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BackgroundIn recent years, the incidence of abdominal obesity among the middle-aged and older adult population in China has significantly increased. However, the gender disparities in the spatial distribution of abdominal obesity incidence and its relationship with meteorological factors among this demographic in China remain unclear. This gap in knowledge highlights the need for further research to understand these dynamics and inform targeted public health strategies.MethodsThis study utilized data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) to analyze the incidence of abdominal obesity among the middle-aged and older adult population in China. Additionally, meteorological data were collected from the National Meteorological Information Center. Using Moran’s I index and Getis-Ord Gi* statistical methods, the spatial distribution characteristics of abdominal obesity incidence were examined. The influence of various meteorological factors on the incidence of abdominal obesity in middle-aged and older adult males and females was investigated using the q statistic from the Geodetector method. Furthermore, Multi-Scale Geographically Weighted Regression (MGWR) analysis was employed to explore the impact of meteorological factors on the spatial heterogeneity of abdominal obesity incidence from a gender perspective.ResultsThe spatial distribution of abdominal obesity among middle-aged and older adult individuals in China exhibits a decreasing trend from northwest to southeast, with notable spatial autocorrelation. Hotspots are concentrated in North and Northeast China, while cold spots are observed in Southwest China. Gender differences have minimal impact on spatial clustering characteristics. Meteorological factors, including temperature, sunlight, precipitation, wind speed, humidity, and atmospheric pressure, influence incidence rates. Notably, temperature and sunlight exert a greater impact on females, while wind speed has a reduced effect. Interactions among various meteorological factors generally demonstrate bivariate enhancement without significant gender disparities. However, gender disparities are evident in the influence of specific meteorological variables such as annual maximum, average, and minimum temperatures, as well as sunlight duration and precipitation, on the spatial heterogeneity of abdominal obesity incidence.ConclusionMeteorological factors show a significant association with abdominal obesity prevalence in middle-aged and older adults, with temperature factors playing a prominent role. However, this relationship is influenced by gender differences and spatial heterogeneity. These findings suggest that effective public health policies should be not only gender-sensitive but also locally adapted.

Livestock presence impacts plant biodiversity (species richness) in grassland ecosystems, yet extent and direction of grazing impacts on biodiversity vary greatly across inter-annual periods. In this study, an 8-year (2014-2021) grazing gradient experiment with sheep was conducted in a semi-arid grassland to investigate the impact of grazing under different precipitation variability on biodiversity. The results suggest no direct impact of grazing on species richness in semi-arid Stipa grassland. However, increased grazing indirectly enhanced species richness by elevating community dominance (increasing the sheltering effect of Stipa grass). Importantly, intensified grazing also regulates excessive community biomass resulting from increased inter-annual wetness (SPEI), amplifying the positive influence of annual humidity index on species richness. Lastly, we emphasize that, in water-constrained grassland ecosystems, intra-annual precipitation variability (PCI) was the most crucial factor driving species richness. Therefore, the water-heat synchrony during the growing season may alleviate physiological constraints on plants, significantly enhancing species richness as a result of multifactorial interactions. Our study provides strong evidence for how to regulate grazing intensity to increase biodiversity under future variable climate patterns. We suggest adapting grazing intensity according to local climate variability to achieve grassland biodiversity conservation.

Background: Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. Nevertheless, there is a lack of epidemiological research examining whether Se can mitigate the adverse effects of cadmium (Cd) and lead (Pb) on hand grip strength (HGS) in middle-aged and elderly individuals.Methods: This study used data from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). HGS measurements were conducted by trained examiners with a dynamometer. Concentrations of Se, Cd, and Pb in blood were determined via inductively coupled plasma mass spectrometry. We employed linear regression, restricted cubic splines, and quantile g-computation (qgcomp) to assess individual and combined associations between heavy metals and HGS. The study also explored the potential influence of Se on these associations.Results: In both individual metal and multi-metal models adjusted for confounders, general linear regression showed Se’s positive association with HGS, while Cd and Pb inversely related to it. At varying Se-Cd and Se-Pb concentrations, high Se relative to low Se can attenuate Cd and Pb’s HGS impact. An inverted U-shaped correlation exists between Se and both maximum and combined HGS, with Se’s benefit plateauing beyond approximately 200 μg/L. Stratified analysis by Se quartiles reveals Cd and Pb’s adverse HGS effects diminishing as Se levels increase. Qgcomp regression analysis detected Se alleviating HGS damage from combined Cd and Pb exposure. Subsequent subgroup analyses identified the sensitivity of women, the elderly, and those at risk of diabetes to HGS impairment caused by heavy metals, with moderate Se supplementation beneficial in mitigating this effect. In the population at risk for diabetes, the protective role of Se against heavy metal toxicity-induced HGS reduction is inhibited, suggesting that diabetic individuals should particularly avoid heavy metal-induced handgrip impairment.Conclusion: Blood Cd and Pb levels are negatively correlated with HGS. Se can mitigate this negative impact, but its effectiveness plateaus beyond 200 μg/L. Women, the elderly, and those at risk of diabetes are more vulnerable to HGS damage from heavy metals. While Se supplementation can help, its protective effect is limited in high diabetes risk groups.

BackgroundHypertension has now developed into a major public health problem worldwide. Under the existing antihypertensive drug treatment paradigm, problems such as decreasing drug resistance and increasing drug side effects can occur for elderly patients. Acupuncture, a core technique in the non-pharmacological treatment of Chinese medicine, plays an important role in the treatment of elevated blood pressure.ObjectiveThis study aimed to systematically evaluate the effect of acupuncture alone or in combination with antihypertensive drugs on the efficiency of reducing blood pressure and controlling blood pressure in elderly patients with hypertension.MethodsArticles of randomized controlled trials of acupuncture for hypertension in the elderly published before November 2022 were searched in 7 databases. The methodological quality of the literature was evaluated using the Cochrane Risk of Bias Assessment Tool. The primary outcome was the efficiency rate of blood pressure reduction, and the secondary outcome was the change in blood pressure after treatment.ResultsThis study conducted a systematic review and meta-analysis of 12 randomized controlled trials with a total of 1,466 subjects. Among the primary outcome—efficiency rate, acupuncture-only treatment (RR = 1.11, 95% CI: 1.03–1.20, P

BackgroundAs a common clinical symptom, insomnia has a high incidence of combined mental illness and it is also a risk factor for the development of depression, anxiety and suicide. As a new concept in the field of health in recent years, mindfulness therapy can improve insomnia, anxiety and depression, which is a new way to solve such diseases.ObjectiveThis study aims to systematically evaluate the effects of mindfulness compared with conventional treatment on scores of the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) in people with insomnia and anxiety-depressive symptoms.MethodsArticles published before October 2022 were searched from seven databases and included in randomized controlled trials (RCTs) to evaluate mindfulness therapy. The assessment tool of Cochrane bias risk was used to evaluate the methodological quality of the literature. The main outcome indicators were HAMD and HAMA scores, and the secondary outcome indicators were SDS and SAS scores.ResultsTen randomized controlled trials including 1,058 subjects were systematically evaluated and meta-analyzed in this study. In the main outcome indicators, there was a significant difference between mindfulness therapy and conventional treatment in reducing HAMD score (MD: −3.67, 95% CI: −5.22–2.11, p

IntroductionThe erythrocyte membranes used in nanovaccines include high membrane stability, long circulation life, adaptability and extremely good bio compatibility. Nanoparticles encapsulated by erythrocyte membranes are widely used as ideal drug delivery vehicles because of their high drug loading, long circulation time, and excellent biocompatibility. The mannose modification of delivery materials can help target mannose receptors (MRs) to deliver antigens to antigen-presenting cells (APCs).MethodsIn this study, the antigen gene gp90 of avian reticuloendotheliosis virus (REV) was encapsulated with carboxymethyl chitosan (CS) to obtain CSgp90 nanoparticles, which were coated with mannose-modied fowl erythrocyte membranes to yield CS-gp90@M-M nanoparticles. The physicochemical characterization and immune response of the CS-gp90@M-M nanoparticles were investigated in vitro and in vivo.ResultsCS-gp90@M-M nanoparticles were rapidly phagocytized in vitro by macrophages to induce the production of cytokines and nitric oxide. In vivo, CS-gp90@M-M nanoparticles increased cytokine levels, the CD4+/8+ ratio, REV-specific antibodies in the peripheral blood of chicks, and the mRNA levels of immune-related genes in the spleen and bursa of immunized chicks. CS-gp90@M-M nanoparticles could be targeted to lymphoid organs to prolong the retention time of the nanoparticles at the injection site and lymphatic organs, leading to a strong, sustained immune response. Moreover, the CS-gp90@M-M nano-vaccine showed a lasting immunoprotective effect and improved the body weight of chicks after the challenge.ConclusionOverall, CS-gp90@M-M nanoparticles can be used in vaccine designs as an effective delivery carrier with immune response-enhancing effects.

PurposeSorafenib is a multi-kinase inhibitor that is used as a standard treatment for advanced hepatocellular carcinoma (HCC). However, the mechanism of sorafenib resistance in HCC is still unclear. It has been shown that CISD2 expression is related to the progression and poor prognosis of HCC. Here, we show a new role for CISD2 in sorafenib resistance in HCC.MethodsBioinformatic analysis was used to detect the expression of negative regulatory genes of ferroptosis in sorafenib-resistant samples. The concentration gradient method was used to establish sorafenib-resistant HCC cells. Western blot was used to detect the protein expression of CISD2, LC3, ERK, PI3K, AKT, mTOR, and Beclin1 in HCC samples. Quantitative real-time PCR (qPCR) was used to detect gene expression. CISD2 shRNA and Beclin1 shRNA were transfected to knock down the expression of the corresponding genes. Cell viability was detected by a CCK-8 assay. ROS were detected by DCFH-DA staining, and MDA and GSH were detected with a Lipid Peroxidation MDA Assay Kit and Micro Reduced Glutathione (GSH) Assay Kit, respectively. Flow cytometry was used to detect apoptosis and the levels of ROS and iron ions.ResultsCISD2 was highly expressed in HCC cells compared with normal cells and was associated with poor prognosis in patients. Knockdown of CISD2 promoted a decrease in the viability of drug-resistant HCC cells. CISD2 knockdown promoted sorafenib-induced ferroptosis in resistant HCC cells. The levels of ROS, MDA, and iron ions increased, but the change in GSH was not obvious. Knockdown of CISD2 promoted uncontrolled autophagy in resistant HCC cells. Inhibition of autophagy attenuated CISD2 knockdown-induced ferroptosis. The autophagy promoted by CISD2 knockdown was related to Beclin1. When CISD2 and Beclin1 were inhibited, the effect on ferroptosis was correspondingly weakened.ConclusionInhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant HCC.

Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.

Motivation: Pentatricopeptide repeat (PPR), which is a triangular pentapeptide repeat domain, plays an important role in plant growth. Features extracted from sequences are applicable to PPR protein identification using certain classification methods. However, which components of a multidimensional feature (namely variables) are more effective for protein discrimination has never been discussed. Therefore, we seek to select variables from a multidimensional feature for identifying PPR proteins.Method: A framework of variable selection for identifying PPR proteins is proposed. Samples representing PPR positive proteins and negative ones are equally split into a training and a testing set. Variable importance is regarded as scores derived from an iteration of resampling, training, and scoring step on the training set. A model selection method based on Gaussian mixture model is applied to automatic choice of variables which are effective to identify PPR proteins. Measurements are used on the testing set to show the effectiveness of the selected variables.Results: Certain variables other than the multidimensional feature they belong to do work for discrimination between PPR positive proteins and those negative ones. In addition, the content of methionine may play an important role in predicting PPR proteins.

ObjectiveTuberculosis (TB) is the leading cause of mortality worldwide. Previous studies have reported that TB susceptibility can be caused by vitamin D deficiency, which is affected by polymorphisms in the vitamin D receptor (VDR) gene. However, these results have been inconsistent. Therefore, we performed a meta-analysis to investigate the association between VDR polymorphisms and TB susceptibility.MethodsWe systematically searched for relevant literature in PubMed, Embase, and Medline databases through December 31st, 2022. Inclusion and exclusion criteria were made to ensure that HIV-negative population is the targeted subjects. The pooled odds ratio (OR) and 95% confidence interval (CI) were then used to assess the strength of the association, and the quality of the included articles was evaluated using the Newcastle–Ottawa Scale. Potential sources of heterogeneity were evaluated based on subgroup and meta-regression analyses.ResultsIn our meta-analysis, we found that the FokI polymorphism in the VDR gene was associated with increased TB susceptibility in the allele and recessive genotype models (OR f vs. F = 1.235, 95%CI: 1.035–1.475; OR ff vs. Ff + FF = 1.317, 95%CI: 1.005–1.727. Further subgroup analysis based on ethnicity demonstrated the association with the risk of TB in all genotype models of the FokI polymorphism for Han population. Meta-regression analysis also indicated that ethnicity could be a potential source of heterogeneity in the FokI and BsmI polymorphisms in the VDR gene. However, publication year was another source of heterogeneity for the TaqI polymorphism.ConclusionIn summary, the FokI polymorphism in the VDR gene was found to increase the risk of TB in the HIV-negative population, both overall and in Asian populations. The findings presented in this paper could provide clues for preventing TB from the perspective of vitamin D supplementation, which is a controversial topic in the field of medicine and health.

The brachial cleft carcinoma is an extremely rare head and neck facial malignancy, and there is some disagreement about its differential diagnosis. In this paper, we report a 63-year-old male patient who had a mass on the left side of the neck and diagnosed as the brachial cleft carcinoma by intraoperative biopsy pathology. However, this patient was diagnosed with the carcinoma of the left soft palate more than 20 days after surgery and esophageal cancer 2 years later, and was treated accordingly. Therefore, it is hard to confirm whether the branchial cleft carcinoma is primary or metastatic. In fact, the diagnostic criteria for primary squamous cell carcinoma of branchial cleft cysts are very rigorous. Confirmation of the diagnosis is based on pathological examination of the branchial cleft cyst epithelium lined with squamous cells, meanwhile, a thorough examination should also be performed to exclude the presence of other primary cancers.

ObjectivesThe objective of this study was to evaluate the association between weight-adjusted waist index (WWI) and the prevalence of kidney stones among adults in the United States.MethodsThe cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2007-2018. A total of 31,344 participants were categorized into two groups: those with kidney stones and those without. WWI was determined by dividing waist circumference (cm) by the square root of body weight (kg). To examine the relationship between kidney stones and WWI, multivariate logistic regression models, smoothed curve fitting, and weighted generalized additive model (GAM) regression were employed. Subgroup analysis and interaction tests were conducted to explore the stability of this association across different groups.ResultsThe final analysis comprised a total of 31,344 participants, including 2,928 individuals who had a history of kidney stones. In the fully adjusted model, an increase in WWI exhibited a positive correlation with the prevalence of kidney stones (OR=1.34, 95% CI: 1.18-1.51). When WWI was converted into quartiles (Q1-Q4), participants in the highest quartile (Q4) had a 69% greater risk of developing kidney stones compared to those in the lowest quartile (Q1) (OR=1.69, 95% CI: 1.28-2.25). This positive association was particularly notable among non-diabetic patients.ConclusionOur study demonstrates a significant positive association between weight-adjusted waist index levels and an elevated prevalence of kidney stones among US adults. Furthermore, this research highlights the potential utility of weight-adjusted waist index in the prevention of kidney stones in the overall population. This relationship is limited and further research is needed to test this hypothesis.

BackgroundMinimal residual disease (MRD) is considered an essential factor leading to relapse within 2 years (early relapse) after radical surgery, which is challenging to be detected by conventional imaging. Circulating tumor DNA (ctDNA) provides a novel approach for detecting MRD and predicting clinical outcomes. Here, we tried to construct a fixed panel for plasma-only ctDNA NGS to enable tumor-uninformed MRD detection in hepatocellular carcinoma (HCC).MethodsHere, we performed the followings: (i) profiling genomic alteration spectrum of ctDNA from the Chinese HCC cohort consisting of 493 individuals by NGS; (ii) screening of MRD monitoring genes; and (iii) performance evaluation of MRD monitoring genes in predicting early relapse in the ZJZS2020 cohort comprising 20 HCC patients who underwent curative resection.ResultsA total of 493 plasma samples from the Chinese HCC cohort were detected using a 381/733-gene NGS panel to characterize the mutational spectrum of ctDNA. Most patients (94.1%, 464/493) had at least one mutation in ctDNA. The variants fell most frequently in TP53 (45.1%), LRP1B (20.2%), TERT (20.2%), FAT1 (16.2%), and CTNNB1 (13.4%). By customized filtering strategy, 13 MRD monitoring genes were identified, and any plasma sample with one or more MRD monitoring gene mutations was considered MRD-positive. In the ZJZS2020 cohort, MRD positivity presented a sensitivity of 75% (6/8) and a specificity of 100% (6/6) in identifying early postoperative relapse. The Kaplan-Meier analysis revealed a significantly short relapse-free survival (RFS; median RFS, 4.2 months vs. NR, P=0.002) in the MRD-positive patients versus those with MRD negativity. Cox regression analyses revealed MRD positivity as an independent predictor of poor RFS (HR 13.00, 95% CI 2.60-69.00, P=0.002).ConclusionsWe successfully developed a 13-gene panel for plasma-only MRD detection, which was effective and convenient for predicting the risk of early postoperative relapse in HCC.

Large mural thrombi in the relatively normal ascending aorta are extremely uncommon conditions that may lead to major adverse cardiovascular events due to new embolism. Because of their changeable variations, the management of these unstable thrombi is challenging and controversial. The size, morphology, location, embolic involvement, and patients’ conditions are all crucial for therapeutic decision-making. Treatment options include anticoagulation, thrombolysis, surgical thrombectomy, and endovascular stenting. Therefore, surgical strategies should be highly individualized. Herein, we present a rare case of a huge thrombus from the ascending aorta to the arch in a 43-year-old man. Considering the high risks of catastrophic embolic events, surgical removal of the aortic mass, thromboendarterectomy, and reconstruction of the arterial wall were performed with a satisfactory outcome. This report illustrates our experience of surgical strategies and perioperative treatments for this challenging case, and contemporary surgical management for mural thrombi in the ascending aorta was also thoroughly discussed.

The worldwide prevalence of pancreatic cancer has been rising in recent decades, and its prognosis has not improved much. The imbalance of substance and energy metabolism in tumour cells is among the primary causes of tumour formation and occurrence, which is often controlled by the neuroendocrine system. We applied Cox and LASSO regression analysis to develop a neuroendocrine regulation- and metabolism-related prognostic risk score model with three genes (GSK3B, IL18 and VEGFA) for pancreatic cancer. TCGA dataset served as the training and internal validation sets, and GSE28735, GSE62452 and GSE57495 were designated as external validation sets. Patients classified as the low-risk population (category, group) exhibited considerably improved survival duration in contrast with those classified as the high-risk population, as determined by the Kaplan-Meier curve. Then, we combined all the samples, and divided them into three clusters using unsupervised clustering analysis. Unsupervised clustering, t-distributed stochastic neighbor embedding (t-SNE), and principal component analysis (PCA) were further utilized to demonstrate the reliability of the prognostic model. Moreover, the risk score was shown to independently function as a predictor of pancreatic cancer in both univariate and multivariate Cox regression analyses. The results of gene set enrichment analysis (GSEA) illustrated that the low-risk population was predominantly enriched in immune-associated pathways. “ESTIMATE” algorithm, single-sample GSEA (ssGSEA) and the Tumor Immune Estimation Resource (TIMER) database showed immune infiltration ratings were enhanced in the low-risk category in contrast with the high-risk group. Tumour immune dysfunction and exclusion (TIDE) database predicted that immunotherapy for pancreatic cancer may be more successful in the high-risk than in the low-risk population. Mutation analysis illustrated a positive link between the tumour mutation burden and risk score. Drug sensitivity analysis identified 44 sensitive drugs in the high- and low-risk population. GSK3B expression was negatively correlated with Oxaliplatin, and IL18 expression was negatively correlated with Paclitaxel. Lastly, we analyzed and verified gene expression at RNA and protein levels based on GENPIA platform, HPA database and quantitative real-time PCR. In short, we developed a neuroendocrine regulation- and metabolism-associated prognostic model for pancreatic cancer that takes into account the immunological microenvironment and drug sensitivity.

Maize grain size is the main factor determining grain yield. Dissecting the genetic basis of maize grain size may help reveal the regulatory mechanism of maize seed development and yield formation. In this study, two associated populations were used for genome-wide association analysis of kernel length, kernel width, kernel thickness, and hundred-kernel weight from multiple locations in AM122 and AM180, respectively. Then, genome-wide association mapping was performed based on the maize 6H90K SNP chip. A total of 139 loci were identified as associated with the four traits with p < 1 × 10−4 using two models (FarmCPU and MLM). The transcriptome data showed that 15 of them were expressed differentially in two maize-inbred lines KB182 (small kernel) and KB020 (big kernel) during kernel development. These candidate genes were enriched in regulating peroxidase activity, oxidoreductase, and leaf senescence. The molecular function was major in binding and catalytic activity. This study provided important reference information for exploring maize kernel development mechanisms and applying molecular markers in high-yield breeding.

It is becoming increasingly clear that environment factors during early life play a pivotal role in the development of allergic asthma. Among these, a traditional farm is one of the strongest protective environments, and the protective effects have been, at least in part, attributed to the high-level exposure to lipopolysaccharide (LPS) on farms. However, the underlying mechanisms remain elusive, especially in ovalbumin (OVA)-induced neonatal allergic asthma model. Here, we used the OVA-induced asthma model in two age groups, neonatal and adult, when mice were first sensitized with peritoneal OVA/alum as neonates and adults, respectively. LPS was injected in the peritoneal cavity before OVA/alum sensitization. The effects of LPS treatment on allergic airway inflammation in the lung and the immune milieu in the peritoneal cavity were determined and compared between these two age groups. We found that LPS treatment abrogated the development of Th2 allergic airway responses in the neonatal group. In the adult group, the ameliorated Th2 allergic responses were accompanied with Th17 responses and neutrophil infiltration upon LPS treatment. We further investigated the immune milieu in the peritoneal cavity to elucidate the underlying mechanisms of this age-dependent difference. Our data show that in neonatal mice, LPS treatment significantly reduced the number of inflammatory monocytes in the peritoneal cavity. In the adult group, LPS treatment shifted the function of these cells which associated with Th1 and Th17 polarization. Our results provide more evidence that immunity in early life is distinct from that in adults, especially in the peritoneal cavity, and emphasize the importance of timing for the intervention of allergic asthma. Our results suggest that LPS treatment during early life is protective for the development of Th2 allergic responses. On the other hand, it might lead to a more severe phenotype of asthma when dampening the Th2 responses in adult mice.

Abdominal aortic aneurysms (AAAs) are typically asymptomatic, and there is a high mortality rate associated with aneurysm rupture. AAA pathogenesis involves extracellular matrix degradation, vascular smooth muscle cell phenotype switching, inflammation, and oxidative stress. There is increasing evidence of excessive adipocyte accumulation in ruptured AAA walls. These excessive numbers of adipocytes in the vascular wall have been closely linked with AAA progression. Perivascular adipose tissue (PVAT), a unique type of adipose tissue, can be involved in adipocyte accumulation in the AAA wall. PVAT produces various chemokines and adipocytokines around vessels to maintain vascular homeostasis through paracrine and autocrine mechanisms in normal physiological conditions. Nevertheless, PVAT loses its normal function and promotes the progression of vascular diseases in pathological conditions. There is evidence of significantly reduced AAA diameter in vessel walls of removed PVAT. There is a need to highlight the critical roles of cytokines, cells, and microRNA derived from PVAT in the regulation of AAA development. PVAT may constitute an important therapeutic target for the prevention and treatment of AAAs. In this review, we discuss the relationship between PVAT and AAA development; we also highlight the potential for PVAT-derived factors to serve as a therapeutic target in the treatment of AAAs.

PurposeLiquid biopsy is attracting attention as a method of real-time monitoring of patients with tumors. It can be used to understand the temporal and spatial heterogeneity of tumors and has good clinical application prospects. We explored a new type of circulating tumor cell (CTC) enrichment technology combined with next-generation sequencing (NGS) to analyze the correlation between genomic alterations in circulating tumor cells of hepatocellular carcinoma and the counts of mesenchymal CTCs and CTC-associated white blood cell (CTC-WBC) clusters.MethodsWe collected peripheral blood samples from 29 patients with hepatocellular carcinoma from January 2016 to December 2019. We then used the CanPatrol™ system to capture and analyze mesenchymal CTCs and CTC-WBC clusters for all the patients. A customized Illumina panel was used for DNA sequencing and the Mann–Whitney U test was used to test the correlation between mesenchymal CTCs, CTC-WBC cluster counts, and specific genomic changes.ResultsAt least one somatic hotspot mutation was detected in each of the 29 sequenced patients. A total of 42 somatic hot spot mutations were detected in tumor tissue DNA, and 39 mutations were detected in CTC-DNA, all of which included common changes in PTEN, MET, EGFR, RET, and FGFR3. The number of mesenchymal CTCs was positively correlated with the somatic genomic alterations in the PTEN and MET genes (PTEN, P = 0.021; MET, P = 0.008, Mann–Whitney U test) and negatively correlated with the somatic genomic alterations in the EGFR gene (P = 0.006, Mann–Whitney U test). The number of CTC-WBC clusters was positively correlated with the somatic genomic alterations in RET genes (P = 0.01, Mann–Whitney U test) and negatively correlated with the somatic genomic alterations in FGFR3 (P = 0.039, Mann–Whitney U test).ConclusionsWe report a novel method of a CTC enrichment platform combined with NGS technology to analyze genetic variation, which further demonstrates the potential clinical application of this method for spatiotemporal heterogeneity monitoring of hepatocellular carcinoma. We found that the number of peripheral blood mesenchymal CTCs and CTC-WBC clusters in patients with hepatocellular carcinoma was related to a specific genome profile.

Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week’s GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.

Aim: Circulating tumor cells (CTC) are a precursor to metastasis in several types of cancer and are occasionally found in the bloodstream in association with immune cells, such as white blood cells (WBCs). CTC-associated WBC (CTC-WBC) clusters can promote CTC appreciation and metastasis, suggesting that patients with CTC-WBC clusters found in the peripheral blood may have a worse prognosis. However, it is unclear whether CTC-WBC clusters are present in the peripheral blood of patients with hepatocellular carcinoma (HCC) and suggest a poor prognosis for HCC.Methods: We collected peripheral blood from 214 patients with HCC from January 2014 to December 2016. CanPatrol™ CTC analysis technology was used to isolate and count CTCs and CTC-WBC clusters in the patients' peripheral blood. Chi-squared analysis was used to calculate the correlation between the CTC-WBC clusters and clinicopathological characteristics. Kaplan–Meier survival analysis and Cox regression analysis were used to assess patient prognosis.Results: We used CanPatrol™ CTC analysis technology to count different types of CTCs and CTC-WBC clusters. The results showed that CTC-WBC clusters and tumor size (P = 0.001), tumor number (P = 0.005), portal vein tumor thrombus (P = 0.026), BCLC stage (P < 0.001), AFP level (P = 0.002), and total number of CTCs (P < 0.001) were statistically related. Cox regression analysis revealed that CTC-WBC clusters are an independent prognostic indicator of DFS (HR = 1.951, 95%CI:1.348–2.824, P < 0.001) and OS (HR = 3.026, 95%CI:1.906–4.802, P < 0.001) in HCC patients. Using Kaplan–Meier analysis, we found that positive CTC-WBC cluster patients had significantly shorter DFS and OS than patients with negative CTC-WBC (P < 0.001 and P < 0.001, respectively).Conclusions: CTC-WBC clusters in the peripheral blood are an independent predictor of DFS and OS, and their presence indicates poor prognosis in patients with HCC.