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Abstract Objective Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC. Methods Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray’s competing risk model was utilized to evaluate the risk factors contributing to CVM. Results Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54–1.86, p

Abstract Background Currently, culture methods are commonly used in clinical tests to detect pathogenic fungi including Candida spp. Nonetheless, these methods are cumbersome and time-consuming, thereby leading to considerable difficulties in diagnosis of pathogenic fungal infections, especially in situations that respiratory samples such as alveolar lavage fluid and pleural fluid contain extremely small amounts of microorganisms. The aim of this study was to elucidate the utility and practicality of microfluidic chip technology in quick detection of respiratory pathogenic fungi. Methods DNAs of clinical samples (mainly derived from sputa, alveolar lavage fluid, and pleural fluid) from 64 coastal patients were quickly detected using microfluidic chip technology with 20 species of fungal spectrum and then validated by Real-time qPCR, and their clinical baseline data were analyzed. Results Microfluidic chip results showed that 36 cases infected with Candida spp. and 27 cases tested negative for fungi, which was consistent with Real-time qPCR validation. In contrast, only 16 cases of fungal infections were detected by the culture method; however, one of the culture-positive samples tested negative by microfluidic chip and qPCR validation. Moreover, we found that the patients with Candida infections had significantly higher rates of platelet count reduction than fungi-negative controls. When compared with the patients infected with C. albicans alone, the proportion of males in the patients co-infected with multiple Candidas significantly increased, while their platelet counts significantly decreased. Conclusions These findings suggest that constant temperature amplification-based microfluidic chip technology combined with routine blood tests can increase the detection speed and accuracy (including sensitivity and specificity) of identifying respiratory pathogenic fungi.

Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.

Abstract Background Utilizing the traditional Cox regression model to identify the factors affecting the risk of mortality due to microinvasive cutaneous squamous cell carcinoma (micSCC) may produce skewed results. Since cause-specific mortality can guide clinical decision-making, this study employed the Fine-Gray model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify significant predictive variables for the risk of micSCC-related mortality. Methods This study used the information of patients with micSCC who were listed in the SEER database during 2000–2015. Cox regression and Fine-Gray models were utilized for the multivariable analysis, and Gray’s test and the cumulative incidence function were used for the univariable analyses. Results There were 100 patients who died from other reasons and 38 who died from micSCC among the 1259 qualified patients with micSCC. Most were female, white, married, had localized metastasis, etc. According to the univariable Gray’s test (P

BackgroundThere are few research findings on the survival prognosis of spindle cell melanoma (SCM), which is an unusual kind of melanoma. The purpose of this study was to develop a thorough nomogram for predicting the overall survival (OS) of patients with SCM and to assess its validity by comparing it with the conventional American Joint Committee on Cancer (AJCC) staging system.MethodsThe Surveillance, Epidemiology, and End Results database was searched, and 2,015 patients with SCM were selected for the analysis. The patients were randomly divided into training (n = 1,410) and validation (n = 605) cohorts by using R software. Multivariate Cox regression was performed to identify predictive factors. A nomogram was established based on these characteristics to predict OS in SCM. The calibration curve, concordance index (C-index), area under the receiver operating characteristic curve, and decision-curve analysis were utilized to assess the accuracy and reliability of the model. The net reclassification improvement and integrated discrimination improvement were also applied in this model to evaluate its differences with the AJCC model.ResultsThe developed nomogram suggests that race, AJCC stage, chemotherapy status, regional node examination status, marital status, and sex have the greatest effects on OS in SCM. The nomogram had a higher C-index than the AJCC staging system (0.751 versus 0.633 in the training cohort and 0.747 versus 0.650 in the validation cohort). Calibration plots illustrated that the model was capable of being calibrated. These criteria demonstrated that the nomogram outperforms the AJCC staging system alone.ConclusionThe nomogram developed in this study is sufficiently reliable for forecasting the risk and prognosis of SCM, which may facilitate personalized treatment recommendations in upcoming clinical trials.

Abstract Background For the purpose to examine lower limb melanoma (LLM) and its long-term survival rate, we used data from the Surveillance, Epidemiology and End Results (SEER) database. To estimate the prognosis of LLM patients and assess its efficacy, we used a powerful deep learning and neural network approach called DeepSurv. Methods We gathered data on those who had an LLM diagnosis between 2000 and 2019 from the SEER database. We divided the people into training and testing cohorts at a 7:3 ratio using a random selection technique. To assess the likelihood that LLM patients would survive, we compared the results of the DeepSurv model with those of the Cox proportional-hazards (CoxPH) model. Calibration curves, the time-dependent area under the receiver operating characteristic curve (AUC), and the concordance index (C-index) were all used to assess how accurate the predictions were. Results In this study, a total of 26,243 LLM patients were enrolled, with 7873 serving as the testing cohort and 18,370 as the training cohort. Significant correlations with age, gender, AJCC stage, chemotherapy status, surgery status, regional lymph node removal and the survival outcomes of LLM patients were found by the CoxPH model. The CoxPH model’s C-index was 0.766, which signifies a good degree of predicted accuracy. Additionally, we created the DeepSurv model using the training cohort data, which had a higher C-index of 0.852. In addition to calculating the 3-, 5-, and 8-year AUC values, the predictive performance of both models was evaluated. The equivalent AUC values for the CoxPH model were 0.795, 0.767, and 0.847, respectively. The DeepSurv model, in comparison, had better AUC values of 0.872, 0.858, and 0.847. In comparison to the CoxPH model, the DeepSurv model demonstrated greater prediction performance for LLM patients, as shown by the AUC values and the calibration curve. Conclusion We created the DeepSurv model using LLM patient data from the SEER database, which performed better than the CoxPH model in predicting the survival time of LLM patients.

BackgroundThe survival and prognosis of patients are significantly threatened by cutaneous melanoma (CM), which is a highly aggressive disease. It is therefore crucial to determine the most recent survival rate of CM. This study used population-based cancer registry data to examine the 5-year relative survival rate of CM in the US.MethodsPeriod analysis was used to assess the relative survival rate and trends of patients with CM in the Surveillance, Epidemiology, and End Results (SEER) database during 2004–2018. And based on the data stratified by age, gender, race and subtype in the SEER database, a generalized linear model was 12established to predict the 5-year relative survival rate of CM patients from 2019 to 2023.ResultsThe 5-year relative survival increased to various degrees for both total CM and CM subtypes during the observation period. The improvement was greatest for amelanotic melanoma, increasing from 69.0% to 81.5%. The 5-year overall relative survival rates of CM were 92.9%, 93.5%, and 95.6% for 2004–2008, 2009–2013, and 2014–2018, respectively. Females had a marginally higher survival rate than males for almost all subtypes, older people had lower survival rates than younger people, white patients had higher survival rates than nonwhite ones, and urban locations had higher rates of survival from CM than rural locations did. The survival rate of CM was significantly lower for distant metastasis.ConclusionThe survival rate of patients with CM gradually improved overall during 2004–2018. With the predicted survival rate of 96.7% for 2019–2023, this trend will still be present. Assessing the changes experienced by patients with CM over the previous 15 years can help in predicting the future course of CM. It also provides a scientific foundation that associated departments can use to develop efficient tumor prevention and control strategies.

AbstractBackground To investigate the effects of low-dose furosemide and aminophylline on the renal function in patients with septic shock.Methods and Results A total of 109 eligible septic shock patients in the intensive care unit were randomly divided into a control group (n = 55) and an intervention group (n = 54). The control group received normal saline, and the intervention group received low-dose furosemide (0.048 mg/kg.h−1) with aminophylline (0.3 mg/kg.h−1). The primary outcomes included the levels of serum creatinine (Scr), creatinine clearance rate (Ccr), blood urea nitrogen (BUN), glomerular filtration rate (GFR), and urine output on admission and on days 3, 7 and 14. The secondary outcomes were the sequential organ failure assessment (SOFA) scores, continuous renal replacement therapy (CRRT) time and intensive care unit (ICU) mortality, hospital mortality and 28-day mortality. There were no significant differences in the levels of Scr, Ccr, BUN, or GFR between the two groups, while the urine output was higher in the intervention group on days 3, 7, and 14. Compared with the control group, the SOFA scores, ICU mortality, hospital mortality and 28-day mortality were significantly lower in the intervention group on days 3, 7, and 14, the CRRT time was shorter, and the cumulative fluid balance was lower on days 3 and 7 in the intervention group.Conclusions Although low-dose furosemide and aminophylline have fewer protective effects on the renal function in septic shock patients, they could reduce the CRRT time and improve the prognosis.

Abstract Introduction Early diagnosis and potential therapeutic targets of sepsis-induced cardiomyopathy (SIC) remain challenges clinically. Circulating extracellular vesicles from immune cells carrying crucial injurious mediators, including miRNAs in sepsis. However, the impacts of neutrophil-derived extracellular vesicles and their miRNAs in the SIC development are unknown. Objectives The present study focused on the in-depth miRNA expression profiles of neutrophil-derived extracellular vesicles and explored the potential molecular biomarkers during the process of SIC. Methods Neutrophil-derived extracellular vesicles were isolated from the blood samples in three sepsis patients with or without cardiomyopathy on day 1 and day 3 after ICU admission in comparison with three healthy controls. miRNAs were determined by RNA sequencing. The closely related differentially expressed miRNAs with SIC were further validated through qRT-PCR in the other cohorts of sepsis patients with (30 patients) or without cardiomyopathy (20 patients) and the association between miRNAs and the occurrence or disease severity of septic cardiomyopathy were stratified with logistic regression analysis. Results Sixty-eight miRNAs from neutrophil-derived extracellular vesicles were changed significantly between healthy controls and without septic cardiomyopathy patients (61 miRNAs upregulated and seven downregulated). Thirty-eight miRNAs were differentially expressed in the septic cardiomyopathy patients. 27 common differentially expressed miRNAs were found in both groups with similar kinetics (23 miRNAs upregulated and four downregulated). The enriched cellular signaling pathway mediated by miRNAs from sepsis to septic cardiomyopathy was the HIF-1 signaling system modulated septic inflammation. Using multivariate logistic regression analysis, miR-150-5p coupled with NT-pro BNP, LVEF, and SOFA score (AUC = 0.941) were found to be the independent predictors of septic cardiomyopathy. Conclusion miRNAs derived from neutrophil-derived extracellular vesicles play an important role in septic disease severity development towards cardiomyopathy. miR-150-5p may be a predictor of sepsis severity development but warrants further study.

Summary: Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1β from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.

ObjectiveThe purpose of this study was to develop a comprehensive nomogram for the cancer-specific survival (CSS) of white patients with invasive melanoma at back, posterior arm, posterior neck, and posterior scalp (BANS) sites and to determine the validity of the nomogram by comparing it with the conventional American Joint Committee on Cancer (AJCC) staging system.MethodsThis study analyzed the patients with invasive melanoma in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divide the patients into training and validation cohorts at a ratio of 7:3. Multivariable Cox regression was used to identify predictive variables. The new survival nomogram was compared with the AJCC prognosis model using the concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), net reclassification index (NRI), integrated discrimination index (IDI), calibration plotting, and decision-curve analysis (DCA).ResultsA novel nomogram was established to determine the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma. According to the nomogram, the Age at Diagnosis had the greatest influence on CSS in invasive melanoma, followed by Bone Metastasis, AJCC, Stage, Liver Metastasis, Histologic Subtype, Brain Metastasis, Ulceration, and Primary Site. The nomogram had a higher C-index than the AJCC staging system in both the training (0.850 versus 0.799) and validation (0.829 versus 0.783) cohorts. Calibration plotting demonstrated that the model had good calibration ability. The nomogram outperformed the AJCC staging system in terms of AUC, NRI, IDI, and DCA.ConclusionThis was the first study to develop and evaluate a comprehensive nomogram for the CSS of white patients with invasive melanoma at BANS sites using the SEER database. The novel nomogram can assist clinical staff in predicting the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma more accurately than can the AJCC staging system.

BackgroundThis study obtained data on patients with cutaneous malignant melanoma (CMM) from the Surveillance, Epidemiology, and End Results (SEER) database, and used a deep learning and neural network (DeepSurv) model to predict the survival rate of patients with CMM and evaluate its effectiveness.MethodsWe collected information on patients with CMM between 2004 and 2015 from the SEER database. We then randomly divided the patients into training and testing cohorts at a 7:3 ratio. The likelihood that patients with CMM will survive was forecasted using the DeepSurv model, and its results were compared with those of the Cox proportional-hazards (CoxPH) model. The calibration curves, time-dependent area under the receiver operating characteristic curve (AUC), and concordance index (C-index) were used to assess the prediction abilities of the model.ResultsThis study comprised 37,758 patients with CMM: 26,430 in the training cohort and 11,329 in the testing cohort. The CoxPH model demonstrated that the survival of patients with CMM was significantly influenced by age, sex, marital status, summary stage, surgery, radiotherapy, chemotherapy, postoperative lymph node dissection, tumor size, and tumor extension. The C-index of the CoxPH model was 0.875. We also constructed the DeepSurv model using the data from the training cohort, and its C-index was 0.910. We examined how well the aforementioned two models predicted outcomes. The 1-, 3-, and 5-year AUCs were 0.928, 0.837, and 0.855, respectively, for the CoxPH model, and 0.971, 0.947, and 0.942 for the DeepSurv model. The DeepSurv model presented a greater predictive effect on patients with CMM, and its reliability was better than that of the CoxPH model according to both the AUC value and the calibration curve.ConclusionThe DeepSurv model, which we developed based on the data of patients with CMM in the SEER database, was found to be more effective than the CoxPH model in predicting the survival time of patients with CMM.

BackgroundThe aim of this study was to establish and verify a predictive nomogram for patients with cutaneous verrucous carcinoma (CVC) who will eventually survive and to determine the accuracy of the nomogram relative to the conventional American Joint Committee on Cancer (AJCC) staging system.MethodsAssessments were performed on 1125 patients with CVC between 2004 and 2015, and the results of those examinations were recorded in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided at a ratio of 7:3 into the training (n = 787) and validation (n = 338) cohorts. Predictors were identified using stepwise regression analysis in the COX regression model for create a nomogram to predict overall survival of CVC patients at 3-, 5-, and 8-years post-diagnosis. We compared the performance of our model with that of the AJCC prognosis model using several evaluation metrics, including C-index, NRI, IDI, AUC, calibration plots, and DCAs.ResultsMultivariate risk factors including sex, age at diagnosis, marital status, AJCC stage, radiation status, and surgery status were employed to determine the overall survival (OS) rate (P 0.7) revealed that the nomogram exhibited significant discriminative ability. The statistically significant NRI and IDI values at 3-, 5-, and 8-year predictions for overall survival (OS) in the validation cohort (55.72%, 63.71%, and 78.23%, respectively and 13.65%, 20.52%, and 23.73%, respectively) demonstrate that the established nomogram outperforms the AJCC staging system (P < 0.01) in predicting OS for patients with cutaneous verrucous carcinoma (CVC). The calibration plots indicate good performance of the nomogram, while decision curve analyses (DCAs) show that the predictive model could have a favorable clinical impact.ConclusionThis study constructed and validated a nomogram for predicting the prognosis of patients with CVC in the SEER database and assessed it using several variables. This nomogram model can assist clinical staff in making more-accurate predictions than the AJCC staging method about the 3-, 5-, and 8-year OS probabilities of patients with CVC.

Abstract Background Central venous catheter (CVC) insertion complications are a prevalent and important problem in the intensive care unit (ICU), and source control by immediate catheter removal is considered urgent in patients with septic shock suspected to be caused by catheter-related bloodstream infection (CRBSI). We sought to determine the impact of immediate reinsertion of a new catheter (IRINC) on mortality among patients after CVC removal for suspected CRBSI. Methods A propensity score-matched cohort of patients with suspected CRBSI who underwent IRINC or no IRINC in a 32-bed ICU in a university hospital in China from January 2009 through April 2021. Catheter tip culture and clinical symptoms were used to identify patients with suspected CRBSI. The Kaplan–Meier method was used to analyse 30-day mortality before and after propensity score matching, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality in the matched cohort were estimated with Cox proportional hazards models. Results In total, 1,238 patients who had a CVC removed due to suspected CRBSI were identified. Among these patients, 877 (70.8%) underwent IRINC, and 361 (29.2%) did not. Among 682 propensity score-matched patients, IRINC was associated with an increased risk of 30-day mortality (HR, 1.481; 95% CI, 1.028 to 2.134) after multivariable, multilevel adjustment. Kaplan–Meier analysis found that IRINC was associated with the risk of mortality both before matching (P = 0.00096) and after matching (P = 0.018). A competing risk analysis confirmed the results of the propensity score-matched analysis. The attributable risk associated with bloodstream infection was not significantly different (HR, 1.081; 95% CI 0.964 to 1.213) among patients with suspected CRBSI in terms of 30-day mortality compared with that associated with other infections. Conclusions In this cohort study, IRINC was associated with higher 30-day mortality compared to delayed CVC or no CVC among patients with suspected CRBSI. A large-sample randomized controlled trial is needed to define the best management for CVC in cases of suspected CRBSI because IRINC may also be associated with noninfectious complications. Trial registration This study was registered with the China Clinical Trials Registry (URL: http://www.chictr.org.cn/index.aspx ) under the following registration number: ChiCTR1900022175.

IntroductionThis study aimed to develop and validate a nomogram for predicting cancer-specific survival (CSS) in patients with non-keratinized large cell squamous cell carcinoma (NKLCSCC) at 3, 5, and 8 years after diagnosis.MethodsData on SCC patients were collected from the Surveillance, Epidemiology, and End Results database. Training (70%) and validation (30%) cohorts were generated using random selection of patients. Independent prognostic factors were selected using the backward stepwise Cox regression model. To predict the CSS rates in patients with NKLCSCC at 3, 5, and 8 years after diagnosis, all of the factors were incorporated into the nomogram. Indicators such as the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration curve, and decision-curve analysis (DCA) were then used to validate the performance of the nomogram.ResultsThis study included 9,811 patients with NKLCSCC. Twelve prognostic factors were identified by Cox regression analysis in the training cohort, which were age, number of regional nodes examined, number of positive regional nodes, sex, race, marital status, American Joint Committee on Cancer (AJCC) stage, surgery status, chemotherapy status, radiotherapy status, summary stage, and income. The constructed nomogram was validated both internally and externally. The nomogram had good discrimination ability, as indicated by the comparatively high C-indices and AUC values. The nomogram was properly calibrated, as indicated by the calibration curves. Our nomogram was superior to the AJCC model, as illustrated by its superior NRI and IDI values. DCA curves indicated the clinical usability of the nomogram.ConclusionThe first nomogram for prognosis predictions of patients with NKLCSCC has been developed and verified. Its performance and usability demonstrated that the nomogram could be utilized in clinical settings. However, additional external verification is still required.

Background. The objective of this study is to determine the prognostic factors of keratinizing squamous cell carcinoma of the tongue (KTSCC) and to establish a prognostic nomogram of KTSCC to assist clinical diagnosis and treatment. Methods. This study identified 3874 patients with KTSCC from the Surveillance, Epidemiology, and End Results (SEER) database, and these patients were randomly divided into the training (70%, (n = 2711) and validation (30%, n = 1163) cohorts. Cox regression was then used to filter variables. Nomograms were then constructed based on meaningful variables. Finally, the concordance index (C-index), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration charts, and decision-curve analysis (DCA), were used to evaluate the discrimination, accuracy and effectiveness of the model. Results. A nomogram model was established for predicting the 3-, 5-, and 8-year overall survival (OS) probabilities of patients with KTSCC. The model indicated that age, radiotherapy sequence, SEER stage, marital status, tumor size, American Joint Committee on Cancer (AJCC) stage, radiotherapy status, race, lymph node dissection status, and sex were factors influencing the OS of patients with KTSCC. Verified by C-index, NRI, IDI, calibration curve, and DCA curve, our model has better discrimination, calibration, accuracy and net benefit compared to the AJCC system. Conclusions. This study identified the factors that affect the survival of KTSCC patients and established a prognostic nomogram that can help clinicians predict the 3-, 5-, and 8-year survival rates of KTSCC patients.

Abstract Excessive ultraviolet (UV) radiation exposure results in skin chronic photodamage via stimulating reactive oxygen species (ROS) and inflammation. Anthocyanins are a group of flavonoids frequently found in edible plants. Cyanidin‐3‐O‐glucoside (C3G) as a typical anthocyanin shows effective anti‐oxidative and anti‐inflammatory properties. This study aims to investigate whether the topical application of C3G moisturizing gel on mice can protect the skin from UVB‐induced chronic photodamage. The results of in vitro experiment showed that the active ingredient C3G can penetrate the mice skin. The dorsal of Kunming mice were treated with C3G moisturizing gel (100, 200, 300 μmol/L) after UVB exposure. The animal experiment demonstrated that C3G can reduce chronic photodamage caused by UVB. C3G could effectively ameliorate the UVB‐induced epidermal barrier dysfunction including an increase in the skin hydration and decrease in the transepidermal water loss, and have statistically significance. Besides, our results also indicated that C3G inhibited UVB‐induced epidermal hyperplasia, the destruction of collagen fibers, ROS levels, and the expression of COX‐2 and IL‐6. In brief, these results indicate that C3G can reduce UVB‐induced chronic photodamage by inhibiting oxidative stress and inflammation.

Background: Information about critically ill patients with coronavirus disease 2019 (COVID-19) in China but outside of Wuhan is scarce. We aimed to describe the clinical features, treatment, and outcomes of patients with COVID-19 admitted to the intensive care unit (ICU) in Guangdong Province.Methods: In this multicenter, retrospective, observational study, we enrolled consecutive patients with COVID-19 who were admitted to seven ICUs in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatment, and outcomes were collected. Data were compared between patients with and without intubation.Results: A total of 45 COVID-19 patients required ICU admission in the study hospitals [mean age 56.7 ± 15.4 years, 29 males (64.4%)]. The most common symptoms at onset were fever and cough. Most patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all patients. Thirty-six patients (80%) developed acute respiratory distress syndrome at ICU admission, and 15 (33.3%) septic shock. Twenty patients (44.4%) were intubated, and 10 (22.2%) received extracorporeal membrane oxygenation. The 60-day mortality was 4.4% (2 of 45).Conclusion: COVID-19 patients admitted to ICU were characterized by fever, lymphopenia, acute respiratory failure, and multiple organ dysfunction. The mortality of ICU patients in Guangdong Province was relatively low with a small sample size.

Natural isoflavones have been reported to have a potential of antineoplastic activity. However, novel and specific isoflavones are still needed to be explored, and the underlying molecular mechanisms and the intracellular targets of these compounds remain elusive. In our study, we discovered that scandenolone, a natural isoflavonoid derivative from Cudrania tricuspidata fruit, exhibited antineoplastic activity in SK-MEL-28 cells by inducing intrinsic apoptosis and blocking autophagy flux. In addition, scandenolone significantly induced G2/M cycle arrest and inhibited cell migration. The study of the intracellular molecular targets showed that scandenolone binds directly to the active kinase and ATP-binding site of EGFR, which results in downregulating the AKT/mTOR/ERK signaling pathway. Therefore, out results indicate that scandenolone from Cudrania tricuspidata fruit, significantly sensitized SK-MEL-28 cells to apoptosis and repressed the proliferation of the cells, which showed an enormous potential to treat melanoma.

Malignant melanoma is an aggressive skin cancer with a high mortality rate. Nucleolar protein 14 (NOP14) has been implicated in cancer development. However, the role of NOP14 in malignant melanoma progression remains largely unclear. In this study, we observed that malignant melanoma tissue showed NOP14 down-regulation compared to melanocytic nevi tissues. Moreover, we observed that NOP14 expression was significantly associated with melanoma tumor thickness and lymph node metastasis. NOP14 overexpression in melanoma cells suppressed proliferation, caused G1 phase arrest, promoted apoptosis, and inhibited melanoma cell migration and invasion. Further investigations revealed that NOP14 overexpression reduced the expression levels of Wnt3a, β-catenin, and GSK-3β of the Wnt/β-catenin pathway. In summary, we demonstrated that NOP14 inhibited melanoma cell proliferation and metastasis by regulating the Wnt/β-catenin signaling pathway.

[This corrects the article DOI: 10.1371/journal.pone.0167392.].

Ultraviolet radiation is the major environmental harmful factor that has emotional impact on human skin. The aim of the present study was to determine the mechanism of protection of cyanidin-3-O-glucoside against ultraviolet B (UVB) -induced damage to human HaCaT keratinocytes. Our results show that cyanidin-3-O-glucoside decreased the levels of intracellular reactive oxygen species generated by UVB treatment. cyanidin-3-O-glucoside also decreased the UVB-augmented levels of the DNA damage indicators phospho-p53 and phospho-ATM/ATR. In addition, cyanidin-3-O-glucoside protected keratinocytes from UVB-induced injury by overturning the disruption of mitochondrial membrane potential and reversing apoptosis. The expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was attenuated in UVB-exposed cells but restored in UVB/cyanidin-3-O-glucoside-treated cells. Furthermore, expression of the proapoptotic proteins Bcl-2-associated X (Bax) and the key apoptosis executer cleaved caspase-3 were increased in UVB-irradiated cells and decreased in UVB/cyanidin-3-O-glucoside-treated cells. For these reasons, the results demonstrate that cyanidin-3-O-glucoside protects human keratinocytes against UVB-induced oxidative stress and apoptosis. Our study provides a theoretical basis for the use of cyanidin-3-O-glucoside in the fight against light damage .

The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC) terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq) profiling approach, we found that forkhead box c 1 (FOXC1) was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

Objective. To investigate the correlation between TREM-1 and LPS-induced left ventricular systolic dysfunction in BALB/c mice. Methods. Male BALB/c mice were randomly divided into 3 groups: LPS, LPS/TREM-1, and control groups which were injected intraperitoneally with 25 mg/kg LPS, 5 μg TREM-1mAb 1 h after LPS challenge, and sterilized normal saline, respectively. Left ventricular systolic function was monitored by echocardiography at 6 h, 12 h, and 24 h. Meanwhile, TNF-α, IL-1β, and sTREM-1 in serum and myocardium were determined by ELISA or real-time PCR; at last left ventricles were taken for light microscopy examination. Results. FS and EF in LPS/mAbTREM-1 group, significantly declined compared with LPS and control group at 12 h, were accompanied with a markedly increase in serum IL-1β (at 6 h) and sTREM-1 (at 12 h and 24 h) expression. Myocardium TNF-α (at 6 h and 24 h) and sTREM-1 (at 6 h) were significantly higher in LPS/mAbTrem-1-treated mice than in time-matched LPS-treated mice; meanwhile myocardium TNF-α mRNA were markedly increased in comparison with LPS-treated or saline-treated mice at 24 h. Besides, mAbTREM-1 aggravated LPS-induced myocardial damage was observed. Conclusions. Our results suggest that TREM-1 is significantly associated with LPS-induced left ventricular systolic dysfunction in BALB/c mice.

Objective. To investigate the association of serum sTREM-1 with myocardial dysfunction in patients with severe sepsis. Methods. A total of 85 patients with severe sepsis were divided into severe sepsis group (n=40) and septic shock group (n=45). Serum levels of sTREM-1, NT-proBNP, APACHE II score, SOFA score, cardiac index, cardiac function index, global ejection fraction, and left ventricular contractility index were measured on days 1, 3, and 7 after admission to ICU. Results. Serum sTREM-1 levels of patients with septic shock were significantly higher than those with severe sepsis on days 1, 3, and 7. Serum sTREM-1 was positively correlated with APACHE II scores, SOFA scores, and NT-proBNP. However, The sTREM-1 level was markedly negatively correlated with CI, CFI, GEF, and dP/dt max, respectively. Multiple logistic regression analysis showed that sTREM-1 was independent risk factor to NT-proBNP increasing. The optimal cut-off point of sTREM-1 for detecting patients with myocardial dysfunction was 468.05 ng/mL with sensitivity (80.6%) and specificity (75.7%). There is no difference in TREM-1-mRNA expression between the two groups. Conclusions. Serum sTREM-1 is significantly associated with myocardial dysfunction and may be a valuable tool for determining the presence of myocardial dysfunction in patients with severe sepsis.

Background: The survival and prognosis of patients are significantly threatened by cutaneous melanoma (CM), which is a highly aggressive disease. It is therefore crucial to determine the most recent survival rate of CM. This study used population-based cancer registry data to examine the 5-year relative survival rate of CM in the US. Methods: Period analysis was used to assess the relative survival rate and trends of patients with CM in the Surveillance, Epidemiology, and End Results (SEER) database during 2004–2018. And based on the data stratified by age, gender, race and subtype in the SEER database, a generalized linear model was 12established to predict the 5-year relative survival rate of CM patients from 2019 to 2023. Results: The 5-year relative survival increased to various degrees for both total CM and CM subtypes during the observation period. The improvement was greatest for amelanotic melanoma, increasing from 69.0% to 81.5%. The 5-year overall relative survival rates of CM were 92.9%, 93.5%, and 95.6% for 2004– 2008, 2009–2013, and 2014–2018, respectively. Females had a marginally higher survival rate than males for almost all subtypes, older people had lower survival rates than younger people, white patients had higher survival rates than nonwhite ones, and urban locations had higher rates of survival from CM than rural locations did. The survival rate of CM was significantly lower for distant metastasis. Conclusion: The survival rate of patients with CM gradually improved overall during 2004–2018. With the predicted survival rate of 96.7% for 2019–2023, this trend will still be present. Assessing the changes experienced by patients with CM over the previous 15 years can help in predicting the future course of CM. It also provides a scientific foundation that associated departments can use to develop efficient tumor prevention and control strategies. [ABSTRACT FROM AUTHOR]

Sepsis often causes cell death via pyroptosis and hence results in septic cardiomyopathy. Triggering receptors expressed in myeloid cells-1 (TREM-1) may initiate cellular cascade pathways and, in turn, induce cell death and vital organ dysfunction in sepsis, but the evidence is limited. We set to investigate the role of TREM-1 on nucleotide-binding oligomerization domain-like receptors with pyrin domain-3 (NLRP3) inflammasome activation and cardiomyocyte pyroptosis in sepsis models using cardiac cell line (HL-1) and mice. In this study, TREM-1 was found to be significantly increased in HL-1 cells challenged with lipopolysaccharide (LPS). Pyroptosis was also significantly increased in the HL-1 cells challenged with lipopolysaccharide and an NLRP3 inflammasome activator, nigericin. The close interaction between TREM-1 and structural maintenance of chromosome 4 (SMC4) was also identified. Furthermore, inhibition of TREM-1 or SMC4 prevented the upregulation of NLRP3 and decreased Gasdermin-D, IL-1b and caspase-1 cleavage. In mice subjected to caecal ligation and puncture, the TREM-1 inhibitor LR12 decreased the expression of NLRP3 and attenuated cardiomyocyte pyroptosis, leading to improved cardiac function and prolonged survival of septic mice. Our work demonstrates that, under septic conditions, TREM-1 plays a critical role in cardiomyocyte pyroptosis. Targeting TREM-1 and its associated molecules may therefore lead to novel therapeutic treatments for septic cardiomyopathy. [ABSTRACT FROM AUTHOR]