Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma.

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.

Acne-induced pathological scars: pathophysiology and current treatments.

Acne is a common chronic inflammatory dermatosis that can lead to pathological scars (PSs, divided into hypertrophic scars and keloids). These kinds of abnormal scars seriously reduce the quality of life of patients. However, their mechanism is still unclear, resulting in difficult clinical prevention, unstable treatment effects and a high risk of recurrence. Available evidence supports inflammatory changes caused by infection as one of the keys to abnormal proliferation of skin fibroblasts. In acne-induced PSs, increasing knowledge of the immunopathology indicates that inflammatory cells directly secrete growth factors to activate fibroblasts and release pro-inflammatory factors to promote the formation of PSs. T helper cells contribute to PSs via the secretion of interleukin (IL)-4 and IL-13, the pro-inflammatory factors; while regulatory T cells have anti-inflammatory effects, secrete IL-10 and prostaglandin E2, and suppress fibrosis production. Several treatments are available, but there is a lack of combination regimens to target different aspects of acne-induced PSs. Overall, this review indicates that the joint involvement of inflammatory response and fibrosis plays a crucial role in acne-induced PSs, and also analyzes the interaction of current treatments for acne and PS.

Decreased sagittal slope of the medial tibial spine and deep concavity of the lateral tibial spine are risk factors for noncontact anterior cruciate ligament injury.

PURPOSE: This study aimed to assess the relationship between the geometric features of tibial eminence and susceptibility to noncontact anterior cruciate ligament (ACL) injuries. METHODS: Patients with unilateral noncontact knee injuries between 2015 and 2021 were consecutively enroled in this study. Based on knee magnetic resonance imaging (MRI) and arthroscopic visualisation, patients were categorised into the case group (ACL rupture) and control group (ACL intact). Using MRI, the geometric features of tibial eminence were characterised by measuring the sagittal slopes, depth of concavity and coronal slopes of the inclined surfaces of the tibial spines. Univariate and multivariate logistic regressions were conducted to explore independent associations between quantified geometric indices of tibial eminence and the risk of noncontact ACL injuries. RESULTS: This study included 187 cases and 199 controls. A decreased sagittal slope of the medial tibial spine (MTSSS) (combined group: odds ratio [OR]: 0.87 [0.82, 0.92], p < 0.001; females: OR: 0.88 [0.80, 0.98], p = 0.020; males: OR: 0.87 [0.81, 0.93], p < 0.001) and an increased depth of concavity in the lateral tibial spine (LTSD) (combined group: OR: 1.51 [1.24, 1.85], p < 0.001; females: OR: 1.65 [1.12, 2.43], p = 0.012; males: OR: 1.44 [1.11, 1.89], p = 0.007) were independent risk factors for noncontact ACL injuries. Moreover, a steeper coronal slope of the inclined surface of the medial tibial spine was a significant predictor of noncontact ACL injuries for males (MTSCS: OR: 1.04 [1.01, 1.08], p = 0.015) but not for females. CONCLUSION: Geometric features of tibial eminence, particularly a decreased MTSSS and an increased LTSD, were identified as independent risk factors for noncontact ACL injuries. These findings will help clinicians identify individuals at high risk of ACL injury and facilitate the development of targeted prevention strategies. LEVEL OF EVIDENCE: Level III.

Cronkhite-Canada syndrome with esophagus involvement and six-year follow-up: A case report.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare, noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal abnormalities. CCS polyps are distributed through the whole digestive tract, and they are common in the stomach and colon but very uncommon in the esophagus. CASE SUMMARY: Here, we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea, alopecia, and loss of his fingernails. Laboratory data indicated anemia, hypoalbuminemia, hypocalcemia, hypokalemia, and positive fecal occult blood. Endoscopy showed numerous polyps scattered throughout the digestive tract, including the esophagus. He was treated with nutritional support and glucocorticoids with remission of his symptoms. CONCLUSION: Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical symptoms. Treatment should be individualized for each patient according to their therapy response. Surveillance endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.

Life's Essential 8 and osteoporosis in adults aged 50 years or older: data from the National Health and Nutrition Examination Survey.

In this cross-sectional study, we examined the association between Life's Essential 8 (LE8) and bone mineral density (BMD) as well as osteoporosis risk among adults aged 50 and over. The findings of this study revealed that higher LE8 scores were associated with higher BMD and reduced osteoporosis risk. PURPOSE: The objective of the present study was to evaluate the association between Life's Essential 8 (LE8) and bone mineral density (BMD), as well as osteoporosis risk, in adults aged 50 years or over. METHODS: This cross-sectional study recruited individuals who were 50 years old or older from the National Health and Nutrition Examination Survey. LE8 scores were evaluated and calculated according to the scoring algorithm based on the American Heart Association recommendations, which were further categorized into health behaviors (LE8-HB) and health factors (LE8-HF) scores. Furthermore, the present study utilized multivariate linear regression models to examine the correlations between BMD and LE8 scores. In addition, ordinal logistic regression models were employed to determine the associations between the risk of osteoporosis (normal BMD, osteopenia, and osteoporosis) and LE8 scores. RESULTS: The final analysis included a total of 2910 participants, whose mean age was 64.49 ± 9.28 years. LE8 and LE8-HF scores exhibited a negative association with BMD and a positive association with osteoporosis risk in unadjusted models. Nevertheless, after adjustment for covariates, LE8 and LE8-HB scores exhibited a positive association with BMD and a negative association with osteoporosis risk, regardless of age, sex, or menopausal status. CONCLUSIONS: Scoring systems based on multiple lifestyle and behavior factors, similar to LE8, have the potential to become a novel option and be used for osteoporosis risk assessment.

The effect of perioperative sequential application of multiple doses of tranexamic acid on postoperative blood loss after PLIF: a prospective randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) has been utilized in spinal surgery to effectively reduce intraoperative blood loss (IBL) and allogeneic blood transfusion rates. However, the traditional TXA regimen might last the entire duration of hyperfibrinolysis caused by surgical trauma, resulting in its limited ability to reduce postoperative blood loss (PBL). Therefore, the aim of this study was to investigate the effectiveness of perioperative sequential administration of multiple doses of TXA in reducing PBL in patients who underwent posterior lumbar interbody fusion (PLIF). METHODS: From October 2022 to June 2023, 231 patients who were diagnosed with lumbar degenerative disease and scheduled to undergo PLIF were prospectively enrolled in the present study. The patients were randomly divided into three groups. Moreover, all patients received an intravenous injection of TXA at a dose of 15 mg/kg 15 min before the surgical skin incision. Patients in Group A received a placebo of normal saline after surgery, while patients in Group B received three additional intravenous injections of TXA at a dose of 15 mg/kg every 24 h. Patients in Group C received three additional intravenous injections of TXA at a dose of 15 mg/kg every 5 h. The primary outcome measure was PBL. In addition, this study assessed total blood loss (TBL), IBL, routine blood parameters, liver and kidney function, coagulation parameters, fibrinolysis indexes, inflammatory indicators, drainage tube removal time (DRT), length of hospital stay (LOS), blood transfusion rate, and incidence of complications for all subjects. RESULTS: The PBL, TBL, DRT, and LOS of Group B and Group C were significantly lower than those of Group A ( P <0.05). The level of D-dimer (D-D) in Group C was significantly lower than that in Group A on the first day after the operation ( P =0.002), and that in Group B was significantly lower than that in Group A on the third day after the operation ( P =0.003). The interleukin-6 levels between the three groups from 1 to 5 days after the operation were in the order of Group A > Group B > Group C. No serious complications were observed in any patient. The results of multiple stepwise linear regression analysis revealed that PBL was positively correlated with incision length, IBL, smoking history, history of hypertension, preoperative fibrinogen degradation product level, and blood transfusion. It was negatively correlated with preoperative levels of fibrinogen, red blood cells, blood urea nitrogen, and age. Compared to female patients, male patients had an increased risk of PBL. Finally, the incidence of PBL was predicted. CONCLUSIONS: Sequential application of multiple doses of TXA during the perioperative period could safely and effectively reduce PBL and TBL, shorten DRT and LOS, reduce postoperative D-D generation, and reduce the postoperative inflammatory response. In addition, this study provided a novel prediction model for PBL in patients undergoing PLIF.

Associations of the serum vitamin D with mortality in postmenopausal women.

PURPOSE: Current evidence on the association of serum vitamin D with mortality in postmenopausal women is limited and inconsistent. Therefore, the purpose of this study was to examine the relationship between serum vitamin D and mortality in postmenopausal women. METHODS: In this study, we used data from the NHANES (2001-2018) and conducted a multivariate Cox regression model to examine associations between serum vitamin D and all-cause mortality, cardiovascular mortality (CVD), and cancer mortality. RESULTS: In a median follow-up period of 8.3 years, 1905 deaths of all causes were reported, 601 were due to CVD, and 385 deaths were due to cancer. After multivariable adjustment, higher serum vitamin D levels were significantly associated with a reduced risk of death. Compared to participants with lower vitamin D levels (<25 nmol/L), those with higher vitamin D levels (≥75.0 nmol/L) had a lower risk of all-cause mortality (hazard ratio 0.60, 95 % confidence interval 0.49 to 0.74), a lower risk of cardiovascular mortality (0.51, 0.35 to 0.74), and a lower risk of cancer mortality (0.43, 0.28 to 0.67). Moreover, we observed an L-shaped dose-response relationship of serum vitamin D levels with all-cause mortality, and cancer mortality, with this inflexion point being 55.9 nmol/L, and 51.2 nmol/L, respectively. CONCLUSIONS: Higher concentrations of serum vitamin D substantially correlated with a reduction in mortality risk from all-cause, CVD, and cancer in postmenopausal women. These results imply that upholding adequate vitamin D levels may help prevent premature death in postmenopausal women.

Inflammatory endotypes of adenoidal hypertrophy based on a cluster analysis of biomarkers.

OBJECTIVE: To identify adenoid inflammatory endotypes based on inflammatory markers, match endotypes to phenotypes, and predict endotypes. METHODS: This cross-sectional study included 72 children with adenoid hypertrophy. Thirteen inflammatory markers and total immunoglobulin E (TIgE) in adenoid tissue were analyzed using Luminex and enzyme-linked immunosorbent assay (ELISA) for performing cluster analysis. Correlation analysis was used to examine the characteristics of each cluster. Receiver operating characteristic (ROC) curve analysis was performed to screen for preoperative characteristic data with predictive value for adenoid inflammation endotype. RESULTS: The patients were divided into four clusters. Cluster 1 exhibited non-type 2 signatures with low inflammatory marker concentrations, except for the highest expression of Th1-related cytokines. Cluster 2 showed a non-type 2 endotype with the highest concentration of interleukin (IL)-17A and IL-22. Cluster 3 exhibited moderate type 2 inflammation, with the highest concentration of neutrophil factors. Cluster 4 demonstrated significant type 2 inflammation and moderate neutrophil levels. The proportions of AR and serum TIgE levels increased from clusters 1 to 4, and there was a gradual increase in the prevalence of chronic sinusitis from low to high neutrophilic inflammation. The area under the ROC curve for serum TIgE was higher than those for combined or other separate preoperative characteristics for predicting non-type 2 and type 2 inflammation in the adenoid tissue. CONCLUSIONS: The evaluation of cytokines in adenoid tissue revealed four endotypes. Serum TIgE level was an important indicator of the endotype of adenoid inflammation. Identification of adenoid inflammatory endotypes can facilitate targeted treatment decisions.

Correction: Jin et al. Effects of Zinc Source and Level on the Intestinal Immunity of Xueshan Chickens under Heat Stress. Animals 2023, 13, 3025.

There were some errors in the original publication [...].

Effects of Zinc Source and Level on the Intestinal Immunity of Xueshan Chickens under Heat Stress.

Heat stress can cause intestinal inflammation, impaired barrier integrity, and decreased immunity in poultry. While zinc is known to mitigate the adverse effects of heat stress, how the dietary supplementation of different sources and levels of it can improve the heat stress capacity of Chinese landraces remains unclear. This study investigated Xueshan chickens, which are an important local breed in China. The effects of different levels of ZnS and Zn-Prot M on their intestinal immune function under heat stress were compared. We found that different levels of ZnS and Zn-Prot M could effectively reduce the secretion level of IL-6 in the serum, and 60 mg/kg was optimal. Compared with ZnS, Zn-Prot M significantly increased duodenal villus height and VH/CD ratio, thus Zn-Prot M was more effective than ZnS. Both ZnS and Zn-Prot M significantly down-regulated TNF-α, IL-1ß, and MyD88 in 102-day-old duodenum, and IL-1ß, IL-6, and NFKBIA in jejunum and ileum at 74, 88, and 102 days old, with 60 mg/kg Zn-Prot M determined as optimal. In conclusion, our study demonstrates that Zn-Prot M is superior to ZnS in improving intestinal immunity in Xueshan chickens, and 60 mg/kg is the optimal addition dose.

Bone mineral density is associated with composite dietary antioxidant index among US adults: results from NHANES.

This cross-sectional study investigated the relationship between composite dietary antioxidant index (CDAI) and individual dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoids, and bone mineral density (BMD) in the US population aged 20 years older. We found a positive correlation between CDAI and femoral BMD. Moreover, higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. INTRODUCTION: While individual dietary antioxidants have shown beneficial effects on bone metabolism, the diverse and potentially interacting nature of dietary components may limit the accuracy of evaluating their impact on bone health. Thus, this study aims to investigate the association between CDAI and BMD. Additionally, we explore the relationship between the intake of individual components of the CDAI and BMD. METHODS: The CDAI is a novel index evaluating total dietary antioxidant intake, considering vitamins A, C, and E, zinc, selenium, and carotenoids. A cross-sectional analysis was conducted using data from participants aged ≥ 20 in the National Health and Nutrition Examination Survey (2005-2010, 2013-2014, and 2017-2018). We utilized multivariate linear regression models to examine the relationship between CDAI, individual dietary antioxidants, including vitamins A, C, and E, zinc, selenium, carotenoids, and femoral BMD. RESULTS: The final analysis included 10,584 participants with a mean age of 50.73 ± 16.65 years. After multivariate adjustment, the second to fourth quartiles of CDAI (- 2.00-0.04, 0.04-2.54, and 2.54-70.78) exhibited higher femoral BMD compared to the first quartile of CADI (- 7.34 to - 2.00). Multiple regression analysis revealed that higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. CONCLUSIONS: CDAI serves as a comprehensive tool for evaluating the overall antioxidant capacity of antioxidants in diets. Additionally, our study shows a positive correlation between CDAI and BMD, which indicates that the combined intake of dietary antioxidants may help reduce the risk of osteoporosis in adults.

A novel primary osteoporosis screening tool (POST) for adults aged 50 years and over.

PURPOSE: This study aimed to develop and validate a simple primary osteoporosis screening tool (POST) based on adults aged 50 years and older. METHODS: This study included participants aged ≥50 from the National Health and Nutrition Examination Survey. Osteoporosis was defined according to bone mineral density values. The POST was developed based on methods from previous studies. Moreover, we plotted the receiver operating characteristic curves to calculate the area under the curve (AUC) and determine the optimal cut-off value according to the weighted Youden index. In addition, we compared the performances in identifying individuals with osteoporosis between the POST and the Osteoporosis Self-assessment Tool (OST). Finally, we also assessed the performance of the POST in the Chinese population. RESULTS: Finally, a total of 6665 individuals were included in this study. The AUC values of the POST for identifying individuals with osteoporosis in the development cohort and the validation cohort were 0.81 (95% CI: 0.79-0.83) and 0.81 (95% CI: 0.77-0.84), respectively. Moreover, a POST-score ≥7 was determined as the threshold to identify individuals with osteoporosis, in which the sensitivity was greater than 90%. In addition, the POST showed significantly higher sensitivity than the OST. Finally, the POST showed an AUC of 0.75 (95% CI: 0.65-0.85) among 94 Chinese subjects aged ≥50 years old. CONCLUSIONS: POST is a convenient and effective tool for osteoporosis screening among adults aged 50 years and over, which might provide new methodological support for future osteoporosis screening.

Selective Oxidation of Methane to Methanol over Au/H-MOR.

Selective oxidation of methane to methanol by dioxygen (O2) is an appealing route for upgrading abundant methane resource and represents one of the most challenging reactions in chemistry due to the overwhelmingly higher reactivity of the product (methanol) versus the reactant (methane). Here, we report that gold nanoparticles dispersed on mordenite efficiently catalyze the selective oxidation of methane to methanol by molecular oxygen in aqueous medium in the presence of carbon monoxide. The methanol productivity reaches 1300 µmol gcat-1 h-1 or 280 mmol gAu-1 h-1 with 75% selectivity at 150 °C, outperforming most catalysts reported under comparable conditions. Both hydroxyl radicals and hydroperoxide species participate in the activation and conversion of methane, while it is shown that the lower affinity of methanol on gold mainly accounts for higher methanol selectivity.

Orthogonal Combinatorial Raman Codes Enable Rapid High-Throughput-Out Library Screening of Cell-Targeting Ligands.

High-throughput assays play an important role in the fields of drug discovery, genetic analysis, and clinical diagnostics. Although super-capacity coding strategies may facilitate labeling and detecting large numbers of targets in a single assay, practically, the constructed large-capacity codes have to be decoded with complicated procedures or are lack of survivability under the required reaction conditions. This challenge results in either inaccurate or insufficient decoding outputs. Here, we identified chemical-resistant Raman compounds to build a combinatorial coding system for the high-throughput screening of cell-targeting ligands from a focused 8-mer cyclic peptide library. The accurate in situ decoding results proved the signal, synthetic, and functional orthogonality for this Raman coding strategy. The orthogonal Raman codes allowed for a rapid identification of 63 positive hits at one time, evidencing a high-throughput-out capability in the screening process. We anticipate this orthogonal Raman coding strategy being generalized to enable efficient high-throughput-out screening of more useful ligands for cell targeting and drug discovery.

Radiographic OA, bone marrow lesions, higher body mass index and medial meniscal root tears are significantly associated with medial meniscus extrusion with OA or medial meniscal tears: a systematic review and meta-analysis.

PURPOSE: Medial meniscus extrusion (MME) refers to the protrusion of the medial meniscus beyond the tibial edge by more than 3 mm, leading to a deficiency of the hoop strain. MME commonly occurs in conjunction with osteoarthritis (OA) or medial meniscal tears (MMT). However, factors associated with concomitant MME in patients with OA or MMT have not been systematically reviewed. This study aims to perform a systematic review and meta-analysis to identify factors associated with concomitant MME in OA or MMT. METHODS: The systematic review of the literature was performed according to PRISMA. A literature search was conducted in 4 databases. All original human studies that reported the available evidence on factors associated with concomitant MME in patients with OA or MMT were included. Pooled binary variables were analyzed by odds ratios (OR) and 95% CIs, and pooled continuous variables were evaluated by mean difference (MD) and 95% CIs. RESULTS: Ten studies on OA (5993 patients) and eight studies on MMT (872 patients) met the inclusion criteria. The overall pooled incidence of MME was 43% (95% CI, 37-50%) for OA, 61% (95% CI 43-77%) for MMT, and 85% (95% CI 72-94%) for medial meniscal root tears (MMRT). For the population with OA, Factors significantly associated with MME included radiographic OA [OR 4.24; 95% CI 3.07-5.84; P < 0.0001], bone marrow lesions [OR, 3.35; 95% CI 1.61-6.99; P = 0.0013], cartilage damage [OR, 3.25; 95% CI 1.60-6.61; P = 0.0011], and higher body mass index (BMI) [MD, 1.81; 95% CI 1.15-2.48; P < 0.0001]. Factors strongly associated with increased risk of MME for MMT included medial meniscal root [OR, 8.39; 95% CI 2.84-24.82; P < 0.0001] and radial tears [OR, 2.64; 95% CI 1.18-5.92; P < 0.0001]. CONCLUSION: Radiographic OA, bone marrow lesions, cartilage damage, and higher BMI were significantly associated with concomitant MME with OA. Furthermore, medial meniscal root and radial tears were significantly associated with an increased risk of MME in patients with MMT. LEVEL OF EVIDENCE: IV.

DFMA-oriented modular and parametric design and secondary splitting of vertical PC components.

The design and production of assembled buildings are difficult to standardise, which limits their extensive application. In this paper, the design for manufacture and assembly (DFMA) concept is applied to the design of vertical precast concrete (PC) components for assembled buildings. Taking vertical PC components as an example, the rapid modelling and whole life-cycle application of DFMA-oriented PC components for assembled buildings are investigated. Firstly, the modular design method is introduced. By combining parametric design and building information modelling (BIM), we propose a modular, parametric design method and process of PC components based on DFMA. Secondly, the design of standard modules after secondary splitting is introduced for a better DFMA-oriented parametric design of PC components. We explored the secondary development process of DFMA and BIM and the module creation process of the parametric standard based on family templates and DFMA. Thirdly, based on the parametric standard module, the application of the optimised whole life cycle of design, manufacture and assembly of PC components is introduced. Finally, the feasibility of this method is verified by practical cases. The design process for PC components is fast, accurate and standardised. The integrated application of BIM is accelerated, and digital collaboration in assembly construction is strengthened. The study results are conducive to establishing a standardised design and production system for PC components, reducing design costs, improving design efficiency and the comprehensive benefits of assembled buildings.

Long Noncoding RNA LINC00578 Inhibits Ferroptosis in Pancreatic Cancer via Regulating SLC7A11 Ubiquitination.

Background: Pancreatic cancer is a highly aggressive malignancy worldwide with rapid development and an exceedingly poor prognosis. lncRNAs play crucial roles in regulating the biological behaviors of tumor cells. In this study, we discovered that LINC00578 acted as a regulator of ferroptosis in pancreatic cancer. Methods: A series of loss- and gain-of-function experiments in vitro and in vivo were performed to explore the oncogenic role of LINC00578 in pancreatic cancer development and progression. Label-free proteomic analysis was performed to select LINC00578-related differentially expressed proteins. Pull-down and RNA immunoprecipitation assays were carried out to determine and validate the binding protein of LINC00578. Coimmunoprecipitation assays were used to investigate the association of LINC00578 with SLC7A11 in ubiquitination and to confirm the interaction between ubiquitin-conjugating enzyme E2 K (UBE2K) and SLC7A11. An immunohistochemical assay was used to confirm the correlation between LINC00578 and SLC7A11 in the clinic. Results: LINC00578 positively regulated cell proliferation and invasion in vitro and tumorigenesis in vivo in pancreatic cancer. LINC00578 can obviously inhibit ferroptosis events, including cell proliferation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) depolarization. In addition, the LINC00578-induced inhibitory effect on ferroptosis events was rescued by SLC7A11 knockdown. Mechanistically, LINC00578 directly binds UBE2K to decrease the ubiquitination of SLC7A11, thus accelerating SLC7A11 expression. In the clinic, LINC00578 is closely associated with clinicopathologic factors and poor prognosis and correlated with SLC7A11 expression in pancreatic cancer. Conclusions: This study elucidated that LINC00578 acts as an oncogene to promote pancreatic cancer cell progression and suppress ferroptosis by directly combining with UBE2K to inhibit the ubiquitination of SLC7A11, which provides a promising option for the diagnosis and treatment of pancreatic cancer.

Biomechanical Comparison of Anatomic Versus Lower of Anteromedial and Anterolateral Tibial Tunnels in Posterior Cruciate Ligament Reconstruction.

OBJECTIVE: In order to reduce the "killer turn" effect, various tibial tunnels have been developed. However, few studies investigated the biomechanical effects of different tibial tunnels during PCL reconstruction. This study aims to compare the time-zero biomechanical properties of anteromedial, anterolateral, lower anteromedial, and lower anterolateral tibial tunnels in transtibial posterior cruciate ligament (PCL) reconstruction under load-to-failure loading. METHODS: Porcine tibias and bovine extensor tendons were used to simulate in vitro transtibial PCL reconstruction. Forty bovine extensor tendons and 40 porcine tibias were randomly divided into four experimental groups: anteromedial tunnel group (AM group, n = 10), anterolateral tunnel group (AL group, n = 10), lower anteromedial tunnel group (L-AM group, n = 10), and lower anterolateral tunnel group (L-AL group, n = 10). The biomechanical test was then carried out in each group using the load-to-failure test. The ultimate load (in newtons), yield load (in newtons), tensile stiffness (in newtons per millimeter), load-elongation curve, failure mode, and tibial tunnel length (in millimeter) were recorded for each specimen. One-way analysis of variance (ANOVA) was used to compare the mean differences among the four groups. RESULTS: The biomechanical outcomes showed that there were no differences in the mean tensile stiffness and failure mode among four groups. The ultimate load and yield load of the L-AM group were significantly higher than those of other three groups (P < 0.05). For the AM group, its ultimate load is significantly higher than that of the L-AL group (P < 0.05), and its yield load is higher than that of the AL group and L-AL group (P < 0.05). However, we found no significant differences in either ultimate load or yield load between AL group and L-AL group (P > 0.05). There was significant statistical difference in the length of tibial tunnel between anatomic groups (AM and AL) and lower groups (L-AM and L-AL) (P < 0.05). CONCLUSION: Compared with the anteromedial, anterolateral, and lower anterolateral tibial tunnel, the lower anteromedial tibial tunnel showed better time-zero biomechanical properties including ultimate load and yield load in transtibial PCL reconstruction.

Screening and identification of potential hub genes and immune cell infiltration in the synovial tissue of rheumatoid arthritis by bioinformatic approach.

Background: Rheumatoid arthritis (RA) is an autoimmune disease that affects individuals of all ages. The basic pathological manifestations are synovial inflammation, pannus formation, and erosion of articular cartilage, bone destruction will eventually lead to joint deformities and loss of function. However, the specific molecular mechanisms of synovitis tissue in RA are still unclear. Therefore, this study aimed to screen and explore the potential hub genes and immune cell infiltration in RA. Methods: Three microarray datasets (GSE12021, GSE55457, and GSE55235), from the Gene Expression Omnibus (GEO) database, have been analyzed to explore the potential hub genes and immune cell infiltration in RA. First, the LIMMA package was used to screen the differentially expression genes (DEGs) after removing the batch effect. Then the clusterProfiler package was used to perform functional enrichment analyses. Second, through weighted coexpression network analysis (WGCNA), the key module was identified in the coexpression network of the gene set. Third, the protein-protein interaction (PPI) network was constructed through STRING website and the module analysis was performed using Cytoscape software. Fourth, the CIBERSORT and ssGSEA algorithm were used to analyze the immune status of RA and healthy synovial tissue, and the associations between immune cell infiltration and RA-related diagnostic biomarkers were evaluated. Fifth, we used the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to validate the expression levels of the hub genes, and ROC curve analysis of hub genes for discriminating between RA and healthy tissue. Finally, the gene-drug interaction network was constructed using DrugCentral database, and identification of drug molecules based on hub genes using the Drug Signature Database (DSigDB) by Enrichr. Results: A total of 679 DEGs were identified, containing 270 downregulated genes and 409 upregulated genes. DEGs were primarily enriched in immune response and chemokine signaling pathways, according to functional enrichment analysis of DEGs. WGCNA explored the co-expression network of the gene set and identified key modules, the blue module was selected as the key module associated with RA. Seven hub genes are identified when PPI network and WGCNA core modules are intersected. Immune infiltration analysis using CIBERSORT and ssGSEA algorithms revealed that multiple types of immune infiltration were found to be upregulated in RA tissue compared to normal tissue. Furthermore, the levels of 7 hub genes were closely related to the relative proportions of multiple immune cells in RA. The results of the qRT-PCR demonstrated that the relative expression levels of 6 hub genes (CD27, LCK, CD2, GZMB, IL7R, and IL2RG) were up-regulated in RA synovial tissue, compared with normal tissue. Simultaneously, ROC curves indicated that the above 6 hub genes had strong biomarker potential for RA (AUC >0.8). Conclusions: Through bioinformatics analysis and qRT-PCR experiment, our study ultimately discovered 6 hub genes (CD27, LCK, CD2, GZMB, IL7R, and IL2RG) that closely related to RA. These findings may provide valuable direction for future RA clinical diagnosis, treatment, and associated research.

Metabolic associated fatty liver disease and bone mineral density: a cross-sectional study of the National Health and Nutrition Examination Survey 2017-2018.

This research is a cross-sectional study based on the participants aged 50 years and older from National Health and Nutrition Examination Survey (NHANES) database. The metabolic associated fatty liver disease (MAFLD) population has higher BMD and a lower risk of osteoporosis than those without MAFLD. INTRODUCTION: MAFLD is a new definition presented by panel of experts based on non-alcoholic fatty liver disease in 2020. However, the link between MAFLD and bone mineral density (BMD) is uncertain. Thus, the present study aimed to investigate the relationship between MAFLD and BMD. METHODS: This cross-sectional study included subjects aged ≥ 50 years from the National Health and Nutrition Examination Survey 2017-2018. Multivariate linear regression models were performed to investigate the association between MAFLD and BMD. Moreover, the relationship between MAFLD and osteoporosis was assessed using multiple logistic regression models. RESULTS: Finally, 817 participants (non-MAFLD, n = 436; MAFLD, n = 381) were included in the final analysis. The results demonstrated that participants with MAFLD showed higher femoral BMDs than those without MAFLD, especially among males aged ≥ 50 years and females aged ≥ 65 years. Moreover, the results showed that obese men (BMI ≥ 30 kg/m2) with MAFLD had higher femoral BMDs than the control group according to subgroup analyses stratified by BMI, but this trend was not present in women. In addition, multiple logistic regression models showed that participants with MAFLD had no increased risks of osteoporosis. CONCLUSION: The present study found that the MAFLD population has higher BMD and a lower risk of osteoporosis than those without MAFLD. Because the present study was a cross-sectional study, we could not identify the cause-effect relation between MAFLD and BMD. Therefore, additional research needs to be performed to explore the influences of MAFLD on bone metabolism in the future.