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BackgroundThe effectiveness and safety of a novel class of hypoglycemic medications known as sodium-glucose cotransporter 2 (SGLT2) inhibitors have not been completely established in relation to acute heart failure (AHF). Consequently, we sought to compare the prognostic and safety outcomes of patients administered SGLT2 inhibitors for the treatment of AHF.MethodsAn extensive search of the Web of Science, PubMed, and EMBASE was conducted for randomized controlled trials and observational studies that have evaluated the use of SGLT2 inhibitors in AHF from the inception of these drugs to the present. We compiled data related to cardiovascular safety and prognosis. Aggregated risk ratios (RR), mean differences (MD), or standardized mean differences (SMD) were generated for all outcomes, with 95% confidence intervals (CIs), to evaluate the predictive significance of SGLT2 inhibitors in patients with AHF.ResultsWe identified 4,053 patients from 13 studies. Patients experienced a substantial reduction in all-cause mortality (RR = 0.82, 95% CI: 0.70–0.96, P = 0.01), readmission rates (RR = 0.85, 95% CI: 0.74–0.98, P = 0.02), the number of heart failure exacerbation events (RR = 0.69, 95% CI: 0.50–0.95, P = 0.02), and the number of rehospitalization events due to heart failure (RR = 0.71, 95% CI: 0.58–0.86, P

Introduction: Mild stenosis [degree of stenosis (DS) < 50%] is commonly labeled as nonobstructive lesion. Some lesions remain stable for several years, while others precipitate acute coronary syndromes (ACS) rapidly. The causes of ACS and the factors leading to diverse clinical outcomes remain unclear.Method: This study aimed to investigate the hemodynamic influence of mild stenosis morphologies in different coronary arteries. The stenoses were modeled with different morphologies based on a healthy individual data. Computational fluid dynamics analysis was used to obtain hemodynamic characteristics, including flow waveforms, fractional flow reserve (FFR), flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI).Results: Numerical simulation indicated significant hemodynamic differences among different DS and locations. In the 20%–30% range, significant large, low-velocity vortexes resulted in low TAWSS (40 dyne/cm2), rapidly expanding the high TAWSS area (averagely increased by 0.46 cm2) in left main artery and left anterior descending artery (LAD), where high OSI areas remained extensive (>0.19 cm2).Discussion: While mild stenosis does not pose any immediate ischemic risk due to a FFR > 0.95, 20%–50% stenosis requires attention and further subdivision based on location is essential. Rapid progression is a danger for lesions with 20%–30% DS near the stenoses and in the proximal LAD, while lesions with 30%–50% DS can cause plaque injury and rupture. These findings support clinical practice in early assessment, monitoring, and preventive treatment.

Fibroblastic reticular cells (FRCs) are a subpopulation of stromal cells modulating the immune environments in health and disease. We have previously shown that activation of TLR9 signaling in FRC in fat-associated lymphoid clusters (FALC) regulate peritoneal immunity via suppressing immune cell recruitment and peritoneal resident macrophage (PRM) retention. However, FRCs are heterogeneous across tissues and organs. The functions of each FRC subset and the regulation of TLR9 in distinct FRC subsets are unknown. Here, we confirmed that specific deletion of TLR9 in FRC improved bacterial clearance and survival during peritoneal infection. Furthermore, using single-cell RNA sequencing, we found two subsets of FRCs (CD55hi and CD55lo) in the mesenteric FALC. The CD55hi FRCs were enriched in gene expression related to extracellular matrix formation. The CD55lo FRCs were enriched in gene expression related to immune response. Interestingly, we found that TLR9 is dominantly expressed in the CD55lo subset. Activation of TLR9 signaling suppressed proliferation, cytokine production, and retinoid metabolism in the CD55lo FRC, but not CD55hi FRC. Notably, we found that adoptive transfer of Tlr9-/–CD55lo FRC from mesenteric FALC more effectively improved the survival during peritonitis compared with WT-FRC or Tlr9-/–CD55hi FRC. Furthermore, we identified CD55hi and CD55lo subsets in human adipose tissue-derived FRC and confirmed the suppressive effect of TLR9 on the proliferation and cytokine production in the CD55lo subset. Therefore, inhibition of TLR9 in the CD55lo FRCs from adipose tissue could be a useful strategy to improve the therapeutic efficacy of FRC-based therapy for peritonitis.

IntroductionRestored cardiopulmonary function is efficiently achieved by utilizing extracorporeal membrane oxygenation (ECMO). Nevertheless, the incidence of Clostridioides difficile infection (CDI) associated with ECMO is relatively uncommon.Case presentationIn this report, we present the case of a 59-year-old male with severe chest pain due to acute myocardial infarction, subsequently necessitating ECMO support. During the first day of hospitalization, pulmonary infections were observed, and piperacillin-tazobactam was prescribed for 7 days at low dosages. However, the patient developed severe diarrhea 4 days later. After ruling out common pathogens, we suspected the occurrence of CDI and performed genetic testing for C. difficile toxin, confirming our diagnosis. The prescription of vancomycin resulted in slight improvement, while fecal microbiota transplantation (FMT) proved to be more effective.ConclusionIn this case, temporary application of ECMO was applied, and the anti-infective treatment relied on the use of antibiotics at short-term, low-dose, and low CDI risk. Hence, the occurrence of CDI was considered an uncommon event, which may serve as a reference for future cases.

IntroductionGanmai Dazao Decoction is a traditional Chinese recipe, and is composed of licorice, floating wheat, and jujube.MethodsEffects of lactic acid bacteria fermentation on the physicochemical properties, antioxidant activity, and γ-aminobutyric acid of Ganmai Dazao Decoction were studied. The changes of small and medium molecules in Ganmai Dazao Decoction before and after fermentation were determined by LC–MS non-targeted metabolomics.ResultsThe results showed that the contents of lactic acid, citric acid, acetic acid, and total phenol content increased significantly, DPPH free radical clearance and hydroxyl free radical clearance were significantly increased. γ-aminobutyric acid content was 12.06% higher after fermentation than before fermentation. A total of 553 differential metabolites were detected and identified from the Ganmai Dazao Decoction before and after fermentation by partial least squares discrimination and VIP analysis.DiscussionAmong the top 30 differential metabolites with VIP values, the content of five functional substances increased significantly. Our results showed that lactic acid bacteria fermentation of Ganmai Dazao Decoction improves its antioxidant effects and that fermentation of Ganmai Dazao Decoction with lactic acid bacteria is an innovative approach that improves the health-promoting ingredients of Ganmai Dazao Decoction.

IntroductionMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Ursolic acid (UA) can be used in the MS treatment with anti-inflammatory and neuroprotective activities. However, UA is insoluble in water, which may affect its medication effectiveness. In our previous study, UAOS-Na, a water-soluble derivative of UA was obtained. In this study, we evaluated the pharmacological effects and explored its underlying mechanism of UAOS-Na on experimental autoimmune encephalomyelitis (EAE).MethodsFirstly, the pharmacodynamics of UAOS-Na was investigated in EAE and Cuprizone-induced mice. And then the possible mechanisms were investigated by TMT proteomics and verified by in vitro and in vivo experiments.ResultsUAOS-Na (30 mg/kg/d) delayed the onset time of EAE from 11.78 days post immunization (dpi) to 14.33 dpi, reduced the incidence from 90.0% to 42.9%. UAOS-Na (60 mg/kg/d) reduced the serum levels of IFN-γ, IL-17A, TNF-α and IL-6, reduced the mononuclear cell infiltration of spinal cord, and inhibited the overexpression of key transcription factors T-bet and ROR-γt of EAE mouse spinal cord. In addition, UAOS-Na attenuated demyelination and astrogliosis in the CNS of EAE and cuprizone-induced mice. Mechanistically, proteomics showed that 96 differential expression proteins (DEPs) were enriched and 94 were upregulated in EAE mice compared with normal group. After UAOS-Na treatment, 16 DEPs were enriched and 15 were downregulated, and these DEPs were markedly enriched in antigen processing and presentation (APP) signaling pathway. Moreover, UAOS-Na downregulated the protein levels of Tapbp and H2-T23 in MHC-I antigen presentation pathway and reduced the proliferation of splenic CD8 T cells, thereby inhibiting the CNS infiltration of CD8 T cells.ConclusionOur findings demonstrated that UAOS-Na has both myelin protective and anti-inflammatory effects. And it could reduce the inflammation of MS by downregulating the expression of Tapbp and H2-T23 in the MHC-I antigen presentation pathway.

BackgroundThe developments in cosmetic sciences and technologies have generated a gap between the cosmetics and their users. Users including regular customers, clinicians, industry personnel, researchers, testing agencies, beauty salon workers, and mass media hardly possess the ability to distinguish truth from falsehood. The gap remained as one major reason for inappropriate cosmetics usage, insufficient efficacy, and even cosmetics adverse reactions (CARs).MethodsAiming at enhancing the relevant practitioners’ cosmetic and dermatologic sciences, we launched a cosmetic and dermatologic sciences continuing medical education (CME) since 2008. The objective of the current study was to evaluate the effectiveness of the CME. We summarized and analyzed the project for the last 15 years. Meanwhile, an online survey consisted of three parts was performed to evaluate the CME and to collect the trainees’ comments.ResultsA total of 3,923 trainees have participated in the CME project from 2008 to 2022. The trainees included clinicians, industry staffs, biomedical researchers, third-party cosmetics testing staffs, beauty salon staffs, students, and media staffs. The trainees had theory courses on cosmetic and dermatologic sciences, cosmetics DIY practice & video watching, and an optional guided tour during the 4.5-day CME. Eight hundred and twenty-three trainees and 586 control subjects responded to the online survey. The comprehensive test in the second part of the survey demonstrated that compared with the control group, the CME project significantly enhanced the trainees’ perception and knowledge regarding the cosmetics formula sciences, basic dermatologic sciences, cosmetics usage, noninvasive measurements, new advances, CARs, and laws (p = 0.000). Trainees of all occupations ranked “basic dermatologic sciences and skin diseases” as the most significant sections. Trainees of all occupations believed the CME has contributed most in “understand the function & efficacy of cosmetics.” We noticed the occupational variances. Over 97% of trainees were willing to recommend the CME to the others.ConclusionThe CME project significantly enhanced the trainees’ cosmetic and dermatologic sciences, which bridged the gap between cosmetics and public skin health. This multidisciplinary CME also contributed to establishing an interdisciplinary interaction and cooperation platform for the multiple occupations involved in the public skin health maintenance and promotion.

BackgroundMagnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) and stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) are two effective, minimally invasive treatments for epilepsy with focal cortical dysplasia (FCD). The purpose of this study is to conduct a meta-analysis to evaluate and compare the efficacy and safety of these two therapies in epilepsy patients with FCD.MethodsWe searched PubMed, Embase, Cochrane, and other databases for articles published before March 2023. The primary objective was to compare the effectiveness and complications of MRgLiTT and SEEG-RFTC in epilepsy patients with FCD. The second objective was to determine which method provides a better prognosis for specific subgroup patients.ResultsAccording to the inclusion and exclusion criteria, 18 studies were included, comprising 270 FCD patients including 37 patients from 6 MRgLiTT studies and 233 from 12 SEEG-RFTC studies. There were no significant differences between MRgLiTT and SEEG-RFTC groups in the seizure-freedom rate (59%, 95% CI 44–74%; 52%, 95% CI 47–57%, P = 0.86) and the rate of ≥50% seizure-reduction of FCD (90%, 95% CI 80–100%; 90%, 95% CI 86–94%, P = 0.42). Both methods had low complication rates (17.1%, 28/159) and long-term complication (2.5%, 4/159) rate, with no significant difference between them (P = 0.17).ConclusionBoth MRgLiTT and SEEG-RFTC are safe and minimally invasive treatments for patients with FCD. They have comparable performance in terms of postoperative seizure-freedom rates in patients with FCD, and both can be used as treatment options for patients with FCD. Our study found that SEEG-RFTC had a better therapeutic effect in the FCD2b subgroup.

IntroductionThe tumor microenvironment of hepatocellular carcinoma is composed of multiple cells, and the interactive communication between cells drives tumor progression and characterizes the tumor. Communication between cells is mainly achieved through signal transduction between receptor ligands, and the rise of single-cell technology has made it possible to analyze the communication network between cells.MethodsWe applied a train of bioinformatic techniques and in vitro experiments. We analyzed the composition of the microenvironment of liver cancer by combining single-cell sequencing data and transcriptome sequencing data from liver cancer to construct molecular typing and risk models for LRs. Then, we analyzed association of it with prognosis, mutation, KEGG, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB) and drug sensitivity in liver cancer. qPCR and was used to identify SLC1A5 expression in LIHC cell lines and CCK8, transwell and cell colony formation were performed to validate the function of SLC1A5. Meanwhile, we also performed polarization of macrophages.ResultsIn this experiment, we found that liver cancer tissues are rich in immune and mesenchymal cells, and there is extensive signaling between individual cells, so we constructed molecular typing and risk models for LRs. Combining clinical data revealed significant differences in clinical characteristics, prognosis and mutated genes between the molecular typing of receptor-ligand pairs, as well as in sensitivity to drugs; similarly, there were significant prognostic differences between the risk models. There were also notable differences in activated signaling pathways, infiltrating immune cells and immune subtypes. Subsequently, we used siRNA to knock down SLC1A5 in hepatocellular carcinoma cells and found that cell proliferation, migration and invasion were diminished.ConclusionsIn conclusion, our LRs model may become a marker to guide clinical treatment and prognosis.

BackgroundFunctional constipation (FCon) is a common functional gastrointestinal disorder (FGID). Studies have indicated a higher likelihood of psychiatric disorders, such as anxiety, depression, sleep disturbances, and impaired concentration, among patients with FCon. However, the underlying pathophysiological mechanisms responsible for these symptoms in FCon patients remain to be fully elucidated. The human brain is a complex network architecture with several fundamental organizational properties. Neurological interactions between gut symptoms and psychiatric issues may be closely associated with these complex networks.MethodsIn the present study, a total of 35 patients with FCon and 40 healthy controls (HC) were recruited for a series of clinical examinations and resting-state functional magnetic imaging (RS-fMRI). We employed the surface-based analysis (SBA) approach, utilizing the Schaefer cortical parcellation template and Tikhonov regularization. Graph theoretical analysis (GTA) and functional connectivity (FC) analysis of RS-fMRI were conducted to investigate the aberrant network alterations between the two groups. Additionally, correlation analyses were performed between the network indices and clinical variables in patients with FCon.ResultsAt the global level, we found altered topological properties and networks in patients with FCon, mainly including the significantly increased clustering coefficient (CP), local efficiency (Eloc), and shortest path length (LP), whereas the decreased global efficiency (Eglob) compared to HC. At the regional level, patients with FCon exhibited increased nodal efficiency in the frontoparietal network (FPN). Furthermore, FC analysis demonstrated several functional alterations within and between the Yeo 7 networks, particularly including visual network (VN), limbic network (LN), default mode network (DMN), and somatosensory-motor network (SMN) in sub-network and large-scale network analysis. Correlation analysis revealed that there were no significant associations between the network metrics and clinical variables in the present study.ConclusionThese results highlight the altered topological architecture of functional brain networks associated with visual perception abilities, emotion regulation, sensorimotor processing, and attentional control, which may contribute to effectively targeted treatment modalities for patients with FCon.

BackgroundThe increasing prevalence of diabetes and its significant impact on mortality and morbidity rates worldwide has led to a growing interest in understanding its common risk factors, particularly in relation to chronic kidney disease (CKD). This research article aims to investigate the shared risk factors between type 1 diabetes (T1D), type 2 diabetes (T2D), and CKD using a Mendelian randomization (MR) design.MethodsThe study utilized genome-wide association study (GWAS) datasets for T1D, T2D, and CKD from the FinnGen research project. GWAS summary statistics datasets for 118 exposure traits were obtained from the IEU OpenGWAS database. MR analyses were conducted to examine the causal relationships between exposure traits and each of the three outcomes. Multiple methods, including inverse-variance weighted, weighted median, and MR-Egger, were employed for the MR studies.ResultsPhenome-wide MR analyses revealed that eosinophil percentage exhibited a significant and suggestive causal association with T1D and CKD, respectively, suggesting its potential as a shared risk factor for T1D and CKD. For T2D, 34 traits demonstrated significant associations. Among these 34 traits, 14 were also significantly associated with CKD, indicating the presence of common risk factors between T2D and CKD, primarily related to obesity, height, blood lipids and sex hormone binding globulin, blood pressure, and walking pace.ConclusionThis research has uncovered the eosinophil percentage as a potential common risk factor for both T1D and CKD, while also identifying several traits, such as obesity and blood lipids, as shared risk factors for T2D and CKD. This study contributes to the understanding of the common risk factors between diabetes and CKD, emphasizing the need for targeted interventions to reduce the risk of these diseases.

InstructionLynch syndrome (LS) is the most common inherited cancer predisposition disorder of colorectal cancer (CRC) which is associated with pathogenic variants in 4 mismatch repair (MMR) genes. Here, we reported a multi-generation Chinese family clinically diagnosed with LS.MethodsTo identify the underlying pathogenic gene variants, 30 whole blood samples and 4 colorectal cancer tissue samples and their clinical data were obtained from this four-generation family. Microsatellite instability-high (MSI) testing, immunohistochemistry (IHC), and Whole-Exome Sequencing (WES) were performed to identify the MMR/MSI and the underlying gene variants. The minigene splicing assay and in vitro splicing assay were used to explore the function of this variant.ResultsMSI-H and dMMR was revealed by the MSI testing and IHC, Whole-Exome Sequencing (WES) in 3 patients successfully identified a splicing variant (c.793-1G>A) in intron 4 of MSH2. Sanger sequencing validated the WES results, and all the “healthy” individuals carrying the variant have been identified in the family by PCR. Bioinformatics analysis and in vitro minigene assay showed that the pathogenic variant affected the splicing process of MSH2 gene to generate 2 kinds defective transcription products, and consequently reduced the expression of MSH2 protein. The mutation carriers were later recommended for colonoscopy and other important cancer diagnostic inspections every 1-2 years because they both have a higher risk of LS.DiscussionWe found a pathogenic splicing variant (rs863225397, c.793-1G>A) of MSH2 gene, and furtherly confirmed that this mutation plays an important role in LS patients of this pedigree based on the vitro study. Our study indicates that one splicing mutation in the MSH2 gene (c.793-1G>A) causes LS and highlights the importance of LS gene testing.

The ancient traditional Chinese drink Bian-Que Triple-Bean Soup made by fermentation (FTBS) of Lactococcus lactis subsp. lactis YM313 and Lacticaseibacillus casei YQ336 is a potential functional drink. The effect of fermentation on the flavor and biological activity of FTBS was evaluated by analyzing its chemical composition. Five volatile flavors were detected in modified FTBS. Fermentation decreased the proportion of nonanal (beany flavor substances) but significantly increased the total flavone contents, phenol contents and many bioactive small molecule substances in FTBS. The changes of these substances led to the significant improvement of FTBS sensory evaluation, antioxidant activity and prebiotic potential. This research provides a theoretical basis for the application of Lactic acid bacteria (LAB) in the fermentation of edible plant-based foods and transformation from traditional food to industrial production.

BackgroundPrior observational studies have found an association between kidney function and cardiovascular diseases (CVDs). However, these studies did not investigate causality. Therefore, the aim of this study is to examine the causal relationship between kidney function and CVDs.MethodsWe utilized data from the eICU Collaborative Research Database (eICU-CRD) from the years 2014-2015 to evaluate the observational association between renal failure (RF) and CVDs. To investigate the causal effects of kidney function (estimated glomerular filtration rate [eGFR] and chronic kidney disease [CKD]) and CVDs (including atrial fibrillation [AF], coronary artery disease [CAD], heart failure [HF], any stroke [AS], and any ischemic stroke [AIS]), we conducted a two-sample bidirectional Mendelian randomization (MR) analysis.ResultsIn the observational analysis, a total of 157,883 patients were included. After adjusting for potential confounding factors, there was no significant association between baseline RF and an increased risk of developing CVDs during hospitalization [adjusted odds ratio (OR): 1.056, 95% confidence interval (CI): 0.993 to 1.123, P = 0.083]. Conversely, baseline CVDs was significantly associated with an increased risk of developing RF during hospitalization (adjusted OR: 1.189, 95% CI: 1.139 to 1.240, P < 0.001). In the MR analysis, genetically predicted AF was associated with an increased risk of CKD (OR: 1.050, 95% CI: 1.016 to 1.085, P = 0.004). HF was correlated with lower eGFR (β: -0.056, 95% CI: -0.090 to -0.022, P = 0.001). A genetic susceptibility for AS and AIS was linked to lower eGFR (β: -0.057, 95% CI: -0.079 to -0.036, P < 0.001; β: -0.029, 95% CI: -0.050 to -0.009, P = 0.005; respectively) and a higher risk of CKD (OR: 1.332, 95% CI: 1.162 to 1.528, P < 0.001; OR: 1.197, 95% CI: 1.023 to 1.400, P = 0.025; respectively). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of kidney function on CVDs. Outcomes remained consistent in sensitivity analyses.ConclusionOur study provides evidence for causal effects of CVDs on kidney function. However, the evidence to support the causal effects of kidney function on CVDs is currently insufficient. Further mechanistic studies are required to determine the causality.

ObjectiveThis study aims to analyze the current research status of acupuncture in the treatment of mild cognitive impairment (MCI) using bibliometric methods, explore current research hotspots, and predict future research trends.MethodsLiterature on acupuncture for MCI in China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases were searched from their inception to December 31, 2022. Articles were then filtered using inclusion and exclusion criteria and imported into VOSviewer 1.6.11 and CiteSpace 6.1.6msi software for descriptive analysis of publication numbers, network analysis of author/institution collaborations, and cluster analysis of keywords, as well as analysis of keyword emergence and linear relationships with time.ResultsThe Chinese and English databases included 243 and 565 relevant articles, respectively. The overall volume of Chinese and English literature was stable, with the annual volume generally increasing. In terms of countries, institutions, and authors, China had the highest number of English-language publications; however, the number of joint publications among institutions/authors was low. Research institutions were independent and dispersed, with no collaborative teams formed around a single institution/author. The hotspots in Chinese literature were “needling, treatment, electric acupuncture, nimodipine, cognitive training” and other clinical research directions. The hotspots in English literature were “acupuncture, electro-acupuncture, Alzheimer’s disease, dementia, cognitive impairment, memory, vascular dementia, mild cognitive impairment, stroke, hippocampus, injury,” and other mechanisms of action.ConclusionThe popularity of acupuncture for MCI is increasing year by year. Acupuncture for MCI, along with cognitive training, can help improve cognitive function. “Inflammation” is the frontier of acupuncture for MCI research. In the future, strengthening effective communication and cooperation among institutions, especially international cooperation, is essential for conducting high-quality research on acupuncture for MCI. This will help obtain high-level evidence and improve the output and translation of research results.

ObjectiveThe purpose of this study was to investigate the effects of the location of transverse carpal ligament (TCL) transection on the biomechanical property of the carpal arch structure. It was hypothesized that carpal tunnel release would lead to an increase of the carpal arch compliance (CAC) in a location-dependent manner.MethodsA pseudo-3D finite element model of the volar carpal arch at the distal carpal tunnel was used to simulate arch area change under different intratunnel pressures (0–72 mmHg) after TCL transection at different locations along the transverse direction of the TCL.ResultsThe CAC of the intact carpal arch was 0.092 mm2/mmHg, and the simulated transections ranging from 8 mm ulnarly to 8 mm radially from the center point of the TCL led to increased CACs that were 2.6–3.7 times of that of the intact carpal arch. The CACs after radial transections were greater than those ulnarly transected carpal arches.ConclusionThe TCL transection in the radial region was biomechanically favorable in reducing carpal tunnel constraint for median nerve decompression.

ObjectivesTo develop and validate a contrast-enhanced CT-based radiomics nomogram for the diagnosis of neuroendocrine carcinoma of the digestive system.MethodsThe clinical data and contrast-enhanced CT images of 60 patients with pathologically confirmed neuroendocrine carcinoma of the digestive system and 60 patients with non-neuroendocrine carcinoma of the digestive system were retrospectively collected from August 2015 to December 2021 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and randomly divided into a training cohort (n=84) and a validation cohort (n=36). Clinical characteristics were analyzed by logistic regression and a clinical diagnosis model was developed. Radiomics signature were established by extracting radiomic features from contrast-enhanced CT images. Based on the radiomic signature and clinical characteristics, radiomic nomogram was developed. ROC curves and Delong’s test were used to evaluate the diagnostic efficacy of the three models, calibration curves and application decision curves were used to analyze the accuracy and clinical application value of nomogram.ResultsLogistic regression results showed that TNM stage (stage IV) (OR 6.8, 95% CI 1.320-43.164, p=0. 028) was an independent factor affecting the diagnosis for NECs of the digestive system, and a clinical model was constructed based on TNM stage (stage IV). The AUCs of the clinical model, radiomics signature, and radiomics nomogram for the diagnosis of NECs of the digestive system in the training, validation cohorts and pooled patients were 0.643, 0.893, 0.913; 0.722, 0.867, 0.932 and 0.667, 0.887, 0.917 respectively. The AUCs of radiomics signature and radiomics nomogram were higher than clinical model, with statistically significant difference (Z=4.46, 6.85, both p < 0.001); the AUC difference between radiomics signature and radiomics nomogram was not statistically significant (Z=1.63, p = 0.104). The results of the calibration curve showed favorable agreement between the predicted values of the nomogram and the pathological results, and the decision curve analysis indicated that the nomogram had favorable application in clinical practice.ConclusionsThe nomogram constructed based on contrast-enhanced CT radiomics and clinical characteristics was able to effectively diagnose neuroendocrine carcinoma of the digestive system.

ContextSevere acute respiratory syndrome-coronavirus 2 (COVID-19) vaccines may incur changes in thyroid functions followed by mood changes, and patients with Hashimoto thyroiditis (HT) were suggested to bear a higher risk.ObjectivesWe primarily aim to find whether COVID-19 vaccination could induce potential subsequent thyroid function and mood changes. The secondary aim was to find inflammatory biomarkers associated with risk.MethodsThe retrospective, multi-center study recruited patients with HT receiving COVID-19–inactivated vaccines. C-reactive proteins (CRPs), thyroid-stimulating hormones (TSHs), and mood changes were studied before and after vaccination during a follow-up of a 6-month period. Independent association was investigated between incidence of mood state, thyroid functions, and inflammatory markers. Propensity score–matched comparisons between the vaccine and control groups were carried out to investigate the difference.ResultsFinal analysis included 2,765 patients with HT in the vaccine group and 1,288 patients in the control group. In the matched analysis, TSH increase and mood change incidence were both significantly higher in the vaccine group (11.9% versus 6.1% for TSH increase and 12.7% versus 8.4% for mood change incidence). An increase in CRP was associated with mood change (p< 0.01 by the Kaplan–Meier method) and severity (r = 0.75) after vaccination. Baseline CRP, TSH, and antibodies of thyroid peroxidase (anti-TPO) were found to predict incidence of mood changes.ConclusionCOVID-19 vaccination seemed to induce increased levels and incidence of TSH surge followed by mood changes in patients with HT. Higher levels of pre-vaccine serum TSH, CRP, and anti-TPO values were associated with higher incidence in the early post-vaccine phase.

Tendinopathy is a common disease in orthopaedics, seriously affecting tendon functions. However, the effects of non-surgical treatment on tendinopathy are not satisfactory and surgical treatments possibly impair the function of tendons. Biomaterial fullerenol has been proved to show good anti-inflammatory effects on various inflammatory diseases. For in vitro experiments, primary rat tendon cells (TCs) were treated by interleukin-1 beta (IL-1β) combined with aqueous fullerenol (5, 1, 0.3 μg/mL). Then inflammatory factors, tendon-related markers, migration and signaling pathways were detected. For in vivo experiments, rat tendinopathy model was constructed by local injection of collagenase into Achilles tendons of rats and fullerenol (0.5, 1 mg/mL) was locally injected 7 days after collagenase injection. Inflammatory factors and tendon-related markers were also investigated. Fullerenol with good water-solubility showed excellent biocompatibility with TCs. Fullerenol could increase expression of tendon-related factors (Collagen I and tenascin C) and decrease expression of inflammatory factors (matrix metalloproteinases-3, MMP-3, and MMP-13) and reactive oxygen species (ROS) level. Simultaneously, fullerenol slowed the migration of TCs and inhibited activation of Mitogen-activated protein kinase (MAPK) signaling pathway. Fullerenol also attenuated tendinopathy in vivo, including reduction of fiber disorders, decrease of inflammatory factors and increase of tendon markers. In summary, fullerenol is a promising biomaterial that can be used to treat tendinopathy.

IntroductionAs a form of platform economy, telemedicine is not growing as fast as other digital platforms. The existing literature seldom pays attention to how licensing policy affects the development of telemedicine platform models.MethodsThis paper uses the method of multi-case study and the theory of policy implementation as mutual adaptation to research the influence mechanism of telemedicine platform licensing policy on the platform model in China.ResultsThe findings of the current study are as follows: (1) three models can be classified in accordance with different platform providers in China: medical institution platform, Internet company platform and local government platform; (2) bargaining power, reputation mechanism and resource specificity are important dimensions in the analysis of platform models; (3) as an implementer in the process of licensing policy, the platform provider can not only directly determine the establishment and formation of platform model but also indirectly affect the sustainable development of platform model by affecting the supplier and the demander of platform; and (4) The impact between licensing policy and platform model is dynamic and bidirectional, mainly exerted via administrative orders, market-oriented mechanism and medical insurance.ConclusionsThe research enlightens practical exploration in telemedicine and enriches the theoretical innovation in platform.

ObjectiveTo investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes.MethodsThis was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis.ResultsThe prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline.ConclusionAnemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

In the traditional feudalistic society of China, there is a characteristic residential pattern of several core families with common ancestors living together in one house, as far as possible. Hence, the habitation of large families and their social dynamic always have a complex function and hierarchical structure. In this article, we consider a courtyard in South China as an example to enable a discussion of the mathematical relationship among the five basic functional spaces in it. Based on Zipf’s law, we find that the distribution of the five types of spaces, from large to small, can be described by the Pareto distribution with a shape parameter close to −1. Moreover, the Zipf parameters of different houses in the same area conform to the double Pareto distribution. This suggests that the size and shape of a residence also follows well-defined scaling laws. Additionally, it indicates that houses, at least traditional Chinese houses, have strong self-organization and self-similarity. It also shows that the power law of the Pareto distribution is applicable not only to the macro scale of the city but also the micro scale of housing.

In recent years, the exopolysaccharide (EPS) produced by deep-sea bacteria has attracted the interest of various researchers. In the present study, we have explored the properties and structure of a novel exopolysaccharide (called BPS) produced by Bacillus enclensis AP-4 from deep-sea sediments. The maximum yield of BPS was 4.23 ± 0.17 g L−1 in a 2216E modified medium. 1H NMR studies of the purified BPS displayed α and β-configuration sugar residues, including mannose, glucosamine, glucose, galactose, and xylose in a molar ratio of 1.00: 0.09: 0.04: 0.09: 0.07. BPS showed a molecular weight of 23,434 Da and was abundant in hydroxyl and amino residues. In addition, BPS exhibited a rod-like structure with a rough surface and was dominated by C, N, and O elements. The exopolysaccharide demonstrated remarkable thermal stability, high degradation temperature, and excellent emulsification capacity compared to most reported exopolysaccharides. Moreover, BPS displayed better quenching activities against the four radicals, which provided favorable protection for the strain. Finally, the freezing experiment investigated the cryoprotective effect of BPS on E. coli and S. aureus. BPS effectively improved the cell survival ratio and maintained the activity of Na+/K+-ATPase, which facilitates culture preservation. To the best of our knowledge, our work is the first report suggesting that marine exopolysaccharide has dual-activity. This work presents the foundation for the analysis of the structure and properties of exopolysaccharides produced by deep-sea bacteria.

Epimedium brevicornum Maxim. (Epimedii Folium) is a traditional medicine widely utilized in China for sexual dysfunction and osteoporosis treatment. Recently, studies have reported that Epimedium flavonoid icariin displayed hair growth and melanogenic ability by targeting tyrosinase activity. Nevertheless, icariin hydrolysate icariside II and icaritin cause depigmentation due to their tyrosinase inhibition. These pigment functional discrepancies from Epimedium constituents arouse our great interest. Then, this study focused on the pigmentation effects of Epimedii Folium extract (EFE) on melanin synthesis and melanosome biogenesis/transfer, and further identified the bioactive constituents. First, in in vitro systemic studies, we discovered that the potent melanogenic and repigmented effects of EFE were dependent on concentration and amount of time in multi-melanocytes, normal human skin tissue, and vitiligo perilesional areas. In vivo, EFE exhibited repigmented effect on two kinds of depigmented models of N-phenylthiourea-induced zebrafish and hydroquinone-induced mice. Mechanistically, EFE strongly promoted tyrosinase activity and upregulated the protein expression of tyrosinase families which finally contribute to melanin biosynthesis by activating the MAPK/ERK1/2 signal pathway. In addition, EFE effectively increased melanosome number, accelerated melanosome maturity and cytoplasmic transport through the growth/extension of melanocyte dendrites, and induced melanosome transfer from melanocyte to keratinocyte for pigmentation. The six main flavonoid ingredients were identified among EFE. Compared to others, epimedin B (EB) was confirmed as a high-content, low-toxicity, and effective melanogenic compound in EFE. Taking all these together, this study systematically demonstrates the potential pigmentation effect of Epimedium brevicornum Maxim., and clarifies its related molecular mechanisms and melanogenesis basis. These results give additional insight into Epimedium herb pharmacology and may provide a novel therapy basis for hypopigmentation disorders.

Eliminating or reducing ecological risks can help to observably guarantee the national security. In this article constructs a regional ecological risk evaluation framework is constructed on the basis of the Pressure-state-response model from three dimensions: social, environmental and natural dimension, and the quantitative research method is taken to investigate the ecological risks in 30 Chinese provinces from 2006 to 2017. Taking the establishment of a carbon emission trading market as a quasi-natural experiment, the author further explores the impact of market-based environmental policies on regional ecological risks and their heterogeneity, channels of action, and the synergistic effects of government intervention. It is found that: 1) The implementation of market-based environmental policies can improve regional responsiveness to ecological risks and significantly reduce the level of regional ecological risks, meanwhile the research results pass the identification assumptions and robustness tests. 2) The effects of market-based environmental policies are affected by the operational characteristics of market prices, liquidity and relative transaction scale. (iii)There are two essential approaches for market-based environmental policies to reduce regional ecological risks, named industrial structure upgrading and technology development. 4) Moderate government intervention can produce synergistic effects in the process of regional ecological risk reduction by market-based environmental policies, and it is able to maintain intervention produces policy synergistic effects within a temperate condition. In a word, these findings can provide both an important basis for adjusting the implementation scope and operational structure of market-based environmental policies. On the other hand, it can also offer a significant policy insight for regional ecological risk evaluation and management.

Biological control is an effective measure in the green control of rice diseases. To search for biocontrol agents with broad-spectrum and high efficiency against rice diseases, in this study, a strain of antagonistic bacterium BR-01 with strong inhibitory effect against various rice diseases was isolated from Bolbostemmatis Rhizoma by plate confrontation method. The strain was identified as Bacillus velezensis by morphological observation, physiological and biochemical identification, and molecular characterization by 16S rDNA and gyrB gene sequencing analysis. The confrontation test (dual culture) and Oxford cup assays demonstrated that B. velezensis BR-01 had strong antagonistic effects on Magnaporthe oryzae, Ustilaginoidea virens, Fusarium fujikuroi, Xanthomonas oryzae pv. Oryzicola, and Xanthomonas oryzae pv. oryzae, the major rice pathogens. The genes encoding antimicrobial peptides (ituA, ituD, bmyB, bmyC, srfAA, fenB, fenD, bacA, and bacD) were found in B. velezensis BR-01 by PCR amplification with specific primers. B. velezensis BR-01 could produce protease, cellulase, β-1,3-glucanase, chitinase, indoleacetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase, and might produce three lipopeptide antibiotics, surfactin, iturin, and fengycin based on Liquid chromatography–mass spectrometry (LC-MS) results. Furthermore, the plant assays showed that B. velezensis BR-01 had significant control effects on rice bacterial blight and bacterial leaf streak by pot experiments in greenhouse. In conclusion, B. velezensis BR-01 is a broad-spectrum antagonistic bacterium and has the potential as the ideal biocontrol agent in controlling multiple rice diseases with high efficiency.

The non-uniform growth and development of crops within Chinese Solar Greenhouses (CSG) is directly related to the micro-light climate within canopy. In practice, reflective films are used to improve micro-light climate within plant canopy by homogenizing light distribution and so increasing total plant light interception. However, as to our knowledge, the contributions to light distribution within canopy have not been investigated for passive reflector like reflective films. Field experiments dealing with light conditions and growth behavior over time, are complicated to carry out, time-consuming and hard to control, while however, accurate measurements of how reflective films influence the micro-light climate of canopy are an essential step to improve the growth conditions for any crop. Here, we propose a supplementary light strategy using reflective films to improve light distribution within plant canopy. Based on the example of CSG, a 3D greenhouse model including a detailed 3D tomato canopy structure was constructed to simulate the influence of supplementary reflective films to improve micro-light climate. Comparison of measured solar radiation intensity with predicted model data demonstrated that the model could precisely predict light radiation intensity over time with different time points and positions in the greenhouse. A series of reflective film configurations were investigated based on features analysis of light distribution in the tomato canopy on sunny days using the proposed model. The reflective film configuration scheme with the highest impact significantly improved the evenness of horizontal and vertical light distribution in tomato canopy. The strategy provided here can be used to configure reflective films that will enhance light conditions in CSG, which can be applied and extended in different scenarios.

Background: Epithelial–mesenchymal transition (EMT) and the immune microenvironment play important roles in the progression of gastric cancer (GC), but the joint role of both in GC is not clear.Methods: We identified EMT- and immune-related genes (EIRGs), and the molecular subtypes of EIRGs were identified by unsupervised cluster analysis. Then, we constructed an accurate EIRG_score model by using differential genes of molecular subtypes. The correlation of EIRG_score with prognosis, immune infiltration, gene mutation, chemotherapeutic drug sensitivity, and immunotherapy response was comprehensively analyzed. In addition, we investigated the biological function of EIRG_score via in vitro experiments.Results: A total of 808 GC patients were classified into two molecular subtypes, which were enriched in EMT and immune-related biological pathways and significantly correlated with prognosis and immune infiltration. The constructed EIRG_score had an important role in predicting prognosis and immunotherapeutic response. The higher EIRG_score was associated with worse prognosis, higher abundance of immunosuppressive cell infiltration, lower immune checkpoint genes expression, lower tumor mutation burden, microsatellite instability-high, lower chemotherapeutic drug sensitivity, and poorer immunotherapeutic response.Conclusion: EIRG_score may be used as a biomarker to assess prognosis and guide precise treatment.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide due to the high incidence rate of metastasis and recurrence. Semaphorin 3d (Sema3d) has been shown to play a critical role in vascular development during early embryogenesis and several forms of cancer progression via regulating cell migration. However, the function of Sema3d in hepatocellular carcinoma (HCC) remains elusive. This study aimed to explore the function and mechanisms of Sema3d in HCC. In our study, Sema3d expression was significantly downregulated in HCC tissues and cell lines. Downregulated Sema3d was closely correlated with aggressive clinicopathological features and poor clinical outcomes in HCC patients. Moreover, overexpression of Sema3d in HCCLM3 cells was significantly inhibited and knockdown of Sema3d in PLC/PRF/5 cells promoted proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of HCC cells in vitro and tumor growth, EMT, and metastasis in vivo. Furthermore, the RNA sequencing and gene set enrichment analysis (GSEA) indicated that these phenotypic and functional changes in Sema3d-interfered HCC cells were mediated by the Pi3k/Akt signaling pathway, and co-IP–combined mass spectrometry indicated Sema3d might interact with FLNA. Finally, we proved that Sema3d exerted its tumor-restraining effect by interacting with FLNA to inactivate the Pi3k/Akt signaling pathway and remodel the cytoskeleton. Our data showed that Sema3d restrained hepatocellular carcinoma proliferation, invasion, and metastasis through inactivating Pi3k/Akt via interaction with FLNA, which may serve as a novel prognostic predictor and a potential therapeutic target for HCC patients.

Background: The function of olfactomedin-like 2B (OLFML2B), as a member of the olfactomedin domain-containing protein family, remains ambiguous, especially in tumors. The current study explores the possible correlation between OLFML2B, prognosis, and immune infiltration in pan-cancer.Methods: We applied a number of bioinformatics techniques to probe the prospective function of OLFML2B, consisting of its association with prognosis, clinicopathology, alteration, GSEA, tumor microenvironment (TME), immune-associated genes, immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity in several cancer types. qPCR and immunohistochemistry were used to identify OLFML2B expression in LIHC cell lines and liver cancer tissues.Results: We discovered that OLFML2B was overexpressed in 14 cancers and positively related to several cancer type prognoses. The expression of OLFML2B was further validated in the LIHC cell lines. OLFML2B expression was bound up with TMB in 13 cancers, MSI in 10 cancers, and TME in almost all cancers. Furthermore, OLFML2B was highly co-expressed with genes encoding immune activators and immune suppressors. We further found that OLFML2B played a role in infiltrating different types of immune cells, such as macrophages and cancer-associated fibroblasts. OLFML2B may influence various cancer and immune-related pathways, such as the PI3K-Akt signaling pathway, ECM–receptor interaction, focal adhesion, and leukocyte transendothelial migration. In addition, OLFML2B may increase drug resistance of binimetinib, cobimentinib, and trametinib.Conclusion: Our outcomes reveal that OLFML2B may act as a prognostic marker and a potential target in immunotherapy for diverse tumors due to its oncogenesis function and immune infiltration.

Inspired by the distinct metabolic pathway of tumor cells, here a new anti-cancer therapy (i.e., Cu-TCPP(Fe) metal-organic frameworks (MOFs) with sonosensitizer for sonodynamic therapy (SDT) and tumor microenvironment (TME)-specific release of copper/iron for chemical catalysis) is introduced and verified. Upon exposure to ultrasound, the porphyrin structure in the MOFs yields reactive oxygen species (ROS), and the copper/iron induces the Fenton reaction in the TME existing H2O2 and acid. Thus, highly toxic ROS are generated through these TME-specific reactions to trigger the apoptosis and death of tumor cells. The current work paves a new avenue to design SDT with catalytic nanomedicine for the selective and effective treatment of tumors.

PurposeThe majority of solitary brain metastases appear similar to glioblastomas (GBMs) on magnetic resonance imaging (MRI). This study aimed to develop and validate an MRI-based model to differentiate intracranial metastases from GBMs using automated machine learning.Materials and MethodsRadiomics features from 354 patients with brain metastases and 354 with GBMs were used to build prediction algorithms based on T2-weighted images, contrast-enhanced (CE) T1-weighted images, or both. The data of these subjects were subjected to a nested 10-fold split in the training and testing groups to build the best algorithms using the tree-based pipeline optimization tool (TPOT). The algorithms were independently validated using data from 124 institutional patients with solitary brain metastases and 103 patients with GBMs from the cancer genome atlas.ResultsThree groups of models were developed. The average areas under the receiver operating characteristic curve (AUCs) were 0.856 for CE T1-weighted images, 0.976 for T2-weighted images, and 0.988 for a combination in the testing groups, and the AUCs of the groups of models in the independent validation were 0.687, 0.831, and 0.867, respectively. A total of 149 radiomics features were considered as the most valuable features for the differential diagnosis of GBMs and metastases.ConclusionThe models established by TPOT can distinguish glioblastoma from solitary brain metastases well, and its non-invasiveness, convenience, and robustness make it potentially useful for clinical applications.

Kinesin superfamily member 2C (KIF2C) is an essential regulator of the cell cycle and its aberrant expression can promote tumor progression. However, the mechanism of KIF2C in pan-cancer is unclear.Data were obtained from public databases, including The Cancer Genome Atlas (TCGA), UALCAN, TIMER and CellMiner. The data came from public databases such as The Cancer Genome Atlas (TCGA), UALCAN, TIMER, and CellMiner. We analyzed the correlation of KIF2C with expression, prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repairs (MMR), immune infiltration and anticancer drug sensitivity by R language.KIF2C was highly expressed in several tumors and correlated with poor prognosis. KIF2C expression was significantly correlated with TMB, MSI, MMRs, and immune checkpoint genes, and with the level of immune cell infiltration such as tumor-associated macrophage (TAM), cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs) and Tregs. The GO and KEGG results suggest that KIF2C is involved in immune regulation in addition to cell cycle regulation.In addition, KIF2C is associated with DNA methylation, m6A modifications and m7G modifications. Our data suggest that KIF2C is a prognostic biomarker linked to immunosuppression, targeting KIF2C may improve the outcome of immunotherapy. Our findings indicate that KIF2C is a prognostic biomarker associated with immunosuppression, and that targeting KIF2C may improve the outcome of immunotherapy.

Xanthomonas oryzae pv. textitoryzae (Xoo) is a causal agent of rice bacterial leaf blight (BLB), the major rice disease, which is seriously constraining rice production in Asia. The interaction between Xoo and rice is in a dynamic process, essentially the co-evolution. Tracking the occurrence of plant diseases and identifying the epidemic pathogens in time are critical to assessing the epidemic disease status and understanding the pathogen evolution. In 2020, the occurrences of rice BLB were spotted in many places of Guangxi, the major rice growing region in China. Two of the 2020-epidemic Xoo strains, namely, GXO20-01 and GXO20-06, were isolated from low land and high mountain paddies in Guangxi, respectively, and were demonstrated to be race R8 of Chinese Xoo strains, but with significantly different virulence on certain susceptible varieties of rice. The HiFi PacBio sequencing revealed that GXO20-01 and GXO20-06 share the highly syntenic genome structures and the major genome contents, but only differ in

AimNotwithstanding that unprecedented endovascular progress has been achieved in recent years, it remains unclear what is the best strategy to preserve the blood perfusion of abdominal visceral arteries and promote positive aortic remodeling in patients with distal dilatation of chronic aortic dissection in abdominal visceral part (CADAV) after aortic repair. The present study developed a Road Block Strategy (RBS) to solve this conundrum.Methods and ResultsThis prospective single-center clinical study included patients suffering from symptomatic distal dilatation of CADAV after aortic repair treated with RBS from January 2015 to December 2019 and followed up regularly for at least 2 years. Stent grafts were implanted first to cover distal tears and expand the true lumen. Device embolization was performed to induce proximal and distal segmental false lumen thrombosis (FLT) apart from the level of the ostia of vital branches. Successful RBS was performed in 13 patients. Significant differences were found in maximum true lumen diameter (p < 0.05), blood flow area in false lumen (FL) (p < 0.001), and the ratio of blood lumen to FL area (p < 0.05) between the pre-procedure and the latest follow-up results. No aortic rupture, vital branches occlusion, thoracic and abdominal pain, or death occurred during hospitalization and follow-up.ConclusionsOur findings suggest that RBS is feasible in treating distal dilatation of chronic aortic dissection after prior proximal repair, inducing false lumen thrombosis, preventing deterioration of aortic dissection, and maintaining the patency of abdominal visceral arteries.

The colistin resistance gene mcr-1 is emerging as a global public health concern, altering the regulation of colistin usage globally since 2017, especially in China. However, few studies have revealed the impact of policy change on the epidemiology of mcr-positive Enterobacteriaceae (MCRPE) in patients. Here, we describe a molecular epidemiological study to investigate the MCRPE in patients in China from 2009–2019. During the surveillance period, 26,080 non-duplicated Enterobacteriaceae isolates were collected in Beijing. Colistin-resistant isolates were screened by enrichment culture supplemented with colistin, and the presence of the mcr gene was determined by PCR amplification. MCRPE isolates were then analyzed by susceptibility testing, genotyping, and risk factor analysis. Of the 26,080 isolates, mcr-1 was detected in 171 (1.1%) of 15,742 Escherichia coli isolates and 7 (0.1%) of 10,338 Klebsiella pneumoniae isolates. The prevalence of mcr-1-positive E. coli (MCRPEC) showed an increasing trend from 2009 to 2016, while a decreasing trend was observed since 2017. Multi-locus sequence typing analysis showed that MCRPEC isolates had extremely diverse genetic backgrounds, and most of these isolates were non-clonal. The prevalence of MCRPE in China remained at a low level, and even showed a declining trend over the last 3 years after the banning of colistin usage as feed additive in food animal in 2017. However, colistin permission in clinical therapy could still increase the risk of MCRPE transmission and intractable infections, active surveillance and monitoring strategies of MCRPE are recommended to prolong the clinical longevity of colistin.

Determine the level of significance of planting strategy and plant architecture and how they affect plant physiology and dry matter accumulation within greenhouses is essential to actual greenhouse plant management and breeding. We thus analyzed four planting strategies (plant spacing, furrow distance, row orientation, planting pattern) and eight different plant architectural traits (internode length, leaf azimuth angle, leaf elevation angle, leaf length, leaflet curve, leaflet elevation, leaflet number/area ratio, leaflet length/width ratio) with the same plant leaf area using a formerly developed functional–structural model for a Chinese Liaoshen-solar greenhouse and tomato plant, which used to simulate the plant physiology of light interception, temperature, stomatal conductance, photosynthesis, and dry matter. Our study led to the conclusion that the planting strategies have a more significant impact overall on plant radiation, temperature, photosynthesis, and dry matter compared to plant architecture changes. According to our findings, increasing the plant spacing will have the most significant impact to increase light interception. E–W orientation has better total light interception but yet weaker light uniformity. Changes in planting patterns have limited influence on the overall canopy physiology. Increasing the plant leaflet area by leaflet N/A ratio from what we could observe for a rose the total dry matter by 6.6%, which is significantly better than all the other plant architecture traits. An ideal tomato plant architecture which combined all the above optimal architectural traits was also designed to provide guidance on phenotypic traits selection of breeding process. The combined analysis approach described herein established the causal relationship between investigated traits, which could directly apply to provide management and breeding insights on other plant species with different solar greenhouse structures.

Objective: To investigate the factors associated with recurrence/progression after endoscopic endonasal resection of suprasellar craniopharyngiomas. Special attention was paid to assess the impact of pituitary stalk preservation on tumor recurrence/progression and endocrinological outcomes.Methods: We retrospectively recruited 73 patients with suprasellar craniopharyngiomas undergone endoscopic endonasal approach (EEA) surgery from September 2014 to May 2019 and assessed their clinical characteristics, surgical outcomes, and recurrence/progression. Stalk preservation or sacrifice was determined by reviewing operative records, videos, and post-operative magnetic resonance imaging.Results: Gross total resection (GTR) was achieved in 51 cases (69.9%). Tumor recurrence was seen in 5 cases (9.8%) and progression was seen in 8 cases (36.4%), respectively. GTR (OR = 0.248 CI 0.081–0.759; p = 0.015) was the only independent factor influencing recurrence/progression. Kaplan-Meier survival analysis showed that the mean recurrence/progression-free survival were 53 (95% CI 48–59) and 39 (95% CI 28–50) months, respectively, in patients with and without GTR (p = 0.011). Pituitary stalk preservation was more common in cases with peripheral type tumors (83% vs. 30%, p < 0.01). Preserving the pituitary stalk does not appear to decrease the percentage of GTR (75.5% vs. 55.0%, p = 0.089), or increase the rate of tumor recurrence (12.5% vs. 0%, p = 0.508) or progression (46.2% vs. 22.2%, p = 0.486). However, surgically induced hypothyroidism (60.5% vs. 100%, p = 0.041) and diabetes insipidus (35.1% vs. 81.8%, p = 0.017) were significantly lower in patients with stalk preservation. For patients who had hypopituitarism before EEA, there was no difference between those with and without stalk preservation regarding post-operative hypopituitarism (p > 0.05).Conclusion: GTR is the only independent predictor of recurrence/progression after EEA surgery for suprasellar craniopharyngiomas. Preserving the pituitary stalk does not appear to increase the risk of non-GTR and tumor recurrence/progression and might help reduce the risk of surgically induced hypothyroidism and diabetes insipidus. We recommend preserving the pituitary stalk in peripheral type suprasellar craniopharyngiomas with normal pituitary function, especially in cases without hypothyroidism or diabetes insipidus. On the other hand, stalk sacrifice could be considered in central type tumors with severe pre-operative endocrinopathy.

BackgroundBrain invasion in meningioma has independent associations with increased risks of tumor progression, lesion recurrence, and poor prognosis. Therefore, this study aimed to construct a model for predicting brain invasion in WHO grade II meningioma by using preoperative MRI.MethodsOne hundred seventy-three patients with brain invasion and 111 patients without brain invasion were included. Three mainstream features, namely, traditional semantic features and radiomics features from tumor and tumor-to-brain interface regions, were acquired. Predictive models correspondingly constructed on each feature set or joint feature set were constructed.ResultsTraditional semantic findings, e.g., peritumoral edema and other four features, had comparable performance in predicting brain invasion with each radiomics feature set. By taking advantage of semantic features and radiomics features from tumoral and tumor-to-brain interface regions, an integrated nomogram that quantifies the risk factor of each selected feature was constructed and had the best performance in predicting brain invasion (area under the curve values were 0.905 in the training set and 0.895 in the test set).ConclusionsThis study provided a clinically available and promising approach to predict brain invasion in WHO grade II meningiomas by using preoperative MRI.

Purpose: To investigate the incidence, characteristics, and risk factors of sports-related eye injuries among athletes in Tianjin, China.Methods: A cross-sectional study was carried out from March 2018 to October 2018. In this study, the athletes from Tianjin University of Sports, Tianjin Vocational College of Sports, and Tianjin provincial sports teams were selected for general investigation. In total, 1,673 athletes were invited and 1,413 participated in the study (response rate of 84.5%).Results: In total, 1,413 athletes were enrolled; 151 had suffered from sports-related eye injuries, with an incidence of 10.7% (95% CI: 9.1–12.0%). Handball (38.5%) was the sport with the highest incidence of eye injuries, followed by water polo (36.4%) and diving (26.7%). Overall, 42.4% of the athletes were injured by ball and 22.5% of injuries came from teammates. The eye injuries usually occurred during training (64.2%) and competitions (14.6%). Adnexa wound (51.7%) was the most common type of injury. About 11.9% of the athletes with eye injuries had the impaired vision; 66.7% failed to see doctors on time. The athletes 4 h a day increased the risk of eye injuries (OR = 2.21, 95% CI: 1.42–3.43).Conclusion: The incidence of sports-related eye injuries among athletes was 10.7% in Tianjin, China. Handball, water polo, and diving were the most common activities of injury. Age, family income, and training time were the risk factors for sports-related eye injuries.

BackgroundSolitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported.MethodTwenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed.ResultsThe male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%).ConclusionEither surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders

PurposeThe present study aimed to preoperatively predict the status of 1p/19q based on radiomics analysis in patients with World Health Organization (WHO) grade II gliomas.MethodsThis retrospective study enrolled 157 patients with WHO grade II gliomas (76 patients with astrocytomas with mutant IDH, 16 patients with astrocytomas with wild-type IDH, and 65 patients with oligodendrogliomas with mutant IDH and 1p/19q codeletion). Radiomic features were extracted from magnetic resonance images, including T1-weighted, T2-weighted, and contrast T1-weighted images. Elastic net and support vector machines with radial basis function kernel were applied in nested 10-fold cross-validation loops to predict the 1p/19q status. Receiver operating characteristic analysis and precision-recall analysis were used to evaluate the model performance. Student’s t-tests were then used to compare the posterior probabilities of 1p/19q co-deletion prediction in the group with different 1p/19q status.ResultsSix valuable radiomic features, along with age, were selected with the nested 10-fold cross-validation loops. Five features showed significant difference in patients with different 1p/19q status. The area under curve and accuracy of the predictive model were 0.8079 (95% confidence interval, 0.733–0.8755) and 0.758 (0.6879–0.8217), respectively, and the F1-score of the precision-recall curve achieved 0.6667 (0.5201–0.7705). The posterior probabilities in the 1p/19q co-deletion group were significantly different from the non-deletion group.ConclusionCombined radiomics analysis and machine learning showed potential clinical utility in the preoperative prediction of 1p/19q status, which can aid in making customized neurosurgery plans and glioma management strategies before postoperative pathology.

IntroductionBrown adipose tissue (BAT) becomes the favorite target for preventing and treating metabolic diseases because the activated BAT can produce heat and consume energy. The brain, especially the hypothalamus, which secretes Neuropeptide Y (NPY), is speculated to regulate BAT activity. However, whether NPY is involved in BAT activity’s central regulation in humans remains unclear. Thus, it’s essential to explore the relationship between brain glucose metabolism and human BAT activity.MethodsA controlled study with a large sample of healthy adults used Positron emission tomography/computed tomography (PET/CT) to noninvasively investigate BAT’s activity and brain glucose metabolism in vivo. Eighty healthy adults with activated BAT according to the PET/CT scan volunteered to be the BAT positive group, while 80 healthy adults without activated BAT but with the same gender, similar age, and BMI, scanning on the same day, were recruited as the control (BAT negative). We use Statistical parametric mapping (SPM) to analyze the brain image data, Picture Archiving & Communication System (PACS), and PET/CT Viewer software to calculate the semi-quantitative values of brain glucose metabolism and BAT activity. ELISA tested the levels of fasting plasma NPY. The multiple linear regression models were used to analyze the correlation between brain glucose metabolism, the level of NPY, and the BAT activity in the BAT positive group.Results(1) Compared with controls, BAT positive group showed significant metabolic decreases mainly in the right Insula (BA13a, BA13b) and the right claustrum (uncorrected P 0.05), while the correlation between the BA13a metabolic values and BAT activity still was significant (P< 0.05).ConclusionsRegional brain glucose metabolism is closely related to healthy adults’ BAT activity, which may be mediated by NPY.

PurposeIt is difficult for doctors to decide whether patients with suspected coronary heart disease classified as Coronary Artery Disease Reporting and Data System (CAD-RADS) < 3 should be administered preventive treatment, or whether non-atherosclerotic chest pain should be considered. The aim of the current study was to investigate coronary hemodynamic characteristics in such patients, which may provide more information on their stenosis and be helpful for initial diagnoses.MethodsTwo patient-specific models were reconstructed based on the coronary computed tomographic angiography underwent in 2012. Patient 1 was classified as CAD-RADS 0, and was readmitted to hospital due to coronary artery disease within 5 years. Patient 2 was classified as CAD-RADS 2, and has experienced no adverse events to date. Computational fluid dynamics (CFD) analysis was used to obtain hemodynamic parameters including flow rate waveform, flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI).ResultsPatient 1 exhibited no physiological characteristics of right coronary artery flow waveform, large areas of low TAWSS, and slow blood flow in the proximal and middle segments of the left anterior descending branch. Patient 2 exhibited reduced coronary supply, small and separate areas of abnormal TAWSS, and a higher left anterior descending branch OSI than patient 1.ConclusionHemodynamic abnormalities may play an important role in the prognosis of patients with coronary stenosis, and patient-specific hemodynamic characteristics may facilitate more accurate initial diagnosis, and better management. Overall hemodynamics (along the whole vessel) warranted attention at the time of the initial visit in patients classified as CAD-RADS < 3.

ContextHypothalamic obesity (HO) is a severe complication following craniopharyngioma, but studies regarding the sequelae in adult-onset patients with craniopharyngioma are sparse.ObjectiveThe objective of the study was to describe weight changes after surgical treatment in adult-onset craniopharyngioma patients and to analyze risk factors for postoperative weight gain and HO.Subjects and MethodA retrospective analysis was conducted of 120 adult-onset patients who underwent surgery for craniopharyngioma and follow-up at the institution of the authors between January 2018 and September 2020. Clinical characteristics, anthropometric data, image features, treatment modalities, and endocrine indices were collected. Multivariable logistic regression analysis was used to identify independent risk factors for postoperative weight gain and HO.ResultsForty-nine (40.8%) patients had clinically meaningful weight gain (≥5%) in a median follow-up time of 12.0 months (range 1.0–41.0 months) after surgery. The mean postoperative weight gain in this subgroup was 17.59 ± 12.28 (%). Weight gain continued in the first year following surgery. Patients with lower preoperative BMI [OR 0.78, 95% CI (0.67–0.90), P = 0.001] and the adamantinomatous subtype [OR 3.46, 95% CI (1.02–11.76), P = 0.047] were more likely to experience postoperative weight gain ≥5%. The prevalence of HO was 19.2% preoperatively and increased to 29.2% at last follow-up postoperatively. Only preoperative BMI [OR 2.51, 95% CI (1.64–3.85), P < 0.001] was identified as an independent risk factor for postoperative HO.ConclusionsHO is a common complication in patients with adult-onset craniopharyngioma. Patients with higher preoperative BMI had a greater risk for developing HO postoperatively.

Background: Glioma-related epilepsy (GRE) is the most common presenting sign of patients with diffuse glioma. According to clinical experience, new-onset postoperative seizures can be observed even in patients without preoperative GRE. The current study mainly aimed to explore the risk factors of new-onset postoperative seizures in those patients. In addition, the prognostic value of new-onset postoperative seizures was also discussed.Methods: Data of 313 patients without GRE were retrospectively reviewed. Chi-square test or Fisher's exact test were first performed to compare categorical variables between patients with new-onset postoperative seizures and those without. Subsequently, binary logistic regression analysis was conduct to further assess risk factors of new-onset postoperative seizures. Kaplan-Meier and Cox analysis were used to investigate the prognostic value of new-onset postoperative seizures for progression-free survival (PFS) and overall survival (OS).Results: Patients with low-grade tumors (p = 0.006), isocitrate dehydrogenase 1 (IDH1) mutation (p = 0.040) or low Ki-67 expression (p = 0.005) showed a higher incidence of new-onset postoperative seizures. IDH1 mutation was identified as the only independent predictor for new-onset postoperative seizures (OR, 2.075; 95% CI, 1.051–4.098; p = 0.035). Additionally, new-onset postoperative seizure occurrence was demonstrated as an independent predicter of prolonged OS (OR, 0.574; 95% CI, 0.335–0.983; p = 0.043), while younger age, gross total resection, low-grade and IDH1 mutation were independently correlated with prolonged OS and PFS.Conclusions: IDH1 mutation is an independent predictor for new-onset postoperative seizures in patients without preoperative GRE. Moreover, new-onset postoperative seizures can independently predict prolonged OS in those patients. The results of the current study can contribute to improving the individualized management of diffuse glioma.

Different DNA methylation patterns presented on different tissues or cell types are considered as one of the main reasons accounting for the tissue-specific gene expressions. In recent years, many methods have been proposed to identify differentially methylated regions (DMRs) based on the mixture of methylation signals from homologous chromosomes. To investigate the possible influence of homologous chromosomes on methylation analysis, this paper proposed a method (MHap) to construct methylation haplotypes for homologous chromosomes in CpG dense regions. Through comparing the methylation consistency between homologous chromosomes in different cell types, it can be found that majority of paired methylation haplotypes derived from homologous chromosomes are consistent, while a lower methylation consistency was observed in the breast cancer sample. It also can be observed that the hypomethylation consistency of differentiated cells is higher than that of the corresponding undifferentiated stem cells. Furthermore, based on the methylation haplotypes constructed on homologous chromosomes, a method (MHap_DMR) is developed to identify DMRs between differentiated cells and the corresponding undifferentiated stem cells, or between the breast cancer sample and the normal breast sample. Through comparing the methylation haplotype modes of DMRs in two cell types, the DNA methylation changing directions of homologous chromosomes in cell differentiation and cancerization can be revealed. The code is available at: https://github.com/xqpeng/MHap_DMR.

ObjectiveTo determine the risk factors for erectile dysfunction (ED) in male patients with acromegaly and to prospectively investigate the short-term changes of erectile function after surgery or medical treatment.MethodsSixty-three male patients were subjected to nocturnal penile tumescence and rigidity (NPTR) test for the evaluation of erectile function. The measurement of serum nitric oxide (NO) was also performed. Twenty-seven patients were re-evaluated by NPTR after surgery or long-term somatostatin analogues (SSA) treatment.ResultsTwenty-two patients (34.9%) had ED. Patients with ED showed higher random GH (17.89 [10.97-44.19] μg/L vs 11.63 [4.31-28.80] μg/L, p = 0.020) and GH nadir (GHn) (10.80 [6.69-38.30] μg/L vs 8.76 [3.62-18.19] μg/L, p = 0.044) during oral glucose tolerance test (OGTT). The NO levels of ED patients were lower than non-ED patients (9.15 [5.58-22.48] μmol/L vs 16.50 [12.33-31.78] μmol/L, p = 0.012). After treatment, patients who present improvement in erectile function showed lower post-GHn (0.07 [0.03-0.12] ng/ml vs 1.32 [0.09-3.60] ng/ml, p = 0.048) and post-IGF-1 index (1.03 ± 0.38 vs 1.66 ± 0.95, p = 0.049). The multivariate analysis indicated post-GHn was still associated with the improvement of erectile function after correction of other covariates (OR: 0.059, 95% CI: 0.003-1.043, p = 0.053).ConclusionsExcessive GH is related to ED in male patients with acromegaly. GH normalization after treatment is beneficial for short-term erectile function recovery.