Natural Affinity Driven Modification by Silicene to Construct a "Thermal Switch" for Tumorous Bone Loss.

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

FAT1 inhibits the proliferation of DLBCL cells via increasing the m6A modification of YAP1 mRNA.

Emerging evidence shows that FAT atypical cadherin 1 (FAT1) mutations occur in lymphoma and are associated with poorer overall survival. Considering that diffuse large B cell lymphoma (DLBCL) is the category of lymphoma with the highest incidence rate, this study aims to explore the role of FAT1 in DLBCL. The findings demonstrate that FAT1 inhibits the proliferation of DLBCL cell lines by downregulating the expression of YAP1 rather than by altering its cellular localization. Mechanistic analysis via meRIP-qPCR/luciferase reporter assays showed that FAT1 increases the m6A modification of YAP1 mRNA 3'UTR and the subsequent binding of heterogeneous nuclear ribonucleoprotein D (HNRNPD) to the m6A modified YAP1 mRNA, thus decreasing the stability of YAP1 mRNA. Furthermore, FAT1 increases YAP1 mRNA 3'UTR m6A modification by decreasing the activity of the TGFß-Smad2/3 pathway and the subsequent expression of ALKBH5, which is regulated at the transcriptional level by Smad2/3. Collectively, these results reveal that FAT1 inhibits the proliferation of DLBCL cells by increasing the m6A modification of the YAP1 mRNA 3'UTR via the TGFß-Smad2/3-ALKBH5 pathway. The findings of this study therefore indicate that FAT1 exerts anti-tumor effects in DLBCL and may represent a novel target in the treatment of this form of lymphoma.

Prediction of risk factors for intraoperative hypotension during general anesthesia undergoing carotid endarterectomy.

Objective: Carotid endarterectomy (CEA) has been considered as "gold standard" treatment for patients with significant carotid stenosis Intra-operative hypotension was a risk factor for post-operative complications in patients undergoing CEA. This study aimed to investigate the predictors for intra-operative hypotension during CEA. Methods: This retrospective study included consecutive patients underwent CEA from June 1, 2020 to May 31, 2021 in the neurosurgery department of Xuanwu Hospital, Capital Medical University. The intraoperative hypotension was defined as blood pressure (BP) of 20% below standard value for longer than 5 min. Univariable and multivariable analyses were performed to identify the prediction of risk factors for intraoperative hypotension. Results: Overall, 367 patients were included, and 143 (39.0%) patients had hypotension during CEA procedure. Univariate analysis indicated Grade 3 hypertension (P = 0.002), peripheral artery disease (P = 0.006) and shunting (P = 0.049) were associated with occurrence of intraoperative hypotension during CEA procedure. On multivariable analysis, Grade 3 hypertension (P = 0.005), peripheral artery disease (P = 0.009), and shunting (P = 0.034) were all found to be independent predicting factors of hypotension during the CEA process. Conclusion: Intraoperative hypotension is a dynamic phenomenon may be affected by patients with grade 3 hypertension, peripheral artery disease and intra-operative shunting. It is necessary to pay special attention to these patients, both intraoperatively and postoperatively, to improve the final clinical outcome.

Multimodal Analgesia With Sevoflurane Provides Enhanced Intraoperative Analgesic Effects in Percutaneous Nephrolithotomy: A Randomized, Blinded Clinical Trial.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is the first-line and guideline-recommended treatment for large renal calculi. Multimodal analgesia (MMA) comprising a combination of different analgesics is an increasingly popular method for pain control as it has been shown to reduce postoperative pain and reduce opioid use and the risk of opioid misuse, with a shorter recovery time in various procedures and patient populations. OBJECTIVE: In this study, we tested the hypothesis that MMA with propofol and sevoflurane (PS) can decrease pain intensity during surgery and used IoC2 as a real-time index of the analgesic effect of sevoflurane. STUDY DESIGN: Prospective, single-center, double-blind, randomized controlled clinical trial. SETTING: Xuanwu Hospital of Capital Medical University. METHODS: Patients scheduled for elective percutaneous nephrolithotomy from January 2020 to July 2020 were randomized into 2 groups, standard multimodal analgesia (propofol + sevoflurane group) and control (propofol [P] group). The PS group received propofol 2.5 mg/kg/h along with 1% sevoflurane after induction for 30 minutes during the main anesthetic procedure, and the P group received propofol 5 mg/kg/h by intravenous infusion during the operation. Index of consciousness 2 (IoC2), namely nociception index, intraoperative hemodynamic fluctuation, bispectral index (BIS), electromyography, postanesthesia care unit (PACU) length of stay, visual analog scale (VAS) score, and Aldrete and Steward scores were recorded. RESULTS: A total of 153 patients undergoing PCNL were enrolled. The demographic and clinical characteristics were similar between the 2 groups. IoC2 was reduced in the PS group compared to the P group at T10, T11, T12, T13, T14, and T15 time points, indicating that analgesia was more effective in the former. The BIS of the PS group did not differ significantly from that of the P group except at T12, T13, T14, and T15. PACU length of stay was shorter in the PS group than in the P group (mean [SD]: 54.35 [16.61] vs 47.39 [13.15], P = 0.04). VAS pain scores did not differ significantly between the 2 groups. CONCLUSION: MMA with propofol and sevoflurane provided better analgesia than propofol alone and may be an effective method to reduce stress and the intraoperative nociceptive stimulus response in patients undergoing PCNL, thereby promoting rapid postoperative recovery.

O-Arm-Navigated, Robot-Assisted Versus Conventional CT Guided Radiofrequency Ablation in Treatment of Osteoid Osteoma: A Retrospective Cohort Study.

Background: Osteoid osteoma is a common benign bone tumor, and clinically there is severe local pain that typically worsens at night. The conventional CT-guided radiofrequency ablation (RFA) was widely used in the treatment of osteoid osteoma (OO), which could result in some radiation-related and imprecise complications due to the overdose of radiation exposure. This study aimed to compare the surgical effect of robot-assisted RFA with O-arm navigation and conventional CT-guided RFA in the treatment of OO. Methods: Sixty-two patients who underwent robot-assisted RFA with O-arm navigation (Robot-RFA, n = 24) or CT-guided RFA (CT-RFA, n = 38) were included in this retrospective cohort study. The mean follow-up time was 23.3 months. The intra-operative data, primary technical success rate, visual analog scale (VAS), and post-operative complications were analyzed. Results: Primary technical success was obtained in 23 patients who had robot-assisted RFA, and 35 patients who had conventional CT-guided RFA. One patient in Robot-RFA group and three patients in CT-RFA group with pain recurrence received repeat-RFA and had a secondary success. Mean operation time and dose of radiation exposure were lower in Robot-RFA group than that in CT-RFA group. The Robot-RFA group took fewer K-wire adjustment times for each patient than the CT-RFA group. There was a statistically significant difference in the mean operation time, dose of radiation exposure, and K-wire adjustment times between the groups (p < 0.05). No complications associated with the procedure were reported in the two groups during the follow-up period. Conclusion: Robot-assisted RFA with O-arm navigation is a safer and more precise strategy in the treatment of osteoid osteoma with less operation time and radiation exposure compared with the conventional CT-guided radiofrequency ablation.

Comprehensive analysis of natural polysaccharides from TCMs: a generic approach based on UPLC-MS/MS.

Here, we report a new application using liquid chromatography-electrospray mass spectrometry (UHPLC-ESI-MS) using aldononitrile acetate derivatives for simultaneous baseline separation and detection of eight neutral saccharides, two uronic acids, one ketose, and eight alditols within 14 min. The separation was performed on a Cortecs C18 column using acetonitrile (A) and water (B) as the mobile phase with gradient elution. The target components were detected in selected ion monitoring (SIM) mode by mass spectrometry with an electrospray ionization (ESI) source operating in positive ionization mode. A comparison with traditional methods was used to determine the validity of the results. The UHPLC-ESI-MS method was used for quantitative analysis of free carbohydrates in water extracts of Crataegus pinnatifida as well as determination of Polygonatum cyrtonema and Glossy ganoderma monosaccharides in polysaccharides. The results demonstrate that this protocol is a comprehensive and effective technique for qualitative and quantitative analysis of plant polysaccharides from TCMs.

Hypothermia selectively protects the anterior forebrain mesocircuit during global cerebral ischemia.

Hypothermia is an important protective strategy against global cerebral ischemia following cardiac arrest. However, the mechanisms of hypothermia underlying the changes in different regions and connections of the brain have not been fully elucidated. This study aims to identify the metabolic nodes and connection integrity of specific brain regions in rats with global cerebral ischemia that are most affected by hypothermia treatment. 18F-fluorodeoxyglucose positron emission tomography was used to quantitatively determine glucose metabolism in different brain regions in a rat model of global cerebral ischemia established at 31-33°C. Diffusion tensor imaging was also used to reconstruct and explore the brain connections involved. The results showed that, compared with the model rats established at 37-37.5°C, the rat models of global cerebral ischemia established at 31-33°C had smaller hypometabolic regions in the thalamus and primary sensory areas and sustained no obvious thalamic injury. Hypothermia selectively preserved the integrity of the anterior forebrain mesocircuit, exhibiting protective effects on the brain during the global cerebral ischemia. The study was approved by the Institutional Animal Care and Use Committee at Capital Medical University (approval No. XW-AD318-97-019) on December 15, 2019.

Donut-like MOFs of copper/nicotinic acid and composite hydrogels with superior bioactivity for rh-bFGF delivering and skin wound healing.

BACKGROUND: Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. RESULTS: Herein, we have prepared a new donut-like metal-organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. CONCLUSIONS: Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.

Processed Multiparameter Electroencephalogram-Guided General Anesthesia Management Can Reduce Postoperative Delirium Following Carotid Endarterectomy: A Randomized Clinical Trial.

Background: Patients undergoing carotid endarterectomy (CEA) for severe carotid stenosis are vulnerable to postoperative delirium, a complication frequently associated with poor outcome. This study investigated the impact of processed electroencephalogram (EEG)-guided anesthesia management on the incidence of postoperative delirium in patients undergoing CEA. Methods: This single-center, prospective, randomized clinical trial on 255 patients receiving CEA under general anesthesia compared the outcomes of patient state index (PSI) monitoring [SEDLine Brain Function Monitor (Masimo, Inc, Irvine, CA)] (standard group, n = 128) with PSI combined with density spectral array(DSA) -guided monitoring (intervention group, n = 127) to reduce the risk of intraoperative EEG burst suppression. All patients were monitored by continuous transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to avoid perioperative cerebral hypoperfusion or hyperperfusion. According to the surgical process, EEG suppression time was calculated separately for three stages: S1 (from anesthesia induction to carotid artery clamping), S2 (from clamping to declamping), and S3 (from declamping to the end of surgery). The primary outcome was incidence of postoperative delirium according to the Confusion Assessment Method algorithm during the first 3 days post-surgery, and secondary outcomes were other neurologic complications and length of hospital stay. Results: There were no episodes of cerebral hypoperfusion or hyperperfusion according to TCD and NIRS monitoring in either group during surgery. The incidence of postoperative delirium within 3 days post-surgery was significantly lower in the intervention group than the standard group (7.87 vs. 28.91%, P < 0.01). In the intervention group, the total EEG suppression time and the EEG suppression time during S2 and S3 were shorter (Total, 0 "0" vs. 0 "1.17" min, P = 0.04; S2, 0 "0" vs. 0 "0.1" min, P < 0.01; S3, 0 "0" vs. 0 "0" min, P = 0.02). There were no group differences in incidence of neurologic complications and length of postoperative hospital stay. Conclusion: Processed electroencephalogram-guided general anesthesia management, consisting of PSI combined with DSA monitoring, can significantly reduce the risk of postoperative delirium in patients undergoing CEA. Patients, especially those exhibiting hemodynamic fluctuations or receiving surgical procedures that disrupt cerebral perfusion, may benefit from the monitoring of multiple EEG parameters during surgery. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03622515.

Configuration of short- and long-threaded cannulated screws in proximal femoral plating decreases varus collapse of femoral neck fractures: A retrospective cohort study.

OBJECTIVES: Proximal femoral plating serves as a good alternative for the fixation of femoral neck fractures, but fixation loss still occurs. This study aimed to evaluate the effect of a hybrid configuration of short- and long-threaded cannulated screws in proximal femoral plating in terms of decreasing varus collapse of femoral neck fractures. MATERIALS AND METHODS: We retrospectively analyzed 86 patients with femoral neck fractures who were fixed by proximal femoral plating from January 2015 to June 2019. These patients were divided into two groups according to screw configuration: short- and long-threaded cannulated screws (SLTS, n = 38) and short-threaded cannulated screws (STS, n = 48). Radiological and clinical outcomes including screw withdraw, nonunion, avascular necrosis, caput-collum-diaphysis (CCD) angle, amount of femoral neck shortening (FNS), and Harris Hip Score (HHS) were compared between the groups. RESULTS: Preoperative characteristics including age, gender, Garden type, duration of surgery, and reduction quality were not significantly different between the two groups (p > 0.05). Less decreased CCD angle was observed in the SLTS group (-0.4° (-1.4 - 1.8)) compared with that in the STS group (7.9° (6.3 - 11.0)) (p < 0.001). The SLTS group also presented with fewer amount of FNS (3.2 (2.7 - 3.8) mm vs. 5.1 (4.2 - 5.9) mm, p < 0.001). Bone union was achieved in all patients and no avascular necrosis was observed during the follow-up. The HHS was higher in the SLTS group (86.4 ± 5.1) than that in the STS group (81.5 ± 4.5) (p < 0.001). CONCLUSION: The hybrid configuration of short- and long-threaded screws in proximal femoral plating offers better resistance against varus collapse and yields better functional outcomes in femoral neck fractures.

Influence of three different anesthesia protocols on aged rat brain: a resting-state functional magnetic resonance imaging study.

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups. METHODS: Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests. RESULTS: Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed. CONCLUSION: ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.

Dynamic limited axial compression yields favorable functional outcomes in the fixation of Pauwels type-3 femoral neck fractures: A retrospective cohort study.

PURPOSE: Pauwels type-3 femoral neck fractures are challenging injuries to manage with high rates of complications after internal fixation and no consensus has been reached regarding the optimal fixation construct. The current study aims to evaluate the effect of dynamic limited axial compression in parallel screws combined with medial buttress plate (SMBP) or lateral compression plate (LCP) fixation of Pauwels type-3 femoral neck fractures. METHODS: We performed a retrospective analysis of 51 cases of Pauwels type-3 femoral neck fractures who were fixed by SMBP or LCP. Specifically, the screw fixing the femoral head in the buttress plate was omitted. Postoperative complications and functional outcomes were mainly studied. RESULTS: With a mean follow-up of 19.9 months, the rate of neck shortening was higher in the LCP group than that in SMBP group (32.1% vs. 8.7%, p = 0.04). Neither nonunion nor avascular necrosis was observed in both groups. Good-to-excellent Harris hip score accounts for 95.2% in SMBP group and 89.3% in LCP group (p = 0.40). Moreover, older age, fracture comminution and compression plate fixation predispose to neck shortening. CONCLUSION: Dynamic limited axial compression by SMBP or LCP fixation was effective to improve the functional outcome of patients with Pauwels type-3 femoral neck fractures.

MicroRNA expression in the hippocampal CA1 region under deep hypothermic circulatory arrest.

Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs (miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection (cyclin dependent kinase, CDK16 and SLC1A2), central nervous system development (FOXO3, TYRO3, and SLC1A2), ion transmembrane transporter activity (ATP2B2 and SLC1A2), and interleukin-6 receptor binding (IL6R) - these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017 (approval No. XW-INI-AD2017-0112).

EphA2 antagonism alleviates LPS-induced acute lung injury via Nrf2/HO-1, TLR4/MyD88 and RhoA/ROCK pathways.

Eph receptor tyrosine kinases have a wide range of biological functions and have gradually been recognized increasingly as key regulators of inflammation and injury diseases. Although previous studies suggested that EphA2 receptor may be involved in the regulation of inflammation and vascular permeability in injured lung, the detailed effects of EphA2 on LPS-induced acute lung injury (ALI) are still inadequate and the underlying mechanism remains poorly understood. In this study, we detected the effects of EphA2 antagonism on inflammation, pulmonary vascular permeability and oxidative stress in LPS-induced ALI and investigate the potential mechanism. Our results showed that EphA2 antagonism markedly inhibited the cytokines release and inflammatory cells infiltration in BALF, prevented the LPS-induced elevations of MPO activity and MDA level in lung tissues. Our study also found that EphA2 antagonism significantly decreased the wet/dry ratios, reduced the Evans blue albumin extravasation in lung tissues and obviously alleviated the LPS-induced increment of pulmonary vascular permeability. Mechanistically, EphA2 antagonism significantly increased the activation of Nrf2 along with its target antioxidant enzyme HO-1 and inhibited the expressions of TLR4/MyD88 in lung tissues and A549 alveolar epithelial cells. Furthermore, EphA2 antagonism dramatically inhibited the LPS-evoked activations of RhoA/ROCK in lung tissues. In conclusion, our data indicate that EphA2 receptor plays an essential role in LPS-induced ALI and EphA2 antagonism has protective effects against LPS-induced ALI via Nrf2/HO-1, TLR4/MyD88 and RhoA/ROCK pathways. These results suggest that antagonism of EphA2 may be an effective therapeutic strategy for the treatment of ALI.

Protective effect of dexmedetomidine on kidney injury of parturients with preeclampsia undergoing cesarean section: a randomized controlled study.

The present study aimed to elucidate the effects of dexmedetomidine on kidney injury of parturients with preeclampsia (PE) undergoing cesarean section. Total 134 cesarean delivery women with PE were randomly divided into intervention group (IG) and control group (CG). Both groups underwent combined spinal and epidural anesthesia (CSEA), the IG was treated with 0.4 µg/(kg·min) dexmedetomidine for 10 min before surgery. The CG was treated with equivalent saline. Heart rate (HR), blood pressure, oxygen saturation (SpO2) of the two groups were measured at different time point after administration. Level of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Visual analogue score (VAS), Ramsay sedation score (RSS), and kidney injury related indexes were evaluated at different time points. The plasma-drug concentration of patients was determined by High Performance Liquid Chromatography (HPLC) method. Compared with CG, HR, PE, and diastolic blood pressure (DBP) showed lower level while SpO2 showed higher level in IG. Furthermore, expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-10 in IG was decreased after drug administration, the contents of ß2-MG, KIM-1 and urine protein were also decreased in contrast to the CG (all P<0.05). Besides, VAS score was decreased but Ramsay score was increased in the IG (both P<0.05). The results of HPLC showed that the half life of dexmedetomidine was about 20 min and it is speculated that the drug can be quickly metabolized within 24 h. Dexmedetomidine exerted protective effects on kidney injury of parturients with PE undergoing cesarean section.

Structural characteristics and hepatoprotective potential of Aralia elata root bark polysaccharides and their effects on SCFAs produced by intestinal flora metabolism.

The structural characteristics of the polysaccharides from Aralia elata root barks (AERP) were systematically investigated by FT-IR, HPSEC-ELSD and colorimetric methods as well as by GCMS based monosaccharide compositions, Smith degradations, and methylation analysis. The result showed average molecular weights of AERP were between 42.7 kDa and 93.9 kDa. AERP was composed of Ara, Rha, GlcA, Man, Glc, and Gal in a molar ratio of 22.2: 10.3: 8.1: 32.7: 5.7: 21.2 along with a small number of sulfate (3.38%) and acetyl (4.87%) groups. The abundant glycosidic linkages of Man, Ara, Gal, and Rha were observed as more than 90% of all the monosaccharides detected. Studies to evaluate hepatoprotective potentials of AERP showed that they had potent hepatoprotective effects in vivo in carbon tetrachloride-induced acute liver injury (CIALI) in mice by histopathological evaluation, biochemical examinations and ELISA assays. GCMS was further used to determine the effects of AERP on the chemical profiles of nine common short-chain fatty acids (SCFAs) produced by intestinal flora metabolism in CIALI mice. These findings not only provide novel insights into the pharmacological actions of AERP on the protection from CIALI in mice, but they also demonstrate that determining SCFA profiles by targeted GC-MS metabolomics is an effective technique to investigate the molecular mechanisms of the effects of plant polysaccharides on intestinal flora metabolism.

A generic strategy based on gas phase decomposition of protonated and ammoninted precursors producing predictable MRM-MS ion pairs and collision energies for direct analysis of plant triterpene glycosides.

Optimization of multiple reaction monitoring mass spectrometry (MRM-MS) parameters of triterpene glycosides (TGs) using traditional infusion methods remains to be labor-intensive. However, it was found that mild gas phase decompositions of protonated and ammoninted precursors (DPAP) of TGs could produce a series of abundant dehydrated product ions of aglycones ([A+H-nH2O]+ (n = 0, 1, 2, 3…)) with high efficiency and stability. Based on these considerations and findings, an innovative ESI+-MRM-DPAP-MS strategy was devised on a QTRAP 4000 instrument allowing for rapid the qualitative and quantitative analysis of plant TGs. A detailed study of 85 model compounds from 20 herbal medicines was implemented for validation and evaluation of the ESI+-MRM-DPAP-MS strategy proposed. The central composition design confirmed that collision energy (CE) played more significant roles than declustering potentials (DP) for the formation of these Q1/Q3 ion pairs based on MRM-DPAP-MS. It is also noted that Q1 and Mw were the most important factors for the prediction of CE values by a partial least square regression model. Here, we demonstrated this generic workflow and its merits in: (1) early prediction and selection of MRM ion pairs, no matter which type of TGs, employing a new-found Q1/Q3 calculation formula (Q1=[M+H/NH4]+ and Q3= [A+H-nH2O]+ (n = 0, 1, 2, 3…)); (2) direct determination of practicable CE values using TGs-specific CE-estimating linear equations; (3) appearances of excellent sensitivity, stability and repeatability through real application in Aralia elata, Panax notoginseng and Caulophyllum robustum; (4) seamless application of optimal CE parameters in other triple quadrupole MS instruments such as Thermo TSQ Quantum Ultra. The ESI+-MRM- DPAP-MS may service as an effective and feasible approach for analytical characterization of biological TGs from herbal medicines.

Ulinastatin May Significantly Improve Postoperative Cognitive Function of Elderly Patients Undergoing Spinal Surgery by Reducing the Translocation of Lipopolysaccharide and Systemic Inflammation.

Background: Studies have shown that perioperative inflammatory response is one of the important factors that caused postoperative cognitive dysfunction (POCD). Ulinastatin is a broad-spectrum protease inhibitor that inhibits inflammatory. We investigated the effects of ulinastatin on inflammatory response and early postoperative cognitive function in elderly patients undergoing spinal surgery. Methods: This clinical trial was approved by the Xuanwu Hospital Ethical Committee (Registration number: ChiCTR-IPR-16008931). Sixty elderly patients undergoing elective spinal surgery with American Society of Anesthesiologists (ASA) status of I-II were randomized into ulinastatin and control groups; total intravenous anesthesia was performed. The elderly patients in ulinastatin group underwent intravenous infusion of ulinastatin 10,000 units/kg following anesthesia induction and before surgical incision, and 5000 units/kg on post-operative days 1 and 2. Cognitive function was determined with Montreal Cognitive Assessment (MOCA) test preoperatively and on post-operative day 7 by a neurologist. Serum lipopolysaccharide (LPS), interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloprotease-9 (MMP-9) concentration levels were measured at baseline, the end of surgery, and on post-operative days 1 and 3. Results: All elderly patients completed the study. Ulinastatin infusion significantly reduced the incidence of POCD in elderly patients undergoing spine surgery (ulinastatin group 16% vs. control group 43%, χ 2 = 5.079, P = 0.024, P < 0.05). The elderly patients in ulinastatin group exhibited lower serum LPS, IL-6, CRP, and MMP-9 concentrations, as well as a shortened peak value duration, compared with those in the control group following surgery (P < 0.05). Conclusion: Systemic inflammation and translocation of LPS were inhibited by the infusion of ulinastatin in elderly patients undergoing spinal surgery. The anti-inflammation intervention with ulinastatin can significantly improve the elderly patients' postoperative cognitive function.

MicroRNAs of microglia: Wrestling with central nervous system disease.

Microglia serve as brain-resident myeloid cells that affect cerebral development, ischemia, neurodegeneration, and neuro-viral infection. MicroRNAs play a key role in central nervous system disease through post-transcriptional regulation. Indeed, evidence shows that microRNAs are one of the most important regulators mediating microglial activation, polarization, and autophagy, and subsequently affecting neuroinflammation and the outcome of central nervous system disease. In this review, we provide insight into the function of microRNAs, which may be an attractive strategy and influential treatment for microglia-related central nervous system dysfunction. Moreover, we comprehensively describe how microglia fight against central nervous system disease via multiple functional microRNAs.