Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.

BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

MOF-818 nanoparticles as radical scavengers to improve the aging resistance of silk fabric.

Silk fabrics hold immense historical value as precious legacies left by our ancestors, yet they face significant damage during archaeological excavations, necessitating urgent protective measures. However, The current protective materials can't effectively prevent the degradation of silk fabrics. Nanotechnology has emerged as a promising avenue for the consolidation and preservation of silk fabrics, offering novel concepts and materials. In this study, we propose an innovative and cost-effective method that uses the MOF-818 with a radical scavenging ability to enhance the protection of silk fabrics. The resulting demonstrates that the MOF-818 was the large surface area and porous properties, which exhibited excellent superoxide dismutase (SOD)-like activity at 10 ug/mL. The silk fabrics treated by MOF-818 displays small color difference, reduced the oxidation of functional group and prevents the degradation of silk fabrics. The successful development of this nanocomposite marks a significant advancement in silk protection, opening new horizons for the preservation of silk cultural relics.

Distinct pathway activities are associated with prognosis and response to bortezomib-containing treatment in MCL1-M based molecular subtypes of multiple myeloma.

Multiple myeloma (MM) is the second most prevalent hematological malignancy and remains incurable with remarkable heterogeneity in prognosis and treatment response across the patients. Clinical diagnosis and the existing molecular classification systems are inadequate for predicting treatment responses. Based on the convergence between plasma cell development and MM pathogenesis, we identified a gene co-expression module centered on the plasma cell survival regulator MCL1 (MCL1 module, MCL1-M) in the transcriptomes of pre-treated MM, which enabled stratification of MM patients into MCL1-M high and MCL1-M low molecular subtypes with subtype-specific prognosis and response to bortezomib-containing treatment. Here, we aimed to examine the mechanism underlying the disparate prognosis and treatment responses between the two molecular subtypes. Our findings reveal that MCL1-M high MM displays significant activation of pathways associated with cell proliferation, while MCL1-M low MM exhibits activation of immune-related signaling pathways. The relative enrichment of immune cells within the bone marrow microenvironment of MCL1-M low MM, particularly plasmacytoid dendritic cells, likely contributes to the activation of immune-related signaling pathways in this subset of myeloma cells. Using phase III trial data, we show that responses to bortezomib-containing treatment are associated with the extent of unfolded protein response (UPR) signaling activity. Further, bortezomib-mediated killing of MM cells could be enhanced or inhibited by in vitro manipulation of UPR activities in representative cell lines. In conclusion, MCL1-M based molecular subtypes of MM are characterized by distinct signaling activities from both malignant cells and bone marrow microenvironment, which may drive distinct prognosis and treatment responses.

PTBP1-mediated repression of neuron-specific CDC42 splicing constitutes a genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype glioblastoma.

Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform.  Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. PTBP1 is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.

Combined associations of visceral adipose tissue and adherence to a Mediterranean lifestyle with T2D and diabetic microvascular complications among individuals with prediabetes.

BACKGROUND: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. METHODS: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. RESULTS: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC. CONCLUSION: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D.

Population pharmacokinetics of fluconazole for prevention or treatment of invasive candidiasis in Chinese young infants.

The dosing of fluconazole for young infants remains empirical because of the limited pharmacokinetic (PK) data. We aimed to establish a population PK model and assess the systematic exposure-response of commonly used regimens of fluconazole in Chinese infants. We included infants with a postnatal age of less than 120 days and received intravenous fluconazole. Both scheduled and scavenged plasma samples were collected, and fluconzaole concentration was determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using Phoenix NLME, and then Monte Carlo simulation was conducted to predict the probability of target attainment (PTA) of empirically used regimens of both prophylactic and therapeutic purposes. Based on 304 plasma samples from 183 young infants, fluconazole concentration data was best described by a one-compartment model with first-order elimination. Gestational Age (GA), postnatal age (PNA), and body weight (BW) were included in the final model as CL = 0.02*(GA/214)2.77*(PNA/13)0.24*exp(nCL); V = 1.56*(BW/1435)0.90*exp(nV). Model validation revealed the final model had qualified stability and acceptable predictive properties. Monte Carlo simulation indicated that under the same minimum inhibitory concentration (MIC) value and administration regimen, PTA decreased with GA and PNA. The commonly used prophylactic regimens can meet the clinical need, while higher doses might be needed for treatment of invasive candidiasis. This population PK model of fluconazole discriminated the impact of GA and PNA on CL and BW on V. Dosing adjustment was needed according to the GA and PNA of infants to achieve targeted exposures.

Impact of healthy lifestyle on the incidence and progression trajectory of mental disorders: A prospective study in the UK Biobank.

BACKGROUND: Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking. METHODS: 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression. RESULTS: Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2-4 years and 4-6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively. LIMITATION: The generalizability to other ethnic groups is limited. CONCLUSION: This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows.

[Effects of plumbagin on proliferation and apoptosis of human hepatocellular carcinoma cells based on CKB/p53 signaling pathway].

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

Helicobacter pylori disrupts gastric mucosal homeostasis by stimulating macrophages to secrete CCL3.

BACKGROUND: Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. METHODS: The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. RESULTS: After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. CONCLUSIONS: In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.

Association between multiple-heavy-metal exposures and systemic immune inflammation in a middle-aged and elderly Chinese general population.

BACKGROUND: Exposure to heavy metals alone or in combination can promote systemic inflammation. The aim of this study was to investigate potential associations between multiple plasma heavy metals and markers of systemic immune inflammation. METHODS: Using a cross-sectional study, routine blood tests were performed on 3355 participants in Guangxi, China. Eight heavy metal elements in plasma were determined by inductively coupled plasma mass spectrometry. Immunoinflammatory markers were calculated based on peripheral blood WBC and its subtype counts. A generalised linear regression model was used to analyse the association of each metal with the immunoinflammatory markers, and the association of the metal mixtures with the immunoinflammatory markers was further assessed using weighted quantile sum (WQS) regression. RESULTS: In the single-metal model, plasma metal Fe (log10) was significantly negatively correlated with the levels of immune-inflammatory markers SII, NLR and PLR, and plasma metal Cu (log10) was significantly positively correlated with the levels of immune-inflammatory markers SII and PLR. In addition, plasma metal Mn (log10 conversion) was positively correlated with the levels of immune inflammatory markers NLR and PLR. The above associations remained after multiple corrections. In the mixed-metal model, after WQS regression analysis, plasma metal Cu was found to have the greatest weight in the positive effects of metal mixtures on SII and PLR, while plasma metals Mn and Fe had the greatest weight in the positive effects of metal mixtures on NLR and LMR, respectively. In addition, blood Fe had the greatest weight in the negative effects of the metal mixtures for SII, PLR and NLR. CONCLUSION: Plasma metals Cu and Mn were positively correlated with immunoinflammatory markers SII, NLR and PLR. While plasma metal Fe was negatively correlated with immunoinflammatory markers SII, NLR, and PLR.

Current research on the interaction between Helicobacter pylori and macrophages.

Helicobacter pylori (H. pylori) is a gram-negative bacteria with a worldwide infection rate of 50%, known to induce gastritis, ulcers and gastric cancer. The interplay between H. pylori and immune cells within the gastric mucosa is pivotal in the pathogenesis of H. pylori-related disease. Following H. pylori infection, there is an observed increase in gastric mucosal macrophages, which are associated with the progression of gastritis. H. pylori elicits macrophage polarization, releases cytokines, reactive oxygen species (ROS) and nitric oxide (NO) to promote inflammatory response and eliminate H. pylori. Meanwhile, H. pylori has developed mechanisms to evade the host immune response in order to maintain the persistent infection, including interference with macrophage phagocytosis and antigen presentation, as well as induction of macrophage apoptosis. Consequently, the interaction between H. pylori and macrophages can significantly impact the progression, pathogenesis, and resolution of H. pylori infection. Moreover, macrophages are emerging as potential therapeutic targets for H. pylori-associated gastritis. Therefore, elucidating the involvement of macrophages in H. pylori infection may provide novel insights into the pathogenesis, progression, and management of H. pylori-related disease.

Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy.

Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory. Here, we developed a hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts for the controlled delivery of NK cells to enhance the therapy of solid tumors. Surface-functionalized HAp nanobelts modified with agonistic antibodies against NKG2D and 4-1BB and cytokines IL-2 and IL-21 support survival and dynamic activation. Thus, the HAp-modified chitosan (CS) thermos-sensitive hydrogel not only improved the retention of NK cells for more than 20 days in vivo but also increased NK cell function by more than one-fold. The unique architecture of this biomaterial complex protects NK cells from the hostile tumor environment and improves antitumor efficacy. The generation of a transient inflammatory niche for NK cells through a biocompatible hydrogel reservoir may be a conversion pathway to prevent cancer recurrence of resectable tumors.

Plumbagin Regulates Snail to Inhibit Hepatocellular Carcinoma Epithelial-Mesenchymal Transition in vivo and in vitro.

Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-ß-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-ß-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot. Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells. Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.

Modified Bilhaut-Cloquet procedure for Wassel type III-IV polydactyly.

BACKGROUND: To investigate the functional and aesthetic results of a new modified Bilhaut-Cloquet procedure for the treatment of Wassel type III-IV thumb polydactyly. METHODS: Thirteen patients with Wassel type III-IV thumb polydactyly who visited the Department of Orthopedics of Hebei Provincial Children's Hospital from 2019 to 2022 were selected. The surgical procedure involved a modified Bilhaut-Cloquet surgery, where two-thirds of the distal part of the dominant finger was retained as the p body of the reconstructed thumb. The triangular bone block of the ablated distal thumb that did not contain the epiphysis and articular cartilage was sutured and fixed, and the neurovascular flap of the ablated distal thumb was used as an augmenting segment of the reconstructed thumb, with the nail bed and nail matrix exquisitely sutured. The evaluation performed according to the Japanese Society for Surgery of the Hand (JSSH) system. RESULTS: All 13 children showed bone healing, no wound infection, nonunion, or deformity healing. None of the children showed a significant reduction in the active and passive mobility of the thumb postoperatively compared with preoperatively. Postoperative evaluation was performed based on the JSSH score, with a mean of 17.15 points (14-19 points), with 11 children rated as excellent and two as good. No severe nail ridges, nail gaps, or nail split deformities of the thumb were observed postoperatively. Postoperative metacarpophalangeal and interphalangeal joint movements were not reduced compared with preoperative movements. All parents were satisfied with the appearance and function of the reconstructed thumb. CONCLUSION: The modified Bilhaut-Cloquet procedure designed in this study was satisfactory for Wassel type III-IV thumb polydactyly without affecting the stability of the interphalangeal joints and preserving joint mobility. The postoperative thumb has a comparable circumference and nail width and was cosmetically and functionally satisfactory, especially for the asymmetric two thumbs, which achieved favorable results.

Association between plasma and dietary trace elements and obesity in a rural Chinese population.

Trace elements may play an important role in obesity. This study aimed to assess the plasma and dietary intake levels of four trace elements, Mn, Cu, Zn and Se in a rural Chinese population, and analyse the relationship between trace elements and obesity. A cross-sectional study involving 2587 participants was conducted. Logistic regression models were used to analyse the association between trace elements and obesity; restricted cubic spline (RCS) models were used to assess the dose-response relationship between trace elements and obesity; the weighted quantile sum (WQS) model was used to examine the potential interaction of four plasma trace elements on obesity. Logistic regression analysis showed that plasma Se concentrations in the fourth quartile (Q4) exhibited a lower risk of developing obesity than the first quartile (Q1) (central obesity: OR = 0·634, P = 0·002; general obesity: OR = 0·525, P = 0·005). Plasma Zn concentration in the third quartile (Q3) showed a lower risk of developing obesity in general obesity compared with the first quartile (Q1) (OR = 0·625, P = 0·036). In general obesity, the risk of morbidity was 1·727 and 1·923 times higher for the second and third (Q2, Q3) quartiles of dietary Mn intake than for Q1, respectively. RCS indicated an inverse U-shaped correlation between plasma Se and obesity. WQS revealed the combined effects of four trace elements were negatively associated with central obesity. Plasma Zn and Se were negatively associated with obesity, and dietary Mn was positively associated with obesity. The combined action of the four plasma trace elements had a negative effect on obesity.

Leveraging a disulfidptosis­related lncRNAs signature for predicting the prognosis and immunotherapy of glioma.

BACKGROUND: Gliomas, a prevalent form of primary brain tumors, are linked with a high mortality rate and unfavorable prognoses. Disulfidptosis, an innovative form of programmed cell death, has received scant attention concerning disulfidptosis-related lncRNAs (DRLs). The objective of this investigation was to ascertain a prognostic signature utilizing DRLs to forecast the prognosis and treatment targets of glioma patients. METHODS: RNA-seq data were procured from The Cancer Genome Atlas database. Disulfidptosis-related genes were compiled from prior research. An analysis of multivariate Cox regression and the least absolute selection operator was used to construct a risk model using six DRLs. The risk signature's performance was evaluated via Kaplan-Meier survival curves and receiver operating characteristic curves. Additionally, functional analysis was carried out using GO, KEGG, and single-sample GSEA to investigate the biological functions and immune infiltration. The research also evaluated tumor mutational burden, therapeutic drug sensitivity, and consensus cluster analysis. Reverse transcription quantitative PCR was conducted to validate the expression level of DRLs. RESULTS: A prognostic signature comprising six DRLs was developed to predict the prognosis of glioma patients. High-risk patients had significantly shorter overall survival than low-risk patients. The robustness of the risk model was validated by receiver operating characteristic curves and subgroup survival analysis. Risk model was used independently as a prognostic indicator for the glioma patients. Notably, the low-risk patients displayed a substantial decrease in the immune checkpoints, the proportion of immune cells, ESTIMATE and immune score. IC50 values from the different risk groups allowed us to discern three drugs for the treatment of glioma patients. Lastly, the potential clinical significance of six DRLs was determined. CONCLUSIONS: A novel six DRLs signature was developed to predict prognosis and may provide valuable insights for patients with glioma seeking novel immunotherapy and targeted therapy.

Study on aging behavior of polyethylene glycol under three wavelengths of ultraviolet light irradiation.

PEG2000 (polyethylene glycol, molecular weight: 2000) is commonly used for the dehydration and reinforcement of waterlogged wooden cultural relics, but its photo-aging degradation will seriously affect the long-term conservation of the wooden cultural relics. In this study, the photo-aging characteristics and mechanisms of PEG2000 under UV (ultraviolet) irradiations of three wavelengths were comprehensively investigated, and the surface morphology, crystal structure, and relative molecular weight of PEG2000 were systematically characterized. The results showed that PEG2000 showed a higher gloss loss rate, carbonyl index and crystallinity, and a wider molecular weight distribution with increasing aging time, especially under the irradiation of 313 nm ultraviolet light. The evolution of the PEG2000 from surface to interior during photoaging was elucidated by SEM (scanning electron microscopy) and FTIR (Fourier transform infrared spectroscopy), and it was determined that photodegradation not only occurs on the surface of PEG2000 but also gradually extends to the interior of the sample with the prolongation of irradiation time, resulting in the transformation of the basic component unit of spherical crystals in PEG2000 from fibrous crystals to spherical particles. Based on 1H-NMR (nuclear magnetic resonance spectroscopy), the photochemical reactions for the generation of degradation products were proposed, and it was found that the degradation occurred at the C-H and C-O-C bonds on the main chain, forming a large number of ester and ethoxy structures. The aging degree of PEG2000 was evaluated from the perspective of surface morphology and chemical structure by gloss and FTIR spectroscopy, and it was found that the combination of gloss loss rate and carbonyl index was more suitable to evaluate the aging degree of the sample. The relevant theoretical research will provide reliable guidance for the preservation of polyethylene glycol in waterlogged wooden cultural relics.

ApoE gene polymorphisms and metals and their interactions with cognitive function.

OBJECTIVE: To analyze the relationship between plasma metal elements, ApoE gene polymorphisms and the interaction between the two and impaired cognitive function in elderly population. METHOD: A stratified sample was drawn according to the age of the study population, and 911 subjects were included. Baseline information and health indicators were obtained, and cognitive function status was assessed by health examination, a general questionnaire and Mini-Mental Status Examination. Plasma metal elements were measured, and SNP typing was performed. Binary logistic regression was used to analyze the factors influencing cognitive function status and the association between the SNP genetic pattern of the ApoE gene and cognitive function. RESULTS: The differences in gene frequencies and genotype frequencies of the ApoE rs7412 and rs7259620 genotype frequencies were statistically different between the cognitive impairment group and the control group (P < 0.05). statistically differences were found for the codominant model in rs7412-TT compared with the CC genotype (OR = 3.112 (1.159-8.359), P = 0.024) and rs7259620-AA compared with the GG genotype (OR = 1.588 (1.007-2.504), P = 0.047). Statistically differences were found in the recessive models rs7412-TT compared with (CC + CT) (OR = 2.979 (1.112-7.978), P = 0.030), rs7259620-AA compared with (GG + GA), and rs405509-GG compared with (TT + TG) (OR = 1.548(1.022-2.344), P = 0.039) all of which increased the risk of developing cognitive impairment. The differences in plasma Fe, Cu, and Rb concentrations between the case and control groups were significant (P < 0.05). The regression results showed that the plasma Cd concentrations in the Q1 range was a protective factor for cognitive function compared with Q4 (0.510 (0.291-0.892), P = 0.018). Furthermore, there was a multiplicative interaction between the codominant and recessive models for the Q2 concentrations of Cd and the rs7259620 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (codominant model OR = 3.577 (1.496-8.555), P = 0.004, recessive model OR = 3.505 (1.479-8.307), P = 0.004). There was also a multiplicative interaction between Cd and the recessive model at the rs405509 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (OR = 3.169 (1.400-7.175), P = 0.006). CONCLUSION: The ApoE rs7412, rs7259620 and rs405509 loci were associated with cognitive impairment in the elderly population, and there was an interaction between plasma metalloid Cd and the rs7259620 and rs405509 loci that increased the risk of cognitive impairment in the elderly population.

Ferritin light chain promotes the reprogramming of glioma immune microenvironment and facilitates glioma progression.

Background: Tumor-associated macrophages (TAMs), the most abundant non-tumor cell population in the glioma microenvironment, play a crucial role in immune evasion and immunotherapy resistance of glioblastoma (GBM). However, the regulatory mechanism of the immunosuppressive TME of GBM remains unclear. Methods: Bioinformatics were used to analyse the potential role of ferritin light chain (FTL) in GBM immunology and explore the effects of FTL on the reprogramming of the GBM immune microenvironment and GBM progression. Results: The FTL gene was found to be upregulated in TAMs of GBM at both the bulk and single-cell RNA-seq levels. FTL contributed to the protumor microenvironment by promoting M2 polarization in TAMs via inhibiting the expression of iPLA2ß to facilitate the ferroptosis pathway. Inhibition of FTL in TAMs attenuated glioma angiogenesis, promoted the recruitment of T cells and sensitized glioma to anti-PD1 therapy. Conclusion: Our study suggested that FTL promoted the development of an immunosuppressive TME by inducing M2 polarization in TAMs, and inhibition of FTL in TAMs reprogrammed the TME and sensitized glioma to anti-PD1 therapy, providing a new strategy for improving the therapeutic effect of anti-PD1.