Assessing Consciousness in Patients With Disorders of Consciousness Using a Musical Stimulation Paradigm and Verifiable Criteria.

Numerous studies have shown that musical stimulation can activate corresponding functional brain areas. Electroencephalogram (EEG) activity during musical stimulation can be used to assess the consciousness states of patients with disorders of consciousness (DOC). In this study, a musical stimulation paradigm and verifiable criteria were used for consciousness assessment. Twenty-nine participants (13 healthy subjects, 6 patients in a minimally conscious state (MCS) and 10 patients in a vegetative state (VS)) were recruited, and EEG signals were collected while participants listened to preferred and relaxing music. Fusion features based on differential entropy (DE), common spatial pattern (CSP), and EEG-based network pattern (ENP) features were extracted from EEG signals, and a convolutional neural network-long short-term memory (CNN-LSTM) model was employed to classify preferred and relaxing music.The results showed that the average classification accuracy for healthy subjects reached 85.58%. For two of the patients in the MCS group, the classification accuracies reached 78.18% and 66.14%, and they were diagnosed with emergence from MCS (EMCS) two months later. The accuracies of three patients in the VS group were 58.18%, 64.32% and 62.05%, with two patients showing slight increases in scale scores. Our study suggests that musical stimulation could be an effective method for consciousness detection, with significant diagnostic implications for patients with DOC.

Individualized music induces theta-gamma phase-amplitude coupling in patients with disorders of consciousness.

Objective: This study aimed to determine whether patients with disorders of consciousness (DoC) could experience neural entrainment to individualized music, which explored the cross-modal influences of music on patients with DoC through phase-amplitude coupling (PAC). Furthermore, the study assessed the efficacy of individualized music or preferred music (PM) versus relaxing music (RM) in impacting patient outcomes, and examined the role of cross-modal influences in determining these outcomes. Methods: Thirty-two patients with DoC [17 with vegetative state/unresponsive wakefulness syndrome (VS/UWS) and 15 with minimally conscious state (MCS)], alongside 16 healthy controls (HCs), were recruited for this study. Neural activities in the frontal-parietal network were recorded using scalp electroencephalography (EEG) during baseline (BL), RM and PM. Cerebral-acoustic coherence (CACoh) was explored to investigate participants' abilitiy to track music, meanwhile, the phase-amplitude coupling (PAC) was utilized to evaluate the cross-modal influences of music. Three months post-intervention, the outcomes of patients with DoC were followed up using the Coma Recovery Scale-Revised (CRS-R). Results: HCs and patients with MCS showed higher CACoh compared to VS/UWS patients within musical pulse frequency (p = 0.016, p = 0.045; p < 0.001, p = 0.048, for RM and PM, respectively, following Bonferroni correction). Only theta-gamma PAC demonstrated a significant interaction effect between groups and music conditions (F (2,44) = 2.685, p = 0.036). For HCs, the theta-gamma PAC in the frontal-parietal network was stronger in the PM condition compared to the RM (p = 0.016) and BL condition (p < 0.001). For patients with MCS, the theta-gamma PAC was stronger in the PM than in the BL (p = 0.040), while no difference was observed among the three music conditions in patients with VS/UWS. Additionally, we found that MCS patients who showed improved outcomes after 3 months exhibited evident neural responses to preferred music (p = 0.019). Furthermore, the ratio of theta-gamma coupling changes in PM relative to BL could predict clinical outcomes in MCS patients (r = 0.992, p < 0.001). Conclusion: Individualized music may serve as a potential therapeutic method for patients with DoC through cross-modal influences, which rely on enhanced theta-gamma PAC within the consciousness-related network.

A Hybrid BCI Integrating EEG and Eye-Tracking for Assisting Clinical Communication in Patients With Disorders of Consciousness.

Assessing communication abilities in patients with disorders of consciousness (DOCs) is challenging due to limitations in the behavioral scale. Electroencephalogram-based brain-computer interfaces (BCIs) and eye-tracking for detecting ocular changes can capture mental activities without requiring physical behaviors and thus may be a solution. This study proposes a hybrid BCI that integrates EEG and eye tracking to facilitate communication in patients with DOC. Specifically, the BCI presented a question and two randomly flashing answers (yes/no). The subjects were instructed to focus on an answer. A multimodal target recognition network (MTRN) is proposed to detect P300 potentials and eye-tracking responses (i.e., pupil constriction and gaze) and identify the target in real time. In the MTRN, the dual-stream feature extraction module with two independent multiscale convolutional neural networks extracts multiscale features from multimodal data. Then, the multimodal attention strategy adaptively extracts the most relevant information about the target from multimodal data. Finally, a prototype network is designed as a classifier to facilitate small-sample data classification. Ten healthy individuals, nine DOC patients and one LIS patient were included in this study. All healthy subjects achieved 100% accuracy. Five patients could communicate with our BCI, with 76.1±7.9% accuracy. Among them, two patients who were noncommunicative on the behavioral scale exhibited communication ability via our BCI. Additionally, we assessed the performance of unimodal BCIs and compared MTRNs with other methods. All the results suggested that our BCI can yield more sensitive outcomes than the CRS-R and can serve as a valuable communication tool.

Increased Adrenocorticotropic Hormone Levels Predict Recovery of Consciousness in Patients With Disorders of Consciousness.

The potential influence of pituitary-related hormones (including both pituitary gland and target gland hormones) on functional recovery after traumatic brain injury has been observed. However, the relationship between these hormones and the recovery of consciousness in patients with disorders of consciousness (DOC) remains unclear. In this retrospective and observational study, 208 patients with DOC were recruited. According to the Glasgow Outcome Scale (GOS) scores after 6 months, patients with DOC were categorized into two subgroups: a favorable prognosis subgroup (n = 38) comprising those who regained consciousness (GOS score ≥3), and a poor prognosis subgroup (n = 156) comprising those who remained in DOC (GOS score <3). Comparative analyses of pituitary-related hormone levels between the two subgroups were conducted. Further, a binary logistic regression analysis was conducted to assess the predictive value of pituitary-related hormones for the patients' prognosis. The favorable prognosis subgroup showed a significant increase in adrenocorticotropic hormone (ACTH) levels (p = 0.036). Moreover, higher ACTH levels and shorter days since injury were significantly associated with a better prognosis, with odds ratios (ORs) of 0.928 (95% confidence interval [CI] = 0.873-0.985, p = 0.014) and 1.015 (95% CI = 1.005-1.026, p = 0.005), respectively. A subsequent receiver operating characteristic (ROC) analysis demonstrated the potential to predict patients' prognosis with an area under the curve value of 0.78, an overall accuracy of 75.5%, a sensitivity of 77.5%, and a specificity of 66.7%. Our findings indicate that ACTH levels could serve as a clinically valuable and convenient predictor for patients' prognosis.

Soluble CD80 oral delivery by recombinant Lactococcus suppresses tumor growth by enhancing antitumor immunity.

CD80 is an important co-stimulatory molecule that participates in the immune response. Soluble CD80 can induce T cell activation and overcome PDL1-mediated immune suppression. In this study, we aimed to construct recombinant Lactococcus lactis for oral delivery of the soluble CD80 (hsCD80) protein or the fusion protein containing the cholera toxin B subunit (CTB) and hsCD80 (CTB-hsCD80) under the control of the nisin-inducible expression system. The recombinant L. lactis expressed and secreted hsCD80 or CTB-hsCD80 fusion proteins after induction by nisin in vitro and in the enteric cavity. Additionally, the CTB-hsCD80 fusion protein showed uptake by intestinal epithelial cells, was cleaved by the furin protease, and was released as free hsCD80 protein into the blood circulation. Orally administered hsCD80 and CTB-hsCD80 containing L. lactis increased the proportion of activated T cells in the spleen and intestinal epithelium, inhibited tumor growth, and prolonged the survival of tumor-bearing mice. The hsCD80-containing L. lactis showed greater therapeutic effects on primary colonic adenoma in APCmin/- mice and completely suppressed tumor growth. Further, recombinant CTB-hsCD80 in L. lactis was more efficient than hsCD80-containing bacteria in inhibiting the growth of xenografted colon cancer and melanoma cells. hsCD80 engineered probiotics may serve as a promising new approach for antitumor immunotherapy, especially for colorectal cancer.

Effects of ambient temperature on atopic dermatitis and attributable health burden: a 6-year time-series study in Chengdu, China.

Background: Despite increasing public concerns about the widespread health effects of climate change, the impacts of ambient temperature on atopic dermatitis (AD) remain poorly understood. Objectives: We aimed to explore the effect of ambient temperature on AD and to estimate the burdens of AD attributed to extreme temperature. Methods: Data on outpatients with AD and climate conditions in Chengdu, China were collected. A distributed lag nonlinear model (DLNM) was adopted to explore the association between daily mean temperature and AD outpatient visits. Subgroup analysis was used to identify vulnerable populations. Attributable burden was estimated by the epidemiological attributable method. Results: We analyzed 10,747 outpatient visits from AD patients at West China Hospital in Chengdu between January 1, 2015, and December 31, 2020. Both low (<19.6 °C) and high temperatures (>25.3 °C) were associated with increased AD outpatient visits, with the increase being more pronounced at low temperature, as evidenced by a 160% increase in visits when the temperature dropped below zero from the minimum mortality temperature (22.8 °C). Children and males were the most susceptible populations. Approximately 25.4% of AD outpatient visits were associated with temperatures, causing an excessive 137161.5 US dollars of health care expenditures during this 6-year period. Conclusions: Both high and low temperatures, particularly low temperatures, were significantly associated with an increased risk of AD, with children and males showing the strongest associations. Extreme environmental temperature has been identified as one of the major factors promoting the development of AD. However, individual patient-level exposures still needed to be investigated in future studies to confirm the causality between temperature and AD.

Tim3scFv-Transforming Lactobacillus Inhibits Transplanted Tumor of Renal-Cell Carcinoma.

INTRODUCTION: T-cell immunoglobulin-3 (Tim-3) antibody drugs can treat malignant renal tumors but are expensive. To overcome this limitation, Lactococcus lactis host bacteria were used to express Tim-3 single-chain antibodies. METHODS: The pLAN-CTB-Tim3scFv plasmid was constructed using molecular cloning technology and transformed into Lactococcus lactis. Expression and immune activity of proteins in the transformed bacteria were analyzed using Western blotting and enzyme-linked immunosorbent assay in vitro. A mouse subcutaneously transplanted tumor model of renal adenocarcinoma was constructed. The promoting effect of transformed bacteria on mouse spleen lymphocyte activation and their inhibitory effect on transplanted tumors were analyzed. RESULTS: Transformed L. lactis NZ-CTB-Tim3scFv and NZ-Tim3scFv were successfully constructed. CTB-Tim3scFv secreted by NZ-CTB-Tim3scFv showed immunological activity. Compared with the NZ-Tim3scFv and NZ-Vector groups, the subgroups of splenic lymphocytes in the NZ-CTB-Tim3scFv group had a higher proportion of CD3+CD4+, CD3+CD8a+, and CD3+CD69+ cells. Ki67 and CD31 expression in the NZ-CTB-Tim3scFv group was significantly reduced. Tumor volume in the NZ-CTB-Tim3scFv group increased the least. DISCUSSION/CONCLUSION: Secretion of CTB-Tim3scFv promoted the proliferation and activation of spleen lymphocytes and inhibited growth, cell proliferation, and angiogenesis of tumors. The proposed method is low cost and convenient with potential to become a new immunotherapy approach for renal-cell carcinoma.

CircRNA_001895 promotes sunitinib resistance of renal cell carcinoma through regulation of apoptosis and DNA damage repair.

Sunitinib, an inhibitor of receptor tyrosine kinase, possesses anti-tumor activity in renal cell carcinoma (RCC) through its anti-angiogenic effects. However, patients with advanced RCC are resistant to sunitinib. Dysregulated circRNAs has been shown to be associated with drug resistance in various tumors. However, little is known about the effect of circRNA_001895 on sunitinib resistance of RCC. First, the expression of circRNA_001895 was found to be higher in sunitinib-resistant RCC tissues than chemosensitive tumor tissues. Half maximal inhibitory concentration of sunitinib-resistant RCC cells (786-O/R and ACHN/R) was higher than sunitinib-sensitive 786-O and ACHN cells. CircRNA_001895 was also upregulated in 786-O/R and ACHN/R cells. Second, data from colony formation and flow cytometry analysis showed that knockdown of circRNA_001895 suppressed cell proliferation and promoted cell apoptosis in 786-O/R and ACHN/R cells. Moreover, the protein expression of phosphorylated histone H2AX (γH2AX) was enhanced, while phosphorylated DNA-dependent protein kinase (p-DNA-PK) and Rad51 were reduced in 786-/R and ACHN/R by knockdown of circRNA_001895. Lastly, knockdown of circRNA_001895 conferred sensitivity of in vivo tumor growth to sunitinib. In conclusion, circRNA_001895 was implicated in the sunitinib resistance in RCC through regulation of apoptosis and DNA damage repair, suggesting that circRNA_001895 might be a potential therapeutic target for advanced RCC.

Construction and Characterization of n6-Methyladenosine-Related lncRNA Prognostic Signature and Immune Cell Infiltration in Kidney Renal Clear Cell Carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) lacks effective prognostic biomarkers and the role and mechanism of N6-methyladenosine (m6A) modification of long noncoding RNAs (lncRNAs) in KIRC remain unclear. Methods: We extracted standard mRNA-sequencing and clinical data from the TCGA database. The prognostic risk model was obtained by Lasso regression and Cox regression. We randomly divided the samples into training and test sets, each taking half of the cases. Based on Lasso regression and Cox regression for training set, the prognostic risk signature was constructed; risk scores were calculated with the R package "glmnet." Based on the median value of the prognostic risk score, risk scores were calculated for each patient and we divided all KIRC samples into high-risk and low-risk groups. Then, high- and low-risk subtypes were established and their prognosis, clinical features, and immune infiltration microenvironment were evaluated in test set and the entire sampled data set. The reliability of the prognostic model was confirmed by receiver operating characteristic curve analysis. Results: We found 28 prognostic m6A-related lncRNAs and established a m6A-related lncRNAs prognostic signature. Risk score=AC015813.1∗(0.0086)+EMX2OS∗(-0.0101)+LINC00173∗(0.0309)+PWAR5∗(-0.0146)+SNHG1∗(0.0043). The signature showed a better predictive ability than other clinical indicators, including tumor node metastasis classification (TNM), histological, and pathological stages. In the high-risk group, M0 macrophages, CD8+ T cells, and regulatory T cells had significantly higher scores. Contrarily, in the low-risk group, activated dendritic cells, M1 macrophages, mast resting cells, and monocytes had significantly higher scores. In the high-risk group, LSECtin was overexpressed. In the low-risk group, PD-L1 was overexpressed. Moreover, high-risk patients may benefit more from AZ628. Conclusions: In conclusion, prognosis prediction of patients with KIRC and new insights for immunotherapy are provided by the m6A-related lncRNA prognostic signature.

Metal-Cyclic Dinucleotide Nanomodulator-Stimulated STING Signaling for Strengthened Radioimmunotherapy of Large Tumor.

Combined treatment of immunotherapy and radiotherapy shows promising therapeutic effects for the regression of a variety of cancers. However, even multi-modality therapies often fail to antagonize the regression of large tumors due to the extremely immunosuppressive tumor microenvironment (TME). Here, a radioimmunotherapeutic paradigm based on stimulator of interferon genes (STING)-dependent signaling is applied to preclude large tumor progression by utilizing the metal-cyclic dinucleotide (CDN) nanoplatform, which integrates STING agonist c-di-AMP and immunomodulating microelement manganese (II) within the tannic acid nanostructure (TMA-NPs). As observed by magnetic resonance imaging, the localized administration of TMA-NPs effectively relieves hypoxia within TME and causes radical oxygen species overproduction and apoptosis in cancer cells after exposure to X-ray irradiation. The DNA fragments released from the apoptotic cells after the combined treatment augment the production of endogenous CDNs in cancer cells, hence significantly activating the STING-mediated pathway for stronger anti-tumor immunity. The localized therapy of TMA-NPs + X-ray not only inhibits the primary large tumor progression but also retards distant tumor growth by promoting dendritic cell maturation and activating cytotoxic immune cells whil suppressing immunosuppressive cells. Therefore, this work represents the combinatorial potency of TMA-NPs and X-rays on large tumor regression through strengthened STING-mediated radioimmunotherapeutics.

Interference With Redox Homeostasis Through a G6PD-Targeting Self-Assembled Hydrogel for the Enhancement of Sonodynamic Therapy in Breast Cancer.

Sonodynamics has emerged as a new potential therapy for breast cancer in recent years. However, GSH-mediated redox systems in cancer cells make them tolerable to oxidative stress-related therapy. Herein, in this study, with G6PD, the gatekeeper enzyme of the pentose phosphate pathway, as the regulative target, a self-assembled thermosensitive chitosan-pluronic hydrogel coloaded with ICG (sono-sensitive agent) and RRx-001 (IR@CPGel) was successfully prepared to enhance SDT through interference with redox homeostasis. Both in vitro and in vivo antitumor investigations verified that when integrated with sonodynamic therapy applied in breast cancer treatment, local administration of IR@CPgel could enhance ROS generation under LIFU irradiation and trigger the intrinsic apoptotic pathway of cancer cells, thus effectively inhibiting tumor growth in a safe manner. Moreover, RRx-001 may interfere with redox homeostasis in cancer cells by downregulating G6PD expression. Due to this redox imbalance, proapoptotic signals, such as P21 and P53, were enhanced, and metastasis-related signals, including MMP-2, ZEB1 and HIF-1α, were effectively reduced. Taken together, this work aimed to enhance the efficacy of sonodynamic therapy through local administration of self-assembled IR@CPGel to interfere with redox homeostasis and thus amplify the oxidative stress microenvironment in tumor tissues. In a word, this work provides a new strategy for the SDT enhancement in breast cancer therapy.

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy.

Intratumoral immunotherapeutic hydrogel administration is emerging as an effective method for inducing a durable and robust antitumor immune response. However, scaffold hydrogels that can synergize with the loaded drugs, thus potentiating therapeutic efficacy, are limited. Here, we report a ternary hydrogel composed of polyvinyl alcohol (PVA), polyethylenimine (PEI)‒a cationic polymer with potential immunoactivation effects, and magnesium ions‒a stimulator of the adaptive immune response, which exhibits an intrinsic immunomodulation function of reversing the immunologically "cold" phenotype of a murine breast tumor to a "hot" phenotype by upregulating PD-L1 expression and promoting M1-like macrophage polarization. PEI hydrogel (PEIGel) encapsulating an immune checkpoint blockade (ICB) inhibitor‒anti-PD-L1 antibody (α-PDL1) exhibits synergistic effects resulting in elimination of primary tumors and remote metastases and prevention of tumor relapse after surgical resection. A preliminary mechanistic study revealed a probably hidden role of PEI in modulating the polyamine metabolism/catabolism of tumors to potentiate the immune adjuvant effect. These results deepen our understanding of the innate immune activation function of PEI and pave the way for harnessing PEI as an immune adjuvant for ICB therapy.

A multifunctional nanotheranostic agent potentiates erlotinib to EGFR wild-type non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as Erlotinib, have demonstrated remarkable efficacy in the treatment of non-small cell lung cancer (NSCLC) patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type (wt) EGFR tumours has been shown to be marginal. Methods that can sensitize Erlotinib to EGFR wild-type NSCLC remain rare. Herein, we developed a multifunctional superparamagnetic nanotheranostic agent as a novel strategy to potentiate Erlotinib to EGFR-wt NSCLCs. Our results demonstrate that the nanoparticles can co-escort Erlotinib and a vascular epithermal growth factor (VEGF) inhibitor, Bevacizumab (Bev), to EGFR-wt tumours. The nanotheranostic agent exhibits remarkable effects as an inhibitor of EGFR-wt tumour growth. Moreover, Bev normalizes the tumour embedded vessels, further promoting the therapeutic efficacy of Erlotinib. In addition, the tumour engagement of the nanoparticles and the vascular normalization could be tracked by magnetic resonance imaging (MRI). Collectively, our study, for the first time, demonstrated that elaborated nanoparticles could be employed as a robust tool to potentiate Erlotinib to EGFR-wt NSCLC, paving the way for imaging-guided nanotheranostics for refractory NSCLCs expressing EGFR wild-type genes.

Pseudogene HSPB1P1 contributes to renal cell carcinoma proliferation and metastasis by targeting miR-296-5p to regulate HMGA1 expression.

With the aid of next-generation sequencing technology, pseudogenes have been widely recognized as functional regulators in the development and progression of certain diseases, especially cancer. Our present study aimed to investigate the functions and molecular mechanisms of HSPB1-associated protein 1 pseudogene 1 (HSPB1P1) in renal cell carcinoma (RCC). HSPB1P1 expression at the mRNA levels was determined by quantitative real-time polymerase chain reaction, and its clinical significance was assessed. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were detected by transwell assays. The location of HSPB1P1 in RCC cells was detected by subcellular distribution analysis. The direct relationship between HSPB1P1 and miR-296-5p/HMGA1 axis was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Our results identify the elevated expression of HSPB1P1 in RCC tissues and cell lines, which predicted advanced progression and poor prognosis in patients with RCC. Knockdown of HSPB1P1 suppressed cell proliferation, migration, and invasion, and reversed epithelial-mesenchymal transition process in RCC. HSPB1P1 was mostly enriched in the cytoplasm and functioned as a miRNA sponge for miR-296-5p and then regulated high-mobility group A1 expression. In conclusion, our study indicated that HSPB1P1 contributed to RCC progression by targeting the miR-296-5p/HMGA1 axis, and should be considered as a promising biomarker and therapeutic target for clinical applications.

Nomogram for accurate and quantitative prediction of the risk of psoriatic arthritis in Chinese adult patients with moderate and severe plaque psoriasis.

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory form of arthritis that appears approximately 7-10 years after psoriasis and remains undiagnosed in most of patients. Currently, only a few quantitative and succinct PsA-risk prediction models are available. OBJECTIVES: The aim of this study was to establish and validate a prediction model for quantitatively assessing the risk of PsA in moderate and severe plaque psoriasis patients. MATERIALS & METHODS: A non-interventional and cross-sectional study was conducted. Demographic, clinical, and laboratory records were collected and blindly reviewed. Logistic regression was used to develop this prediction model. With C-index and calibration curve, internal validation was performed. Five-fold cross validation, external validation and decision curve analysis (DCA) were also applied to assess this model. RESULTS: Among 405 patients, 111 patients had PsA. Arthralgia (OR = 39.346; 95% CI: 20.139-82.579), C-reactive protein (OR = 2.008; 95% CI: 1.051-3.838), lymphocyte level (OR = 0.341; 95% CI: 0.177-0.621), hypertension (OR = 0.235; 95% CI: 0.077-0.660) and disease duration (OR = 1.033; 95% CI: 0.998-1.071) were identified as potential predictors affecting the risk of transition from moderate and severe PsO to PsA. C-index for the prediction nomogram was 0.911 (95% CI: 0.879-0.943), and was confirmed to be 0.905 through 1000-time bootstrapping internal validation. Cross validation and external validation were preformed and proved the accuracy and generalizability of this prediction model. CONCLUSION: This study establishes a quantitative predictive nomogram with good predictive power for assessing the risk of PsA in patients with moderate and severe PsO.

Serum Uric Acid Concentrations and Risk of Adverse Outcomes in Patients With COVID-19.

Background: Although hyperuricemia frequently associates with respiratory diseases, patients with severe coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) can show marked hypouricemia. Previous studies on the association of serum uric acid with risk of adverse outcomes related to COVID-19 have produced contradictory results. The precise relationship between admission serum uric acid and adverse outcomes in hospitalized patients is unknown. Methods: Data of patients affected by laboratory-confirmed COVID-19 and admitted to Leishenshan Hospital were retrospectively analyzed. The primary outcome was composite and comprised events, such as intensive care unit (ICU) admission, mechanical ventilation, or mortality. Logistic regression analysis was performed to explore the association between serum concentrations of uric acid and the composite outcome, as well as each of its components. To determine the association between serum uric acid and in-hospital adverse outcomes, serum uric acid was also categorized by restricted cubic spline, and the 95% confidence interval (CI) was used to estimate odds ratios (OR). Results: The study cohort included 1854 patients (mean age, 58 years; 52% women). The overall mean ± SD of serum levels of uric acid was 308 ± 96 µmol/L. Among them, 95 patients were admitted to ICU, 75 patients received mechanical ventilation, and 38 died. In total, 114 patients reached composite end-points (have either ICU admission, mechanical ventilation or death) during hospitalization. Compared with a reference group with estimated baseline serum uric acid of 279-422 µmol/L, serum uric acid values ≥ 423 µmol/L were associated with an increased risk of composite outcome (OR, 2.60; 95% CI, 1.07- 6.29) and mechanical ventilation (OR, 3.01; 95% CI, 1.06- 8.51). Serum uric acid ≤ 278 µmol/L was associated with an increased risk of the composite outcome (OR, 2.07; 95% CI, 1.18- 3.65), ICU admission (OR, 2.18; 95% CI, 1.17- 4.05]), and mechanical ventilation (OR, 2.13; 95% CI, 1.06- 4.28), as assessed by multivariate analysis. Conclusions: This study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation.

A bibliometric analysis of international publication trends in premature ejaculation research (2008-2018).

The incidence of premature ejaculation (PE) has been on the rise over the years. Thus, significant research efforts have been directed toward understanding the pathogenesis and hence treatment of PE. Here, we performed a comprehensive analysis of the worldwide trends in research outputs in the field of PE. This study investigated the universal findings of previous PE studies and the trending issues surrounding the condition. We employed the Web of Science Core Collection for data collection. The Excel (2016) and CiteSpace IV were used for information analysis. The information was categorized using journal names, institutions, research frontiers, citation reports, regions/countries, and authors. A sum of 886 publications concerning PE between 2008 and 2018 were identified as of July 6, 2019. The highest number of publications was identified in the Journal of Sexual Medicine published. The United States of America (USA) had the highest number of publications and H-index value. The highest co-citations were from Waldinger MD. The most common keyword was 'drug treatment'. A steady pattern was observed for PE publications done between the period of 2008-2018. Thus, the USA is at the forefront of research on PE research. The interesting advanced research frontiers were drug treatment, circumcision, and sertraline.

In vivo tracking on longer retention of transplanted myocardin gene-modified adipose-derived stem cells to improve erectile dysfunction in diabetic rats.

BACKGROUND: Stem cell therapy has revealed a promising future for treating erectile dysfunction (ED), but the fate and curative mechanism of intracavernosal transplanted stem cells are under further exploration. This study aimed to demonstrate the effects of myocardin gene modification on improving erectile function and prolonging the retention of implanted adipose-derived stem cells (ASCs) using in vivo small animal imaging. METHODS: ASCs were isolated, cultured, and identified by flow cytometry and osteogenic and adipogenic induction. The effects of gene modification on cell proliferation, apoptosis, and contraction were determined by CCK-8, EdU, flow cytometry, and collagen gel lattice contraction assays as well as confocal microscopy. A total of 20 normal and 60 diabetes mellitus ED to (DMED) Sprague-Dawley rats were recruited to the 7 day and 21 day groups. Each group contained subgroups of 10 rats each: the negative control (NC), DMED + ASCs plus Ad-Luc-Myocardin, DMED + ASCs plus Ad-Luc, and DMED + phosphate buffer solution (PBS) groups. Erectile function was evaluated with the intracavernosal pressure/mean arterial pressure (△ICP/MAP) ratio. In vivo small animal imaging and an EdU cell tracking strategy were introduced to detect the transplanted ASCs, and IHC and WB were performed to assess smooth muscle cell protein levels. RESULTS: The ASCs expressed high CD29 and CD90 and scant CD45, while the multi-induction potential was verified by oil red O and alizarin red staining. Gene transfection of myocardin had no significant influence on ASC apoptosis but inhibited cell proliferation and promoted cell contraction. Myocardin combined with ASCs enhanced the therapeutic potential of ASCs for improving the △ICP/MAP ratio as well as α-SMA and calponin expression. In vivo imaging confirmed that ASCs resided within the cavernous body in 21 days, while only a few red EdU dots were detected. CONCLUSIONS: Myocardin induced ASC differentiation towards smooth muscle-like cells and enhanced the therapeutic potential of ASCs for ameliorating ED in STZ-induced diabetic rats. Notably, in vivo small animal tracking was an effective strategy for monitoring the implanted stem cells, and this strategy might have advantages over traditional EdU assays.

[Phenotypic modulation of bladder smooth muscle in diabetic rats].

OBJECTIVE: To investigate whether phenotypic modulation of bladder smooth muscle occurs in diabetic rats. METHODS: Thirty-two male SD rats were randomly assigned into diabetic group and control group. Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (60 mg/kg). Nine weeks later, the bladder tissues of the rats were examined for structural changes using HE and Masson's trichrome staining , and the expressions of myocardin, α-SMA, and SMMHC in bladder smooth muscles were detected with RT-PCR and Western blotting. RESULTS: Compared with the control group, the diabetic rats showed obvious polydipsia and polyuria with significantly increased collagenous fibers and lowered expressions of myocardin, α-SMA, and SMMHC in the bladder tissue (P<0.05). CONCLUSION: s In rats at 9 weeks after diabetic model establishment, phenotypic transition of the bladder smooth muscles occurs to cause bladder contractile dysfunction, which may play an important role in the pathology of diabetic bladder dysfunction.