Deletion of TECRL promotes skeletal muscle repair by up-regulating EGR2.

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further show that TECRL deletion led to the upregulation of the histone acetyltransferase general control nonderepressible 5, which enhances the transcription of EGR2 through acetylation. Importantly, we showed that AAV9-mediated TECRL silencing improved muscle repair in mice. These findings shed light on myogenic regeneration and muscle repair.

Calibration-free, high-precision, and robust terahertz ultrafast metasurfaces for monitoring gastric cancers.

Optical sensors, with great potential to convert invisible bioanalytical response into readable information, have been envisioned as a powerful platform for biological analysis and early diagnosis of diseases. However, the current extraction of sensing data is basically processed via a series of complicated and time-consuming calibrations between samples and reference, which inevitably introduce extra measurement errors and potentially annihilate small intrinsic responses. Here, we have proposed and experimentally demonstrated a calibration-free sensor for achieving high-precision biosensing detection, based on an optically controlled terahertz (THz) ultrafast metasurface. Photoexcitation of the silicon bridge enables the resonant frequency shifting from 1.385 to 0.825 THz and reaches the maximal phase variation up to 50° at 1.11 THz. The typical environmental measurement errors are completely eliminated in theory by normalizing the Fourier-transformed transmission spectra between ultrashort time delays of 37 ps, resulting in an extremely robust sensing device for monitoring the cancerous process of gastric cells. We believe that our calibration-free sensors with high precision and robust advantages can extend their implementation to study ultrafast biological dynamics and may inspire considerable innovations in the field of medical devices with nondestructive detection.

White and Gray Matter Abnormalities in Young Adult Females with Dependent Personality Disorder: A Diffusion-Tensor Imaging and Voxel-Based Morphometry Study.

We applied diffusion-tensor imaging (DTI) including measurements of fractional anisotropy (FA), a parameter of neuronal fiber integrity, mean diffusivity (MD), a parameter of brain tissue integrity, as well as voxel-based morphometry (VBM), a measure of gray and white matter volume, to provide a basis to improve our understanding of the neurobiological basis of dependent personality disorder (DPD). DTI was performed on young girls with DPD (N = 17) and young female healthy controls (N = 17). Tract-based spatial statistics (TBSS) were used to examine microstructural characteristics. Gray matter volume differences between the two groups were investigated using voxel-based morphometry (VBM). The Pearson correlation analysis was utilized to examine the relationship between distinct brain areas of white matter and gray matter and the Dy score on the MMPI. The DPD had significantly higher fractional anisotropy (FA) values than the HC group in the right retrolenticular part of the internal capsule, right external capsule, the corpus callosum, right posterior thalamic radiation (include optic radiation), right cerebral peduncle (p < 0.05), which was strongly positively correlated with the Dy score of MMPI. The volume of gray matter in the right postcentral gyrus and left cuneus in DPD was significantly increased (p < 0.05), which was strongly positively correlated with the Dy score of MMPI (r1,2= 0.467,0.353; p1,2 = 0.005,0.04). Our results provide new insights into the changes in the brain structure in DPD, which suggests that alterations in the brain structure might implicate the pathophysiology of DPD. Possible visual and somatosensory association with motor nerve circuits in DPD.

The development of cortical functional hierarchy is associated with the molecular organization of prenatal/postnatal periods.

The human cerebral cortex conforms to specific functional hierarchies facilitating information processing and higher-order cognition. Prior studies in adults have unveiled a dominant functional hierarchy spanning from sensorimotor regions to transmodal regions, which is also present in younger cohorts. However, how the functional hierarchy develops and the underlying molecular mechanisms remain to be investigated. Here, we set out to investigate the developmental patterns of the functional hierarchy for preschool children (#scans = 141, age = 2.41-6.90 years) using a parsimonious general linear model and the underlying biological mechanisms by combining the neuroimaging developmental pattern with two separate transcriptomic datasets (i.e. Allen Human Brain Atlas and BrainSpan Atlas). Our results indicated that transmodal regions were further segregated from sensorimotor regions and that such changes were potentially driven by two gene clusters with distinct enrichment profiles, namely prenatal gene cluster and postnatal gene cluster. Additionally, we found similar developmental profiles manifested in subsequent developmental periods by conducting identical analyses on the Human Connectome Projects in Development (#scans = 638, age = 5.58-21.92 years) and Philadelphia Neurodevelopment Cohort datasets (#scans = 795, age = 8-21 years), driven by concordant two gene clusters. Together, these findings illuminate a comprehensive developmental principle of the functional hierarchy and the underpinning molecular factors, and thus may shed light on the potential pathobiology of neurodevelopmental disorders.

Association of sleep quality on the night of operative day with postoperative delirium in elderly patients: A prospective cohort study.

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.

Ultrasensitive Terahertz Biodetection Enabled by Quasi-BIC-Based Metasensors.

Advanced sensing devices, highly sensitive, and reliable in detecting ultralow concentrations of circulating biomarkers, are extremely desirable and hold great promise for early diagnostics and real-time progression monitoring of diseases. Nowadays, the most commonly used clinical methods for diagnosing biomarkers suffer from complicated procedures and being time consumption. Here, a chip-based portable ultra-sensitive THz metasensor is reported by exploring quasi-bound states in the continuum (quasi-BICs) and demonstrate its capability for sensing low-concentration analytes. The designed metasensor is made of the designed split-ring resonator metasurface which supports magnetic dipole quasi-BIC combining functionalized gold nanoparticles (AuNPs) conjugated with the specific antibody. Attributed to the strong near-field enhancement near the surface of the microstructure enabled by the quasi-BICs, light-analyte interactions are greatly enhanced, and thus the device's sensitivity is boosted significantly. The system sensitivity slope is up to 674 GHz/RIU, allowing for repeatable resolving detecting ultralow concentration of C-reactive protein (CRP) and Serum Amyloid A (SAA), respectively, down to 1 pM. The results touch a range that cannot be achieved by ordinary immunological assays alone, offering a novel non-destructive and rapid trace measured approach for next-generation biomedical quantitative detection systems.

Airway management in out-of-hospital cardiac arrest: A systematic review and network meta-analysis.

OBJECTIVES: Airway management during cardiopulmonary resuscitation is particularly important for patients with out-of-hospital cardiac arrest (OHCA). This study was performed to compare the efficacy of the most commonly used out-of-hospital airway management methods in increasing the survival to discharge in patients with OHCA. METHODS: We screened all relevant literature from database inception to 21st January 2019 in PubMed, Web of Science, Embase, and the Cochrane Library. We included all randomized controlled trials (RCTs) of airway management for OHCA in adults (≥16 years of age) with no limitations on publication status, publication date, or language. The primary outcome was survival to discharge. The secondary outcomes were the overall airway technique success rate, return of spontaneous circulation, and survival to hospital admission. RESULTS: Overall, from 1986 to 2018, 9 RCTs involving 13,949 patients were included in the network meta-analysis, and the efficacy of six airway management methods for patients with OHCA were compared. However, none of the results were statistically significant. CONCLUSIONS: As the gold standard of airway management for patients with out-of-hospital cardiac arrest in most countries, endotracheal intubation (ETI) has been widely used for many years. However, our systematic review and network meta-analysis showed that ETI is no better than other methods in increasing the survival to discharge. This is not directly proportional to the various preparations required before ETI. Additional randomized controlled trials are needed to identify more effective methods and improve patients' outcome.

Pancreatic follicular dendritic cell sarcoma: a case report.

BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is a rare, low-to-moderate-grade malignant tumor, which occurs in the dendritic cells of the germinal center. Pancreatic FDCS (PFDCS) is extremely rare, with only a few reported cases. Presently, the etiology and pathogenesis of pancreatic FDCS are still unclear, and the clinical symptoms and signs as well as the laboratory diagnosis lack specificity. Although PFDCS presents better histological and morphological characteristics and a distinct immunophenotype, it can be easily missed and/or misdiagnosed if it occurs outside the node. Lymph node FDCS are easier to diagnose because of the rarity of fusiform cell tumors in lymph nodes. CASE DEMONSTRATION: Herein, we reported a 67-year-old female patient with upper-left abdominal pain without obvious cause and was admitted for treatment. A computed tomography (CT) scan revealed a cystic solid mass in the pancreatic tail toward the greater curvature of the stomach, with an obvious enhancement of the cyst wall in enhanced scanning. Subsequently, the patient underwent surgical resection and the resected sample was sent for pathological biopsy. According to the results, the pathology was consistent with the histological morphology and immunohistochemical characteristics of FDCS, and the Epstein-Barr virus (EBV)-encoded RNA was negative for in situ hybridization. Three months post-resection, the patient returned to the hospital for chemotherapy. This case report is aimed to improve the clinical recognition of FDCS. CONCLUSION: Pancreatic FDCS is a rare disease. Herein, we have reported a case of pancreatic FDCS and analyzed its clinical and pathological features and differential diagnosis to improve the understanding of FDCS.

Structural brain alterations in young adult males with narcissistic personality disorder: a diffusion tensor imaging study.

PURPOSES: 1. To find a difference in white matter (WM) between young adult males with narcissistic personality disorder (NPD) and healthy controls (HCs). 2. To find some correlations between white matter in the abnormal regions of NPD group and the pathological narcissism inventory (PNI). MATERIALS AND METHODS: Eighteen male participants with NPD (age M = 18.39, SD = 0.164; education M = 12.33, SD = 0.14) were included in our experiment. NPD participants met the DSM-IV criteria for NPD and without other personality disorders evaluated by trained clinical psychiatrists using the Structured Clinical Interview of DSM-IV for Personality Disorders (SCID-II). Moreover, healthy controls were also confirmed to be free of any axis I or II disorders and matched with education level, age and handedness (age M = 18.83 years, SD = 0.246; education M = 12.56, SD = 0.202; all participants were right handed). Those who have had major life events in the last six months, mental and physical illnesses, claustrophobia and oral implants have been excluded. We used tract-based spatial statistics (TBSS) on diffusion tensor images (DTI) and analysis of Pearson correlation between abnormal brain regions of white matter fibers and the pathological narcissism inventory. RESULTS: There was no significant difference in age and education level between NPD and HCs (p > 0.05). There were significant differences in PNI score and its subscales between NPD group and HCs (p < 0.01). Fractional anisotropy (FA) values were found decreased mainly in the right superior longitudinal fasciculus and the bilateral posterior thalamic radiation (include optic radiation). Lower axial diffusivity (AD) values were identified mostly in the left retrolenticular part of internal capsule and the left posterior thalamic radiation (include optic radiation). There existed a significant correlation between DTI data and pathological narcissism inventory. CONCLUSIONS: The decreased brain white matter microstructures among three clusters were found in the association, projection/thalamic and connection pathways of white matter in young adult males with NPD. The abnormal white matter brain regions may be one of the neuropathological basis of the pathogenesis of young males with NPD, and it may be related to white matter development in early adulthood.

Ultrafast Modulation of THz Waves Based on MoTe2-Covered Metasurface.

The sixth generation (6G) communication will use the terahertz (THz) frequency band, which requires flexible regulation of THz waves. For the conventional metallic metasurface, its electromagnetic properties are hard to be changed once after being fabricated. To enrich the modulation of THz waves, we report an all-optically controlled reconfigurable electromagnetically induced transparency (EIT) effect in the hybrid metasurface integrated with a 10-nm thick MoTe2 film. The experimental results demonstrate that under the excitation of the 800 nm femtosecond laser pulse with pump fluence of 3200 µJ/cm2, the modulation depth of THz transmission amplitude at the EIT window can reach 77%. Moreover, a group delay variation up to 4.6 ps is observed to indicate an actively tunable slow light behavior. The suppression and recovery of the EIT resonance can be accomplished within sub-nanoseconds, enabling an ultrafast THz photo-switching and providing a promising candidate for the on-chip devices of the upcoming 6G communication.

[Exercise preconditioning attenuates the lipid metabolic disorder induced by chronic high fat diet feeding in mice].

Mounting evidence has shown that exercise exerts extensive beneficial effects, including preventing and protecting against chronic diseases, through improving metabolism and other mechanisms. Recent studies have shown that exercise preconditioning affords significant cardioprotective effects. However, whether exercise preconditioning improves high fat diet (HFD)-induced obesity and lipid metabolic disorder remains unknown. The study was aimed to explore the effects of exercise preconditioning on HFD-induced obesity and lipid metabolic disorder in mice. 4-week-old C57BL/6 mice were subjected to swimming or sedentary control for 3 months, and then were fed with normal diet (ND) or HFD for 4 more months. The results showed that the blood glucose was decreased, and the glucose tolerance and grip strength were increased in exercised mice after training. Exercise preconditioning failed to improve HFD-induced body weight gain, but improved HFD-induced glucose intolerance. Exercise preconditioning showed no significant effects on both exercise capacity and physical activity in ND- and HFD-fed mice. HFD feeding increased total cholesterol and low density lipoprotein (LDL) levels in circulation, promoted subcutaneous fat and epididymal fat accumulation in mice. Exercise preconditioning increased circulating high density lipoprotein (HDL) and decreased circulating LDL, without affecting the subcutaneous fat and epididymal fat in HFD-fed mice. HFD feeding increased liver weight and hepatic total cholesterol contents, and dysregulated the expressions of several mitochondria function-related proteins in mice. These abnormalities were partially reversed by exercise preconditioning. Together, these results suggest that exercise preconditioning can partially reverse the HFD-induced lipid metabolic disorder and hepatic dysfunction, and these beneficial effects of exercise sustain for a period of time, even after exercise is discontinued.

[Study on protective effect of Chaihu Shugan Powder against liver injury in rats with intrahepatic cholestasis by regulating FXR/Nrf2/ARE pathway].

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.

Optically Controlled Ultrafast Terahertz Metadevices with Ultralow Pump Threshold.

Arming metasurface with active materials furnishes a feasible solution to dynamically control over terahertz (THz) waves, which is extremely significant for the realization of upcoming sixth generation telecommunications. However, the present active materials are mainly limited to single external driving field, hindering the capability of metasurface for flexible manipulation of THz waves. Besides, less attention has been paid to the energy question how to significantly reduce the pump threshold for achieving the desired function. Here, a germanium (Ge) hybrid Fano metasurface under dual-stimulus control is experimentally demonstrated. Photoexcitation of Ge thin film enables 100% modulation depth of Fano resonance and ultrafast switching time within 10 ps. By adding current-bias, the pump threshold to modulate the metasurface is greatly reduced from 1600 to 200 µJ cm-2 . Different from the optical modulation independent of film thickness, it is found that the current function is in proportion with the thickness of Ge thin film. Moreover, it is demonstrated that compared to the single optical-stimulus, the THz amplitude modulation is increased by 56.3% under dual-stimulus function. This work naturally improves the flexibility and practicality of Ge-based metadevice and inspires more innovations to boost the development of switchable sensing, lasing spacer, and nonlinear systems.

Ultra-thin and broadband surface wave meta-absorber.

Perfect absorbers are highly desired in many engineering and military applications, including radar cross section (RCS) reduction, cloaking devices, and sensor detectors. However, most types of present absorbers can only absorb space propagation waves, but absorption for surface waves has not been researched intensively. Surface waves are easily excited on the interfaces between metal and dielectrics for electronic devices, which decreases their working performances due to the electromagnetic disturbances. Thus, it is of great significance to design appropriate absorbers to dissipate undesirable surface waves. Here, we propose the concept of a surface wave absorber, analyze its working principle, and prove its good performances experimentally. To demonstrate our concept, we design and fabricate a realistic surface wave absorber that is fixed on a metal surface. Experiments are performed to verify its electromagnetic characteristics. The results show that our designed meta-absorber can achieve an excellent surface wave absorption within a wide frequency window (5.8-11.2 GHz) and exhibit a very high efficiency over than 90%, but only with the thickness of 1 mm (0.028 λ). Our device can help to solve the issues of absorption at large angles, and it can find wide applications in large antenna array design and other communication systems.

High-performance meta-absorber for the surface wave under the spoof surface plasmon polariton mode.

Perfect absorbers are highly desired in many engineering and military applications, including radar cross section (RCS) reduction, cloaking devices, and sensor detectors. However, most types of present absorbers can only absorb space propagation waves, yet absorption for the surface wave (SW) has not been researched intensively. In reality, when the space wave illuminates on the metal under large oblique angles, surface waves can be excited on the interface between metal and dielectric and thus would increase the RCS and influence the stealth performance. Here, based on the wave vector and impedance matching theories, we propose a broadband absorber for the surface wave under spoof surface plasmon polariton (SSPP) mode. The former theory ensures that surface waves can enter the absorber efficiently, and the latter guarantees perfect absorption. The experimental results indicate that our absorber can achieve a broadband (9.4-18 GHz) performance with an absorption ratio better than 90%, which is in great agreement with the simulations. Therefore, our device can be applied in RCS reduction for the metal devices, antenna array decoupling and many other applications. Also, this work provides a unique methodology to design new types of broadband surface wave absorbers.

Targeting Lymphocyte Activation Gene 3 to Reverse T-Lymphocyte Dysfunction and Improve Survival in Murine Polymicrobial Sepsis.

BACKGROUND: Lymphocyte activation gene 3 (LAG-3) is one of the immune checkpoint molecules, negatively regulating the T-cell reactions. The present study investigated the role of LAG-3 in sepsis-induced T-lymphocyte disability. METHODS: Mice sepsis was induced by cecal ligation and puncture (CLP). LAG-3 expression on some immune cells were detected 24 hours after CLP. LAG-3 knockout and anti-LAG-3 antibody were applied to investigate the effects on the survival, bacterial clearance. Cytokine levels, T-cell counts, and the presence of apoptosis (in blood, spleen, and thymus) were also determined. In vitro T-cell apoptosis, interferon γ secretion, and proliferation were measured. The expression of interleukin 2 receptor on T cells was also determined after CLP. RESULTS: LAG-3 was up-regulated on CD4+/CD8+ T, CD19+ B, natural killer, CD4+CD25+ regulatory T cells and dendritic cells. Both LAG-3 knockout and anti-LAG-3 antibody had a positive effect on survival and on blood or peritoneal bacterial clearance in mice undergoing CLP. Cytokine levels and T-cell apoptosis decreased in anti-LAG-3 antibody-treated mice. Induced T-cell apoptosis decreased, whereas interferon γ secretion and proliferation were improved by anti-LAG-3 antibody in vitro. Interleukin 2 receptor was up-regulated on T cells in both wild-type and LAG-3-knockout mice undergoing CLP. CONCLUSIONS: LAG-3 knockout or anti-LAG-3 antibody blockade protected mice undergoing CLP from sepsis-associated immunodysfunction and may be a new target for the treatment.

Anti-fibrosis potential of pirarubicin via inducing apoptotic and autophagic cell death in rabbit conjunctiva.

This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5 min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5 µmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15 µmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600 µmol/L MMC, both 7.5 µmol/L and 15 µmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5 µmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5 µmol/L prevented postoperative conjunctival fibrosis in an animal model.

Real-world data for health technology assessment for reimbursement decisions in Asia: current landscape and a way forward.

There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.

Pulse pressure variation shows a direct linear correlation with tidal volume in anesthetized healthy patients.

BACKGROUND: The settings of mechanical ventilation, like tidal volume (VT), occasionally need to be adjusted in the process of anesthesia for some special reasons. The aim of this study was therefore to assess the relationship between pulse pressure variations (PPVs) in different settings of VT in anesthetized healthy patients under mechanical ventilation. METHODS: Sixty nine ASA I-II patients scheduled for gastrointestinal surgery under general anesthesia were included in this prospective study. All the patients were ventilated at a VT of 6, 8 or 10 ml/kg (predicted body weight) with no positive end expiratory pressure (PEEP) in a random order after intubation. PPV, mean arterial blood pressure, and other hemodynamic and respiratory parameters were recorded in each VT setting respectively after Partial Pressure of End-Tidal Expiration Carbon Dioxide (PetCO2) maintained between 30 mmHg and 40 mmHg by changing Respiratory Rate (RR) before incision. RESULTS: The values of PPV at different settings of VT showed a tight correlation between each other (6 vs. 8 ml/kg: r = 0.97, P < 0.0001; 6 vs.10 ml/kg: r = 0.95, P < 0.0001; 8 vs. 10 ml/kg: r = 0.98, P < 0.0001, respectively). CONCLUSION: There is a direct linear correlation between PPVs at different tidal volumes in anesthetized ASA I-II patients. PPV in any of the 3 VT settings (6, 8 or 10 ml/kg) can deduce that in any other 2 settings. Further studies are needed to explore the effect of intraoperative confounders for this knowledge to be clinically applied. TRIAL REGISTRATION: NCT01950949 , www.clinicaltrials.gov , July 26, 2013.

Graphene quantums dots combined with endonuclease cleavage and bidentate chelation for highly sensitive electrochemiluminescent DNA biosensing.

A novel strategy for highly sensitive electrochemiluminescence (ECL) detection of DNA was proposed based on site-specific cleavage of BamHI endonuclease combined with the excellent ECL activity of graphene quantum dots (GQDs) and bidentate chelation of the dithiocarbamate DNA (DTC-DNA) probe assembly. The difference between photoluminescence and ECL spectral peaks suggested that a negligible defect existed on the GQDs surface for generation of an ECL signal. The formed DTC-DNA was directly attached to the gold surface by bidentate anchoring (S-Au-S bonds), which conferred a strong affinity between the ligands and the gold surface, increasing the robustness of DNA immobilization on the gold surface. BamHI endonuclease site-specifically recognized and cleaved the duplex symmetrical sequence, which made the double-stranded DNA fragments and GQDs break off from the electrode surface, inducing a decrease of the ECL signal. Using hepatitis C virus-1b genotype complementary DNA (HCV-1b cDNA) as a model, a novel signal-off ECL DNA biosensor was developed based on variation of the ECL intensity before and after digestion of the DNA hybrid. Electrochemical impedance spectroscopy confirmed the successful fabrication of the ECL DNA biosensor. This ECL biosensor for HCV-1b cDNA determination exhibited a linear range from 5 fM to 100 pM with a detection limit of 0.45 fM at a signal-to-noise ratio of 3 and showed satisfactory selectivity and good stability, which validated the feasibility of the designed strategy. The proposed strategy may be conveniently combined with other specific biological recognition events for expansion of the biosensing application, especially in clinical diagnoses.