Reversible regulation of enzyme-like activity of molybdenum disulfide quantum dots for colorimetric pharmaceutical analysis / 药物分析学报

Regulating the catalytic activity of nanozymes is significant for their applications in various fields.Here,we demonstrate a new strategy to achieve reversible regulation of the nanozyme's activity for sensing purpose.This strategy involves the use of zero-dimensional M0S2 quantum dots(MQDs)as the building blocks of nanozymes which display very weak peroxidase(POD)-like activity.Interestingly,such POD-like activity of the MQDs largely enhances in the presence of Fe3+while diminishes with the addition of captopril thereafter.Further investigations identify the mechanism of Fe3+-mediated aggregation-induced enhancement of the POD-like activity and the inhibitory effect of captopril on the enhance-ment,which is highly dependent on their concentrations.Based on this finding,a colorimetric method for the detection of captopril is developed.This sensing approach exhibits the merits of simplicity,rapidness,reliability,and low cost,which has been successfully applied in quality control of captopril in pharmaceutical products.Moreover,the present sensing platform allows smartphone read-out,which has promising applications in point-of-care testing devices for clinical diagnosis and drug analysis.

Clinicopathological characteristics and prognosis of non-hypertensive IgA nephropathy patients with microangiopathy lesions / 中华肾脏病杂志

Objective:To evaluate the clinicopathological characteristics and prognosis of IgA nephropathy (IgAN) patients with microangiopathy lesions and with no hypertension.Methods:Adult IgAN patients without hypertension were selected from Peking University First Hospital. All kidney biopsies were independently reviewed by 2 investigators. Patients were divided into three groups (microangiopathy group, simple arterio/arteriolosclerosis group and normal vascular group) by renal arteriolar lesions. Composite kidney end point event defined as a ≥30% reduction in estimated glomerular filtration rate (eGFR) and end-stage kidney disease. Cox regression analysis was used to test the association between microangiopathy lesions and the outcomes.Results:A total of 420 patients were included in this study, of which 37(8.8%) patients had renal arteriolar microangiopathy lesions, 134 (31.9%) patients had simple arterio/ arteriolosclerosis, and the others had no vascular lesion. Compared with simple arterio/arteriolosclerosis group or non-vascular lesion group, patients with renal arteriolar microangiopathy lesions had more severe urine protein ( P=0.002), worse renal function ( P<0.001), higher proportion of segmental glomerulosclerosis and/or balloon adhesion (S1), tubular atrophy/interstitial fibrosis (T1/2), cellular/fibrocellular crescents (C1/2) (all P<0.05). During the follow-up, 20(54.1%) patients with microangiopathy lesions, 45(33.6%) patients with simple arterio/arteriolosclerosis and 82(32.9%) patients without vascular lesion reached the composite kidney end points ( χ2=6.491, P=0.039). In a multivariable Cox regression model, the presence of microangiopathy lesions was an independent risk factor for kidney disease progression in IgAN patients ( HR=1.872, 95% CI 1.044-3.357, P=0.035), and simple arterio/arteriolosclerosis was not a risk factor for kidney disease progression. Conclusion:It is not uncommon for non-hypertensive patients with IgAN having microangiopathy lesions, which suggests that hypertension is not the sole risk factor for microangiopathy lesions.

Analysis on clinical features of 106 type 2 diabetic patients complicated with insulin autoimmune syndrome / 中华内分泌代谢杂志

Objective:To analyze the clinical features of type 2 diabetic patients with insulin autoimmune syndrome after treatment with exogenous insulin.Methods:A total of 106 patients with type 2 diabetes diagnosed with exogenous insulin-related insulin autoimmune syndrome (EIAS) were included from September 2017 to March 2019 in the Department of Endocrinology, Zhongshan Hospital, Fudan University. The clinical data, physical examination, and laboratory examination results of patients were collected.Results:Of the 106 patients, 84 (79.24%) used premixed human insulin or premixed insulin analogs, and 18 patients (16.98%) presented recurrent hypoglycemia. The arginine stimulation test showed that the median value of the baseline insulin was 73.40 (23.07-146.75) μU/ml, and the median ratio of 4 minute insulin to 0 minute insulin was 1.27 (1.03-1.85), with the mean of the ratio 1.72±1.47. The ratio of baseline insulin (μU/ml) to C-peptide (ng/ml) was 44.60 (14.92-87.93), with an average of 81.92±130.93. Taking the two-fold upper limit of fasting insulin reference value (49.8 μU/ml) as the cut-off point, the subjects were divided into insulin accumulation group (baseline insulin≥49.8 μU/ml) and insulin non-accumulation group (baseline insulin <49.8 μU/ml). Among the 66 patients in the insulin accumulation group, 14 patients had hypoglycemia (21.21%) and 4 patients in the insulin non-accumulation group presented hypoglycemia (10%). The ratio of 4 minute insulin to baseline insulin, ratio of baseline insulin to C-peptide, blood glucose level standard deviation (SDBG) and maximum blood glucose fluctuation amplitude (LAGE) in the insulin accumulation group were significantly higher than those in the insulin non-accumulation group (all P<0.05). Among 66 patients in the insulin accumulation group, 36 patients changed the type of insulin preparafion (insulin treatment group), 30 patients were changed from insulin to oral hypoglycemic agents (oral medication group). After treatment, both SDBG and LAGE in the two groups were significantly lower than before treatment ( P<0.05). Conclusions:With the aggravation of exogenous insulin accumulation, the fluctuation of blood glucose and the proportion of hypoglycemia were significantly increased. There was a characteristic change in islet function in patients with insulin autoimmune syndrome. After arginine stimulation, there was no significant peak of insulin secretion, showing a " high-level" curve. The baseline insulin/C-peptide ratio was significantly increased. The prognosis of EIAS patients is good after timely diagnosis and adjustment of treatment.

Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders

Epstein-Barr virus, a ubiquitous human herpesvirus, can induce both lytic and latent infections that result in a variety of human diseases, including lymphoproliferative disorders. The oncogenic potential of Epstein-Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein-Barr virus encodes a series of products that mimic several growth, transcription and anti-apoptotic factors, thus usurping control of pathways that regulate diverse homeostatic cellular functions and the microenvironment. However, the exact mechanism by which Epstein-Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases often have overlapping clinical symptoms as well as histologic and immunophenotypic features because both lymphoid cell types derive from a common precursor. Accurate classification of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases is a prerequisite for appropriate clinical management. Currently, the treatment of most T/natural killer cell lymphoproliferative diseases is less than satisfactory. Novel and targeted therapies are strongly required to satisfy clinical demands. This review describes our current knowledge of the genetics, oncogenesis, biology, diagnosis and treatment of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases.

Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes

Human papillomaviruses (HPVs) including high-risk (HR) and low-risk (LR) subtypes have distinguishable variation on both genotypes and phenotypes. The co-infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accumulating reports have focused on the interaction between virus and host, particularly the role of human microRNAs (miRNAs) in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miRNAs, miR-875 and miR-3144, and is located in E6 oncogene open reading frame (ORF) and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosis in HPV16-positive cervical cancer cells. This study provides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low expressed human miRNAs on tumour suppression.

Relationship between the serum level of β2-microglobin and international prognostic index and the prognostic analysis of patients with peripheral T-cell lymphoma / 白血病·淋巴瘤

Objective To determine the relationship between the serum level of β2-microglobin (β2-MG)and international prognostic index (IPI) and investigate the role of IPI in predicting the prognosis and making individualized therapy for peripheral T-cell lymphoma (PTCL).Methods Eighty-one patients with PTCL were treated by standard CHOP regimen.The clinical characteristics,response,long-term surival rates and the relationship between serum level of β2-MG and IPI scores were analyzed retrospectively.Results Eighty-one patients were eligible.All of them were treated by CHOP regimen.The overall response rate (RR) was 82.7 ％ with 53.1％ complete remission (CR) rate.The RR of IPI low risk,low-intermediate risk,high-intermediate risk,and high risk were 95.7 ％,87.5 ％,53.8 ％ and 20.0 ％,with CR rate 74.5 ％,37.5 ％,15.4 ％ and 0,respectively (P ＜0.05).The median survival times (MST) were 31.2 months at a median follow-up of 30 months (2-98 months).The acturial 1-,3-,and 5-year overall survival (OS) rates were 83.5 ％,41.8 ％ and 34.7 ％,respectively.The 5-year OS rates of low risk,low-intermediate risk,high-intermediate risk,high risk were 57.3 ％,55.9 ％,0 and 0,respectively (P ＜0.05).The OS rates of low risk group (IPI 0-2 scores) and high risk group (IPI 3-5 scores) were 54.8 ％ and 0,respectively (P ＜0.05).Serum levels of β2-MG were significantly elevated in the high risk group than those in the low risk group.The proportion of abnormal serum level of [β2-MG were also significantly elevated in the high risk group than those in the low risk group.The results of multivariante analysis showed that serum level of β2-MG and IPI scores were independent prognostic factors for PTCL (P＜0.05).Conclusion The serum level of β2-MG with IPI scores system can be uscd for evaluating the prognosis of PTCL patients.

Clinical Outcomes of Patients with Relapse and Refractory Non-Hodgkin's Lymphoma Treated by DHAOx Regimen / 中山大学学报(医学科学版)

[Objective]To evaluate the clinical efficacy and side effects of DHAOx±R regimen in the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL).[Methods]Twenty patients with relapsed or refractory NHL were enrolled into this study in Cancer Center of Sun Yat-sen University.These patients were treated with DHAOx±R regimen(Dexamethasone 20 mg/day intravenous(Ⅳ)on day 1 to day 4,cytarabine 2 000 mg/m~2 3 h Ⅳ,every 12 hours on day 2;oxaliplatin 130 mg/m~2 2 h Ⅳ on day 1;with or without rituximab 375 ms/m~2 on day 0).Six patients were followed by high dose chemotherapy with autologous peripheral blood stem cell transplantation.Response to treatment wag assessed according to The International Working Group Criteria,including CR,PR,SD and PD.Side effects were graded according to WHO criteria,including 0-Ⅳ grades.[Results]Twenty patients received 47 cycles chemotherapy,13 patients(65%)received DHAOx chemotherapy and 7(35%)received DHAOx+R.The response rate(RR)for the whole group was 55%(11/20)with comeplete response(CR)rate 35%(7/20).The response can also be obtained in the patients who were already treated by platinum-based regimen before.The major toxicity Wag myelosuppression.The incidence of grade Ⅲ～Ⅳ neutropenia Wag 35%(16/47),and febrile neutropenia was 17%(8/47).The incidence of grade Ⅲ～Ⅳ thrombocytopenia was 20%(9/47).Eight cycles(17%)occurred mild neumtoxicity.With median follow-up of 12 months,1 and 2-year overall survival rate were 70.6%.[Conclusion]DHAOx was an effective regimen for recurrent and relapsed NHL patients with mild side effects and further investigation is needed.

Long-term Outcomes of Patients with Newly Diagnosed NK/T-cell Lymphoma Treated by EPOCH Regimen / 中山大学学报(医学科学版)

[Objective]This study was aimed to evaluate treatment outcomes and toxicity of continuous-infusion EPOCH regimen for NK/T-cell lymphoma(NK/TCL).[Methods]From June 2003 to June 2008,34 patients including 30 nasal NK/TCL (88.2%)and 4 nasal type NK/TCL(11.8%)received doxorubicin,vincfistine,etoposide over 96 hours infusion with bolus eyelophosphamide and oral predinisone(EPOCH)chemotherapy as first-line treatment.Median cycles of EPOCH administered were 2.5(1-6 cycles).Additional involved field radiation therapy(IFRT)was administered to patients with localized nasal focus after chemotherapy.[Results]Among 34 patients,33 were eligible for response evaluation.The response rate(RR)was 60.6% (20/33)with complete remission(CR)rate of 45.5%(15/33).The RR of patients with nasal NK/TCL was 66.7%(20/30)with CR rate of 50%(15/30).Only one of the 3 nasal type NK/TCL patients achieved stable disease(SD),the other 2 had progressive disease(PD)during chemotherapy.After a median follow-up of 22(2-68)months,the estimated 3-year overall survival rate(OS)was 52.2%.For patients with nasal NK/TCL,the estimated median survival time was not reached,the 3-year OS was 59.4%.For patients with nasal type NK/TCL,the estimated median survival time was only 7 months.The CR rate was 75.0% for localized nasal NK/TCL who received initial EPOCH chemotherapy followed IFRT with the 3-year OS of 75.0%.Major adverse effect was myelosuppression.The incidence of grade Ⅲ～Ⅳ neutropenia was 30.9%.No treatment-related mortality occurred.[Conclusions]EPOCH regiment was effective and well tolerant for nasal NK/TCL.Combined EPOCH chemotherapy followed by IFRT produced promising outcome for patients with localized disease.However,patients with nasal type NK/TCL responded poorly and more efficacious treatment strategies are urgently needed.

Preliminary outcomes of patients with relapsed or refractory NK/T-cell lymphoma treated by SMILE regimen / 白血病·淋巴瘤

Objective To evaluate the efficacy and toxicity of SMILE regimen for NK/T-cell lymphoma. Methods From November 2006 to February 2008, 5 patients with relapsed and 5 with first treatment NK/T-cell lymphoma were involved in this study. These patients were treated with SMILE regimen including methotrexate, isofosfamide, L-asparaginase and etoposide.1 patient were treated with autolognus hematopoietic stem cell transplantation (AHSCT), and 2 patients received local regional radiation following SMILE. Results Among 10 patients, 8 were eligible to response evaluation. The overall response rate for whole group was 50 %(4/8) without complete remission. The overall response rate for both previously untreated and relapsed patients were 50 %(2/4). Major toxicity were bone marrow supression and transient transaminase elevation, the incidence of grade Ⅲ -Ⅳ neutroponia was 65 %, and febrile neutropenia was 25 %, Grade Ⅲ transaminase elevation was 10 %. Other toxicities were mild, no treatment-related mortality occurred. 26.1% cycles discontinued due to severe side effect. Conclusion SMILE may be an effective regimen for relapsed or refractory NK/T-cell lymphoma while significant toxicities were observed. Further investigation is requried before SMILE become a standard combination for relapsed or refractory NK/T-cell lymphoma.