On-chip all-optical second-order ordinary differential equation solver based on a single microdisk resonator.

This paper proposes an all-optical second-order ordinary differential equation (SODE) solver based on a single microdisk resonator. We validate the feasibility of our structure for constant and complex coefficient SODE solutions for Gaussian and super-Gaussian pulses. The results demonstrate a good agreement between the solutions obtained with the designed structure and those obtained through mathematical calculations for both constant and complex coefficient SODEs. We also discuss the influence of input optical signal pulse width on solution result deviations. Furthermore, we validate the capability of the designed structure to achieve tunable solutions for complex-coefficient SODEs with a tuning power of less than 10 mW. The device footprint is approximately 20×30 µm2, and it is 3-4 times smaller than the current smallest solving unit. The maximum Q-factor reaches 9.8×104. The proposed device avoids the traditional approach of cascading two resonators for SODE solving. Moreover, achieving mode alignment within the same resonator reduces the process challenges associated with aligning multiple devices in a cascade. Furthermore, it offers wider applicability for solving SODEs, namely, the ability to solve both constant and complex coefficient SODEs with complete derivative terms.

Mapping protein-exopolysaccharide binding interaction in Staphylococcus epidermidis biofilms by live cell proximity labeling.

Bacterial biofilms consist of cells encased in an extracellular polymeric substance (EPS) composed of exopolysaccharides, extracellular DNA, and proteins that are critical for cell-cell adhesion and protect the cells from environmental stress, antibiotic treatments, and the host immune response. Degrading EPS components or blocking their production have emerged as promising strategies for prevention or dispersal of bacterial biofilms, but we still have little information about the specific biomolecular interactions that occur between cells and EPS components and how those interactions contribute to biofilm production. Staphylococcus epidermidis is a leading cause of nosocomial infections as a result of producing biofilms that use the exopolysaccharide poly-(1→6)-ß-N-acetylglucosamine (PNAG) as a major structural component. In this study, we have developed a live cell proximity labeling approach combined with quantitative mass spectrometry-based proteomics to map the PNAG interactome of live S. epidermidis biofilms. Through these measurements we discovered elastin-binding protein (EbpS) as a major PNAG-interacting protein. Using live cell binding measurements, we found that the lysin motif (LysM) domain of EbpS specifically binds to PNAG present in S. epidermidis biofilms. Our work provides a novel method for the rapid identification of exopolysaccharide-binding proteins in live biofilms that will help to extend our understanding of the biomolecular interactions that are required for bacterial biofilm formation.

[Early identification and influencing factors of post-traumatic stress disorder in high-stress rescue workers].

Objective: To explore the risk intensity and related influencing factors of post-traumatic stress disorder (PTSD) among high-stress rescue workers, and to provide effective tools for the risk assessment of PTSD in military rescue workers. Method: From June to August 2022, cluster sampling was used to select the high-stress rescue personnel of an Army department as the survey subjects. The acute Stress reaction (ASD) scale and PTSD checklist were used to evaluate the risk of PTSD in military rescue personnel. Multivariate logistic regression were used to analyze the influencing factors of PTSD. Results: The age of 4 460 subjects was (24.38±4.072) years old, including 4 396 males (98.6%). The positive rate of initial screening for ASD was 2.85% (127/4 460). The positive rate of PTSD was 0.67% (30/4 460). Multivariate logistic regression model analysis showed that female, older age, recent trauma exposure history, passive smoking and alcohol consumption were at higher risk of ASD, the values of OR (95%CI) were 4.183 (1.819-9.618), 6.278 (1.363-28.912), 3.094 (1.500-6.379), 2.059 (1.298-3.267) and 2.607 (1.614-4.211), respectively; Lower education level was associated with lower risk of ASD, OR (95%CI) was 0.593 (0.359-0.978); People who are older, thinner, have a history of mental illness, and drink alcohol were at higher risk for PTSD, the values of OR (95%CI) were 20.144 (2.459-165.043), 10.287 (2.218-47.700), 91.104 (8.592-965.980) and 2.866 (1.144-7.180), respectively. Conclusion: Gender, age, education level, passive smoking, alcohol consumption, past history of mental illness and body mass index may be related to the potential risk of PTSD in rescue workers,passive smoking, alcohol consumption, and weight controlling should be focused on to reduce potential risks of PTSD.

Panels of circulating microRNAs as potential diagnostic biomarkers for breast cancer: a systematic review and meta-analysis.

PURPOSE: Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC. METHODS: Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC. RESULTS: Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944. CONCLUSION: We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case-control studies for clinical use.

Hexokinase 2: The preferential target of trehalose-6-phosphate over hexokinase 1.

Cancer-related metabolic features are in part maintained by hexokinase 2 upregulation, which leads to high levels of glucose-6-phosphate (G6P) and is needed to provide energy and biomass to support rapid proliferation. Using a humanized model of the yeast Saccharomyces cerevisiae, we explored how human hexokinase 2 (HK2) behaves under different nutritional conditions. At high glucose levels, yeast presents aerobic glycolysis through a regulatory mechanism known as catabolic repression, which exerts a metabolic adaptation like the Warburg effect. At high glucose concentrations, HK2 did not translocate into the nucleus and was not able to shift the metabolism toward a highly glycolytic state, in contrast to the effect of yeast hexokinase 2 (Hxk2), which is a crucial protein for the control of aerobic glycolysis in S. cerevisiae. During the stationary phase, when glucose is exhausted, Hxk2 is shuttled out of the nucleus, ceasing catabolic repression. Cells harvested at this condition display low glucose consumption rates. However, glucose-starved cells expressing HK2 had an increased capacity to consume glucose. In those cells, HK2 localized to mitochondria, becoming insensitive to G6P inhibition. We also found that the sugar trehalose-6-phosphate (T6P) is a human HK2 inhibitor, like yeast Hxk2, but was not able to inhibit human HK1, the isoform that is ubiquitously expressed in almost all mammalian tissues. In contrast to G6P, T6P inhibited HK2 even when HK2 was associated with mitochondria. The binding of HK2 to mitochondria is crucial for cancer survival and proliferation. T6P was able to reduce the cell viability of tumor cells, although its toxicity was not impressive. This was expected as cell absorption of phosphorylated sugars is low, which might be counteracted using nanotechnology. Altogether, these data suggest that T6P may offer a new paradigm for cancer treatment based on specific inhibition of HK2.

The effectiveness of using the perioscope as an adjunct to non-surgical periodontal therapy: Clinical and radiographic results.

BACKGROUND: It is well known that following root surface debridement (RSD) residual deposits remain. Periodontal endoscopy has provided a method of directly visualizing root surfaces during periodontal debridement in an intact pocket without the need for surgical incision. The aim of this study was to determine if periodontal debridement using endoscopic visualization was more effective in improving clinical and radiographic parameters as compared to RSD. METHODS: Thirty-eight subjects were randomized into RSD with perioscope (n = 19) or RSD only (n = 19) groups. A full-mouth evaluation included probing pocket depths (PPDs), clinical attachment levels (CAL), bleeding on probing (BOP) and plaque scores (PI) recorded at baseline, 3 and 12 months and compared among groups. Radiographs were taken at sites with deepest pockets at baseline and 12-month and the change in radiographic bone levels (RBL) compared. An independent samples T-test was used to assess statistical significance. RESULTS: Both groups had significant improvements in clinical outcomes. The test (T) group had a significantly lower percentage of PPDs 7 to 9 mm at three (0.72 ± 1.2%) and 12 months (0.5 ± 1.0%) as compared with the control (C) group (2.25 ± 2.9%; 1.84 ± 2.3%). At 12 months, the test group recorded a significantly lower mean PPD (T: 2.70 + 0.2 mm; C: 2.98 ± 0.4 mm), BOP% (T: 4.3 ± 3.2%; C: 11.95 ± 7.1%), PI% (T: 25.61 ± 3.9%; C: 30.11 ± 6.3%) and less change in gingival recession (T: -0.13 ± 0.2 mm; C: -0.50 ± 0.6 mm) (P < 0.05). More radiographic bone gain was observed in the test group (0.69 ± 0.3 mm) as compared with the control group (0.49 ± 0.2 mm). This was also observed around multi-rooted teeth (T: 0.83 ± 0.45 mm; C: 0.46 ± 0.36 mm). CONCLUSION: The adjunctive use of the perioscope provided a slight benefit to the outcomes of non-surgical therapy particularly at deeper probing depths.

Speciation and Potential Ecological Risk of Heavy Metals in Soils from Overlapped Areas of Farmland and Coal Resources in Northern Xuzhou, China.

Contamination caused by heavy metals (HMs) in soil of overlapped area of farmland and coal resources (OAFCR) has impact on crops. The concentrations and speciation of As, Cd, Cr, Cu, Pb and Zn were investigated in topsoil of an OAFCR in Xuzhou, China. The results showed that mean concentrations of all six metals were higher than the background values of Xuzhou city and Cd was moderate accumulated with the maximum Igeo equalled to 2.13. Cd showed moderate contamination level (IPi = 1.75) and potential ecological risk (Er = 44.06). Most of the total Cr, Cu, Ni, Pb, and Zn were presented in the residual forms (above 60%), and the percentages of reducible, oxidisable and residual forms of Pb were 23%, 21% and 43% respectively. Pb and Cd reflected a moderate degree of potential ecological risk and a considerable migration risk and ecotoxicity.

Loss of CD73 shifts transforming growth factor-ß1 (TGF-ß1) from tumor suppressor to promoter in endometrial cancer.

In many tumors, CD73 (NT5E), a rate-limiting enzyme in adenosine biosynthesis, is upregulated by TGF-ß and drives tumor progression. Conversely, CD73 is downregulated in endometrial carcinomas (EC) despite a TGF-ß-rich environment. Through gene expression analyses of normal endometrium samples of the uterine cancer TCGA data set and genetic and pharmacological studies, we discovered CD73 loss shifts TGF-ß1 from tumor suppressor to promoter in EC. TGF-ß1 upregulated CD73 and epithelial integrity in vivo in the normal endometrium and in vitro in early stage EC cells. With loss of CD73, TGF-ß1-mediated epithelial integrity was abrogated. EC cells developed TGF-ß1-mediated stress fibers and macromolecule permeability, migration, and invasion increased. In human tumors, CD73 is downregulated in deeply invasive stage I EC. Consistent with shifting TGF-ß1 activity, CD73 loss increased TGF-ß1-mediated canonical signaling and upregulated cyclin D1 (CCND1) and downregulated p21 expression. This shift was clinically relevant, as CD73Low/CCND1High expression associated with poor tumor differentiation, increased myometrial and lymphatic/vascular space invasion, and patient death. Further loss of CD73 in CD73Low expressing advanced stage EC cells increased TGF-ß-mediated stress fibers, signaling, and invasiveness, whereby adenosine A1 receptor agonist, CPA, dampened TGF-ß-mediated invasion. These data identify CD73 loss as essential for shifting TGF-ß activity in EC.

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers.

CD73, a cell surface 5'nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

The Hypoxia-Adenosine Link during Intestinal Inflammation.

Intestinal inflammation is a key element in inflammatory bowel disease and is related to a combination of factors, including genetics, mucosal barrier dysfunction, bacteria translocation, deleterious host-microbe interactions, and dysregulated immune responses. Over the past decade, it has been appreciated that these inflammatory lesions are associated with profound tissue hypoxia. Interestingly, an endogenous adaptive response under the control of hypoxia signaling is enhancement in adenosine signaling, which impacts these different endpoints, including promoting barrier function and encouraging anti-inflammatory activity. In this review, we discuss the hypoxia-adenosine link in inflammatory bowel disease, intestinal ischemia/reperfusion injury, and colon cancer. In addition, we provide a summary of clinical implications of hypoxia and adenosine signaling in intestinal inflammation and disease.

Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System.

Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA's Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss.

Value of microsurgical varicocelectomy for severe oligo-asthenospermia patients failed in fertilization assisted by in vitro fertilization.

OBJECTIVE: To investigate the clinical effect of microsurgical varicocelectomy on severe oligo-asthenospermia patients failing in fertilization assisted by intracytoplasmic sperm injection. PATIENTS AND METHODS: From January 2013 to August 2014, forty-nine patients with severe oligo-asthenospermia and serious varicoceles were treated by microsurgical varicocelectomy after failing in fertilization assisted by intracytoplasmic sperm injection (ICSI), eleven of whom had varicoceles on the left side and thirty-eight had bilateral varicoceles. Patients were followed up for the natural pregnancy condition, changes of routine semen parameters and reproductive hormone level and the embryonic development and outcome of next IVF-ET (ICSI) cycles within 6 months. RESULTS: After surgery, 61.2% (30/49) of spouses obtained clinical pregnancy. Among whom 22.4% (11/49) were naturally pregnant, 32.65% (16/49) were conceived after second IVF-ET assistance, and 6.1% (3/49) were conceived with the third or further assistance of ICSI-ET. The overall miscarriage rate was 16.7% (5/30). All of the patients had improvement in the sperm concentration and forward motility. The sperm concentration increased from (10.53 ± 8.76) × 106/ml to (20.23 ± 11.76) × 106/ml. The ratio of forward motile sperm was increased to (30.52 ± 18.78) % from (8.75.52 ± 6.36) % (p < 0.01). The serum total testosterone (T) improved from (2.19 ± 1.03) ng/ml to (4.05 ± 0.64) ng/ml (p < 0.05). Serum follicle-stimulating hormone (FSH) changed from (5.23 ± 1.26) mIU/ml to (3.76 ± 2.22) mIU/ml after the procedure. Luteinizing hormone (LH) changed from (4.38 ± 1.36) to (3.98 ± 1.38) mIU/ml. Estrogen (E2) changed from 40.28 ± 7.26 pg/ml to 35.24 ± 5.75 pg/ml. Prolactin (PRL) level elevated from (18.24 ± 4.28) to (17.16 ± 2.16) ng/ml (p > 0.05). The fertility rate of in vitro fertilization significantly improved to (83.36 ± 19.36) % from (72.36 ± 17.88) % (p < 0.05). The rate of 2PN ratio increased from (66.73 ± 17.93) % to (75.96 ± 20.39) %. The cleavage rate increased from (83.26 ± 32.33) % to (90.35 ± 23.66). The abnormal fertility rate were (5.36 ± 12.58) % and (7.26 ± 13.89) % before and after the procedure (p > 0.05), while the rate of high-quality embryos increased significantly from (34.36 ± 33.27) % to (55.67 ± 23.36) % (p < 0.05). The rate of transferable embryos remained without significant change (70.67 ± 30.6% before and 60.53 ± 30.27% after the procedure). The anabiosis rate of frozen embryo increased from (66.32 ± 30.69) % to (89.72 ± 29.69) %. The further blastocyst rate improved from (10.98 ± 9.7) % to (30.27 ± 15.33) % (p < 0.01). CONCLUSIONS: The microsurgical varicocelectomy effectively improved sperm parameters, the fertility rate of oocyte fertilized in vitro and the anabiosis rate and blastocyst rate of the frozen embryo for on patients with severe oligo-asthenospermic, and further increased the odds of natural pregnancy, the rate of high-quality embryos and the success rate of in vitro fertilization.

Cardioprotection against experimental myocardial ischemic injury using cornin.

Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

Cardioprotection against experimental myocardial ischemic injury using cornin

Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

Prevention of etomidate-induced myoclonus during anesthetic induction by pretreatment with dexmedetomidine

Myoclonus induced by etomidate during induction of general anesthesia is undesirable. This study evaluated the effect of dexmedetomidine (DEX) pretreatment on the incidence and severity of etomidate-induced myoclonus. Ninety patients undergoing elective surgical procedures were randomly allocated to three groups (n=30 each) for intravenous administration of 10 mL isotonic saline (group I), 0.5 µg/kg DEX in 10 mL isotonic saline (group II), or 1.0 µg/kg DEX in 10 mL isotonic saline (group III) over 10 min. All groups subsequently received 0.3 mg/kg etomidate by intravenous push injection. The incidence and severity of myoclonus were recorded for 1 min after etomidate administration and the incidence of cardiovascular adverse events that occurred between the administration of the DEX infusion and 1 min after tracheal intubation was recorded. The incidence of myoclonus was significantly reduced in groups II and III (30.0 and 36.7%), compared with group I (63.3%). The incidence of severe sinus bradycardia was significantly increased in group III compared with group I (P<0.05), but there was no significant difference in heart rate in groups I and II. There were no significant differences in the incidence of low blood pressure among the 3 groups. Pretreatment with 0.5 and 1.0 µg/kg DEX significantly reduced the incidence of etomidate-induced myoclonus during anesthetic induction; however, 0.5 µg/kg DEX is recommended because it had fewer side effects.

Prevention of etomidate-induced myoclonus during anesthetic induction by pretreatment with dexmedetomidine.

Myoclonus induced by etomidate during induction of general anesthesia is undesirable. This study evaluated the effect of dexmedetomidine (DEX) pretreatment on the incidence and severity of etomidate-induced myoclonus. Ninety patients undergoing elective surgical procedures were randomly allocated to three groups (n=30 each) for intravenous administration of 10 mL isotonic saline (group I), 0.5 µg/kg DEX in 10 mL isotonic saline (group II), or 1.0 µg/kg DEX in 10 mL isotonic saline (group III) over 10 min. All groups subsequently received 0.3 mg/kg etomidate by intravenous push injection. The incidence and severity of myoclonus were recorded for 1 min after etomidate administration and the incidence of cardiovascular adverse events that occurred between the administration of the DEX infusion and 1 min after tracheal intubation was recorded. The incidence of myoclonus was significantly reduced in groups II and III (30.0 and 36.7%), compared with group I (63.3%). The incidence of severe sinus bradycardia was significantly increased in group III compared with group I (P<0.05), but there was no significant difference in heart rate in groups I and II. There were no significant differences in the incidence of low blood pressure among the 3 groups. Pretreatment with 0.5 and 1.0 µg/kg DEX significantly reduced the incidence of etomidate-induced myoclonus during anesthetic induction; however, 0.5 µg/kg DEX is recommended because it had fewer side effects.

Proximal femoral nails antirotation, Gamma nails, and dynamic hip screws for fixation of intertrochanteric fractures of femur: A meta-analysis.

BACKGROUND: Which surgical strategy is the best one for intertrochanteric fractures remains a controversial issue. Dynamic hip screw (DHS) and Gamma nail were commonly used but often associated with some complications, such as fixation failure and implant-related fractures. Meanwhile, proximal femoral nail anti-rotation (PFNA) fixation has recently been developed for minimally invasive surgery to reduce the complications rate. To facilitate the clinical decision-making, we conducted an updated meta-analysis to discuss the optimal treatment of intertrochanteric fractures aiming to determine which implant gives the lower rates of blood loss, complications (peri-implant fracture, fixation failure, infection, thromboembolic), reoperation, and mortality, as well as the minimal duration related to surgery (fluoroscopic exposure, surgery and hospital stay). PATIENTS AND METHODS: Seven electronic databases were searched for randomized controlled trials (including OVID, Springer, Google Scholar, PubMed, Cochrane library, Embase, and Web of Science). Fourteen studies with 1983 patients were included. The modified Jadad Scale was used to assess the methodological quality of these studies. Risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool. Comparison among the three groups was based on twelve indicators, including operative time, fluoroscopy time, operative blood loss, length of hospital stays, wound infection or hematoma, pneumonia, thromboembolic complications, fixation failure, operative fracture of femur, later fracture of femur, reoperation, and mortality. RESULTS: (1) PFNA group versus DHS group: PFNA was associated with less blood loss (mean difference (MD) -253.86, 95% CI -270.25 to 237.47; P<0.00001) and lower rate of fixation failure (MD 0.20, 95% CI 0.07 to 0.59; P=0.004), but led to more fluoroscopy time (MD 2.11, 95% CI 1.78 to 2.43; P<0.00001). (2) PFNA group versus Gamma nail group: PFNA led to less blood loss (MD -55.30, 95% CI -60.07 to -50.53; P<0.00001), shorter fluoroscopy time (MD -0.50, 95% CI -0.55 to -0.45; P<0.00001) and length of hospital stay (MD -0.20, 95% CI -0.27 to -0.13; P<0.00001). (3) DHS group versus Gamma nail group: DHS was associated with lower rate of operative fracture of femur (MD 0.31, 95% CI 0.11 to 0.89; P=0.03), later fracture of femur (MD 0.16, 95% CI 0.06 to 0.43; P=0.0004), and reoperation (MD 0.49, 95% CI 0.27 to 0.88; P=0.02), but caused more blood loss (MD 29.49, 95% CI 8.27 to 50.70; P=0.006). In contrast, there was no difference regarding operative time, infection hematoma, pneumonia, thromboembolic events, and mortality. DISCUSSION: PFNA should be a priority choice for treatment of intertrochanteric fractures with minimal rate of fixation failure, less blood loss and shorter length of hospital stay. DHS has distinct advantages over Gamma nail with lower rate of plant-related complications and should be preferred device for intertrochanteric fractures. However, owing to the low quality evidence currently available, more high-quality RCTs are needed to confirm these findings. LEVEL OF EVIDENCE: Level II.

Effects of local vibration on bone loss in -tail-suspended rats.

We investigated the effects of vibration (35 Hz, 45 Hz and 55 Hz) as countermeasure locally applied to unloading hind limbs on bone, muscle and Achilles tendon. 40 female Sprague Dawley rats were divided into 5 groups (n=8, each): tail-suspension (TS), TS plus 35 Hz/0.3 g vibration (TSV35), TS plus 45 Hz/0.3 g vibration (TSV45), TS plus 55 Hz/0.3 g vibration (TSV55) and control (CON). After 21 days, bone mineral density (BMD) and the microstructure of the femur and tibia were evaluated by µCT in vivo. The biomechanical properties of the femur and Achilles tendon were determined by a materials testing system. Ash weight of bone, isotonic contraction and wet weight of soleus were also investigated. 35 Hz and 45 Hz localized vibration were able to significantly ameliorate the decrease in trabecular BMD (expressed as the percentage change from TS, TSV35: 48.11%, TSV45: 31.09%), microstructure and ash weight of the femur and tibia induced by TS. Meanwhile, 35 Hz vibration significantly improved the biomechanical properties of the femur (57.24% bending rigidity and 41.66% Young's modulus vs. TS) and Achilles tendon (45.46% maximum load and 66.67% Young's modulus vs. TS). Additionally, Young's modulus of the femur was highly correlated with microstructural parameters. Localized vibration was useful for counteracting microgravity-induced musculoskeletal loss. In general, the efficacy of 35 Hz was better than 45 Hz or 55 Hz in tail-suspended rats.

Curculigoside A induces angiogenesis through VCAM-1/Egr-3/CREB/VEGF signaling pathway.

Curculigoside A may be a powerful way of protecting the brain against a wide variety of injury. In the present study, we sought to elucidate whether Curculigoside A contributes to induce angiogenesis and its mechanisms. To this end, we examined the role of Curculigoside A on proliferation, invasion, and tube formation in the human brain microvascular endothelial cell line (HBMEC) in vitro. For studying mechanism, the cAMP response element-binding protein (CREB) inhibitor 2-naphthol-AS-E-phosphate (KG-501), early growth response 3 (Egr-3) siRNA, vascular endothelial growth factor (VEGF) antagonist sFlt-1 and VEGF receptor 2 (VEGFR2) blocker SU-1498 were used. Human brain microvascular endothelial cell line (HMBEC) proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Scratch adhesion test was used to assess the ability of invasion. A matrigel tube formation assay was performed to test capillary tube formation ability. Vascular cell adhesion molecule 1 (VCAM-1)/Egr-3/CREB/VEGF pathway activation in HMBEC was tested by Western blot analysis. Our data suggested that Curculigoside A induced angiogenesis in vitro by enhancing the proliferation, invasion and tube formation. VEGF expression was increased by Curculigoside A and counteracted by the soluble VEGF receptor 1 (sFlt-1, VEGF antagonist) and KG-501 in HMBEC. Tube formation was enhanced by Curculigoside A and counteracted by VEGF receptor blocker-SU1498, KG-501 and Egr-3 siRNA. It may be suggested that Curculigoside A induces angiogenesis in vitro via a programed VCAM-1/Egr-3/CREB/VEGF signaling axis.

Bone and muscle structure and quality preserved by active versus passive muscle exercise on a new stepper device in 21 days tail-suspended rats.

Human performance in microgravity is characterized by reversed skeletal muscle actions in terms of active vs. passive mode contractions of agonist/antagonist groups that may challenge principal biodynamics (biomechanical forces translated from muscle to bone) of the skeletal muscle-bone unit. We investigated active vs. passive muscle motions of the unloaded hindlimb skeletal muscle-bone unit in the 21 days tail-suspended (TS) rat using a newly designed stepper exercise device. The regimen included both active mode motions (TSA) and passive mode motions (TSP). A TS-only group and a normal cage group (CON) served as positive or negative controls. The muscle and bone decrements observed in TS-only group were not seen in the other groups except TSP. Active mode motions supported femur and tibia bone quality (5% BMD, 10% microtrabecular BV/TV, Tb.Th., Tb.N. parameters), whole soleus muscle/myofiber size and type II distribution, 20% increased sarcolemma NOS1 immunosignals vs. CON, with 25% more hybrid fiber formation (remodeling sign) for all TS groups. We propose a new custom-made stepper device to be used in the TS rat model that allows for detailed investigations of the unique biodynamic properties of the muscle-bone unit during resistive-load exercise countermeasure trials on the ground or in microgravity.