A 3-month-old neonatal rhesus macaque HFMD model caused by coxsackievirus B1 infection and viral tissue tropism.

Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.

Paper-Based Microfluidic Analytical Device Patterned by Label Printer for Point-of-Care Blood Glucose and Hematocrit Detection Using 3D-Printed Smartphone Cassette.

This study presents a portable, low-cost, point-of-care (POC) system for the simultaneous detection of blood glucose and hematocrit. The system consists of a disposable origami microfluidic paper-based analytical device (µPAD) for plasma separation, filtration, and reaction functions and a 3D-printed cassette for hematocrit and blood glucose detection using a smartphone. The origami µPAD is patterned using a cost-effective label printing technique instead of the conventional wax printing method. The 3D-printed cassette incorporates an array of LED lights, which mitigates the effects of intensity variations in the ambient light and hence improves the accuracy of the blood glucose and hematocrit concentration measurements. The hematocrit concentration is determined quantitatively by measuring the distance of plasma wicking along the upper layer of the origami µPAD, which is pretreated with sodium chloride and Tween 20 to induce dehydration and aggregation of the red blood cells. The filtered plasma also penetrates to the lower layer of the origami µPAD, where it reacts with embedded colorimetric assay reagents to produce a yellowish-brown complex. A color image of the reaction complex is captured using a smartphone inserted into the 3D-printed cassette. The image is analyzed using self-written RGB software to quantify the blood glucose concentration. The calibration results indicate that the proposed detection platform provides an accurate assessment of the blood glucose level over the range of 45-630 mg/dL (R2 = 0.9958). The practical feasibility of the proposed platform is demonstrated by measuring the blood glucose and hematocrit concentrations in 13 human whole blood samples. Taking the measurements obtained from commercial glucose and hematocrit meters as a benchmark, the proposed system has a differential of no more than 6.4% for blood glucose detection and 9.1% for hematocrit detection. Overall, the results confirm that the proposed µPAD is a promising solution for cost-effective and reliable POC health monitoring.

Transcriptome profiling reveals the genes involved in tuberous root expansion in Pueraria (Pueraria montana var. thomsonii).

BACKGROUND: Pueraria is a dry root commonly used in Traditional Chinese Medicine or as food and fodder, and tuberous root expansion is an important agronomic characteristic that influences its yield. However, no specific genes regulating tuberous root expansion in Pueraria have been identified. Therefore, we aimed to explore the expansion mechanism of Pueraria at six developmental stages (P1-P6), by profiling the tuberous roots of an annual local variety "Gange No.1" harvested at 105, 135, 165, 195, 225, and 255 days after transplanting. RESULTS: Observations of the tuberous root phenotype and cell microstructural morphology revealed that the P3 stage was a critical boundary point in the expansion process, which was preceded by a thickening diameter and yield gain rapidly of the tuberous roots, and followed by longitudinal elongation at both ends. A total of 17,441 differentially expressed genes (DEGs) were identified by comparing the P1 stage (unexpanded) against the P2-P6 stages (expanded) using transcriptome sequencing; 386 differential genes were shared across the six developmental stages. KEGG pathway enrichment analysis showed that the DEGs shared by P1 and P2-P6 stages were mainly involved in pathways related to the "cell wall and cell cycle", "plant hormone signal transduction", "sucrose and starch metabolism", and "transcription factor (TF)". The finding is consistent with the physiological data collected on changes in sugar, starch, and hormone contents. In addition, TFs including bHLHs, AP2s, ERFs, MYBs, WRKYs, and bZIPs were involved in cell differentiation, division, and expansion, which may relate to tuberous root expansion. The combination of KEGG and trend analyses revealed six essential candidate genes involved in tuberous root expansion; of them, CDC48, ARF, and EXP genes were significantly upregulated during tuberous root expansion while INV, EXT, and XTH genes were significantly downregulated. CONCLUSION: Our findings provide new insights into the complex mechanisms of tuberous root expansion in Pueraria and candidate target genes, which can aid in increasing Pueraria yield.

Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function.

Adiponectin, an adipokine secreted by adipocytes, has anti-atherosclerotic and antithrombotic activities. AdipoRon is synthetic small molecule adiponectin receptor agonist. In this study, we investigated the effect of AdipoRon on platelet activation and thrombus formation. Washed human platelets were prepared from the peripheral blood of healthy donors. In a series of in vitro platelet functional assays, pre-treatment with AdipoRon (10, 20, 40 µg/mL) dose-dependently inhibited the aggregation, granule secretion and spreading of washed human platelets. We showed that AdipoRon (20, 40 µg/mL) significantly inhibited AMPK, Syk, PLCγ2, PI3K, Akt, p38-MAPK and ERK1/2 signalling pathways in washed human platelets. In addition, we demonstrated that the phosphorylation of CKII at Tyr255 was an important mechanism of the integrin αIIbß3-mediated platelet activation. Meanwhile, AdipoR1 deficiency impaired the inhibitory effect of AdipoRon on mouse platelets. In ferric chloride-induced carotid injury model, injection of AdipoRon (5 or 12.5 mg/kg, iv) significantly attenuated arterial thrombosis. In conclusion, AdipoRon attenuates platelet function via the AdipoR1/AMPK/CKII/PI3K/AKT signalling pathways, while exerting a protective effect against arterial thrombosis. This study offers new insights into the fields of cardiovascular disease and antiplatelet drug discovery.Schematic model of AdipoRon regulating platelet activation. (BioRender.com).

To compare the influence of blind insertion and up-down optimized glottic exposure manoeuvre on oropharyngeal leak pressure using SaCoVLM™ video laryngeal mask among patients undergoing general anesthesia.

To compare the potential influences of blind insertion and up-down optimized glottic exposure manoeuvre on the oropharyngeal leak pressure (OPLP) in using SaCoVLM™ video laryngeal mask (VLM) among patients undergoing general anesthesia. A randomized self-control study controlled was conducted to investigate the effect of two insertion techniques on OPLP. A total of 60 patients (male or female, 18-78 years, BMI 18.0-30.0 kg m-2 and ASA I-II) receiving selective surgery under general anesthesia were randomly recruited. After induction of anesthesia, the SaCoVLM™ was inserted by blind insertion manoeuvre. The glottic exposure grading(V1) of the SaCoVLM™ visual laryngeal mask and the OPLP(P1) were recorded. And the glottic exposure grading(V2) and OPLP(P2) of SaCoVLM™ were recorded again when the glottic exposure grading was optimal. The glottis exposure grading and OPLP were compared before and after different insertion manoeuver. The glottic exposure grading (V2) obtained by using up-down optimized glottic exposure manoeuvre was better than that obtained by using blind insertion manoeuvre (V1)(P < 0.001). The OPLP was significantly lower in the blind insertion manoeuvre (P1) than in the up-down optimized glottic exposure manoeuvre (P2) (32.4 ± 5.0 cmH2O vs. 36.3 ± 5.2 cmH2O, P < 0.001). In using SaCoVLM™, higher OPLP and better glottic exposure grading were achieved through up-down optimized glottic exposure manoeuvre, protecting the airway while real-time monitoring of conditions around the glottis, which significantly improves airway safety. Our results suggests that up-down optimized glottic exposure manoeuver may be a useful technique for SaCoVLM™ insertion.Trial registration: ChiCTR, ChiCTR2000028802. Registered 4 January 2020, http://www.chictr.org.cn/ChiCTR2000028802.

Irreducible anteromedial radial head dislocation without fracture caused by transposed biceps tendon in an adult: A case report and literature review.

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of right elbow reveals in a "semi-extended and pronated" elastic fixation position. Radiography and three-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.

Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde.

Crotonaldehyde (CRA)-one of the major environmental pollutants from tobacco smoke and industrial pollution-is associated with vascular injury (VI). We used proteomics to systematically characterize the presently unclear molecular mechanism of VI and to identify new related targets or signaling pathways after exposure to CRA. Cell survival assays were used to assess DNA damage, whereas oxidative stress was determined using colorimetric assays and by quantitative fluorescence study; additionally, cyclooxygenase-2, mitogen-activated protein kinase pathways, Wnt3a, ß-catenin, phospho-ErbB2, and phospho-ErbB4 were assessed using ELISA. Proteins were quantitated via tandem mass tag-based liquid chromatography-mass spectrometry and bioinformatics analyses, and 34 differentially expressed proteins were confirmed using parallel reaction monitoring, which were defined as new indicators related to the mechanism underlying DNA damage; glutathione perturbation; mitogen-activated protein kinase; and the Wnt and ErbB signaling pathways in VI based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Parallel reaction monitoring confirmed significant (p < 0.05) upregulation (> 1.5-fold change) of 23 proteins and downregulation (< 0.667-fold change) of 11. The mechanisms of DNA interstrand crosslinks; glutathione perturbation; mitogen-activated protein kinase; cyclooxygenase-2; and the Wnt and ErbB signaling pathways may contribute to VI through their roles in DNA damage, oxidative stress, inflammation, vascular dysfunction, endothelial dysfunction, vascular remodeling, coagulation cascade, and the newly determined signaling pathways. Moreover, the Wnt and ErbB signaling pathways were identified as new disease pathways involved in VI. Taken together, the elucidated underlying mechanisms may help broaden existing understanding of the molecular mechanisms of VI induced by CRA.

Preliminary evaluation of SaCoVLM™ video laryngeal mask airway in airway management for general anesthesia.

BACKGROUND: To preliminary evaluate the application of SaCoVLM™ video laryngeal mask airway in airway management of general anesthesia. METHODS: We recruited 100 adult patients (ages 18-78 years, male 19, female 81, weight 48-90 kg) with normal predicted airway (Mallampati I ~ II, unrestricted mouth opening, normal head and neck mobility) and ASA I-II who required general anaesthesia. The SaCoVLM™ was inserted after anesthesia induction and connected with the anesthesia machine for ventilation. Our primary outcome was glottic visualization grades. Secondary outcomes included seal pressure, success rate of insertion, intraoperative findings (gastric reflux and contraposition), gastric drainage and 24-h complications after operation. RESULTS: The laryngeal inlet was exposed in all the patients and shown on the video after SaCoVLM™ insertion. The status of glottic visualization was classified: grade 1 in 55 cases, grade 2 in 23 cases, grade 3 in 14 cases and grade 4 in 8 cases. The first-time success rate of SaCoVLM™ insertion was 95% (95% CI = 0.887 to 0.984), and the total success rate was 96% (95% CI = 0.901 to 0.989). The sealing pressure of SaCoVLM™ was 34.1 ± 6.2 cmH2O and the gastric drainage were smooth. Only a small number of patients developed mild complications after SaCoVLM™ was removed (such as blood stains on SaCoVLM™ and sore throat). CONCLUSIONS: The SaCoVLM™ can visualize partial or whole laryngeal inlets during the surgery, with a high success rate, a high sealing pressure and smooth gastroesophageal drainage. SaCoVLM™ could be a promise new effective supraglottic device to airway management during general anesthesia. TRIAL REGISTRATION: ChiCTR, ChiCTR2000028802 .Registered 4 January 2020.

Comparison of SaCoVLM™ video laryngeal mask-guided intubation and i-gel combined with flexible bronchoscopy-guided intubation in airway management during general anesthesia: a non-inferiority study.

BACKGROUND: When a difficult airway is unanticipatedly encountered and the initial laryngoscopic intubation fails, a supraglottic airway device (SAD) may be placed to aid ventilation and oxygenation, and act as a conduit for intubation. SaCoVLM™, as new SAD, can offer a direct vision to guide intubation. However, no study has evaluated the performance of SaCoVLM™ video laryngeal mask (VLM) intubation and i-gel combined with flexible bronchoscopy (FB)-guided intubation in airway management during general anesthesia. METHODS: A total of 120 adult patients were randomly allocated into the SaCoVLM™ group (Group S) and i-gel group (Group I). After induction of general anesthesia, guided tracheal intubation under direct vision of the SaCoVLM™ was conducted in Group S, while Group I received FB-guided tracheal intubation using the i-gel. The success rate of SAD placement, first-pass success rate of guided tracheal tube placement, and total success rate in both groups were recorded. The time for SAD placement, time for guided tracheal intubation, total intubation time (time for SAD placement and intubation), glottic exposure grading and postoperative intubation complications (i.e., dysphagia, hoarseness, pharyngalgia, etc.) of both groups were also compared. RESULTS: The first-time success rate of SAD placement was 98% in two groups. The first-pass success rate of guided endotracheal intubation was 92% in Group S and 93% in Group I (P = 0.74 > 0.05). The total intubation time was 30.8(± 9.7) s and 57.4(± 16.6) s (95% CI = -31.5 to -21.7) in Group S and Group I, respectively (P < 0.01). The total complication rate was 8% in Group S and 22% in Group I (P < 0.05). The laryngeal inlet could be observed in the S group through the visual system of SaCoVLM™. No dysphagia or hoarseness was reported. CONCLUSION: SaCoVLM™ can reveal the position of laryngeal inlet, thus providing direct vision for tracheal intubation. SaCoVLM™ -guided intubation is faster, and does not rely on FB, compared to i-gel combined with FB-guided intubation. Besides, SaCoVLM™ has a lower post-intubation complication rate. TRIAL REGISTRATION: Chinese Clinical Trials Registry (ChiCTR2100043443); Date of registration: 18/02/2021.

Delirium in Older Patients after Combined Epidural-General Anesthesia or General Anesthesia for Major Surgery: A Randomized Trial.

BACKGROUND: Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery. METHODS: Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days. RESULTS: Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001). CONCLUSIONS: Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.

Long-term Survival after Combined Epidural-General Anesthesia or General Anesthesia Alone: Follow-up of a Randomized Trial.

BACKGROUND: Experimental and observational research suggests that combined epidural-general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural-general anesthesia improves long-term survival in elderly patients. METHODS: This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. RESULTS: Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural-general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural-general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural-general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural-general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. CONCLUSIONS: In elderly patients having major thoracic and abdominal surgery, combined epidural-general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference.

Glyoxal damages human aortic endothelial cells by perturbing the glutathione, mitochondrial membrane potential, and mitogen-activated protein kinase pathways.

BACKGROUND: Exposure to glyoxal, the smallest dialdehyde, is associated with several diseases; humans are routinely exposed to glyoxal because of its ubiquitous presence in foods and the environment. The aim of this study was to examine the damage caused by glyoxal in human aortic endothelial cells. METHODS: Cell survival assays and quantitative fluorescence assays were performed to measure DNA damage; oxidative stress was detected by colorimetric assays and quantitative fluorescence, and the mitogen-activated protein kinase pathways were assessed using western blotting. RESULTS: Exposure to glyoxal was found to be linked to abnormal glutathione activity, the collapse of mitochondrial membrane potential, and the activation of mitogen-activated protein kinase pathways. However, DNA damage and thioredoxin oxidation were not induced by dialdehydes. CONCLUSIONS: Intracellular glutathione, members of the mitogen-activated protein kinase pathways, and the mitochondrial membrane potential are all critical targets of glyoxal. These findings provide novel insights into the molecular mechanisms perturbed by glyoxal, and may facilitate the development of new therapeutics and diagnostic markers for cardiovascular diseases.

Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.

[Active components and mechanism of Taohong Siwu Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking technology].

This paper aimed to investigate the active components and mechanism of Taohong Siwu Decoction in the treatment of primary dysmenorrhea(PD) based on network pharmacology and molecular docking technology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to search the chemical compositions and targets of six herbs in Taohong Siwu Decoction. The targets for PD treatment were selected through the databases of DrugBank, OMIM, TTD and CTD, and gene annotation of the targets was conducted with UniProt database. Cytoscape 3.7.2 was then used to construct the drug-compound-target network. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Taohong Siwu Decoction in the treatment of PD were selected according to the topological parameters. David database was used for GO enrichment analysis and KOBAS 3.0 was used for KEGG enrichment analysis. The molecular docking technology was used to connect the components with higher medium values in the network with core targets. The results showed that the network contained 36 compounds such as quercetin, kaempferol, luteolin, myricanone and ferulic acid, and 99 targets such as PTGS2, PTGS2, PGR and PPARG. Totally 102 GO terms were obtained by GO functional enrichment analysis(P<0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P<0.05), mainly involving inflammatory factors, hormone regulation, central analgesia, amino acid metabolism and spasmolysis. The results of molecular docking showed that the main active components can spontaneously bind to the targets. This study preliminarily revealed the mechanism of Taohong Siwu Decoction for treatment of primary dysmenorrheal through multi-components, multi-targets and multi-pathways, providing theoretical references for further researches on mechanism of Taohong Siwu Decoction.

Pharmacological actions of miltirone in the modulation of platelet function.

Salvia miltiorrhiza Bunge contains various active constituents, some of which have been developed as commercially available medicine. Moreover, some other ingredients in Salvia miltiorrhiza play roles in anti-platelet activity. The aim of the present study was to investigate the effects and the underlying mechanism of miltirone, a lipophilic compound of Salvia miltiorrhiza Bunge. The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments. Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer. Clot retraction and spreading were imaged by digital camera and fluorescence microscope. Ferric chloride-induced carotid injury model and pulmonary thromboembolism model were used to check miltirone antithrombotic effect in vivo. To elucidate the mechanisms of anti-platelet activity of miltirone, flow cytometry and western blotting were performed. Miltirone (2, 4, 8 µM) was shown to suppress platelet aggregation, dense granule, and α granule secretion in a dose-dependent manner. Meanwhile, miltirone inhibited the clot retraction and spreading of washed platelets. It reduced the phosphorylation of PLCγ2, PKC, Akt, GSK3ß and ERK1/2 in the downstream signal pathway of collagen receptor. It also reduced the phosphorylation of Src and FAK in the integrin αIIbß3-mediated "outside-in" signaling, while it did not suppress the phosphorylation of ß3. In addition, miltirone prolonged the occlusion time and reduced collagen/epinephrine-induced pulmonary thrombi. Miltirone suppresses platelet "inside-out" and "outside-in" signaling by affecting PLCγ2/PKC/ERK1/2, PI3K/Akt, and Src/FAK signaling. Therefore, miltirone might represent a potential anti-platelet candidate for the prevention of thrombotic disorders.

Myocardial injury in elderly patients after abdominal surgery.

BACKGROUND: The development of sensitive myocardial-specific cardiac biomarkers allows for detection of very small amounts of myocardial injury or necrosis. Myocardial injury (MI) as a prelude of the serious perioperative complication myocardial infarction, should be paid more attention, especially in elderly susceptible patients. Myocardial injury after abdominal surgery in elderly patients has not been described yet. The objectives of this study were to identify the incidence, predictors, characteristics and the impact of MI on outcome in elderly patients underwent abdominal surgery. METHODS: Patients aged ≥ 65 who underwent abdominal surgery longer than 2 h between January 2016 and March 2017 were reviewed. Patients with peak troponin I level of 0.04 ng/ml or greater (abnormal laboratory threshold) within once-administration-period and without non-ischemia troponin elevation proof (e.g., sepsis) were assessed for characteristics and prognosis. Risk factors of MI were determined by multivariable regression. RESULTS: Among 285 patients with whole information, 36 patients (12.6%) suffered MI, only 2 patients (0.7%) fulfilled definition of myocardial infarction. With most of them occurred within first 7 days after surgery. Multivariable analysis showed that coronary artery disease (CAD) history [odds ratio (OR) 2.817, P = 0.015], non-laparoscopic surgery (OR 5.181, P = 0.030), blood loss ≥ 800 ml (OR 3.430, P = 0.008), non-venous maintain (OR 2.105, P = 0.047), and infection (OR 4.887, P = 0.008) as risk factors for MI. MI was associated with longer hospital stay (P = 0.006), more cardiac consultation (P = 0.011), higher infection(P = 0.016) and reoperation(P = 0.026) rate. CONCLUSION: MI is common in elderly patients who underwent abdominal surgery, while myocardial infarction is infrequent. They are both associated with risk factors and worse prognosis. MI deserves more attention especially in elderly patients. Troponin I measurement is a useful test after massive surgery, which can help risk-stratifying patients, effective preventing, prompt managing and predicting outcomes. Routine monitoring of cardiac biomarkers especially within 7 days after abdominal surgery in elderly patients is recommended.

A Retrospective Study of Percutaneous Balloon Kyphoplasty for the Treatment of Symptomatic Schmorl's Nodes: 5-Year Results.

BACKGROUND Despite literature supporting the efficiency of percutaneous balloon kyphoplasty (PKP) in treating osteoporotic and malignant vertebral compression fractures, few reports exist that document its use for treatment of symptomatic Schmorl's nodes (SNs) refractory to conservative treatment. Patients with symptomatic SNs could have pain in the vertebrae similar to an acute vertebral compression fracture. MRI is very helpful in diagnosing symptomatic SNs when x-ray and CT scan are unremarkable. In painful cases, the vertebrae bone marrow around the SNs is hyperintense on T2-weighted subsequence. We evaluated the long-term safety and effectiveness of PKP for the treatment of symptomatic SNs not responding to conservative therapy. MATERIAL AND METHODS From January 2008 to December 2012, 32 patients suffering from symptomatic SNs underwent 43 PKP procedures. Outcome data, including mean height ratio of anterior and middle vertebral body, Visual Analog Scale (VAS score) for pain measurement, Oswestry Disability Indexes (ODI score) and SF-36 questionnaires for function measurement were recorded preoperatively, postoperatively, and at one month, six months, two years, and five years after treatment. RESULTS Thirty-two patients were treated successfully with PKP. Clinically asymptomatic cement leakage was observed in three (6.98%) of the treated vertebral bodies. The mean height ratio of anterior and middle vertebral bodies changed from 98.2±1.6% preoperatively to 98.5±1.4% postoperatively (p>0.05) and 98.3±1.5% preoperatively to 98.8±1.9% postoperatively (p>0.05). The mean VAS scores, ODI score, and SF-36 scores for physical function (PF), bodily pain (BF), social functioning (SF), and vitality (VT) all showed significant improvements (p<0.05). During the 5-year follow-up, the stabilization of the height of the vertebral body and functional improvements were all maintained. CONCLUSIONS PKP is a safe and effective procedure for the treatment of symptomatic SNs refractory to conservative therapy.

Ambient fine particles (PM2.5 ) attenuate collagen-induced platelet activation through interference of the PLCγ2/Akt/GSK3ß signaling pathway.

AIMS: It has been proven that carbon nanoparticles or diesel exhaust particles stimulate platelet activation. However, the effect of fine particle matter (PM2.5 ) on platelet activation remains unknown, which motivates this study. METHODS: PM2.5 samples were collected in an urban area of Zhengzhou, China. To study the morphological characteristics and the mass concentrations of trace elements of PM2.5 samples, a filed-emission scanning electron microscope, the Image-J software, and an inductively coupled plasma mass spectrometry were used. Washed human platelets or platelet-rich-plasma were used to study the effect of PM2.5 on platelet aggregation, P-selectin expression, or platelet signaling pathways. The cytotoxicity in platelets exposed to PM2.5 was evaluated by a lactate dehydrogenase assay kit. In addition, platelet adhesion and spreading were studied on collagen-coated surfaces in stable conditions. RESULTS: The filed-emission scanning electron microscope scanning showed that PM2.5 samples varied in shape and size distributions. The mean equivalent spherical diameter of these particles was 1.97 ± 0.04 µm, of which 82.40% were particles with equivalent spherical diameters of less than 2.5 µm. The mass concentration of Ca was higher than that of other elements. The other elements followed the trend of Al>Fe>Zn>Mg>Pb>K>Mn>Cu>Ti>Ba>As>Sr>Sn>Sb>Cd>B>Se>Mo>Ag>Ni>TI>V>Co. Furthermore, pretreatment of PM2.5 significantly inhibited rather than potentiated collagen-induced platelet aggregation and P-selectin expression, whereas it had no significant effect on ADP-induced platelet aggregation and P-selectin expression. The lactate dehydrogenase analysis showed trivial cytotoxic effect of PM2.5 exposure on platelets. Pretreatment of PM2.5 inhibited platelet adhesion on immobilized collagen-coated surfaces; however, it almost did not impact the platelet spreading. Immunoblotting analysis indicated that PM2.5 reduced collagen-induced phosphorylation of phospholipase C gamma-2 (PLCγ2) at Tyr759, Akt at Ser473, and glycogen synthase kinase 3ß (GSK3ß) at Ser9. CONCLUSIONS: PM2.5 attenuated collagen-induced platelet aggregation, α-granule secretion and adhesion, with the potential mechanism of impairing PLCγ2, Akt, and GSK3ß signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 530-540, 2017.

Use of the ETView Tracheoscopic Ventilation Tube in airway management of a patient with unanticipated difficult bag-mask ventilation.

The management of unanticipated difficult airway is a clinical challenge to anesthesiologists. The ETView Tracheoscopic Ventilation Tube (ETView), which is capable of real-time video imaging of the airway without needing additional equipment, may provide a promising settlement for the cases. Here, we reported a successful management of unanticipated difficult bag-mask ventilation airway with the ETView. More importantly, we successfully maintained oxygenation by modifying its injection and suction port.

Impact of CYP2C9 polymorphism found in the Chinese population on the metabolism of propofol in vitro.

The microsomal CYP2C9 alleles involved in the biotransformation of propofol, a widely used anesthetic agent, were investigated in vitro. To examine the enzymatic activity of the CYP2C9 alleles, kinetic parameters for propofol 4-hydroxylation were determined in recombinant human P450s CYP2C9 microsomes from Sf21 insects cells carrying CYP2C9*1 and other variants. Some of the variants showed decreased enzyme activity compared with the wild type, as previously reported. Two variants (CYP2C9*36 and *56) were found substantially to increase intrinsic clearance relative to the wild type variant. Most variants significantly (p<0.05) decreased intrinsic clearance of propofol compared with the wild type, except *11, *47, and *54. This study is the first to report these rare alleles for propofol metabolism, providing fundamental data for further clinical studies on CYP2C9 alleles for propofol metabolism in vivo.