[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

Association between low skeletal muscle mass and subclinical coronary atherosclerosis in asymptomatic individuals evaluated by CT.

AIM: To investigate the associations of skeletal muscle area and density with coronary atherosclerotic plaques and significant stenosis in asymptomatic adults. MATERIALS AND METHODS: A total of 243 consecutive subjects who had voluntarily undergone abdominal unenhanced computed tomography (CT) and coronary CT angiography (CCTA) as part of a general health examination were investigated retrospectively. Skeletal muscle area index (SMI) and skeletal muscle density (SMD) was assessed using CT. Coronary atherosclerotic plaques and stenosis on CCTA were evaluated. The associations of low SMI and low SMD with coronary atherosclerotic plaques and significant stenosis were determined by logistic regression analysis. RESULTS: After adjustment for cardiovascular risk factors, there were significant associations of low SMI or low SMD with atherosclerotic plaque, total significant stenosis, and significant stenosis caused by calcified or mixed plaques (for all p<0.05). In addition, multivariate regression analysis also showed that low SMI was independently associated with calcified plaque (p=0.038) and non-calcified plaque (p=0.006), and individuals with low SMD were more likely to have mixed plaque (p=0.001). CONCLUSION: Assessment of the skeletal muscle on CT help to identify asymptomatic adults at risk for coronary atherosclerosis.

[Primary orbital leiomyosarcoma: a case report].

A 20-year-old girl came to the Tianjin Medical University Eye Hospital because of progressive herniation of her right eye for 3 months. Examination revealed a huge mass behind the right eyeball, which was clinically diagnosed as a space-occupying lesion of the right orbit. Because the tumor was close to the nerve, most of the tumor was resected and pathologically diagnosed as a poorly differentiated leiomyosarcoma. Orbital evisceration was performed later. There was no recurrence during the 10-year follow-up.

[Screening of differently expressed miRNAs and the mechanism of miR-3907 in meibomian gland carcinoma].

Objective: To screen the differently expressed microRNAs (miRNAs) and to explore the effect and mechanism of microRNA-3907 (miR-3907) in meibomian gland carcinoma (MGC). Methods: Experimental research. MGC tissues and para-carcinoma tissues of patients diagnosed with MGC by histopathology were collected from July 2011 to January 2019 in Tianjin Medical University Eye Hospital. The miRNA microarray analysis of MGC and para-carcinoma tissue samples from 5 patients was performed. miR-3907 with a significant up-regulation was selected as a research object. Bioinformatics predicted and dual-luciferase gene reporter assay verified miR-3907 target genes. The protein expression levels of target genes in 18 MGC tissues and 6 para-carcinoma tissue samples were determined by immunohistochemical staining. miR-3907 over-expression, miR-3907 knock-down, target gene knock-down and miR-3907 knock-down with target gene knock-down were respectively performed in MGC cell. The mRNA and protein expressions were validated by real-time PCR and Western blotting after transfection. The cell proliferation and migration ability was detected by cell counting kit-8 and scratch experiment after transfection. The main statistical methods were Fisher's exact test, independent sample t test, two-factor repeated measure analysis of variance. Results: There were 22 differently up-regulated miRNAs and 5 differently down-regulated miRNAs in MGC tissues, of which miR-3907 was significantly up-regulated. Thrombospondin-1 (THBS1) was a target gene of miR-3907 according to bioinformatics and dual-luciferase gene reporter assay. The positive expression rate of THBS1 protein in para-carcinoma tissues (6/6) was significantly higher than that in MGC tissues (5/18), and the difference was statistically significant (P=0.003). Compared with the negative control group, the proliferation ability of the miR-3907 over-expression group was increased at 48 h and 72 h (F=3.70, 2.65; both P<0.01), and the migration rate at 24 h was significantly higher (54.6%±3.4% vs. 34.2%±0.6%; t=8.34, P<0.01). Compared with the negative control group, the proliferation ability of the miR-3907 knock-down group was decreased at 24 h, 48 h and 72 h (F=3.10, 2.17, 3.09; all P<0.05), and the migration rate at 24 h was significantly lower (40.8%±2.8% vs. 69.7%±2.7%; t=10.42, P<0.01). Compared with the negative control group, the THBS1 knock-down group promoted cell proliferation at 24 h, 48 h and 72 h (F=3.84, 3.79, 2.24; all P<0.05), and the migration rate at 24 h was significantly increased (82.5%±1.9% vs. 37.6%±5.1%; t=11.74, P<0.01). Compared with the control group, the miR-3907 knock-down with THBS1 knock-down group increased proliferation at 24 h and 48 h (F=3.97, 3.31; both P<0.05), and the migration healing rate at 24 h was significantly increased (56.9%±2.2% vs. 41.9%±4.3%; t=3.53, P<0.05). Conclusions: There are differently expressed miRNAs between MGC and para-carcinoma tissues, which may be related to the occurrence and development of MGC. miR-3907 in MGC tissues has a significant difference from that in para-carcinoma tissues. Moreover, miR-3907 can play a role in promoting proliferation and migration of MGC by inhibiting the expression of THBS1.

[Proteomic analysis of lacrimal gland adenoid cystic carcinoma with high-grade transformation].

Objective: To analyze the protein expression differences of lacrimal gland adenoid cystic carcinoma (LACC) with high-grade transformation (HGT). Methods: Experimental study. A total of 8 paraffin tissue samples were collected in Tianjin Medical University Eye Hospital from December 2012 to January 2019. According to pathological examination, the samples were divided into the LACC group and the LACC-HGT group, with 4 cases in each group. The LACC group included 2 male samples and 2 female samples, with an average age of 53 years. The LACC-HGT group included 2 male samples and 2 female samples, with an average age of 44 years. Primary cells were cultured from fresh tumor tissue. Isobaric tags for relative and absolute quantification techniques were used to screen the differentially expressed proteins between the two groups, and bioinformatics analysis was conducted for the differentially expressed proteins. Microarray was used to screen differentially expressed mRNAs between LACC and LACC-HGT primary cells. The mass spectrum data were intersected with mRNA microarray data, and quantitative real-time (qRT) PCR was performed to verify the results. Proteomics and microarray data were compared using the independent sample t test. The qRT-PCR data were compared pairwise by one-way analysis of variance. Results: A total of 105 HGT-related differential proteins were detected in this study, including 50 up-regulated proteins and 55 down-regulated proteins. The significantly up-regulated proteins included hemoglobin subunit beta, hemoglobin subunit alpha 1, and collagen type Ⅵ alpha 2 chain; the significantly down-regulated proteins included Cereblon, adenosylhomocysteinase like 2, and ribosomal protein L39 pseudogene 5. Gene ontology analysis results showed that the LACC-HGT differential proteins were mainly located in the cytoplasm, vesicle cavity, and extracellular matrix, had organic acid binding and molecular carrier activity, and participated in the regulation of extracellular matrix composition, immunity, inflammation, apoptosis, and other biological processes. Pathway analysis showed that the LACC-HGT differential proteins were mainly involved in signal pathways such as mitogen-activated protein kinase signal pathway and extracellular matrix proteoglycans and glycan metabolism signal pathway. Protein complex prediction analysis screened out 4 up-regulated protein complexes and 1 down-regulated protein complex. There were 15 LACC-HGT differential proteins that overlapped with mRNA chip differential genes, of which 6 were tumor-related proteins including collagen type XIV alpha 1 chain (COL14A1), EMAP like 4 (EML4), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), NDRG family member 2 (NDRG2), osteoglycin (OGN) an Ras homolog family member C (RhoC). The main function was the movement and migration of tumor cells. The qRT-PCR results showed that the relative expression levels of COL14A1, EML4, ITIH4, NDRG2, OGN, and RhoC in primary LACC-1, LACC-2, LACC-HGT-1, and LACC-HGT-2 cells were significantly different (F=1 675.98, 38.53, 27.37, 16.47, 13.38, 25.22, all P<0.01). For example, the relative expression of COL14A1 in primary LACC-HGT-1 (16.09±0.51) and LACC-HGT-2 (9.96±0.34) cells was significantly higher than that in primary LACC-1 (1.00±0.13) and LACC-2 (0.67±0.08) cells (all P<0.05). Conclusion: There are differentially expressed proteins between LACC-HGT and LACC, among which COL14A1, EML4, ITIH4, NDRG2, OGN, and RhoC may play an important role in LACC-HGT and can be used as potential targets of LACC-HGT in further study. (Chin J Ophthalmol, 2021, 57: 531-539).

[Clinical analysis of adult onset orbital xanthogranuloma].

Objective: To investigate the clinical, imaging and pathological features of adult onset xanthogranuloma. Methods: Retrospective case series study.The clinical data of 4 adult patients with adult onset xanthogranuloma treated in the Tianjin Medical University Eye Hospital from 2015 to 2017 were analyzed. Results: There were 1 male and 3 females, aged 46-73 years, with an average age of 55 years. The duration of eyelid swelling was from 6 months to 6 years. One case was binocular and 3 cases were monocular. There were progressive enlargement of eyelid swelling and subcutaneous cord nodules with poor mobility and no tenderness in all 5 eyes. The eyelid skin in 2 patients (2 eyes) was bulging and yellow. CT examination showed swelling of the eyelids and soft tissue thickening in 5 eyes. There were lacrimal gland enlargement in 3 eyes, upper rectus muscle involvement in 3 eyes, external rectus muscle involvement in 1 eye, lower rectus muscle involvement in 1 eye, superior oblique muscle involvement in 1 eye, and involvement of both the superior and inferior rectus muscles in 1 eye. In 1 patient (1 eye), the lesion showed low and medium signals on T(1) weighted images and T(2) weighted images. Three patients (4 eyes) underwent color Doppler ultrasonography, showing the echo zone in the irregularly shaped eyelid was strong, the internal echo was uneven, the local echo was low, and the boundary was not clear. One of the eyes showed a blood flow signal. All patients underwent surgical resection. The pathological results showed infiltration of foamy tissue cells, Touton cells, lymphocytes and plasma cells. Immunohistochemistry demonstrated 3 patients (4 eyes) expressed CD68, and 1 patient (1 eye) expressed S-100. After 6 months to 2 years of follow-up, 3 patients had no recurrence. One patient developed eye discomfort at 6 months after surgery, and the symptoms were relieved after treatment with triamcinolone. Conclusions: Adult onset xanthogranuloma mainly manifest as eyelid swelling, periorbital mass and skin color changes, generally with no systemic involvement. Imaging examination mainly shows the involvement of soft tissues, lacrimal glands and muscles around the eyelids. The main features of the pathology are infiltration of foamy tissue cells, Touton giant cells, lymphocytes and plasma cells. (Chin J Ophthalmol, 2019, 55: 381-386).

[Preliminary investigation on embolization of orbital vascular malformation with medical glue injection intraoperatively].

Objective: To summarize the treatment outcomes of embolizing orbital vascular malformation with intracavitary injection of medical glue during surgery. Methods: A retrospective case series study was performed on 25 patients with orbital vascular malformation who were treated at Tianjin Medical University Eye Hospital during March 2008 and March 2016. In the 25 patients(25 eyes), 7 were male and 18 were female. The range of age was 2-64 years and the median age was 29 years. The clinical features, operation records, pathological reports and follow-up data were analyzed. Results: The location of vascular malformation involved intraorbital in 11 cases and superficial area of eyelid and(or) face in 5 cases, as for the rest 9 cases, both intraorbital and superficial area were involved. Conjunctiva was involved in 4 patients. Clinical manifestation included intermittent protopsis or mass volumn changed (7 cases), pulsating exophthalmos and vascular murmur (1 case). Imaging examination showed solitary mass with regular shape in 5 cases and space occupying lesion with irregular shape and ill-defined margins in 20 cases. Optic nerve was involved in 7 cases. Surgical debulkling were performed via skin incision on the mass surface (in 3 cases), lateral orbitotomy (in 2 cases), and anterior orbitotomy (in 20 cases). The anterior orbitotomy approaches include skin incision under eyebrow (9 cases), skin incision under lower eyelid eyelash (3 cases), transconjunctiva joint lateral canthus incision (6 cases) and transconjunctiva incision only(2 cases). The intra-orbital part of vascular malformation involved intraconal compartment (10 cases) and extraconal compartment (10 cases). During the operation, vascular malformations were exposed and injected with medical aural and encephalic glue. The amount of injected glue ranged from 0.25 ml to 2.50 ml in divided doses. When the soft venous malformations turned hard, the lesions and remnant glue were fully removed. The whole procedure cause less bleeding and shorter time of operation. Histopathologic diagnosis were intraosseous hemangioma (1 case), arteriovenous malformation (2 cases), venous malformation (22 cases), including varix (4 case) and venous hemangioma (18 cases). One patient suffered from sudden central retinal artery embolism on the third day postoperatively, in which case, visual acuity recovered to 0.6 by timely rescue and appropriate procedure. Topical skin aseptic inflammation took place at the same side of medical glue injection in 3 cases which might be caused by medical glue. These 3 cases had superficial eyelid lesions. Postoperative follow up for patient was conducted from 6 months to 5 years. One young patient underwent recurrent orbital hematoma and many times surgery. Conclusions: Embolization of orbital vascular malformation with medical glue injection intraoperatively can be utilized as an easy approach to control hemorrhage. The surgeon should be careful with the application methods, for instance not to push too quickly, not to pass through the vascular malformation, and to remove the lesions and remnant glue completely, in order to avoid complications. (Chin J Ophthalmol, 2018, 54: 502-508).

[Clinical analysis of patients with orbital nonspecific inflammatory response diseases whose CT or MR images show enlargement of the infraorbital nerves].

Objective: To discuss the clinical features, imaging features, pathological patterns, treatment principles and prognosis of the orbital nonspecific inflammatory response diseases patients whose CT or MR images show enlargement of the infraorbital nerves. Methods: A retrospective case series study. Seven orbital disease patients who were treated at Tianjin Medical University Eye Hospital between March 2013 and May 2017 were included. All patients, imaging pictures showed enlargement of the infraorbital nerve. The medical histories, clinical featuers, imaging features, pathologies, serological examinations, therapeutic processes and prognosis were collected and analyzed. Results: The 7 patients included 4 males and 3 females aged from 55 to 68 years (the average age was 60). Bilateral involvement was present in 5 of 7 patients. The main clinical manifestations include proptosis, increasing of orbital pressure, impairment of visual functions, reduction in ocular motility, facial sensation, periocular ache, involvement of lymph node and salivary gland, etc. CT results showed enlargement of infraorbital nerve, accompanied with or without the destruction of bone. The inflammatory response may involve with extraocular muscles and lacrimal glands, or were shown as lesions with irregular shape and blurred borders. The MR images generally showed equal T(1) and equal T(2) signal, accompanied with evident enlargement of the infraorbital nerve. Of all the 7 patients, 6 underwent operation, and the pathology confirmed that 2 of the 6 were involved with inflammatory pseudotumors and the rest 4 were involved with IgG4-related ophthalmic disease (IgG4-ROD). The level of IgG4 in the serum were detected for 4 patients, the results of 3 were high and the other was normal. Of all the 7 patients,1 patient underwent conservative treatment, but disease recurred for several times, and the serum IgG4 level for the patient was higher than normal;1 inflammatory pseudotumor patient was cured completely only by surgery, and has a favourable prognosis; 1 IgG4-ROD patient accepted glucocorticoid, surgery, radiotherapy and chemotherapy, but disease recurred several times; The rest of the patients accepted glucocorticoid and operation, 2 were sensitive to glucocorticoid, 2 were not sensitive, and 1 involved with recurrence. Conclusions: If orbital nonspecific inflammation response was accompanied with enlargement of infraorbital nerve, it is suggested that patient is more likely to be involved with IgG4-ROD;Pathology and serological tests can be used for the diagnosis of IgG4-ROD, however treatment effect appears to be poor for most patients, and patients prone to relapse. (Chin J Ophthalmol, 2018, 54: 515-519).

Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis.

OBJECTIVES: The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population. DESIGN, SETTING AND PARTICIPANTS: Random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis. All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010. Patients with established dementia before the start of treatment were excluded. Baseline characteristics were matched (by propensity score) in those who did and did not receive statins. RESULTS: A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up. Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics. Adjusted hazard ratios (HRs) for dementia were significantly inversely associated with total or daily equivalent statin dosage (total accumulated dose: HRs 0.829, 0.720 and 0.385 from T1 to T3 vs. control, P < 0.001 for trend; mean daily dose: HRs 0.667, 0.798 and 0.503 from T1 to T3 vs. control, P < 0.001). The results remained robust after propensity adjustment. CONCLUSION: Independent of traditional risk factors, there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins. The more potent statins (e.g. atorvastatin and rosuvastatin) seemed to be particularly effective in the prevention of dementia.

Cryopreservation of germinal vesicle stage porcine oocytes based on intracellular ice formation assessment.

This study aimed at evaluating the feasibility of slow freezing for cryopreservation of germinal vesicle (GV) stage porcine oocytes. In this study, intracellular ice formation (IIF) characteristics of GV porcine oocytes were investigated by using a thermoelectric cooling (TEC) cryomicroscope system. This cryomicroscope system used a thermoelectric cooling (TEC) chip in its cold stage as a heat sink and employed a PID control algorithm to achieve accurate temperature control. The temperature was controlled to a range between 70 degree C and -55 degree C with an accuracy of +/- 0.5 degree C. Five constant cooling rates of 24, 12, 6, 3 and 1.5 degree C/min were tested in experiments in freezing GV porcine oocytes from 20 degree C to -50 degree C in an NCSU-23 medium plus 2.0 M DMSO. The IIF temperature of each individual oocyte was recorded and cumulative IIF probabilities were calculated for each cooling rate. The total cumulative probabilities of IIF temperature distribution were 100 percent, 100 percent, 50.0 percent, 54.3 percent and 58.6 percent at cooling rates of 24, 12, 6, 3 and 1.5 degree C/min, respectively. A Weibull distribution model was found to adequately describe the distribution of IIF temperatures of GV porcine oocytes for the cooling rates tested (R2 = 0.858 +/- 0.09). The IIF experimental results indicate that cooling rates of 6, 3 and 1.5°C/min could be considered as possible cryopreservation protocols. Further experiments were performed to examine the feasibility of using these protocols to cryopreserve GV porcine oocytes. After 44 h of in-vitro maturation in NCSU-23, the survival of thawed oocytes was checked. Porcine oocytes developed from the GV stage to the MII stage by using Hoechst 33258 staining, followed by Lacmoid staining as a secondary check. Normalized survival rates of 37.7 +/- 4.6 percent, 45.0 4.4 percent and 45.4 +/- 5.9 percent were obtained for GV oocytes frozen at 1.5, 3 and 6 degree C/min, respectively. The experimental results indicate that slow freezing is a feasible approach for cryopreservation of GV porcine oocytes when cooling rate is properly selected. This study also demonstrated an efficient approach for investigating optimal cooling rates by assessing the IIF characteristics of GV porcine COCs.

Stable dispersions of hybrid nanoparticles induced by stereocomplexation between enantiomeric poly(lactide) star polymers.

We report the formation and characterization of stable dispersions of hybrid nanoparticles in solution formed via stereocomplexation of enantiomeric poly(lactide) hybrid star polymers. The hybrid starlike polymers, having polyhedral oligomeric silsesquioxane (POSS) nanocages as the core and either poly(L-lactide) (PLLA) or poly(D-lactide) (PDLA) as the arms, are synthesized via ring-opening polymerization of lactide using octafunctional POSS as the macroinitiator. In the solid state, differential scanning calorimetry and wide-angle X-ray scattering measurements confirmed the formation of the stereocomplex in the mixture of POSS-star-PLLA and POSS-star-PDLA (50:50, wt %). In a solution of the same mixture in tetrahydrofuran (THF), sterocomplexation leads to formation of hybrid nanaoparticles. Detailed accounts of the nanoparticle formation and influence of aging and concentration have been presented. It was observed that at low concentration the stereocomplexed nanaoparticles remain stable over 45 days and are not sensitive to dilution, suggesting the formation of a stable hybrid nanoparticle dispersion in solution. In contrast, the aggregates of the individual POSS-star-PLLA or POSS-star-PDLA in THF, formed via weak solvophobic interactions, tended to disintegrate into smaller aggregates on dilution. Exploiting the PLLA-PDLA stereocomplexation with an appropriate molecular design can be a versatile route to develop stable organic/inorganic hybrid nanoparticle dispersions.

Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

Nano-mechanical properties of fluoride-treated enamel surfaces.

Calcium-fluoride-like deposits play a key role in caries prevention by topical fluoride. Previous microhardness analyses have introduced errors due to a substrate effect, and thereby could not substantiate the early loss of these deposits. To address this question, we applied Atomic Force Microscopy (AFM) and a nano-indentation technique in this study to characterize the nano-mechanical properties and topographic structure of enamel surfaces following topical fluoride treatment. The deposits were found to have a low nano-hardness and a high nano-wear depth, which explains the early loss of calcium-fluoride-like deposits. However, a 22% increase in the fluoride concentration could still be detected on the treated enamel surface following the removal of the surface deposits, justifying the long-term effectiveness of topical fluoride treatment.

Highly purified CD38+ and CD38- sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin.

CD38 expression is an important prognostic marker in chronic lymphocytic leukemia (CLL) with high levels of CD38 associated with shorter overall survival. In this study, we used gene expression profiling and protein analysis of highly purified cell-sorted CD38(+) and CD38(-) chronic lymphocytic leukemia cells to elucidate a molecular basis for the association between CD38 expression and inferior clinical outcome. Paired CD38(+) and CD38(-) CLL cells derived from the same patient were shown to be monoclonal by V(H) gene sequencing but despite this, CD38(+) CLL cells possessed a distinct gene expression profile when compared with their CD38(-) sub-clones. Importantly, CD38(+) CLL cells relatively over expressed vascular endothelial growth factor (VEGF) and appeared to preferentially utilize an internal autocrine VEGF survival loop. Elevated VEGF expression was associated with increased expression of the anti-apoptotic protein Mcl-1. Inhibition of VEGF receptor signaling also resulted in a reduction in cell viability. In contrast, exogenous VEGF caused a significant increase in CD38(-) CLL cell viability and a marked induction of Mcl-1; both effects were less obvious in CD38(+) CLL cells. Taken together, our data provide a biological rationale for the poor prognosis of CD38(+) CLL and indicate that both VEGF and Mcl-1 may prove to be useful therapeutic targets.

Anti-site-induced diverse diluted magnetism in LiMgPdSb-type CoMnTiSi alloy.

The effect of three kinds of anti-site disorder to electronic structure and magnetic properties of the LiMgPdSb-type CoMnTiSi alloy are investigated. It was found the Mn-Ti anti-site disorder can induce the diluted magnetism in CoMnTiSi matrix. The magnetic structure has an oscillation between the ferromagnetic and antiferromagnetic states with the different degree of Mn-Ti anti-site disorder. Two novel characteristics: the diluted antiferromagnetic half-metallicity and the diluted zero-gap half-metallity are found in the different degree range of the Mn-Ti anti-site disorder. The Co-Mn and Co-Ti anti-site disorder have little effect on the magnetic properties. The width of energy gap and the intensity of DOS at the Fermi level can be adjusted by the degree of Co-Mn or Co-Ti anti-site disorder. The independent control to the carrier concentration and magnetization can be realized by introducing the different anti-site disorder.

Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins.

Little axonal regeneration occurs after spinal cord injury in adult mammals. Regrowth of mature CNS axons can be induced, however, by altering the intrinsic capacity of the neurons for growth or by providing a permissive environment at the injury site. Fetal spinal cord transplants and neurotrophins were used to influence axonal regeneration in the adult rat after complete spinal cord transection at a midthoracic level. Transplants were placed into the lesion cavity either immediately after transection (acute injury) or after a 2-4 week delay (delayed or chronic transplants), and either vehicle or neurotrophic factors were administered exogenously via an implanted minipump. Host axons grew into the transplant in all groups. Surprisingly, regeneration from supraspinal pathways and recovery of motor function were dramatically increased when transplants and neurotrophins were delayed until 2-4 weeks after transection rather than applied acutely. Axonal growth back into the spinal cord below the lesion and transplants was seen only in the presence of neurotrophic factors. Furthermore, the restoration of anatomical connections across the injury site was associated with recovery of function with animals exhibiting plantar foot placement and weight-supported stepping. These findings suggest that the opportunity for intervention after spinal cord injury may be greater than originally envisioned and that CNS neurons with long-standing injuries can reinitiate growth, leading to improvement in motor function.

Isolation and characterization of a low-molecular weight seed protein from Ricinus communis.

A seed protein with an apparent molecular weight of 5000 has been isolated and purified from Ricinus communis. This protein has a very high content of glutamine and an unusual ultraviolet absorption spectrum. The amino-terminal sequence of 22 residues determined by automatic Edman degradation is: NH2-Pro-Ser-Gln-Gln-Gly-Cys-Cys-Gly-Gln-Ile-Gln-Glu-Gln-Gln-Asn-Leu-Arg-Gln-Cys-Gln-Glu-Tyr-.

Detection of Helicobacter pylori by polymerase chain reaction assay using gastric biopsy specimens taken for CLOtest.

The concordance rate between a rapid urease test (CLOtest) and polymerase chain reaction (PCR) assay for the detection of Helicobacter pylori in gastric biopsy samples was investigated. To avoid the bias produced by patchy distribution of the organism in the stomach, the samples used for these two tests were not obtained from two different sites of the antrum. Instead, the PCR assay was performed with the the same biopsy sample that was taken for the CLOtest. Among 82 biopsy samples included for this study, 56 were positive and 26 were negative by CLOtest. Of the 56 CLOtest-positive samples, 52 (93%) were also positive by PCR assay, and of the 26 CLOtest-negative samples, 20 (78%) were negative by PCR assay. The total concordance rate of these two tests was 87.6%. Of the 4 cases with CLOtest-positive and PCR-negative results, 3 had been treated with long-term H2 blockers. Of the 6 patients with CLOtest-negative and PCR-positive results, 4 suffered from recurrent or poorly healing duodenal ulcers. Interestingly, a significantly lower density of the PCR products was observed during electrophoresis analysis for all the 6 cases, presumably due to a small number of H. pylori in these samples. These results indicated that PCR might be used as a complementary assay for CLOtest. False negative results by CLOtest might occur when only a small amount of H. pylori was present in the samples, which could be detected by subsequent PCR assays using the same biopsy specimens. The clinical significance of such CLOtest-negative and PCR-positive cases requires further study.

Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells.

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.