OBJECTIVE: To explore the genetic basis for a rare case of acute B-lymphocytic leukemia (B-ALL) with double Philadelphia chromosomes (Ph) and double derivative chromosome 9s [der(9)]. METHODS: A patient with double Ph and double der(9) B-ALL who presented at Shanghai Zhaxin Intergrated Traditional Chinese and Western Medicine Hospital in June 2020 was selected as the subject. Bone marrow morphology, flow cytometry, G-banding karyotyping, fluorescence in situ hybridization (FISH), genetic testing and chromosomal microarray analysis (CMA) were used to analyze bone marrow samples from the patient at various stages. RESULTS: At initial diagnosis, the patient's bone marrow morphology and flow immunotyping have both supported the diagnosis of B-ALL. G-banded karyotyping of the patient indicated double Ph, in addition with hyperdiploid chromosomes involving translocations between chromosomes 9 and 22. BCR-ABL1 fusion gene was positive. Genetic testing at the time of recurrence revealed presence of a heterozyous c.944C>T variant in the kinase region of the ABL1 gene. FISH showed a signal for ABL1-BCR fusion on both chromosome 9s. CMA showed that the mosaicism homozygosity ratio of chromosome 9 was about 40%, and the mosaicism duplication ratio of chromosome 22 was about 43%. CONCLUSION Since both der(9) homologs were seen in 40% of cells, the possible mechanism for the double der(9) in this patient may be similar to that of double Ph, which might have resulted from non-disjunction during mitosis in the Ph chromosome-positive cell clone.
Humans ; Philadelphia Chromosome ; In Situ Hybridization, Fluorescence/methods* ; China ; Chromosome Aberrations ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Translocation, Genetic ; Fusion Proteins, bcr-abl/genetics* ; Chromosomes, Human, Pair 9/genetics*

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Objective:To investigate the clinical characteristics and therapeutic methods of coronary artery aneurysm (CAA).Methods:The clinical data and coronary angiography of 32 patients confirmed by coronary angiography as coronary aneurysm in Shenzhen Hospital of Southern Medical University and Shenzhen People′s Hospital were collected. They were followed up, and the different therapeutic methods were analyzed.Results:Thirty-two cases (1.8%) of coronary artery aneurysms were found in 1 778 patients undergoing coronary angiography. The main sites of coronary ectasia were right coronary artery, anterior descending branch and circumflex branch, and the left main branch was rare. Among the patients with coronary artery aneurysms, there were 25 patients with coronary artery stenosis. All the 32 patients were given anticoagulant, antiplatelet, improvement of coronary spasm and statin therapy, among whom 2 patients were treated with stent implantation and 6 patients were treated with coronary artery bypass graft (CABG) and ligation of coronary aneurysm. During the follow-up (average 15 months) of 1 patient, acute myocardial infarction reoccurred, and coronary angiography indicated that the stenosed coronary segments after artery ectasia was occluded because of thromboembolism. In the remaining patients, there were no major cardiovascular events such as angina pectoris, acute myocardial infarction and sudden cardiac death.Conclusions:Coronary artery aneurysm is not a rare heart disease. Coronary thromboembolism, thrombosis and vasospasm are the main causes of angina pectoris and myocardial infarction. Anticoagulant, antiplatelet, antispasmodic drugs and suitable coronary artery bypass can significantly improve the clinical prognosis of patients with coronary artery aneurysm.

Objective:To understand the spatial distribution of small mammals in the areas of natural focus disease in Qinghai Province, and to identify captured small mammals at the molecular level using mitochondrial cytochrome C oxidase subunit I (COI) gene as molecular marker.Methods:In 2009 - 2016, the distribution of regional spatial, elevation distribution and ecological environment type of captured small mammals were analyzed in 16 cities (counties) of 6 prefectures in Qinghai Province. The partial COI gene fragment sequence (about 650 bp in length) was obtained by PCR amplification, which was further analyzed through homology comparison, genetic distance and phylogenetic analysis.Results:Totally 1 631 small mammals were captured that had belonged to 30 species of 21 genera, 7 families, 3 orders. Among them there were 926 rodent animals that had belonged to 25 species of 19 genera, 5 families, accounting for 56.78%. There was the largest number in Golmud (313 animals), the highest distribution of small mammals was found at the elevation of 2 800 - < 3 000 m (532 animals), the largest number of small mammals was found in the sandy grassland (612 animals). COI genes of 292 small mammals were successfully amplified, and the homology was consistent with the target sequence. The results showed that the intraspecific genetic distance ranged from 0.01% to 2.90%, interspecific genetic distance ranged from 4.00% to 12.00%, intergenus genetic distance was 13.00% - 21.00% and interfamily genetic distance was 22.00% - 25.00%. The interspecific genetic distance was significantly greater than the intraspecific genetic distance. Neighbor-Joining tree showed that the same species were clustered into a single branch with high support form a total of 20, with a confidence level of 98% to 100%.Conclusions:The spatial distribution of small mammals is influenced by geographical factors such as region, elevation and ecological environment in Qinghai Province. Molecular identification can make up for the shortcomings in morphological identification.

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.
Animals ; Carcinoma, Non-Small-Cell Lung ; immunology ; therapy ; Cell Line, Tumor ; ErbB Receptors ; immunology ; metabolism ; Female ; Humans ; Immunotherapy, Adoptive ; methods ; Lung Neoplasms ; immunology ; therapy ; Mice ; Mice, Inbred NOD ; Receptors, Chimeric Antigen ; immunology ; T-Lymphocytes ; immunology ; Xenograft Model Antitumor Assays

Objective To analyze and review clinical characteristics of brucellosis and improve awareness of brucellosis and level of diagnosis.Methods Totally 72 in-patients treated for brucellosis from March 2012 to June 2015 in Affiliated Hospital of Jining Medical University were retrospectively analyzed for epidemiology,clinical feature,laboratory data,treatment and prognosis.Results A total of 72 cases were confirmed and included.Thirty seven patients (51.39％) had definitely contact history with raw meat or progeny and 3 (4.17％) with brucellosis patients.The common clinical presentations included persistent fever (100.00 ％,72/72),followed by headache (87.50％,63/72),chills (48.61％,35/72),muscle-joint pain (47.22％,34/72) and cough (43.06％,31/72).The laboratory test showed there were 14 patients (19.44％,14/72) with decreased leukopenia,49 patients (68.06％,49/72) with elevated C-reactive protein and 46 patients (63.89％,46/72) with elevated procalcitonin.Abnormal liver function showed elevated alanine aminotransferase (69.44％,50/72),aspartate aminotransferase (66.67％,48/72) and alkaline phosphatase (61.11％,44/72) with proportions.The mainly abnormal imaging features showed hepatomegaly,splenomegaly,lymphadenopathy,pulmonary infiltrating and nodules.Sixty-five patients (90.28％) had positive blood culture and 13 cases (18.06％) had positive marrow culture.Seventy-two patients were cured after active medical treatment and no recurrence after 1 year of follow-up.Conclusions Brucellosis is a invasive infectious disease with many systemic involvements,whose clinical symptoms are not typical.For those patients with long-term fever of unknown origin and poor effect anti-infection treatment,especially complicated with multi-system damage hepatomegaly,splenomegaly,lymphadenopathy,brucellosis should be suspected and be treated early.

Objective To study the relationship between level of plasma glucose and cognitive function in patients with Parkinson's disease.Methods Two hundred PD patients were assessed cognitive function using Mini-Mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Wechsler Intelligence Scale and Wechsler Memory Scale.The patients were divided into cognitive normal group (n=91) and cognitive impairment group (n=109).One hundred twenty-six normal subjects were enrolled as control group (n=126).The levels of fasting plasma glucose (FPG),postprandial plasma glucose (2hPPG),glycosylated hemoglobin (HbAlc) and the prevalence of diabetes mellitus were compared among the groups.The effect of blood glucose level on the cognitive function of PD patients was analyzed by Binary Logistic Regression.Results The levels of FPG,HbAlc and the prevalence of diabetes mellitus [5.19 (0.72),5.7％ (0.5％),14％] were significantly higher than those in the normal control group [4.85(0.79),5.6％ (0.5％),6％] (P＜0.05).The levels of FPG in PD patients with cognitive impairment [5.21 (1.32)] was significantly higher than that in PD patients with cognitive normal group [4.81 (0.95)] (P＜0.05).Although 2hPPG and HbAlc increased slightly in PD patients with cognitive impairment,the difference did not reach an significant level (P＞0.05).Binary Logistic Regression analysis showed that FPG(OR:1.764;95％ CI:0.06-3.244;P=0.068) was not associated with the impaired cognitive function in PD patients.Conclusion The present study has not revealed an association between the incidence of cognitive impairment in patients with PD and plasma glucose level although high plasma glucose may be a high risk factor for PD patients.

Objective To study the effect of black granule capsules(BGCs) on growth of transplanted mouse hepatocarcinoma cells, cell proliferation cycle and apoptosis.Methods KM mouse were subcutaneously inoculated with Hepatocarcinoma cells (H22) and randomly divided into the model control group, the positive control group, the low, medium and high does of BGC group after 24h. The positive control group received intraperitoneal injection with 30 mg/kg cyclophosphamide. Mice of BGC groups were intragastricaly with different dosage of BGC (400, 800, 1 600 mg/kg). The model control group received intragastricaly with normal saline. The drugs were administrated once a day for seven days. The tumor inhibition rate was calculated at 24 h after the last administration. Flow cytometry was used to detect changes of cell cycle and apoptosis in harvested H22 tumor cells.Results The group of high does showed significant inhibitory effect on the growth of transplanted H22 tumor cells withthe inhibitory rate 38.78% (male) and 43.57% (female). Compared with model control group, groups of different dosages decreased time of G0-G1 phase (58.06% ± 9.65%, 55.10% ± 5.89%, 61.36% ± 15.95%vs. 74.47% ± 2.63%), increased tiem of Sphase (33.96% ± 11.90%, 32.67% ± 4.04%, 33.89% ± 9.82%vs. 14.37% ± 4.92%), and increased the apoptosis rate (31.12% ± 1.85%, 31.89% ± 2.16%, 40.64% ± 0.55%vs.21.75% ± 2.64%).Conclusion BGC has antitumor effect on mouse hepatocarcinoma H22 tumor cells, and its mechanism was to regulate cell proliferation cycle and induce the apoptosis.

Adult ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Transplantation Chimera ; Transplantation, Homologous

Objective To investigate the efficacy and effects on cognitive functioning of antipsychotic addition to serotonin reuptake inhibitors in patients with treatment-refractory obsessive-compulsive disorder. Methods 58 therapy-resistant OCD patients were randomly grouped and receipt 8-week quetiapine-augmentation treatment or placebo respectively. At baseline and post-treatment, in order to evaluate symptom, executive functions, attention and memory, all patients were measured with Yale-Brown Obsessive-Compulsive Scale and cognitive functioning test, which included Wisconsin Card Sorting Test, Stroop Color Word Test,Continuous Performance Test and Memory Scale. Results Comparing quetiapine-augmentation group and placebo, there was significant difference of Y-BOCS total score between baseline and post-treatment (baseline:28.5±4.4,26.3±6.5,post-treatment:18.5±6.4,25.7±5.4, respectively,P=0.01). There was no major effects on cognitive functioning, apart from a failure to maintain set on the WCST (baseline:1.2±1.1,1.3±1.4,post-treatment:1.6±1.0,1.5±1.2,respectively,P=0.03).Conclusion It was effective of quetiapine-augmentation treatment on refractory OCD. There was no major effects on cognitive functioning of quetiapine-augmentation treatment.