Minimally invasive surgeries for spontaneous hypertensive intracerebral hemorrhage (MISICH): a multicenter randomized controlled trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. METHODS: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0-2 at the 6-month follow-up. RESULTS: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000). CONCLUSIONS: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811614.

A Unified Spatio-Temporal Inference Network for Car-Sharing Serial Prediction.

Car-sharing systems require accurate demand prediction to ensure efficient resource allocation and scheduling decisions. However, developing precise predictive models for vehicle demand remains a challenging problem due to the complex spatio-temporal relationships. This paper introduces USTIN, the Unified Spatio-Temporal Inference Prediction Network, a novel neural network architecture for demand prediction. The model consists of three key components: a temporal feature unit, a spatial feature unit, and a spatio-temporal feature unit. The temporal unit utilizes historical demand data and comprises four layers, each corresponding to a different time scale (hourly, daily, weekly, and monthly). Meanwhile, the spatial unit incorporates contextual points of interest data to capture geographic demand factors around parking stations. Additionally, the spatio-temporal unit incorporates weather data to model the meteorological impacts across locations and time. We conducted extensive experiments on real-world car-sharing data. The proposed USTIN model demonstrated its ability to effectively learn intricate temporal, spatial, and spatiotemporal relationships, and outperformed existing state-of-the-art approaches. Moreover, we employed negative binomial regression with uncertainty to identify the most influential factors affecting car usage.

Diverse glasses revealed from Chang'E-5 lunar regolith.

Lunar glasses with different origins act as snapshots of their formation processes, providing a rich archive of the Moon's formation and evolution. Here, we reveal diverse glasses from Chang'E-5 (CE-5) lunar regolith, and clarify their physical origins of liquid quenching, vapor deposition and irradiation damage respectively. The series of quenched glasses, including rotation-featured particles, vesicular agglutinates and adhered melts, record multiple-scale impact events. Abundant micro-impact products, like micron- to nano-scale glass droplets or craters, highlight that the regolith is heavily reworked by frequent micrometeorite bombardment. Distinct from Apollo samples, the indigenous ultra-elongated glass fibers drawn from viscous melts and the widespread ultra-thin deposited amorphous rims without nanophase iron particles both indicate a relatively gentle impact environment at the CE-5 landing site. The clarification of multitype CE-5 glasses also provides a catalogue of diverse lunar glasses, meaning that more of the Moon's mysteries, recorded in glasses, could be deciphered in future.

High-Flow Nasal Oxygen versus Noninvasive Ventilation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients: A Meta-Analysis of Randomized Controlled Trials.

Background: High-flow nasal cannula (HFNC) can be used in stable chronic obstructive pulmonary disease (COPD) patients, but the effect of HFNC on clinical outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is still uncertain. Methods: We searched electronic literature databases for randomized controlled trials (RCTs) comparing HFNC with noninvasive ventilation (NIV) in hypercapnic patients with AECOPD. The primary endpoint of this meta-analysis was PaCO2, PaO2, and SpO2. The secondary outcomes were the respiratory rate, mortality, complications, and intubation rate. Results: We included 7 RCTs with a total of 481 patients. There were no significant differences on measures of PaCO2 (MD = -0.42, 95%CI -3.60 to 2.75, Z = 0.26, and P = 0.79), PaO2 (MD = -1.36, 95%CI -4.69 to 1.97, Z = 0.80, and P = 0.42), and SpO2 (MD = -0.78, 95%CI -1.67 to 0.11, Z = 1.72, P = 0.08) between the HFNC group and the NIV group. There was no significant difference in measures of the mortality and intubation rate between the HFNC group (OR = 0.72, 95%CI 0.30 to 1.69, Z = 0.76, and P = 0.44) and the NIV group (OR = 2.38, 95%CI 0.49 to 11.50, Z = 1.08, and P = 0.28), respectively. But the respiratory rate in the HFNC group was lower than that in the NIV group (MD = -1.13, 95%CI -2.13 to -0.14, Z = 2.23, and P = 0.03), and fewer complications were found in the HFNC group (OR = 0.26, 95%CI 0.14 to 0.47, Z = 4.46, and P < 0.00001). Conclusion: NIV was noninferior to HFNC in decreasing PaCO2 and increasing PaO2 and SpO2. Similarly, the mortality and intubation rate was similar among the two groups. The respiratory rate and complications were inferior in the AECOPD group treated with HFNC.

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

A novel method for the bronchial occlusion of prolonged air leakage using customized endobronchial plugs.

Background: The management of prolonged air leakage (PAL) is a significant clinical challenge, particularly for patients who are unfit for surgical treatment. The use of endoscopic interventions with occlusive devices has been reported previously; however, local availability and cost may represent potential hurdles, especially in developing countries. In this study, we presented a conical endobronchial plug of our design and evaluated the efficacy of making use of that in the treatment of PAL as a novel method. Methods: This retrospective study included a total of 23 patients with PAL who were not suitable for surgery and underwent bronchial occlusion using customized plugs. The responsible bronchi were identified by the balloon occlusion test or by end-tidal carbon dioxide detection. In each case, the plug was grasped at the knot of the tip with forceps and then inserted into the target bronchus with a flexible bronchoscope. Results: Of the 23 patients with intractable pneumothorax, 1 to 3 plugs (median =1) were successfully inserted into the affected bronchi of each patient for bronchial occlusion. Air leakage showed complete cessation in 13 patients (56.5%) and reduction in seven patients (30.4%). A total of 20 patients (87.0%) experienced successful removal of the drainage tube following plug occlusion or presented with additional pleurodesis. Complications included expectoration of the plug (n=1) and fever (n=1); no other severe complications were observed. Conclusions: Bronchial occlusion using customized endobronchial plugs appears to be an effective and simple option for the management of PAL in patients who are not suitable for surgery, especially in developing countries, as the customized plug is a cost-effective alternative.

Mobile internet-based mixed-reality interactive telecollaboration system for neurosurgical procedures: technical feasibility and clinical implementation.

OBJECTIVE: To increase access to health interventions and healthcare services for patients in resource-constrained settings, strategies such as telemedicine must be implemented for the allocation of medical resources across geographic boundaries. Telecollaboration is the dominant form of surgical telemedicine. In this study, the authors report and evaluate a novel mobile internet-based mixed-reality interactive telecollaboration (MIMIT) system as a new paradigm for telemedicine and validate its clinical feasibility. METHODS: The application of this system was demonstrated for long-distance, real-time collaboration of neuroendoscopic procedures. The system consists of a local video processing workstation, a head-mounted mixed-reality display device, and a mobile remote device, connected over mobile internet (4G or 5G), allowing global point-to-point communication. Using this system, 20 cases of neuroendoscopic surgery were performed and evaluated. The system setup, composite video latency, technical feasibility, clinical implementation, and future potential business model were analyzed and evaluated. RESULTS: The MIMIT system allows two surgeons to perform complex visual and verbal communication during the operation. The average video delay time is 184.25 msec (range 160-230 msec) with 4G mobile internet, and 23.25 msec (range 20-26 msec) with 5G mobile internet. Excellent image resolution enabled remote neurosurgeons to visualize all critical anatomical structures intraoperatively. Remote instructors could easily make marks on the surgical view; then the composite image, as well as the audio conversation, was transferred to the local surgeon. In this way, a real-time, long-distance collaboration can occur. This system was used for 20 neuroendoscopic surgeries in various cities in China and even across countries (Boston, Massachusetts, to Jingzhou, China). Its simplicity and practicality have been recognized by both parties, and there were no technically related complications recorded. CONCLUSIONS: The MIMIT system allows for real-time, long-distance telecollaborative neuroendoscopic procedures and surgical training through a commercially available and inexpensive system. It enables remote experts to implement real-time, long-distance intraoperative interaction to guide inexperienced local surgeons, thus integrating the best medical resources and possibly promoting both diagnosis and treatment. Moreover, it can popularize and improve neurosurgical endoscopy technology in more hospitals to benefit more patients, as well as more neurosurgeons.

Bronchoscopic Treatment of Giant Emphysematous Bullae with Endobronchial Silicone Plugs.

Purpose: Surgical bullectomy is the standard treatment of giant emphysematous bulla (GEB). However, bronchoscopic treatment should be considered as an alternative approach for patients who are unfit for surgical treatment. The study aimed to evaluate the clinical efficacy of endobronchial occlusion for the treatment of GEB using silicone plugs. Methods: This retrospective study recruited four patients with GEB who were unsuitable for surgery. Preoperative planning was performed using high-resolution computed tomography and a virtual bronchoscopic navigation system. Customized silicone plugs were then placed in the target airway via bronchoscopy to cause GEB regression and atelectasis. Results: All procedures were completed successfully in four patients. Three months after the procedures, compared with baseline, increases in the mean forced expiratory volume in 1 s (from 1.20 L/s to 1.33 L/s), forced vital capacity (from 2.63 L to 2.90 L), diffusion lung capacity for carbon monoxide (from 29% to 41% of the predicted value) and 6-minute walking test (from 412 m to 474 m) were observed. Additionally, the mean total lung capacity (from 6.80 L to 6.35 L), residual volume (from 3.97 L to 3.52 L), and St. George's Respiratory Questionnaire scores (from 67 to 45) were all lower than baseline data. Conclusion: Our preliminary results demonstrated that the endobronchial placement of silicone plugs could be a low-cost, safe, and effective choice for the treatment of GEB in surgically unfit patients.

LncRNA FGD5-AS1 drives the malignant development of gastric cancer by negatively interacting with FZD3.

We aimed to detect the expression pattern of long non-coding RNA (lncRNA) FGD5-AS1 in gastric cancer (GC) samples and its impact on driving the development of GC. FGD5-AS1 levels in 66 cases of GC tissues and paracancerous ones were detected. Its influences on clinical features and prognosis in GC patients were analyzed. In AGS and SGC-7901 cells with FGD5-AS1 knockdown, phenotype changes were assessed through cell counting kit-8 (CCK-8), Transwell and wound healing assay. The downstream target of FGD5-AS1 was searched by a bioinformatics tool and confirmed by dual-luciferase reporter assay. Their interaction in regulating the malignant development of GC was finally explored. FGD5-AS1 was upregulated in GC tissues compared to paracancerous ones. GC patients expressing a high level of FGD5-AS1 had higher risk of lymphatic metastasis or distant metastasis and worse prognosis than those with a low level. Knockdown of FGD5-AS1 weakened proliferative and metastatic abilities in AGS and SGC-7901 cells. FZD3 was the downstream target of FGD5-AS1. Protein levels of FZD3 and FZD5 were upregulated, while b-catenin, TGF-b and MMP9 were downregulated in GC cells with FGD5-AS1 knockdown. Knockdown of FZD3 abolished the regulatory effects of FGD5-AS1 on malignant phenotypes of GC cells. FGD5-AS1 is upregulated in GC samples, which is linked to metastasis and prognosis in GC. It drives proliferative and metastatic abilities in GC cells via negatively interacting with FZD3.

An Augmented Neural Network for Sentiment Analysis Using Grammar.

Understanding human sentiment from their expressions is very important in human-robot interaction. But deep learning models are hard to represent grammatical changes for natural language processing (NLP), especially for sentimental analysis, which influence the robot's judgment of sentiment. This paper proposed a novel sentimental analysis model named MoLeSy, which is an augmentation of neural networks incorporating morphological, lexical, and syntactic knowledge. This model is constructed from three concurrently processed classical neural networks, in which output vectors are concatenated and reduced with a single dense neural network layer. The models used in the three grammatical channels are convolutional neural networks (CNNs), long short-term memory (LSTM) networks, and fully connected dense neural networks. The corresponding output in the three channels is morphological, lexical, and syntactic results, respectively. Experiments are conducted on four different sentimental analysis corpuses, namely, hotel, NLPCC2014, Douban movie reviews dataset, and Weibo. MoLeSy can achieve the best performance over previous state-of-art models. It indicated that morphological, lexical, and syntactic grammar can augment the neural networks for sentimental analysis.

Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis.

BACKGROUND: Sepsis is defined as a systemic inflammatory response to microbial infections with multiple organ dysfunction. This study analysed untargeted metabolomics combined with proteomics of serum from patients with sepsis to reveal the underlying pathological mechanisms involved in sepsis. METHODS: A total of 63 patients with sepsis and 43 normal controls were enrolled from a prospective multicentre cohort. The biological functions of the metabolome were assessed by coexpression network analysis. A molecular network based on metabolomics and proteomics data was constructed to investigate the key molecules. RESULTS: Untargeted metabolomics analysis revealed widespread dysregulation of amino acid metabolism, which regulates inflammation and immunity, in patients with sepsis. Seventy-three differentially expressed metabolites (|log2 fold change| > 1.5, adjusted P value < 0.05 and variable importance in the projection (VIP) > 1.5) that could predict sepsis were identified. External validation of the hub metabolites was consistent with the derivation results (area under the receiver operating characteristic curve (AUROC): 0.81-0.96/0.62-1.00). The pentose phosphate pathway was found to be related to sepsis-associated encephalopathy. Phenylalanine metabolism was associated with sepsis-associated acute kidney injury. The key molecular alterations of the multiomics network in sepsis compared to normal controls implicate acute inflammatory response, platelet degranulation, myeloid cell activation involved in immune response and phenylalanine, tyrosine and tryptophan biosynthesis, and arginine biosynthesis. CONCLUSIONS: Integrated analysis of untargeted metabolomics and proteomics revealed characteristic metabolite and protein alterations in sepsis, which were mainly involved in inflammation-related pathways and amino acid metabolism. This study depicted the pathological characteristics and pathways involved in sepsis and potential therapeutic targets.

Exosomes Derived from Mesenchymal Stem Cells Ameliorate the Progression of Atherosclerosis in ApoE-/- Mice via FENDRR.

Exosomes (EXO) are extracellular vesicles with lipid bilayer membrane structure containing noncoding RNA, DNA, and other molecules which mediate biological functions. The importance of EXO derived from mesenchymal stem cells (MSCs) has been underlined in cardiovascular diseases. However, the functional role of long non-coding RNA (lncRNA) released by MSCs-EXO on atherosclerosis (AS) was unknown. We aimed to investigate the effects of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) released from MSC-derived EXO on AS. The accumulation of oxidized low-density lipoprotein (oxLDL) caused AS in mice and damage to human vascular endothelial cells (HUV-EC-C). MSC-EXO restored HUV-EC-C activity and alleviated arterial injury. LncRNA microarrays revealed that FENDRR was delivered to cells and tissues by MSC-EXO. FENDRR bound to microRNA (miR)-28 to regulate TEA domain transcription factor 1 (TEAD1) expression. Moreover, FENDRR knockdown exacerbated cell injury and arterial injury in mice. miR-28 inhibitor reversed the effects of FENDRR silencing and reduced atherosclerotic plaque formation. While loss of TEAD1 mitigated the effect of miR-28 inhibitor and accentuated HUV-EC-C injury in vitro and AS symptoms in vivo. Our results demonstrated that MSC-EXO secreted FENDRR to treat AS. FENDRR competed with TEAD1 to bind to miR-28, thereby reducing HUV-EC-C injury and atherosclerotic plaque formation.

Early Pulmonary Rehabilitation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Randomized Controlled Trials.

Pulmonary rehabilitation (PR) is an essential method for Acute exacerbation in chronic obstructive pulmonary disease (AECOPD) recovery. We perform a meta-analysis to compare early PR with usual care. A literature search was performed through these databases: PubMed, MEDLINE database, Google Scholar, Cochrane, Embase from inception to July 2021. Eligible trials were clinical randomized controlled trials comparing the effects of early PR and usual care in AECOPD patients. The primary endpoint of this meta-analysis was FEV1% predicted, 6-min walk test (6MWD), modified Medical Research Council (mMRC) and George Respiratory Questionnaire-total (SGRQ-total). The secondary outcomes were borg dyspnea score, short-form 36 health survey questionnaire physical (SF-36 physical) and SF-36 mental. We included 13 RCTs with a total of 866 patients. There were no significant effects of the PR group on measures of FEV1% predicted (MD = 0.50, 95%CI -1.43 to 2.44, Z = 0.51, p = 0.61), borg dyspnea score (MD = -0.88, 95%CI -1.89 to 0.13, Z = 1.71, p = 0.09) and SF-36 mental (MD = 4.34, 95%CI -1.64 to 10.32, Z = 1.42, p = 0.16) compared with usual care. PR group achieved better 6MWD (MD = 97.58, 95%CI 17.21 to 177.96, Z = 2.38, p = 0.02), mMRC (MD = -0.36, 95%CI -0.52 to -0.21, Z = 4.56, p ˂ 0.00001), SGRQ-total (MD= -9.67, 95%CI -16.23 to -3.11, Z = 2.89, p = 0.004) and SF-36 physical (MD = 4.98, 95%CI 0.60 to 9.35, Z = 2.23, p = 0.03) compared with usual care group. Early PR in AECOPD patients would lead to better 6MWD, mMRC, SGRQ-total and SF-36 physical. But there were no significant effects of the PR group on measures of FEV1% predicted, borg dyspnea score and SF-36 mental.

Glassy or Amorphous? A Demonstration Using G-Phase Copper Containing a Fivefold Twinning Structure.

The G-phase, a new metastable phase with its potential energy sitting right in the middle of the glass and crystal, was recently discovered in some simulations when the molten metallic liquid was quenched down to room temperature. In comparison with ordinary glass, the G-phase has a more ordered short-range structure but a similarly disordered long-range structure. The question is whether the G-phase can be termed a new type of glass. In this work, G-phase Cu is made in a molecular dynamics simulation using rapid quenching or isothermal annealing. Weak oscillations are found in the long-range atomic structure. The pseudo-fictive temperature is significantly lower than the Kauzmann temperature; fivefold twinning structures are distinguished in the G-phase whose constituent atoms are face-center-cubic or hexagonal-cubic-packed. This evidence suggests that G-phase Cu is not a glass. However, the G-phase is also metastable against crystallization. Therefore, G-phase Cu is neither a glass nor a crystal but belongs to a new mesophase.

Clinical investigation of lipopolysaccharide in the persistence of metabolic syndrome (MS) through the activation of GRP78-IRE1α-ASK1 signaling pathway.

OBJECTIVE: Endoplasmic reticulum stress (ERS) might play a pivotal role in the persistence of metabolic syndrome (MS). Lipopolysaccharide (LPS) derived from various gram-negative bacteria could result in the ERS. Therefore, we aimed to investigate the association between LPS and ERS in MS. METHOD: We enrolled 86 patients with MS and 42 healthy people aged 35-65 years. Body weight, waist circumference, blood pressure were measured. LPS, LBP and inflammation factors, fasting plasma glucose (FPG), insulin, total cholesterol (TC), triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), free fatty acid (FFA) were analyzed in blood plasma of patient's cohort. Body mass index (BMI) and HOMA-IR were calculated. The mRNA and protein expression of ERS GRP78, IRE1α, ASK1 and IKKß, JNK1 were measured in blood plasma of patient's cohort by RT-PCR and Elisa. MS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans. RESULTS: BMI, waist circumference, blood pressure, FPG, insulin, HOMA-IR, TC, triglyceride, HDL-C, LDL-C, FFA and LPS, LBP, TNF-α, CRP, IL-1, IL-6, MCP-1 were significantly higher in patients with MS than healthy people (P < 0.001). The correlation analysis suggested that LPS were associated with TNF-α, IL-1, IL-6, MCP-1, LBP, FFA, HOMA-IR potently (P < 0.05). The marker gene and protein expressions of ERS (GRP78, IRE1α, ASK1, IKKß and JNK) were significantly overexpressed in patients with MS and were positive correlation with LPS (P < 0.05). CONCLUSION: LPS may play an important role in mediating chronic low-grade inflammation by activating the ERS GRP78-IRE1α-ASK1 signaling pathway, contributing to the persistence of MS.

Empagliflozin for the treatment of non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials.

The efficacy of empagliflozin for non-alcoholic fatty liver disease remains controversial. This meta-analysis aims to explore the influence of empagliflozin versus placebo on the treatment of non-alcoholic fatty liver disease and we have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2021 for related randomized controlled trials (RCTs). Three RCTs involving 212 patients are included in the meta-analysis. Compared with control group for non-alcoholic fatty liver disease, empagliflozin treatment has no improvement in controlled attenuation parameter (CAP) score, hepatic steatosis and liver stiffness measurement (LSM) score, alanine aminotransferase (ALT), aspartate-aminotransferase (AST), low density lipoprotein (LDL) or triglyceride (TG). These indicate that empagliflozin treatment may be not effective for non-alcoholic fatty liver disease.

Genistein suppresses ox-LDL-elicited oxidative stress and senescence in HUVECs through the SIRT1-p66shc-Foxo3a pathways.

The anti-senescence function of genistein is related to inhibiting oxidative stress, however, the mechanism has not been clarified. The present study aimed to explore the effects of genistein on oxidized low-density lipoprotein (ox-LDL)-induced endothelial senescence and the role of the sirtuin-1 (SIRT1)-66-kDa Src homology 2 domain-containing protein (p66Shc)-forkhead box protein O3 (Foxo3a) pathways in the process. In this paper, human umbilical vein endothelial cells were pretreated with 1000 nM genistein for 30 min and then incubated with 50 mg/L ox-LDL for another 12 h; meanwhile, the functions of adenovirus-mediated overexpression of p66shc and small interfering RNA-mediated silencing of SIRT1 were investigated. Results showed that genistein pretreatment alleviated ox-LDL-induced mitochondrial reactive oxygen species, the levels of oxidatively modified DNA (8-OHdG) and pai-1, and the activity of SA-ß-gal, which was associated with mitigating p66shc. Further studies indicated the inhibitory effect of genistein on p66shc was correlated with suppressing the acetylation and phosphorylation of p66shc, and ameliorating its mitochondrial translocation by activating SIRT1. Moreover, the inactivated p66shc could enhance the activity of Foxo3a via restraining the phosphorylation and triggering nucleus accumulation. The study demonstrates genistein could prevent ox-LDL-induced mitochondrial oxidative stress and senescence through the SIRT1-p66shc-Foxo3a pathways.

Large mediastinal mass diagnosed as Nocardia infection by endobronchial ultrasound-guided transbronchial needle aspiration in a ceramic worker: A case report.

Background: Nocardia is a ubiquitous soil saprophyte transmitted through airborne or direct cutaneous inoculation routes. Although Nocardia is more common in immunocompromised patients, Nocardia may also arise in apparently immunocompetent patients. Case presentation: We report a rare case of Nocardia infection presenting as a large mediastinal mass in an immunocompetent ceramic worker. A 54-year-old man with no previous history of immune dysfunction, a ceramic worker by profession, was referred and admitted to our hospital because of a persistent fever for 19 days. Chest CT showed a large middle mediastinal mass. However, conventional anti-infective treatment was ineffective. Under the guidance of the Virtual bronchoscopic navigation (VBN) system, he underwent Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The purulent exudate obtained by EBUS-TBNA was further identified as Nocardia by weak acid-fast and metagenomic next-generation sequencing (mNGS). He was subsequently treated with intravenous imipenem/amikacin, switched to intravenous imipenem and oral trimethoprim/sulfamethoxazole, and the clinical symptoms were significantly improved. Conclusions: Even in immunocompetent patients, Nocardiosis cannot be excluded. For the public, especially soil contact workers, precautions should be taken to avoid Nocardia infection from occupational exposure. This rare case may provide a diagnosis and treatment reference for clinicians.

Serum proteomics reveals disorder of lipoprotein metabolism in sepsis.

Sepsis is defined as an organ dysfunction syndrome and it has high mortality worldwide. This study analysed the proteome of serum from patients with sepsis to characterize the pathological mechanism and pathways involved in sepsis. A total of 59 patients with sepsis were enrolled for quantitative proteomic analysis. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network specific to sepsis. Key regulatory modules that were detected were highly correlated with sepsis patients and related to multiple functional groups, including plasma lipoprotein particle remodeling, inflammatory response, and wound healing. Complement activation was significantly associated with sepsis-associated encephalopathy. Triglyceride/cholesterol homeostasis was found to be related to sepsis-associated acute kidney injury. Twelve hub proteins were identified, which might be predictive biomarkers of sepsis. External validation of the hub proteins showed their significantly differential expression in sepsis patients. This study identified that plasma lipoprotein processes played a crucial role in sepsis patients, that complement activation contributed to sepsis-associated encephalopathy, and that triglyceride/cholesterol homeostasis was associated with sepsis-associated acute kidney injury.