Sub-region based radiomics analysis for prediction of isocitrate dehydrogenase and telomerase reverse transcriptase promoter mutations in diffuse gliomas.

AIM: To enhance the prediction of mutation status of isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter, which are crucial for glioma prognostication and therapeutic decision-making, via sub-regional radiomics analysis based on multiparametric magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective study was conducted on 401 participants with adult-type diffuse gliomas. Employing the K-means algorithm, tumours were clustered into two to four subregions. Sub-regional radiomics features were extracted and selected using the Mann-Whitney U-test, Pearson correlation analysis, and least absolute shrinkage and selection operator, forming the basis for predictive models. The performance of model combinations of different sub-regional features and classifiers (including logistic regression, support vector machines, K-nearest neighbour, light gradient boosting machine, and multilayer perceptron) was evaluated using an external test set. RESULTS: The models demonstrated high predictive performance, with area under the receiver operating characteristic curve (AUC) values ranging from 0.918 to 0.994 in the training set for IDH mutation prediction and from 0.758 to 0.939 for TERT promoter mutation prediction. In the external test sets, the two-cluster radiomics features and the logistic regression model yielded the highest prediction for IDH mutation, resulting in an AUC of 0.905. Additionally, the most effective predictive performance with an AUC of 0.803 was achieved using the four-cluster radiomics features and the support vector machine model, specifically for TERT promoter mutation prediction. CONCLUSION: The present study underscores the potential of sub-regional radiomics analysis in predicting IDH and TERT promoter mutations in glioma patients. These models have the capacity to refine preoperative glioma diagnosis and contribute to personalised therapeutic interventions for patients.

[Analysis on the use of HIV post-exposure prophylaxis and related factors in men who have sex with men in Qingdao].

Objective: To understand the use of post-exposure prophylaxis (PEP) and analyze related factors among men who have sex with men (MSM) in Qingdao, and provide a reference for the AIDS prevention and control in this population. Methods: A cross-sectional survey conducted from April 2022 to February 2023. Relying on MSM social groups in Qingdao, a snowball sampling method was applied to recruit research subjects who met the inclusion criteria of age ≥18 years old, having had homosexual anal or oral sex in the past six months, and HIV-negative or infection status unknown. The sample size was estimated at 566. Data on demographic characteristics, sexual behavior characteristics, PEP use, and others of the research subjects was collected through on-site questionnaires. The logistic regression model was used to analyze the factors associated with using PEP. Results: A total of 811 participants were recruited, mainly aged 25-34 (53.6%, 435/811), unmarried (74.7%, 606/811), with an average monthly income of ≥5 000 yuan (52.2%, 423/811), and having lived in Qingdao for ≥10 years (75.6%, 613/811). The proportion of those who knew the HIV status of their sexual partners in the last six months was 67.1% (544/811), and those with HIV-positive partners were 3.6% (29/811). In the last six months, the proportion of participants who had group sex (86.4%, 701/811), unprotected anal sex (98.2%, 796/811), and use of club drugs (80.3%, 651/811) was high. Moreover, 28.4% (230/811) had used PEP. The multivariate logistic regression analysis showed that the factors related to the use of PEP included divorced or widowed (aOR=5.46,95%CI:1.96-15.17), average monthly income ≥5 000 yuan (aOR=2.04,95%CI:1.44-2.89), same-sex sexual orientation (aOR=0.40,95%CI:0.22-0.71), having HIV-positive sexual partners in the last six months (aOR=2.54,95%CI:1.13-5.71) and having been tested for HIV ≥3 times in the last six months (aOR=1.46,95%CI:1.04-2.06). Conclusions: The prevalence of risk behaviors among MSM in Qingdao was high, and the use of PEP was low. In the future, it is essential to increase HIV/AIDS prevention education among MSM, promote MSM to know the HIV status of their sexual partners, and reduce the prevalence of risk behaviors among this population. Additionally, explore medical insurance reimbursement plans for PEP to reduce utilization costs and promote the use of PEP by MSM after HIV exposure occurs as soon as possible.

Clinical consequence of vessel perforations during endovascular treatment of acute ischemic stroke.

PURPOSE: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry. METHODS: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR). RESULTS: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2-3.2)) and distal occlusion locations (aOR 2.2  (95% CI 1.3-3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23-0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome. CONCLUSION: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk.

Silicon nanowire FET biosensor and its application in acute myocardial infarction.

Over the last two decades, silicon nanowire field-effect transistors (SiNW-FETs) with prominent merits of high surface-to-volume ratio, excellent biocompatibility and mature fabrication with standard silicon technology, have been widely studied as ultrahigh sensitive biosensors for the detection of target biomolecules, such as proteins, nucleic acids, cells and viruses so on. Herein we present a comprehensive review of the fundamental aspects of SiNW-FET biosensors, involving the working principle and the device fabrication, surface functionalization, and system integration with fluid exchange and electrical detection. Futhermore, we emphatically discuss the electrical detection of cardiac-specific biomarkers related to acute myocardial infarction disease. SiNW-FET biosensors are being increasingly exploited as promising diagnostic devices, which provide high sensitivity, high integration density, high speed sampling, strong specificity, and real-time and label-free detection for simple and cheap clinical testing.

Clinical application of laparoscopic continuous interposition jejunostomy with double-tract anastomosis and esophagogastric anastomosis: a retrospective study.

OBJECTIVE: The aim of this study was to compare the early clinical outcomes of laparoscopic-assisted proximal gastrectomy with continuous interposition of jejunal cis-peristaltic dual-channel anastomosis and esophagogastric anastomosis. PATIENTS AND METHODS: A retrospective analysis of 130 patients who underwent laparoscopic-assisted radical resection of proximal gastric cancer in the Department of Gastrointestinal Surgery at the Affiliated Hospital of Chengde Medical College between June 2018 and October 2022 was conducted. Continuous interposition jejunal double-channel anastomosis (double-tract anastomosis) was used in 71 patients and esophagogastric anastomosis (esophagogastrostomy) in 59 patients. The basic clinical data, preoperative and postoperative clinical test indexes, postoperative complications and improvement of symptoms compared to preoperative ones, basic nutritional status and Visick classification of esophageal reflux symptoms at 6 months after surgery were compared between the two groups. Postoperative contrast images of patients in the continuous interposition jejunal double-tract group were collected and analyzed for the ratio of contrast agent remaining in the stomach to that remaining in the small intestinal channel. RESULTS: A total of 130 cases meeting the criteria were included in this study, including 71 cases involving the double-tract (DT) anastomosis method and 59 cases involving the esophagogastrostomy (EG) anastomosis method. There was no significant difference in preoperative information and perioperative safety between the two groups. Visick score of the DT group was significantly better than that of the EG group. CONCLUSIONS: Double-tract jejunal anastomosis can effectively improve esophageal reflux symptoms after proximal gastrectomy. At the same time, its anastomotic method also improves the nutritional status in the short term compared to the esophagogastric anastomosis and is a more ideal procedure for reconstructing the digestive tract after proximal gastrectomy.

[In vitro activity of ß-lactamase inhibitors avibanvctam and relebactam in combination with ß-lactams against multidrug-resistant Mycobacterium tuberculosis and mutations of resistance genes].

Objective: To evaluate the activity of six ß-lactams in combination with three ß-lactamase inhibitors against mycobacterium tuberculosis(MTB) in vitro. Methods: A total of 105 multidrug-resistant tuberculosis (MDR-TB) strains from different regions of Henan province from January to September 2020 were included in this study. Drug activity of six ß-lactams (biapenem, meropenem, imipenem, doripenem, ertapenem and tebipenem) alone or in combination with ß-lactamase inhibitors (clavulanic acid, avibactam and relebactam) was examined by minimum inhibitory concentration method (MICs) against 105 clinical isolates. Mutations of blaC, ldtmt1 and ldtmt2 were analyzed by PCR and DNA sequencing. Chi-square test was used to compare the antimicrobial activities of different ß-lactam drugs. Results: Out of the ß-lactams used herein, tebipenem was the most effective against MDR-TB and had an MIC50 value of 8 mg/L(χ2=123.70,P=0.001). Besides, after the addition of ß-lactamase inhibitors, the MICs of most ß-lactam drugs were reduced more evidently in the presence of avibactam and relebactam compared to clavulanic acid.Especially, relebactam decreased both the MIC50 and MIC90 of telbipenem by 16-fold, and diluted the MIC of 23 (21.90%) and 41 (39.04%) isolatesby 32-fold and 16-fold.In addition, a total of 13.33% (14/105) of isolates harbored mutations in the blaC gene, with three different nucleotide substitutions: AGT333AGG, AAC638ACC and ATC786ATT. For the strains with Ser111Arg and Asn213Thr substitution in BlaC, the MIC values of the meropenem-clavulanate combination were reduced compared with a synonymous single nucleotide polymorphism (SNP) group. Conclusions: Both avibactam and relebactam had better synergistic effects on ß-lactams than clavulanic acid. The combination of tebipenem and relebactam showed the most potent activity against MDR-TB isolates. In addition, the Ser111Arg and Asn213Thr substitution of BlaC may be associated with an increased susceptibility of MDR-TB isolates to meropenem in the presence of clavulanate.

[Progress in research on HIV self-testing and associated factors among men who have sex with men in China].

HIV testing is the first step in HIV prevention and control, the rate of HIV infection is high and the rate of HIV testing is low among men who have sex with men (MSM) in China. HIV self-testing provides MSM with a new choice and plays a vital role in expanding the coverage of HIV testing in this population. This paper reviews HIV self-testing and associated factors among MSM in China and provides a reference for promoting HIV self-testing in this population.

[Research advances of cognition and willingness to use HIV pre-exposure prophylaxis drug among female sex workers].

Female sex workers (FSW) are in a weak position in the process of sexual behavior and have a high risk of HIV infection. Promoting pre-exposure prophylaxis (PrEP) in this population can prevent HIV infection. This article reviews the cognition, willingness, influencing factors, and potential risk compensation of PrEP in FSW to provide a reference for expanding the use of PrEP in this population.

Unveiling the Enhancement of Spontaneous Emission at Exceptional Points.

Exceptional points (EPs), singularities of non-Hermitian physics where complex spectral resonances degenerate, are one of the most exotic features of nonequilibrium open systems with unique properties. For instance, the emission rate of quantum emitters placed near resonators with EPs is enhanced (compared to the free-space emission rate) by a factor that scales quadratically with the resonance quality factor. Here, we verify the theory of spontaneous emission at EPs by measuring photoluminescence from photonic-crystal slabs that are embedded with a high-quantum-yield active material. While our experimental results verify the theoretically predicted enhancement, they also highlight the practical limitations on the enhancement due to material loss. Our designed structures can be used in applications that require enhanced and controlled emission, such as quantum sensing and imaging.

Observation of Spin Splitting Torque in a Collinear Antiferromagnet RuO_{2}.

Current-induced spin torques provide efficient data writing approaches for magnetic memories. Recently, the spin splitting torque (SST) was theoretically predicted, which combines advantages of conventional spin transfer torque (STT) and spin-orbit torque (SOT) as well as enables controllable spin polarization. Here we provide the experimental evidence of SST in collinear antiferromagnet RuO_{2} films. The spin current direction is found to be correlated to the crystal orientation of RuO_{2} and the spin polarization direction is dependent on (parallel to) the Néel vector. These features are quite characteristic for the predicted SST. Our finding not only presents a new member for the spin torques besides traditional STT and SOT, but also proposes a promising spin source RuO_{2} for spintronics.

[Analysis on off-label use of drugs in pediatric guidelines and consensus published by Chinese authors].

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.

[Effects of interpregnancy interval on pregnancy outcomes of subsequent pregnancy: a multicenter retrospective study].

Objective: To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy. Methods: A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO's recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics. Results: A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant (P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% (OR=1.42, 95%CI: 1.07-1.88, P=0.015), 46% (OR=1.46, 95%CI: 1.13-1.88, P=0.004), and 64% (OR=1.64, 95%CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study (P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age (OR=2.87, 95%CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 (OR=1.59, 95%CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes (OR=1.58, 95%CI: 1.18-2.13, P=0.002) and premature delivery (OR=1.52, 95%CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM (OR=5.34, 95%CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM (OR=1.44, 95%CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia (OR=4.11, 95%CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia (OR=1.46, 95%CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery (OR=1.47, 95%CI: 1.13-1.92, P=0.004). Conclusions: Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Genome-wide association study of fleece traits in Inner Mongolia Cashmere goats.

Inner Mongolia Cashmere goat is a well-known local cashmere goat breed in China. It is famous for excellent fleece quality and a significant advantage in cashmere yield compared to other cashmere goat breeds. In this study, a genome-wide association study was used to investigate fiber length, fiber diameter, and cashmere yield of 192 Inner Mongolia Cashmere goats using the Illumina GoatSNP52K Beadchip panel. We discovered that four single nucleotide polymorphisms (SNPs) reached genome-wide significance levels. These SNPs were located in some genes, e.g. FGF12, SEMA3D, EVPL, and SOX5, possibly related to fleece traits in Inner Mongolia Cashmere goat. Gene ontology enrichment analysis revealed that these genes were enriched in several biological pathways that were involved in hair follicle development in cashmere goats. In summary, the identified significant SNPs and genes provide useful information to explore genetic mechanisms underlying the variation in fleece traits and genomic selection of Chinese cashmere goat.

[Effect of glucose on Akt2 mRNA and methylation level and the association between early-pregnancy Akt2 mRNA level in peripheral blood and pre-pregnancy BMI and GDM].

Objective: To explore the effect of glucose on Akt2 gene methylation and mRNA level in the trophoblast cell line HTR8/SVneo and the association between first-trimester Akt2 mRNA level in peripheral blood and pre-pregnancy body mass index (BMI) and gestational diabetes mellitus (GDM). Methods: The cell model of intrauterine hyperglycemia in pregnant women with GDM was established, and divided into 5 groups based on the different glucose concentrations (2.5, 5.0, 10.0, 25.0, and 40.0 mmol/L). The mRNA levels of Akt2 gene were detected by real-time quantitative PCR, and the methylation levels of Akt2 gene promoter region were detected by mass spectrometry. According to pre-pregnancy BMI and diagnosis of GDM, 60 pregnant women who had given birth at Peking University First Hospital during December 2014 to July 2016 were classified into overweight non-GDM group, overweight GDM group, obese non-GDM group and obese GDM group. Real-time quantitative PCR analyses were used to detect the levels of Akt2 mRNA in first-trimester peripheral blood of the 4 groups. Results: (1) Level of Akt2 mRNA significantly rose with the glucose concentration of medium increased, showing concentration dependency (all P<0.05). Compared with the 25.0 mmol/L group, the following methylation levels changed significantly (all P<0.05): cytosine-phosphate-guanine (CpG) 10, CpG23, and CpG24.5 of Akt2 gene promoter region in the 5.0 mmol/L group, CpG23 and CpG24.5 in the 2.5 mmol/L group, and CpG10 in the 10.0 mmol/L group. Compared with the 5.0 mmol/L group, CpG10 in the 40.0 mmol/L group showed methylation change (P<0.05). (2) Compared with the overweight non-GDM group [1.04(0.90~1.26)], overweight GDM group [2.10(1.85~2.28)] and obese GDM group [1.68(0.82~2.43)] all had higher Akt2 mRNA levels and the differences were statistically significant (all P<0.05). Compared to obese GDM group [1.68(0.82~2.43)], the level of Akt2 mRNA was higher in overweight GDM group [2.10(1.85~2.28)] and lower in obese non-GDM group [1.00(0.71~2.17)], but the differences were not statistically significant (all P>0.05). Conclusions: Glucose might affect Akt2 mRNA level by changing the methylation of Akt2 gene promoter region, and the change might appear in the first trimester of pregnant women with GDM, especially for women with lower pre-pregnancy BMI.

Association between SLCO1B1 polymorphism distribution frequency and blood lipid level in Chinese adults.

BACKGROUND: The variation of serum lipid levels can be part-related to certain genes. One such gene, SLCO1B1, encodes a transporter that may have a role in lipid metabolism. We hypothesised that differences in certain SLCO1B1 genotypes are related to levels of serum lipids. MATERIALS AND METHODS: We recruited 636 subjects who were genotyped for SLCO1B1 variants *1a, *1b, *5 and *15. Routine liver function tests, renal function tests and routine lipid indices were measured by standard techniques. RESULTS: The most frequent genotypes were *1b/*1b (29.3%), *1b/*15 (27.5%), *1a/*1b (21.1%), *1a/*15 and *1b/*5 (10.2%) and *1a/*1a (8.5%). There were significant differences in levels of triglycerides and HDL in the four SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1a/*1b and *1b/*15 (all p < 0.05). CONCLUSION: The genotypes *1a/*1a and *1a/*1b indicate a high risk of cardiovascular disease, while the *1b/*1b group may have a relatively low risk. SLCO1B1 may be involved in the metabolism of triglycerides and HDL. We have provided a tool for identifying potentially high-risk groups that could be helpful for early diagnosis and prevention, individualized drug therapy and even gene therapy.

Design of super-strong and thermally stable nanotwinned Al alloys via solute synergy.

Al alloys have widespread industrial applications. However, their mechanical strength is often much lower than steels. Here, we investigate the influence of solutes on achieving ultrahigh strength and thermal stability of nanotwinned Al alloys. In situ micropillar compression tests show the addition of a small amount of Ti can significantly increase the mechanical strength of Al-Ni alloys to 2 GPa. Deformation induced detwinning, Ni segregation and grain coarsening as discovered in binary Al-Ni alloys are mostly absent in the ternary Al-Ni-Ti alloys. Moreover, the ternary Al-Ni-Ti alloys have outstanding thermal stability. Density function theory calculations reveal the synergetic pinning effect of Ni-Ti solute pairs on incoherent twin boundaries. This study demonstrates that the proper selection of synergistic solute pairs is critical to improve the thermal stability and mechanical properties of nanotwinned Al alloys.

[The inhibitory effect of CtBP-interacting protein on the oxidative damage of cerebral endothelia cells].

Objective: To explore the effect of CtBP-Interacting protein (CtIP) on oxidative damage of cerebral endothelia cells and its mechanism. Method: Cerebral endothelia cells were stimulated by TBHP to induce oxidative damage. The cell line of CtIP gene were prepared by over-expression and interfering lentivirus technology. Cell damage was detected by immunofluorescence assay of cysteinyl aspartate specific proteinase-3 (Caspase-3). The expression of CtIP and Caspase-3 protein was detected by Western blotting, and the related genes of CtIP signaling pathway were detected by Realtime RT-PCR. Result: The results of immunofluorescence and Western blotting showed that overexpression of CtIP inhibited the Caspase-3 expression reducing to 1/3 level compared with normal cultured cerebral endothelia cells. Interfering with CtIP expression resulted in the Caspase-3 expression increased significantly to 4/5 level compared with normal cultured cerebral endothelia cells and cerebral endothelia cells were damaged more severely. Realtime RT-PCR data showed that expression of CtIP significantly increased the expression of BRCA1 and ZBRK1 genes, but inhibited the expression of p21 gene. Conclusion: It is confirmed that CtIP gene has the significantly inhibitory effect on injured cerebral endothelia cells, and the regulatory relationship between CtIP gene and BRCA1, ZBRK1 and p21 genes in the process of injury are determined.

Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing-remitting multiple sclerosis in a real-world clinical setting: PROTEC.

BACKGROUND: Patient-reported outcomes (PRO) and clinical outcomes give a broad assessment of relapsing-remitting multiple sclerosis (RRMS) disease. OBJECTIVE: The aim is to evaluate the effectiveness of delayed-release dimethyl fumarate (DMF) on disease activity and PROs in patients with RRMS in the clinic. METHODS: PROTEC, a phase 4, open-label, 12-month observational study, assessed annualized relapse rate (ARR), proportion of patients relapsed, and changes in PROs. Newly diagnosed and early MS (≤3.5 EDSS and ≤1 relapse in the prior year) patient subgroups were evaluated. RESULTS: Unadjusted ARR at 12 months post-DMF versus 12 months before DMF initiation was 75% lower (0.161 vs. 0.643, p < 0.0001) overall (n = 1105) and 84%, 77%, and 71% lower in newly diagnosed, ≤3.5 EDSS, and ≤1 relapse subgroups, respectively. Overall, 88% of patients were relapse-free 12 months after DMF initiation (84%, newly diagnosed; 88%, ≤3.5 EDSS; 88%, ≤1 relapse). PRO measures for fatigue, treatment satisfaction, daily living, and work improved significantly over 12 months of DMF versus baseline. CONCLUSION: At 12 months after versus 12 months before DMF initiation, ARR was significantly lower, the majority of patients were relapse-free, and multiple PRO measures showed improvement (overall and for subgroups), suggesting that DMF is effective based on clinical outcomes and from a patient perspective.Clinical trial: A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes (PROTEC), NCT01930708, https://clinicaltrials.gov/ct2/show/NCT01930708.