BACKGROUNDIn tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model.

METHODS(99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity.

RESULTS(99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01).

CONCLUSIONThis study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.

Animals ; Annexin A5 ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Apoptosis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Histidine ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Mice ; Organotechnetium Compounds ; Paclitaxel ; therapeutic use ; Radiopharmaceuticals

OBJECTIVETo investigate the possible role of inflammation factors in the pathogenesis of impaired glucose tolerance (IGT) with concurrent obstructive sleep apnea/hypopnea syndrome (OSAHS) in pregnant women.

METHODSTwenty-five pregnant women with IGT and concurrent OSAHS and 35 pregnant women with IGT but not OSAHS were monitored for all night polysomnography (PSG), and the apnea hypopnea index (AHI) and the lowest pulse oxygen saturation (LSpO2) were recorded. The body mass index, glycated serum protein (GSP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured in these women.

RESULTSIL-6 and TNF-α levels increased significantly in women with IGT and OSAHS as compared with those in women without OSAHS. AHI showed significant positive correlations to GSP, IL-6 and TNF-α, whereas LSpO2 was inversely correlated to GSP, IL-6 and TNF-α. IL-6 and TNF-α were significantly correlated to GSP, with correlation coefficients of 0.510 and 0.476, respectively.

CONCLUSIONThe inflammatory factors may play important roles in IGT complicated by OSAHS in pregnant women, and as a potential risk factor, OSAHS may contribute to the occurrence of progression of IGT.

Adult ; Blood Glucose ; metabolism ; Female ; Glucose Tolerance Test ; Humans ; Interleukin-6 ; blood ; Oximetry ; Oxygen ; blood ; Oxygen Consumption ; physiology ; Pregnancy ; Pregnancy Complications ; blood ; Sleep Apnea Syndromes ; blood ; physiopathology ; Tumor Necrosis Factor-alpha ; blood

Fluorescence intraoperative cholangiography (IOC) is a potential alternative for identifying anatomical variation and preventing iatrogenic bile duct injuries by using the near-infrared probe indocyanine green (ICG).However,the dynamic process and mechanism of fluorescenceIOC have not been elucidated in previous publications.Herein,the optical properties of the complex of ICG and bile,dynamic fluorescence cholangiography and iatrogenic bile duct injuries were investigated.The emission spectrum of ICG in bile peaked at 844 nm and ICG had higher tissue penetration.Extrahepatic bile ducts could fluoresce 2 min after intravenous injection,and the fluorescence intensity reached a peak at 8 min.Inaddition,biliary dynamics were observed owing to ICG excretion from the bile ducts into the duodenum.Quantitative analysis indicated that ICG-guided fluorescence IOC possessed a high signal to noise ratio compared to the surrounding peripheral tissue and the portal vein.Fluorescence IOC was based on rapid uptake of circulating ICG in plasma by hepatic cells,excretion of ICG into the bile and then its interaction with protein molecules in the bile.Moreover,fluorescence IOC was sensitive to detect bile duct ligation and acute bile duct perforation using ICG in rat models.All of the results indicated that fluorescence IOC using ICG is a valid alternative for the cholangiography of extrahepatic bile ducts and has potential for measurement of biliary dynamics.

OBJECTIVETo study the application value of normal sperm morphology on the outcomes of classic in vitro fertilization and embryo transfer (IVF-ET).

METHODSThis study included 659 infertile couples admitted to our center for IVF-ET. Based on the percentage of morphologically normal sperm (MNS), we divided the patients into groups A (n = 112, MNS < 2%), B (n = 180, MNS > or = 2 - < 4%), C (n = 74, MNS > or = 4 - < 5%), and D (n = 293, MNS > or = 5%), and compared the rates of fertilization, normal fertilization, embryos obtained, biochemical pregnancy, clinical pregnancy, implantation, and live birth among different groups.

RESULTSThe mean fertilization rate was significantly higher in groups C (71.90%) and D (72.89%) than in A (57.97%) and B (63.29%) (P < 0.05), with no remarkable differences either between A and B (P > 0.05) or between C and D (P > 0.05). The normal fertilization rate was also significantly higher in group D (57.16%) than in A (46.52%) and B (50.89%) (both P < 0.05) as well as in C (54.67%) than in A (P < 0.05). The rate of embryos obtained, too, was markedly higher in group D (55.62%) than in B (45.75%) (P < 0.05), but none with remarkable difference from other groups (all P > 0.05). There were no statistically significant differences among the four groups in the rates of biochemical pregnancy, clinical pregnancy, implantation, abortion, and live birth (all P > 0.05).

CONCLUSIONThe rate of MNS had some influence on IVF-ET, and 5% MNS exhibited a higher value than 4% MNS in predicting the outcomes of IVF.

Adult ; Embryo Implantation ; Female ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies ; Spermatozoa ; cytology

Biomarkers ; blood ; Cell-Derived Microparticles ; metabolism ; Coronary Disease ; blood ; Humans ; Inflammation ; blood

AIM:To observe the effects of panaxadiol saponins(PDS)on up-regulation of MAPK/ERK signal pathway in bone marrow cells and increase in regulatory T(Treg)cells in spleen tissue of aplastic anemia(AA)mice,and to explore the mechanisms.METHODS:For preparation of immune-mediated AA model,BALB/c mice were exposed to sublethal dose(5.0 Gy)of [60Co]-γradiation, followed by transplantation of lymphocytes from DBA /2 donor mice. BALB/c mice(n=60)were randomly divided into 6 groups,including normal mouse group,AA model group,PDS treat-ment groups at low,medium and high doses,and cyclosporine group as positive control.PDS and cyclosporine were given by gavage for 14 d.The peripheral blood cell counts and bone marrow pathological examination were tested.The protein levels of MEK1/2,p-MEK1/2,ERK1/2 and p-ERK1/2 in the bone marrow cells were analyzed by Western blot and im-munohistochemistry experiment.Flow cytometry was used to detect the proportion of Treg cells in spleen tissue of each group.RESULTS:The peripheral blood cell counts were significantly decreased in AA mouse group as compared with nor -mal mouse group(P<0.05).The bone marrow sections showed markedly inhibition status of hematopoiesis and the de -crease in cellularity.In response to PDS treatment,the peripheral blood cell counts and Treg cells in the spleen tissues of AA mouse treated with PDS were significantly increased in a dose-dependent manner(P<0.05).Treatment with PDS at medium and high doses up-regulated the protein levels of MEK1/2,p-MEK1/2,ERK1/2 and p-ERK1/2 in the bone mar-row of AA mice(P<0.05).CONCLUSION:PDS is effective to enhance recovery of hematopoietic function in AA mice. This effect may be related to up-regulating multiple protein kinases of MAPK/ERK signal pathway in the bone marrow cells of AA mice.In addition,PDS has an impact on immune function of AA mice.

Objective: To investigate the clinical and imaging features of myelin oligodendrocyte glycoprotein antibody(MOG) encephalomyelitis in children. Methods: The clinical, laboratory finding, imaging and follow-up data of 13 children with MOG encephalomyelitis (MOG-EM) diagnosed by Children′s Hospital of Nanjing Medical University from December 2016 to December 2018 were retrospectively analyzed. Results: Among the 13 children, 4 cases were male and 9 cases were female, the median age was 8 years old and 1 month.Symptoms of the first episode included fever, drowsiness in 2 cases, visual acuity in 5 cases, convulsions in 3 cases, urinary retention in 2 cases, and ataxia in 2 cases.Abnormalities were found in 12 cases by the head magnetic resonance imaging(MRI), most of which showed extensive or isolated subcortical white matter lesions, and a few deep gray matter nuclei and brainstem were involved; 3 cases of spinal MRI abnormalities, mainly characterized by long segmental transverse myelitis; 6 cases optic nerve MRI abnormalities were found in 6 cases, manifested as disease side optic nerve or optic chiasm abnormal signals; the titer of serum MOG antibody was 110-1320 in 13 cases.All children responded well to glucocorticoids and gamma globulin, and all symptoms were alleviated after treatment.Two patients had recurrence during the follow-up period, which was characterized by optic neuritis.After azathioprine addition, there was no recurrence after 1 to 2 years of follow-up. Conclusions Children with MOG antibody encephalomyelitis present a decline in visual acuity commonly.The images are mainly acute disseminated encephalomyelitis-like changes, immunosuppressive therapy is effective, generally with a better prognosis.

BACKGROUNDAvailable drug-eluting stents (DES) have achieved great success in reducing restenosis rates. Recently, investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid (PLGA) polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.

METHODSA prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients (TIVOLI group: 168 patients; ENDEAVOR group: 156 patients) at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions (lesion length &le; 40 mm, reference vessel diameter 2.25-4.00 mm). The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years, including major adverse cardiac events (cardiac death, myocardial infarction, or target-lesion revascularization) and stent thrombosis.

RESULTSAngiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group (in-stent (0.25 ± 0.33) mm vs. (0.57 ± 0.55) mm, diff (95%CI) -0.23 (-0.32, -0.14), P < 0.0001; in-segment (0.25 ± 0.33) mm vs. (0.42 ± 0.55) mm, diff (95%CI) -0.13 (-0.23, -0.02), P = 0.0083). The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group (P = 0.0229). Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization (4.2% vs. 9.6%, P = 0.0495) at 2 years. The two-year major adverse cardiac events (MACE) rate was lower for the TIVOLI group, but not significantly different (6.6% vs. 10.9%, P = 0.1630).

CONCLUSIONSTIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization (TLR) at 2 years. The MACE rate at 2 years was comparable in both groups.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Artery Disease ; drug therapy ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Polymers ; chemistry ; Sirolimus ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Fanconi-Bickel syndrome (FBS, OMIM 227810), a rare autosomal recessive disorder of carbohydrate metabolism, is caused by SLC2A2 (GLUT2) mutations. The study reported 3 cases of FBS who were confirmly diagnosed by SLC2A2 gene analysis. The three patients showed typical features like glycogen storage disease and proximal renal tubular nephropathy. Homozygous splice-site mutation IVS8+5G>C (c.1068+5 G>C) was found in patient A and homozygous nonsense mutation c.1194T>A (p.Tyr398X) in patient B. Patient C harboured a missense mutation c.380C>A (p.Ala127Asp) and a de novo insertion c.970dupT (p.324TyrfsX392) which was not inherited from her parents. Four mutations were identified in the 3 Chinese FBS patients. Except IVS8+5G>C mutation, the other 3 mutations were novel in Chinese population. To the best of our knowledge, patient C may be the first FBS case worldwide with de novo mutation.
Fanconi Syndrome ; genetics ; Female ; Glucose Transporter Type 2 ; genetics ; Humans ; Mutation

Cancer is the leading cause of death in China． In recent years，Chinese government has advocated tremendous efforts in advancing research on cancer prevention and control，and has made great advancement． In this review，we briefly summarized the current research progress on cancer epidemiology in China，including the aspects of cancer burden，cancer－related risk factors and its intervention，screening and early detection，implementation plan of cancer prevention and control ( 2019－2022) ，in order to provide technical support and theoretical evidence in implementing effective cancer prevention and control in China in the future．