Epidemiological characteristics of patients with Hutchinson-Gilford progeria syndrome and progeroid laminopathies in China.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. This study aims to investigate the epidemiological and genotypic characteristics of patients with HGPS/PL in China. METHODS: Using a cross-sectional study design, general characteristics and genotypic data of 46 patients with HGPS/PL from 17 provinces in China were analyzed. RESULTS: Among the 46 patients with HGPS/PL, 20 patients are HGPS, and the rest are PL; the identified total prevalence of HGPS/PL is 1/23 million. Among 42 patients with gene reports, 3 carried compound heterozygous mutations in the ZMPSTE24 while the other 39 carried LMNA mutations. Among PL, LMNA c.1579 C > T homozygous mutation was the most common. The onset of classic genotype HGPS is skin sclerosis in the first month after birth. The primary clinical manifestations of PL patients include skin abnormalities, growth retardation, and joint stiffness. The median age of onset for PL was 12 (6,12) months. CONCLUSIONS: In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL were located in LMNA, and the rest in ZMPSTE24. Most patients of HGPS/PL have skin abnormalities as the earliest manifestation. Compared to PL, the classic genotype HGPS starts earlier. IMPACT STATEMENT: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. To date, there is a paucity of epidemiological data related to HGPS/PL in China. This study first examined the genotypic, phenotypic, and prevalence characteristics of 40-50% of the cases of HGPS/PL in mainland China through a collaborative international registry effort. In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL are located in LMNA. LMNA c.1579 C > T homozygous mutations are the most common form of gene mutations among the Chinese PL population.

Hutchinson-Gilford progeria syndrome complicated with stroke: A report of 2 cases and literature review.

Background: Hutchinson-Gilford Progeria Syndrome (HGPS) is a ultrarare, fatal autosomal dominant disorder. The pathogenesis of the disease is a mutation in LMNA, which leads to the accumulation of progerin in cells, impairing the normal physiological functions. Stroke and transient ischemic attack seriously affect the survival rate and quality of life of HGPS children, although the literature of this aspect is limited. This study summarizes the clinical manifestations and related imaging features of HGPS children with stroke to improve pediatric clinicians' understanding of this disease. Case presentation: Both children have a de novo heterozygous mutation of LMNA [c.1824C > T ( p.G608G)]. Case 1. At the age of 4 years, the child had a cerebral infarction, which manifested as blurred vision and communication disturbance. Multiple abnormal signals were observed on the head MRI in the bilateral frontoparietal cortex, bilateral semiovale center, lateral ventricle, and deep frontal and parietal lobes. Multiple abnormal white matter signals on head MRA: bilateral internal carotid artery stenosis with basilar artery, and bilateral thickening of the posterior communicating artery. Case 2. At the age of 8.5 years, the child presented with cerebral infarction, which manifested as decreased muscle strength and choking after drinking water. MRI of the head showed that the bilateral frontal lobes were small with multiple abnormal signal shadows in the bilateral center of the semiovale and the lateral ventricle. Brain MRA revealed that the bilateral internal carotid arteries (C5-7) were narrow and uneven in thickness, and the A1 segment of the left anterior cerebral artery was narrower than the contralateral one. After symptomatic and supportive treatment, the two children improved. Conclusion: Hemiplegia and physical weakness are the most prevalent stroke symptoms in children with HGPS, followed by headache, epilepsy, dysarthria, and psychosis as the primary manifestation in some children. Stroke in children with HGPS is mostly ischemic cerebral infarction caused by an insufficient cerebral blood supply. Pediatric cerebral infarction mainly occurs in the large vascular area, involving all vascular areas, with the internal carotid artery and middle cerebral artery being the most commonly accumulated.

[Orthogonal analysis of physical parameters optimization of microbubble-enhanced sono-thrombolysis].

OBJECTIVE: To investigate the main influence factors of microbubble-enhanced sono-thrombolysis by an orthogonal array experimental design (OAD) and to confirm the optimal parameters of microbubble-enhanced sono-thrombolysis in vitro. METHODS: The peripheral blood was collected from 50 female Sprague Dawley rats to prepare the standard plasma, and then 100 microL standard plasma and 25 microL thrombin (0.15 U/microL) were mixed and incubated in 37 degrees C water bath for 3, 6, 12, and 24 hours respectively to prepare corresponding standardized thrombus. The physical parameters for the designed experiments included transmit powers of ultrasound (factor A: 5%, 25%, 50%, and 100%), microbubble volume (factor B: 50, 100, 200, and 400 microL), urokinase (UK) concentration (factor C: 100, 200, 400, and 800 U/mL), and thrombolysis time (factor D: 10, 20, 30, and 40 minutes), respectively. Then an OAD based on four parameters and four levels [L16(4(5))] was employed to optimize the thrombolysis conditions. The ultrasound frequency was 1.82 MHz. HE staining and scanning electron microscope (SEM) were used to observe the clots before and after thrombolysis. The thrombolysis rate was measured. RESULTS: HE staining and SEM observation showed that the fibrin was dissolved after thrombolysis. According to the OAD, the optimal parameter combination was C4-D4-A1-B4, indicating UK concentration 800 U/mL, thrombolysis time 40 minutes, transmit power of ultrasound 5%, and microbubble volume 400 microL, respectively. The four factors above had significant influence on thrombolysis (P < 0.05), and UK concentration was the most significant. There were significant differences in thrombolysis between different thrombolysis time (P < 0.05). CONCLUSION: Under the condition of fixed ultrasound frequency, microbubble-enhanced sono-thrombolysis efficiency is better in lower transmit power of ultrasound, higher UK concentration, longer thrombolysis time, higher microbubble volume, and shorter thrombolysis time.

[Effect of diagnostic ultrasound-mediated microbubble contrast and urokinase on augmentation thrombolysis and optimization of the major parameters: an in vitro study].

OBJECTIVE: To investigate the efficacy of diagnostic ultrasound and microbubble contrast (MB) on enhancing thrombolysis in combination with urokinase (UK) and to determine the optimal combination for thrombolysis in vitro. METHODS: Four types of standardized red thrombus were prepared in vitro, including 3-hour-old (3 h), 6-hour-old (6 h), 12-hour-old (12 h), and 24-hour-old (24 h). The major parameters for the designed experiments included transmit powers of ultrasound (factor A, 5%, 25%, 50%, 100%), MB volumes (factor B, 50 microL, 100 microL, 200 microL, 400 microL), UK concentrations (factor C, 100 U/mL, 200 U/mL, 400 U/mL, 800 U/mL), and lysis time (factor D, 10 min, 20 min, 30 min, 40 min). An orthogonal array experimental design (OAD) based on four levels L16 (4(5)) of the above four parameters was employed to optimize the thrombolysis conditions. During the procedure of thrombolysis, the diagnostic ultrasound frequency was fixed at 1.82 MHz. The histopathological changes measured by HE staining and scanning electron microscope (SEM) were carried out to observe the clots before and after thrombolysis. The loss of clot weight before and after treatment was measured to determine the lysis efficiency (LE). Analysis of variance (ANOVA) was performed to assess the LE according to the L16 (4(5)) matrix. RESULTS: The HE staining and SEM observation of thrombolysis under the following experimental conditions of 5% ultrasound transmit power, 400 microL MB volume, 800 U/mL UK concentration, and 40 min lysis time showed remarkable disaggregation of fibrin nets. The above four factors had significant impact on thrombus (all P < 0.05), among which UK concentrations (factor C) was the most significant one. The optimal scheme was determined as a C4-D4-A1-B4 mode, with UK concentration 800 U/mL, lysis time 40 min, transmit power 5%, and MB volume 400 microL, respectively. The LE curves for 3h clots were superior to the others. The lysis efficiencies for the clots showed significant differences among different type of thrombus (all P < 0.05). CONCLUSION: 1.82 MHz diagnostic ultrasound and microbubble contrast can be applied to augment thrombolysis in vitro even with a transmit power as low as 5%. Under the condition of fixed ultrasound frequency, the LE of thrombus increase with increased UK concentrations, lysis time and MB volumes, and decrease with increased thrombus ages.

[Characteristics of the patients with primary Sjögren's syndrome complicated with lymphoma].

OBJECTIVE: To improve the understanding of diagnosis and treatment of patients with primary The data of clinical features, laboratory Sjögren's syndrome (pSS) complicated with lymphoma. METHODS: findings, therapeutic response and follow-up of patients with primary Sjögren's syndrome complicated with lymphoma from January 2006 to January 2011 in our single center were retrospectively analyzed. RESULTS: Totally twelve inpatients with pSS complicated with lymphoma were diagnosed, which accounted for 1.29% of newly-diagnosed lymphoma inpatients during the same period. The characteristic immunologic changes were hyperimmunoglobulinemia, hypocomplementemia and decrease of CD4 T cell number. In our study, non-Hodgkin's lymphoma (NHL) was the most common type, and the main pathological subtype was diffuse large B cell lymphoma (DLBCL). Most of the patients were in advanced stages, Ann Arbor stage IIl-IV, at diagnosis. Extranodal involvement was common, most frequently in the livers and the lungs. All of the patients received combination chemotherapy. Most of the NHL patients received CHOP/R-CHOP-like regimens, and the Hodgkin's lymphoma (HL) patient received AVD regimen. The median follow-up time was 27 months (range 1-56 months). In terms of median survival time and overall survival there were no statistical significant differences between both low C3 and low C4 group and control group (P > 0.05). In terms of median survival time and overall survival there were no statistical significant differences between rituximab treatment group and control group (P > 0.05). CONCLUSION: The patients with pSS complicated with lymphoma were not uncommon clinically. Hypocomplementemia could not be identified as a risk factor for the prognosis of pSS complicated with lymphoma in our study. Although expected prognosis of these patients was unfavorable, we found that treatment with rituximab combination chemotherapy could not improve the therapeutic effects and survival of patients with pSS complicated with lymphoma.

[Antitumor effects of matrix protein of vesicular stomatic virus on EL4 lymphoma mice].

OBJECTIVE: To explore antitumor effects of plasmid pcDNA3. 1-MP encoding matrix protein of vesicular stomatitis virus (VSV) complexed with cationic liposome (DOTAP:CHOL) in mice with EL4 lymphoma. METHODS: C57BL/6 mouse model with EL4 lymphoma was established. Sixty mice bearing EL4 lymphoma were divided randomly into five groups including Lip-MP, Lip-pVAX, Lip, ADM and NS groups, which were intravenously injected with liposome-pcDNA 3. 1-MP complex, liposome-pVAX complex, empty liposome, Adriamycin and normal saline respectively every three days. Tumor volumes and survival time were monitored. Microvessel density and tumor proliferative index in tumor tissues were determined by CD31, Ki-67 immunohistochemistry staining, meanwhile the tumor apoptosis index was measured by TUNEL method. RESULTS: From 6 days after treatments on, the tumor volume in Lip-MP group was much smaller than that in Lip-pVAX, Lip and NS group (P < 0.05). The median survival time of mice in Lip-MP group, 44 days after inoculation of tumor cells, was significantly higher than that in other groups (P < 0.05), which was 39 days, 38.5 days and 34 days in Lip-pVAX, Lip and NS groups respectively. The MVD value in tumor tissues in Lip-MP group was less than that in Lip-pVAX, Lip and NS groups (P < 0.05). Ki67 staining revealed that Lip-MP complex apparently suppressed the proliferation of EL4 tumor cells in vivo (P < 0.05). TUNEL assays showed that apoptosis index of tumor cells in Lip-MP group, 10.60 +/- 1.71, was much higher than that in other three groups (P < 0.05). CONCLUSIONS: Lip-MP complex, the plasmid encoding matrix protein of VSV (VSV-MP) encapsulated in cationic liposome, significantly inhibited the growth of tumor and prolonged the survival of mice bearing EL4 lymphoma, which may be related to the induction of tumor cell apoptosis, inhibition of tumor angiogenesis, and suppression of tumor cell proliferation.