Effectiveness of remimazolam besylate combined with alfentanil for fiberoptic bronchoscopy with preserved spontaneous breathing: a prospective, randomized, controlled clinical trial.

OBJECTIVE: The novel short-acting benzodiazepine remimazolam besylate acts rapidly and is used to induce easily controlled sedation. The aim of this study was to investigate the effects of remimazolam besylate combined with alfentanil in patients undergoing fiberoptic bronchoscopy with preserved spontaneous breathing. PATIENTS AND METHODS: 192 patients undergoing painless fiberoptic bronchoscopy were randomly assigned to either propofol (P group) or remimazolam besylate (R group); both groups also received alfentanil 10 µg/kg. The respiratory rate was recorded during the inspection. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2), Narcotrend values and Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scores were recorded after entry to the operating room (T0), 1 min (T1), 2 min (T2) and 3 min (T3) after anesthesia, immediately after the bronchoscope entered the vocal cords (T4), when the bronchoscope reached the carina (T5), the patient's eyes opened (T6), and 30 min postoperatively (T7). Secondary outcomes included intraoperative hypotension and body movement grading, etc. RESULTS: There was less respiratory depression during the inspection in the R group than in the P group (p < 0.01). The rate of hypotension during the examination was higher in the P group than in the R group (p < 0.01). Narcotrend values in the P group were less for the R group at the T1-T5 time points (p < 0.01). No difference in the number of body movements ≥ grade 3 was found between the two groups (p > 0.05). CONCLUSIONS: Remimazolam besylate combined with alfentanil for painless fiberoptic bronchoscopy can better preserve the patient's spontaneous breathing and reduce the incidence of respiratory depression during the inspection than propofol.

Anatomical characteristics and significance of the metopism and Wormian bones in dry adult-Chinese skulls.

BACKGROUND: This study aimed to investigate the incidence, topographical distribution, morphology, and interrelationship of the metopism and Wormian bones (WBs) in dry adult-Chinese skulls. MATERIALS AND METHODS: In this study, 285 dried adult-Chinese skull specimens from the Department of Anatomy at the Southern Medical University were examined. The incidence of different types of metopism and WBs were recorded. The length of the metopic suture was measured using a flexible ruler. Additionally, the lengths and widths of the WBs were measured using a vernier calliper. RESULTS: The incidence of metopism and WBs in Chinese adults were estimated at 10.18% (29/285) and 63.86% (182/285), respectively. The metopism always accompanied WBs (26/29, 89.66%), but the WBs did not necessarily accompany metopism (26/182, 14.29%). The locations of the WBs in the order of decreasing incidence were the lambdoid suture (78.57%, 143/182), pterion (34.62%, 63/182), asterion (12.09%, 22/182), lambda (8.24%, 15/182), sagittal suture (4.95%, 9/182), and Inca bone (3.85%, 7/182). These locations differed in topographical distribution and morphological patterns. CONCLUSIONS: Chinese adults differ in incidence of metopism and WBs from adults of other races, indicating racial differences. The characteristics of WBs vary depending on the cranial site of occurrence. The metopism always accompanies WBs, but the WBs do not necessarily accompany metopism.

Quantum-enhanced radiometry via approximate quantum error correction.

Quantum sensing based on exotic quantum states is appealing for practical metrology applications and fundamental studies. However, these quantum states are vulnerable to noise and the resulting quantum enhancement is weakened in practice. Here, we experimentally demonstrate a quantum-enhanced sensing scheme with a bosonic probe, by exploring the large Hilbert space of the bosonic mode and developing both the approximate quantum error correction and the quantum jump tracking approaches. In a practical radiometry scenario, we attain a 5.3 dB enhancement of sensitivity, which reaches 9.1 × 10-4 Hz-1/2 when measuring the excitation population of a receiver mode. Our results demonstrate the potential of quantum sensing with near-term quantum technologies, not only shedding new light on the quantum advantage of sensing, but also stimulating further efforts on bosonic quantum technologies.

PGDIS position statement on the transfer of mosaic embryos 2021.

Chromosome testing strategies, such as preimplantation genetic testing for aneuploidy (PGT-A), improve initial IVF outcomes by avoiding unwitting transfer of aneuploid embryos in morphology-based selection practices. Newer technologies have revealed that some embryos may appear to have intermediate whole chromosome (or parts of a chromosome termed segmental) copy number results suggesting trophectoderm mosaicism. An embryo with a trophectoderm mosaic-range result may be the only option for transfer for some patients. Recent data suggest that such mosaic embryos can be transferred without added risk of abnormal birth outcomes but may be associated with increased implantation failure and miscarriage rates, with higher values of mosaicism appearing to be less favourable for producing good outcomes. In this Position Statement, we provide guidance to laboratories, clinics, clinicians and counsellors to assist in discussions on the utility and transfer of mosaic embryos.

Serum and exosomal hsa_circ_0000907 and hsa_circ_0057362 as novel biomarkers in the early diagnosis of diabetic foot ulcer.

OBJECTIVE: Diabetic foot ulcer (DFU) is a serious chronic complication leading to disability and death in patients suffering from diabetes. Currently, there is no effective marker for its early diagnosis. The aim of this study is to analyze the difference of circRNA expression profiles between DFU and normal human wounds (NHW) and to screen serum biomarkers for the early diagnosis of DFU. MATERIALS AND METHODS: Differentially expressed circRNAs were screened by bioinformatics analysis, using GSE114248 chip data downloaded from GEO database, including 5 pairs of tissue samples from DFU patients and NHW cases. Accordingly, 20 cases of DFU (Wagner grade 0~2), 20 non-DFU diabetes and 20 healthy controls were selected in the screening test, and the total RNAs of serum and serum-derived exosomes were extracted. The screened circRNAs were verified in the third largest cohort, and the ROC curves were drawn to assess the diagnostic efficiency. RESULTS: As discovered by experiment, there were a total of 67 circRNAs presented differential expressions between the two groups, with 28 circRNAs upregulated and 39 circRNAs downregulated in DFU group. Two types of circRNAs, hsa_circ_0000907 and hsa_circ_0057362, were selected as candidate biomarkers in current study and validated in a large cohort. The AUCs of serum hsa_circ_0000907 and hsa_circ_0057362 to diagnose early DFU were 0.9389 and 0.8792, respectively, and the AUCs of exosomal hsa_circ_0000907 and hsa_circ_0057362 to diagnose early DFU were 0.8783 and 0.8481, respectively. Furthermore, the expressions of serum hsa_circ_0000907 and hsa_circ_0057362 were negatively correlated with ankle brachial index (ABI) and transcutaneous oxygen pressure (TcPO2) in DFU patients. CONCLUSIONS: Serum and exosomal hsa_circ_0000907 and hsa_circ_0057362, especially hsa_circ_0000907, have novel diagnostic capabilities in the early diagnosis of DFU.

Epidemiology of infertility in China: a population-based study.

OBJECTIVE: To assess the current prevalence of and risk factors for infertility among couples of reproductive age in China. DESIGN: Population-based cross-sectional study. SETTING: We approached 25 270 couples in eight provinces/municipalities, of whom 18 571 (response rate 74%) were interviewed. POPULATION: Couples living together and married for more than 1 year, of whom the female spouse was 20-49 years old. METHODS: Women were approached via telephone and face-to-face conversation to complete the standardised and structured questionnaire by trained interviewers. MAIN OUTCOME MEASURES: Prevalence of and risk factors for infertility. RESULTS: Among women 'at risk' of pregnancy, the prevalence of infertility was 15.5% (2680/17 275). Among 10 742 women attempting to become pregnant, the prevalence of infertility was 25.0% (2680/10 742), which increased with age in the second population. Among women who failed to achieve pregnancy in the last 12 months, 3470 finished our questionnaire about fertility care, and 55.2% (1915/3470) of them had sought medical help. Sociodemographic risk factors for infertility included lower educational level [adjusted odds ratio (aOR) 3.4, 95% CI 2.0-5.5] and employment (aOR 2.3, 95% CI 1.9-2.9). Clinical risk factors were irregular menstrual cycle (aOR 1.8, 95% CI 1.2-2.5), light menstrual blood volume (aOR 1.6, 95% CI 1.2-2.0), history of cervicitis (aOR 1.5, 95% CI 1.2-2.0) and endometriosis (aOR 3.1, 95% CI 1.1-9.3), previous stillbirth (aOR 2.1, 95% CI 1.3-3.3) and miscarriage (aOR 2.7, 95% CI 2.1-3.5). In addition, history of operation was a significant risk factor of infertility. CONCLUSIONS: Among couples of reproductive age in China, the prevalence of infertility was 25%, and almost half of the couples experiencing infertility had not sought medical help. TWEETABLE ABSTRACT: In China, 25% of couples actively attempting to become pregnant suffered infertility.

Effects of epoxyeicosatrienoic acids (EETs) on retinal macular degeneration in rat models.

OBJECTIVE: Here we use a rat model to investigate the effects of epoxyeicosatrienoic acids (EETs) on retinal macular degeneration along with pathological and physiological mechanisms of the disease. MATERIALS AND METHODS: Six choroidal neovascularization (CNV) rats were created with a 532 nm laser and received intravitreal injections of EETs in both eyes. On day 1, 3, 7 and 14 after photocoagulation, the thickness and area of CNV were measured with HE staining and choroidal flat mounts. COX-2 and VEGF levels in CNV were detected by immunohistochemistry method. Protein and mRNA expression were studied by Western blotting and RT-PCR. RESULTS: 14 days after photocoagulation, CNV thickness and area were significantly reduced (p<0.01) in the treatment group compared with the control group. COX-2 and VEGF had high expression in vascular endothelial cells and stromal cells of CNV. Peak expression of COX-2 and VEGF was significantly higher (p<0.01) in the treatment group than in the control group. 7 days after photocoagulation, VEGF protein and mRNA expression were significantly lower (p<0.05) in the treatment group than in the control group, whereas COX-2 mRNA showed no significant difference (p>0.05). FFA found that CNV fluorescein leakage area was significantly reduced (p<0.05) in the treatment group than in the control group. 14 days after photocoagulation, neovascularization area was significantly smaller (p<0.05) in the treatment group than in the control group. Vitreous EETs levels in the treatment group were significantly higher than in the control group. Compared with the control group, the celecoxib treatment group had significantly increased vitreous EETs (p<0.05). CONCLUSIONS: Intravitreal injection of celecoxib could suppress the thickness and area of laser-induced macular degeneration CNV. It also improved the vitreous EETs levels in CNV model rats. COX-2 expression was upregulated in the early generation of laser-induced CNV, which may play an important role in regulating expression of VEGF.

USP22 down-regulation facilitates human retinoblastoma cell aging and apoptosis via inhibiting TERT/P53 pathway.

OBJECTIVE: Retinoblastoma is the most common malignant intraocular tumor in childhood, and still lacks effective treatment. The immortality of tumor cell can be attributed to elevated telomerase activity, which has been considered as tumor marker and treatment target. USP22 is one of the important targets for inhibiting tumor growth, but clear illustration regarding its effects of telomerase, tumor cell immortality and retinoblastoma cell aging or apoptosis via suppressing TERT/P53 signal pathway remains to be elusive. MATERIALS AND METHODS: MTT was used for describing cell proliferation, and Western blot was used to test protein expression level of USP22, TERT and P53. RT-qPCR was used to test USP22 mRNA level, followed by TRAP method to detect telomerase activity. Flow cytometry and comet assay were used to quantify cell apoptosis and DNA damage. Cell aging was measured by ß-galactosidase. RESULTS: The overexpression of USP22 significantly enhanced cell proliferation potency and telomerase activity, elevated TERT expression level, inhibited p53 expression and cell aging, as well as decreased cell apoptosis or DNA damage. Down-regulation of USP22 contributed to opposite effects. CONCLUSIONS: USP22 played an important role in retinoblastoma cell proliferation/aging and apoptosis. The reduction of USP22 expression facilitated human retinoblastoma cell aging or apoptosis via suppressing TERT/P53 signal pathway. USP22, thus, may work as a target for treating retinoblastoma.

Immune complexes induce TNF-α and BAFF production from U937 cells by HMGB1 and RAGE.

OBJECTIVE: This study investigated the effects of immune complexes (ICs) on tumor necrosis factor α (TNF-α) and B cell-activating factor (BAFF) production from U937 cells and further explored the mechanism. MATERIALS AND METHODS: U937 cells were incubated with necrosis supernatant or systemic lupus erythematosus (SLE) sera alone, or their combination. The expression of TNF-α and BAFF was determined by Real-time polymerase chain reaction and enzyme-linked immunosorbent assay. High mobility group box protein 1(HMGB1) A-box was produced by gene recombination. HMGB1 A-box and anti-receptor for advanced glycation end products (RAGE) antibody were adopted in the blocking experiments. The importance of DNA for cytokine induction was investigated by DNase treatment. RESULTS: The combination of necrosis supernatant and SLE sera induced the expression of TNF-α and BAFF significantly increased compared to necrosis supernatant or SLE sera alone. Recombinant HMGB1 A-box protein was purified, and TNF-α and BAFF production, which were induced by this combination, was blocked via HMGB1 A-box and anti-RAGE antibody. Moreover, we found that DNA component is important for the immunostimulatory activity of this combination. CONCLUSIONS: ICs containing DNA can promote TNF-α and BAFF production in U937 cells, and this process can be mediated by HMGB1 and RAGE. One possible mechanism of increasing BAFF production in SLE is proposed in this study whereby B cell activation, antibody production and ICs stimulated monocytes may create a vicious cycle that leads to B cell hyperactivity, which can be of importance for SLE etiopathogenesis.

Clinical significance of up-regulated lncRNA NEAT1 in prognosis of ovarian cancer.

OBJECTIVE: The purpose of the present study was to examine the expression levels of lncRNA NEAT1 in fresh ovarian cancer (OC) tissue and matched adjacent normal tissue specimens, and investigate the clinical significance of NEAT1 in OC. PATIENTS AND METHODS: NEAT1 levels in OC tissues and matched adjacent normal tissue specimens were tested by qRT-PCR. Then, statistical analysis was performed to explore the associations of NEAT1 expression with the clinical features and the prognosis of OC. RESULTS: NEAT1 is upregulated in ovarian cancer tissues compared with the corresponding adjacent non-neoplastic tissues. The expression level of NEAT1 was positively correlated with FIGO stage (p = 0.004), tumor grade (p = 0.009) and distant metastasis (p = 0.000). Also, the Kaplan-Meier survival curves revealed that high NEAT1 expression was associated with poor prognosis in OC patients. Multivariate Cox regression analysis showed that NEAT1 expression level (p < 0.001) was an independent factor in predicting the overall survival of OC patients. CONCLUSIONS: These results suggest that NEAT1 has a potential to function as a clinical biomarker for predicting disease invasiveness and prognosis of patients with OC.

Statin-treated patients with aneurysmal subarachnoid haemorrhage: a meta-analysis.

OBJECTIVE: The cerebral vasospasm, delayed ischemic neurological deficit (DIND), mortality and poor neurological outcome induced by aneurysmal subarachnoid haemorrhage (SAH) remain the major causes of morbidity and mortality in aneurysmal SAH patients. The effects of statin-treated for aneurysmal SAH patients were not comprehensively assessed. PATIENTS AND METHODS: A systematically literature search was conducted in PubMed, EMBASE, ScienceDirect and Web of Science to identify relevant studies update to March 2015. Data were extracted and appraised independently by two authors. Moreover, fixed or random effects models were applied to calculate pooled results based on the degree of heterogeneity. RESULT: Nine RCTs and three observational studies with a total of 1957 patients met the inclusion criteria. The results showed that statin treatment was not associated with a decrease in the occurrence of DIND (RR: 0.81, 95% CI: 0.66-1.00, p = 0.05), mortality (RR: 0.90, 95% CI: 0.69-1.18, p = 0.46) and poor neurological outcome (RR: 1.02, 95% CI: 0.86-1.20, p = 0.84), nonetheless, had a potential effect on reducing the incidence of vasospasm (RR: 0.77, 95% CI: 0.66-0.89, p = 0.0006). CONCLUSIONS: This meta-analysis indicated that the use of statins decreases the occurrence of cerebral vasospasm, whereas did not support a beneficial effect of statins on the occurrence of DIND, death or poor neurological outcomes in patients with aneurysmal SAH.

Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014.

With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22,774 and 84,572 annually. Rates of extended-spectrum ß-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.

VEGF Trapon inhibits tumor growth in papillary thyroid carcinoma.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many disease. Angiogenesis from thyroid cancer cell plays the important roles in post-surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). Vascular endothelial growth factor (VEGF) Trapon is a newly developed VEGF-blocking agent with stronger affinity and broader activity than the anti-VEGF antibody bevacizumab. In this study, we tested the activity of VEGF Trapon on a PTC model in vivo. MATERIALS AND METHODS: BC-PAP (derived from papillary carcinomas) transfected with a luciferase-expressing vector were injected into the back to mice. I.p. treatment with VEGF Trapon or control protein (25 mg/kg twice weekly) was started shortly after tumor injection to prevent tumor development (prevention model) or after established tumors were formed to inhibit tumor growth and metastasis formation (intervention model). RESULTS: In the prevention model, VEGF Trapon inhibited tumor growth by 73 ± 12% compared with control (p = 0.014) and significantly prolonged survival. In the intervention model, VEGF Trapon inhibited tumor growth by 68 ± 7% (p < 0.01). Microvascular density was reduced by 56% due to VEGF Trapon treatment (p < 0.01). CONCLUSIONS: VEGF Trapon is a potent inhibitor of BC-PAP tumor growth, angiogenesis and blocks the biological function of VEGF in vivo. These results support further clinical development of VEGF Trapon for PTC and other cancer types.

Knockdown of S100A4 chemosensitizes human laryngeal carcinoma cells in vitro through inhibition of Slug.

OBJECTIVE: S100A4 and Slug are known to be closely involved in resistance to chemotherapy. Furthermore, Slug signal was regulated by S100A4. Targeted therapy reducing S100A4 expression and Slug pathway activity may overcome the chemoresistance of human cancers. We hypothesized that over-expression of S100A4 and Slug was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether S100A4 silencing inhibited Slug, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin. MATERIALS AND METHODS: We investigated the effects of S100A4 and Slug silencing by siRNA transfection on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. In order to confirm the correlation between S100A4 and Slug signals, siRNA transfected Hep-2 cells were over-expressed by pSlug transfection, then explored the effect of S100A4 silencing on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. Real-time RT-PCR and Western blotting confirmed the presence of S100A4 mRNA, Slug mRNA and proteins in Hep-2 cells. RESULTS: We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with S100A4 and Slug expression. Knockdown of S100A4 and Slug markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth and increased apoptosis. Knockdown of S100A4 may significantly reduce the levels of S100A4 mRNA, Slug mRNA and proteins, in cisplatin-treated Hep-2 cells. Re-expression of Slug in S100A4 siRNA transfected Hep-2 cells restored the cisplatin resistance in the Hep-2 cells. CONCLUSIONS: Overexpression of S100A4 may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Knockdown of S100A4 enhances the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of Slug expression.

The activation of G protein-coupled receptor 30 (GPR30) inhibits proliferation of estrogen receptor-negative breast cancer cells in vitro and in vivo.

There is an urgent clinical need for safe and effective treatment agents and therapy targets for estrogen receptor negative (ER-) breast cancer. G protein-coupled receptor 30 (GPR30), which mediates non-genomic signaling of estrogen to regulate cell growth, is highly expressed in ER--breast cancer cells. We here showed that activation of GPR30 by the receptor-specific agonist G-1 inhibited the growth of ER--breast cancer cells in vitro. Treatment of ER--breast cancer cells with G-1 resulted in G2/M-phase arrest, downregulation of G2-checkpoint regulator cyclin B, and induction of mitochondrial-related apoptosis. The G-1 treatment increased expression of p53 and its phosphorylation levels at Serine 15, promoted its nuclear translocation, and inhibited its ubiquitylation, which mediated the growth arrest effects on cell proliferation. Further, the G-1 induced sustained activation and nuclear translocation of ERK1/2, which was mediated by GPR30/epidermal growth factor receptor (EGFR) signals, also mediated its inhibition effects of G-1. With extensive use of siRNA-knockdown experiments and inhibitors, we found that upregulation of p21 by the cross-talk of GPR30/EGFR and p53 was also involved in G-1-induced cell growth arrest. In vivo experiments showed that G-1 treatment significantly suppressed the growth of SkBr3 xenograft tumors and increased the survival rate, associated with proliferation suppression and upregulation of p53, p21 while downregulation of cyclin B. The discovery of multiple signal pathways mediated the suppression effects of G-1 makes it a promising candidate drug and lays the foundation for future development of GPR30-based therapies for ER- breast cancer treatment.

Formation of and countermeasures for subacute coronary stent thrombosis in elderly diabetic patients.

The aim of this study was to evaluate and investigate the pathogenetic mechanism and countermeasures of subacute thrombosis (SAT) after coronary stenting in elderly diabetic patients. The clinical characteristics and pathogenetic mechanisms in 3 cases of SAT after stent implantations in elderly diabetic patients were retrospectively examined to determine the treatment strategies for SAT. Among 98 patients with diabetes who had coronary stents implanted or were >60 years of age, three (3.06%) had SAT. One case of SAT was diagnosed by angiography; coronary balloon dilatation, thrombolysis, and re-perfusion resulted in full recovery in this case. The second case involved potential SAT, and in the third case, SAT was not ruled out. Two cases were characteristic of ST-segment elevation myocardial infarction, and one case, in which SAT was not ruled out, resulted in sudden death. SAT within a stent may be related to intraoperative stent malapposition caused by a grade C lesion, age, diabetes, chronic total occlusion, or postoperative irregular administration of medication.

Activation of eIF2α signaling cascade is associated with testosterone-induced cell apoptosis in INS-1 cells.

Hyperandrogenemia is associated with insulin resistance and type 2 diabetes in women with polycystic ovary syndrome raising the possibility that androgen receptor signaling pathway plays an important role in the development and progression of ß-cell dysfunction. Testosterone is the major circulating androgen in women. In this study, we investigated the effect of testosterone on INS-1 cells to find whether excess androgen could produce endoplasmic reticulum (ER) stress thereby contributing to ß-cell dysfunction. The role of testosterone in INS-1 cell apoptosis was detected by flow cytometry and electron microscopy. Expression of BIP, ATF4, and CHOP were assessed by RT-PCR and Western blot. Testosterone/AR could not only initiate cell apoptosis but also induce the activation of eukaryotic initiation factor 2 alpha (eIF2α) cascades in INS-1 cells. Treatment of ER stress inhibitor or flutamide (AR inhibitor) could inhibit testosterone-induced cell apoptosis and CHOP expression. These results suggest that testosterone/AR pathway caused INS-1 cell apoptosis was at least in part through eIF2α/CHOP cascades.

Modelling convection-enhanced delivery in normal and oedematous brain.

Convection-enhanced delivery (CED) could have clinical applications in the delivery of neuroprotective agents in brain injury states, such as ischaemic stroke. For CED to be safe and effective, a physician must have accurate knowledge of how concentration distributions will be affected by catheter location, flow rate and other similar parameters. In most clinical applications of CED, brain microstructures will be altered by pathological injury processes. Ischaemic stroke and other acute brain injury states are complicated by formation of cytotoxic oedema, in which cellular swelling decreases the fractional volume of the extracellular space (ECS). Such changes would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. Quantitative characterization of these changes will help confirm this prediction and assist in efforts to model the distribution of therapeutic agents. Three-dimensional computational models based on a Nodal Point Integration (NPI) scheme were developed to model infusions in normal brain and brain with cytotoxic oedema. These models were compared to experimental data in which CED was studied in normal brain and in a middle cerebral artery (MCA) occlusion model of cytotoxic oedema. The computational models predicted concentration distributions with reasonable accuracy.