6,tumor necrosis factor,C-reactive protein and fasting blood glucose,glycosylated hemoglobin and postprandial blood glucose levels were significantly lower than those of the control group[(7.63± 1.12)dvs(8.68± 1.30)d;(7.23± 0.95)d vs(7.89± 1.20)d;(11.14± 1.56)d vs(12.12± 1.89)d];[(12.12± 1.89)d vs(ll.20± 1.34)d;(6.89± 0.96)d vs(8.23± 1.10)d;(1.65± 0.23)d vs(3.65± 0.48)d] (P＜0.05).After treatment,the INS level of observation group was significantly lower than that of the control group (P＜0.05) and the GLP-1 level was significantly higher than that of the control group (P＜0.05).Conclusion:Metformin combined with vildagliptin could effectively control the blood glucose of patients with newly diagnosed type 2 diabetes and enhance the safety.

Study on prognostic significances of different cytogenetic risk categories in patients with primary myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze significances of different cytogenetic categories for prognostic stratification in patients with primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Chromosomal abnormalities of 532 primary MDS patients were categorized according to cytogenetic categories of International Prognostic Scoring System (IPSS), Revised IPSS (IPSS-R), and German-Austrian (G-A). Prognostic impacts of different cytogenetic categories and frequent isolated anomalies were investigated.</p><p><b>RESULTS</b>Of 532 patients, 346(65%) patients had clonal cytogenetic abnormalities, including 200(38%) patients had 1 abnormality, 61(11%) patients had 2 abnormalities, and 85(16%) patients had complex abnormalities. Trisomy 8 was the most frequent karyotype abnormality, occurring in 31% of the patients with clonal cytogenetic abnormalities, other frequent anomalies were -7/del(7q)(13%), del(20q)(12%), del(5q)(9%), -18(5%), -21(5%), i(17q)(5%), -Y(4%), -17(4%), +21(4%), -13/del(13q)(4%), and -22(4%). The proportion of poor karyotypes of IPSS was higher in RAEBI and RAEBII among the World Health Organization classifications than in subgroups with less than 5% blasts. The follow-up data were available for 310 patients with a median follow-up duration of 14.5 months. Median survival was 59 months for patients with normal karyotypes and 26 months for those with abnormal karyotypes. According to IPSS cytogenetic categories, the median survivals of good-risk subgroup, intermediate-risk subgroup and poor-risk subgroup were 59, 43 and 12 months, respectively (P < 0.01). For IPSS-R cytogenetic groups, the median survivals of good-risk subgroup, intermediate-risk(int-risk) subgroup, poor-risk and very poor-risk subgroup were 59, 36, 15, and 10 months, respectively (P < 0.01). According to G-A classification, the median survivals of good-risk subgroup, int-1-risk subgroup, int-2-risk subgroup and poor-risk subgroup were 59, 44, 15, and 11 months, respectively (P < 0.01). In frequent isolated karyotypic abnormalities, +8 had a median survival of 44 months, i(17q) had a median survival of 12 months, and -7/del(7q) had a median survival of 14 months.</p><p><b>CONCLUSION</b>In comparison with IPSS and G-A categories, IPSS-R cytogenetic categories are more sophisticated, and can stratify prognosis effectively, but prognostic significances of some karyotypes in IPSS-R still need to be confirmed.</p>

Cyclosporine A in combination with thalidomide for the treatment of patients with myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficiency and side-effects of the combination of cyclosporine A (CsA) and thalidomide in patients with myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>A total of thirty-seven patients with MDS-RCMD or-RAEB-I were treated with CsA in combination with thalidomide. The initial CsA dose of 3 mg×kg(-1)×d(-1) was administered, all patients had their CsA blood concentration concurrently monitored until it reached and maintained between 100 and 200 µg/L. The initial dose of thalidomide was 50 mg/d, with increasing dose of 50 mg every week until the maximum of 200 mg/d. The hematological response was assessed according to the modified criteria of the International Working Group, and adverse events were graded with the Common Toxicity Criteria (v3.0) of the National Cancer Institute. The response duration and overall survival of the patients were also observed.</p><p><b>RESULTS</b>19/37 cases (51.4%) achieved hematologic improvement (HI)-erythroid response (HI-E), 9/29 cases (31.0%) HI-platelet response (HI-P) and 7/33 cases (21.2%) HI-neutrophil response (HI-N). 15 of 32 transfusion-dependent patients (46.9%) achieved transfusion independence. The median response duration of HI-E, HI-P and HI-N were 88 (4 - 88) weeks, 78 (8 - 84(+)) weeks and 78 (10 - 84(+)) weeks respectively. The median overall survival was 52 months on a 29 (4 - 103) months median follow-up. Some patients developed grades I-II hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rashes or numbness, and all were tolerable and reversible. No grade III or severer adverse events were observed.</p><p><b>CONCLUSION</b>CsA in combination with thalidomide appears to be effective mainly in inducing HI-E and relatively well-tolerated for the treatment of patients with MDS.</p>

Re-evaluation of classification of myelodysplastic syndromes with low percentage bone marrow blasts / 中华血液学杂志

<p><b>OBJECTIVE</b>To apply the WHO criteria and the minimal diagnostic criteria to the classification of myelodysplastic syndromes (MDS) with low percentage (< 0.050) bone marrow (BM) blasts.</p><p><b>METHODS</b>Two hundred and ten MDS patients with less than 0.050 BM blasts diagnosed between 1988 and 2005 according to FAB criteria were retrospectively reclassified with WHO criteria (2001) and minimal diagnostic criteria.</p><p><b>RESULTS</b>According to the WHO criteria, 5 patients were diagnosed as refractory anemia (RA), 7 as refractory anemia with ringed sideroblasts (RARS), 76 as refractory cytopenia with multilineage dysplasia (RCMD), 9 as RCMD-RS, 35 as MDS-unclassified (MDS-U), 3 as 5q - syndromes, and the rest 75 patients could not be classified suitably. Among the latter 75 patients 16 BM smears showed dysplasia in more than 2 cell lineage but only unilineage cytopenia in peripheral blood (PB). Nine of them were reclassified as RCMD after followed up for more than half a year. Forty-four BM smears showed erythroid dysplasia only, but bicytopenia or pancytopenia in PB. Twenty-seven of them were classified as RCMD after follow-up. Fifteen BM smears not showed dysplasia in any myeloid lineage were reclassified as MDS (5 patients), HS-MDS (5 patients) and idiopathic cytopenia of uncertain significance (ICUS) (5 patients) according to the MDS minimal diagnostic criteria.</p><p><b>CONCLUSION</b>According to WHO criteria (2001), RA is the least diagnosis in MDS. The minimal diagnostic criteria for MDS classification of patients not fulfilled the standard criteria of MDS.</p>

Studying of clinical and laboratory features of chronic eosinophilic leukemias /hypereosinophilic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory features of chronic eosinophilic leukemias (CEL) and hypereosinophilic syndrome (HES).</p><p><b>METHODS</b>The clinical manifestations, laboratory parameters were retrospectively analyzed in 20 patients with HES/CEL. Detection of the FIP1L1-PDGFRA fusion gene was performed by nested RT-PCR. JAK2 V617F mutation screening was processed through allele-specific PCR combined with sequence analysis. PCR-RFLP was used to discriminate homozygous from heterozygous mutation patterns. TCR gamma rearrangement was detected by PCR.</p><p><b>RESULTS</b>Of the 20 patients, 19 were males and one female, with a median age of 33 (20 to 57) years. The FIP1L1-PDGFRA fusion gene positivity in bone marrow mononuclear cells in 12 cases was identified. All the breakpoints were identified by direct sequencing of cloned RT-PCR products in FIP1L1 intron 10 - 12 and in PDGFRA exon 12. In CEL the most common involved organs were lungs, heart and nervous system. Splenomegaly was significantly more frequent in CEL than in HES (92.5% vs 42.5%, P = 0.031). Anemia and myelofibrosis were common in CEL. There was no significant difference in circulating absolute eosinophil, leukocyte, platelet counts, hemoglobin level and percentages of eosinophil and blast cell in bone marrow between CEL and HES. The morphological abnormalities of eosinophils on bone marrow smear were easily found in CEL, including hypogranularity, and cytoplasmic vacuolization, increased basophilic granule. One patient with HES was found to have heterozygous JAK2 V617F mutation. Six patients had TCR gamma rearrangement, including 4 CEL and 2 HES.</p><p><b>CONCLUSIONS</b>(1) There is a male predominance in HES/CEL, and the median age was in the thirties. (2) The most common involved organs in CEL were lung, heart and nervous system. Bone marrow morphology might be of a little help in diagnosis of CEL. (3) JAK2 V617F may be involved in the pathogenesis of HES. (4) Patients with CEL carried the FIP1L1-PDGFRA fusion gene and TCR gamma rearrangement concurrently, their relationship warrants further study.</p>

Preliminary study of diagnosis of patients with myelodysplastic syndromes by routine laboratory parameters / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the value of routine laboratory parameters in diagnosis of myelodysplastic syndromes (MDS) and differential diagnosis of patients with hypoplastic MDS from chronic aplastic anemia (CAA) for providing reference standard for primary hospitals.</p><p><b>METHODS</b>The laboratory parameters at diagnosis of 152 MDS patients with less than 0.05 bone marrow blasts and 86 CAA patients were retrospectively analyzed.</p><p><b>RESULTS</b>There were significant differences between MDS and CAA in Hb, red cell distribution width-coefficient variation (RDW-CV), immature reticulocyte fraction (IRF), BPC, the ratio of G1 (the sum percentage of myeloblast and promyelocyte) to G2 (the sum percentage of neutrophilic myelocyte and metamyelocyte) (Ratio G), the ratio of El (the sum percentage of proerythroblast and early erythroblast) to E2 (the sum percentage of intermediate erythroblast and late erythroblast) (Ratio E), megakaryocyte count (Meg), erythroblast PAS, neutrophil alkaline phosphatase (N-ALP), and serous levels of indirect bilirubin (IBIL), lactose dehydrogenase (LDH), folic acid (FA), VitB12 and ferritin. Chromosome abnormalities were found in 74 MDS patients (48.7%) but in none of CAA patients (P < 0.001). Furthermore, for differentiating MDS with less than 0.05 blasts from CAA, the sensitivity and specificity of combination of Meg, PAS, and IBIL level was 89.1% and 92.7%, the Youden index (gamma) was 0.818. Moreover, in the seven hypoplastic MDS cases, BPC, myeloblast percentage, Ratio G, Meg, erythroblast PAS and FA were statistically different from those of CAA; the sensitivity and specificity of combination of PAS and BPC was 85.7% and 100%, the gamma was 0.857; the sensitivity and specificity combination of Ratio G, Meg PAS was 85.7% and 98.8% respectively, the gamma was 0.845.</p><p><b>CONCLUSION</b>The routine laboratory parameters, especially BPC, Meg, Ratio G, PAS, IBIL may be helpful for the diagnosis of MDS and differential diagnosis of hypoplastic MDS from CAA.</p>

Long-term therapeutic outcome of patients with acute promyelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the long-term therapeutic outcome of patients with acute promyelocytic leukemia(APL).</p><p><b>METHODS</b>Newly diagnosed APL patients were treated with ATRA as induction therapy followed by 3-4 courses of combined consolidation chemotherapy and 2 year maintenance therapy with ATRA and 6-MP + methrotrexate, alternatively. Patients were regularly monitored with nested RT-PCR for PML-RARalpha fusion transcript at the end of consolidation chemotherapy and in the following 4 to 5 years.</p><p><b>RESULTS</b>A total of 81 patients with APL were entered the trial, 75 (92.6%) patients achieved CR. Early death (ED) rate was 6.6%. ED patients had significantly higher WBC count and higher percentage of peripheral promyelocyte than those achieved CR. Of 65 patients received consolidation, 60 (92.3%) were proved PML-RARalpha fusion gene negative at the end of the 3rd courses and 3 (4.6%) the end of the 4th courses of consolidation. The mean follow-up was 21.2 (8-64) months, 6 patients relapsed (relapse rate 9.2%). The 5-year Kaplan-Meier estimates of overall survival (OS) rate was (86.6 +/- 4.6)%. For 65 patients received consolidation therapy, the 5-year relapse-free survival (RFS) rate was 82.7%. COX-regression analyses showed only high WBC count (>10 x 10(9)/L) had an adverse prognostic influence on OS.</p><p><b>CONCLUSION</b>More than 80% of APL patients treated with systemic therapy could experience long-term relapse-free survival.</p>

PTD-hEGF fusion protein--gene expression and function analysis / 生物工程学报

To produce membrane-permeable human epidermal growth factor (hEGF), a pPTD-hEGF prokaryocyte expression vector was constructed and transformed into E. coli BL 21 (DE3). The PTD-hEGF fusion protein was induced by 0.3 mmol/L of IPTG expressed in the form of inclusion body with an yield of 40% of the total protein in the cells, and then purified by Ni2+ -NTA affinity chromatography. The SDS-PAGE analysis showed a single fusion protein band with a molecular weight of 16 kD. The amino acid sequence was checked by MALDI-TOF-MS analysis. The genetic engineering PTD-hEGF fusion protein obviously promoted the proliferation and growth of the HEK-293 cells in vitro.

Clinical and laboratory study of 4 cases of myelodysplastic syndromes with t (1;3) (p36; q21) / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical features of myelodysplastic syndromes (MDS) patients with t (1; 3) (p36; q21) and the expression of the involved genes.</p><p><b>METHODS</b>4 cases of MDS with t (1; 3) (p36; q21) were reported. The expression level of two transcription forms (PR-containing form MEL1 and PR-lacking form MEL1s) of MEL1 gene in normal fetus tissues, 2 healthy donor bone marrows and bone marrows from 3 MDS patients with t (1; 3) (p36; q21) were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>MDS patients with t (1; 3) (p36; q21) mainly presented with debility. Hemogram was macrocytic anemia, normal or elevated white blood cell and platelet counts. The bone marrow showed tri-lineage dysplasia especially dysmegakaryocytopoiesis. The patients had poor prognosis. MEL1 form was mainly expressed in the normal fetus tissues and healthy bone marrows, while the bone marrow cells from MDS patients with t (1; 3) (p36; q21) mainly or only expressed MEL1s.</p><p><b>CONCLUSIONS</b>MDS patients with t (1; 3) (p36; q21) may be a new unique entity. Overexpression of MEL1s induced by t (1; 3) (p36; q21) might play an important role in the pathogenesis of this entity.</p>

Study of genes involved in chronic myeloid leukemia with t (3; 21) (q26; q22) in blastic crisis / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore genes involved in chronic myeloid leukemia (CML) with t (3; 21) (q26; q22) chromosome translocation in blastic crisis.</p><p><b>METHODS</b>A case of CML patient with t (3; 21) (q26; q22) in blastic crisis was reported. AML1 and bcr/abl genes were detected by FISH in interphase and metaphase cells. Genes involved in t (3; 21) (q26; q22) were analysed by RT-PCR and sequencing.</p><p><b>RESULTS</b>AML1 gene hybridization signal was detected in der (3) and der (21) chromosomes. AML1-Evi1, AML1-MDS1-Evi1, AML1-EAP fusion transcripts and Evi1 gene were detected in mRNA level, but no AML1-Evi1 fusion transcript. The mRNA expression level of AML1-MDS1-Evi1 fusion gene was 1.58 and 1.54 times higher than that of AML1-MDS1 and AML1-EAP, respectively. The mRNA expression level of Evi1 gene of the patient was 2.71 times higher than that of HEL cell line.</p><p><b>CONCLUSION</b>t (3; 21) (q26; q22) resulted in the AML1-MDS1-Evi1, AML1-MDS1, AML1-EAP fusion transcripts, and Evi1 gene was also activated by the translocation. These secondary aberrations should be the molecular basis of CML patient with t (3; 21) (q26; q22) in blastic crisis.</p>