The HIV capsid mimics karyopherin engagement of FG-nucleoporins.

HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus1,2. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore3. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport4. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.

Experimental demonstration of optical stochastic cooling.

Particle accelerators and storage rings have been transformative instruments of discovery, and, for many applications, innovations in particle-beam cooling have been a principal driver of that success1. Stochastic cooling (SC), one of the most important conceptual and technological advances in this area2-6, cools a beam through granular sampling and correction of its phase-space structure, thus bearing resemblance to a 'Maxwell's demon'. The extension of SC from the microwave regime up to optical frequencies and bandwidths has long been pursued, as it could increase the achievable cooling rates by three to four orders of magnitude and provide a powerful tool for future accelerators. First proposed nearly 30 years ago, optical stochastic cooling (OSC) replaces the conventional microwave elements of SC with optical-frequency analogues and is, in principle, compatible with any species of charged-particle beam7,8. Here we describe a demonstration of OSC in a proof-of-principle experiment at the Fermi National Accelerator Laboratory's Integrable Optics Test Accelerator9,10. The experiment used 100-MeV electrons and a non-amplified configuration of OSC with a radiation wavelength of 950 nm, and achieved strong, simultaneous cooling of the beam in all degrees of freedom. This realization of SC at optical frequencies serves as a foundation for more advanced experiments with high-gain optical amplification, and advances opportunities for future operational OSC systems with potential benefit to a broad user community in the accelerator-based sciences.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

p120 regulates E-cadherin expression in nasal epithelial cells in chronic rhinosinusitis.

BACKGROUND: The epithelial barrier plays an important role in the regulation of immune homeostasis. The effect of the immune environment on E-cadherin has been demonstrated in previous studies. This discovery prompted new research on the targeting mechanism of E-cadherin in chronic rhinosinusitis (CRS). METHODS: E-cadherin and p120 expression was determined by quantitative RT-PCR, and western blot. The interaction between E-cadherin and p120 was assessed by immunofluorescence staining and coimmunoprecipitation assays. Human nasal epithelial cells (HNECs) were cultured with submerged methods and transfected with p120-specific small interfering RNA. In other experiments, HNECs differentiated with the air-liquid interface (ALI) method were stimulated with various cytokines and Toll-like receptor (TLR) agonists. The barrier properties of differentiated HNECs were determined by assessing fluorescent dextran permeability. RESULTS: E-cadherin and p120 expression was decreased in HNECs from patients with CRS, and the p120 protein expression level was positively correlated with that of E-cadherin. Two isoforms of p120 (p120-1 and p120-3) were expressed in HNECs, with p120-3 being the main isoform. Knocking down p120 in HNECs cultured under submerged conditions significantly reduced the E-cadherin protein expression. The Rac1 inhibitor NSC23766 reversed the protein expression of E-cadherin in p120 knockdown experiments. Inflammatory mediators, including IL-4, TNF-α, TGF- ß, LPS and IFN-Î, reduced E-cadherin and p120 protein expression and increased paracellular permeability. Dexamethasone abolished the downregulation of E-cadherin and p120 caused by inflammatory mediators. CONCLUSIONS: p120 is involved in regulating E-cadherin protein expression in CRS. Dexamethasone may alleviate the reduction in E-cadherin and p120 protein expression caused by inflammatory mediators.

Disrupting a phospholipase A2 gene increasing lipid accumulation in the oleaginous yeast Yarrowia lipolytica.

AIMS: Phospholipase A2 (PLA2 ) is a diverse superfamily that hydrolyzes fatty acyl ester bonds at the sn-2 position of phospholipids. The correlation between phospholipid metabolism and the anabolism of neutral lipids remains unclear in yeasts. This study aims to explore the effects of PLA2 on lipid accumulation in the oleaginous yeast Yarrowia lipolytica. METHODS AND RESULTS: This study identified an actively expressed phospholipase A2 gene (PLA2-3, YAIL0_E16060g) in Y. lipolytica by quantitative PCR analysis. The gene PLA2-3 was disrupted in the strain po1gΔKu70 by homologous recombination and in the strain po1g-G3 by a CRISPR-Cas9 system, which caused an increase in stress sensitivity while the cell growth was not altered under fermentative conditions. Lipid production was performed in both flasks and bioreactors. The results showed that the lipid titre and lipid content were improved over 25% and 8-30%, respectively, in PLA2-3 disrupted strains compared to the controls. CONCLUSIONS: Disruption of the phospholipase PLA2-3 gene could effectively improve lipid production in Y. lipolytica. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presented a strategy on improving the lipid production of oleaginous yeasts and a similar strategy might be used in other oleaginous microbes.

[Clinical efficacy and safety analysis of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma: a multicenter retrospective study].

Objective: To analyze the clinical efficacy and safety of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma (HCC). Methods: Ninety-four cases with mid-and advanced-stage HCC who received camrelizumab combined with apatinib as second-line treatment were enrolled. Routine blood test, blood biochemical indexes, tumor stage, tumor imaging characteristics, previous treatment strategies and other clinical data before treatment were documented. Imaging examination follow-up results and adverse reactions during treatment were followed up until the end of follow-up or loss of follow-up or death. Kaplan-Meier method was used to analyze the clinical efficacy. Results: As of the last follow-up, 94 cases with mid-and advanced-stage HCC had received camrelizumab combined with apatinib as second-line treatment. Among them, 15 cases were lost to follow-up, 31 cases died, and 48 cases survived. The overall remission rate was 31.9%. The overall disease control rate was 71.3%. The median time to disease-free progression was 6.6 months. The median time to disease progression was not yet available. The 1-year cumulative survival rate was 62.3%. Grade 3 and above adverse reactions mainly included were thrombocytopenia (7.4%), abdominal pain (4.3%), active hepatitis (4.3%), leukopenia (4.3%), diarrhea (3.2%), hand-foot syndrome (3.2%). All adverse reactions were effectively controlled. Conclusion: Camrelizumab combined with apatinib can effectively prolong the survival period of patients with mid-and advanced-stage HCC, and it is well tolerated.

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Amplification of flat laser pulse train.

We present modeling and measurements of flattop amplification of a laser pulse train in a diode pumped Nd:YLF system. We establish a theoretical model, accounting for the transverse Gaussian shape of an amplified laser beam, in order to explain remaining slopes in the pulse train energy. The influence of the transverse Gaussian shape on the train's flatness has been experimentally verified. Based on the model we are able to increase the total amplification of a long train of infrared seed beam in the drive laser system at the Fermilab Accelerator Science and Technology facility. The single-pass amplifier improvements resulted in a gain of ∼7 with flat output pulse train for up to 1000 seed pulses.

Circular RNA expression profile analysis of severe acne by RNA-Seq and bioinformatics.

BACKGROUND: Acne is a common chronic skin disease with a multifactorial aetiology and pathogenesis. Recently, circular RNAs (circRNAs) have been identified as a key factor in regulating gene expression through circRNA-miRNA-mRNA networks in many biological processes and human diseases. However, the circRNAs expression in patients with acne is still unknown. OBJECTIVE: To investigate circRNA expression profile in severe acne. METHODS: The expression profile of circRNAs in three paired lesional skin and adjacent non-lesional skin in severe acne was detected by high-throughput RNA sequencing technology and bioinformatics analysis. The candidate circRNAs were validated by PCR, Sanger sequencing and qRT-PCR in the separate group (n = 4). The circRNA-miRNA-mRNA interaction networks were predicted. RESULTS: A total of 538 circRNAs including 271 up- and 267 downregulated circRNAs were differentially expressed in lesional skin compared with adjacent non-lesional skin in severe acne. Gene Ontology and KEGG pathway enrichment analyses revealed that the aberrantly expressed circRNAs were primarily involved in inflammatory, metabolism and immune responses. Five candidate circRNAs (circRNA_0084927, circRNA_0001073, circRNA_0005941, circRNA_0086376 and circRNA_0018168) were validated to have significant decrease in severe acne by PCR, Sanger sequencing and qRT-PCR, in agreement with the results from RNA-Seq data analysis. The five identified circRNAs were predicted to interact with 213 miRNAs and regulated target gene expression. CONCLUSION: This study firstly showed that circRNAs were differentially expressed in severe acne and suggested that circRNAs could be used as a potential biomarker for the drug targets of acne.

Distribution and quantitative analysis of CIDEa and CIDEc in broiler chickens: accounting for differential fat deposition between strains.

1. Differences in the expression of CIDEa and CIDEc in 20 different tissues were examined. Both CIDEa and CIDEc mRNA transcripts were predominantly but variably expressed in white adipose tissue (WAT) but were also expressed at moderate levels in the kidney and liver and at lower levels in the ovary. Interestingly, among WAT types, both CIDEa and CIDEc were expressed at the lowest levels in heart coronary WAT. 2. To better understand the roles of CIDEa and CIDEc in the fat deposition of broiler chickens, the differences in lipid droplet (LD) size and mRNA levels of CIDEa and CIDEc between lean-type and fat-type broiler chicken lines were studied. LD sizes were larger in fat-type broiler lines, and CIDEa and CIDEc mRNA levels in white adipose, kidney and liver tissues were significantly higher in fat-type broiler lines than in their lean counterparts. 3. Developmental expression patterns of CIDEa and CIDEc mRNA were analysed in different tissue types (WAT, liver and kidney) in Arbor Acres broiler chickens, and CIDEa and CIDEc mRNA expression levels increased during sequential developmental stages, achieving peak expression levels at week 6. 4. These observations suggest that the functions of CIDEa and CIDEc reflect inherent characteristics of lipid metabolism that contribute to the differences in fat deposition between strains. The results in this study contribute to a more robust understanding of the tissue distribution and expression patterns of CIDEa and CIDEc mRNA and facilitate further research concerning the molecular mechanism underlying fat deposition in broiler chickens.

[The application of stereo-electroencephalography guided radiofrequency thermocoagulation in refractory temporal epilepsy].

Objective: To investigate the clinical value of stereo-electroencephalography guided radiofrequency thermos-coagulation (RFTC) in drug resistant temporal epilepsy. Methods: The clinical data of 12 patients with refractory temporal epilepsy who underwent implantation of SEEG electrodes and radiofrequency thermos-coagulation from July 2016 to November 2017 were analysed retrospectively. Results: The mean follow-up time was 6.4±4.6 months after thermos-coagulation, and 10.2±3.5 months after resection. Engel Ⅰa was observed in 9 cases, with Ⅱa, Ⅲa and Ⅳa 1 cases respectively. Nine patients experienced a ≥50% decrease of seizure frequency after RFTC (R+ , 75%), of whom one had got a sustained seizure free for 15 months and the other with decrease of seizure frequency by over 90% for 14 months. There was a statistical significance in seizure frequency between pre- and post-thermo-coagulation (P=0.008). Ten cases underwent open surgery following SEEG-guided RFTC, of them 8 cases got seizure free. RFTC was effective in 6 of 8 cases. In our group, all patients have not suffered from any neurologic and cognitive deficiency, and even several patients have some improvements on memory quotient. Conclusions: Although it is less effective than resective surgery, SEEG-guided RFTC can be a relatively safe, effective treatment because of its precision and minimal invasion for patients with complex drug resistant temporal epilepsy, especially for impossible any cortical resection. In addition, its effect may be a predictor of outcome after conventional cortectomy.

[Trichloroethylene-induced abnormal methylation on promoter region of SET in hepatic L-02 cells].

Objective: To explore the trichloroethylene-induced alteration of methylation on the promoter region of SET and related mechanisms in hepatic L-02 cells. Methods: L-02 cells were treated with different concentrations of TCE(0 mmol/L, 1 mmol/L, 2 mmol/L, 4 mmol/L, 8 mmol/L) for 24 h. The genomic DNA were then extracted and modified by bisulfite sodium. The DNA methylation was then analyzed using bisulfite sequencing PCR (BSP). Results: The overall methylation on promoter region of SET was decreased along with the increased concentrations of TCE in hepatic L-02 cells. Moreover, 73 CpG islands were found abnormally altered, among which 9 were predicted in transcriptional factor binding regions. Conclusion: The decreased levels of CpG islands in the transcriptional factor binding region may contribute to the elevation of SET in TCE-induced hepatotoxicity.

A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance).

BACKGROUND: This multicenter, phase II trial tested the tolerability and efficacy of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma (FL). PATIENTS AND METHODS: Patients with grade 1-3a FL, stage 3-4 or bulky stage 2, FL international prognostic index (FLIPI) 0-2, and no prior therapy were eligible to receive rituximab 375 mg/m2 weekly during cycle 1 and day 1 of cycles 4, 6, 8, and 10, plus lenalidomide 20-25 mg on days 1-21 for twelve 28-day cycles. The primary objectives were to evaluate response rates [complete (CR) and overall] and time to progression. Secondary objectives included toxicity, response according to polymorphisms in FcgR2A and FcgR3A, and changes in circulating pro-angiogenic cells. RESULTS: From October 2010 to September 2011, 66 patients were enrolled. Median age was 53 years, 34 were female, 15 had bulky disease, 21 were FLIPI 0-1, 43 FLIPI 2, and 2 FLIPI 3. One patient withdrew before receiving treatment. Fifty-one patients completed 12 cycles of lenalidomide. Reasons for discontinuation included withdrawal (n = 6), adverse events (n = 6), progression (n = 2). Grade 3-4 hematologic toxicity included neutropenia (21%), lymphopenia (9%), and thrombocytopenia (2%), infection (11%), and rash (8%). Grade 1-2 toxicity included fatigue (78%), diarrhea (37%), rash (32%), and febrile neutropenia in one patient. The overall response rate was 95%; the CR rate was 72% (95% confidence interval, 60% to 83%). With a median follow-up of 5 years, the 2- and 5-year progression-free survival were 86% and 70%, respectively, and the 5-year overall survival was 100%. There was no association between CR rate or PFS and FLIPI, histological grade, bulky disease, FcgR2A/FcgR3A polymorphism, or change in circulating endothelial cell/hematopoietic progenitor cell. CONCLUSION: Lenalidomide plus rituximab was associated with low rates of grade 3-4 toxicity, yielded a CR rate and PFS similar to chemotherapy-based treatment and may represent a reasonable alternative to immunochemotherapy in previously untreated FL. CLINICALTRIALS.GOV IDENTIFIER: NCT01145495.

Expressions of H2AX in cervical squamous carcinoma and their clinical significances.

OBJECTIVE: To evaluate the expression and clinical significance of H2AX in cervical squamous carcinoma. MATERIALS AND METHODS: The expression of H2AX in the cervical squamous carcinoma of 37 patients and in the normal cervical tissue of 15 patients was detected by immuneohistochemical method. Chi-square, correlation analysis, and Kaplan-Meier were utilized to analyze the data. RESULTS: The positive expression rate of H2AX in cervical squamous carcinoma was higher than that in normal cervical tissues (p = 0.016) . The expression of H2AX was negatively correlated with FIGO staging, vaginal invasion, and parametrial infiltration (p < 0.05). Survival analysis showed the expression intensity of H2AX had no significant effect on the prognosis. CONCLUSION: H2AX was an anticancer protein for cervical squamous carcinoma.

[An investigation of trichloroethylene-induced effects on histone methylation in L-02 hepatic cells].

Objective: To further explore TCE-induced hepatotoxicity and its mechanisms by identification of trichloroethylene (TCE) induced abnormal histone methylation in human liver cells. Methods: L-02 cells were treated with 0 and 8 mmol/L TCE for 24 h. Histones were extracted by acid. Liquid chromatography electrospray ionization tandem mass spectrometry (ESI-LC-MS/MS) were used to identify and quantify TCE related histone methylations. TCE induced abnormal methylation of H3K79 me2 and H3K79 me3 were validated by Western blot analysis. The further analysis of the function of histone abnormal methylation modifications were done by single cell gel electrophoresis (SCGE) and Western blot analysis of p53 and ɤH2AX. Results: After treatment with TCE for 24 h in L-02 cells, the 36 TCE related histone methylation sites in 28 peptide segments were identified by MS. After treatment with TCE in concentrations of 0 and 8.0 mmol/L in L-02 cells for 24 h, the relative expression level of histone H3K79 me3 were 1.00±0.06, 0.70±0.09 (t=15.01, P=0.015); the relative expression level of histone H3K79 me2 were 1.00±0.05, 0.74±0.07 (t=16.69, P=0.018); the Olive Tail Moment about DNA damage were 1.46±0.28, 3.12± 0.68 (t=15.22, P=0.018); the relative expression levels of p53 were 1.00±0.04, 1.24±0.04 (t=18.71, P= 0.012); and the relative expression levels of ɤH2AX were 1.00 ± 0.03, 1.56 ± 0.11 (t=8.32, P=0 045). Conclusion: TCE can induce changes in the relative expression level of H3K79 me2 and H3K79 me3 in L-02 cell, and induce DNA damage, suggesting that TCE may induce changes in the relative expression level of H3K79 me2 and H3K79 me3 by DNA damage.

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas.

Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the 'R(2)' regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R(2), immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R(2) treatment, and optimal strategies for managing adverse events are discussed here.

Laparoscopic subtotal hysterectomy due to giant uterine fibroids: a case report.

The laparoscopic subtotal hysterectomy (LSH) was given to a patient whose uterus was about seven-month pregnanacy because of fibroids. The biggest problem was the operation space and visual field was too narrow. Different from the usual procedure we do, we morcellated the uterus at the beginning to expand the space. Loop ligature of the uterine isthmus was adopted to block uterine ateries before morcellating the uterus. After the adnexa exposed totally, we started to cut off the round ligaments, proper ligaments and fallopian tubes like usual. It was the first time we did LSH for so giant uterus in our hospital, although which was usually suitable for the uterus smaller than four-month pregnancy. But if the uterine ateries can be blocked effectively at the beginning, the uterus can be morcellated and the space will be enlarged. The laparoscopic subtotal hysterectomy will also be completed successfully.

[Functional mapping of the insular and opercular cortex: A study using SEEG electrical stimulation in epileptic patients].

OBJECTIVE: Insular and opercular cortex is involved in complicated physiological function.Insular seizures involve extensive epileptic network, which results in the complex and diverse semiology.Electrical cortical stimulation(ECS) can explore the functional mapping and symptomatogenic zone. METHODS: The clinical presurgical evaluation and ECS data of 20 patients whose electrode contacts were located in the insular and opercular were analyzed retrospectively.CT scan/3D MRI data fusion was performed in order to accurately identify and locate each contact and check the electrode trajectory by the MRI images performed after the electrodes were removed.ECS was applied between two contiguous contacts.Stimulation usually lasted for 5 s at 50 Hz(pulse width=0.3 ms). Depending on the area of stimulated cortex, the stimulation intensities ranged from 0.2 to 3.0 mA.The classification of the insular were anterior short gyrus, middle short gyrus, precentral gyrus, postcentral gyrus, posterior long gyrus and insular pole.The classification of the opercular were orbital, frontal, precentral, central, parietal and temporal opercular. RESULTS: One hundred and six contacts were located in the insular and 51 responses were evoked (48.11%). Four hundred eighteen contacts were located in the insular and 132 responses were evoked (31.58%). We classified the principal responses as somatosensory, pain, auditory, oropharyngeal, speech disturbances and neurovegetative response.Somatosensory responses were mainly evoked in parietal opercular and postcentral gyrus, while pain response distributed sporadically.Auditory were only evoked in temporal opercular(transverse temporal gyri) and posterior long gyrus.Oropharyngeal symptoms were only evoked in central opercular.Speech disturbances were located in precentral and central opercular and neurovegetative responses were mainly evoked in insular pole and middle short gyrus. CONCLUSIONS: These findings may indicate a functional specificity for the insular gyrus and opercular, which contribute to the understanding of anatomo-functional organization and the role in insular and opercular epileptic network.Moreover, it could optimize the implantation strategy for exploring these structures.

Deletion of the lmna gene induces growth delay and serum biochemical changes in C57BL/6 mice.

The A-type lamin deficient mouse line (Lmna (-/-) ) has become one of the most frequently used models for providing insights into many different aspects of A-type lamin function. To elucidate the function of Lmna in the growth and metabolism of mice, tissue growth and blood biochemistry were monitored in Lmna-deficient mice, heterozygous (Lmna (+/-) ) and wide-type (Lmna (+) (/) (+) ) backcrossed to C57BL/6 background. At 4 weeks after birth, the weight of various organs of the Lmna (-/-), Lmna (+/-) and Lmna (+) (/) (+) mice was measured. A panel of biochemical analyses consisting of 15 serological tests was examined. The results showed that Lmna deficient mice had significantly decreased body weight and increased the ratio of organ to body weight in most of tissues. Compared with Lmna (+) (/) (+) and Lmna (+/-) mice, Lmna (-/-) mice exhibited lower levels of ALP (alkaline phosphatase), Chol (cholesterol), CR (creatinine), GLU (glucose), HDL (high-density lipoprotein cholesterol) and higher levels of ALT (alanine aminotransferase) (p<0.05). Lmna (-/-) mice displayed higher AST (aspartate aminotransferase) values and lower LDL (lowdensity lipoprotein cholesterol), CK-MB (creatine kinase-MB) levels than Lmna (+) (/) (+) mice (p<0.05). There were no significant differences among the three groups of mice with respect to BUN (blood urea nitrogen), CK (creatine kinase), Cyc C (cystatin C), TP (total protein), TG (triacylglycerols) and UA (uric acid) levels (p>0.05). These changes of serological parameters may provide an experimental basis for the elucidation of Lmna gene functions.

Autophagy inhibition induces enhanced proapoptotic effects of ZD6474 in glioblastoma.

BACKGROUND: Autophagy is a lysosomal degradation pathway that can provide energy through its recycling mechanism to act as a cytoprotective adaptive response mediating treatment resistance in cancer cells. We investigated the autophagy-inducing effects of ZD6474, a small-molecule inhibitor that blocks activities of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and RET tyrosine kinases. METHODS: We investigated the effects of ZD6474 on autophagy in glioblastomas cells. The ZD6474 mechanism of action was determined by western blot. We then examined the impacts of the inhibition of autophagy in combination with ZD6474 on cell apoptosis in vitro. Furthermore, we evaluated the synergistic anticancer activity of combination treatment with an autophagy inhibitor (chloroquine) and ZD6474 in U251 glioblastoma cells xenograft model. RESULTS: ZD6474-induced autophagy was dependent on signalling through the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. ZD6474-induced autophagy was inhibited by both knockdown of the ATG7 and Beclin 1 gene, essential autophagy genes, and pharmacologic agents (chloroquine and 3-methyalanine) treatment. Both treatments also dramatically sensitised glioblastoma cells to ZD6474-induced apoptosis, decreasing cell viability in vitro. Furthermore, in a xenograft mouse model, combined treatment with ZD6474 and chloroquine significantly inhibited U251 tumour growth, and increased the numbers of apoptotic cells compared with treatment with either agent alone. CONCLUSION: Autophagy protects glioblastoma cells from the proapoptotic effects of ZD6474, which might contribute to tumour resistance against ZD6474 treatment.