Functional genomics analysis reveals the evolutionary adaptation and demographic history of pygmy lorises.

Lorises are a group of globally threatened strepsirrhine primates that exhibit many unusual physiological and behavioral features, including a low metabolic rate, slow movement, and hibernation. Here, we assembled a chromosome-level genome sequence of the pygmy loris (Xanthonycticebus pygmaeus) and resequenced whole genomes from 50 pygmy lorises and 6 Bengal slow lorises (Nycticebus bengalensis). We found that many gene families involved in detoxification have been specifically expanded in the pygmy loris, including the GSTA gene family, with many newly derived copies functioning specifically in the liver. We detected many genes displaying evolutionary convergence between pygmy loris and koala, including PITRM1. Significant decreases in PITRM1 enzymatic activity in these two species may have contributed to their characteristic low rate of metabolism. We also detected many evolutionarily convergent genes and positively selected genes in the pygmy loris that are involved in muscle development. Functional assays demonstrated the decreased ability of one positively selected gene, MYOF, to up-regulate the fast-type muscle fiber, consistent with the lower proportion of fast-twitch muscle fibers in the pygmy loris. The protein product of another positively selected gene in the pygmy loris, PER2, exhibited weaker binding to the key circadian core protein CRY, a finding that may be related to this species' unusual circadian rhythm. Finally, population genomics analysis revealed that these two extant loris species, which coexist in the same habitat, have exhibited an inverse relationship in terms of their demography over the past 1 million years, implying strong interspecies competition after speciation.

LncRNA NEAT-2 regulate the function of endothelial progenitor cells in experimental Sepsis model.

BACKGROUND: Sepsis is a life-threatening disease with a limited effectiveness and the potential mechanism remains unclear. LncRNA NEAT-2 is reported to be involved in the regulation of cardiovascular disease. This study aimed to investigate the function of NEAT-2 in sepsis. METHODS: We built sepsis animal model with Male Balb/C mice induced by cecal ligation and puncture (CLP). A total of 54 mice were randomly assigned into eight groups: sham operation group (n = 18), CLP group (n = 18), CLP plus si-control group (n = 3), CLP plus si-NEAT2 group (n = 3), CLP plus mimic control group (n = 3), CLP plus miR-320 group (n = 3), CLP plus normal saline group (n = 3), and normal control group (n = 3). The number of peripheral endothelial progenitor cells (EPCs), the expression level of NEAT-2 and miR-320 were detected during progression of sepsis, as well as the number of peripheral EPCs and level of TNF-α, IL-6, VEGF, ALT, AST and Cr. In addition, the function of EPCs was evaluated after NEAT-2 knockdown and miR-320 overexpression in vitro. RESULTS: The number of circulating EPCs increased significantly in sepsis. NEAT-2 expression was significantly increased in the progress of sepsis, accompanied with miR-320 downregulated. NEAT-2 knockdown and miR-320 overexpression attenuated hepatorenal function and increased cytokines in sepsis. Moreover, NEAT-2 knockdown and miR-320 overexpression decreased the proliferation, migration and angiogenesis of endothelial progenitor cells in vitro. CONCLUSIONS: LncRNA-NEAT2 regulated the number and function of endothelial progenitor cells via miR-320 in sepsis, which may contribute to the development of novel potential clinical therapy for sepsis.

Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.

Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

Helicobacter Pylori Related Gastric Cancer Screening and Cost-Effectiveness Analysis: A Hospital-Based Cross-Sectional Study (SIGES).

To evaluate the effectiveness of Helicobacter pylori (Hp) related gastric cancer screening (Hp-GCS) and cost-effectiveness of protocol candidates in a hospital-based cross-sectional study. A total of 163 gastric cancer patients in West China Hospital were retrospectively collected according to ICD-10 code and histologic proof between April 1, 2013 and March 31, 2014, and 15,599 cancer-free controls were simultaneously collected from the health checkup registry. Hp infection was examined by urea breath test (UBT). The prevalence of Hp infection was compared between patients and controls. The diagnostic performance of UBT-based predictive index was tested in both training and validation settings. Cost-effectiveness analysis was conducted to assess candidates of Hp-GCS protocols. The prevalence of Hp infection was 55.8% and 41.2% in gastric cancers and controls, respectively (p < 0.001). UBT-based model showed moderate diagnostic strength in Hp-GCS (AUC = 0.78, 95% CI 0.74-0.82), better than UBT alone (p < 0.001). The sensitivity and specificity of UBT-based index were 80.2% and 61.9% at optimal cutoff in training setting, comparable in validation setting, which sensitivity and specificity were 76.9% and 59.6%. Number needed to screen was decreased along with older age, as well as stronger positivity of UBT. The optimal cost-effective Hp-GCS protocol with detection rate (DR = 77.9%) was endoscopic screening in age 40-59 years and positive UBT, or age ≥60 years without UBT. Incremental analysis suggested a preferable protocol as endoscopic screening in age ≥40 years without UBT (DR = 93.3%). UBT had moderate diagnostic strength in massive gastric cancer screening, and might be cost-effective in middle-aged population (40-59 years). More robust Hp-GCS protocol needs further investigate in test methods and individual biologic features.

Microplitis bicoloratus bracovirus regulates cyclophilin A-apoptosis-inducing factor interaction to induce cell apoptosis in the insect immunosuppressive process.

Microplitis bicoloratus bracovirus (MbBV) induces apoptosis in hemocytes of the host (Spodoptera litura) via the cyclophilin A (CypA)-mediated signaling pathway. However, the mechanisms underlying CypA-mediated signaling during apoptosis remain largely unknown. Therefore, in this study, we investigated how CypA and apoptosis-inducing factor (AIF) interact during MbBV-mediated apoptosis. Our findings showed that MbBV induces apoptosis through the CypA-AIF axis of insect immune suppression. In MbBV-infected Spli221 cells, both the expression of the cypa gene and the release of AIF from the mitochondria increased the number of apoptotic cells. CypA and AIF underwent concurrent cytoplasm-nuclear translocation. Conversely, blocking of AIF release from mitochondria not only inhibited the CypA-AIF interaction but also inhibited the cytoplasmic-nuclear translocation of AIF and CypA. Importantly, the survival of the apoptotic phenotype was significantly rescued in MbBV-infected Spli221 cells. In addition, we found that the cyclosporine A-mediated inhibition of CypA did not prevent the formation of the CypA and AIF complex; rather, this only suppressed genomic DNA fragmentation. In vitro experiments revealed direct molecular interactions between recombinant CypA and AIF. Taken together, our results demonstrate that the CypA-AIF interaction plays an important role in MbBV-induced innate immune suppression. This study will help to clarify aspects of insect immunological mechanisms and will be relevant to biological pest control.

XIST as a valuable biomarker for prognosis and clinical parameters in diverse tumors: a comprehensive meta- and bioinformatics analysis.

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been found dysregulated in a variety of human tumors and influenced the clinicopathologic characteristics in cancer patients. Therefore, we systematically searched relevant literature that has identified the correlation of lncRNA XIST expression and clinical outcomes of tumor patients and conducted this meta-analysis to elucidate the clinical prognostic value of long noncoding RNA XIST in human tumors. A comprehensive literature search was performed from PubMed, Web of Science, EMBASE, and Cochrane library databases up to August 1, 2019. Pooled hazard ratios (HRs) or odds ratios (ORs) with a 95% confidence interval (95% Cl) were calculated to evaluate the prognosis, as well as the clinicopathological parameters of XIST, respectively. We also further validated this meta-analysis using The Cancer Genome Atlas (TCGA) dataset. The outcome revealed that XIST overexpression in tumor tissue was interacted to a poor overall survival (OS) (HR=0.52, 95% CI: 0.44-0.61, p<0.0001), disease-free survival (DFS) (HR=0.50; 95% CI: 0.36-0.69, p<0.0001), tumor type (digestive system malignancies, HR=0.53; 95% CI: 0.44-0.63, p<0.0001); nondigestive system malignancies, HR=0.48; 95% CI: 0.34-0.67, p<0.0001), lymph node metastasis(LNM) (OR=0.61, 95% CI: 0.37-1.00; p=0.048), differentiation (OR=1.46; 95% CI: 0.94-2.29; p=0.096), distant metastasis (DM) (OR=0.48, 95% CI: 0.31-0.75; p=0.001), tumor size (OR=0.59, 95% CI: 0.38-0.92; p=0.019), and tumor stage (OR=2.36; 95% CI: 1.62-3.43; p<0.001). XIST could have potential value in early diagnosis and result in prediction and provide a novel view for the therapeutic target in clinical application.

Stepwise reduction of bone mineral density increases the risk of cage subsidence in oblique lumbar interbody fusion patients biomechanically: an in-silico study.

BACKGROUND: Cage subsidence causes poor prognoses in patients treated by oblique lumbar interbody fusion (OLIF). Deterioration of the biomechanical environment initially triggers cage subsidence, and patients with low bone mineral density (BMD) suffer a higher risk of cage subsidence. However, whether low BMD increases the risk of cage subsidence by deteriorating the local biomechanical environment has not been clearly identified. METHODS: OLIF without additional fixation (stand-alone, S-A) and with different additional fixation devices (AFDs), including anterolateral single rod screws (ALSRs) and bilateral pedicle screws (BPSs) fixation, was simulated in the L4-L5 segment of a well-validated finite element model. The biomechanical effects of different BMDs were investigated by adjusting the material properties of bony structures. Biomechanical indicators related to cage subsidence were computed and recorded under different directional moments. RESULTS: Overall, low BMD triggers stress concentration in surgical segment, the highest equivalent stress can be observed in osteoporosis models under most loading conditions. Compared with the flexion-extension loading condition, this variation tendency was more pronounced under bending and rotation loading conditions. In addition, AFDs obviously reduced the stress concentration on both bony endplates and the OLIF cage, and the maximum stress on ALSRs was evidently higher than that on BPSs under almost all loading conditions. CONCLUSIONS: Stepwise reduction of BMD increases the risk of a poor local biomechanical environment in OLIF patients, and regular anti-osteoporosis therapy should be considered an effective method to biomechanically optimize the prognosis of OLIF patients.

Genomic and Phenotypic Analyses Reveal Mechanisms Underlying Homing Ability in Pigeon.

The homing pigeon was selectively bred from the domestic pigeon for a homing ability over long distances, a very fascinating but complex behavioral trait. Here, we generate a total of 95 whole genomes from diverse pigeon breeds. Comparing the genomes from the homing pigeon population with those from other breeds identifies candidate positively selected genes, including many genes involved in the central nervous system, particularly spatial learning and memory such as LRP8. Expression profiling reveals many neuronal genes displaying differential expression in the hippocampus, which is the key organ for memory and navigation and exhibits significantly larger size in the homing pigeon. In addition, we uncover a candidate gene GSR (encoding glutathione-disulfide reductase) experiencing positive selection in the homing pigeon. Expression profiling finds that GSR is highly expressed in the wattle and visual pigment cell layer, and displays increased expression levels in the homing pigeon. In vitro, a magnetic field stimulates increases in calcium ion concentration in cells expressing pigeon GSR. These findings support the importance of the hippocampus (functioning in spatial memory and navigation) for homing ability, and the potential involvement of GSR in pigeon magnetoreception.

Wild-type p53-induced phosphatase 1 down-regulation promotes apoptosis by activating the DNA damage-response pathway in amyotrophic lateral sclerosis.

Accumulation of DNA damage has been detected in the spinal cord of patients as well as in the G93A mouse model of amyotrophic lateral sclerosis (ALS). Wild-type p53-induced phosphatase 1 (Wip1) is a p53-inducible serine/threonine phosphatase that terminates DNA-damage responses via dephosphorylation of DNA-damage response proteins, namely ataxia-telangiectasia mutated (ATM) kinase, checkpoint kinase 2, and p53, thus enhancing cell proliferation. However, the role of Wip1, DNA-damage responses, and their interaction in ALS development remains to be elucidated. Here, we showed that Wip1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro. The DNA-damage response was activated in superoxide dismutase 1 (SOD1) G93A-transfected cells. However, increased expression of Wip1 improved cell viability and inhibited the DNA-damage response in mutated SOD1G93A cells. Further studies demonstrated that decreased Wip1 expression reduced cell viability and further activated the DNA-damage response in chronic H2O2-treated NSC34 cells. In contrast, Wip1 promoted cell survival and suppressed DNA damage-induced apoptosis during persistent DNA damage conditions. Over-expression of Wip1 in the central nervous system (CNS) can delay the onset of disease symptoms, extended the survival, decreased MN loss improved motor function and inhibit the DNA-damage response in SOD1 G93A mice. Furthermore, homeodomain-interacting protein kinase 2 (HIPK2) promoted the degradation of Wip1 via the ubiquitin-proteasome system during chronic stress. These findings indicate that persistent accumulation of DNA damage and subsequent chronic activation of the downstream DNA damage-response ATM and p53 pro-apoptotic signaling pathways may trigger neuronal dysfunction and neuronal death in ALS. Wip1 may play a protective role by targeting the DNA-damage response in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS.

Combined non-intubated anaesthesia and paravertebral nerve block in comparison with intubated anaesthesia in children undergoing video-assisted thoracic surgery.

BACKGROUND: This study is to investigate if non-intubated anaesthesia combined with paravertebral nerve block (PVNB) can enhance recovery in children undergoing video-assisted thoracic surgery (VATS). METHODS: A randomized controlled trial including 60 patients aged 3 to 8 years old who underwent elective VATS was performed. They were randomly assigned to receive non-intubated anaesthesia combined with PVNB or general anaesthesia with tracheal intubation (1:1 ratio). The primary outcome was the length of postoperative in-hospital stay. The secondary outcomes included emergence time, the incidence of emergence delirium, time to first feeding, time to first out-of-bed activity, pain score and in-hospital complications. RESULTS: The non-intubated group had shorter postoperative in-hospital stay than the control group (4 days [IQR, 4-6] vs 5 days [IQR, 5-8], 95% CI 0-2; P = .013). When compared to the control group, the incidence of emergence delirium (odds ratio [OR] 3.39, 95% CI 1.01-11.41; P = .043), emergence time, duration in the PACU, time to first eating food, first out-of-bed activity, pain score and consumption of sufentanil (at 6 and 12 hours after surgery) were decreased in the intervention group. In contrast, the incidence of airway complications was higher in the control than the intervention group (27.6% vs 6.9%, P = .037). There was no statistical significance in the occurrence of PONV, pneumothorax and other complications between the two groups. CONCLUSIONS: Non-intubated anaesthesia combined with PVNB enhances recovery in paediatric patients for video-assisted thoracic surgery although further multi-centre study is needed.

Analysis of risk factors and prevention strategies for functional delayed gastric emptying in 1243 patients with distal gastric cancer.

BACKGROUND: Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication. METHODS: Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression. RESULT: In multivariable analysis, age (OR 1.081, 95% CI, 1.047-1.117), BMI (OR 1.233, 95% CI, 1.116-1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829-8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325-6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632-7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963-5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086-1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003-1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068-0.785) was independent protective factor of FDGE. CONCLUSION: Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.

Development and validation of a nomogram for preoperative prediction of lymph node metastasis in early gastric cancer.

BACKGROUND: The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients. METHODS: This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram. RESULTS: Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively. CONCLUSIONS: Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.

Spodoptera litura cyclophilin A is required for Microplitis bicoloratus bracovirus-induced apoptosis during insect cellular immune response.

Microplitis bicoloratus bracovirus (MbBV) is a polydnavirus found in the parasitic wasp M. bicoloratus. Although MbBV is a known inducer of apoptosis in host hemocytes, the mechanism by which this occurs remains elusive. In this study, we found that expression of cyclophilin A (CypA) was significantly upregulated in Spodoptera litura hemocytes at 6-day post-parasitization. Similar results were reported in High Five cells (Hi5 cells) infected by MbBV, suggesting that the upregulation of CypA is linked to MbBV infection in insect cells. cDNA encoding CypA was cloned from parasitized hemocytes of S. litura, and bioinformatic analyses showed that S. litura CypA belongs to the cyclophilin family of proteins. Overexpression of S. litura CypA in Hi5 cells revealed that the protein promotes MbBV-induced apoptosis in vitro. Conversely, suppression of the expression and activity of CypA protein significantly rescued the apoptotic phenotype observed in MbBV-infected Hi5 cells, suggesting that it plays a key role in this process. MbBV infection also promoted the cytoplasmic-nuclear translocation of CypA in Hi5 cells. Taken together, these results suggest that MbBV infection upregulates the expression of CypA, which is required for MbBV-mediated apoptosis. Our findings provide insight into the role that CypA plays in insect cellular immune response.

Effect of Dexmedetomidine-Mediated Insulin-Like Growth Factor 2 (IGF2) Signal Pathway on Immune Function and Invasion and Migration of Cancer Cells in Rats with Ovarian Cancer.

BACKGROUND The aim of this study was to explore the effect of dexmedetomidine (DEX)-mediated insulin-like growth factor 2 (IGF2) signal pathway on immune function and cancer cell invasion and migration in rats with ovarian cancer. MATERIAL AND METHODS Forty rats with ovarian cancer were divided into 4 groups: model group, and low dose (0.2 µg/kg/hour DEX), medium dose (1.0 µg/kg/hour DEX), and high dose (5.0 µg/kg/hour DEX) DEX groups. In addition, 10 Fischer344 rats were selected as a normal group. Human NUTU-19 poorly differentiated epithelial ovarian cancer cell line cells were divided into 4 groups: a blank group and low dose, medium dose, and high dose DEX NUTU-19 groups. RESULTS Compared with the normal group, in the other groups the serum interleukin (IL)-2 and interferon gamma (INF-γ) levels, CD4⁺ and CD8⁺ percentages, CD4⁺/CD8⁺ ratio, and transformation rate of splenic lymphocytes were decreased, and the serum tumor necrosis factor alpha (TNF-alpha) level, IGF2, insulin-like growth factor 1 receptor (IGF1R), insulin receptor substrate 1 (IRS1) mRNA, and protein expressions in ovarian tissue were increased (all P<0.05). Results in the DEX groups compared with model group were the opposite of those in the other groups compared with normal group (all P<0.05). Compared with the blank group, in the other groups the proliferation, invasion, and migration of ovarian cancer cells were reduced significantly (all P<0.05). Compared with the low dose DEX NUTU-19 group, in the high dose DEX NUTU-19 group the invasion and migration of ovarian cancer cells weakened significantly (both P<0.05). CONCLUSIONS A certain dose of DEX can effectively inhibit IGF2 signal pathway activation to improve the immune function of rats with ovarian cancer, inhibiting the invasion and migration of ovarian cancer cells.

Low power consumption thermo-optic switch formed by an integrated processing method.

In this paper, an integrated processing method was demonstrated to fabricate the polymer-based thermo-optic (TO) switch with low power consumption. The characteristic parameters of the switch were carefully designed and simulated. The air trench structure was exploited to reduce the power consumption, which can be formed with the waveguide simultaneously by the integrated processing method. Moreover, the introduced polymer/silica hybrid waveguide structure can also improve the response time of the device. A typical fabricated switch presented a low switching power of 5.2 mW. The measured switching rise time and fall time are 192.2 and 201.1 µs, respectively.

Quantitative ultra-high-performance liquid chromatography-tandem mass spectrometry for determination of dexmedetomidine in pediatric plasma samples: Correlation with genetic polymorphisms.

Dexmedetomidine is an important sedative agent administered as premedication to achieve procedural sedation in children. To describe the correlation between the genetic state and the concentration of dexmedetomidine, it is necessary to develop a specific, time-saving and economical method for detection of dexmedetomidine in plasma samples. In this work, an ultra-high-performance liquid chromatography (UHPLC)-tandem mass spectrometry method has been established and validated for detection of dexmedetomidine in plasma from pediatric population. After a simple liquid-liquid extraction with an organic solution, the analytes were separated on an ACQUITY BEH C18 column (2.1 mm × 50 mm, 1.7 µm particle size) by gradient elution with the mobile phase of acetonitrile and 1‰ aqueous formic acid (flow rate 0.3 mL min-1 ). Mass spectrometry measurements were performed under the positive selected reaction monitoring and the mass transitions monitored were m/z 201.3 → 95.1, 204.2 → 98.0 for dexmedetomidine and deuterated medetomidine (internal standard), respectively. Validation of the method based on China Food and Drug Administration guidelines showed acceptable selectivity. The UHPLC method employed a stable isotope-labeled internal standard, showed good specificity and was successfully used to detect dexmedetomidine in plasma samples from 260 pediatric patients. A subsequent application of this method to a pharmacogenetic study was also described. Importantly, this is the first study to report the correlation between CYP2A6 rs835309 activity and concentration of dexmedetomidine.

Dexmedetomidine versus sufentanil with high- or low-concentration ropivacaine for labor epidural analgesia: A randomized trial.

AIM: To study analgesic effects of dexmedetomidine or sufentanil, both combined with ropivacaine, in epidural analgesia during labor. METHODS: We recruited 160 primigravidae with full-term pregnancy who received epidural anesthesia during labor and randomized them into four groups to receive epidural administration of ropivacaine combined with sufentanil (RS1 and RS2 groups) or with dexmedetomidine (RD1 and RD2 groups). Systolic blood pressure, diastolic blood pressure and heart rate before anesthesia (T1 ), 15 min after anesthesia induction (T2 ), on delivery (T3 ) and 2 h postpartum (T4 ), together with visual analogue scale scores, Bromage scores, Ramsay scores, adverse reactions during analgesia and urinary retention at 6 and 24 h postpartum were recorded; the pH, PCO2 and PO2 of umbilical cord arterial blood and Apgar scores at 1, 5 and 10 min after childbirth were assessed. RESULTS: RS1 group had significantly lower systolic blood pressure, diastolic blood pressure and heart rate than RD1 group at T2 and T3 (all P < 0.05), but not at T1. At T2 and T3 , the other three groups were lower than RS2 group in visual analogue scale and Ramsay scores (all P < 0.05). After childbirth, RD2 group had significantly higher PO2 result than other three groups (P < 0.05). At 6 h postpartum, RD2 group had significantly fewer cases of urinary retention than RD1 and RS1 groups (both P < 0.05). CONCLUSION: A relatively low concentration of ropivacaine, combined with dexmedetomidine, is better in analgesia during labor.

A randomized controlled trial of oral chloral hydrate vs intranasal dexmedetomidine plus buccal midazolam for auditory brainstem response testing in children.

BACKGROUND: Moderate to deep sedation is required for an auditory brainstem response test when high-intensity stimulation is used. Chloral hydrate is the most commonly used sedative, whereas intranasal dexmedetomidine is increasingly used in pediatric non-painful procedural sedations. OBJECTIVE: The aim of this study was to compare the sedation success rate after oral chloral hydrate at 50 mg kg-1 and intranasal dexmedetomidine at 3 µg kg-1 plus buccal midazolam at 0.1 mg kg-1 for an auditory brainstem response test. METHODS: Children who required an auditory brainstem response test were recruited and randomly assigned to receive oral chloral hydrate at 50 mg kg-1 and intranasal placebo, or intranasal dexmedetomidine at 3 µg kg-1 with buccal midazolam 0.1 mg kg-1 . The primary outcome was the rate of successful sedation for auditory brainstem response tests. RESULTS: Fifty-seven out of 82 (69.5%) were successfully sedated after chloral hydrate, while 70 out of 78 (89.7%) children were successfully sedated with dexmedetomidine plus midazolam combination, with the odd ratio (95% CI) for successful sedation between dexmedetomidine plus midazolam combination and chloral hydrate estimated to be 3.84 (1.61-9.16), P = 0.002. Dexmedetomidine plus midazolam was associated with quicker onset with median onset time 15 (IQR 11.0-19.8) for dexmedetomidine plus midazolam and 20 (IQR 15.0-27.0) for chloral hydrate respectively, with difference between median (95% CI) of 5 [3-8], P < 0.0001). The behavior observed during drug administration of intranasal dexmedetomidine and buccal midazolam was better that of the children who had oral chloral hydrate. No children required oxygen therapy or medical intervention for hemodynamic disturbances in this study and the incidence of hypotension and bradycardia was similar. CONCLUSION: Intranasal dexmedetomidine plus buccal midazolam was associated with higher sedation success with deeper level of sedation, with similar discharge time and adverse event rate when compared to chloral hydrate.

Comparison of rescue techniques for failed chloral hydrate sedation for magnetic resonance imaging scans--additional chloral hydrate vs intranasal dexmedetomidine.

BACKGROUND: Chloral hydrate, a commonly used sedative in children during noninvasive diagnostic procedures, is associated with side effects like prolonged sedation, paradoxical excitement, delirium, and unpleasant taste. Dexmedetomidine, a highly selective α-2 agonist, has better pharmacokinetic properties than chloral hydrate. We conducted this prospective, double-blind, randomized controlled trial to evaluate efficacy of intranasal dexmedetomidine with that of a second oral dose of chloral hydrate for rescue sedation during magnetic resonance imaging (MRI) studies in infants. METHODS: One hundred and fifty infants (age group: 1-6 months), who were not adequately sedated after initial oral dose of 50 mg · kg(-1) chloral hydrate, were randomly divided into three groups with the following protocol for each group. Group C: second oral dose chloral hydrate 25 mg · kg(-1); Group L and Group H: intranasal dexmedetomidine in a dosage of 1 and 2 mcg · kg(-1), respectively. Status of sedation, induction time, time to wake up, vital signs, oxygen saturation, and recovery characteristics were recorded. RESULTS: Successful rescue sedation in Groups C, L, and H were achieved in 40 (80%), 47 (94%), and 49 (98%) of infants, respectively, on an intention to treat analysis, and the proportion of infants successfully sedated in Group H was more than that of Group L (P ˂ 0.01). There were no significant differences in sedation induction time; however, the time to wake up was significantly shorter in Group L as compared to that in Group C or H (P < 0.01). No significant adverse hemodynamic or hypoxemic effects were observed in the study. CONCLUSION: Intranasal dexmedetomidine induced satisfactory rescue sedation in 1- to 6-month-old infants during MRI study, and appears to cause sedation in a dose-dependent manner.