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Changqing Liu,1,2,* Qi Sun,1,2,* Junmei Xu,1,2 Weiyun Shen,1,2 Hui Li,1,2 Lin Yang1,2 1Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Li, Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Fax +86 85295970, Email lihui_1166@csu.edu.cn Lin Yang, Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, Fax +86 85295970, Email linyang@csu.edu.cnBackground: Neuropathic pain (NP) is known to be highly correlated with microglial polarization, of which the regulatory mechanism remains to be elucidated. Here, the aim of this study is to further investigate the relationship between bone morphogenetic protein 4 (BMP4) and microglial polarization in the process of NP.Methods: Firstly, normal adult rats received intrathecal BMP4 administration to assess BMP4ʹs effect on microglial polarization. Secondly, a BMP4 antagonist – Noggin – was applied to a rat NP model achieved by L5 spinal nerve ligation (SNL) to investigate whether antagonizing BMP4 signaling could alleviate allodynia by reversing the imbalance of the M1/M2 polarization ratio. In both experiments, Von-Frey filaments were used to test the changes in the paw withdrawal threshold (PWT), and Western blotting, immuno-fluorescence, PCR and flow cytometry were further performed to investigate microglial activity and the expression patterns of M1 and M2 markers, respectively.Results: Firstly, BMP4 administration induced a significant PWT decrease and microglial activation in normal rats; Western blotting, PCR and flow cytometry further revealed that M1 markers including CD16, MHCII, and TNF-α showed a marked elevation after BMP4 application; while M2 markers, such as Arg-1, CD204 and IL-4, peaked at an early stage (P1 or P4) and then fell to the Sham level on P7, leading to a persistent imbalance of the M1/M2 ratio throughout the 1st week. Secondly, Noggin treatment significantly relieved allodynia and microglial activation in SNL rats. Moreover, Noggin persistently downregulated the M1 marker levels and simultaneously induced a late-stage elevation of M2 markers expressions, thereby reversing the imbalance of the M1/M2 polarization ratio.Conclusion: Our results indicate that BMP4 has the ability to induce microglial polarization. Antagonizing BMP4 signaling can relieve pain behavior via mitigating microglial activation and reversing the imbalance of the M1/M2 polarization ratio in the process of NP.Keywords: bone morphogenetic protein-4, Noggin, microglia, polarization, neuropathic pain

Infection, predominantly induced by gram-negative bacteria, is a critical health problem and a leading cause of death worldwide. Advance of techniques, such as antibiotics and life-supporting modality, allows a decreasing death rate of patients with infection in recent decades. Nevertheless, infection-associated complications, in particular cognitive dysfunction, largely influence the mortality of patients and the life quality of survivors. However, the effective medicine is still scant due to the poor interpretion of underlying mechanisms. Herein, we determined multiple cytokines of cerebrospinal fluid in mice challenged with various doses of lipopolysaccharides (LPS)-a pathogenic component of gram-negative bacteria, and found that IL-1β, the downstream of NLRP3 inflammasome, was boosted to a peak extent after a challenge of LPS in high dose. Genetically knockout of Nlrp3 or the downstreams, such as Asc and Gsdmd, dramatically restored LPS-induced cognitive impairment, which was attributed to inhibiting microglia-induced A1 astrocytes and so-caused neo-neuron decline. Taken together, NLRP3 inflammasome of microglia promotes transformation of A1 astrocytes and consequently exacerbates neo-neuron decline, resulting in cognitive impairment after a challenge of LPS. Our study thus discovers a novel understanding in the pathogenesis of LPS-induced cognitive dysfunction, and indicates that NLRP3 inflammasome would be a promising target in the treatment of the syndrome.

Myocardial ischemia reperfusion injury (MIRI) means complete or partial artery obstruction of coronary artery, and ischemic myocardium will be recirculating in a period of time. Although the ischemic myocardium can be restored to normal perfusion, its tissue damage will instead be progressive. An aggravated pathological process. MIRI is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. Therefore, the research and development of drugs for the prevention and treatment of this period has also become the focus. This article first studied pathophysiology of MIRI, and reviewed the research progress of MIRI-related drugs. Research results show that: MIRI is inevitable for myocardial ischemia, with the possible to double damage via the ischemic condition. Therefore, it is a serious complication and one of the most popular diseases in the world. It has always been difficult to find an effective treatment for this disease, because it is difficult to explore the inflammation behind its pathophysiology.

The aim of this study was to explore whether ice slush (IS) causing local hypothermia can effectively inhibit the oculocardiac reflex (OCR) during strabismus surgery.This prospective, randomized, double-blind study included 58 patients with concomitant strabismus scheduled for lateral rectus (LR) recession under general anesthesia. Patients were randomly allocated to receive IS (IS group) or standard treatment (control group) with sterile saline at room temperature before surgery. OCR was defined as a sudden decrease in heart rate (HR) of15% from baseline. If one incidence of the OCR was found in 1 patient in any stage (0/I/II/III), the patient was defined as an OCR responder, and the incidence of overall OCR was the incidence of OCR responders. The primary outcome was the incidence of overall OCR during all stages of the surgery, which was analyzed by the Z test and computed based on the absolute risk difference with 2-sided 95% confidence intervals (CIs) using the Newcombe method.The overall OCR occurred in 19 of 29 patients (62.5% [95% CI, 45.7-82.1]) in the IS group and 28 of 29 patients (96.6% [95% CI, 82.2-99.9]) in the control group (absolute risk difference, -31.0% [95% CI, -49.4 to -11.0]; Z test, P.001), which demonstrated that the incidence of overall OCR in IS group was significantly lower than that in the control group.IS on the ocular surface causing local hypothermia is a promising and easily accessible method to reduce the overall OCR, which can improve the safety of strabismus surgery.

Introduction: Sepsis remains a devastating disease with a high fatality rate in most nations. Heart failure accounts for around half of all deaths in sepsis patients. Because of the peculiarities of cardiac tissue, the specific mechanism of sepsis-induced cardiac dysfunction remains largely unknown. Objectives: The goal of this study was to develop a more complete understanding of the molecular pathways of septic cardiomyopathy by doing an integrated proteome and metabolomics analysis on a sepsis-infected mouse model. Methods: The CLP mice were utilized as a model in this study to investigate the impact of septic cardiomyopathy on the molecular changes in heart tissues through combining metabolomics and proteomics studies. Results: The present findings suggest that 118 proteins (75-upregulated and 43-downregulated) and 138 metabolites (124-upregulated and 14-downregulated) were significantly altered. Additionally, these compounds play a significant role in biological processes, such as platelet activation, mineral absorption, drug metabolism, terpenoid backbone biosynthesis, and butanoate metabolism. The comprehensive analysis discovered that prostaglandin H2, prostaglandin I2, thromboxane A2, and L-Glutamine might play essential roles in combating sepsis-induced heart dysfunction. Conclusions: Overall, this work adds to our understanding of the implications of sepsis-induced cardiac dysfunction and may lead to identifying novel potential biomarkers and a better understanding of sepsis pathophysiology.

Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The CLP-induced sepsis mouse model was established and the septic mice were examined for histopathological changes using HE staining. KLF13 expression in septic mouse heart and LPS-induced cellular inflammation model was detected. Pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 level, inflammatory cytokines (IL-1β, TNF-α, IL-8 and MCP-1) production and IκB-α protein level and p65 phosphorylation in septic mice and LPS-induced cells were detected to evaluate cardiomyocyte apoptosis, inflammatory response and NF-κB pathway activation. KLF13 was overexpressed in vivo and in vitro to explore its specific effect on sepsis-induced myocardial injury. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in myocardial cells. KLF13 was downregulated in the septic mouse heart and LPS-induced cellular inflammation model. Septic heart and LPS-induced cell model showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-κB pathway (increased p65 phosphorylation and decreased IκB-α protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially the NF-κB signalling) and cardiomyocyte apoptosis.

Xu Zhao,1,&ast; Jitao Zhang,1,&ast; Wenjuan Zhang,2 Ruping Dai,1 Junmei Xu,1 Zhijian Li,1 Lin Yang1 1Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Yang; Zhijian LiDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaFax +86 73185295970; Fax +86 73185295970Email linyang@csu.edu.cn; lizhijian@csu.edu.cnBackground: Bone morphogenetic protein-4 (BMP4) has been identified as an inflammation regulator in the diseases of arteries and other organs. However, the relationship between circulating BMP4 and perioperative inflammation remains unclear.Patients and Methods: Forty patients undergoing lobectomy were randomly allocated into the Control group (not receiving flurbiprofen) and the Flurb group (received 100mg flurbiprofen during surgery). Arterial blood was obtained before surgery (T1), at the end of surgery (T2), and 24 hours after surgery (T3) to test the plasma concentrations of BMP4, its antagonist Noggin, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-10. The relationship between BMP4 and other variables and the effects of flurbiprofen on BMP4 changes were investigated.Results: A total of 35 patients were included. Circulating BMP4 was positively correlated with IL-1β (P< 0.01, r=0.575) and TNF-α (P< 0.01, r=0.491), negatively correlated with IL-10 (P< 0.01, r=− 0.675), but not correlated with Noggin. The plasma concentrations of BMP4, IL-1β, and TNF-α increased at T2 (P< 0.01, compared with T1) and decreased at T3 (P< 0.05, compared with T2). BMP4 concentrations at T3 were significantly higher than at T1 in the Control group (P< 0.05), while showing no significant difference in the Flurb group. However, in the Flurb group, the relative changes of BMP4 and IL-1β at T2 and T3 were significantly lower than those in the Control group.Conclusion: Circulating BMP4 was elevated during surgery and highly correlated with inflammation cytokines. The elevation of BMP4 and inflammatory cytokines could be alleviated by flurbiprofen, indicating that BMP4 may exert pro-inflammatory properties via cyclooxygenase-II signaling pathways.Keywords: bone morphogenetic protein-4, Noggin, inflammation, non-steroidal anti-inflammatory drugs, perioperative, cyclooxygenase-II

Purpose To investigate the most effective goal-directed hemodynamic therapy (GDHT) in surgical patients. Methods GDHTs were classified as methods for intravascular volume, preload, stroke volume, cardiac output, oxygen delivery, systemic oxygenation, or tissue oxygenation optimization, alone or in combination. Their relative effectiveness and ranking were assessed using network meta-analysis and the surface under the cumulative ranking curve (SUCRA), respectively. Results 101 randomized controlled trials investigating GDHT effectiveness in surgical patients were eligible. The most commonly reported outcomes were 30-day mortality, acute kidney injury (AKI), and arrhythmia. Mortality was significantly reduced by GDHTs aimed at intravascular volume and cardiac output optimization (OR 0.40; 95% CrI 0.14–0.997; low quality). AKI was significantly reduced by GDHT aimed at intravascular volume optimization (OR 0.26; 95% CrI 0.08–0.71; moderate quality). No GDHT significantly reduced arrhythmia. GDHT aimed at intravascular volume and stroke volume optimization was likely most effective for mortality reduction (SUCRA = 78.8%) while that aimed at intravascular volume, stroke volume, and cardiac output optimization was likely most effective for AKI reduction (SUCRA = 85.4%). Conclusions Different GDHTs likely have different and outcome-dependent effectiveness in surgical patients. GDHTs aimed at intravascular volume, stroke volume, and cardiac output optimization are likely most effective as per the overall evidence. Systematic review registration PROSPERO registration number: CRD42020159978.

Rationale: Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervoussystem (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiplesclerosis (MS) is unknown. Methods: Peripheral blood and post-mortem brain and spinal cord specimens were obtained from multiple sclerosis patients to analyze proBDNF expression in peripheral lymphocytes and infiltrating immune cells in the lesion site. The proBDNF expression profile was also examined in the experimental autoimmune encephalomyelitis (EAE) mouse model, and polyclonal and monoclonal anti-proBDNF antibodies were used to explore their therapeutic effect in EAE. Finally, the role of proBDNF in the inflammatory immune activity of peripheral blood mononuclear cells (PBMCs) was verified in vitro experiments. Results: High proBDNF expression was detected in the circulating lymphocytes and infiltrated inflammatory cells at the lesion sites of the brain and spinal cord in MS patients. In the EAE mouse model, proBDNF was upregulated in CNS and in circulating and splenic lymphocytes. Systemic but not intracranial administration of anti-proBDNF blocking antibodies attenuated clinical scores, limited demyelination, and inhibited proinflammatory cytokines in EAE mice. Immuno-stimulants treatment increased the proBDNF release and upregulated the expression of p75 neurotrophic receptors (p75NTR) in lymphocytes. The monoclonal antibody against proBDNF inhibited the inflammatory response of PBMCs upon stimulations. Conclusion: The findings suggest that proBDNF from immune cells promotes the immunopathogenesis of MS. Monoclonal Ab-proB may be a promising therapeutic agent for treating MS. Refereed/Peer-reviewed

The elderly are vulnerable to perioperative acute kidney injury. The aim of this study was to determine the risk factors that associated with acute kidney injury among elderly patients.Clinical data of elderly patients ( 65 years) who underwent noncardiac, nonrenal surgery between Dec 1 2009 and July 1 2016 were collected for this single-centered historical cohort study. Univariate and multivariate analyses were conducted to explore the risk factors that contribute to acute kidney injury, which was defined as a serum creatinine increase0.3 mg/dL within 48 h or 1.5 times increase in serum creatinine within 7 days after surgery.7775 patients were eligible for the final analysis, among which 511 (6.57%) patients developed acute kidney injury. We observed 21 risk factors being associated with perioperative acute kidney injury, with the most important disposing factors being history of kidney disease (adjusted OR = 2.94, 95% CI 2.25-3.84), operation time 180 min (aOR = 2.93, 95% CI 2.04-4.24), preoperative eGFR [15, 30) (aOR = 2.43, 95% CI 1.29-4.45), and protective factor being intraoperative use of sufentanil (aOR = 0.35, 95% CI 0.23-0.54).This study determined risk factors for perioperative acute kidney injury among the elderly in the Second Xiangya Hospital and visualized the risk factors using nomogram and Excel calculator, which may provide some clues to further investigations. Overall, the prevalence of AKI among this large cohort is 6.57%.http://www.chictr.org.cn ; ChiCTR1900027007; October 28, 2019.

BACKGROUND: Early identification of vulnerable plaques at risk of rupture could help prevent cerebral ischemic stroke in patients with carotid artery disease. OBJECTIVE: To investigate the correlation between contrast-enhanced ultrasound (CEUS) perfusion patterns and serum lipid signatures of carotid artery plaques with the degree of carotid stenosis. METHODS: A total of 80 patients with carotid artery plaques who underwent CEUS were included. All patients underwent CEUS, computed tomography angiography or digital subtraction angiography, and serum lipid testing. RESULTS: The contrast agent enhancement levels and the CEUS perfusion patterns in the plaques were associated with the degree of carotid stenosis (P 0.05). There was no significant difference in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides with respect to contrast agent enhancement levels (P > 0.05) or the degree of stenosis (P > 0.05). CONCLUSION: A high level of CEUS perfusion and increased serum FFA levels are indicative of vulnerable carotid plaques, which may be useful for the prediction of stroke in patients with carotid artery disease.

Myocardial infarction is a major cause of death worldwide. Despite our understanding of the pathophysiology of myocardial infarction and the therapeutic options for treatment have improved substantially, acute myocardial infarction remains a leading cause of morbidity and mortality. Recent findings revealed that GRP78 could protect myocardial cells against ischemia reperfusion injury‐induced apoptosis, but the exact function and molecular mechanism remains unclear. In this study, we aimed to explore the effects of GRP78 on hypoxia/reperfusion (H/R)‐induced cardiomyocyte injury. Intriguingly, we first observed that GRP78 overexpression significantly protected myocytes from H/R‐induced apoptosis. On mechanism, our work revealed that GRP78 protected myocardial cells from hypoxia/reperfusion‐induced apoptosis via the activation of the Nrf2/HO‐1 signaling pathway. We observed the enhanced expression of Nrf2/HO‐1 in GRP78 overexpressed H9c2 cell, while GRP78 deficiency dramatically antagonized the expression of Nrf2/HO‐1. Furthermore, we found that blocked the Nrf2/HO‐1 signaling by the HO‐1 inhibitor zinc protoporphyrin IX (Znpp) significantly retrieved H9c2 cells apoptosis that inhibited by GRP78 overexpression. Taken together, our findings revealed a new mechanism by which GRP78 alleviated H/R‐induced cardiomyocyte apoptosis in H9c2 cells via the promotion of the Nrf2/HO‐1 signaling pathway., GRP78 overexpression protected myocardial cells from hypoxia/reperfusion (H/R)‐induced apoptosis through regulating the Nrf2/HO‐1 signaling pathway. Taken together, our findings revealed a new mechanism by which GRP78 alleviated H/R‐induced cardiomyocyte apoptosis in H9c2 cells via the promotion of the Nrf2/HO‐1 signaling pathway.

Temporary COVID-19 specialty hospitals proved to be useful in the control of an infectious crisis in a large epicenter, and hopefully this approach provides a blueprint for the management of future epidemics or pandemics.

In order to study the storage and management mechanism of raster data and vector data for different purposes in data services, a research method of big data storage and indexing mechanism based on spatiotemporal information cloud platform is proposed. This paper discusses the application of big data storage index in virtualization platform, cloud management software, and storage management, so that Hadoop cluster can use the dynamic expansion ability of cloud platform to obtain better expansion ability. High performance statistical applications for geographical conditions are constructed. A high performance geostatistical analysis system Hadoop-Geostatistics is designed and implemented. A variety of spatial statistics index calculation, flow, and MapReduce algorithm was realized. The experimental results show that in the cluster environment, the time consumption is basically the same as that of the single index calculation, while in the single computer environment, when the comprehensive index is calculated in parallel for 10,000 statistical objects, the system performance drops rapidly and reaches an early inflection point. In the comprehensive statistical concurrent calculation, when the time consumption reaches 5 × 10^7, the amount of calculation data is as high as 7000, which increases linearly. The experimental data show that the designed spatiotemporal information cloud platform model can store spatial big data, and the storage method is very accurate. By establishing a spatiotemporal information cloud platform, cloud computing technology can provide higher spatial information services.

BACKGROUND: The aim of this research is to analyze the efficacy of neostigmine in the treatment of postoperative urinary retention (POUR). METHODS: In this research, we screened multiple databases including PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI). After a systematic search process, data extraction was conducted. Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. RESULTS: After searching for articles, 20 eligible trials including 1,850 patients after surgery were extracted. Our results suggested that the neostigmine group had a higher effective rate for urinary retention than the Chinese traditional and physical therapy group (OR =7.47, 95% CI: 4.10–13.59, overall effect P

Background: Many patients with type A aortic dissection (AAD) show low lymphocyte counts pre-operatively. The present study investigated the prognostic values of lymphopenia and lymphocyte subsets for the postoperative major adverse events (MAEs) in AAD patients undergoing surgery, and explore mechanisms of lymphopenia.Methods: We retrospectively analyzed pre-operative lymphocyte counts in 295 AAD patients treated at two hospitals, and evaluated their correlation with MAEs. We prospectively recruited 40 AAD patients and 20 sex- and age-matched healthy donors (HDs), and evaluated lymphocyte subsets, apoptosis, and pyroptosis by flow cytometry.Results: Multivariable regression analysis of the retrospective cohort revealed pre-operative lymphopenia as a strong predictor of MAEs (odds ratio, 4.152; 95% CI, 2.434–7.081; p < 0.001). In the prospective cohort, lymphocyte depletion in the AAD group was mainly due to loss of CD4+ and CD8+ T cells as compared with HDs (CD4+ T cells: 346.7 ± 183.6 vs. 659.0 ± 214.6 cells/μl, p < 0.0001; CD8+ T cells: 219.5 ± 178.4 vs. 354.4 ± 121.8 cells/μl, p = 0.0036). The apoptosis rates of CD4+ and CD8+ T cells were significantly higher in AAD patients relative to HDs (both p < 0.0001). Furthermore, the pre-operative CD4+ T cells count at a cut-off value of 357.96 cells/μl was an effective and reliable predictor of MAEs (area under ROC curve = 0.817; 95% CI, 0.684-0.950; sensitivity, 74%; specificity, 81%; p < 0.005). Pre-operative lymphopenia, mainly due to CD4+ T cells exhaustion by apoptosis, correlates with poor prognosis in AAD patients undergoing surgery.Conclusion: Pre-operative lymphopenia in particular CD4+ T lymphopenia via apoptosis correlates with poor prognosis in AAD patients undergoing surgery.

Continuous thoracic paravertebral block (TPVB) connected with patient-controlled analgesia (PCA) pump is an effective modality to reduce postoperative pain following thoracic surgery. For the PCA settings, the programmed intermittent bolus infusion (PIBI) and continuous infusion (CI) are commonly practiced. However, the comparative effectiveness between the 2 approaches has been inconsistent. Thus, the aim of this study was to explore the optimal PCA settings to treat postthoracotomy pain by combing PIBI and CI together.All enrolled patients undergoing thoracoscopic surgery accepted ultrasound-guided TPVB catheterization before the surgery and then were randomly allocated in to 3 groups depending on different settings of the PCA pump connecting to the TPVB catheter: the PIBI+CI, PIBI, and CI groups. Numerical Rating Scales were evaluated for each patient at T1 (1 h after extubation), T2 (12 h after the surgery), T3 (24 h after the surgery), T4 (36 h after the surgery), and T5 (48 h after the surgery). Besides, the consumptions of PCA ropivacaine, the number of blocked dermatomes at T3, and the requirement for extra dezocine for pain relief among the 3 groups were also compared.First, the Numerical Rating Scale scores in the PIBI+CI group were lower than the CI group at T2 and T3 (P0.05) when patients were at rest and were also lower than the CI group at T2, T3, and T4 (P0.01) and the PIBI group at T3 when patients were coughing (P0.01). Second, the 2-day cumulative dosage of PCA in the PIBI+CI group was lower than both the CI and PIBI groups (P0.01). Third, the number of blocked dermatomes in the PIBI and PIBI+CI groups were comparable and were both wider than the CI group at T3 (P0.01). Finally, a smaller proportion (not statistically significant) of patients in the PIBI+CI group (5.26%, 2/38) had required dezocine for pain relief when compared with the PIBI group (19.44%, 7/36) and the CI group (15.79%, 6/38).The combination of PIBI and CI provides superior analgesic modality to either PIBI or CI alone in patients undergoing thoracoscopic surgery. Therefore, it should be advocated to improve the management of postoperative pain, clinical outcomes, and ultimately patient satisfaction.

To explore the effect of intrathecal administration of exogenous noggin (NOG) on the pain behavior in the neuropathic pain (NP) rats through LA total of 40 adult male Sprague Dawley (SD) rats were randomly divided into 3 groups: a control group (Compared with the control group, the PWT in the SNL group was markedly decreased at each time point, together with the increase in GFAP, IL-6 and the ratio of p-STAT3/STAT3 (allThe intrathecal administration of NOG may alleviate NP in the SNL rats through inhibiting astrocyte activation and down-regulating the STAT3 signal pathway.

BACKGROUND Post-operative cognitive dysfunction (POCD) is a decline of cognitive status that commonly occurs after surgery in elderly patients. Whether DNA methylation is associated with the development of POCD remains unclear. METHODS Subjects (N = 124) older than 65 years-of-age undergoing hip replacement surgery were enrolled. A battery of neuropsychiatric tests was used to examine the perioperative cognitive function of the patients. Early POCD was analyzed using the reliable change index (RCI), and subjects were diagnosed with POCD if RCI

Background and Objective. Diabetic neuropathic pain (DNP) is a common complication associated with diabetes. Currently, its underlying pathomechanism remains unknown. Studies have revealed that the recruitment of blood monocyte-derived macrophages (MDMs) to the spinal cord plays a pivotal role in different models of central nervous system injury. Therefore, the present study aimed at exploring the infiltration and function of MDMs in DNP using a mice model. Methods. Diabetes was induced using streptozotocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Quantitative analysis of CD11b was performed and visualized by immunofluorescence. Spinal cord cells were isolated from myelin and debris by Percoll gradient. Flow cytometry was used to label CD11b and CD45 antibodies to differentiate MDMs (CD45highCD11b+) from resident microglia (CD45lowCD11b+). Mice were injected with clodronate liposomes to investigate the role of MDMs in DNP. The successful depletion of monocytes was determined by flow cytometry. Results. The DNP mice model was successfully established. Compared with nondiabetic mice, diabetic mice displayed a markedly higher level of CD11b immunofluorescence in the spinal cord. The number of CD11b-positive microglia/macrophages gradually increased over the 28 days of testing after STZ injection, and a significant increase was observed on Day 14 (P<0.01) and 28 (P<0.01). Further analysis by flow cytometry showed that the infiltration of peripheral macrophages began to increase in 2 weeks (P<0.001) and reached a maximum at 4 weeks (P<0.001) post-STZ injection compared to the control. The depletion of MDMs by clodronate liposomes alleviated diabetes-induced tactile allodynia (P<0.05) and reduced the infiltration of MDMs (P<0.001) as well as the expression of IL-1β and TNF-α in the spinal cord (P<0.05). Conclusions. The infiltration of blood MDMs in the spinal cord may promote the development of painful neuropathy in diabetes.

Objectives Asymptomatic and symptomatic patients may transmit severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), but their clinical features and immune responses remain largely unclear. We aimed to characterise the clinical features and immune responses of asymptomatic and symptomatic patients infected with SARS‐CoV‐2. Methods We collected clinical, laboratory and epidemiological records of patients hospitalised in a coronavirus field hospital in Wuhan. We performed qualitative detection of anti‐SARS‐CoV‐2 immunoglobulin M (IgM) and immunoglobulin G (IgG) using archived blood samples. Results Of 214 patients with SARS‐CoV‐2, 26 (12%) were asymptomatic at hospital admission and during hospitalisation. Most asymptomatic patients were ≤ 60 years (96%) and females (65%) and had few comorbidities (, We studied a cohort of 26 asymptomatic and 188 symptomatic patients in a coronavirus field hospital. We found asymptomatic cases, mostly young females ≤ 60 years, in approximately 12% of nonseverely ill cases. More than 90% of cases experienced immunoglobulin M (IgM)/immunoglobulin G (IgG) seroconversion at the time of virus clearance, whereas the median time from the first virus‐positive tests to IgG/IgM seroconversion was significantly shorter in asymptomatic than in symptomatic patients. Compared with symptomatic patients, asymptomatic patients had lower IgG/IgM titres and plasma neutralisation capacity at the time of virus clearance.

Since the outbreak of COVID-19, the prevention and control of nosocomial infections has been highly valued. Airway management, including endotracheal intubation, extubation, and suction, has been considered as the high-risk virus-spreading procedures, which can put the health providers at a high risk of nosocomial infections. As hospitals at all levels will gradually resume their routine medical work, effective managements for the airway of the silent asymptomatic carriers and patients with delayed symptoms, treatment for severe patients, and prevention of cross infection in hospital have become the focus for the current prevention and control of nosocomial infections. Under the guidance of partitioned and graded prevention and differential control strategies at this stage, we comprehensively analyzed four main intubation methods used in the current clinical work including rapid sequence intubation, laryngeal mask insertion, intubation guided by video flexible intubating scope and awake tracheal intubation. Furthermore, we discussed and summarized intubation and protection strategies for 3 categories of patients during the COVID-19 pandemic, providing evidence for protecting medical stuff in operating room and ICU against severe acute respiratory syndrome coronavirus 2 infection.自2019冠状病毒病(coronavirus disease 2019，COVID-19)暴发以来，医院感染预防和控制工作得到高度重视。气道管理相关操作，包括气管插管、拔管、吸痰等，被视为医院内严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2，SARS-CoV-2)传播最危险的操作之一。随着各级医院逐步恢复包括择期手术在内的常规医疗工作，如何针对隐性的无症状携带者和延迟出现症状的COVID-19患者进行有效气道管理，从而安全地开展常规手术和重症患者的治疗，防止医院交叉感染，已成为当前医院感染控制工作的重点。在现阶段分区分级、差异化防控策略的指导下，我们综合分析了目前临床工作中主要使用的4种插管方式——快速诱导插管、喉罩置入术、可视插管软镜(video flexible intubating scope，VFIS)引导下气管插管、清醒气管插管，探讨并总结了COVID-19疫情期间3类患者的气管插管及防护策略，为手术室和ICU医护人员的安全防控提供依据。.

Objectives: To provide a reference for CT imaging changes for patients discharged from a Fangcang shelter hospital, a large-scale, temporary hospital for the centralized treatment of patients with mild to moderate Coronavirus disease 2019 (COVID-19) to provide essential functions (isolation, triage, basic medical care, frequent monitoring and rapid referral, essential living and social engagement) to them..Methods: Patients with mild to moderate COVID-19 admitted to the Wuchang Fangcang Shelter Hospital who had undergone pre-discharge and previous CT scans were included. Changes in the CT imaging features were defined as progression, no change, improvement or recovery. Basic patient information was obtained, and imaging signs were compared between the two CT scans.Results: A total of 83 patients were included. The median age was 53 years old. The course of disease was 28.3±10.7 days. CT imaging changes indicated progression, no change, improvement, and recovery in 3, 12, 66, and 2 patients, respectively. Between the two CT scans, the imaging signs showed a significant reduction in consolidation, a significant increase in fibrosis, and a reduction or / and thinning of ground-glass opacities. None of the patients showed signs of deterioration on follow-up and thus did not need to return to the hospital for treatment.Conclusion: In the COVID-19 Fangcang shelter hospital, given the shortage of medical staff and lack of medical resources, CT imaging diagnostic methods can be used to accurately discharge patients who had met the discharge criteria for isolation and observation from the Fangcang Shelter Hospital.

To explore the association between obesity and cognitive impairment in children with mild or moderate obstructive sleep apnea-hypopnea syndrome (OSAHS).A total of 71 children with obesity and 71 age- and sex- matched children who were non-obese were included. The Wechsler Intelligence Scale for Children fourth edition (WISC-IV) was adopted to evaluate the cognition of the participating children. Pearson and partial correlation analysis were performed to investigate the relationships between neurocognitive functions and demographic and polysomnography parameters. Two-way Analysis of Variance was performed to evaluate the effect of obesity and apnea-hypopnea index (AHI) on cognitive functions.Full-scale intelligence quotient (FSIQ, 92.4 ± 12.3 vs. 98.6 ± 13.1; P 0.01), verbal comprehension index (VCI, 92.8 ± 10.8 vs. 98.7 ± 10.9; P 0.01), working memory index (WMI, 92.6 ± 11.3 vs. 96.5 ± 11.0; P = 0.04) and perceptual reasoning index (PRI, 93.8 ± 12.1 vs. 99.2 ± 12.5; P 0.01) were significantly lower in the children with obesity compared with those in the control group. Partial correlation analysis showed that FSIQ were negatively and significantly correlated with body mass index (BMI, r = -0.347, P 0.01) and AHI (r = -0.304, P 0.01). Two-way ANOVA revealed that both obesity and AHI had independent effects on FSIQ (both P 0.05). The interaction between the effect of obesity and AHI on cognitive functions was not significant, indicating that obesity is a risk factor of cognitive impairment independent of AHI.Obesity aggravates cognitive impairment in children with mild or moderate OSAHS.Children diagnosed with OSAHS and obesity are recommended to control their body weight for the prevention, management and treatment of cognitive impairment.

Background: COVID-19 cases in children are gradually increasing with limited information Epidemiological and clinical characteristics of children with mild dis

Background: COVID-19 cases in children are gradually increasing with limited information Epidemiological and clinical characteristics of children with mild dis

Pleomorphic adenoma (PA), Warthin's tumor (WT) and mucoepidermoid carcinoma (MEC) are three common subtypes of salivary gland tumors, for which the occurrence site is located in the parotid gland. Accurately diagnosing the subtypes of parotid tumors plays a vital role in the surgical treatment. Unfortunately, the current studies mainly focus on the binary classification of parotid tumors. The preoperative multi-classification of them has still been underexplored. For the purpose of broadening the application area of the predictive models and facilitating the clinical preoperative diagnosis, we suggested a multi-classification model, which was constructed by combining the variable combination population analysis (VCPA) algorithm with the partial least squares regression (PLSR), to simultaneously discriminate the three subtypes of parotid tumors as well as the normal parotid gland tissue based on the Raman spectra of the tissue samples. In addition, we investigated the impact of generating Raman spectra from different sampling locations on the reliability of the predictive models. For the validation set, the overall accuracy in predicting the subtypes of parotid tumors and the normal parotid gland tissue was 0.867. Similarly, the accuracies achieved by the models constructed with the Raman spectra from two different sampling locations were 0.877 and 0.883, respectively, indicating the minor influence of the sampling locations on the predictive models. Our findings can be helpful for establishing the method of rapidly diagnosing the salivary gland tumors preoperatively in clinics. Moreover, the characteristic wavenumbers used in model construction were highly associated with the variations of the structures and contents of nucleic acids, collagen, proteins, lipids and DNA/RNA in gland tissue, which revealed the mainly difference among three types of parotid tumors and can be conductive to better understanding the molecular mechanisms of them.

BACKGROUND Neuropathic pain (NPP) arises from a lesion or dysfunction of the somatosensory nervous system. Recent studies have demonstrated multiple microRNAs (miRNAs) play key roles in NPP development. This study aimed to investigate the effects of miR-128 on microglial cells. MATERIAL AND METHODS We established a compressive spinal cord injury (SCI) model and collected the spinal cord segment-derived conditioned medium (CM). We then measured the expression of miR-128 in the murine microglial cell line BV2 treated with CM-SCI or CM obtained from control (CM-NC). Furthermore, lentivirus production of miR-128 and scrambled control were transfected into BV2 cells, which were first treated with CM-SCI or CM-NC. Moreover, the effects of miR-128 on cell viability, M1/M2 microglial gene expression, inflammatory cytokines concentration, and the protein expression of P38 and phosphorylated P38 (P-P38) were investigated. RESULTS The expression of miR-128 was downregulated in murine microglial BV2 cells treated with CM-SCI. Overexpression of miR-128 markedly promoted the viability of murine microglial cells. In addition, miR-128 overexpression significantly decreased the expression levels of microglial M1 phenotypic markers CD86 and CD32, and increased the expression levels of M2 phenotypic markers Arg1 and CD206. Furthermore, miR-128 overexpression obviously decreased the concentration of TNF-α, IL-1β, and IL-6. We found that miR-128 overexpression significantly downregulated the expression levels of P38 andP-P38. CONCLUSIONS Our findings indicate that down-regulation of miR-128 in murine microglial cells may contribute to the development of NPP following SCI via activation of P38. MiR-128 may be a potential intervention target for NPP.

Shivering associated with spinal anesthesia during Cesarean delivery is an uncomfortable experience for the parturient, which may also cause adverse effects. In this prospective, randomized, double-blind, placebo-controlled study, we sought to evaluate the effect of intrathecal dexmedetomidine, administered as an adjunct to hyperbaric bupivacaine for Cesarean delivery, on the incidence and severity of shivering associated with spinal anesthesia. Patients undergoing Cesarean delivery were randomly allocated to three groups of 30 patients each. Experimental treatments were added to hyperbaric bupivacaine as follows: Patients in group I (control) were administered isotonic saline. Patients in groups II and III received dexmedetomidine (2.5, 5 µg, respectively), mixed with isotonic saline. Shivering was observed in 11, 10 and 2 patients in groups I, II and III, respectively. The incidence of shivering in group III was significantly lower than that in groups I (p=0.005) and II (p=0.01). The severity of shivering was significantly different between the three groups (p=0.01). There were no significant inter-group differences with respect to mean arterial pressure and heart rate at any time point after administration of intrathecal local anesthesia (p>0.05). Intrathecal dexmedetomidine (5 µg) administered as an adjunct to hyperbaric bupivacaine during Cesarean delivery significantly reduced the incidence and intensity of shivering associated with spinal anesthesia.

Diabetes mellitus (DM) might increase the incidence and mortality of cardiac failure after acute myocardial infarction (AMI) in patients. We attempted to investigate whether Caveolin-3 showed beneficial effects in DM patient post-MI injury through the cAMP/PKA and BDNF/TrkB signaling pathways. The activity of ADRB2 and cAMP/PKA signaling were impaired in nondiabetic ischemia-reperfusion (I/R) group compared with the sham and DM groups and were more impaired in diabetic I/R group than in the I/R group. In H9C2 cells, high-glucose (HG) stimulation further enhanced H/R injury by promoting cell apoptosis, inhibiting cell viability, and suppressing TrkB and Akt signaling; in contrast, the ADRB2 agonist isoprenaline (ISO) significantly attenuated the above-described effects of HG stimulation. Caveolin-3 overexpression promoted the localization of ADRB2 on the membrane of the HG-stimulated H9C2 cells, subsequently inhibiting apoptosis and promoting cell viability. Under HG stimulation, Caveolin-3 overexpression enhanced the activity of the cAMP/PKA and BDNF/TrkB signaling pathways, whereas ADRB2 silencing reversed the effects of Caveolin-3 overexpression. In conclusion, ADRB2 agonist promoted the activity of the BDNF/TrkB and cAMP/PKA signaling pathways, mitigating the HG-aggravated H/R injuries in H9C2 cells. Caveolin-3 exerts a protective effect on diabetic hearts against I/R damage through the β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways.

Brain-derived neurotrophic factor precursor (proBDNF) has been reported to strengthen the dysfunction of monocytes/macrophages in animal studies. However,it is still unknown the roles of proBDNF in the dysfunction of monocytes in the inflammatory diseases in humans. In the present study, we showed that proBDNFand pan neurotrophic receptor p75 were significantly upregulated in monocytes from healthy donors (HD) after lipopolysaccharide treatment. Exogenous proBDNF treatment upregulated CD40 and proinflammatory cytokines expression in monocytes including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. InStanford type-A acute aortic dissection (AAD) patients, proBDNF was upregulatedin CD14+CD163+CX3CR1+ M2- but not CD14+CD68+CCR2+M1-like monocytes.In addition, sera from AAD patients activated gene expression of proinflammatory cytokines in cultured PBMCs from HD, which was attenuated by proBDNF monoclonal antibody (Ab-proB) treatment. These findings suggested that upregulation ofproBDNF in M2-like monocytes may contribute to the proinflammatory response in the AAD. Refereed/Peer-reviewed

The processes involved in the progression of myocardial cells towards hypertrophy and its gradual transition to heart failure represent a multifactorial health disorder. The aim of this study was to identify the molecular mechanism(s) underlying the abnormal overexpression of miR-23b-5p and its involvement in the promotion of cardiac hypertrophy and dysfunction via HMGB2. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-23b-5p expression under conditions of thoracic aortic constriction (TAC)-/angiotensin-II (Ang-II)-induced cardiac dysfunction. Cardiac structures and functions were assessed by echocardiography and invasive pressure-volume analysis. HMGB2 expression under conditions of cardiac hypertrophy was detected by western blotting. The biochemical relationship between miR-23b-5p and HMGB2 was verified using a luciferase reporter vector, lentiviral construct comprising the miR-23b-5p mimic sequence, and microRNA inhibitor (miR-inhibitor). The expression levels of miR-23b-5p were increased in the hearts under conditions of both Ang-II- and TAC-induced cardiac hypertrophy. The results of the luciferase activity analysis showed that HMGB2 is a supposed target of miR-23b-5p. miR-23b-5p overexpression in vivo aggravated pressure overload-induced cardiac hypertrophy and dysfunction, whereas the miR-inhibitor increased HMGB2 expression and reversed these effects. In the present study, we observed that miR-23b-5p mediates and is involved in the aggravation of cardiac hypertrophy and dysfunction via the HMGB2 signaling pathway.

Study objective To investigate which hemodynamic management strategy is most effective in reducing surgical site infection (SSI). Design Network meta-analysis of randomized controlled trials. Setting Perioperative setting. Patients Surgical patients. Interventions Usual care vs. optimized hemodynamic management, including goal-directed hemodynamic therapy (GDHT) and liberal/restrictive fluid therapy. Measurements The primary outcome was SSI arising within postoperative 30 days. The secondary outcomes included postoperative respiratory and urinary system infectious complications and sepsis/septic shock. The effect and ranking were assessed using network meta-analysis and the surface under the cumulative ranking curve (SUCRA) scores, respectively. Main results We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science for eligible randomized controlled trials from inception to October 11, 2019. Fifty-three eligible studies reported SSI and comprised of 56 GDHT groups (patients, n = 4205) and 51 usual care groups (patients, n = 3895). Comparing with usual care, GDHTs aimed at intravascular volume and stroke volume optimization (odds ratio (OR), 0.28 [95% credible interval (CrI), 0.13 to 0.56]; moderate quality), stroke volume and cardiac output optimization (OR, 0.34 [95% CrI, 0.16 to 0.70]; moderate quality), and intravascular volume and cardiac output optimization (OR, 0.51 [95% CrI, 0.24 to 0.99]; low quality) significantly reduced SSI. GDHT strategy aimed at intravascular volume and stroke volume optimization was likely most effective (SUCRA = 80%). Certain GDHTs significantly reduced respiratory infectious complications; however, no GDHT significantly reduced urinary infectious complications and sepsis/septic shock. GDHT strategy aimed at intravascular volume, stroke volume, and cardiac output optimization was likely most effective for reducing respiratory infectious complications (SUCRA = 88%). Conclusions Different hemodynamic managements exert different effectiveness for SSI reduction. GDHTs aimed at intravascular volume, stroke volume, and cardiac output optimization are likely most effective based on the overall evidence.

Background The lncRNA NKILA has been reported to interact with NF-κB and has an important role in various human diseases. However, the role of NKILA in myocardial ischaemic injury is still unknown. Methods We established cell and animal models of myocardial ischaemic injury. We confirmed our findings by overexpressing NKILA, silencing myocardin and using an NF-κB pathway inhibitor in a hypoxia/reoxygenation (H/R) model of H9c2 cells. An animal model of ischaemia-reperfusion (I/R) injury was established by LAD ligation. Overexpression of NKILA was achieved by adeno-associated virus (AAV) injection through the tail vein. Annexin-V/PI staining and flow cytometric analysis were performed to test cell apoptosis. ELISAs were used to determine the secretion of inflammatory factors. TTC, HE and TUNEL staining were performed to study myocardial pathological injury. qRT-PCR or Western blotting were used to test the expression levels of NKILA, myocardin, the NF-κB pathway and apoptosis-related proteins. Results H/R and I/R treatment significantly suppressed the expression of NKILA and activated the NF-κB pathway, resulting in the loss of myocardin. Overexpressing NKILA led to the suppressio n of the NF-κB pathway and successfully prevented the cell apoptosis and inflammatory responses caused by H/R stimulation in H9c2 cells. Silencing myocardin reversed the protective effect of NKILA and led to severe injury in the H9c2 cells that underwent H/R. Furthermore, the NF-κB pathway inhibitor BAY11-7028 reduced the H/R injury in H9c2 cells with little effect on NKILA expression. Similar results were confirmed in an animal model of myocardial I/R injury and showed that overexpression of NKILA inhibited I/R-triggered myocardial injury in vivo. Conclusion NKILA enhanced the expression of myocardin via inhibiting the NF-κB signalling pathway and preventing cell apoptosis and the inflammatory response of cardiomyocytes, thus ameliorating myocardial I/R injury.

The current study was intended to investigate the effect of ketamine (KET) on complete Freund’s adjuvant (CFA)-induced arthritis in rats. The CFA was administered in the hind paw of the rats for the induction of adjuvant-induced arthritis. The paw swelling of experimental animals was measured as hind paw volume. Hematoxylin and eosin staining was estimated and pathological changes in the joint tissues were observed under a light microscope. Furthermore, the bicinchoninic acid assay was used for protein quantification. The antibody-reactive bands were visualized using enhanced chemiluminescence. The present study showed that KET significantly reduces the severity of arthritis in CFA mice. The therapeutic effects were linked with reduced joint swelling and destruction, as evidenced by analyzing rat paws. The KET also revealed to attenuate the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In western blot analysis, KET inhibit phosphorylation of MAPKs, IκBα and nuclear translocation NF-κB in the inflammatory joints of AIA rats. Moreover, KET showed to induce apoptosis via mitochondrial signalling pathways (Bcl2, Bax, cytochrome C, cleaved caspase-3 and cleaved caapse-9). Taken together, KET show significant anti-rheumatoid arthritis activity via multiple mechanisms and may thus have therapeutic benefits for RA.

To investigate the effect of the aroma therapy and music intervention on anxious and pain for the breast cancer patients in the perioperative period and the potential mechanisms. Methods: A total of 100 breast cancer patients who received surgical treatment in the comprehensive hospitals of Hunan province were recruited for this study. Patients were assigned randomly into a control group, an aroma therapy group, a music intervention group, and a joint-therapy group (n=25 per group). The patients in the control group received regular post-surgical nursery, while the patients from other groups received aroma therapy, music intervention, or both in addition to the regular nursery. The scale of anxiety and pain were measured. The measurements were carried at three time points, namely 30 min before the surgery (T1), 30 min after the recovery period of anesthesia (T2), and 4 hours after the removal of anesthesia tubing (T3). Repeated ANOVA was used to perform statistic analysis. Results: The scale of pain was significantly increased at the post-operation (T2, T3) compared to pre-surgery (T1). The therapeutic group showed significant decrease in pain at post-operation (T3) comparing with the control group (P0.05). The scale of anxiety was the highest at pre-surgery (T1). During anaesthesia recovery, the anxiety of patients at post-operation T2 and T3 in the therapeutic groups significantly decreased compared with the control group (P0.05). Conclusion: Both the aroma therapy and the music therapy can decrease the stress-responsive anxiety and pain for the breast cancer patients in the perioperative period.目的：探讨芳香疗法和音乐干预对乳腺癌患者围手术期焦虑及疼痛反应的影响。方法：招募湖南省某综合性三级甲等医院乳甲外科收治的100例接受乳腺癌根治术治疗的患者，将患者随机分为对照组、芳香治疗组、音乐干预组及联合干预组，每组25例。对照组给予常规护理；在常规护理基础上，芳香治疗组及音乐干预组在手术前60 min及术后麻醉苏醒拔出气管插管后立即给予芳香干预或音乐干预；联合干预组在常规护理基础上同时给予芳香及音乐干预。对各组患者在术前30 min(T1)、术后麻醉苏醒拔除气管导管后30 min(T2)及拔管4 h(T3)3个时间点的焦虑、疼痛进行评分并比较。结果：患者术后(T2，T3)疼痛程度明显高于术前(T1)，与对照组比较，各干预组在T3时间点疼痛程度明显减轻(P0.05)；患者术前焦虑状态最明显(T1)，随着麻醉苏醒，患者焦虑状态逐渐减轻，与对照组比较，各干预组在术后(T2，T3)焦虑程度明显降低(P0.05)。结论：芳香疗法和音乐干预能减轻乳腺癌患者围手术期的焦虑与疼痛，使患者在情绪体验及躯体反应两方面获得良好的改善。.

The aim of this study was to identify the role of the precursor of the brain-derived neurotrophic factor (pro-BDNF) in myocardial hypoxia/reoxygenation injury (H/R) and to address the underlying mechanisms. For this purpose, myocardial microvascular endothelial cells (MMECs) exposed to a high concentration of glucose (30 mM) for 48 h were subjected to 4 h of hypoxia followed by 2 h of reoxygenation. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and flow-cytometric analysis were performed to detect apoptosis. Cell scratch and capillary-like-structure formation assays were employed to evaluate cell function. The levels of apoptosis-related proteins were evaluated by Western blotting and immunofluorescence assays. Our results showed that H/R resulted in MMEC injury, as indicated by significant increases in TUNEL-positive cell numbers and a reduction in MMEC migration and in capillary-like-structure formation coupled with increased pro-BDNF protein expression. In addition, overexpression of pro-BDNF in MMECs via a viral vector led to increased pro-BDNF expression, and this upregulation induced apoptosis. Mechanistic experiments revealed that H/R did not influence BDNF, JNK, and caspase 3 expression, but upregulated pro-BDNF, p75NTR, sortilin, phospho-JNK, and cleaved caspase 3 protein levels. In contrast, neutralization of endogenous pro-BDNF with an antibody significantly attenuated H/R-induced upregulation of pro-BDNF, p75NTR, sortilin, p-JNK, and cleaved caspase 3 protein levels, indicating that p75NTR-sortilin signaling and activation of JNK and caspase 3 may be involved in these effects. In conclusion, H/R-induced injury may be mediated by pro-BDNF, at least in part through the regulation of p75NTR-sortilin signaling and activation of JNK and caspase 3.