CCDC92 promotes podocyte injury by regulating PA28α/ABCA1/cholesterol efflux axis in type 2 diabetic mice.

Podocyte lipotoxicity mediated by impaired cellular cholesterol efflux plays a crucial role in the development of diabetic kidney disease (DKD), and the identification of potential therapeutic targets that regulate podocyte cholesterol homeostasis has clinical significance. Coiled-coil domain containing 92 (CCDC92) is a novel molecule related to metabolic disorders and insulin resistance. However, whether the expression level of CCDC92 is changed in kidney parenchymal cells and the role of CCDC92 in podocytes remain unclear. In this study, we found that Ccdc92 was significantly induced in glomeruli from type 2 diabetic mice, especially in podocytes. Importantly, upregulation of Ccdc92 in glomeruli was positively correlated with an increased urine albumin-to-creatinine ratio (UACR) and podocyte loss. Functionally, podocyte-specific deletion of Ccdc92 attenuated proteinuria, glomerular expansion and podocyte injury in mice with DKD. We further demonstrated that Ccdc92 contributed to lipid accumulation by inhibiting cholesterol efflux, finally promoting podocyte injury. Mechanistically, Ccdc92 promoted the degradation of ABCA1 by regulating PA28α-mediated proteasome activity and then reduced cholesterol efflux. Thus, our studies indicate that Ccdc92 contributes to podocyte injury by regulating the PA28α/ABCA1/cholesterol efflux axis in DKD.

Quantum Emitters with Narrow Band and High Debye-Waller Factor in Aluminum Nitride Written by Femtosecond Laser.

Solid-state quantum emitters (QEs) are central components for photonic-based quantum information processing. Recently, bright QEs in III-nitride semiconductors, such as aluminum nitride (AlN), have attracted increasing interest because of the mature commercial application of the nitrides. However, the reported QEs in AlN suffer from broad phonon side bands (PSBs) and low Debye-Waller factors. Meanwhile, there is also a need for more reliable fabrication methods of AlN QEs for integrated quantum photonics. Here, we demonstrate that laser-induced QEs in AlN exhibit robust emission with a strong zero phonon line, narrow line width, and weak PSB. The creation yield of a single QE could be more than 50%. More importantly, they have a high Debye-Waller factor (>65%) at room temperature, which is the highest result among reported AlN QEs. Our results illustrate the potential of laser writing to create high-quality QEs for quantum technologies and provide further insight into laser writing defects in relevant materials.

Central anterior chamber depth correlated with white-to-white distance in normal, long, and short eyes.

PURPOSE: To explore the associations between central anterior chamber depth (CACD) and other anterior segment biometric parameters and to determine the possible determinants of CACD in short, normal, and long eyes. METHODS: The biometric data of pre-operation patients aged 50-80 years with coexisting cataract and primary angle-closure disease or senile cataract were reviewed. Axial length (AL), CACD, lens thickness (LT), central corneal thickness (CCT), and white-to-white distance (WTW) were measured by Lenstar optical biometry (Lenstar 900). The data of 100 normal eyes (AL = 22 to 26 mm), 100 short eyes (AL ≤ 22 mm), and 100 long eyes (AL ≥ 26 mm) were consecutively collected for subsequent analyses. RESULTS: The mean age of the subjects was 66.60 ± 7.85 years, with 25.7% of the sample being men. Both CACD and WTW were found to be smallest in short eyes and were smaller in normal eyes than in long eyes (F = 126.524, P < 0.001; F = 28.458, P < 0.001). The mean LT was significantly thicker in short eyes than in normal and long eyes (4.66 mm versus 4.49 mm versus 4.40 mm; F = 18.099, P < 0.001). No significant differences were observed in CCT between the three AL groups (F = 2.135, P = 0.120). Stepwise regression analysis highlighted AL, LT, and WTW as three independent factors associated with CACD in the normal AL group. In the short AL group and long AL group, LT and WTW were independent factors associated with CACD. CONCLUSIONS: CACD increases as AL elongates and reaches a peak when AL exceeds 26 mm. Furthermore, CACD showed inverse correlation with LT and positive correlation with WTW. A relatively small WTW results in an anteriorly positioned lens, and thus, a decrease in CACD.

GPR97 deficiency ameliorates renal interstitial fibrosis in mouse hypertensive nephropathy.

Hypertensive nephropathy (HTN) ranks as the second-leading cause of end-stage renal disease (ESRD). Accumulating evidence suggests that persistent hypertension injures tubular cells, leading to tubulointerstitial fibrosis (TIF), which is involved in the pathogenesis of HTN. G protein-coupled receptors (GPCRs) are implicated in many important pathological and physiological processes and act as important drug targets. In this study, we explored the intrarenal mechanisms underlying hypertension-associated TIF, and particularly, the potential role of GPR97, a member of the adhesion GPCR subfamily, in TIF. A deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mouse model was used. We revealed a significantly upregulated expression of GPR97 in the kidneys, especially in renal tubules, of the hypertensive mice and 10 patients with biopsy-proven hypertensive kidney injury. GPR97-/- mice showed markedly elevated blood pressure, which was comparable to that of wild-type mice following DOCA/salt treatment, but dramatically ameliorated renal injury and TIF. In NRK-52E cells, we demonstrated that knockdown of GPR97 suppressed the activation of TGF-ß signaling by disturbing small GTPase RhoA-mediated cytoskeletal reorganization, thus inhibiting clathrin-mediated endocytosis of TGF-ß receptors and subsequent Smad activation. Collectively, this study demonstrates that GPR97 contributes to hypertension-associated TIF at least in part by facilitating TGF-ß signaling, suggesting that GPR97 is a pivotal intrarenal factor for TIF progression under hypertensive conditions, and therapeutic strategies targeting GPR97 may improve the outcomes of patients with HTN.

A CT-based nomogram established for differentiating gastrointestinal heterotopic pancreas from gastrointestinal stromal tumor: compared with a machine-learning model.

OBJECTIVE: To identify CT features and establish a nomogram, compared with a machine learning-based model for distinguishing gastrointestinal heterotopic pancreas (HP) from gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: This retrospective study included 148 patients with pathologically confirmed HP (n = 48) and GIST (n = 100) in the stomach or small intestine that were less than 3 cm in size. Clinical information and CT characteristics were collected. A nomogram on account of lasso regression and multivariate logistic regression, and a RandomForest (RF) model based on significant variables in univariate analyses were established. Receiver operating characteristic (ROC) curve, mean area under the curve (AUC), calibration curve and decision curve analysis (DCA) were carried out to evaluate and compare the diagnostic ability of models. RESULTS: The nomogram identified five CT features as independent predictors of HP diagnosis: age, location, LD/SD ratio, duct-like structure, and HU lesion/pancreas A. Five features were included in RF model and ranked according to their relevance to the differential diagnosis: LD/SD ratio, HU lesion/pancreas A, location, peritumoral hypodensity line and age. The nomogram and RF model yielded AUC of 0.951 (95% CI: 0.842-0.993) and 0.894 (95% CI: 0.766-0.966), respectively. The DeLong test found no statistically significant difference in diagnostic performance (p > 0.05), but DCA revealed that the nomogram surpassed the RF model in clinical usefulness. CONCLUSION: Two diagnostic prediction models based on a nomogram as well as RF method were reliable and easy-to-use for distinguishing between HP and GIST, which might also assist treatment planning.

Curcumin alleviates bisphenol AF-induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway.

Bisphenol AF (BPAF), a BPA-substitute, has been widely used in industrial compounds throughout the world. Several studies have shown that BPAF has endocrine interference and reproductive toxicity. However, the toxic effects of BPAF on pregnancy and placenta of goats are still unclear. Therefore, the objective of this study was to reveal the toxic effect of BPAF by using an in vitro culture model of caprine endometrial epithelial cells (EECs) and further attempted to alleviate the toxicity by curcumin pretreatment. The results showed that BPAF induces significant effects on EECs, including decreased cell viability and mitochondrial membrane potential (△ψm), elevating intracellular reactive oxygen species (ROS), promoting cell apoptosis through upregulating the expression of Bax, Cytochrome c, and downregulating the expression of Bcl-2. Meanwhile, BPAF induced dysregulation of oxidative stress by increasing the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) but decreasing the activities of superoxide dismutase (SOD). However, curcumin pretreatment could significantly attenuate BPAF-induced toxic effects in EECs. Further study revealed that BPAF treatment could activate mitogen-activated protein kinase (MAPK) pathway and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, but curcumin pretreatment significantly inhibited the activation of MAPK signal pathway and Nrf2 expression induced by BPAF. Overall, this study indicated that curcumin could prevent BPAF-induced EECs cytotoxicity, which provides a potential therapeutic strategy for female infertility associated with BPAF exposure.

Rational Design of Quinoxalinone-Based Red-Emitting Probes for High-Affinity and Long-Term Visualizing Amyloid-ß In Vivo.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with insidious onset, and the deposition of amyloid-ß (Aß) is believed to be one of the main cause. Fluorescence imaging is a promising technique for this task, but the Aß gold standard probe ThT developed based on this still has shortcomings. The development of a new fluorescent probe to detect Aß plaques is thought to be essential. Herein, a series of red to near-infrared emitting fluorescent probes QNO-ADs with newly quinoxalinone skeleton are designed to detect Aß plaques. They all demonstrate excellent optical properties and high binding affinity (∼Kd = 20 nM) to Aß aggregates. As the most outstanding candidate, QNO-AD-3 shows significant signal-to-noise (S/N) ratio at the level of in vitro binding studies, and the brilliant fluorescence staining results in favor of grasping the approximate distribution of Aß plaques in the brain slice. In vivo Aß plaques imaging suggests that QNO-AD-3 can cross the BBB and have a long retention time in the brain with low biological toxicity. In addition, the results of docking theoretical calculation also provide some references for the design of Aß probe. Overall, given the high affinity of QNO-AD-3 and the ability to monitor Aß plaques for a long time that is not common now, we believe QNO-AD-3 will be an effective tool for an Aß-related matrix and AD disease research in the future.

mTOR regulates cocaine-induced behavioural sensitization through the SynDIG1-GluA2 interaction in the nucleus accumbens.

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

Ultra-thin layered double hydroxide-mediated photothermal therapy combine with asynchronous blockade of PD-L1 and NR2F6 inhibit hepatocellular carcinoma.

BACKGROUND: The efficacy of immune checkpoint blockade (ICB), in the treatment of hepatocellular carcinoma (HCC), is limited due to low levels of tumor-infiltrating T lymphocytes and deficient checkpoint blockade in this immunologically "cool" tumor. Thus, combination approaches are needed to increase the response rates of ICB and induce synergistic antitumor immunity. METHODS: Herein, we designed a pH-sensitive multifunctional nanoplatform based on layered double hydroxides (LDHs) loaded with siRNA to block the intracellular immune checkpoint NR2F6, together with the asynchronous blockade surface receptor PD-L1 to induce strong synergistic antitumor immunity. Moreover, photothermal therapy (PTT) generated by LDHs after laser irradiation modified an immunologically "cold" microenvironment to potentiate Nr2f6-siRNA and anti-PD-L1 immunotherapy. Flow cytometry was performed to assess the immune responses initiated by the multifunctional nanoplatform. RESULTS: Under the slightly acidic tumor extracellular environment, PEG detached and the re-exposed positively charged LDHs enhanced tumor accumulation and cell uptake. The accumulated siRNA suppressed the signal of dual protumor activity in both immune and H22 tumor cells by silencing the NR2F6 gene, which further reduced the tumor burden and enhanced systemic antitumor immunity. The responses include enhanced tumor infiltration by CD4+ helper T cells, CD8+ cytotoxic T cells, and mature dendritic cells; the significantly decreased level of immune suppressed regulator T cells. The therapeutic responses were also attributed to the production of IL-2, IFN-γ, and TNF-α. The prepared nanoparticles also exhibited potential magnetic resonance imaging (MRI) ability, which could serve to guide synergistic immunotherapy treatment. CONCLUSIONS: In summary, the three combinations of PTT, NR2F6 gene ablation and anti-PD-L1 can promote a synergistic immune response to inhibit the progression of primary HCC tumors and prevent metastasis. This study can be considered a proof-of-concept for the targeting of surface and intracellular immune checkpoints to supplement the existing HCC immunotherapy treatments.

Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer.

BACKGROUND: Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. METHODS: We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. RESULTS: Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. CONCLUSION: This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.

[Preparation of salvianolic acid B, tanshinone â ¡_A, and glycyrrhetinic acid lipid emulsion and its protective effect against acute liver injury induced by acetaminophen].

Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.

[Preparation of tanshinone â ¡_A-glycyrrhetinic acid solid lipid nanoparticles and its inhibitory effect on acne].

The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.

Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis.

BACKGROUND: Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progression. METHODS: The morphology, elemental composition, and tumour microenvironment responses of various organic/inorganic nanoplatforms were characterised by different analytical methods. Their in vivo and in vitro tumour-targeting efficacy and imaging capability were analysed by magnetic resonance imaging. Confocal microscopy, flow cytometry, and western blotting were used to investigate the therapeutic efficacy and mechanisms of complementary ferroptosis/apoptosis mediated by the nanoplatforms. RESULTS: The nanoplatform consisted of a silica shell doped with iron and disulphide bonds and an etched core loaded with doxorubicin that generates hydrogen peroxide in situ and enhances ferroptosis. It relied upon transferrin for targeted drug delivery and could be activated by the tumour microenvironment. Glutathione-responsive biodegradability could operate synergistically with the therapeutic interaction between doxorubicin and iron and induce tumour cell death through complementary ferroptosis and apoptosis. The nanoplatform also has a superparamagnetic framework that could serve to guide and monitor treatment under T2-weighted magnetic resonance imaging. CONCLUSION: This rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy.

Chinese orthopaedic nurses' knowledge, attitude and venous thromboembolic prophylactic practices: A multicentric cross-sectional survey.

BACKGROUND: Venous thromboembolism is a severe preventable complication among orthopaedic surgical patients. Integrating therapeutic guidelines into clinical practice can help improve patient safety and reduce the burden of this pathology. Improving the quality of patient care is important for bridging the gap between the prophylaxis for venous thromboembolism and therapeutic guidelines. OBJECTIVES: This study aimed at evaluating the knowledge, attitude, and venous thromboembolism and prophylaxis practices of Chinese orthopaedic nurses to guide quality care improvements. METHODS: The data used in this study are secondary data obtained from a multicentric survey. An anonymous questionnaire was used to measure the attitude and knowledge of venous thromboembolic prophylaxis among orthopaedic nurses. VTE prophylactic practices were extracted from medical records within the electronic case report form immediately after the nurses' investigations. The STROBE statement for observational studies was applied. RESULTS: Results indicated that although 94.0% of the responding nurses had attended training courses in their wards, a majority of them (68.9%) achieved a median knowledge score of 7 points or below (range 0-9). Knowledge regarding the proper use of prophylaxis, identification of risk factors, signs and symptoms for pulmonary embolism was limited. Self-reported attitudes underestimate the relationships between venous thromboembolism and low-quality nursing care. Pharmacological prophylaxis was highly used (90.9%), while the utilisation of mechanical prophylaxis and its proper use was relatively low. CONCLUSIONS: Chinese orthopaedic nurses demonstrated enthusiasm for venous thromboembolism and prophylaxis. Their knowledge needs to be improved, including the proper use of prophylaxis, identification of risk factors, signs and symptoms. Mechanical prophylaxis practice for VTE prevention after THA and TKA surgical procedures is not optimistic. Further studies should analyse the causes from multiple perspectives, including the availability of resources, the knowledge and attitude of doctors, nurses and patients. RELEVANCE TO CLINICAL PRACTICE: The findings from this study can be used to develop and implement interventions for venous thromboembolism after orthopaedic surgery.

MiR-455-5p ameliorates HG-induced apoptosis, oxidative stress and inflammatory via targeting SOCS3 in retinal pigment epithelial cells.

Diabetic retinopathy (DR) remains the leading cause of blindness in adults with diabetes mellitus. Numerous microRNAs (miRNAs) have been identified to modulate the pathogenesis of DR. The main purpose of this study was to evaluate the potential roles of miR-455-5p in high glucose (HG)-treated retinal pigment epithelial (RPE) cells and underlying mechanisms. Our present investigation discovered that the expression of miR-455-5p was apparently downregulated in ARPE-19 cells stimulated with HG. In addition, forced expression of miR-455-5p markedly enhanced cell viability and restrained HG-induced apoptosis accompanied by decreased BCL2-associated X protein (Bax)/B-cell leukemia/lymphoma 2 (Bcl-2) ratio and expression of apoptotic marker cleaved caspase-3 during HG challenged. Subsequently, augmentation of miR-455-5p remarkably alleviated HG-triggered oxidative stress injury as reflected by decreased the production of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content as well as NADPH oxidase 4 expression, concomitant with enhanced the activities of superoxide dismutase, catalase, and GPX stimulated with HG. Furthermore, enforced expression of miR-455-5p effectively ameliorated HG-stimulated inflammatory response as exemplified by repressing the secretion of inflammatory cytokines interleukin 1ß (IL-1ß), IL-6, and tumour necrosis factor-α in ARPE-19 cells challenged by HG. Most importantly, we successfully identified suppressor of cytokine signaling 3 (SOCS3) as a direct target gene of miR-455-5p, and miR-455-5p negatively regulated the expression of SOCS3. Mechanistically, restoration of SOCS3 abrogated the beneficial effects of miR-455-5p on apoptosis, accumulation of ROS, and inflammatory factors production in response to HG. Taken together, these findings demonstrated that miR-455-5p relieved HG-induced damage through repressing apoptosis, oxidant stress, and inflammatory response by targeting SOCS3. The study gives evidence that miR-455-5p may serve as a new potential therapeutic agent for DR treatment.

Endocrine Regulator rFGF21 (Recombinant Human Fibroblast Growth Factor 21) Improves Neurological Outcomes Following Focal Ischemic Stroke of Type 2 Diabetes Mellitus Male Mice.

Background and Purpose- The complexity and heterogeneity of stroke, as well as the associated comorbidities, may render neuroprotective drugs less efficacious in clinical practice. Therefore, the development of targeted therapies to specific patient subsets has become a high priority in translational stroke research. Ischemic stroke with type 2 diabetes mellitus has a nearly double mortality rate and worse neurological outcomes. In the present study, we tested our hypothesis that rFGF21 (recombinant human fibroblast growth factor 21) administration is beneficial for improving neurological outcomes of ischemic stroke with type 2 diabetes mellitus. Methods- Type 2 diabetes mellitus db/db and nondiabetic genetic control db/+ mice were subjected into permanent focal ischemia of distal middle cerebral artery occlusion, we examined the effects of poststroke administration with rFGF21 in systemic metabolic disorders, inflammatory gatekeeper PPARγ (peroxisome proliferator-activated receptor γ) activity at 3 days, mRNA expression of inflammatory cytokines and microglia/macrophage activation at 7 days in the perilesion cortex, and last neurological function deficits, ischemic brain infarction, and white matter integrity up to 14 days after stroke of db/db mice. Results- After permanent focal ischemia, diabetic db/db mice presented confounding pathological features, including metabolic dysregulation, more severe brain damage, and neurological impairment, especially aggravated proinflammatory response and white matter integrity loss. However, daily rFGF21 treatment initiated at 6 hours after stroke for 14 days significantly normalized systemic metabolic disorders, rescued PPARγ activity decline, inhibited proinflammatory cytokine mRNA expression, and M1-like microglia/macrophage activation in the brain. Importantly, rFGF21 also significantly reduced white matter integrity loss, ischemic brain infarction, and neurological function deficits up to 14 days after stroke. The potential mechanisms of rFGF21 may in part consist of potent systematic metabolic regulation and PPARγ-activation promotion-associated antiproinflammatory roles in the brain. Conclusions- Taken together, these results suggest rFGF21 might be a novel and potent candidate of the disease-modifying strategy for treating ischemic stroke with type 2 diabetes mellitus.

Risk Factors for Early Postoperative Small Bowel Obstruction after Elective Colon Cancer Surgery: An Observational Study of 1,244 Consecutive Patients.

BACKGROUND: Early postoperative small bowel obstruction (EPSBO) is a common complication following colon cancer surgery. EPSBO is associated with increased hospital stays, mortality rates, and healthcare costs. The purpose of this study was to identify risk factors for EPSBO following elective colon cancer surgery. STUDY DESIGN: We retrospectively reviewed the clinicopathological variables of 1,244 patients with colon cancer who underwent partial colectomy from January 2000 to December 2014. A multivariable logistic regression model was used to identify risk factors for EPSBO. RESULTS: The EPSBO rate was 3.5%. In multivariate analysis, preoperative bowel obstruction (OR 2.378; 95% CI 0.986-5.735, p = 0.054), weight loss >10% of body weight (OR 3.029; 95% CI 1.000-9.178, p = 0.05), albumin level (in g/L; OR 0.966; 95% CI 0.937-0.996, p = 0.024), and surgical duration (in min; OR 1.008; 95% CI 1.003-1.012, p = 0.003) were significant predictors of EPSBO. CONCLUSION: EPSBO is more likely to develop in the presence of poor systemic conditions (e.g., weight loss >10% of body weight, hypoalbuminemia, and preoperative bowel obstruction) and following operations of longer duration. These predictors may facilitate the stratification of patients at risk for EPSBO following surgery for elective colon cancer.

Demographic profile and ocular characteristics of stage 5 retinopathy of prematurity at a referral center in Northwest China: implications for implementation.

BACKGROUND: Severe retinopathy of prematurity (ROP) with extremely unfavorable prognosis among infants can do great damage to individuals and bring tremendous social-economic burden. The purpose of this study is to describe the demographic and ocular characteristics of infants who presented with stage 5 ROP in order to identify reasons why they have become blind, and to identify contributing factors in order to focus great attention on the current ROP program and to inspire more effort in ROP screening in middle income countries. METHODS: A retrospective review of consecutive infants with stage 5 ROP from December 2010 to December 2016 in Department of Ophthalmology, Xijing Hospital. Various parameters retrieved included birthweight, gestational age, age at initial examination, postmenstrual age, screening details, check-up details and reasons for consultation. Ocular findings were recorded and also detected by ultrasonography. RESULTS: A retrospective review of 20 consecutive infants with stage 5 ROP are included. Mean birthweight was1712.3 ± 512.97 g and mean gestational age at birth was 32.1 ± 2.21 weeks. Median age at first consultancy was 9.7 month. Median postmenstrual age first consultancy was 52 weeks. All infants were never screened for ROP before they came to the referral center. Of twenty stage 5 ROP infants, 13 cases presented with bilateral stage 5 features. Of the 40 eyes of 20 infants, 33 eyes were diagnosed as stage 5. Leukocoric pupil, closed funnel configuration of retinal detachment (RD), posterior synechia, extraretinal fibrovascular proliferation and retinal folds were the most significant indicators of bad prognosis. Ten eyes appeared no fixation to light, while 30 eyes exhibited following to light or following to toys. CONCLUSIONS: Our study shows that in relatively less-developed regions of China, more needs to be done to spread awareness about the disease among pediatricians, neonatologists and ophthalmologists as well as parents of premature infants. Thus, a comprehensive control system which is a whole network of propaganda, screening, treatment and follow-up are encouraged especially in less developed areas in China as well as worldwide.

Multi-wavelength Yb:YAG/Nd3+:YVO4 continuous-wave microchip Raman laser.

Multi-wavelength continuous-wave (CW) Raman lasers in a laser diode pumped Yb:YAG/Nd3+:YVO4 microchip Raman laser have been demonstrated for the first time to our best knowledge. The multi-wavelength laser of the first Stokes radiation around 1.08 µm has been achieved with a Raman shift of 261 cm-1 for a-cut Nd:YVO4 crystal corresponding to the fundamental wavelength at 1.05 µm. Multi-wavelength laser operation simultaneously around 1.05 and 1.08 µm has been achieved under the incident pump power between 1.5 and 1.7 W. Multi-wavelength Raman laser with frequency separation of 1 THz around 1.08 µm has been obtained when the incident pump power is higher than 1.7 W. The maximum Raman laser output power of 260 mW at 1.08 µm is obtained and the corresponding optical-to-optical conversion efficiency is 4.2%. Elliptically polarized fundamental laser and linearly polarized Raman laser were observed in an Yb:YAG/Nd:YVO4 CW microchip Raman laser. The experimental results of linearly polarized, multi-wavelength Yb:YAG/Nd:YVO4 CW microchip Raman laser with adjustable frequency separation provide a novel approach for developing potential compact laser sources for Terahertz generation.

Comparison of 5-Aminolevulinic Acid Photodynamic Therapy and Clobetasol Propionate in Treatment of Vulvar Lichen Sclerosus.

The aim of this study was to evaluate the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of vulvar lichen sclerosus (VLS) and compare its effectiveness with that of clobetasol propionate. Four sessions of topical photodynamic therapy (PDT) were administered at 2-week intervals (n = 20). Clobetasol propionate (0.05%) was used daily for 8 weeks (n = 20). The rate of complete response in the PDT group (14/20) was double that of the clobetasol propionate group (7/20) (p < 0.05, 2 = 4.912). Horizontal visual analogue scores indicated that PDT was more effective than clobetasol propionate. Pain intensity numeric rating scale values for PDT were between 3.05 and 4.45. One month after the final session of PDT, only one patient relapsed and all 7 patients in clobetasol propionate group relapsed. ALA-PDT is a well-tolerated and effective option for the treatment of VLS.