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Approximately one-third of postoperative patients are troubled by postoperative pain. Effective treatments are still lacking. The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF)-VGF (non-acronymic) in dorsal root ganglia (DRG) in postoperative pain. Pain behaviors were assessed through measurements of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Transcriptome analysis was conducted to identify potential targets associated with postoperative pain. Western blotting, immunofluorescence, and ELISA were employed to further detect macrophage activation as well as the expression of BDNF, VGF, TNF-α, IL-1β, and IL-6. Results showed that plantar incision induced both mechanical and thermal hyperalgesia. Transcriptome analysis suggested that plantar incision caused upregulation of BDNF and VGF. The expressions of BDNF and VGF were upregulated in isolectin B4-positive (IB4+) and calcitonin gene-related peptide-positive (CGRP+) neurons, rather than neurofilament 200-positive (NF200+) neurons. The activation of BDNF-VGF pathway upregulated expression of IL-6, TNF-α, and IL-1β and promoted the activation of macrophages. In conclusion, BDNF-VGF pathway aggravates acute postoperative pain by promoting macrophage activation and pro-inflammatory cytokine production, which may provide a new target for the treatment of postoperative pain. [ABSTRACT FROM AUTHOR]

Chemotherapy‐based combination regimens are recommended as first‐line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD‐OxPt (IV) nanoparticles (NPs) via host‐guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD‐OxPt (IV) NPs exhibit prolonged circulation in the blood and intra‐tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD‐OxPt (IV) NPs exhibited proton‐driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD‐OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53‐mediated DNA repair. Supramolecular nanofibers can further serve as the "ammunition depot" to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino‐like cell death and enhanced immunogenicity. Furthermore, DAS@CD‐OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis. [ABSTRACT FROM AUTHOR]

Expanding and enhancing the quality of consumption is crucial to satisfy the increasing demand for a higher standard of living. However, the rising risk of chronic diseases impacts not only the level of consumption but also impedes the optimization of consumption patterns. This research utilizes Staggered Difference-in-Differences (DID) and Difference-in-Differences-in-Differences (DDD) models to evaluate the effects of chronic disease shocks on both the levels and structures of household consumption, leveraging data from the China Family Panel Studies (CFPS) across four survey waves from 2012 to 2018. Additionally, the study examines the effects and mechanisms of the multi-level health insurance system in mitigating the impact of chronic disease shocks. The study discerns a significant decrease in household consumption expenditure, obstruction in the enhancement of consumption structures, and a constriction of consumption diversity attributable to chronic disease shocks. Heterogeneous analysis reveals that the impact of chronic shocks varies across factors such as age, capital endowment, urban versus rural residence, and the availability of healthcare resources. Moreover, the analysis highlights the heterogeneous mitigating effects of the multi-level health insurance system, particularly through diminishing out-of-pocket medical expenses and the propensity for precautionary savings. The findings accentuate the imperative for the enhancement and equalization of the multi-level health insurance system to fortify household consumption, offering significant policy insights for the realization of the "Healthy China" vision. JEL Classification : P36, D12. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) may lead to healthy tissue damage, tumor metastasis, and recurrence, which makes mild photothermal therapy (mild PTT) stand out. However, overcoming heat resistance, insufficient therapeutic effect, and poor photothermal conversion efficiency has become new challenge. Herein, we report a dynamic supramolecular nanocarrier formed from amide-sericin and aldehyde-polyhydroxy glucan (denoted as SDA), the loose cavity of which can be filled by using the pharmaceutical combination of lonidamine (LND) and NIR-II photothermal agent of IR-1061, producing SDLI with a tighter inner hole, smaller and uniform particle size and excellent stability due to multiple pulling forces. Moreover, the intricate internal network structure prevents the hydrophobic IR-1061 from forming aggregates in the small cavity, and the photothermal conversion efficiency (PCE) can reach 48.9%. At the acidic tumor microenvironment of pH 6.5, the controlled release of LND can solve the problem of heat resistance of NIR-II mild PTT and significantly improve the therapeutic effect of NIR-II mild PTT. Meanwhile, SDLI also shows a reasonable tumor inhibition rate, so the synergistic strategy of inhibiting tumor energy metabolism and NIR-II mild PTT to magnify mitochondrial oxidative stress, continuous cell stress state-induced immunogenic cell death to promote the induction of tumor apoptosis is proposed to achieve more effective cancer treatment. [ABSTRACT FROM AUTHOR]

Sulfur dispersion and its electrical conductivity are the key for lithium-sulfur batteries with good cycling stability. In this work, a flexible film composed of reduced graphene oxide (rGO) and sulfur is fabricated from the self-assembly aggregation of sulfur-coated rGO sheets. Not only the three-dimensional rGO network enormously improves the electrical conductivity of the film, but also the strong interaction between well-dispersed sulfur molecules and rGO sheets ensures the stability of sulfur during charge/discharge. Furthermore, the rGO/S film can be directly used as cathode without any binders, conductive additives, and aluminum current collectors. The electrochemical result shows that the rGO/S film has excellent cycling stability with a high rate capacity 485 mAh/g at a current rate of 2C. [ABSTRACT FROM AUTHOR]

Circadian rhythm involved with physiology has been reported to affect pharmacokinetics or pharmacodynamics. We hypothesized that circadian variations in physiology disturb anesthesia and eventually affect recovery after anesthesia. A retrospective cohort study initially included 107,406 patients (1 June 2016–6 June 2021). Patients were classified into morning or afternoon surgery groups. The primary outcome was daytime variation in PACU (post-anesthesia care unit) recovery time and Steward score. Inverse probability weighting (IPW) approach based on propensity score and univariable/multivariable linear regression were used to estimate this outcome. Of 28,074 patients, 13,418 (48%) patients underwent morning surgeries, and 14,656 (52%) patients underwent afternoon surgeries. LOWESS curves and IPW illustrated daytime variation in PACU recovery time and Steward score. Before adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (median [interquartile range], 57 [46, 70] vs. 54 [43, 66], p < 0.001) and a higher Steward score (5.62 [5.61, 5.63] vs. 5.66 [5.65, 5.67], p < 0.001). After adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (58 [46, 70] vs. 54 [43, 66], p < 0.001). In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time (coefficient, −3.20; 95% confidence interval, −3.55 to −2.86). Among non-cardiac surgeries, daytime variation might affect recovery after general anesthesia. These findings indicate that the timing of surgery improves recovery after general anesthesia, with afternoon surgery providing protection. In this retrospective cohort study of 28,074 participants, the afternoon surgery group has a higher Steward score than the morning surgery group. In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time. Among non-cardiac surgeries, daytime variation affects the recovery after general anesthesia, with afternoon surgery providing protection. [ABSTRACT FROM AUTHOR]

Background: Perioperative neurocognitive disorders (PND) with a high incidence frequently occur in elderly surgical patients closely associated with prolonged anesthesia-induced neurotoxicity. The neuromorphopathological underpinnings of anesthesia-induced neurotoxicity have remained elusive. Methods: Prolonged anesthesia with sevoflurane was used to establish the sevoflurane-induced neurotoxicity (SIN) animal model. Morris water maze, elevated plus maze, and open field test were employed to track SIN rats' cognitive behavior and anxiety-like behaviors. We investigated the neuropathological basis of SIN through techniques such as transcriptomic, electrophysiology, molecular biology, scanning electron microscope, Golgi staining, TUNEL assay, and morphological analysis. Our work further clarifies the pathological mechanism of SIN by depleting microglia, inhibiting neuroinflammation, and C1q neutralization. Results: This study shows that prolonged anesthesia triggers activation of the NF-κB inflammatory pathway, neuroinflammation, inhibition of neuronal excitability, cognitive dysfunction, and anxiety-like behaviors. RNA sequencing found that genes of different types of synapses were downregulated after prolonged anesthesia. Microglial migration, activation, and phagocytosis were enhanced. Microglial morphological alterations were also observed. C1qa, the initiator of the complement cascade, and C3 were increased, and C1qa tagging synapses were also elevated. Then, we found that the "Eat Me" complement pathway mediated microglial synaptic engulfment in the hippocampus after prolonged anesthesia. Afterward, synapses were remarkably lost in the hippocampus. Furthermore, dendritic spines were reduced, and their genes were also downregulated. Depleting microglia ameliorated the activation of neuroinflammation and complement and rescued synaptic loss, cognitive dysfunction, and anxiety-like behaviors. When neuroinflammatory inhibition or C1q neutralization occurred, complement was also decreased, and synaptic elimination was interrupted. Conclusions: These findings illustrated that prolonged anesthesia triggered neuroinflammation and complement-mediated microglial synaptic engulfment that pathologically caused synaptic elimination in SIN. We have demonstrated the neuromorphopathological underpinnings of SIN, which have direct therapeutic relevance for PND patients. [ABSTRACT FROM AUTHOR]

Background: Perioperative neurocognitive disorders (PND) with a high incidence frequently occur in elderly surgical patients closely associated with prolonged anesthesia-induced neurotoxicity. The neuromorphopathological underpinnings of anesthesia-induced neurotoxicity have remained elusive. Methods: Prolonged anesthesia with sevoflurane was used to establish the sevoflurane-induced neurotoxicity (SIN) animal model. Morris water maze, elevated plus maze, and open field test were employed to track SIN rats' cognitive behavior and anxiety-like behaviors. We investigated the neuropathological basis of SIN through techniques such as transcriptomic, electrophysiology, molecular biology, scanning electron microscope, Golgi staining, TUNEL assay, and morphological analysis. Our work further clarifies the pathological mechanism of SIN by depleting microglia, inhibiting neuroinflammation, and C1q neutralization. Results: This study shows that prolonged anesthesia triggers activation of the NF-κB inflammatory pathway, neuroinflammation, inhibition of neuronal excitability, cognitive dysfunction, and anxiety-like behaviors. RNA sequencing found that genes of different types of synapses were downregulated after prolonged anesthesia. Microglial migration, activation, and phagocytosis were enhanced. Microglial morphological alterations were also observed. C1qa, the initiator of the complement cascade, and C3 were increased, and C1qa tagging synapses were also elevated. Then, we found that the "Eat Me" complement pathway mediated microglial synaptic engulfment in the hippocampus after prolonged anesthesia. Afterward, synapses were remarkably lost in the hippocampus. Furthermore, dendritic spines were reduced, and their genes were also downregulated. Depleting microglia ameliorated the activation of neuroinflammation and complement and rescued synaptic loss, cognitive dysfunction, and anxiety-like behaviors. When neuroinflammatory inhibition or C1q neutralization occurred, complement was also decreased, and synaptic elimination was interrupted. Conclusions: These findings illustrated that prolonged anesthesia triggered neuroinflammation and complement-mediated microglial synaptic engulfment that pathologically caused synaptic elimination in SIN. We have demonstrated the neuromorphopathological underpinnings of SIN, which have direct therapeutic relevance for PND patients. [ABSTRACT FROM AUTHOR]

The susceptibility of different individuals to anesthetics varies widely, and sevoflurane is no exception. We hypothesized that polymorphisms in genes involved in pharmacokinetics and pharmacodynamics may explain this variation. A total of 151 individuals undergoing otorhinolaryngology surgery were included. The influence of genetic polymorphisms on sevoflurane sensitivity were investigated through SNaPshot technology. Individuals carrying KCNK2 rs6686529 G > C, MTRR rs3733784 TT, rs2307116 GG, or rs1801394 AA polymorphisms had a higher sensitivity to the sedative effect of sevoflurane than those without those polymorphisms. The univariate linear regression analysis indicated that MTRR rs3733784 TT, rs2307116 GG, and rs1801394 AA were potentially significant predictors of higher sensitivity to the sedative effect of sevoflurane. Moreover, CYP2E1 rs3813867 G > C and rs2031920 C > T, GABRG1 rs279858 T > C, KCNK3 rs1275988 CC, GRIN2B rs1806201 GG, MTRR rs2307116 G > A, and rs1801394 A > G were associated with a higher sensitivity to the cardiovascular effect of sevoflurane. Our results suggested that 9 single nucleotide polymorphisms in genes involved in metabolizing enzymes, transport proteins, target proteins of sevoflurane and folate metabolism may help to explain individual differences in the susceptibility to the sedative or cardiovascular effect of sevoflurane. [ABSTRACT FROM AUTHOR]

Background: Tau pathology is observed during autopsy in many patients with Parkinson's disease dementia (PDD). Positron emission tomography (PET) imaging using the tracer 18F‐florzolotau has the potential to capture tau accumulation in the living brain. Objective: The aim was to describe the results of 18F‐florzolotau PET/CT (computed tomography) imaging in patients with PDD. Methods: Ten patients with PDD, 9 with Parkinson's disease with normal cognition (PD‐NC), and 9 age‐matched healthy controls (HCs) were enrolled. Clinical assessments and 18F‐florzolotau PET/CT imaging were performed. Results: 18F‐Florzolotau uptake was significantly higher in the cortical regions of patients with PDD compared with both PD‐NC and HCs, especially in the temporal lobe. Notably, 18F‐florzolotau uptake in the occipital lobe of patients with PDD showed a significant correlation with cognitive impairment as reflected by Mini‐Mental State Examination (MMSE) scores. Conclusions: 18F‐Florzolotau PET imaging can effectively capture the occurrence of tau pathology in patients with PDD, which was also linked to MMSE scores. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Clinical and animal studies demonstrated that neuroinflammation from anesthesia (sevoflurane) is the main contributor to cause perioperative neurocognitive disorders (PND). Recently, it was reported that microglia respond to hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which was the target of sevoflurane. Whether HCN channels are involved in the induction of neuroinflammation after sevoflurane exposure is still unclear. Results: Sevoflurane exposure had increased cognitive dysfunction and anxiety-like behaviors in rats. Rats inhaled with sevoflurane had activated microglia and increased neuroinflammation (IL-1β, IL-6, and TNF-α) in the hippocampus. RNA sequencing identified 132 DEGs (86 up-regulated and 46 down-regulated DEGs [differentially expressed genes]) in the hippocampus of PND rats. RNA-sequencing also uncovered that sevoflurane exposure down-regulates HCN2 expression. Pathway and process enrichment analysis suggests DEGs are mainly enriched in regulation of system process, positive regulation of glutamate secretion, secretion, regulation of synaptic transmission, regulation of nervous system process, behavior, negative regulation of sodium ion transport, and learning or memory. We validated that sevoflurane exposure can down-regulate the levels of PEX5R/Trip8b (an interaction partner and auxiliary subunit of HCN channels) and HCN1-4 channels in the hippocampus of PND rats. We used immunofluorescence staining to identify that HCN2 co-labels with neurons (Neun), astrocytes (GFAP), and microglia (iba1). We observed that the co-labeling of HCN2 with neurons or microglia decreased in the hippocampus and cortex after sevoflurane exposure. Blocking HCN2 by ZD7288 treatment further activated microglia and aggravated sevoflurane exposure-induced anxiety-like behavior, cognitive impairment, and neuroinflammation. Conclusions: We concluded that sevoflurane exposure can induce an increased level of neuroinflammation, microglial activation, cognitive dysfunction, and anxiety-like behaviors in rats. HCN2 channel, as the target of sevoflurane action, mediates this process. HCN2 might be a target for the treatment and prevention of sevoflurane-induced PND. [ABSTRACT FROM AUTHOR]

Purpose: Pyrotinib, a novel human epidermal growth factor receptor 2 (HER2)-targeted tyrosine kinase inhibitor (TKI), has led to remarkable survival outcomes in HER2-positive advanced breast cancer (ABC) in clinical trials and was approved for second-line standards of treatment for HER2+ ABC in China. However, the clinical trials could not fully reflect reality of clinical practice, and predictive factors were still lacking. This study aimed to assess the actual efficacy and safety of pyrotinib in HER2+ ABC in real-world setting. Patients and Methods: In this multicenter, retrospective, observational real-world study, we analyzed 171 patients with HER2+ ABC, who received pyrotinib-based treatment from November 2017 to November 2020. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Results: Up to November 30, 2021, the median PFS (mPFS) was 12.0 months for all patients. One hundred and sixty-two patients (94.7%) with measurable lesions had been included in efficacy assessment. The ORR and CBR were 45.1% and 81.5%, respectively. A significantly longer PFS was reported in patients who received pyrotinib as first-line treatment, had the ECOG-PS of 0– 1, as well as those who were lapatinib-naive. In addition, multivariable analysis indicated that ECOG-PS of 2– 4, positive hormone receptor (HR) status, and presence of visceral metastasis were independent negative predictors of PFS. As far as we know, this study first reported the survival outcome of pyrotinib cross-line treatment, with a mPFS of 5.0 months. All grades of adverse events (AEs) occurred in 171 patients (100%), and the most common AE was diarrhea (86.5%). Conclusion: This study further demonstrated the outstanding efficacy and safety of pyrotinib and reported the potential predictors of survival in HER2+ ABC. [ABSTRACT FROM AUTHOR]

Myocardial fibrosis (MF) is a common pathological feature of many heart diseases and seriously threatens the normal activity of the heart. Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a novel dammarane-type saponin, was obtained from the hydrolysates of total gypenosides. It has been reported to exert a beneficial anti-inflammatory effect. In our study, we attempted to investigate the efficiency and possible molecular mechanism of Gyp I in cardiac injury treatment induced by ISO. In vitro, Gyp I was found to increase the survival rate of H9c2 cells and inhibit apoptosis. Combined with molecular docking and Western blot analysis, Gyp I was confirmed to regulate the TLR4/NF-κB/NLRP3 signaling pathway. In vivo, C57BL6 mice were subcutaneously injected with 10 mg/kg ISO to induce heart failure. Mice were given a gavage of Gyp I (10, 20, or 40 mg/kg/d for three weeks). Pathological alterations, fibrosis-, inflammation-, and apoptosis-related molecules were examined. By means of cardiac function detection, biochemical index analysis, QRT-PCR monitoring, histopathological staining, immunohistochemistry, and Western blot analysis, it was elucidated that Gyp I could improve cardiac dysfunction, alleviate collagen deposition, and reduce myocardial fibrosis (MF). In summary, we reported for the first time that Gyp I showed good myocardial protective activity in vitro and in vivo, and its mechanism was related to the TLR4/NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies. Methods: Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology. Results: Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3—11.4] cases per day, with 7.3 [3.2—13.6] performed in Grade III hospitals and 3.4 [1.8—6.8] performed in Grade II hospitals (z = -7.065, p < 0.001). Conclusions: Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions. [ABSTRACT FROM AUTHOR]

Background: Self-efficacy, as the vital determinant of behavior, influencing clinicians' situation awareness, work performance, and medical decision-making, might affect the incidence of anesthesia-related adverse events (ARAEs). This study was employed to evaluate the association between perceived self-efficacy level and ARAEs. Methods: A cross-sectional study was performed in the form of an online self-completion questionnaire-based survey. Self-efficacy was evaluated via validated 4-point Likert scales. Internal reliability and validity of both scales were also estimated via Cronbach's alpha and validity analysis. According to the total self-efficacy score, respondents were divided into two groups: normal level group and high level group. Propensity score matching and multivariable logistic regression were employed to identify the relationship between self-efficacy level and ARAEs. Results: The response rate of this study was 34%. Of the 1011 qualified respondents, 38% were women. The mean (SD) age was 35.30 (8.19) years. The Cronbach's alpha of self-efficacy was 0.92. The KMO (KMO and Bartlett's test) value of the scale was 0.92. ARAEs occurred in 178 (33.0%) of normal level self-efficacy group and 118 (25.0%) of high level self-efficacy group. Before adjustment, high level self-efficacy was associated with a decreased incidence of ARAEs (RR [relative risk], 0.76; 95% CI [confidence interval], 0.62–0.92). After adjustment, high level self-efficacy was also associated with a decreased incidence of ARAEs (aRR [adjusted relative risk], 0.63, 95% CI, 0.51–0.77). In multivariable logistic regression, when other covariates including years of experience, drinking, and the hospital ranking were controlled, self-efficacy level (OR [odds ratio], 0.62; 95% CI, 0.46–0.82; P = 0.001) was significantly correlated with ARAEs. Conclusions: Our results found a clinically meaningful and statistically significant correlation between self-efficacy and ARAEs. These findings partly support medical educators and governors in enhancing self-efficacy construction in clinical practice and training. [ABSTRACT FROM AUTHOR]

Rocuronium is widely utilized in clinical general anaesthesia, and individual differences in pharmacology and clearance have been observed. Two hundred thirty‐six Chinese patients undergoing selective thyroid/breast mass resection were studied. Total intravenous anaesthesia was induced with a single dose of propofol (2 mg·kg−1), sufentanil (0.5 μg·kg−1), and rocuronium (0.6 mg·kg−1) and maintained with propofol (3–5 mg·kg−1·h−1) and remifentanil (0.2–0.4 μg·kg−1·min−1). Intubation conditions and a train‐of‐four index of patients were utilized to assess the effects and duration of rocuronium. The data from 228 patients were analysed and reported. Genotypes NR1I2 rs2472677 C > T, NR1I2 rs6785049 G > A, SLCO1B1 rs4363657 T > C, SLCO1A2 rs4762699 T > C, and UGT1A1 rs4148323 G > A contributed to individual variation in rocuronium. Of the clinical variables tested, age, BMI, total dose of propofol, NR1I2 rs2472677, and SLCO1A2 rs4762699 correlated significantly (P < 0.05 for all) with the clinical duration or total clinical action time of rocuronium in a multiple linear regression model. No significant interactions were observed in intubation conditions. Genetic variations in NR1I2 rs2472677, NR1I2 rs6785049, SLCO1B1 rs4363657, SLCO1A2 rs4762699, and UGT1A1 rs4148323 were related to extensive interindividual variability in the clinical duration and total clinical action time of rocuronium. [ABSTRACT FROM AUTHOR]

Sevoflurane can induce memory impairment during clinical anesthesia; however, the underlying mechanisms are largely unknown. TASK-3 channels are one of the potential targets of sevoflurane. Accumulating evidence supports a negative role of intracranial theta rhythms (4–12 Hz) in memory formation. Here, we investigated whether TASK-3 channels contribute to sevoflurane-induced memory impairment by regulating hippocampal theta rhythms. In this study, the memory performance of mice was tested by contextual fear conditioning and inhibitory avoidance experiments. The hippocampal local field potentials (LFPs) were recorded from chronically implanted electrodes located in CA3 region. The results showed that sevoflurane concentration-dependently impaired the memory function of mice, as evidenced by the decreased time mice spent on freezing and reduced latencies for mice to enter the shock compartment. Our electrophysiological results revealed that sevoflurane also enhanced the spectral power of hippocampal LFPs (1–30 Hz), particularly in memory-related theta rhythms (4–12 Hz). These effects were mitigated by viral-mediated knockdown of TASK-3 channels in the hippocampal CA3 region. The knockdown of hippocampal TASK-3 channels significantly reduced the enhancing effect of sevoflurane on hippocampal theta rhythms and alleviated sevoflurane-induced memory impairment. Our data indicate that sevoflurane can increase hippocampal theta oscillations and impair memory function via TASK-3 channels. [ABSTRACT FROM AUTHOR]

Background: Accruing positron emission tomography (PET) studies have suggested that dopaminergic functioning and metabolic changes are correlated with cognitive dysfunction in Parkinson's disease (PD). Yet, the relationship between dopaminergic or cerebral metabolism and different cognitive domains in PD is poorly understood. To address this scarcity, we aimed to investigate the interactions among dopaminergic bindings, metabolic network changes, and the cognitive domains in PD patients. Methods: We recruited 41 PD patients, including PD patients with no cognitive impairment (PD-NC; n = 21) and those with mild cognitive impairment (PD-MCI; n = 20). All patients underwent clinical evaluations and a schedule of neuropsychological tests and underwent both 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) PET imaging. Results: 11C-CFT imaging revealed a significant positive correlation between executive function and striatal dopamine transporter (DAT) binding at both the voxel and regional levels. Metabolic imaging revealed that executive function correlated with 18F-FDG uptake, mainly in inferior frontal gyrus, putamen, and insula. Further analysis indicated that striatal DAT binding correlated strictly with metabolic activity in the temporal gyrus, medial frontal gyrus, and cingulate gyrus. Conclusion: Our findings might promote the understanding of the neurobiological mechanisms underlying cognitive impairment in PD. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to synthesize a new kind of a cationic-type UV-curing prepolymer diepoxycyclohexylethyl tetramethyldisiloxane, which is used to replace the current prepolymers' common cycloaliphatic epoxy resins to prepare a novel 3D printing stereolithography material. Design/methodology/approach: Diepoxycyclohexylethyl tetramethyldisiloxane was characterized and analyzed by FT-IR and 1HMR. Diepoxycyclohexylethyl tetramethyldisiloxane was compounded with a polycaprolactone polyol, some acrylates and photoinitiators to prepare a novel 3D printing stereolithography resin (3DPSLR11). Optical properties of 3DPSLR11 were investigated by HRPL-150A stereolithography apparatus and INITELLI-RAY400 UV-curing system. Tensile mechanical properties of printed 3DPSLR11 specimens were tested by WDW-50-type universal testing machine, and the glass transition temperature (Tg) was determined by DMA. Rectangle plates and double-cantilever parts were fabricated by using the stereolithography apparatus with 3DPSLR11 as the printing material, and the dimension shrinkage factors and the curl factors of the parts were investigated. Findings: The experimental results showed that the critical exposure (Ec) of the 3D printing 3DPSLR11 was 11.6 mJ/cm2, its penetration depth (Dp) was 0.18 mm, the tensile strength of the cured 3DPSLR11 was 40.1 MPa, the tensile modulus was 1,741.4 MPa, the elongation at break was 15.3%, Tg was 113°C, the dimension shrinkage factor was less than 0.85% and the curl factor was less than 8.00%. Originality/value: In this work, a novel 3D printing 3DPSLR11 was prepared with diepoxycyclohexylethyl tetramethyldisiloxane as a main prepolymer. The novel 3DPSLR11 possessed excellent photosensitivity, and its cured products had good mechanical and thermal properties. The accuracy and resolution of the fabricated parts were high with 3DPSLR11 for stereolithography in 3D printing, which showed that 3DPSLR11 has potential application value as 3D printing material. [ABSTRACT FROM AUTHOR]

Background: Quality of life (QoL) was worse in Parkinson's disease patients with mild cognitive impairment (PD-MCI) or dementia (PDD) than PD patients with normal cognition (PD-NC). The aim of this study was to investigate and compare the potential heterogeneous determinants of QoL in PD patients with different cognitive statuses. Methods: We recruited 600 PD patients, including 185 PD-NC patients, 336 PD-MCI patients and 79 PDD patients, in this cross-sectional study. All patients completed the QoL assessment by the 39-item Parkinson's Disease Questionnaire (PDQ-39), as well as clinical evaluations and neuropsychological tests. The determinants of the QoL were analyzed by multiple stepwise regression analysis. Results: QoL was more impaired across the three groups (PD-NC < PD-MCI < PDD). The Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score, Geriatric Depression Rating Scale (GDS) score and daily levodopa equivalent dose (LED) were independent variables of PDQ-39 in PD-NC patients. The GDS score, disease duration, UPDRS-III score, Epworth Sleepiness Score (ESS) and sex were independent variables of PDQ-39 in PD-MCI patients. The GDS score and disease duration were independent variables of PDQ-39 in PDD patients. Conclusion: The determinants of QoL in PD-NC, PD-MCI and PDD patients were heterogeneous. Motor function was considered to be the most crucial determinant for QoL in PD-NC, while depression was indicated to be the most vital determinant for PD-MCI and PDD. For QoL improvement, clinicians might need to focus more on motor function in PD-NC patients and on depression in PD-MCI and PDD patients. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease with mild cognitive impairment (PD-MCI) or dementia (PDD) has been shown to be correlated with poor quality of life (QoL). The association between specific cognitive domains and QoL is less clear. Objective: To determine how the cognitive domains affect QoL in different cognitive states in PD. Methods: We recruited 600 PD patients, including 185 PD patients with normal cognition (PD-NC), 336 PD-MCI patients, and 79 PDD patients. All patients underwent a scale-based assessment (PDQ-39) for QoL, as well as clinical evaluations and neuropsychological tests. Results: Compared to PD-NC group, QoL became more impaired in the PD-MCI and PDD groups. Generalized linear model revealed that no neuropsychological test was significantly associated with QoL in PD-NC group; neuropsychological tests in attention and language domains were significantly associated with QoL in PD-MCI patients; neuropsychological tests in memory and language domains were significantly associated with QoL in PDD patients. Conclusions: Cognitive domains contribute differently to QoL in PD. These findings may prompt clinicians to target specific cognitive domains for improving QoL in the PD patients. [ABSTRACT FROM AUTHOR]

Bis[2-(3,4-epoxycyclohexyl)ethyl]octamethyltetrasiloxane is also called diepoxycyclohexylethyl octamethyltetrasiloxane. In the present paper, diepoxycyclohexylethyl octamethyltetrasiloxane was synthesized, and the synthesized product was characterized by FTIR and 1HMR. The synthesized product was compounded with some acrylates and an expoxide as well as photoinitiators to obtain a 3D printing stereolithography resin (3DSLR111). The properties of 3DSLR111 and its UV-cured samples were investigated by some instruments and equipments. The experimental results show that the critical exposure (Ec) of 3DSLR111 is 10.1 mJ/cm2, its penetration depth (Dp) is 0.15 mm, and its viscosity at 30 °C is 319 mPa·s. Some samples were printed with 3DSLR111, and their linear shrinkage and warping factor were evaluated. The linear shrinkage and the curl distortion factor are less than 0.80% and 7.30%, respectively, which indicates that the sample printed with 3DSLR111 has high accuracy, and that the synthesized diepoxycyclohexylethyl octamethyltetrasiloxane can be well applied to the preparation of the photosensitive resin for stereolithography 3D printing. [ABSTRACT FROM AUTHOR]

A novel cationic photosensitive resin (3DSLR-01) for stereolithography 3D printing was prepared with 3,4-epoxycyclohexylmethyl-3',4'-epoxycyclohexane carboxylate (2021P), 1,4-cyclohexanedimethanol glycidyl ether (JX-026), diglycidyl 4,5-epoxycyclohexane-1,2-dicarboxylate (S-186), polycaprolactone polyol(Polyol-0305), novolac epoxy resin(F-51), bis(3-ethyl-3-oxetanylmethyl) ether (S-221) and a mixture of triarylsulfonium hexafluoroantimonate salts solution (UVI-6976). The properties of the photosensitive resin and its UV-cured films were investigated by some instruments and equipment. The experimental results show that the critical exposure (Ec) of the photosensitive resin is 16.3 mJ/cm2, the penetration depth (Dp) is 0.14 mm, and the optical property of the photosensitive resin is excellent. Rectangle plates were printed by using a stereolithography apparatus (HRPL-150A) with the photosensitive resin as the manufacturing material, and the shrinkage rates of the plates were less than 0.60%, which showed that the accuracy of the manufactured plates was very high. [ABSTRACT FROM AUTHOR]

Background/Aims: Neurotoxic A1 astrocytes are induced by inflammation after spinal cord injury (SCI), and the inflammation-related Nuclear Factor Kappa B (NFκB) pathway may be related to A1-astrocyte activation. Mesenchymal stem cell (MSC) transplantation is a promising therapy for SCI, where transplanted MSCs exhibit anti-inflammatory effects by downregulating proinflammatory factors, such as Tumor Necrosis Factor (TNF)-α and NFκB. MSC-exosomes (MSC-exo) reportedly mimic the beneficial effects of MSCs. Therefore, in this study, we investigated whether MSCs and MSC-exo exert inhibitory effects on A1 astrocytes and are beneficial for recovery after SCI. Methods: The effects of MSC and MSC-exo on SCIinduced A1 astrocytes, and the potential mechanisms were investigated in vitro and in vivo using immunofluorescence and western blot. In addition, we assessed the histopathology, levels of proinflammatory cytokines and locomotor function to verify the effects of MSC and MSC-exo on SCI rats. Results: MSC or MSC-exo co-culture reduced the proportion of SCIinduced A1 astrocytes. Intravenously-injected MSC or MSC-exo after SCI significantly reduced the proportion of A1 astrocytes, the percentage of p65 positive nuclei in astrocytes, and the percentage of TUNEL-positive cells in the ventral horn. Additionally, we observed decreased lesion area and expression of TNFα, Interleukin (IL)-1α and IL-1β, elevated expression of Myelin Basic Protein (MBP), Synaptophysin (Syn) and Neuronal Nuclei (NeuN), and improved Basso, Beattie & Bresnahan (BBB) scores and inclined-plane-test angle. In vitro assay showed that MSC and MSC-exo reduced SCI-induced A1 astrocytes, probably via inhibiting the nuclear translocation of the NFκB p65. Conclusion: MSC and MSC-exo reduce SCI-induced A1 astrocytes, probably via inhibiting nuclear translocation of NFκB p65, and exert antiinflammatory and neuroprotective effects following SCI, with the therapeutic effect of MSCexo comparable with that of MSCs when applied intravenously. [ABSTRACT FROM AUTHOR]

Objective: To investigate if the role of Cav-1 in GDM-induced macrosomia is through regulating AMPK signaling pathway in placenta. Methods: We used diagnostic criteria of gestational diabetes mellitus (GDM) and macrosomia to separate and compare placental protein and mRNA levels from GDM with macrosomia group (GDMM), GDM with normal birth weight group (GDMN) and normal glucose tolerance (NGT) with normal birth weight group (CON). Western blotting was performed to examine differentially expressed proteins of caveolin-1 (Cav-1) and Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway related proteins, including phosphorylated-AMPKα(Thr172), AMPKα, phosphorylated-Acetyl-CoA carboxylase(Ser79) (p-ACC(Ser79)), ACC and glucose transporter 1 (GLUT1) in placenta between the three groups. The mRNA levels of Cav-1, AMPKα, ACC and GLUT1 in placenta were measured by real time-PCR. Results: In the GDMM placenta group, both protein and mRNA levels of Cav-1 were down-regulated, while GLUT1 was up-regulated; the phosphorylation and mRNA levels of ACC and AMPKα were decreased, but total ACC protein levels were increased compared to both the GDMN (p<0.05) and CON groups (p<0.05). In GDMM placenta group, there was a significant negative correlation observed between neonatal birth weight (NBW) and protein expression levels of Cav-1, p-ACC(Ser79) and p-AMPKα(Thr172) (p<0.05), while positive relationship with ACC and GLUT1 protein levels. Besides, in GDMM group placental mRNA levels, NBW had a positive correlation with GLUT1 (p<0.05), while negative with Cav-1, AMPKα and ACC expression (p<0.05). Cav-1 protein expression was positively associated with p-AMPK and p-ACC (p<0.05), and negatively associated with GLUT1 (p<0.05). Interestingly, p-AMPK protein expression was closely related to p-ACC (p<0.05), but not with GLUT1. Conclusion: GDM-induced macrosomias have more severe inhibition of Cav-1 expression in placenta. Cav-1 is associated with placental glucose and fatty acid transport via the induction of AMPK signaling pathway and the reduction of GLUT1 signaling pathway to reverse GDM-induced macrosomia. [ABSTRACT FROM AUTHOR]

Quantitative real-time polymerase chain reaction (qRT-PCR) is one of the most common methods for gene expression studies. Data normalization based on reference genes is essential for obtaining reliable results for qRT-PCR assays. This study evaluated potential reference genes of Chinese yam (Dioscorea opposita Thunb.), which is an important tuber crop and medicinal plant in East Asia. The expression of ten candidate reference genes across 20 samples from different organs and development stages was assessed. We identified the most stable genes for qRT-PCR studies using combined samples from different organs. Our results also suggest that different suitable reference genes or combinations of reference genes for normalization should be applied according to different organs and developmental stages. To validate the suitability of the reference genes, we evaluated the relative expression of PE2.1 and PE53, which are two genes that may be associated with microtuber formation. Our results provide the foundation for reference gene(s) selection in D. opposita and will contribute toward more accurate gene analysis studies of the genus Dioscorea. [ABSTRACT FROM AUTHOR]

Loss of DBC2 (deleted in breast cancer 2) gene expression is frequent in breast cancer tissues. This can be explained by homozygous deletions or other mutations in a minority of cases but alternative mechanisms need to be investigated. Here, DBC2 expression was significantly suppressed compared with normal breast tissues in breast cancer tissues when analyzed by RT-PCR. Furthermore, DNA methylation on DBC2 was more prevalent in breast tumors than in normal tissues. DBC2 mRNA levels correlated with the degree of DBC2 methylation in breast cancer tissues and in a breast cancer cell line (T47D). Clinico-pathological correlation analysis showed that DBC2 promoter methylation was associated with tumor-node-metastasis stages II and III/IV, lymph node metastasis, p53 mutation, and HER2-positive status. Thus loss of DBC2 expression is caused by abnormal methylation of DBC2 and might have a role in breast cancer development. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate a prototype surface reaction-type pre-reacted glass-ionomer (S-PRG) filler-containing endodontic sealer (S-PRG sealer) in terms of its ion-releasing ability and the incorporation of the released ions by root canal dentin. Materials and Methods: The concentration of ions in the set S-PRG sealer was measured by ICPS and with a fluoride ion electrode. Element mapping and chemical component bulk analysis of the outermost dentin of the S-PRG sealer-dentin interface were performed by SEM-EPMA. The incorporation depth of the elements in dentin was measured by element line scanning. Results and Discussion: Ions released from the S-PRG sealer (Al, B, F, Na, Si, Sr, and Zn) were detected over time. The incorporation of fluoride (F), strontium (Sr), silicon (Si), and boron (B) was observed along the outermost dentin of the S-PRG sealer-dentin interface by EPMA analysis, and the incorporation depth increased with prolonged immersion. Conclusion: The continuous release of ions from the S-PRG sealer and their subsequent incorporation by root canal dentin were confirmed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the ultrastructures and chemical compositions of precipitates formed on mineral trioxide aggregate (MTA; White ProRoot MTA) immersed in distilled water (DW) or phosphate buffered saline (PBS). based on the attribution that MTA's bioactivity and sealing ability are influenced by its interaction with the external fluid environment. After 1 and 14 days of immersion, precipitates formed on MTA disks were analyzed using wavelength-dispersive X-ray spectroscopy electron probe microanalyzer with image observation function (SEM-EPMA; EPMA16O1, Shimadzu, Kyoto, Japan), and Fourier transform-infrared (FT-IR) spectroscopy. On DW specimens, cubic-like crystals containing Ca, O, and C (17, 66, and 17 at% respectively) were produced. State analysis of calcium kβ spectrum also revealed calcium hydroxide. On PBS specimens, acicular-spherical and lath-like crystals with Ca/P molar ratios of 1.42 and 1.58 respectively were produced. In conclusion, the precipitates formed on DW specimens were identified as calcium carbonate and calcium hydroxide primarily, whereas the precipitates on PBS specimens were inferred to be amorphous calcium phosphate. [ABSTRACT FROM AUTHOR]

This study sought to evaluate the pH value, film thickness, filler particle percentage, and morphological changes of self-adhesive resin luting cements. Products tested were G-Cem, Maxcem, Smart Cem, and RelyX™ Unicem. Cement pH was measured with pH test paper. Filler particle percentage was calculated after cement samples were incinerated at 750°C. To test film thickness, mixed cements were placed between two glass plates and compressed using a loading device. For morphological changes, specimen surfaces were observed by SEM after treatment with various media. There were significant differences among the cement pH values measured at 20 seconds after light curing, and at 90 seconds and 48 hours after mixing. Filler particle percentage was directly proportional to film thickness. Degradation of cement surfaces was also detected after surface polishing and immersion in water, acetic acid, and acetone. In conclusion, significant differences were found in the surface properties of the materials tested, and these differences might lead to differences in their clinical performance. [ABSTRACT FROM AUTHOR]

In this study, a newly developed S-PRG (surface pre-reacted glass-ionomer) filler-containing one-step adhesive, called SI (SI-IB3551, Prototype), was evaluated regarding its fluoride release behavior. As a result, fluoride ion distribution in the tooth structures and acid resistance of cavity margins were also evaluated. In addition, Absolute® (a fluoride-releasing one-step adhesive; AB) was evaluated in comparison to G-Bond® (a non-fluoride-releasing one-step adhesive: GB) which was used as a negative control. Concentration of fluoride released was measured using a fluoride ion selective electrode after immersion of each material in distilled water. Fluoride distribution in tooth adhesive interfacial areas was examined with EPMA following cavity preparation in human premolars and having treated resin restorations with each material To evaluate acid resistance, restored specimens were immersed in an acetic acid buffer (0.2 M, pH 4.5) for 12 hours and then the cavity margins were observed using scanning electron microscopy. Amounts of fluoride released from AB and SI were significantly greater than that from GB. Further, significant differences in fluoride release were detected between AB and SI. A layer of increased fluoride density was clearly detected at the enamel- and dentin-SI interfaces. In terms of acid resistance, an acid resistance zone was also formed adjacent to the tooth-adhesive interface of AB and SI specimens. However, in GB specimen, acid resistance zone was not observed These findings suggested that one step adhesives displayed a favorable fluoride release property, thereby contributing positively to inhibition of recurrent caries. [ABSTRACT FROM AUTHOR]

In this study, enamel micro marks produced around flowable composite restorations were observed using a stereomicroscope and a scanning confocal laser microscope (SCLM). The effects of polymerization shrinkage, mobility of composite and polishing period after filling on the incidence of marginal enamel micro-cracks were examined. Enamel micro- cracks were observed on all of the composite restorations when the restoration was polished immediately after filling. Enamel micro cracks distributed approximately parallel to the cavity margin and located 0.01-0.3 mm from the restored cavity margin. The occurrence of enamel micro-cracks was higher in conventional hybrid composite restorations than in flowable composites, and when polished 15 minutes after filling (as compared to 24 hours after filling). [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose: The purpose of this study was to evaluate the effect of various media on the color stability of compomer and to compare these results to those of other materials that could be used in similar clinical circumstances. Materials and Methods: In this test, six materials (shade A2) were used: four compomers (Dyract, Compoglass F, Xeno, F2000), one composite resin (Clearfil AP-X), and one resin-modified glass ionomer cement (Fuji II LC). There were four test solutions: one alcoholic (whiskey), two low pH soft drinks (Coca Cola, orange juice), and deionized water as a control. A plastic ring mold (9-mm diameter x 1-mm height) was used to prepare 120 disk specimens. For 60 days, the test specimens were immersed in the various media daily for 3 hours then transferred to the deionized water. Color was measured by CIE L* a* b* relative to CIE source against a white background, using a colorimeter. Color change (Δ*) was calculated as Δ*= [(δ*)2+ (δ*)2+ (Δ*)2]1/2. Color changes (Δ*) were recorded after 1, 7, 30, and 60 days. Results: The results indicated that compomer and resin-modified glass ionomer were susceptible to discoloration in various solutions over an extended period of time. Composite resin showed minimal perceptible color change. Specimens immersed in whiskey showed a significantly high perceptible color change (p < .0001). Water caused no perceptible color changes. CLINICAL SIGNIFICANCE Compomer and resin-modified glass ionomer materials are susceptible to discoloration by various media. [ABSTRACT FROM AUTHOR]

The comparative study of organic matter in carbonate rocks and argillaceous rocks from the same horizon indicates that the organic thermal maturities of carbonate rocks are much lower than those of argillaceous rocks. And extensive analysis of extracted and inclused organic matter from the same sample shows that inclused organic matter is different from extracted organic matter, and the thermal maturity of the former is usually lower than that of the latter in terms of biomarker structural parameters. It seems that carbonate minerals could preserve organic matter and retard organic maturation. The inclused organic matter, abundant in most carbonate rocks, will be released from minerals and transformed into oil and gas during the high thermal maturity stage. [ABSTRACT FROM AUTHOR]