Search

BackgroundSevere burns can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) due to inflammation-immunity dysregulation. This study aimed to identify key immune-related molecules and potential drugs for immune regulation in severe burn treatment.MethodMicroarray datasets GSE77791 and GSE37069 were analyzed to identify immune-related differentially expressed genes (DEGs), enriched pathways and prognosis-related genes. The DGIdb database was used to identify potentially clinically relevant small molecular drugs for hub DEGs. Hub DEGs were validated by total RNA from clinical blood samples through qPCR. The efficacy of drug candidates was tested in a severe burn mouse model. Pathologic staining was used to observe organ damage. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the serum IL-1b, IL-6, TNF-a and MCP-1 contents. Activation of the NF-κB inflammatory pathway was detected by western blotting. Transcriptome sequencing was used to observe inflammatory-immune responses in the lung.ResultsA total of 113 immune-related DEGs were identified, and the presence of immune overactivation was confirmed in severe burns. S100A8 was not only significantly upregulated and identified to be prognosis-related among the hub DEGs but also exhibited an increasing trend in clinical blood samples. Methotrexate, which targets S100A8, as predicted by the DGIdb, significantly reduces transcription level of S100A8 and inflammatory cytokine content in blood, organ damage (lungs, liver, spleen, and kidneys) and mortality in severely burned mice when combined with fluid resuscitation. The inflammatory-immune response was suppressed in the lungs.ConclusionS100A8 with high transcription level in blood is a potential biomarker for poor severe burn prognosis. It suggested that methotrexate has a potential application in severe burn immunotherapy. Besides, it should be emphasized that fluid resuscitation is necessary for the function of methotrexate.

BackgroundTriple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. This study aimed to develop and validate a nomogram based on clinicopathological characteristics to predict rapid relapse in TNBC patients treated with neoadjuvant chemotherapy (NAC) first.MethodsThe clinicopathological data of 504 TNBC patients treated with NAC first in Tianjin Medical University Cancer Hospital were analyzed retrospectively, with 109 rapid relapsed patients, and 395 non-rapid relapsed patients, respectively. Based on clinicopathologic characteristics, and follow-up data were analyzed. The independent predictors of clinicopathological characteristics were identified by logistic regression analysis and then used to build a nomogram. The concordance index (C-index), the area under the curve (AUC) of receiver operating characteristic (ROC), and calibration plots were used to evaluate the performance of the model.ResultsUnivariate and multivariate logistic regression analyses showed that age at diagnosis (age≥50 years, OR = 0.325,95% CI:0.137–0.771), Nodal staging (N3 staging, OR = 13.669,95% CI:3.693–50.592),sTIL expression levels (sTIL intermediate expression, OR = 0.272,95% CI:0.109–0.678; sTIL high expression, OR = 0.169,95% CI:0.048–0.594), and NAC response (ORR, OR = 0.059,95% CI:0.024–0.143) were independent predictors of rapid relapse in TNBC patients treated with NAC firstly. Among these independent predictors, age ≥ 50 years, sTIL intermediate expression, sTIL high expression, and ORR in NAC were independent protective factors for rapid relapse in TNBC NAC patients. N3 staging was an independent risk factor for rapid relapse in TNBC NAC patients. The ROC curve, calibration curve, and decision curve analysis were used to validate the model. The C-Index of the training sets and validation sets were 0.938 and 0.910, respectively. The Brier scores of the training sets and validation sets were 0.076 and 0.097, respectively.ConclusionThis study developed and verified a nomogram for predicting rapid relapse in TNBC NAC patients, and the predictive model had high discrimination and accuracy.

ObjectiveThis investigation aimed to explore the potential causal relationship between physical activity, sedentary behavior and the risk of sepsis.MethodsUsing a two-sample Mendelian randomization approach, this study evaluated the association between physical activity (including moderate to vigorous physical activity [MVPA], vigorous physical activity [VPA], and accelerometer assessed physical activity) and sedentary behaviors (including television watching, computer use, and driving) with the risk of sepsis. This assessment was based on whole-genome association study data from the UK Biobank and the FinnGen database. Causal inferences were estimated using inverse variance-weighted, weighted median, and MR-Egger methods. Sensitivity analyses were performed using Cochran’s Q test, the MR-Egger intercept test, and the leave-one-out method.ResultsThe risk of sepsis was significantly inversely associated with genetically predicted MVPA (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.24–0.93, P = 0.0296) and VPA alone (OR 0.19, 95% CI 0.04–0.87, P = 0.0324). Conversely, prolonged driving time showed a significant positive association with the risk of sepsis (OR 3.99, 95% CI 1.40–11.40, P = 0.0097).ConclusionThis study provides preliminary evidence of a causal relationship between MVPA and VPA and a reduced risk of sepsis, while prolonged sedentary behaviors such as driving are positively associated with an increased risk of sepsis. These findings provided essential scientific evidence for the development of effective sepsis prevention strategies.

Nicotine is the primary addictive component of cigarette smoke and is associated with various smoking-related diseases. However, recent research has revealed its broader cognitive-enhancing and anti-inflammatory properties, suggesting its potential therapeutic applications in several conditions. This review aims to examine the double-edged nature of nicotine, encompassing its positive and negative effects. We provide a concise overview of the physiochemical properties and pharmacology of nicotine, including insights into nicotine receptors. Therefore, the article is divided into two main sections: toxicity and therapeutic potential. We comprehensively explored nicotine-related diseases, focusing on specific signaling pathways and the underlying mechanisms that contribute to its effects. Furthermore, we addressed the current research challenges and future development perspectives. This review aims to inspire future researchers to explore the full medical potential of nicotine, which holds significant promise for the clinical management of specific diseases.

Tumors present a formidable health risk with limited curability and high mortality; existing treatments face challenges in addressing the unique tumor microenvironment (hypoxia, low pH, and high permeability), necessitating the development of new therapeutic approaches. Under certain circumstances, certain bacteria, especially anaerobes or parthenogenetic anaerobes, accumulate and proliferate in the tumor environment. This phenomenon activates a series of responses in the body that ultimately produce anti-tumor effects. These bacteria can target and colonize the tumor microenvironment, promoting responses aimed at targeting and fighting tumor cells. Understanding and exploiting such interactions holds promise for innovative therapeutic strategies, potentially augmenting existing treatments and contributing to the development of more effective and targeted approaches to fighting tumors. This paper reviews the tumor-promoting mechanisms and anti-tumor effects of the digestive tract microbiome and describes bacterial therapeutic strategies for tumors, including natural and engineered anti-tumor strategies.

BackgroundTislelizumab is the first PD-1 inhibitor in China to demonstrate superior efficacy in second-line or third-line treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of tislelizumab compared to docetaxel from a Chinese healthcare system perspective.MethodsA dynamic Markov model was developed to evaluate the cost-effectiveness of tislelizumab in comparison to docetaxel in second or third-line treatment. The efficacy data utilized in the model were derived from the RATIONALE-303 clinical trial, while cost and utility values were obtained from the drug data service platform and published studies. The primary outcomes of the model encompassed quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to validate the robustness of the base case analysis results.ResultsThe tislelizumab group demonstrated a cost increase of CNY 117,473 and a gain of 0.58 QALYs compared to the docetaxel group, resulting in an ICER value of CNY 202,927 per QALY gained.ConclusionThe administration of tislelizumab in patients with advanced or metastatic NSCLC not only extends the progression-free survival (PFS) and overall survival (OS). Moreover, this treatment demonstrates a favorable cost-effectiveness profile across the Chinese population.

BackgroundMetabolic dysregulation represents a defining characteristic of Type 2 diabetes (T2DM). Nevertheless, there remains an absence of substantial evidence establishing a direct causal link between circulating blood metabolites and the promotion or prevention of T2DM. In addressing this gap, we employed Mendelian randomization (MR) analysis to investigate the potential causal association between 1,091 blood metabolites, 309 metabolite ratios, and the occurrence of T2DM.MethodsData encompassing single-nucleotide polymorphisms (SNPs) for 1,091 blood metabolites and 309 metabolite ratios were extracted from a Canadian Genome-wide association study (GWAS) involving 8,299 participants. To evaluate the causal link between these metabolites and Type 2 diabetes (T2DM), multiple methods including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode were employed. p-values underwent correction utilizing False Discovery Rates (FDR). Sensitivity analyses incorporated Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, Steiger test, leave-one-out analysis, and single SNP analysis. The causal effects were visualized via Circos plot, forest plot, and scatter plot. Furthermore, for noteworthy, an independent T2DM GWAS dataset (GCST006867) was utilized for replication analysis. Metabolic pathway analysis of closely correlated metabolites was conducted using MetaboAnalyst 5.0.ResultsThe IVW analysis method utilized in this study revealed 88 blood metabolites and 37 metabolite ratios demonstrating a significant causal relationship with T2DM (p < 0.05). Notably, strong causal associations with T2DM were observed for specific metabolites: 1-linoleoyl-GPE (18:2) (IVW: OR:0.930, 95% CI: 0.899–0.962, p = 2.16 × 10−5), 1,2-dilinoleoyl-GPE (18:2/18:2) (IVW: OR:0.942, 95% CI: 0.917–0.968, p = 1.64 × 10−5), Mannose (IVW: OR:1.133, 95% CI: 1.072–1.197, p = 1.02 × 10−5), X-21829 (IVW: OR:1.036, 95% CI: 1.036–1.122, p = 9.44 × 10−5), and Phosphate to mannose ratio (IVW: OR:0.870, 95% CI: 0.818–0.926, p = 1.29 × 10−5, FDR = 0.008). Additionally, metabolic pathway analysis highlighted six significant pathways associated with T2DM development: Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Glycerophospholipid metabolism, Alpha-Linolenic acid metabolism, Sphingolipid metabolism, and Alanine, aspartate, and glutamate metabolism.ConclusionThis study identifies both protective and risk-associated metabolites that play a causal role in the development of T2DM. By integrating genomics and metabolomics, it presents novel insights into the pathogenesis of T2DM. These findings hold potential implications for early screening, preventive measures, and treatment strategies for T2DM.

Fluoride-resistant Streptococcus mutans (S. mutans) might affect the ecological balance of biofilms in the presence of fluoride. We used a S. mutans and Candida albicans (C. albicans) cross-kingdom biofilm model to investigate whether fluoride-resistant S. mutans in biofilms would support C. albicans growth under fluoride stress and attenuate the in vitro anti-caries effect of fluorine. The impact of fluoride-resistant S. mutans on formation of cross-kingdom biofilms by S. mutans and C. albicans in the presence of fluoride was investigated in vitro using the crystal violet staining assay. Biofilm constitution was determined using colony-forming unit (CFU) counts and fluorescent in situ hybridization (FISH). Extracellular polysaccharide (EPS) generation in biofilms was determined by EPS/bacterial dying and water-insoluble polysaccharide detection. Acid production and demineralization were monitored using pH, lactic acid content, and transversal microradiography (TMR). The gene expression of microorganisms in the cross-kingdom biofilm was measured using qRT-PCR. Our results showed that both C. albicans and fluoride-resistant S. mutans grew vigorously, forming robust cross-kingdom biofilms, even in the presence of sodium fluoride (NaF). Moreover, fluoride-resistant S. mutans-containing cross-kingdom biofilms had considerable cariogenic potential for EPS synthesis, acid production, and demineralization ability in the presence of NaF than fluoride-sensitive S. mutans-containing biofilms. Furthermore, the gene expression of microorganisms in the two cross-kingdom biofilms changed dissimilarly in the presence of NaF. In summary, fluoride-resistant S. mutans in cross-kingdom biofilms supported C. albicans growth under fluoride and might attenuate the anti-caries potential of fluorine by maintaining robust cross-kingdom biofilm formation and cariogenic virulence expression in vitro in the presence of NaF.

With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.

BackgroundThe aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5.MethodsWe classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction (p 14, which corresponded to the maximum Youden index (Youden index = 0.751).ResultsThe latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction.ConclusionThis study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area.

PurposeThis study aimed to investigate the risk factors of prognosis and hemorrhagic transformation after mechanical thrombectomy (MT) in patients with posterior circulation acute ischemic stroke (PC-AIS) caused by large vessel occlusion. We sought to develop a nomogram for predicting the risk of poor prognosis and symptomatic intracerebral hemorrhage (sICH) in patients with PC-AIS.MethodsA retrospective analysis was conducted on 81 patients with PC-AIS who underwent MT treatment. We collected clinical information from the patients to assessed sICH and prognosis based on CT results and National Institutes of Health Stroke Scale (NIHSS) scores. Subsequently, they were followed up for 3 months, and their prognosis was assessed using the Modified Rankin Scale. We used the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression to determine the factors affecting prognosis to construct a nomogram. The nomogram’s performance was assessed through receiver operating characteristic curves, calibration curves, decision curve analysis, and clinical impact curves.ResultsAmong the 81 patients with PC-AIS, 33 had a good prognosis, 48 had a poor prognosis, 19 presented with sICH, and 62 did not present with sICH. The results of the LASSO regression indicated that variables, including HPT, baseline NIHSS score, peak SBP, SBP CV, SBP SD, peak SBP, DBP CV, HbA1c, and BG SD, were predictors of patient prognosis. Variables such as AF, peak SBP, and peak DBP predicted the risk of sICH. Multivariate logistic regression revealed that baseline NIHSS score (OR = 1.115, 95% CI 1.002–1.184), peak SBP (OR = 1.060, 95% CI 1.012–1.111), SBP CV (OR = 1.296, 95% CI 1.036–1.621) and HbA1c (OR = 3.139, 95% CI 1.491–6.609) were independent risk factors for prognosis. AF (OR = 6.823, 95% CI 1.606–28.993), peak SBP (OR = 1.058, 95% CI 1.013–1.105), and peak DBP (OR = 1.160, 95% CI 1.036–1.298) were associated with the risk of sICH. In the following step, nomograms were developed, demonstrating good discrimination, calibration, and clinical applicability.ConclusionWe constructed nomograms to predict poor prognosis and risk of sICH in patients with PC-AIS undergoing MT. The model exhibited good discrimination, calibration, and clinical applicability.

Several mutations in the IRF6 gene have been identified as a causative link to VWS. In this investigation, whole-exome sequencing (WES) and Sanger sequencing of a three-generation pedigree with an autosomal-dominant inheritance pattern affected by VWS identified a unique stop-gain mutation—c.748C>T:p.R250X—in the IRF6 gene that co-segregated exclusively with the disease phenotype. Immunofluorescence analysis revealed that the IRF6-p.R250X mutation predominantly shifted its localization from the nucleus to the cytoplasm. WES and protein interaction analyses were conducted to understand this mutation’s role in the pathogenesis of VWS. Using LC-MS/MS, we found that this mutation led to a reduction in the binding of IRF6 to histone modification-associated proteins (NAA10, SNRPN, NAP1L1). Furthermore, RNA-seq results show that the mutation resulted in a downregulation of TGFβ2-AS1 expression. The findings highlight the mutation’s influence on TGFβ2-AS1 and its subsequent effects on the phosphorylation of SMAD2/3, which are critical in maxillofacial development, particularly the palate. These insights contribute to a deeper understanding of VWS’s molecular underpinnings and might inform future therapeutic strategies.

BackgroundWith the global rise in obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease. Concurrently, depression is a highly prevalent mental disorder. As the incidence of MASLD and depression continues to increase, a growing body of research indicates a potential association between the two conditions. However, the direction of causality between depression and MASLD remains uncertain. To address this gap, our study utilizes a two-sample Mendelian randomization (MR) approach to explore the bidirectional causal relationship between depression and MASLD.MethodsWe extracted single nucleotide polymorphisms (SNPs) associated with depression and MASLD from pooled data of genome-wide association studies (GWAS). A comprehensive assessment of possible causality was also performed. Possible mediating effects of liver enzymes on MASLD were also assessed.ResultsA total of three GWAS pooled data on depression as well as GWAS data related to MASLD and GWAS data on four liver enzymes were used in this study. Our findings indicated a strong causal relationship between depression and MASLD (OR, 1.557; 95% CI, 1.097–2.211; P = 0.016). And we found a mediating effect of gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). ALT 10% (95% CI: 7% - 13%, P< 0.0002). AST, 4.14% (95% CI: 2.34% - 5.94%, P < 0.05). GGT 0.19% (95% CI: 0.15% - 0.22%, P< 0.000000002). However, we did not find a mediating effect of alkaline phosphatase (ALP). Our inverse MR analysis did not reveal any causal relationship between MASLD and depression.ConclusionsThe MR analysis revealed a positive causal relationship between depression and MASLD, while no reverse causal relationship was identified. Liver enzymes may mediate the role between depression and MASLD.

PurposeThe purpose of this study was to provide advice for the indication of regional nodal irradiation (RNI) in patients with one to two positive sentinel lymph nodes (SLNs) without axillary lymph node dissection (ALND).MethodsWe conducted a retrospective study in Shandong Cancer Hospital, Fudan University Shanghai Cancer Center, and West China Hospital. Logistic analysis was performed in order to explore the influencing factors of positive non-SLNs (NSLNs) and >3 positive nodes among patients with one to two SLNs+. Then, nomograms were constructed.ResultsBetween May 2010 and 2020, among the 2,845 patients with one to two SLNs+ undergoing ALND (1,992 patients in the training set and 853 patients in the validation set), there were 34.3% harbored NSLNs+ and 15.6% harbored >3 positive nodes. Multivariate analysis showed that cN stage, the number of positive/negative SLN, pathological tumor stage, lympho-vascular invasion (LVI), multicenter, and molecular subtypes were significantly associated with NSLN metastasis. Similarly, multivariate analysis also showed that cN stage, the number of positive/negative SLNs, pathological tumor stage, and LVI could be independent predictors of >3 positive nodes. Then, nomograms for NSLN metastasis and >3 positive nodes were constructed using these parameters, respectively.ConclusionsThe nomograms will be useful in estimating positive NSLNs and >3 positive nodes, and they might provide advice for the optimization of RNI.

Accumulating studies have indicated that the gut microbiota plays a pivotal role in the onset of autoimmune diseases by engaging in complex interactions with the host. This review aims to provide a comprehensive overview of the existing literatures concerning the relationship between the gut microbiota and autoimmune diseases, shedding light on the complex interplay between the gut microbiota, the host and the immune system. Furthermore, we aim to summarize the impacts and potential mechanisms that underlie the interactions between the gut microbiota and the host in autoimmune diseases, primarily focusing on systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, type 1 diabetes mellitus, ulcerative colitis and psoriasis. The present review will emphasize the clinical significance and potential applications of interventions based on the gut microbiota as innovative adjunctive therapies for autoimmune diseases.

The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping useful for the identification of organisms, illumination of metabolic pathways, and determination of microbiota. It can accurately obtain all the nucleic acid information in the test sample. Anthrax is one of the most important zoonotic diseases, infecting mainly herbivores and occasionally humans. The disease has four typical clinical forms, cutaneous, gastrointestinal, inhalation, and injection, all of which may result in sepsis or meningitis, with cutaneous being the most common form. Here, we report a case of cutaneous anthrax diagnosed by mNGS in a butcher. Histopathology of a skin biopsy revealed PAS-positive bacilli. Formalin-fixed paraffin-embedded (FFPE) tissue sample was confirmed the diagnosis of anthrax by mNGS. He was cured with intravenous penicillin. To our knowledge, this is the first case of cutaneous anthrax diagnosed by mNGS using FFPE tissue. mNGS is useful for identifying pathogens that are difficult to diagnose with conventional methods, and FFPE samples are simple to manage. Compared with traditional bacterial culture, which is difficult to cultivate and takes a long time, mNGS can quickly and accurately help us diagnose anthrax, so that anthrax can be controlled in a timely manner and prevent the outbreak of epidemic events.

The tissues or organs derived decellularized extracellular matrix carry immunogenicity and the risk of pathogen transmission, resulting in limited therapeutic effects. The cell derived dECM cultured in vitro can address these potential risks, but its impact on wound remodeling is still unclear. This study aimed to explore the role of decellularized extracellular matrix (dECM) extracted from adipose derived stem cells (ADSCs) in skin regeneration.Methods: ADSCs were extracted from human adipose tissue. Then we cultivated adipose-derived stem cell cells and decellularized ADSC-dECM for freeze-drying. Western blot (WB), enzyme-linked immunosorbent assay (ELISA) and mass spectrometry (MS) were conducted to analyzed the main protein components in ADSC-dECM. The cell counting assay (CCK-8) and scratch assay were used to explore the effects of different concentrations of ADSC-dECM on the proliferation and migration of human keratinocytes cells (HaCaT), human umbilical vein endothelia cells (HUVEC) and human fibroblasts (HFB), respectively. Moreover, we designed a novel ADSC-dECM-CMC patch which used carboxymethylcellulose (CMC) to load with ADSC-dECM; and we further investigated its effect on a mouse full thickness skin wound model.Results: ADSC-dECM was obtained after decellularization of in vitro cultured human ADSCs. Western blot, ELISA and mass spectrometry results showed that ADSC-dECM contained various bioactive molecules, including collagen, elastin, laminin, and various growth factors. CCK-8 and scratch assay showed that ADSC-dECM treatment could significantly promote the proliferation and migration of HaCaT, human umbilical vein endothelia cells, and human fibroblasts, respectively. To evaluate the therapeutic effect on wound healing in vivo, we developed a novel ADSC-dECM-CMC patch and transplanted it into a mouse full-thickness skin wound model. And we found that ADSC-dECM-CMC patch treatment significantly accelerated the wound closure with time. Further histology and immunohistochemistry indicated that ADSC-dECM-CMC patch could promote tissue regeneration, as confirmed via enhanced angiogenesis and high cell proliferative activity.Conclusion: In this study, we developed a novel ADSC-dECM-CMC patch containing multiple bioactive molecules and exhibiting good biocompatibility for skin reconstruction and regeneration. This patch provides a new approach for the use of adipose stem cells in skin tissue engineering.

BackgroundIn sepsis patients, kidney damage is among the most dangerous complications, with a high mortality rate. In addition, major adverse kidney events within 30 days (MAKE30) served as a comprehensive and unbiased clinical outcome measure for sepsis patients due to the recent shift toward targeting patient-centered renal outcomes in clinical research. However, the underlying predictive model for the prediction of MAKE30 in sepsis patients has not been reported in any study.MethodsA cohort of 2,849 sepsis patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database was selected and subsequently allocated into a training set (n = 2,137, 75%) and a validation set (n = 712, 25%) through randomization. In addition, 142 sepsis patients from the Xi’An No. 3 Hospital as an external validation group. Univariate and multivariate logistic regression analyses were conducted to ascertain the independent predictors of MAKE30. Subsequently, a nomogram was developed utilizing these predictors, with an area under curve (AUC) above 0.6. The performance of nomogram was assessed through calibration curve, receiver operating characteristics (ROC) curve, and decision curve analysis (DCA). The secondary outcome was 30-day mortality, persistent renal dysfunction (PRD), and new renal replacement therapy (RRT). MAKE30 were a composite of death, PRD, new RRT.ResultsThe construction of the nomogram was based on several independent predictors (AUC above 0.6), including age, respiratory rate (RR), PaO2, lactate, and blood urea nitrogen (BUN). The predictive model demonstrated satisfactory discrimination for MAKE30, with an AUC of 0.740, 0.753, and 0.821 in the training, internal validation, and external validation cohorts, respectively. Furthermore, the simple prediction model exhibited superior predictive value compared to the SOFA model in both the training (AUC = 0.710) and validation (AUC = 0.692) cohorts. The nomogram demonstrated satisfactory calibration and clinical utility as evidenced by the calibration curve and DCA. Additionally, the predictive model exhibited excellent accuracy in forecasting 30-day mortality (AUC = 0.737), PRD (AUC = 0.639), and new RRT (AUC = 0.846) within the training dataset. Additionally, the model displayed predictive power for 30-day mortality (AUC = 0.765), PRD (AUC = 0.667), and new RRT (AUC = 0.783) in the validation set.ConclusionThe proposed nomogram holds the potential to estimate the risk of MAKE30 promptly and efficiently in sepsis patients within the initial 24 h of admission, thereby equipping healthcare professionals with valuable insights to facilitate personalized interventions.

BackgroundMerkel cell carcinoma (MCC) is a rare type of invasive neuroendocrine skin malignancy with high mortality. However, with years of follow-up, what is the actual survival rate and how can we continually assess an individual’s prognosis? The purpose of this study was to estimate conditional survival (CS) for MCC patients and establish a novel CS-based nomogram model.MethodsThis study collected MCC patients from the Surveillance, Epidemiology, and End Results (SEER) database and divided these patients into training and validation groups at the ratio of 7:3. CS refers to the probability of survival for a specific timeframe (y years), based on the patient’s survival after the initial diagnosis (x years). Then, we attempted to describe the CS pattern of MCCs. The Least absolute shrinkage and selection operator (LASSO) regression was employed to screen predictive factors. The Multivariate Cox regression analysis was applied to demonstrate these predictors’ effect on overall survival and establish a novel CS-based nomogram.ResultsA total of 3,843 MCC patients were extracted from the SEER database. Analysis of the CS revealed that the 7-year survival rate of MCC patients progressively increased with each subsequent year of survival. The rates progressed from an initial 41–50%, 61, 70, 78, 85%, and finally to 93%. And the improvement of survival rate was nonlinear. The LASSO regression identified five predictors including patient age, sex, AJCC stage, surgery and radiotherapy as predictors for CS-nomogram development. And this novel survival prediction model was successfully validated with good predictive performance.ConclusionCS of MCC patients was dynamic and increased with time since the initial diagnosis. Our newly established CS-based nomogram can provide a dynamic estimate of survival, which has implications for follow-up guidelines and survivorship planning, enabling clinicians to guide treatment for these patients better.

Canine parvovirus (CPV) is one of the most common lethal viruses in canines. The virus disease is prevalent throughout the year, with high morbidity and mortality rate, causing serious harm to dogs and the dog industry. Previously, yeast two hybrid method was used to screen the protein chaperonin containing TCP-1 (CCT7) that interacts with VP2. However, the mechanism of interactions between CCT7 and VP2 on CPV replication remains unclear. In this study, we first verified the interaction between CCT7 and viral VP2 proteins using yeast one-to-one experiment and co-immunoprecipitation (CoIP) experiment. Laser confocal microscopy observation showed that CCT7 and VP2 were able to co-localize and were mostly localized in the cytoplasm. In addition, the study of VP2 truncated mutant found that the interaction region of VP2 with CCT7 was located between amino acids 231 and 320. Cycloheximide (CHX) chase experiments showed that CCT7 can improve the stability of VP2 protein. After further regulation of CCT7 expression in F81 cells, it was found that the expression level of VP2 protein was significantly reduced after knocking down CCT7 expression by RNA interference (RNAi) or HSF1A inhibitor, and increased after overexpressing host CCT7. The study reveals the role of VP2 interacting protein CCT7 in the replication process of CPV, which could provide a potential target for the prevention and control of CPV.

IntroductionEpistasis is currently a topic of great interest in molecular and quantitative genetics. Arabidopsis thaliana, as a model organism, plays a crucial role in studying the fundamental biology of diverse plant species. However, there have been limited reports about identification of epistasis related to flowering in genome-wide association studies (GWAS). Therefore, it is of utmost importance to conduct epistasis in Arabidopsis.MethodIn this study, we employed Levene’s test and compressed variance component mixed model in GWAS to detect quantitative trait nucleotides (QTNs) and QTN-by-QTN interactions (QQIs) for 11 flowering-related traits of 199 Arabidopsis accessions with 216,130 markers.ResultsOur analysis detected 89 QTNs and 130 pairs of QQIs. Around these loci, 34 known genes previously reported in Arabidopsis were confirmed to be associated with flowering-related traits, such as SPA4, which is involved in regulating photoperiodic flowering, and interacts with PAP1 and PAP2, affecting growth of Arabidopsis under light conditions. Then, we observed significant and differential expression of 35 genes in response to variations in temperature, photoperiod, and vernalization treatments out of unreported genes. Functional enrichment analysis revealed that 26 of these genes were associated with various biological processes. Finally, the haplotype and phenotypic difference analysis revealed 20 candidate genes exhibiting significant phenotypic variations across gene haplotypes, of which the candidate genes AT1G12990 and AT1G09950 around QQIs might have interaction effect to flowering time regulation in Arabidopsis.DiscussionThese findings may offer valuable insights for the identification and exploration of genes and gene-by-gene interactions associated with flowering-related traits in Arabidopsis, that may even provide valuable reference and guidance for the research of epistasis in other species.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial effect of prodigiosin against MRSA with a minimum inhibitory concentration as low as 2.5 mg/L. The results of scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy indicated that prodigiosin inhibited biofilm formation in S. aureus USA300, while also destroying the structure of the cell wall and cell membrane, which was confirmed by transmission electron microscopy. At a prodigiosin concentration of 1.25 mg/L, biofilm formation was inhibited by 76.24%, while 2.5 mg/L prodigiosin significantly reduced the vitality of MRSA cells in the biofilm. Furthermore, the transcriptomic results obtained at 1/8 MIC of prodigiosin indicated that 235and 387 genes of S. aureus USA300 were significantly up- and downregulated, respectively. The downregulated genes were related to two-component systems, including the transcriptional regulator LytS, quorum sensing histidine kinases SrrB, NreA and NreB, peptidoglycan biosynthesis enzymes (MurQ and GlmU), iron-sulfur cluster repair protein ScdA, microbial surface components recognizing adaptive matrix molecules, as well as the key arginine synthesis enzymes ArcC and ArgF. The upregulated genes were mainly related to cell wall biosynthesis, as well as two-component systems including vancomycin resistance-associated regulator, lipoteichoic acid biosynthesis related proteins DltD and DltB, as well as the 9 capsular polysaccharide biosynthesis proteins. This study elucidated the molecular mechanisms through which prodigiosin affects the cell envelope of MRSA from the perspectives of cell wall synthesis, cell membrane and biofilm formation, providing new potential targets for the development of antimicrobials for the treatment of MRSA.

BackgroundIn recent years, the role of gut microbiota and derived metabolites in renal disease has attracted more attention. It has been established that the gut microbiota is a potential target for medical interventions in renal disease including chronic kidney disease (CKD), acute kidney injury (AKI) and renal calculus. Emerging evidence has related dialysis treatment to the microbial composition and function of the intestines, and there are many reports related to HD, but few studies have been related to PD. Previous studies have found that PD patients have intestinal flora disturbances, so we speculate that intestinal flora and its metabolites may be the regulatory factors in long-term therapy of PD. And as far as we know, there have been no studies characterized the gut microbiota in PD patients of different dialysis vintages.MethodsIt is a cross-sectional study based on clinical data and biological samples of 72 patients with CAPD, 13 patients with ESRD and 13 healthy volunteers. The intestinal microecological characteristics of CAPD patients were comprehensively evaluated by combining the intestinal microflora structure, enterotoxin and receptor (serum LPS and LBP), intestinal barrier function index (serum D-Lactate), intestinal uremic toxin (serum IS, PCS, TMAO), fecal SCFAs and other multi-dimensional and multi-omics studies. Furthermore, the changes of intestinal microecology in CAPD patients of different dialysis vintages (≥ 3 and < 12 months, ≥ 12 and < 24 months, ≥ 24 and < 60 months, ≥ 60 months) were further explored, and the correlations between intestinal microecology indicators and some clinical indicators were analyzed. Fecal and serum samples were collected from PD patients (PD group, n = 72), ESRD patients (ESRD group, n = 13) and healthy volunteers (Normal group, n = 13). Fecal samples were subjected to microbiome (16S rDNA) and SCFA (GC-MS) analyses. Serum samples were subjected to LPS, LBP, D-lactate, IS, PCS, and TMAO (ELISA) analyses.ResultsThe diversity and richness of intestinal flora in CAPD patients were lower than those in healthy people and ESRD patients, and the microflora structure was different. Anaerobes of Blautia and facultative anaerobes and aerobic bacteria with Bacilli and Lactobacillales those in Firmicutes are the main intestinal flora in CAPD patients. The abundance of Bacteroidaceae, Bacteroides, Faecalibacterium and other dominant bacteria in the intestinal tract of CAPD patients decreased. Proteobacteria, Enterobacteriaceae and Escherichia-Shigella increased their colonization (LDA > 4). In CAPD patients of different dialysis vintages, there was no significant change in the diversity and richness of microflora, and the microflora structure of PDC group was significantly different from that of PDD, which the abnormal expansion of enterobacter group was more prominent in PDC and the abundance of Bacteroides group was relatively higher in PDD. Intestinal barrier damage, intestinal uremic toxin accumulation and short-chain fatty acid reduction were observed in CAPD patients, such as the serum level of D-Lactate, PCS and TMAO were significantly higher than that in the Normal group (P < 0.05),and the fecal levels of BA and CA were significantly lower (P < 0.05). The intestinal microecological disorder of PDC group, while that of PDD group showed a better trend. Such as the PDC group had a significantly higher serum level of LPS, D-Lactate and TMAO (P < 0.01), and significantly lower serum level of LBP (P < 0.01), and lower fecal levels of AA and BA (P > 0.05) than the PDD group.ConclusionThe intestinal microecology and metabolic system of CAPD patients had changes compared with healthy people and ESRD non-dialysis patients, and there were differences in CAPD patients with different dialysis vintages. PD patients on dialysis for more than 60 months showed a better trend in the intestinal microecology than patients with 24∼36 months, which suggested that the intestinal microecology of PD patients had a certain ability of self-regulation and remodeling under the management of standardized system and it is necessary to strengthen the monitoring of the intestinal status and the occurrence of related complications in PD patients on dialysis of 24∼36 months of dialysis vintage. It is initially considered that the mechanism of intestinal microecology is a potential target for intervention in the diagnosis and treatment of CAPD and incorporating intestinal microecosystem monitoring into the long-term management of CAPD patients is a new strategy.

Introduction: Tocilizumab and baricitinib are recommended treatment options for COVID-19 patients with hyperinflammatory response; however, there is a lack of systematic review directly evaluating their efficacy and safety.Objective: This review was conducted to evaluate the efficacy and safety of tocilizumab and baricitinib in the treatment of hospitalized patients with COVID-19.Methods: Relevant databases were searched for studies that compared the effect or safety of baricitinib or tocilizumab in hospitalized patients with COVID-19. The mortality was the main outcome. The hospital length of stay or adverse drug reactions were taken into consideration as secondary endpoints. The analyses were performed in Revman 5.3 or Stata 16.0. The protocol and analysis plan were pre-registered in PROSPERO, with the registration number CRD42023408219.Results: In total, 10 studies with 2,517 patients were included. The overall pooled data demonstrated that, there was no statistically significant difference in the 28-day mortality rate and the hospital length of stay between the tocilizumab and baricitinib (OR = 1.10, 95% CI = 0.80–1.51, p = 0.57; OR = −0.68, 95% CI = −2.24–0.87, p = 0.39). The adverse reactions including secondary infection rate, thrombotic and bleeding events, and acute liver injury of tocilizumab were significantly higher than that of baricitinib. (OR = 1.49, 95% CI = 1.18–1.88, p < 0.001,OR = 1.52, 95% CI = 1.11–2.08, p = 0.009; OR = 1.52, 95% CI = 1.11–2.08, p = 0.009; OR = 2.24, 95% CI = 1.49–3.35, p < 0.001).Conclusion: In patients hospitalized with COVID-19, no discernible difference in therapeutic efficacy was observed between tocilizumab and baricitinib; however, the group treated with baricitinib demonstrated a significantly lower incidence of adverse effects.

BackgroundAutophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA.MethodsGSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein–protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs.ResultsA total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils.ConclusionCDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy.

IntroductionOrdinal traits are important complex traits in crops, while genome-wide association study (GWAS) is a widely-used method in their gene mining. Presently, GWAS of continuous quantitative traits (C-GWAS) and single-locus association analysis method of ordinal traits are the main methods used for ordinal traits. However, the detection power of these two methods is low.MethodsTo address this issue, we proposed a new method, named MTOTC, in which hierarchical data of ordinal traits are transformed into continuous phenotypic data (CPData).ResultsThen, FASTmrMLM, one C-GWAS method, was used to conduct GWAS for CPData. The results from the simulation studies showed that, MTOTC+FASTmrMLM for ordinal traits was better than the classical methods when there were four and fewer hierarchical levels. In addition, when MTOTC was combined with FASTmrEMMA, mrMLM, ISIS EM-BLASSO, pLARmEB, and pKWmEB, relatively high power and low false positive rate in QTN detection were observed as well. Subsequently, MTOTC was applied to analyze the hierarchical data of soybean salt-alkali tolerance. It was revealed that more significant QTNs were detected when MTOTC was combined with any of the above six C-GWAs.DiscussionAccordingly, the new method increases the choices of the GWAS methods for ordinal traits and helps to mine the genes for ordinal traits in resource populations.

BackgroundCerebral palsy (CP) is a neurodevelopmental disorder characterized by motor impairment. In this study, we aimed to describe the characteristics of amino acids (AA) in the plasma of children with CP and identify AA that could play a potential role in the auxiliary diagnosis and treatment of CP.MethodsUsing high performance liquid chromatography, we performed metabolomics analysis of AA in plasma from 62 CP children and 60 healthy controls. Univariate and multivariate analyses were then applied to characterize different AA. AA markers associated with CP were then identified by machine learning based on the Lasso regression model for the validation of intra-sample interactions. Next, we calculated a discriminant formula and generated a receiver operating characteristic (ROC) curve based on the marker combination in the discriminant diagnostic model.ResultsA total of 33 AA were detected in the plasma of CP children and controls. Compared with controls, 5, 7, and 10 different AA were identified in total participants, premature infants, and full-term infants, respectively. Of these, β-amino-isobutyric acid [p = 2.9*10(−4), Fold change (FC) = 0.76, Variable importance of protection (VIP) = 1.75], tryptophan [p = 5.4*10(−4), FC = 0.87, VIP = 2.22], and asparagine [p = 3.6*10(−3), FC = 0.82, VIP = 1.64], were significantly lower in the three groups of CP patients than that in controls. The combination of β-amino-isobutyric acid, tryptophan, and taurine, provided high levels of diagnostic classification and risk prediction efficacy for preterm children with an area under the curve (AUC) value of 0.8741 [95% confidence interval (CI): 0.7322–1.000]. The discriminant diagnostic formula for preterm infant with CP based on the potential marker combination was defined by p = 1/(1 + e−(8.295–0.3848* BAIBA-0.1120*Trp + 0.0108*Tau)).ConclusionFull-spectrum analysis of amino acid metabolomics revealed a distinct profile in CP, including reductions in the levels of β-amino-isobutyric acid, tryptophan, and taurine. Our findings shed new light on the pathogenesis and diagnosis of premature infants with CP.

BackgroundPolygonatum sibiricum is an understory economic plant, and its dried rhizome is a traditional Chinese medicine. The purpose of this study was to connect the quality improvement of the understory plant P. sibiricum with specific microorganisms.MethodsAmplicon and metabolome sequencing were conducted for P. sibiricum interplanted under three types of trees and in the field, and the relationship between the microbiome and secondary metabolism was explored.ResultsPrincipal component analysis (PCA) divided field cultivated and understory interplanted groups into two classes. A total of 95 different metabolites were found, with four expression patterns. The alpha diversity of rhizosphere bacteria and endosphere fungi in the understory interplanted group was significantly higher than that in the farmland cultivated group. There were 276 different rhizosphere microorganism genera among the four groups; however, only 33 different endosphere genera were observed, indicating that endophytic microbial diversity was relatively stable within the P. sibiricum rhizome, especially for endosphere bacteria. Cointertia analysis (CoIA) suggested that the metabolite changes in P. sibiricum induced by interplanting under different trees were more strongly affected by rhizosphere microorganisms than by endosphere microorganisms. In addition, the interactions between rhizosphere microorganisms and metabolites in the farmland group were weakened compared with those in the underplanted groups. Canonical correspondence analysis (CCA) showed that Aspergillus and Ellin6067 had the greatest influence on the metabolites. Myrmecridium, as a shared microbe in the rhizosphere and endosphere, had interaction effects with the largest number of microbes.ConclusionThis study revealed the interactions between the microbes and metabolites in P. sibiricum and systematically explored the mechanism underlying their correlation, which was mediated by the understory interplanting mode. This study provides feasible strategies for improving the medicinal value of P. sibiricum by regulating microorganisms.

ObjectiveArteriolosclerosis cerebral small vessel disease (CSVD) is a common type of CSVD. This study aimed to explore the factors associated with cognitive function and total MRI burden related to the disease.MethodsThe demographic characteristics, clinical manifestations, cognitive function score, Barthel Index (BI), blood test index, and follow-up results of arteriolosclerosis CSVD patients treated for the first time in our hospital from January 2014 to August 2022 were collected. White matter hyperintensity (WMH) Fazekas score, total MRI burden, and cerebral atrophy grade were evaluated according to brain MRI findings. Factors associated with CSVD cognitive function were analyzed by binary logistic regression. The correlative factors related to the total MRI burden of CSVD were analyzed by ordered multiple logistic regression.ResultsA total of 146 patients were included in this study, of which 132 cases (90.4%) had hypertension. There were 108 patients (74.0%) with cognitive dysfunction, 97 patients (66.4%) with balance and gait disorders, and 83 patients (56.8%) with moderate-to-severe dependence in daily life (BI ≤ 60 points). Of 146 patients, 79 (54.1%) completed clinical and imaging follow-ups for a median of 3 years. The number of patients with cognitive impairment and BI ≤ 60 points after follow-up significantly increased compared with the first admission (P < 0.001). There were also significant differences in total MRI burden (P = 0.001), WMH Fazekas score, and cerebral atrophy grade (P < 0.001). Mean age (P = 0.012), median deep WMH Fazekas score (P = 0.028), and median deep (P < 0.001) and superficial (P =0.002) cerebral atrophy grade of patients with cognitive impairment at first admission were all higher than those with non-cognitive impairment. Multivariate analysis showed that deep cerebral atrophy was independently and significantly associated with cognitive impairment of CSVD (P = 0.024), and hypertension was significantly and independently associated with total MRI burden (P = 0.001).ConclusionThe disease course of arteriolosclerosis CSVD may be related to cognitive function and total MRI burden. Deep cerebral atrophy was an independent risk factor for cognitive dysfunction in arteriolosclerosis CSVD, and hypertension was an independent risk factor for total MRI burden.

ObjectiveThe aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome (MetS).MethodsA comprehensive search for clinical trials was conducted in the following scientific databases: PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine. Randomized controlled trials (RCTs) evaluating the efficacy and safety of curcumin supplement for MetS were identified. A random-effects meta-analysis was performed using inverse variance, and efficacy was expressed as mean difference (MD) with 95% confidence interval (CI). The metabolic syndrome markers that were evaluated in the present study included waist circumference (WC), fasting blood sugar (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), C-reactive protein (CRP), ultrasensitive c-reactive protein (hsCRP), and malondialdehyde (MDA). By employing the Cochrane tool, RCTs were assessed for bias risk.ResultsA total of 785 participants from 13 RCTs were included, with intervention durations ranging from 4 to 12 weeks. Compared with the control group, the curcumin group had positive effects on WC (MD = -2.16, 95% CI: -3.78 to -0.54, p = 0.009, seven studies), FBS (MD = -8.6, 95% CI: -15.45 to -1.75, p = 0.01, nine studies), DBP (MD = -2.8, 95% CI: -4.53 to - 1.06, p = 0.002, five studies), HDL-C (MD = 4.98, 95% CI: 2.58 to 7.38, p < 0.0001, eight studies), TNF-a (MD = -12.97, 95% CI: -18.37 to -7.57, p < 0.00001, two studies), CRP (MD = - 1.24, 95% CI: -1.71 to -0.77, p < 0.00001, two studies), and MDA (MD = -2.35, 95% CI: -4.47 to -0.24, p = 0.03, three studies). These improvements were statistically significant. Meanwhile, there was no significant improvement in SBP (MD = -4.82, 95% CI: -9.98 to 0.35, p = 0.07, six studies), TG (MD = 1.28, 95% CI: -3.75 to 6.30, p = 0.62, eight studies), IL-6 (MD = -1.5, 95% CI: -3.97 to 0.97, p = 0.23, two studies), or hsCRP (MD = -1.10, 95% CI: -4.35 to 2.16, p < 0.51, two studies). FBS, SBP, HDL-C, IL-6, CRP, hsCRP, and MDA had a relatively high heterogeneity.ConclusionCurcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022362553.

Platycladus orientalis, a common horticultural tree species, has an extremely long life span and forms a graceful canopy. Its branches, leaves, and cones have been used in traditional Chinese medicine. However, difficulty in rooting is the main limiting factor for the conservation of germplasm resources. This study shows that the rooting rates and root numbers of cuttings were significantly reduced in ancient P. orientalis donors compared to 5-year-old P. orientalis donors. The contents of differentially accumulated metabolites (DAMs) in phenylpropanoid (caffeic acid and coniferyl alcohol) and flavonoid biosynthesis (cinnamoyl-CoA and isoliquiritigenin) pathways increased significantly in cuttings propagated from ancient P. orientalis donors compared to 5-year-old P. orientalis donors during adventitious root (AR) formation. These DAMs may prevent the ancient P. orientalis cuttings from rooting, and gradual lignification of callus was one of the main reasons for the failed rooting of ancient P. orientalis cuttings. The rooting rates of ancient P. orientalis cuttings were improved by wounding the callus to identify wounding-induced rooting-promoting metabolites. After wounding, the contents of DAMs in zeatin (5′-methylthioadenosine, cis-zeatin-O-glucoside, and adenine) and aminoacyl-tRNA biosynthesis (l-glutamine, l-histidine, l-isoleucine, l-leucine, and l-arginine) pathways increased, which might promote cell division and provided energy for the rooting process. The findings of our study suggest that breaking down the lignification of callus via wounding can eventually improve the rooting rates of ancient P. orientalis cuttings, which provides a new solution for cuttings of other difficult-to-root horticultural and woody plants.

Invasion success of clonal plants is closely related to their unique clonal life history, and clonal division of labor is a crucial clonal trait. However, so far, it is unclear whether invasive alien clonal species generally possess a greater capacity for division of labor than native species and whether this pattern is affected by environmental conditions. To test whether patch contrast affects the differences in the capacity for division of labor between invasive alien and native clonal plants, we selected five pairs of exotic invasive and native clonal plant species that are congeneric and co-occurring in China as experimental materials. We grew the clonal fragment pairs of these invasive and native plants under high, low, or no contrast of reciprocal patchiness of light and nutrient, respectively, with ramet connections either severed (division of labor prevented) or kept intact (division of labor allowed). The results showed that connection significantly decreased the proportion of biomass allocated to roots in distal (younger) ramets, whereas it increased in proximal (older) ramets of all studied plants under high -contrast treatments. This clear pattern strongly indicated the occurrence of division of labor. Furthermore, the connection had a more pronounced effect on the pattern of biomass allocation of invasive alien plants, resulting in a greater increase in biomass for invasive alien plants compared to native plants. These findings suggest that the invasive alien plants possess a greater capacity for division of labor, which may confer a competitive advantage to them over natives, thus facilitating their invasion success in some heterogeneous habitats such as forest edges where light and soil nutrients show a high negative correlation.

Hypertensive cerebral hemorrhage, the most common prevalent of spontaneous cerebral hemorrhage, poses a significant threat to patient mortality and morbidity, while therapeutic options remain limited, making the disease a burden not only for patients’ families but also a major challenge for national healthcare systems. The elevation of intracranial pressure subsequent to hypertensive cerebral hemorrhage is a critical contributor to mortality. However, it often manifests before the onset of clinical symptoms, which are typically atypical, leading to delayed treatment and irreversible consequences for the patient. Hence, early detection of intracranial pressure variations can aid in timely, efficient, and precise treatment, reducing patient mortality. Invasive intracranial pressure monitoring enables real-time, accurate monitoring of intracranial pressure changes, providing clinicians with therapeutic guidance and overcoming the limitations of empirical treatment. This article aims to review the use of invasive intracranial pressure monitoring in postoperative hypertensive cerebral hemorrhage and hopes to contribute to clinical and scientific research.

The dynamic visual acuity test (DVAT) is a functional evaluation tool for the impairment and compensation of the vestibular system, which could reflect the Vestibulo-ocular reflex (VOR) function. We present an overview of DVAT research, displaying recent advances in test methods, application, and influencing factors; and discussing the clinical value of DVAT to provide a reference for clinical application. There are two primary types of DVAT: dynamic-object DVAT and static-object DVAT. For the latter, in addition to the traditional bedside DVAT, there are numerous other approaches, including Computerized DVAT (cDVAT), DVAT on a treadmill, DVAT on a rotary, head thrust DVA (htDVA) and functional head impulse testing (fHIT), gaze shift dynamic visual acuity with walking (gsDVA), translational dynamic visual acuity test (tDVAT), pediatric DVAT. The results of DAVT are affected by subject [occupation, static visual acuity (SVA), age, eyeglass lenses], testing methods, caffeine, and alcohol. DVAT has numerous clinical applications, such as screening for vestibular impairment, assessing vestibular rehabilitation, predicting fall risk, and evaluating ophthalmology-related disorders, vestibular disorders, and central system disorders.

Introduction: Coronavirus disease 2019 (COVID-19) has become a global pandemic and poses a serious threat to human health. Many studies have shown that pre-existing nonalcoholic steatohepatitis (NASH) can worsen the clinical symptoms in patients suffering from COVID-19. However, the potential molecular mechanisms between NASH and COVID-19 remain unclear. To this end, key molecules and pathways between COVID-19 and NASH were herein explored by bioinformatic analysis.Methods: The common differentially expressed genes (DEGs) between NASH and COVID-19 were obtained by differential gene analysis. Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out using the obtained common DEGs. The key modules and hub genes in PPI network were obtained by using the plug-in of Cytoscape software. Subsequently, the hub genes were verified using datasets of NASH (GSE180882) and COVID-19 (GSE150316), and further evaluated by principal component analysis (PCA) and receiver operating characteristic (ROC). Finally, the verified hub genes were analyzed by single-sample gene set enrichment analysis (ssGSEA) and NetworkAnalyst was used for the analysis of transcription factor (TF)-gene interactions, TF-microRNAs (miRNA) coregulatory network, and Protein-chemical Interactions.Results: A total of 120 DEGs between NASH and COVID-19 datasets were obtained, and the PPI network was constructed. Two key modules were obtained via the PPI network, and enrichment analysis of the key modules revealed the common association between NASH and COVID-19. In total, 16 hub genes were obtained by five algorithms, and six of them, namely, Kruppel-like factor 6 (KLF6), early growth response 1 (EGR1), growth arrest and DNA-damage-inducible 45 beta (GADD45B), JUNB, FOS, and FOS-like antigen 1 (FOSL1) were confirmed to be closely related to NASH and COVID-19. Finally, the relationship between hub genes and related pathways was analyzed, and the interaction network of six hub genes was constructed with TFs, miRNAs, and compounds.Conclusion: This study identified six hub genes related to COVID-19 and NASH, providing a new perspective for disease diagnosis and drug development.

Background: JAK2, CALR, and MPL gene mutations are recognized as driver mutations of myeloproliferative neoplasms (MPNs). MPNs without these mutations are called triple-negative (TN) MPNs. Recently, novel mutation loci were continuously discovered using next-generation sequencing (NGS), along with continued discussion and modification of the traditional TN MPN.Case presentation: Novel pathogenic mutations were discovered by targeted NGS in 4 patients who were diagnosed as JAK2 unmutated polycythaemia vera (PV) or TN MPN. Cases 1, 2, and 3 were of patients with PV, essential thrombocythemia (ET), and primary myelofibrosis (PMF); NGS detected JAK2 p.H538_K539delinsQL (uncommon), CALR p.E380Rfs*51 (novel), and MPL p.W515_Q516del (novel) mutations. Case 4 involved a patient with PMF; JAK2, CALR, or MPL mutations were not detected by qPCR or NGS, but a novel mutation SH2B3 p.S337Ffs*3, which is associated with the JAK/STAT signal transduction pathway, was found by NGS.Conclusion: NGS, a more multidimensional and comprehensive gene mutation detection, is required for patients suspected of having MPN to detect non-canonical driver variants and avoid the misdiagnosis of TN MPN. SH2B3 p.S337Ffs*3 can drive MPN occurrence, and SH2B3 mutation may also be a driver mutation of MPN.

BackgroundAlthough cellular and animal studies have reported that resolvin D1 (RvD1) and resolvin D2 (RvD2) are mechanisms involved in the development of type 2 diabetes mellitus (T2DM), the impact of RvD1 and RvD2 on the risk of T2DM at a population level remains unclear.MethodsWe included 2755 non-diabetic adults from a community-based cohort in China and followed them for seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of RvD1 and RvD2 with T2DM probability. Time-dependent receiver operator characteristics (ROC) curve was used to evaluate the predictive performance of RvD1 and RvD2 for the risk of T2DM based on the Chinese CDC T2DM prediction model (CDRS).ResultsA total of 172 incident T2DM cases were identified. Multivariate-adjusted HRs (95% CI) for T2DM across quartiles of RvD1 levels (Q1, Q2, Q3 and Q4) were 1.00, 1.64 (1.03-2.63), 1.80 (1.13-2.86) and 1.61 (1.01-2.57), respectively. Additionally, body mass index (BMI) showed a significant effect modification in the association of RvD1 with incident T2DM (Pinteraction = 0.026). After multivariate adjustment, the HR (95% CI) for T2DM in the fourth compared with the first quartile of RvD2 was 1.94 (95% CI: 1.24-3.03). Time-dependent ROC analysis showed that the area under time-dependent ROC curves of the “CDRS+RvD1+RvD2” model for the 3-, 5- and 7-year risk of T2DM were 0.842, 0.835 and 0.828, respectively.ConclusionsHigher RvD1 and RvD2 levels are associated with a higher risk of T2DM at the population level.

ObjectiveThe aim of this study was to explore the symptoms, treatment, and pathogenesis of ovarian juvenile granulosa cell tumors with Ollier’s disease in children.MethodsFrom October 2019 to October 2020, clinical data were retrospectively analyzed for one case of ovarian juvenile granulosa cell tumors with Ollier’s disease. Whole-exome sequencing and Sanger sequencing were used to detect gene mutation in ovarian tumor and chondroma tissue. NADP-dependent isocitrate dehydrogenase-1 (IDH1) and S6 ribosomal protein expression levels in cells transfected with wild-type or mutant plasmid were analyzed by Western blot.ResultsThe 4-year-old female showed multiple skeletal deformities, bilateral breast development with chromatosis, and vulvar discharge. Sex hormone assay suggested that estradiol and prolactin were elevated, and the x-ray of limbs suggested enchondroma. Pelvic ultrasound and abdominal CT revealed a right ovarian solid mass. Pathologic examination of the right ovarian solid mass showed a juvenile granulosa cell type. A c.394C>T (p. Arg132Cys) mutation of the IDH1 gene was detected in both the ovarian juvenile granulosa cell tumors and enchondroma. Transfection of HeLa cells with either WT or Mut plasmid caused 4.46- or 3.77-fold overexpression of IDH1 gene compared to non-transfected control cells, respectively. R132C mutation inhibited the phosphorylation of S6 ribosomal protein, which is central to the mTOR pathway. Postoperatively, estradiol and prolactin levels fell to values normal for her age and bilateral breast gradual retraction.ConclusionThe incidence of ovarian juvenile granulosa cell tumors with Ollier’s disease in children may be caused by generalized mesodermal dysplasia; IDH1 gene mutation may play a facilitated role in this process. Surgical operation is the main treatment. We suggest that patients with ovarian juvenile granulosa cell tumors and Ollier’s disease should undergo regular investigation.

The Shanxi rift valley is a continental rift system that is characterized by mantle uplift, crustal thinning, and tectonic deformation. A continuous, vertical crustal-deformation field can elucidate the constraints for understanding the mechanisms currently driving the deformation of the rift. Accordingly, we acquired and processed data from 250 continuous and mobile GPS stations located in the Shanxi rift valley and its surrounding region. Accounting for the influence of fault activity, we established the vertical crustal-deformation field of the Shanxi rift valley as a continuous function of space, using an adaptive least-squares collocation method. The main research findings are stated as follows: 1) the adaptive least-squares model yielded a reliable interpolation prediction results with adequate robustness, even for relatively sparse actual observation data. 2) The current general deformation pattern of the Shanxi rift valley exhibits an uplift of the mountainous regions on both sides and subsidence of the central basin. The average uplift rate of the mountain area is 2–3 mm/a, and the subsidence rate of the basin is not uniform and is positively correlated with the spatial distribution of the Cenozoic sediment thickness. However, in certain areas, a high subsidence rate of 10–30 mm/a is associated with human activities such as groundwater exploitation. 3) In summary, the current vertical crustal deformation occurring in the Shanxi rift valley correlates with the pattern over a time scale of millions of years. Overall, it is controlled by regional geological structure pattern, and is influenced by nonstructural factors in the shallow crust, exhibiting both complex and orderly characteristics in its spatial distribution.

Populus is a promising lignocellulosic feedstock for biofuels and bioproducts. However, the cell wall biopolymer lignin is a major barrier in conversion of biomass to biofuels. To investigate the variability and underlying genetic basis of the complex structure of lignin, a population of 409 three-year-old, naturally varying Populus trichocarpa genotypes were characterized by heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR). A subsequent genome-wide association study (GWAS) was conducted using approximately 8.3 million single nucleotide polymorphisms (SNPs), which identified 756 genes that were significantly associated (−log10(p-value)>6) with at least one lignin phenotype. Several promising candidate genes were identified, many of which have not previously been reported to be associated with lignin or cell wall biosynthesis. These results provide a resource for gaining insights into the molecular mechanisms of lignin biosynthesis and new targets for future genetic improvement in poplar.

We demonstrate a Kerr-lens mode-locked femtosecond Yb:YAG thin-disk oscillator and investigate the approach to increase the optical-to-optical efficiency based on the scheme of direct multiple passes of the laser beam through the thin-disk medium. With twelve passes through the thin disk, 266-fs pulses were delivered from the oscillator with an average power of 105.6 W at a repetition rate of 20 MHz. The corresponding optical-to-optical efficiency is 31.1%, which is, to the best of our knowledge, the highest efficiency of any mode-locked thin-disk oscillator with pulse duration below 300 fs. This demonstration paves the way to even more efficient mode-locked femtosecond thin-disk oscillators, and provides an excellent laser source for the applications such as non-linear frequency conversion and high-precision industrial processing.

BackgroundWith the aging population in East Asia, the prevalence of dementia and the need for patient care is increasing. Family caregivers of people with dementia are at risk of physical and mental health problems. Filial piety culture regulates relationships within East Asian families and effects the well-being and behavior of dementia family caregivers (CGs).ObjectiveTo systematically assess the experience of East Asian dementia caregivers in filial culture. Methods: Electronic databases, including MEDLINE, APA PsycINFO, CINAHL (via EBSCOhost), Web of Science, and Cochrane Library, were searched for relevant studies up to July 2021. Only original articles were included.ResultsThirteen eligible studies were included, of which eight were qualitative and five were quantitative. Meta-analysis showed a negative association (r = −0.18, 95%CI [−0.28, −0.08]) between filial culture and caregiver burden. The quantitative studies identified four themes related to dementia caregivers’ experiences: (1) Recognition and understanding of filial piety as part of cultural identity, (2) Role transitions- from child to CG, (3) Filial piety’s constraints on CGs; (4) CGs’ self-compassion through changing cultural norms of filial practice.ConclusionFilial culture influences the whole process behind caregiving for East Asian dementia caregivers. At the same time, cultural transition has also brought about new connotations and practices to filial culture.

ObjectiveThis study provided a systematic analysis of the trend in incidence and incidence-based mortality for cutaneous squamous cell carcinoma (cSCC) on the lips in the USA using demographic characteristics from the Surveillance, Epidemiology, and End Results (SEER) database.MethodsPatients diagnosed with cSCC on the lips between 2000 and 2019 from the 17 registries of the USA were identified. Incidence and incidence-based mortality rates were analyzed using SEER*Stat 8.4.0.1 software. This paper calculated incidence rates and incidence-based mortality rates by 100,000 person-years for sex, age, race, SEER registries, median household income ($/year), rural-urban distribution, and primary site. The annual percent changes (APC) in incidence and incidence-based mortality rates were then calculated using joinpoint regression software.ResultsAmong 8,625 patients diagnosed with cSCC on the lips from 2000 to 2019, men (74.67%), white (95.21%), and 60–79 years old were the most common population, and 3,869 deaths from cSCC on the lips occurred. The overall incidence of cSCC on the lips was 0.516 per 100,000 person-years. cSCC on the lip incidence rates were highest among men, white, and patients aged 60–79 years old. cSCC on the lip incidence rates decreased by 3.210%/year over the study period. The incidence of cSCC on the lips has been decreasing in all sexes, ages, high- or low-income households, and urban or rural patients. The overall incidence-based mortality rate of cSCC on the lips during 2000–2019 was 0.235 per 100,000 person-years. cSCC on the lip incidence-based mortality rates were highest among men, whites, and people older than 80 years old. cSCC on the lip incidence-based mortality increased by 4.975%/year over the study period. cSCC on the lip incidence-based mortality rates increased for all sexes, races, ages, primary sites, high- or low-income households, and urban or rural patients during the study period.ConclusionAmong patients in the USA diagnosed with cSCC on the lips from 2000 to 2019, the overall incidence decreased by 3.210% annually, and incidence-based mortality increased by 4.975%/year. These findings update and supplement the epidemiological information of cSCC on the lips in the USA.

Coronary artery spasm (CAS) is characterized by reversible diffuse or focal vasoconstriction, a phenomenon that plays an important role in the pathogenesis of ischemic heart disease. Fatal arrhythmias, such as ventricular tachycardia/fibrillation and complete atrioventricular block (AV-B), are very common in patients with CAS. Nondihydropyridine calcium channel blockers (CCBs) such as diltiazem were recommended as first-line medications for treating and preventing CAS episodes. However, its use remains controversial in CAS patients with AV-B as this type of CCB can also cause AV-B itself. Here, we present the use of diltiazem in a patient with complete AV-B caused by CAS. The patient's chest pain was rapidly relieved, and complete AV-B was promptly restored to sinus rhythm following the administration of intravenous diltiazem without any adverse effects. In this report, we highlight the useful and effective application of diltiazem for treating and preventing complete AV-B caused by CAS.

IntroductionThe objective of this study is to thoroughly analyze the detailed genomic characteristics of clinical strain 211703 of Aeromonas caviae, which co-carrying blaRSA-1 and blaNDM-1 genes. 211703 was isolated from the patient’s cerebrospinal fluid drainage sample in a Chinese tertiary hospital.MethodsCarbapenemase NDM was detected by the immunocolloidal gold technique. The MIC values were determined by VITEK2. The whole genome sequence of 211703 was analyzed using phylogenetics, genomic comparison, and extensive dissection.ResultsThis study revealed that 211703 only contained a single 4.78 Mb chromosome (61.8% GC content), and no plasmids were discovered in 211703. 15 different types of resistant genes were detected in the genome of 211703, including blaRSA-1 harbored on integrative and mobilizable element (IME) Tn7413a, and blaNDM-1 harbored on integrative and conjugative element (ICE). The ICE and IME were all carried on the chromosome of 211703 (c211703). Detailed comparison of related IMEs/ICEs showed that they shared similar conserved backbone regions, respectively. Comprehensive annotation revealed that blaRSA-1 was carried by the gene cassette of a novel integron In2148 on Tn7413a, and blaNDM-1 was captured by an insertion sequence ISCR14-like on the ICE of 211703. We speculated that mobile genetic elements (MGEs) such as ICE and IME facilitated the spread of resistance genes such as blaRSA-1 and blaNDM-1.DiscussionIn conclusion, this study provides an overall understanding of the genomic characterization of clinically isolated A. caviae 211703, and an in-depth discussion of multiple acquisition methods of drug resistance genes in Aeromonas. To the best of our knowledge, this is the first report of A. caviae carrying blaRSA-1 even both blaRSA-1 and blaNDM-1, and this is the first bacterium carrying blaRSA-1 isolated from the clinical setting.

This study proposes a novel color image encryption algorithm based on a 3D chaotic Hopfield neural network and random row–column permutation. First, a 3D chaotic Hopfield neural network is proposed to produce the random sequence for generating the diffusion and permutation keys. Then, the rows and columns of the original image are randomly arranged according to the permutation key in the permutation process. Three subgraphs are formed by separating the R, G, and B components of the color image in the diffusion process. Each of the three subgraphs is split along the columns to form three parts; the left and middle parts are exchanged. Three diffusion keys are used to encrypt each of the three parts. Finally, the individually encrypted subgraphs are stitched together to obtain the final encrypted image. Simulation results using MATLAB and FPGA and security analysis demonstrate that the encryption scheme has good performance.

Ischemia-reperfusion injury (IRI) is an inevitable pathological process after organic transplantations. Although traditional treatments restore the blood supply of ischemic organs, the damage caused by IRI is always ignored. Therefore, the ideal and effective therapeutic strategy to mitigate IRI is warrented. Curcumin is a type of polyphenols, processing such properties as anti-oxidative stress, anti-inflammation and anti-apoptosis. However, although many researches have been confirmed that curcumin can exert great effects on the mitigation of IRI, there are still some controversies about its underlying mechanisms among these researches. Thus, this review is to summarize the protective role of curcumin against IRI as well as the controversies of current researches, so as to clarify its underlying mechanisms clearly and provide clinicians a novel idea of the therapy for IRI.