TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis.

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity.

Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

Cytosolic mtDNA-cGAS-STING axis contributes to sepsis-induced acute kidney injury via activating the NLRP3 inflammasome.

BACKGROUND: NLRP3 inflammasome activation is significantly associated with sepsis-induced acute kidney injury (S-AKI). Cytosolic DNA derived from damaged mitochondria has been reported to activate NLRP3 inflammasome via upregulating the cyclic GMP-AMP synthase (cGAS)-the stimulator of interferon genes (STING) axis in nucleus pulposus cell and cardiomyocytes. However, the regulatory effect of mitochondria DNA (mtDNA)-cGAS-STING axis on the NLRP3 inflammasome in S-AKI remains unclear. METHODS: In the current study, we established an in vivo model of S-AKI by intraperitoneally injecting male C57BL/6 J mice with lipopolysaccharide (LPS). Next, selective cGAS inhibitor RU.521, and STING agonist DMXAA were intraperitoneally injected in the mice; then, blood urea nitrogen (BUN), serum creatinine (CRE), urinary kidney injury molecular-1 (KIM-1), pathological changes, and infiltrated neutrophils were detected to assess kidney injury. We also performed western blot and immunofluorescence assays to evaluate STING, cGAS, TBK-1, p-TBK-1, IRF3, p-IRF3, NF-kB, p-NF-kB, NLRP3, cleaved caspase-1, caspase-1, GSDMD-N, and GSDMD expression levels in kidney tissues. IL-18 and IL-1ß in renal tissue were identified by ELISA. In vitro, we treated HK-2 cells with LPS to establish a cell model of S-AKI. Furthermore, ethidium bromide (EtBr) was administered to deplete mitochondria DNA (mtDNA). LPS-induced cytotoxicity was evaluated by LDH release assay. Protein expression of cGAS, STING, and NLRP3 in was quantified by western blot. Cytosolic mtDNA was detected by immunofluorescence and q-PCR. Released IL-1ß and IL-18 in HK-2 supernatants were detected by ELISA. RESULTS: LPS injection induced S-AKI in mice, as evidenced by neutrophil infiltration, tubular vacuolation, and increased levels of serum creatinine (CRE), blood urea nitrogen (BUN), and urinary KIM-1. In addition, LPS activated the cGAS-STING axis and NLRP3 inflammasome in vivo, illustrated by increased phosphorylation levels of TBK-1, IRF3, and NF-kB protein, increased ratio of cleaved caspase-1 to caspase-1 and GSDMD-N to GSDMD, and increased IL-1ß and IL-18 levels. Moreover, the cGAS inhibitor RU.521 effectively attenuated NLRP3 inflammasome and S-AKI; however, these effects were abolished by treatment with the STING agonist DMXAA. Furthermore, cytosolic release of mtDNA and activation of the cGAS-STING-NLRP3 axis were observed in LPS-treated HK-2 cells. Inhibiting mtDNA replication by Ethidium Bromide (EtBr) treatment reduced cytosolic mtDNA accumulation and downregulated the cGAS-STING-NLRP3 axis, ameliorating the cytotoxicity induced by LPS. CONCLUSION: This study demonstrated that the cGAS-STING axis was triggered by cytosolic mtDNA and participated in the development of S-AKI by activating NLRP3 inflammasome. Reducing cytosolic mtDNA accumulation or inhibiting the cGAS-STING axis may be potential therapeutic targets for S-AKI.

A dynamic study of the postoperative management of thyroid cancer from 2003 to 2022: a bibliometric analysis.

Background: Over the past 20 years, the global incidence of thyroid cancer has continued to increase. The volume of literature on the postoperative management of thyroid cancer comprises 1,040 articles, from 64 countries, with 1,400 journals publishing the relevant literature, and several guidelines on the treatment of thyroid cancer. This study used bibliometric methods to identify research hotspots and explore future directions in this field. Methods: We comprehensively searched the Science Citation Index Expanded (SCI-E) database of the Web of Science Core Collection (WOSCC) for articles published from 2003 to 2022 on the postoperative management of thyroid cancer. Using CiteSpace 6.1.R6 and Microsoft Office Excel 2010, we evaluated and visualized the search results. Using R Studio, we generated a network of spatial geographic distribution maps and cooperative network. Results: A total of 1,040 publications were included in the study. The results revealed an overall upward trend in the number of publications and citations over the past 20 years. The United States of America (USA) had the largest number of publications and the highest centrality (n=282, centrality =0.28). Johns Hopkins University had highest centrality (centrality =0.15) and was the academic center of the field. Thyroid was the journal with the highest number of citations (n=826), and the American Journal of Surgical Pathology was the journal with the highest centrality (centrality =0.08). The top 10 citations in the literature were mainly guidelines and consensus statements on the management of thyroid cancer. A keyword-based clustering analysis revealed the prominence of clusters of keywords, such as follow-up, recurrent laryngeal nerve, and medullary thyroid carcinoma (MTC). A keyword burst detection analysis showed that the term papillary had the highest burst intensity (strength =8.02), while management guidelines, association guidelines, active surveillance (AS), microcarcinoma, and differentiated thyroid cancer were the current burst words. Conclusions: Over the past two decades, the number of relevant publications in the postoperative management of thyroid cancer field has continued to grow. Among the many research directions, follow-up, recurrent laryngeal nerve, and MTC are research hotspots. Future research is likely to revolve around guidelines and consensus statements on the management of thyroid cancer, AS, and microcarcinoma in differentiated thyroid cancer.

Construction and validation of a clinical prediction model for asymptomatic obstructive coronary stenosis in patients with carotid stenosis.

Background: Coronary artery stenosis occurs frequently in patients with carotid artery stenosis. We developed a clinical predictive model to investigate the clinical risk of asymptomatic obstructive coronary artery stenosis in patients with carotid artery stenosis ≥ 50%. Methods: From January 2018 to January 2022, carotid stenosis patients hospitalized at the First Affiliated Hospital of Zhengzhou University's Department of Endovascular Surgery were subjected to a retrospective analysis of their clinical information and imaging results. Excluded criteria were patients with lacking data, symptomatic coronary stenosis, prior coronary artery bypass grafting, and coronary stent implantation. Patients were separated into case and control groups according to whether or not they had obstructive coronary stenosis. Independent predictors were screened using univariate and multivariate logistic regression, and their accuracy was confirmed using least absolute shrinkage and selection operator (LASSO) regression. A Nomogram prediction model was developed using the aforementioned filtered factors. The model's discrimination and specificity were evaluated using the receiver operating characteristic curve (ROC) and Hosmer-Lemeshow goodness-of-fit test. Internal validation employed the Bootstrap procedure. The clinical decision curve analysis (DCA) of the prediction model was developed to assess the clinical applicability of the model. Results: The investigation included a total of 227 patients, of whom 132 (58.1%) had coronary artery stenosis. Hypertension, Grade I plaque, HbA1c ≥ 7.0%, MPV ≥ 9.2fl, and Fib ≥ 3.0 g/L were independent predictors, with OR values of (2.506, 0.219, 0.457, 1.876, 2.005), according to multivariate logistic regression. Risk factor screening and validation using lasso regression. The predictors chosen based on the optimal λ value are consistent with the predictors identified by multiple regression. The area under the ROC curve (AUC) of the model based on the above predictors was 0.701 (0.633-0.770), indicating that the model discriminated well. The calibration curve of the model closely matched the actual curve, and P > 0.05 in the Hosmer-Lemeshow goodness-of-fit test indicated the model's accuracy. The results of the DCA curve demonstrate the clinical applicability of the prediction model. Conclusion: Hypertension, grade I plaque, HbA1c ≥ 7.0%, MPV ≥ 9.2 fl, and Fib ≥ 3.0 g/L are predictors of asymptomatic coronary stenosis in patients with carotid stenosis ≥50%. The diagnostic model is clinically applicable and useful for identifying patients at high risk.

Quantifying effects of cold acclimation and delayed springtime photosynthesis resumption in northern ecosystems.

Land carbon dynamics in temperate and boreal ecosystems are sensitive to environmental change. Accurately simulating gross primary productivity (GPP) and its seasonality is key for reliable carbon cycle projections. However, significant biases have been found in early spring GPP simulations of northern forests, where observations often suggest a later resumption of photosynthetic activity than predicted by models. Here, we used eddy covariance-based GPP estimates from 39 forest sites that differ by their climate and dominant plant functional types. We used a mechanistic and an empirical light use efficiency (LUE) model to investigate the magnitude and environmental controls of delayed springtime photosynthesis resumption (DSPR) across sites. We found DSPR reduced ecosystem LUE by 30-70% at many, but not all site-years during spring. A significant depression of LUE was found not only in coniferous but also at deciduous forests and was related to combined high radiation and low minimum temperatures. By embedding cold-acclimation effects on LUE that considers the delayed effects of minimum temperatures, initial model bias in simulated springtime GPP was effectively resolved. This provides an approach to improve GPP estimates by considering physiological acclimation and enables more reliable simulations of photosynthesis in northern forests and projections in a warming climate.

Resveratrol­mediated activation of SIRT1 inhibits the PERK­eIF2α­ATF4 pathway and mitigates bupivacaine­induced neurotoxicity in PC12 cells.

Endoplasmic reticulum (ER) stress and apoptosis play significant roles in the development of neurotoxicity caused by bupivacaine (BUP). By activating sirtuin 1 (SIRT1), resveratrol (RSV) can regulate various cellular processes associated with anti-oxidative stress, anti-apoptosis and anti-inflammatory responses, thereby exerting neuroprotective effects. However, it remains unknown whether the activation of SIRT1 by RSV is able to attenuate BUP-induced ER stress and apoptosis. Therefore, the present study aimed to explore the effect of RSV on BUP-induced cytotoxicity in PC12 cells and the underlying mechanism. Cell Counting Kit-8 assays, flow cytometry and inverted phase-contrast microscopy were used to assess the viability, apoptosis rate and morphological changes of the cells, respectively. Western blotting and immunofluorescence staining were used to analyze the levels of SIRT1, the apoptosis-related proteins Bax, Bcl-2 and cleaved caspase-3, the ER stress-related proteins glucose-regulated protein 78, caspase-12 and CHOP, and the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2 α (eIF2α)-activating transcription factor 4 (ATF4) pathway-associated proteins phosphorylated (p)-PERK, PERK, p-eIF2α, eIF2α and ATF4. The results revealed that BUP induced cell apoptosis and decreased cell viability, accompanied by the downregulation of SIRT1. However, RSV restored SIRT1 protein expression, downregulated the expression of the pro-apoptotic protein Bax, upregulated the expression of the anti-apoptotic protein Bcl-2, decreased the apoptosis rate of the cells and increased cell viability. Furthermore, the anti-apoptotic effects exhibited by RSV were associated with inhibition of the PERK-eIF2α-ATF4 pathway of ER stress. However, the protective effect of RSV was significantly mitigated by the SIRT1 inhibitor EX527. These results indicate that the activation of SIRT1 by RSV alleviates BUP-induced PC12 cell ER stress and apoptosis via regulation of the PERK-eIF2α-ATF4 pathway. These findings offer insights into the molecular mechanism underlying BUP-induced apoptosis and suggest the potential of RSV as a therapeutic agent against the neurotoxicity caused by BUP.

Neglected Adult Tinea Capitis in South China: A Retrospective Study in Nanchang, Jiangxi Province, from 2007 to 2021.

Tinea capitis (TC) in adults is much less frequently diagnosed in comparison to TC in children. In this study, we explored retrospectively adult TC in a specialized dermatology hospital, located in South China, during the years 2007-2021. Among 1037 TC cases, 168 (16.2%) patients were older than 18 years. The majority of adults with TC, 77.38% (130/168), were older than 40, with a peak in the age of 51-60 years (40/168, 23.81%). Before presenting at our hospital, many of patients did not got proper treatment due to misdiagnosis or simply did not consulted an appropriate clinic. 60.71% (102/168) of the patients reported symptoms lasting for more than 1 year and 29.76% (50/168) reported chronic scalp problems of at least 10 years. And 27.38% (46/168) of the patients had an immunocompromised status, including long-term use of corticosteroids shampoo, type 2 diabetes mellitus (DM), psoriasis vulgaris, rheumatoid arthritis, systemic lupus erythematosus or bullous pemphigoid. As for clinical presentation, 87.5% (147/168) of the cases presented as black dot type of TC and anthropophilic dermatophytes were the predominant etiology, with Trichophyton violaceum (126), T. tonsurans (15), T. rubrum (8) and T. shoenleinii (6). Grey patch type of TC (3.57%, 6/168) was seldom in Jiangxi Province and zoophilic/geophilic dermatophytes were rare. Our study indicates that anthropophilic Trichophyton species can cause long-lasting TC in adults. Not in all cases, the manifestation had symptom clearly indicating a dermatophyte-related TC. Thus, patients with long-lasting scalp inflammation, also older ones, should be examined for the presence of dermatophyte-related TC.

Ferrostatin-1 ameliorates Bupivacaine-Induced spinal neurotoxicity in rats by inhibiting ferroptosis.

Bupivacaine (BUP) has previously been shown to trigger neurotoxicity after spinal anesthesia. Further, ferroptosis has been implicated in the pathological processes associated with various central nervous system diseases. Although the impact of ferroptosis on BUP-induced neurotoxicity in the spinal cord has not been fully understood, this research aims to investigate this relationship in rats. Additionally, this study aims to determine whether ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, can provide protection against BUP-induced spinal neurotoxicity. The experimental model for BUP-induced spinal neurotoxicity involved the administration of 5% bupivacaine through intrathecal injection. Then, the rats were randomized into the Control, BUP, BUP + Fer-1, and Fer-1 groups. BBB scores, %MPE of TFL, and H&E and Nissl stainings showed that intrathecal Fer-1 administration improved functional recovery, histological outcomes, and neural survival in BUP-treated rats. Moreover, Fer-1 has been found to alleviate the BUP-induced alterations related to ferroptosis, such as mitochondrial shrinkage and disruption of cristae, while also reducing the levels of malondialdehyde (MDA), iron, and 4-hydroxynonenal (4HNE). Fer-1 also inhibits the accumulation of reactive oxygen species (ROS) and restores the normal levels of glutathione peroxidase 4 (GPX4), cystine/glutamate transporter (xCT), and glutathione (GSH). Furthermore, double-immunofluorescence staining revealed that GPX4 is primarily localized in the neurons instead of microglia or astroglia in the spinal cord. In summary, we demonstrated that ferroptosis play a pivotal role in mediating BUP-induced spinal neurotoxicity, and Fer-1 ameliorated BUP-induced spinal neurotoxicity by reversing the underlying ferroptosis-related changes in rats.

Resveratrol Suppresses Bupivacaine-Induced Spinal Neurotoxicity in Rats by Inhibiting Endoplasmic Reticulum Stress via SIRT1 Modulation.

Bupivacaine (BUP) may cause neurotoxic effects after spinal anesthesia. Resveratrol (RSV), a natural agonist of Silent information regulator 1 (SIRT1), protects various tissues and organs from damage by regulating endoplasmic reticulum (ER) stress. The aim of this study is to explore whether RSV could alleviate the neurotoxicity induced by bupivacaine via regulating ER stress. We established a model of bupivacaine-induced spinal neurotoxicity in rats using intrathecal injection of 5% bupivacaine. The protective effect of RSV was evaluated by injecting intrathecally with 30 µg/µL RSV in total of 10 µL per day for 4 consecutive days. On day 3 after bupivacaine administration, tail-flick latency (TFL) tests and the Basso, Beattie, and Bresnahan (BBB) locomotor scores were assessed to neurological function, and the lumbar enlargement of the spinal cord was obtained. H&E and Nissl staining were used to evaluate the histomorphological changes and the number of survival neurons. TUNEL staining was conducted to determine apoptotic cells. The expression of proteins was detected by IHC, immunofluorescence, and western blot. The mRNA level of SIRT1 was determined by RT-PCR. Bupivacaine caused spinal cord neurotoxicity by inducing cell apoptosis and triggering ER stress. RSV treatment promoted the recovery of neurological dysfunction after bupivacaine administration by suppressing neuronal apoptosis and ER stress. Furthermore, RSV upregulated SIRT1 expression and inhibited PERK signaling pathway activation. In summary, resveratrol suppresses bupivacaine-induced spinal neurotoxicity in rats by inhibiting endoplasmic reticulum stress via SIRT1 modulation.

Monitoring nature's calendar from space: Emerging topics in land surface phenology and associated opportunities for science applications.

Vegetation phenology has been viewed as the nature's calendar and an integrative indicator of plant-climate interactions. The correct representation of vegetation phenology is important for models to accurately simulate the exchange of carbon, water, and energy between the vegetated land surface and the atmosphere. Remote sensing has advanced the monitoring of vegetation phenology by providing spatially and temporally continuous data that together with conventional ground observations offers a unique contribution to our knowledge about the environmental impact on ecosystems as well as the ecological adaptations and feedback to global climate change. Land surface phenology (LSP) is defined as the use of satellites to monitor seasonal dynamics in vegetated land surfaces and to estimate phenological transition dates. LSP, as an interdisciplinary subject among remote sensing, ecology, and biometeorology, has undergone rapid development over the past few decades. Recent advances in sensor technologies, as well as data fusion techniques, have enabled novel phenology retrieval algorithms that refine phenology details at even higher spatiotemporal resolutions, providing new insights into ecosystem dynamics. As such, here we summarize the recent advances in LSP and the associated opportunities for science applications. We focus on the remaining challenges, promising techniques, and emerging topics that together we believe will truly form the very frontier of the global LSP research field.

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19.

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

Melatonin ameliorates bupivacaine-induced spinal neurotoxicity in rats by suppressing neuronal NLRP3 inflammasome activation.

Bupivacaine is a common local anesthetic that causes neurotoxicity when used at clinical concentrations. Melatonin (MT), is a potent neuroprotective molecule. The study aimed to characterize the neuroprotective effects of MT on spinal neurotoxicity induced by bupivacaine in rats. It showed that bupivacaine, by intrathecal injection, induced spinal injury, and that the protein levels of Nod-like receptor protein 3 (NLRP3), cleaved caspase-1, and the N-terminal region of gasdermin D (GSDMD-N) were significantly increased. NLRP3 was expressed mainly in neurons and microglia. MT treatment ameliorated bupivacaine-induced spinal cord injury in rats by suppressing activation of neuronal NLRP3 inflammasomes.

Knowledge domain and emerging trends in beta-cell research: A bibliometric and knowledge-map analysis.

Background: Up to now, the physiology, pathology, and recovery of beta-cells have been intensively studied and made great progress, and these are of major significance for the treatment of related diseases. Nevertheless, a comprehensive and objective report on the status of beta-cell research is lacking. Therefore, this study aims to conduct a bibliometric analysis to quantify and identify the current status and trending issues in beta-cell research. Methods: The articles and reviews related to beta-cell were obtained from the Web of Science Core Collection on August 31, 2022. Two scientometric software (CiteSpace 6.1.R3 and VOSviewer 1.6.18) were used to perform bibliometric and knowledge-map analysis. Results: A total of 4098 papers were published in 810 academic journals in 2938 institutions from 83 countries/regions. The number of beta-cell-related publications was increasing steadily. The United States was the most productive country, while Universite libre de Bruxelles, University of Toronto and University of Geneva were the most active institutions. Diabetes published the most beta-cell studies and received the largest number of co-citations. Decio I Eizirik published the most papers and had the most co-citations. Twelve references on reviews and mechanisms were regarded as the knowledge base. Four major aspects of beta-cell research included the pathological mechanism of beta-cell failure, the recovery of beta cells, the risk factor related to beta cells, and the physiology of beta cells. Endoplasmic reticulum stress and oxidative stress have been core elements throughout the research in this field. In addition, beta-cell dedifferentiation, inflammation, autophagy, miRNA, and lncRNA are hot topics nowadays. Additionally, stem cell replacement therapies might be the alternative way to reverse beta-cell failure. Restoring beta-cell mass and function will remain a research goal in the future. Conclusion: This study provided a comprehensive overview of beta-cell research through bibliometric and visual methods. The information would provide helpful references for scholars focusing on beta cells.

Standardization of critical care management of non-critically ill patients with COVID-19.

The large global outbreak of coronavirus disease 2019 (COVID-19) has seriously endangered the health care system in China and globally. The sudden surge of patients with severe acute respiratory syndrome coronavirus 2 infection has revealed the shortage of critical care medicine resources and intensivists. Currently, the management of non-critically ill patients with COVID-19 is performed mostly by non-intensive care unit (ICU) physicians, who lack the required professional knowledge, training, and practice in critical care medicine, especially in terms of continuous monitoring of the respiratory function, intervention, and feedback on treatment effects. This clinical problem needs an urgent solution. Therefore, here, we propose a series of clinical strategies for non-ICU physicians aimed at the standardization of the management of non-critically ill patients with COVID-19 from the perspective of critical care medicine. Isolation management is performed to facilitate the implementation of hierarchical monitoring and intervention to ensure the reasonable distribution of scarce critical care medical resources and intensivists, highlight the key patients, timely detection of disease progression, and early and appropriate intervention and organ function support, and thus improve the prognosis. Different management objectives are also set based on the high-risk factors and the severity of patients with COVID-19. The approaches suggested herein will facilitate the timely detection of disease progression, and thus ensure the provision of early and appropriate intervention and organ function support, which will eventually improve the prognosis.

Decreased T Cell Levels in Critically Ill Coronavirus Patients: Single-Center, Prospective and Observational Study.

BACKGROUND: Since Dec. 2019, the COVID-19 pandemic has been an outbreak. T cells play an important role in dealing with various disease-causing pathogens. However, the role of T cells played in COVID-19 patients is still unknown. Our study aimed to describe the immunologic state of the critically ill COVID-19 patients. METHODS: A total of 63 patients with confirmed COVID-19 pneumonia were admitted to the Department of Intensive Care Unit of the First Affiliated Hospital of Harbin Medical University. The immunologic characteristics (lymphocyte apoptosis, the expression of PD-1 and HLA-DR in T cells, T cell subset levels, redistribution and the production of inflammatory factors) as well as their laboratory parameters were compared between severe group and critical group. RESULTS: The level of T cells in peripheral blood was decreased in critical patients compared with that in severe patients, but the expression levels of PD-1 (CD4+: 24.71% VS 30.56%; CD8+: 33.05% VS 32.38%) and HLA-DR (T cells: 36.28% VS 27.44%; monocytes: 20.58% VS 23.83%) in T cells were not significantly changed, and apoptosis and necrosis were not different in lymphocytes (apoptosis: 1.04% VS 1.27%; necrosis: 0.67% VS 1.11%), granulocytes, or monocytes between those two groups. CONCLUSION: There is severe immunosuppression in critically ill COVID-19 patients. Redistribution of T cells might be the main reason for lymphocytic decline. Decreasing the infiltration of T lymphocytes in the lung may be beneficial for the treatment of COVID-19.

Cytokine Storm May Not Be the Chief Culprit for the Deterioration of COVID-19.

COVID-19 is spreading and ravaging all over the world, and the number of deaths is increasing day by day without downward trend. However, there is limited knowledge of pathogenesis on the deterioration of COVID-19 at present. In this study we aim to determine whether cytokine storm is really the chief culprit for the deterioration of COVID-19. The confirmed COVID-19 patients were divided into moderate group (n = 89), severe group (n = 37), and critical group (n = 41). Demographic data were collected and recorded on admission to ICU. Clinical data were obtained when moderate, severe, or critical COVID-19 was diagnosed, and then compared between groups. The proportion of enrolled COVID-19 patients was slightly higher among males (52.5%) than females (47.5%), with an average age of 64.87 years. The number of patients without comorbidities exceed one third (36.1%), and patients with 1, 2, 3, 4 kinds of comorbidities accounted for 23.0%, 23.0%, 13.1%, and 4.9%, respectively. IL-6, IL-10, TNF, and IFN-γ, including oxygenation index, sequential organ failure assessment score, white blood cell count, lymphocyte count, lymphocyte percentage, platelet, C-reaction protein, lactate dehydrogenase, creatine kinase isoenzyme, albumin, D-Dimer, and fibrinogen showed significant difference between groups. Some, but not all, cytokines and chemokines were involved in the deterioration of COVID-19, and thus cytokine storm maybe just the tip of the iceberg and should be used with caution to explain pathogenesis on the deterioration of COVID-19, which might be complex and related to inflammation, immunity, blood coagulation, and multiple organ functions. Future studies should focus on identification of specific signaling pathways and mechanisms after severe acute respiratory syndrome coronavirus 2 infections (IRB number: IRB-AF/SC-04/01.0).