Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT) / 白血病·淋巴瘤

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Clinical features and genetic analysis of two Chinese pedigrees affected with Joubert syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome.@*METHODS@#Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2.@*RESULTS@#The proband of pedigree 1 was a fetus at 23+5 weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up.@*CONCLUSION@#The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.

Advances in the Diagnosis, Treatment and Prognosis of Lymphangioleiomyomatosis / 罕见病研究

Lymphangioleiomyomatosis (LAM) is a rare, multisystemic, low-grade neoplasm character-ized by diffuse cystic lesions in the lung.In recent years, emerging imaging examination such as 68Ga-NEB PET-CT scan provides efficient and precise non-invasive diagnostic methods to detect lymphatic circulation abnormalities in LAM patients. The long-term efficacy and safety of sirolimus for LAM has accumulated further evidence, and genetic profiling studies have unveiled more information of genetic mechanisms. Prognosis of LAM has been much improved. We briefly reviewed the research advances of LAM in China and other countires.

The diagnostic value of active inflammatory changes of the symphysis pubis on magnetic resonance imaging scans in patients with axial spondyloarthritis and clinical factors analysis / 中华风湿病学杂志

Objective:To evaluate the correlation of active inflammatory changes of the symphysis pubis on magnetic resonance imaging (MRI) scans with clinical factors in patients with axial spondyloarthritis.Methods:We retrospectively evaluated 112 patients with axial spondyloarthritis (ax-SpA) in our hospital from February 2014 to November 2020. Patients were divided into 4 groups: symphysis pubis + sacroiliac arthritis, symphysis pubis + non-sacroiliac arthritis, non-symphysis pubis + sacroiliac arthritis, and non symphysis pubis + non-sacroiliac arthritis group. Intra-group correlation coefficient ( ICC) was used to analyze the correlation between MRI active inflammation of the symphysis pubis and the sacroilioarthritis. Age, sex, symptom duration, smoking, body mass index, human leukocyte antigen (HLA)-B27 positive rate, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) among the four groups were compared by one-way analysis of variance (ANOVA) and Chi-square test. Results:The proportion of active inflammation of the symphysis pubis was 35.7% (40/112). There was no correlation between active inflammation of the symphysis pubis and sacroilioarthritis ( r=-0.06, P=0.559). Twenty-four patients of the 69 patients with sacroilioarthritis had active inflammation of the symphysis pubis, 16 patients of the 43 patients without sacroilioarthritis had active inflammation of the symphysis pubis. In patients without active inflammation of the sacroiliac joint, the CRP and ESR of the active inflammation of the symphysis pubis group was (49±60) mg/L, (40±19) mm/1 h, statistically higher than that of the non-active inflammation group (19±22) mg/L, (22±37) mm/1 h ( t=2.36, P=0.023; t=2.88, P=0.006). In patients who had active inflammation of the symphysis pubis, the symptom duration of the non-active inflammation of the sacroiliac joint, was (14±9) years, which was significantly longer than that of the active inflammation group (5±4) years ( t=4.07, P=0.001). Conclusion:There is no correlation between active inflammatory changes of the symphysis pubis and bone marrow edema of the sacroiliac joint. Therefore, in ax-SpA patients with inflammatory low back pain and/or hip/groin pain, and also with high levels of CRP, ESR, but no active inflammatory changes of the sacroiliac joint on MRI scans, active inflammation of the symphysis pubis should be considered.

Characteristics of nailfold capillaroscopy examination of systemic sclerosis and its value in assessing the development of SSc / 中华风湿病学杂志

Objective:To identify the characteristics of nailfold capillaroscopy (NFC) of systemic sclerosis (SSc) and investigate whether more severe peripheral microangiopathy at NFC were related to the development of SSc.Methods:① The study included 115 patients (60 cases with SSc and 55 patients with other connective tissue diseases). All patients were treated with neither prednisone nor immunosuppressive drugs within 3 months before enrollment. We collected the following data: age, disease duration, disease onset, mRSS, high-resolution chest tomography (HRCT), echocardiography, pulmonary function, nailfold capillaroscopy and routine laboratory assessments. ② All the NFC definitions were used for semi-quantitatively scoring and Cutolo's qualitative assessment. ③ The relationship between NFC changes and joint, visceral involvement and autoantibodies in SSc patients was analyzed. ④ T test, Rank sum test and chi-square test were applied to analyze data. Results:① According to Cutoloqualitative assessment of NFC, patients of SSc with active/late pattern ( n=52) were very common than other CTD ( n=21) ( Z=-3.853, P<0.01). ② According to semiquantitative assessment, the scores of loss of capillaries [(1.67±0.60) vs (0.72±0.46), t=8.347, P<0.01)], irregular enlarged capillaries [(1.22±0.88) vs (0.74±0.50), t=3.178, P<0.01)], hemorrhage [(0.30±0.39) vs (0.10±0.21), t=3.090, P<0.01)], disorganization of the microvascular array [(0.38±0.38) vs (0.18±0.32), t=2.729, P<0.01)] were significantly higher than CTD. ③ The NFC of SSc patients was significantly different from CTD. The number of capillary loss ( Z=-4.194, P<0.01), input capillary dimensions ( t=3.704, P<0.01), output capillary dimensions ( t=3.913, P<0.01), wide diameter of capillary ( t=4.586, P<0.01), tortuous capillaries ( Z=-2.677, P<0.01), gaint capillary ( χ2=8.040, P=0.013), effusion ( Z=-2.278, P=0.023) were more increased than CTD. ④ The NFC pattern of SSc with lung involvement were mainly active and late (66%, 33/50), whereas early and active pattern (60%, 6/10) for those without respiratory system involvement ( Z=10.114, P=0.045) . The NFC pattern of SSc patients with joint involvement were mainly active and late (75%, 12/16), whereas early and active (66%, 29/44) for those without joint involvement ( Z=5.550, P=0.057) . Conclusion:The NFC of SSc patients is significantly different from CTD. NFC may be a suitable tool for disease evaluation.

Advances in quantification of lentiviral vectors / 生物工程学报

Immunotherapy is becoming an effective and less invasive strategy that can be applied to the treatment of various malignancies. Lentiviral vectors (LVs) have shown great potential in immunotherapy as they can stably integrate relatively large foreign DNA, and effectively transduce dividing and non-dividing cells. Clinical application needs high quality LVs, and therefore strict quality control of the final products is necessary to ensure their purity, efficacy and safety. The quantitative detection of LVs is among the key parts of product development and quality control. In this paper, the existing methods for quantitative detection of LVs are summarized, including fluorescence activated cell sorter (FACS), P24 enzyme-linked immuno sorbent assay (P24 ELISA), real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), nanoparticle tracking analysis (NTA), tunable resistive pulse sensing(TRPS) and virus counter(VC).Their advantages and disadvantages are listed, and future development and challenges are discussed.

RUNX1 gene mutations are associated with adverse prognosis of patients with acute myeloidleukemia / 南方医科大学学报

OBJECTIVE@#To explore the rate and distribution of Runt- related transcription factor 1 (RUNX1) gene mutations in patients with acute myeloid leukemia (AML) and the correlation of these mutations with the clinical characteristics and survival outcomes of the patients.@*METHODS@#The genomic DNA extracted from the bone marrow of 158 patients with newly diagnosed AML for PCR amplification of RUNX1 gene and sequence analysis to identify the mutations. The mutations of ASXL1, DNMT3A, TET2, FLT3, CEBPA, NPM1, IDH2, NRAS and c-KIT genes were also examined to analyze their association with RUNX1 gene mutations.@*RESULTS@#Among the 158 AML patients, 19 (12.0%) were found to have RUNX1 mutations in A166G (9 cases), A142T (6 cases) and A162L (4 cases). RUNX1 mutations were more frequent in elderly patients (@*CONCLUSIONS@#RUNX1 gene mutations are associated with an adverse prognosis of patients with AML.

Clinical analysis of cardiac involvement in eosinophilic granulomatosis with polyangiitis: a report of 16 cases / 中华风湿病学杂志

Objective:To analyze the clinical features of patients with cardic involvement in eosinophilic granulomatosis with polyangiitis (EGPA), and to enhance the understanding.Methods:We retrospectively reviewed the clinical data of 16 patients with EGPA with cardiac involvement in Bethune hospital of Shan-xi from Jan 2012 to Jun 2019. T test, rank sum test and χ2 test were used for statistical analysis. Results:16 patients with cardiac involvement. There were 11 males and 9 female. The age of 16 patients with cardiac involvement ranged from 14 to 82 years old, and the average age of onset was (58±14) years. Compared with patients without cardiac invo-lvement was (41±15) years, the difference between the two groups was statistically significant ( t=3.230 , P<0.01). The analysis suggested that age was related to whether or not cardiac involvement. Cardiac related clinical symptoms occurred in 4 patients (25%). One patient presented with cardiac involvement as the initial symptom. The other 12 patients presented abnormal electrocardiogram (ECG), cardiac ultrasound or cardiac magnetic resonance imaging (MRI), including 10 patients (62%) with abnormal ECG, 13 patients (81%) with abnormal cardiac ultrasound examination, and1patient with cardiac MRI suggesting endocarditis. Among 16 patients with EGPA cardiac involvement, 14 presented with pulmonary involvement, 10 cases with nasal involvement, 9 cases with perip-heral neurological involvement, 9 cases with skin involvement, 6 cases with gastrointestinal involvement, 2 cases with kidney damage. Eosinophils (EO) were increased in all 16 patients, with a median value of 2.46 (1.49, 3.94) ×10 9/L, and EO was associated with cardiac involvement. Analysis of perinuclear anti-neutrophil cytoplasmic antibo-dies (pANCA) positive rate showed that only 2 of the 16 patients were positive. There was statistically significant difference ( P=0.017) compared with the group without cardiac involvement (8 patients were positive). All 16 patients were treated with glucocorticoid, 12 patients received immunosuppressive therapy, and 10 patients were treated with cyclophosphamide. During the ollow-up, 1 case died of heart failure, 1 case died of cerebral hemorrhage, 3 cases were lost to follow-up, and the other 11 cases were all stable after discharge. Conclusion:EGPA patients have a high incidence of cardiac involvement, and all cardiac stru-ctures can be involved, and most cardic involvement happens in ANCA negative patients. Cardiac involvement is one of the factors with poor prognosis.

High preoperative pulmonary artery systolic pressure is associated with acute kidney injury and prognosis in patients underwent cardiopulmonary bypass surgery / 中华危重病急救医学

Objective:To observe the relationship between pulmonary artery systolic pressure (PASP) and acute renal injury (AKI) and prognosis after cardiopulmonary bypass (CPB) heart surgery.Methods:The clinical data of 9 860 patients who underwent CPB heart surgery in Beijing Anzhen Hospital from January 1st, 2015 to December 31st, 2016 were analyzed retrospectively. The patients were divided into two groups according to whether AKI occurred after operation. The clinical data were obtained from hospital information system (HIS) and DoCare including general information, types of operation, preoperative complication, ejection fraction, serum creatinine (SCr), PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, blood products and drug usage, postoperative mechanical ventilation duration, length of intensive care unit (ICU) and hospital stay, and perioperative central venous pressure (CVP). Multivariate Logistic regression analysis was used to screen the risk factors of AKI after operation. According to the preoperative PASP level, the patients were divided into ≥ 60 mmHg (1 mmHg = 0.133 kPa) group and < 60 mmHg group, and the incidence of AKI and prognosis after operation were compared between the two groups. All patients were followed up by telephone after discharge, and they were divided into survival group and death group according to the follow-up results, and the clinical data were compared between the two groups. Multivariate Cox regression analysis was used to screen the risk factors of long-term prognosis. Kaplan-Meier survival curve was used to analyze the long-term prognosis of two groups with different preoperative PASP levels.Results:6 285 patients were enrolled in the final analysis. ① Among the 6 285 patients, 2 592 patients (41.2%) suffered from AKI after operation, of whom 1 697 (65.5%) were stage 1 according to Kidney Disease: Improving Global Outcomes (KDIGO), which was the main type of AKI. Univariate analysis showed that age, preoperative ejection fraction, SCr, PASP, coronary heart disease, hypertension, diabetes, intraoperative CPB duration, aortic occlusion duration, fluid balance, red blood cell input and norepinephrine, dopamine, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be the risk factors of AKI after operation. Multivariate Logistic regression analysis showed that preoperative PASP was one of independent risk factors for AKI in patients undergoing CPB heart surgery [odds ratio ( OR) = 4.753, 95% confidence interval (95% CI) was 1.328-8.417, P = 0.004]. The incidence of AKI after operation in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [73.8% (712/965) vs. 35.3% (1 880/5 320), P < 0.01]. ② After a follow-up of (11±3) months, 237 patients (3.8%) died in 6 285 patients. The mortality of patients in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [9.5% (92/965) vs. 2.7% (145/5 320), P < 0.01]. Kaplan-Meier survival curve analysis showed that there was a significant difference between the two groups in cumulative survival rate (Log-Rank test: χ2 = 144.400, P < 0.001). Univariate analysis showed that male, age, preoperative hypertension, ejection fraction, PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be risk factors for long-term death of patients undergoing CPB heart surgery. Multivariate Cox regression analysis showed that for every 1 mmHg increase in preoperative PASP, the long-term mortality increased by 1.126 times [hazard ratio ( HR) = 1.126, 95% CI was 1.003-1.604, P = 0.021]. Conclusion:The increase of PASP is related to AKI after CPB heart surgery, which is an independent risk factor for long-term mortality.

Recurrent Angelman syndrome caused by a rare partial deletion of UBE3A gene / 中华医学遗传学杂志

OBJECTIVE@#To provide genetic testing for two brothers with mental retardation and epilepsy.@*METHODS@#Array comparative genomic hybridization (aCGH) was used to detect copy number variations in the two patients, their parents and maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was utilized to delineate the deleted region in the pedigree.@*RESULTS@#A 138 kb deletion in 15q11.2 region was detected by aCGH in both patients, which encompassed part of the UBE3A gene. MS-MLPA has narrowed down the region to exons 8 to 14 of the UBE3A gene. The same deletion was also found in their mother and grandfather.@*CONCLUSION@#The pathogenesis of this rare form of recurrent Angelman syndrome may be attributed to the partial deletion of maternal UBE3A gene.

Vaccine pretreatment for quantification of 146S antigen in foot-and-mouth disease vaccines by high performance size exclusion chromatography / 生物工程学报

We developed a pre-treatment method to remove interfering substances during quantification of 146S antigens in foot-and-mouth disease (FMD) vaccines by high performance size exclusion chromatography (HPSEC). Three methods, including ultracentrifugation, PEG precipitation and nuclease digestion, were optimized and compared for removal efficiency of the interfering impurities in FMD vaccines. Under optimized conditions, the 146S contents in two batches of FMD vaccines were determined to be 7.1 and 7.6 μg/mL by ultracentrifugation, 9.7 and 10.4 μg/mL by PEG precipitation, and 10.5 and 10.4 μg/mL by nuclease digestion. The optimal condition for nuclease digestion using Benzonase determined by response surface method was as follows: appending Benzonase into 200 μL of antigen phase to a final concentration of 421 U/mL and incubating at 25.1 °C for 1.29 h. This method has advantages including efficient removal of the interfering impurities, fast processing speed, and mild operating conditions. Then 12 bathes of FMD vaccines with different serotypes produced by 4 manufacturers were tested to verify the established treatment method. Results showed the method was applicable to various FMD vaccines with good reproducibility (RSD<5.3%, n=3). The developed method removed interference from impurities during quantification of 146S, and therefore would broaden the application of HPSEC in vaccine quality control and ensure the accuracy and reliability.

Clinical analysis of 8 cases of connective tissue disease complicated with acquired hemophilia A / 中华风湿病学杂志

Objective To analyze the clinical features and treatment of connective tissue disease (CTD) complicated with acquired hemophilia A (AHA).Methods A retrospective analysis of 8 cases of CTD [5 cases of systemic lupus erythematosus (SLE),2 cases of Sj(o)gren's syndrome (SS),1 case of rheumatoid arthritis (RA)] related to clinical manifestations,diagnostic methods,treatment options and outcomes.Results At the onset of AHA,active disease was shown in 7 patients with CTD,and 5 cases had bleeding symptoms in different parts.There were 3 cases of anti-phospholipid syndrome in 5 cases of SLE,2 of which had thrombosis.In 8 patients,the activated partial thromboplastin time (APTF) was prolonged by 1.7 to 3.times,FⅧ∶ C was 9.2％ to 21％ (50％ to 150％),and the factor Ⅷ inhibitor titer was increased by 7.6 to 56 BU/m1 (Bethesda method).Seven patients were treated with sufficient hormones,immunosuppressive agents,human immunoglobulin (IVIG),and blood products.Five patients had clinically improved bleeding tendency and APIT,and one patient was ineffective.Conclusion CTD is easy to combine with AHA.Glucocorticoid combined with immunosuppressive agent can effectively treat CTD-related AHA.For refractory patients,rituximab can be an alternative.

Study on a high-throughput method with LC-MS/MS technique for detecting aflatoxins in ginger / 国际中医中药杂志

Objective@#To optimize the method of simultaneous determination of four aflatoxins (B1, B2, G1 and G2) of ginger by the ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method and high-throughput method.@*Methods@#The aflatoxins were extracted from ginger by methanol-water (80:20, V/V) solution, concentrated and dried with nitrogen. The aflatoxins were detected by UPLC-MS/MS by using Waters Acquity UPLC BEH C18 chromatographic column. The mobile phase was 0.1% formic acid water (A phase) -0.1% formic acid methanol (B phase), gradient elution, flow rate 0.35 ml/min, mass spectrometry was electrospray ion source, positive ion scanning mode, multi reaction ion monitoring were using.@*Results@#Quantification of four aflatoxins by matrix matching standard curve. The linear was good in the range of 0.125-20.000 ng/ml, and the correlation coefficients were all greater than 0.999 0. The ginger sample detection was 0.125-0.300 μg/kg and 0.125-1.000 μg/kg, respectively. The average recoveries were 81.7%-96.0%, and the relative standard deviation (RSD) was lower than 7.53%.@*Conclusions@#This method is simple, rapid, sensitive and low limit of detection, which can meet the requirements for the detection of trace aflatoxins residues in ginger.

Curcumin suppresses cigarette smoke extract-induced oxidative stress through PPARγ/ NF-κB pathway in human bronchial epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of curcumin against cigarette smoke extract (CSE)- induced oxidative stress in human bronchial epithelial cells and explore the underlying mechanism.</p><p><b>METHODS</b>Human bronchial epithelial cell line 16HBE was treated for 24 h with curcumin, CSE, CSE + curcumin, and CSE + curcumin with transfection by a short hairpin RNA targeting PPARγ (shPPARγ). MTT assay was used to observe the changes in the cell viability after the treatments. Quantitative real-time PCR was performed to detect the mRNA expressions of tumor necrosis factor- (TNF-), iNOS and PPARγ in the cells, and the protein expressions of iNOS, PPARγ and the phosphorylation of NF-κB p65 were detected using Western blotting.</p><p><b>RESULTS</b>The treatments did not cause significant changes in the cell viability. Exposure to CSE for 24 h significantly lowered PPARγ expression and increased TNF- and iNOS expressions and phosphorylation of NF-κB p65 in the cells. The effects of CSE were significantly suppressed by curcumin, but transfection of the cells with shRNA-PPARγ obviously abrogated the suppressive effects of curcumin.</p><p><b>CONCLUSIONS</b>Curcumin suppresses CSE-induced oxidative stress and inflammation via the PPARγ/NF-κB signaling pathway in 16HBE cells, suggesting the potential of curcumin in the treatment of chronic obstructive pulmonary disease.</p>

The role of ABCC2 gene in drug-resistant epilepsy / 中国医师杂志

Objective To investigate the role of the ATP binding box C subfamily 2 transporter protein (ABCC2) gene in drug-resistant epilepsy.Methods From February 2014 to February 2018,204 epileptic patients were treated in our hospital,including 41 cases of drug resistance epilepsy (drug resistance group),163 cases of non drug resistant epilepsy (sensitive group).The rs717620 polymorphism of ABCC2 gene and the level of P-glycoprotein (P-gp) in cerebrospinal fluid and serum were detected in two groups.Results The proportion of genotype TT and gene frequency T in the drug resistant group were 24.39％ and 41.46％,respectively,which were significantly higher than those in the sensitive group (P ＜ 0.05).The concentration of P-gp in cerebrospinal fluid of drug resistant group was (21.03 ± 4.21) ng/ml,which was significantly higher than that of the sensitive group (P ＜ 0.05).There was no significant difference in serum P-gp concentration between the drug resistant group and the sensitive group (P ＞ 0.05);The concentration of P-gp in cerebrospinal fluid of patients with genotype TT in drug resistance group was (24.03 ± 3.57) ng/ml,which was significantly higher than that of type CC and CT (P ＜ 0.05).There was no significant difference in the concentration of P-gp in the patients with different genotypes in the drug resistant group (P ＞ 0.05).Conclusions The rs717620 polymorphism of ABCC2 gene may be associated with drug-resistant epilepsy,and may be related to P-gp level in the cerebrospinal fluid.

Genetic analysis of a child with cleidocranial dysplasia and 6q21-q22.31 microdeletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To carry out genetic analysis on a child with developmental delay and multiple malformation.</p><p><b>METHODS</b>The karotypes of the child and her parents were analyzed with routine chromosomal G-banding. Their genomic DNA was analyzed with array comparative genomic hybridization (aCGH).</p><p><b>RESULTS</b>The karyotype of the proband was determined as 46,XX,del(6)(q22),inv(6)(p21.1q21), while no karyotypic abnormality was detected in her parents. aCGH has identified in the child a de novo 800 kb deletion encompassing the RUNX2 gene at 6p21.1 and a de novo 11.79 Mb deletion at 6q21-q22.31.</p><p><b>CONCLUSION</b>Both of the de novo deletions are pathogenic. Deletion of the RUNX2 gene probably underlies the cleidocranial dysplasia in the patient, while the 6q21-q22.31 deletion may result in malformation of the brain.</p>

Using size-exclusion chromatography to quantify the 146S antigen in inactivated foot-and-mouth disease vaccine / 生物工程学报

The aim of this study is to quantify the 146S antigen in foot-and-mouth disease virus (FMDV) inactivated vaccine by size-exclusion chromatography (SEC). The analysis was performed on a TSKgel G4000SWXL column (7.8 mm×30 cm), with a pH 7.2 buffer salt system as the mobile phase. The flow rate was 0.6 mL/min, the injection volume was 100 μL and the detection wavelength was 259 nm. The calibration curve was established by using purified inactivated FMDV (serotype O) 146S antigen; 3 batches of vaccine formulated by inactivated antigen solution were tested to verify the accuracy, reproducibility, specificity and tolerability of the method. At last 16 batches of vaccine were determined by the SEC method. Results showed a good linearity between peak area and concentration of 146S antigen in the range between 0.56 and 67.42 μg/mL (R2=0.996, n=10), and the average recovery rate of 146S antigen in the 3 batches of vaccine formulated in lab were 93.6% (RSD=2.7%, n=3), 102.3% (RSD=2.6%, n=3), and 95.5% (RSD=5.1%, n=3). The method was proved accurate and reliable with good reproducibility (RSD=0.5%, n=6), and applied to determine 16 batches of the commercial FMDV vaccine. According to the above results, the SEC method is high effective for 146S antigen quantify in the inactivated FMDV vaccine and would provide strong support for the vaccine quality control.

Prenatal diagnosis and genetic analysis of a fetus with endocardial cushion defects / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To perform prenatal diagnosis for a fetus with endocardial cushion defect and explore its mechanism.</p><p><b>METHODS</b>The karotypes of the fetus and its parents were analyzed by routine G-banding. Their genomic DNA was also analyzed by array comparative genomic hybridization (aCGH).</p><p><b>RESULTS</b>The fetus and its mother were found to have a karyotype of 46, XX, inv(8)(p21q24.1), while no karyotypic abnormality was detected for the father. aCGH has detected a 15.14 Mb deletion at 8p23.3-p22 and a 6.87 Mb duplication at 8q24.23-q24.3 in the fetus.</p><p><b>CONCLUSION</b>The fetus was diagnosed with Rec8 syndrome. Its abnormal chromosomes have derived from the inv(8) carried by its mother. GATA4 and SOX7 may be the key genes for the endocardial cushion defect found in the fetus.</p>

Genetic diagnosis of a child with aortic stenosis and thumb aplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the molecular mechanism and prognosis of a child with aortic stenosis and thumb aplasia.</p><p><b>METHODS</b>The karotypes of the child and his parents were analyzed with routine G-banding. Their genomic DNA was also analyzed with array comparative genomic hybridization(aCGH) for chromosomal duplications/deletions.</p><p><b>RESULTS</b>No karyotypic abnormality was detected at cytogenetic level for the child and his parents. aCGH identified a de novo 5.86 Mb deletion at 2q22.3-q23.3 in the child.</p><p><b>CONCLUSION</b>The child was diagnosed with 2q23.1 microdeletion syndrome. MBD5 may be the key gene for the 2q23.1 microdeletion syndrome.</p>

Prenatal diagnosis and genetic analysis of a fetus with 2p13.3-p12 microdeletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide prenatal diagnosis for a pregnant woman with a history of Williams-Beuren syndrome pregnancy.</p><p><b>METHODS</b>The karyotypes of the fetus and his parents were analyzed with routine G-banding. Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH).</p><p><b>RESULTS</b>No karyotypic abnormality was detected for the fetus and his parents. aCGH has identified a de novo 5.09 Mb deletion at 2p13.3-p12 in the fetus.</p><p><b>CONCLUSION</b>The 2p13.3-p12 microdeletion carried by the fetus was de novo. As it has involved dosage-sensitive genes SPR and DCTN1, the deletion is probably pathogenic.</p>