Real-world data for the availability of pediatric medicines in Chinese hospitals: a multi-center survey and analysis.

Aim: No information exists on the availability of pediatric medicines in China. This study aimed to access the availability of different types of pediatric medicine and determine their ratio in medical institution drug catalogs. Methods: Based on drug instructions, an expert meeting method was used to divide pediatric medicines into five categories: child-specific medicine (CSM), co-use medicine for adults and children (CMAC), other pediatric medicines (OCM), off-label medicine use (OMU), and non-child medicine (NM). Results: A total of 60 hospitals nationwide participated in this survey, namely, 20 children's hospitals (C-hosp), 14 maternal and child healthcare hospitals (MCHC-hosp), and 26 general hospitals (G-hosp). The average number of drug catalogs in G-hosp was significantly higher than that in C-hosp and MCHC-hosp. CSM accounted for 9.77% of the C-hosp catalog, 7.12% of the MCHC-hosp catalog, and 1% of the G-hosp catalog. The availability rate of CMAC was 49.63% in C-hosp and 40.87% and 31% in MCHC-hosp and G-hosp, respectively. The proportion of OCM in C-hosp (27.28%) was higher than that in MCHC-hosp (13.4%) and G-hosp (5%). The OMU occupied ratio in C-hosp, MCHC-hosp, and G-hosp is not negligible, which was 12.06%, 8.7%, and 10% respectively. The proportion of NM in C-hosp was almost negligible but was 29.91% and 53% in MCHC-hosp and G-hosp, respectively. Compared to the CSM and CMAC listed in China, the share of CSM in C-hosp was close to 40%, which was much higher than that of G-hosp and MCHC-hosp. In contrast, the share of CMAC in G-hosp was nearly 30%, which was significantly higher than that in C-hosp and MCHC-hosp. Health insurance covers most of these five types of pediatric medicines, with the proportion of insured medicines reaching close to 80% in C-hosp and approximately 85% in MCHC-hosp and G-hosp. Discussion: The availability of specific medicines suitable for use in children is generally low, and even CSM in specialized hospitals such as C-hosp cannot meet the relatively high accessibility level of WHO evaluation standards. Policies and measures should be implemented to boost the research and development of pediatric medicines, as well as supplement safety information lacking in instruction manuals.

Sexually concordant selection on floral traits despite greater opportunity for selection through male fitness.

Pollinators are important drivers of floral trait evolution, yet plant populations are not always perfectly adapted to their pollinators. Such apparent maladaptation may result from conflicting selection through male and female sexual functions in hermaphrodites. We studied sex-specific mating patterns and phenotypic selection on floral traits in Aconitum gymnandrum. After genotyping 1786 offspring, we partitioned individual fitness into sex-specific selfed and outcrossed components and estimated phenotypic selection acting through each. Relative fitness increased with increasing mate number, and more so for male function. This led to greater opportunity for selection through outcrossed male fitness, though patterns of phenotypic selection on floral traits tended to be similar, and with better support for selection through female rather than male fitness components. We detected directional selection through one or more fitness component for larger flower number, larger flowers, and more negative nectar gradients within inflorescences. Our results are consistent with Bateman's principles for sex-specific mating patterns and illustrate that, despite the expected difference in opportunity for selection, patterns of variation in selection across traits can be rather similar for the male and female sexual functions. These results shed new light on the effect of sexual selection on the evolution of floral traits.

Rapid evolution of a family-diagnostic trait: artificial selection and correlated responses in wild radish, Raphanus raphanistrum.

The mechanisms underlying trait conservation over long evolutionary time scales are poorly known. These mechanisms fall into the two broad and nonmutually exclusive categories of constraint and selection. A variety of factors have been hypothesized to constrain trait evolution. Alternatively, selection can maintain similar trait values across many species if the causes of selection are also relatively conserved, while many sources of constraint may be overcome over longer periods of evolutionary divergence. An example of deep trait conservation is tetradynamy in the large family Brassicaceae, where the four medial stamens are longer than the two lateral stamens. Previous work has found selection to maintain this difference in lengths, which we call anther separation, in wild radish, Raphanus raphanistrum. Here, we test the constraint hypothesis using five generations of artificial selection to reduce anther separation in wild radish. We found a rapid linear response to this selection, with no evidence for depletion of genetic variation and correlated responses to this selection in only four of 15 other traits, suggesting a lack of strong constraint. Taken together, available evidence suggests that tetradynamy is likely to be conserved due to selection, but the function of this trait remains unclear.

Comparison of Unilateral and Bilateral Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fractures.

Objective: To investigate the clinical efficacy of percutaneous kyphoplasty (PKP) with a unilateral versus bilateral approach in the treatment of osteoporotic vertebral compression fractures (OVCFs). Methods: We retrospectively analyzed a total of 147 patients (unilateral group: 79, bilateral group: 68) with OVCFs treated with PKP at the Department of Spine Surgery, Wuhan Fourth Hospital between August 2020 and January 2022. Patients' personal information, operation time, bone cement injection volume, as well as pre- and post-operative visual analogue scale (VAS), Oswestry disability index (ODI), anterior vertebral body height and Cobb angle were recorded. Results: All 147 patients were successfully treated with PKP and were followed up for at least 6 months. Our results showed that the operative time was significantly shorter in the unilateral group (41.60±5.64) minutes than in the bilateral group (66.53±9.40) minutes, and the volume of bone cement injected was also significantly less in the unilateral group (5.27±0.73) mL than in the bilateral group (6.87±0.93) mL (P<0.01). The VAS score, ODI index, vertebral height and Cobb angle at postoperative follow-up were significantly improved in both groups compared to the preoperative period (P<0.01); However, the difference between the two groups was not statistically significant (P>0.05). Repeat thoracic and lumbar radiographs showed cement leakage in seven cases (8.86%) in the unilateral group and five cases (7.35%) in the bilateral group, but all were asymptomatic and required no further management. During our entire follow-up period, there were five adjacent vertebral fractures in the unilateral group (6.33%) and four in the bilateral group (5.88%). Conclusion: There was no significant difference between the two groups in terms of improvement in VAS score, ODI index, restoration of vertebral body height, and posterior convexity deformity, but unilateral puncture had the advantage of shorter operative time and less cement injection.

Cs2CO3 catalyzed direct aza-Michael addition of azoles to α,ß-unsaturated malonates.

A highly efficient method for the synthesis of azole derivatives via a direct aza-Michael addition of azoles to α,ß-unsaturated malonates using Cs2CO3 as a catalyst, has been successfully developed. A series of azole derivatives have been obtained in up to 94% yield and the reaction could be amplified to gram scale in excellent yield in the presence of 10 mol% of Cs2CO3.

Transamidation and Decarbonylation of N-Phthaloyl-Amino Acid Amides Enabled by Palladium-Catalyzed Selective C-N Bond Cleavage.

Amides are important functional synthons that have been widely used in the construction of peptides, natural products, and drugs. The C-N bond cleavage provides the direct method for amide conversion. However, amides, especially secondary amides, tend to be chemically inert due to the resonance of the amide bond. Here, we describe an efficient Pd-catalyzed transamidation and decarbonylation of multiamide structure molecules through C-N bond cleavage with excellent chemoselectivity. The transamidation of secondary amides and the decarbonylation of phthalimide provide meaningful tools for the modification of amino acid derivatives. Moreover, further transformations of azidation and C(sp3)-H monoarylation emphasized the potential utility of this selective C-N bond cleavage method.

[Clinical Analysis of B-Cell Non-Hodgkin Lymphoma Treated with Modified Conditioning Regimen].

OBJECTIVE: To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma. METHODS: 36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis. RESULTS: The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis. CONCLUSION: The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.

Synthesis of diosgenyl quaternary ammonium derivatives and their antitumor activity.

Giosgenin is a naturally steroidal saponin exhibiting a variety of biological activities including antitumor ones. A series of novel diosgenyl quaternary ammonium derivatives were designed and synthesized to develop potential anti-tumor agents in our research. All novel derivatives were characterized by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. The human cancer cell lines were A549 (Human lung cancer cell), H1975 (Human lung adenocarcinoma cell), A431 (Human skin squamous cell carcinoma), HCT-116 (Human colorectal adenocarcinoma cell), Aspc-1 (Human metastatic pancreatic cancer cell), Ramos (Human B lymphoma cell), HBE (Human bronchial epithelioid cell) and LO2 (Human normal hepatocyte).

Duloxetine combined with intra-articular injection versus intra-articular injection alone for pain relief in knee osteoarthritis: a study protocol for a randomised controlled trial.

INTRODUCTION: Intra-articular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) is a common treatment for osteoarthritis (OA) of the knee. As a drug treatment for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of OA and improve function of the knee joint. However, evidence regarding the efficacy of IA injection of HA+CS combined with duloxetine for pain management in patients with OA of the knee is lacking. The aim of this study was to test the hypothesis that IA injection of HA+CS combined with duloxetine could achieve pain management superior to that of IA injection of HA+CS alone in patients experiencing knee OA pain. METHODS: This study will adopt a prospective, randomised, open-label blind endpoint study design. In total, 150 patients with OA of the knee will be enrolled in the study. The participants will be randomly allocated to receive either a single IA injection of HA+CS combined with duloxetine or a single IA injection of HA+CS alone, and both groups will complete a 24-week follow-up to assess pain and functional improvements. The primary outcome measure is the change in the weekly mean of the 24 hours average pain scores from baseline to the end of 24 weeks in patients with OA of the knee, and the secondary outcomes include the response to treatment, changes from baseline in the brief pain inventory, improvement in the Western Ontario and McMaster Universities Osteoarthritis index scores, patient global impression of improvement scale, Hospital Anxiety and Depression Scale and adverse events during the 24-week follow-up. The data will be analysed by the intention-to-treat principle. ETHICS APPROVAL AND DISSEMINATION: This study was approved by the institutional ethics committee of the Beijing Tiantan Hospital (approval number: KY 2019-086-02). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04117893; Pre-results.

[Clinical Characteristics of 219 Patients with Primary Gastrointestinal Non-Hodgkin's Lymphoma].

OBJECTIVE: To analyze the clinical and pathological characteristics of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL) patients, and to explore the factors affecting the patients' survival and prognosis. METHODS: The clinical data of 219 patients with PGI-NHL diagnosed in our hospital from March 2009 to April 2016 was collected and retrospectively analyzed. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison among the groups, and Cox regression was used for multivariate analysis. RESULTS: Among the 219 patients with PGI-NHL, 126 patients were males and 93 patients were females. 182 patients were IPI 0 to 2 and 37 patients were IPI 3 to 5. There were 205 cases (93.6%) of B cell phenotype and 14 cases (6.4%) of T cell phenotype. 140 patients (63.9%) were patients with primary gastric NHL, including 85 DLBCL and 19 MALT. 79 cases (36.1%) were patients with primary intestinal NHL, including 46 DLBCL, 4 MALT, 7 FL, 3 MCL and 4 Burkitt lymphoma. 23 cases were HP positive and received anti-HP therapy. 57 cases and 32 cases received surgery and chemotherapy respectively. 84 cases received combination treatment of surgery and chemotherapy and 11 cases received combination treatment of radiotherapy and chemotherapy. Overall survival (OS) of indolent B-cell non-Hodgkin's lymphoma was longer than that of invasive B-cell non-Hodgkin's lymphoma, which shows better prognose. Kaplan-Meier analysis showed that there was no difference between progression-free survival (PFS) and OS in the patients with different origin sites, age and sex. There was no significant difference in PFS between B-cell and T-cell-derived patients, whereas OS of B-cell-derived PGI-NHL patients was longer than that of T-cell-derived PGI-NHL patients. The OS and PFS of patients with IPI 0-2 were longer than those of patients with IPI 3-5. According to Lugano and Ann Arbor staging systems, there was no difference in prognosis of patients between phase I/II and III/IV. The prognosis of patients treated with surgery alone was worse than that of patients treated with combination therapy, and the prognosis of patients with surgery combined with chemotherapy was not significantly different from that of patients with chemotherapy alone. CONCLUSION: B-cell phenotype, indolent and low IPI score lymphoma indicate better prognosis, while that of different origin site, sex and age shows no different in prognosis. Surgery is used only for emergency case or pathological materials, and these patients should be treated with chemotherapy-based combined treatment.

[Effect of early acupoint electrical stimulation on lower limb muscle strength in patients with septic shock].

OBJECTIVE: To observe the effect of early acupoint electrical stimulation on the decline of lower limbs muscle strength in patients with intensive care unit-acquired weakness (ICU-AW) caused by septic shock. METHODS: A total of 58 patients with ICU-AW caused by septic shock were randomly divided into an observation group (28 cases, 1 case dropped off ) and a control group (30 cases, 2 cases dropped off ). Patients in both groups received routine basic treatment. In the observation group, acupoint electric stimulation therapy was added at Huantiao (GB 30), Futu (ST 32), Zusanli (ST 36), Xuanzhong (GB 39) and Taichong (LR 3). Unilateral point with electrodes were applied, the SDZ-Ⅱ electronic instrument (discontinuous wave, frequency in 2 Hz, strength in 5 mA) was connected and changed to the other side after 30 min of unilateral treatment.The treatment was given 2 times daily, continued for 7 d or until the medical research council (MRC) score being 54 points or more. The changes of lower limb muscle strength MRC score, modified Rankin scale (MRS) score, bilateral quadriceps thickness and gastrocnemius pinnate angle of both groups were observed before treatment and on discharge. The time of admission to ICU, time of hospitalization, mortality during hospitalization, and mortality 28 d after discharge were compared between the two groups. The MRS scores of the two groups were followed up 28 d after discharge. RESULTS: The MRC scores of lower limb muscle strength in the two groups on discharge were higher than those before treatment (P<0.05), and the MRS scores on discharge and 28 d after discharge in the two groups were lower than those before treatment (P<0.05). The MRC scores of lower limb muscle strength on discharge in the observation group were higher than thoes in the control group (P<0.05), and the MRS scores on discharge and 28 d after discharge in the observation group were lower than those in the control group (P<0.05). On discharge, bilateral quadriceps thickness and gastrocnemius pinnate angle in the two groups were increased compared with those before treatment (P<0.05), and thoese in the observation group was higher than the control group (P<0.05). There was no significant difference between the two groups in the time of admission to ICU, time of hospitalization, mortality during hospitalization, and mortality 28 d after discharge (P>0.05). CONCLUSION: Early acupoint electrical stimulation can improve the lower extremity muscle decline in patients with ICU-AW caused by septic shock.

Risk Factors for Intestinal Barrier Impairment in Patients With Essential Hypertension.

Background: Previous studies have indicated an association between hypertension and intestinal barrier dysfunction in mice models. The present study aims to investigate the association between hypertension and intestinal barrier impairment in humans and identify the novel potential risk factors for hypertension. Methods: Medical data from consecutive inpatients were retrospectively pooled from patient records. We compared intestinal barrier serum markers [diamine oxidase (DAO), lipopolysaccharide (LPS), and D-lactate] between those patients with and without hypertension. Moreover, the associations between intestinal barrier markers and cardiovascular risk, hypertension history, blood pressure control, hypertensive complications, and antihypertensive medication history were also analyzed. Results: Overall, 106 hypertensive and 251 normotensive subjects were included. Patients with hypertension had a higher level of DAO (28.30 vs. 18.73%, P = 0.044) and LPS (22.64 vs. 11.16%, P = 0.005). In hypertensive patients, multivariate logistic regression analyses showed that long hypertension history (≥20 years), poor control of diastolic blood pressure, cardiac and renal complications, and use of multiple antihypertensive medications were risk factors for elevated DAO, while the use of multiple antihypertensive medications was a risk factor for elevated D-lactate (P < 0.05). Conclusions: Hypertension is associated with impairment of intestinal barrier, especially in patients with long duration, poor blood pressure control, cardiac and renal complications, and use of multiple antihypertensive medications. The current study indicates that intestinal barrier dysfunction might be a potential predictor of hypertension.

Effect of Mild Hypothermia on the Diaphragmatic Microcirculation and Function in A Murine Cardiopulmonary Resuscitated Model.

OBJECTIVE: Diaphragm dysfunction often occurs in patients with prolonged mechanical ventilation (MV) after resuscitation. Mild hypothermia (MHT) is a classical treatment to improve the outcomes of cardiac arrest (CA); however, the effect of MHT on diaphragm function remains unclear. In the present study, we aim to investigate the effect of MHT on diaphragmatic microcirculation and function using a murine cardiopulmonary resuscitation model. METHODS: Thirty-two rats were randomly assigned into a resuscitation normothermia group (RNT), an intraresuscitation hypothermia group (IRH), a postresuscitation hypothermia group (PRH), or a sham control group. CA was induced by airway occlusion, and resuscitation was implemented by precordial compression and MV. The diaphragmatic microvascular blood flow velocity, diaphragmatic microcirculation flow index (MFI), and perfused vascular density (PVD) were measured. The diaphragm was then removed for in vitro contractile property examination and cross-sectional area measurement. The lipid peroxidation and superoxide dismutase (SOD) levels in the diaphragm were also assayed. RESULTS: Either early or delayed MHT intervention did not improve the diaphragmatic microvascular blood flow velocity, MFI, and PVD, which were significantly decreased during prolonged MV after resuscitation. Compared with the RNT group, treatment with MHT increased the diaphragm contractility, fiber dimensions, and SOD levels and decreased diaphragm lipid peroxidation. A more significant change in these indices was observed in the IRH group compared with that in the PRH group. CONCLUSION: MHT preserves the diaphragm contractility and fiber dimensions and decreases oxidative stress but does not improve the microcirculatory blood supply during prolonged MV after resuscitation. Early MHT intervention is more efficient in preventing diaphragm dysfunction than delayed intervention after CA.

Solvothermal Synthesis of Humic Acid-Supported CeO2 Nanosheets Composite as High Performance Adsorbent for Congo Red Removal.

Surface properties and structures of materials are essential for their adsorption of pollutants in water. Humic acids (HA)-supported CeO2 nanosheet composites are synthesised by solvothermal method. The size of CeO2 nanosheets are approximately 100-500 nm. The obtained composite exhibits superior adsorption ability for Congo Red (CR) in water, which can be attributed to its unique structure and highly dispersed CeO2 nanosheet. The composite's adsorption behaviour of CR follows a pseudo-second-order mode and Langmuir adsorption model well, and the maximum adsorptive capacity for CR achieves 260 mg g-1. The presence of CeO2 nanosheets enhances surface area and enriches the mesoporous structure of the composites, thereby promoting CR adsorption capacity.

Development of genomic microsatellite markers for Aconitum gymnandrum (Ranunculaceae) by next generation sequencing (NGS).

Mating plays key roles in the demographic and genetic dynamics of populations. Estimates of mating portfolios and system based on progeny array (PA) method required highly polymorphic genetic markers, of which microsatellite is a good choice. In this study, we reported 19 polymorphic microsatellite loci for Aconitum gymnandrum. The number of alleles per locus ranged from 2 to 12. Observed and expected heterozygosity ranged from 0.000 to 1.000 and from 0.219 to 0.842, respectively. Seven loci showed significant deviation from Hardy-Weinberg equilibrium. These markers will provide a useful tool for pollination ecology and population genetic studies of A. gymnandrum in Qinghai-Tibet plateau.

Association between 5α-reductase inhibitors therapy and incidence, cancer-specific mortality, and progression of prostate cancer: evidence from a meta-analysis.

5α-reductase inhibitors (5-ARI) are widely employed for the treatment of benign prostatic hyperplasia. It has been noted that 5-ARI exhibit the potential to attenuate the risk of prostate cancer, but consistent agreement has not been achieved. Moreover, the effect of 5-ARI on cancer-specific mortality and progression of prostate cancer remains unclear. Therefore, the goal of the current meta-analysis was to elucidate the impact of 5-ARI on the incidence and progression of prostate cancer. We searched for all studies assessing the effect of 5-ARI on risk of prostate cancer in PubMed, Embase, Medline, and Cochrane Library databases. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were accepted to evaluate the association between 5-ARI and the risk of prostate cancer. Synthetic results implied that subjects who accepted 5-ARI compared with the placebo group experienced a distinctly weakened overall incidence of prostate cancer (RR = 0.74; 95% CI: 0.66-0.82; P < 0.001). Subgroup analyses further revealed that 5-ARI reduction of the incidence of prostate cancer was limited to low-grade (Gleason score 2-6; RR = 0.68; 95% CI: 0.57-0.81; P < 0.001) and intermediate-grade tumors (Gleason score 7; RR = 0.81; 95% CI: 0.67-0.97; P = 0.023), but not high-grade tumors (Gleason score >7; RR = 1.19; 95% CI: 0.98-1.43; P = 0.069). The results also showed that 5-ARI treatment did not significantly alter prostate cancer-specific mortality (RR = 1.0; 95% CI: 0.95-1.05; P = 0.916). In addition, it was worth noting that 5-ARI treatment acted in a protective role that presented a dramatic benefit to delay the progression of low-risk tumors (RR = 0.58; 95% CI: 0.43-0.78; P < 0.001).

Pediatric drug safety signal detection of non-chemotherapy drug-induced neutropenia and agranulocytosis using electronic healthcare records.

Objectives: This study aimed to develop a procedure to explore the adverse drug reaction signals of drug-induced neutropenia (DIN) or drug-induced agranulocytosis (DIA) in children using an electronic health records (EHRs) database. Methods: A two-stage design was presented. First, the suspected drugs to induce DIN or DIA were selected. Second, the associations were evaluated by a retrospective cohort study. Results: Ten and five drugs were potentially identified to be associated with DIN and DIA, respectively. Finally, five (oseltamivir, chlorpheniramine, vancomycin, meropenem, and ganciclovir) and two (chlorpheniramine, and vancomycin) drugs were found to be associated with DIN and DIA, respectively. Of these, the association between oseltamivir and neutropenia (P = 9.83 × 10-9; OR, 2.10; 95% CI, 1.62-2.69) was considered as a new signal for both adults and children. Chlorpheniramine-induced neutropenia (P = 3.01 × 10-8; OR, 1.59; 95% CI, 1.35-1.87) and agranulocytosis (P = 3.16 × 10-7; OR, 3.76; 95% CI, 2.25-6.26) were considered as new signals in children. Other drugs associated with DIN or DIA were confirmed by previous studies. Conclusion: A method to detect signals for DIN and DIA has been described. Several pediatric drugs were found to be associated with DIN or DIA.

Epidermal growth factor treatment has protective effects on the integrity of the blood-brain barrier against cerebral ischemia injury in bEnd3 cells.

Tight junctions (TJs) serve an important role in maintaining the integrity of the blood-brain barrier (BBB), while neurological disorders, including ischemic stroke, induce TJ disruption and increase BBB permeability; results include edema formation and hemorrhage transformation. Cerebral endothelium protection presents a promising approach in ischemic stroke therapy. In the current study, protective effects of the epidermal growth factor (EGF) on ischemia-induced disruption of BBB integrity were examined using an oxygen-glucose deprivation (OGD) model in bEnd3 cells. Expression levels of claudin-5 and TJ protein-1 (ZO-1) were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Cell viability was evaluated by cell counting kit-8 assay and the endothelial permeability of Lucifer yellow (LY) was assessed using Transwell assays. The results revealed that post-ischemia administration of EGF (250 ng/ml) significantly attenuated the decrease in mRNA (P<0.05) and protein (P<0.01) expression levels of claudin-5 and ZO-1, and the increase in endothelial permeability of LY (P<0.05) induced by 4 h OGD exposure followed by 24 h reoxygenation. In addition, EGF did not significant affect cell viability. The current study suggested a potential of EGF to improve BBB integrity against ischemic injury by upregulating the expression of TJ proteins and reducing endothelial permeability.

Association of PTTG1 polymorphism rs1895320, rs2910200 and rs6882742 with non-functioning pituitary adenomas in Chinese Han population: a case-control study.

Due to absence of clinical manifestations of hormonal hyper secretion, the treatment of Nonfunctioning pituitary adenoma (NFPA) was always delayed. PTTG1 was reported to be overexpressed in most of pituitary tumors, however, the polymorphism of PTTG1 rs1895320, rs2910200 and rs6882742 with NFPA were still not fully elucidated in NFPA. Thus, a hospital based case control study which included 79 patients and 142 healthy control participants were conducted. DNA was extracted from peripheral blood samples and genotyped by Mass Array methods. In addition, a meta-analysis of rs2910200 was also employed to further testify the conclusion. Significant difference were observed between patients and healthy controls under rs2910200 locus between allelic genotype (p = 0.0219). However, no other significant difference was observed in rs1895329 and rs6882742. In addition, a logistic regression analysis showed that the dominant model of rs2910200 were closely correlated with the NFPA susceptibility (OR = 1.951, 95% CI:1.075-3.542, p = 0.028). While no significant difference was observed in the rs1895320 and rs6882742 under dominant model, recessive model and additive model The meta-analysis results showed that the dominant model and heterozygote model can significantly increase the risk of PA (p = 0.007, OR = 1.57, 95% CI:1.14-2.18; p = 0.009, OR = 1.57, 95% CI:1.12-2.19). Whereas no significant difference were observed under the homozygous model and recessive model. In conclusion, the polymorphism of PTTG1 rs2910200 dominant model and T allelic might increase the risk of NFPA.