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Summary: Here, we present a protocol for conducting bibliometric analysis in biomedicine using CiteSpace and VOSviewer. We describe the steps for extracting data from Web of Science, data cleaning, and preprocessing. We then detail procedures for identifying research trends and collaboration networks by visualizing data with CiteSpace; mapping co-authorship, co-citation, and keyword co-occurrence using VOSviewer; and analyzing highly cited literature to identify key publications and trends. Finally, we outline techniques for interpreting the visualizations to draw meaningful conclusions about the research landscape.For complete details on the use and execution of this protocol, please refer to Li et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background There were controversies for the association between computed tomography (CT)‐determined low skeletal muscle mass (SMM) and overall survival (OS) in gastric cancer (GC). In this study, we investigated whether cachexia could be a potential confounding variable for this issue. Methods We retrospectively collected the patients of GC in our institution between July 2016 and January 2021. Preoperative SMM was determined by analyzing the skeletal muscle index of L3 with abdominal CT, and the cut‐offs for low SMM were defined as

Abstract Introduction The main emphasis of the research about adjuvant imatinib for high‐risk gastrointestinal stromal tumors (GISTs) is prolonging the treatment duration and ignores the heterogeneous that 10‐year recurrence rates ranged from about 20%–100%. Thus, this study evaluated the effect of different durations of adjuvant imatinib on outcomes in high‐risk GISTs to explore the feasibility of individual treatment. Methods We analyzed 855 high‐risk GIST patients from three centers who underwent macroscopically complete resection between December 2007 and September 2020. The patients were divided into training (n =564) and two validation cohorts (n = 238 and53) based on their source. Recurrence‐free survival (RFS) was the primary point. Cox multivariate analysis was used to develop the nomogram. C‐index, time‐dependent area under the curves, and calibration plots were used to assess the performance of the nomogram. Results Univariate analysis showed that longer adjuvant imatinib was significantly associated with better 5‐year RFS (p

BackgroundFew studies have investigated the correlation between visceral fat area (VFA) and early postoperative complications in patients with obesity undergoing bariatric surgery. This study aimed to investigate the relationship between VFA and early postoperative complications in patients with obesity following bariatric surgery.MethodsThe study was conducted at a tertiary university hospital. Patients with obesity who underwent laparoscopic sleeve gastrectomy between June 2016 and October 2020 were divided into two groups based on umbilical level VFA: high-VFA group (umbilical level VFA ≥ 100 cm2) and low-VFA group (umbilical level VFA < 100 cm2). Baseline characteristics, intraoperative and postoperative conditions, and early postoperative complications were compared between the groups. The primary outcome was early postoperative complications, and the secondary outcome was postoperative hospital stay.ResultsThe study included 152 patients, with 82 patients in the low-VFA group and 70 patients in the high-VFA group. The high-VFA group had a higher incidence of early postoperative complications (14.29% vs. 2.44%, P = 0.013) than the low-VFA group. The length of postoperative hospital stay did not differ significantly between the groups.ConclusionsOur study suggests that excess VFA is an independent risk factor for early postoperative complications following bariatric surgery, and VFA may be used in preoperative evaluations.

Background. Both low skeletal muscle mass and delirium are prevalent in older hospitalized patients, while their associations are unclear. This systematic review and meta-analysis aim to investigate the associations between low skeletal muscle mass and the incidence of delirium in hospitalized patients. Methods. The PubMed, Web of Science, and Embase were searched for relevant studies published before May 2022, and we conducted this systematic review and meta-analysis according to the PRISMA and MOOSE guidelines. The summary odds ratios (OR) and 95% confidence intervals (CI) were estimated, and subgroup analyses were also conducted according to the age and major surgeries. Results. Finally, nine studies with 3 828 patients were included. The pooled result showed no significant association between low skeletal muscle mass and the incidence of delirium (OR 1.69, 95% CI 0.85 to 2.52). However, sensitivity analysis suggested that one study caused a significant alteration of the summary result, and the meta-analysis of the remaining 8 studies showed that low skeletal muscle mass was significantly associated with an 88% increased incidence of delirium (OR 1.88, 95% CI 1.43 to 2.33). Furthermore, subgroup analyses indicated that low skeletal muscle mass was associated with a higher incidence of delirium in patients ≥75 years old or undergoing major surgeries instead of those

BackgroundFew studies have investigated the relationship between sarcopenia and postoperative pulmonary complications (PPCs) after gastric cancer surgery. This study aimed to explore the impact of sarcopenia on PPCs in patients who had undergone gastric cancer surgery.MethodsWe included patients who underwent a transabdominal radical gastrectomy between June 2016 and October 2020. Patients were divided into two groups according to the median prevalence rate of lumbar triplane skeletal muscle index (L3 SMI): sarcopenia group (≤37.5% percentile in male and female group) and non-sarcopenia group (>37.5% percentile in male and female group). Baseline characteristics, intraoperative and postoperative conditions, pulmonary complications, and overall complications were compared between the two groups. The primary outcome was the incidence of PPCs. The secondary outcomes were overall postoperative complications and length of stay (LOS).ResultsAmong the 143 patients included, 50 had sarcopenia and 93 had not. Compared to the non-sarcopenia group, the sarcopenia group had a higher the incidence of PPCs (22.0% vs. 8.6%, P = 0.024). The incidence of overall postoperative complications in the sarcopenia group was higher than that in the non-sarcopenia group (36.00% vs. 20.43%, P = 0.043). There was no significant difference in the LOS between the two groups.ConclusionsOur research indicates that sarcopenia, preoperative comorbidities, and longer duration of intraoperative oxygen saturation

Abstract Background Most previous studies compared the risk for non-melanoma skin cancer (NMSC) in biologic-treated common inflammatory diseases with the general population. Whether the increased NMSC risk is caused by the disease itself, the biologics, or both remains unknown. Methods We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane Library from inception to May 2021. Studies were included if they assessed the risk of NMSC for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis patients treated with biologics compared with patients not receiving biologics. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model. Results The current meta-analysis included 12 studies. Compared with patients with the inflammatory disease without biologics, patients receiving biological therapy were associated with an increased risk for NMSC (RR 1.25, 95% CI 1.14 to 1.37), especially in patients with RA (RR 1.24, 95% CI 1.13 to 1.36) and psoriasis (RR 1.28, 95% CI 1.07 to 1.52), but not in patients with IBD (RR 1.49, 95% CI 0.46 to 4.91). The risks for squamous cell skin cancer and basal cell skin cancer were both increased for patients receiving biologics. However, the risk of NMSC did not increase in patients treated with biologics less than 2 years. Conclusions Current evidence suggests that increased risk of NMSC was identified in RA and psoriasis treated with biologics compared with patients not receiving biologics, but not in patients with IBD. The inner cause for the increased risk of NMSC in IBD patients should be further discussed.

BackgroundCurrent diagnostic criteria for cancer cachexia are inconsistent, and arguments still exist about the impact of cachexia on the survival of patients with colorectal cancer. In this study, we aim to investigate the prognostic value of a novel cachexia indicator, the cachexia index (CXI), in patients with colorectal cancer.MethodsThe CXI was calculated as skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio. The cut-off value of CXI was determined by the receiver operating characteristic (ROC) curves and Youden’s index. The major outcomes were major complications, overall survival (OS), and recurrence-free survival (RFS).ResultsA total of 379 patients (234 men and 145 women) were included. The ROC curves indicated that CXI had a significantly diagnostic capacity for the detection of major complications. Based on Youden’s index, there were 231 and 148 patients in the low and high CXI groups, respectively. Patients in the low CXI group had significantly older age, lower BMI, and a higher percentage of cachexia and TNM stage II+III. Besides, Patients in low CXI group were associated with a significantly higher rate of major complications, blood transfusion, and longer length of stay. Logistic regression analysis indicated that low CXI, cachexia, and coronary heart disease were independent risk factors for the major complications. Kaplan Meier survival curves indicated that patients with high CXI had a significantly more favorable OS than those with low CXI, while no significant difference was found in RFS between the two groups. Besides, there were no significant differences in OS or RFS between patients with and without cachexia. The univariate and multivariate Cox regression analysis indicated that older age, low CXI, and coronary heart disease instead of cachexia were associated with a decreased OS.ConclusionCXI was better than cachexia in predicting OS and could be a useful prognostic indicator in patients with colorectal cancer, and greater attention should be paid to patients with low CXI.

Soy is rich in plant protein, isoflavones, and polyunsaturated fatty acids. To clarify the associations between soy intake and type 2 diabetes (T2D) and cardiovascular diseases (CVDs) events, we performed a meta-analysis and review. A total of 1963 studies met the inclusion criteria, and 29 articles with 16,521 T2D and 54,213 CVDs events were identified by the eligibility criteria. During a follow-up of 2.5–24 years, the risk of T2D, CVDs, coronary heart disease, and stroke in participants with the highest soy consumption decreased by 17% (total relative risk (TRR) = 0.83, 95% CI: 0.74–0.93), 13% (TRR = 0.87, 95% CI: 0.81–0.94), 21% (TRR = 0.79, 95% CI: 0.71–0.88), and 12% (TRR = 0.88, 95% CI: 0.79–0.99), respectively, compared to the lowest sot consumption. A daily intake of 26.7 g of tofu reduced CVDs risk by 18% (TRR = 0.82, 95% CI: 0.74–0.92) and 11.1 g of natto lowered the risk of CVDs by 17% (TRR = 0.83, 95% CI: 0.78–0.89), especially stroke. This meta-analysis demonstrated that soy consumption was negatively associated with the risks of T2D and CVDs and a specific quantity of soy products was the most beneficial for the prevention of T2D and CVDs. This study has been registered on PROSPERO (registration number: CRD42022360504).

Abstract Objective The purpose of this umbrella review was to assess the associations between sarcopenia and adverse health‐related outcomes. Design An umbrella review of meta‐analyses of observational studies. Setting and Participants Patients with sarcopenia and controls without sarcopenia were included. Measures The PubMed, Web of Science and Embase were searched for relevant systematic review and meta‐analysis. AMSTAR and GRADE system were used for methodological quality and evidence quality assessments, respectively. Results Totally 54 outcomes extracted from 30 meta‐analyses were analyzed. Twenty out of 21 prognostic outcomes indicated that sarcopenia was significantly associated with poorer prognosis of gastric cancer, hepatocellular cancer, urothelial cancer, head and neck cancer, hematological malignancy, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, esophageal cancer, and ovarian cancer. Besides, 10 out of 16 postoperative outcomes suggested that sarcopenia significantly increased the risk of multiple postoperative complications and prolonged the length of hospitalization of patients with digestive cancer. In age‐related outcomes, sarcopenia significantly increased the risk of dysphagia, cognitive impairment, fractures, falls, hospitalization, and all‐cause mortality of elderly populations. Moreover, sarcopenia was also associated with higher level of albuminuria, risk of depression, and several metabolic diseases. Conclusions and Implications Sarcopenia significantly affected a wide range of adverse health‐related outcomes, particularly in patients of tumor and elderly populations. Because evidences of most outcomes were rated as “low” and “very low,” more prospective cohort studies are required in the future.

The current diagnostic criteria for cancer cachexia are inconsistent, and the prognostic value of cachexia in gastric cancer (GC) is controversial. This study aimed to investigate the prognostic value of the cachexia index (CXI) in patients with GC. We calculated the CXI as skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio (NLR), and a total of 161 and 163 patients were included in the high and low CXI groups, respectively. Low CXI was significantly associated with a more advanced tumor–node–metastasis (TNM) stage, a higher level of serum C-reactive protein, serum interleukin-6, and NLR, but also a decreased level of serum prealbumin and albumin. In addition, patients in the low CXI group were more likely to have postoperative pulmonary infections (9.8% vs. 3.7%, p = 0.03). Cox proportional analyses indicated that patients with low CXI (HR 0.45, 95% CI 0.29 to 0.69; p < 0.001) or TNM stage III+IV (HR 4.38, 95% CI 2.54 to 7.55; p < 0.001) had a significantly poorer overall survival (OS). Kaplan–Meier survival curves suggested that patients with low CXI had a significantly decreased OS, which was not affected by subgroup analyses of different sex, age, cachexia, body mass index (BMI), and TNM stage. Furthermore, low CXI combined with cachexia, low BMI, or TNM stage III+IV caused the worst OS in each subgroup analysis, respectively. Our study demonstrated that CXI had a good prognostic value in GC. Greater attention should be paid to patients with low CXI, particularly those combined with cachexia, low BMI, or TNM stage III+IV.

Abstract Previously, our meta‐analysis and other studies have suggested that allium vegetable consumption is beneficial for health, but no umbrella review has been conducted to assess the evidence of the various health benefits of allium vegetable consumption. Therefore, we conducted this umbrella review on this topic. This umbrella review included a total of 16 meta‐analyses with 50 unique outcomes. The most beneficial cancer‐related outcome was shown for gastric cancer (risk ratio 0.78; 95% confidence interval [CI] 0.67–0.91). In addition, only 8 weeks of garlic consumption significantly decreased serum total cholesterol (weighted mean differences −17.20 mg/dl; 95% CI −23.10 to −11.30), and patients with dyslipidemia who consumed garlic experienced more benefits than the whole population. Diabetic patients with longer durations of garlic intake experienced more benefits in terms of fasting blood glucose (FBG), HbA1c, and serum fructosamine than healthy participants, and garlic intake was associated with blood pressure reduction in hypertensive patients but not in normotensive participants. Limited side effects of garlic, such as garlic odor and gastrointestinal complaints, were reported among the included meta‐analyses. Our results suggested that allium vegetables might be beneficial for cancer prevention. In particular, garlic was comparatively safe and is recommended as a long‐term dietary component for patients with dyslipidemia, diabetes, and hypertension.

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68+CD163− macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68+CD163− macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68+CD163− macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes.

Abstract Background The epigenetic-age acceleration (EAA) represents the difference between chronological age and epigenetic age, reflecting accelerated biological aging. Observational studies suggested that oral disorders may impact DNA methylation patterns and aging, but their causal relationship remains largely unexplored. This study aimed to investigate potential causal associations between dental traits and EAA, as well as to identify possible mediators. Methods Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted univariable and multivariable Mendelian randomization (MR) to estimate the overall and independent effects of ten dental traits (dentures, bleeding gums, painful gums, loose teeth, toothache, ulcers, periodontitis, number of teeth, and two measures of caries) on four EAA subtypes (GrimAge acceleration [GrimAA], PhenoAge acceleration [PhenoAA], HannumAge acceleration [HannumAA] and intrinsic EAA [IEAA]), and used two-step Mendelian randomization to evaluate twelve potential mediators of the associations. Comprehensive sensitivity analyses were used to verity the robustness, heterogeneity, and pleiotropy. Results Univariable inverse variance weighted MR analyses revealed a causal effect of dentures on greater GrimAA (β: 2.47, 95% CI: 0.93–4.01, p = 0.002), PhenoAA (β: 3.00, 95% CI: 1.15–4.85, p = 0.001), and HannumAA (β: 1.96, 95% CI: 0.58–3.33, p = 0.005). In multivariable MR, the associations remained significant after adjusting for periodontitis, caries, number of teeth and bleeding gums. Three out of 12 aging risk factors were identified as mediators of the association between dentures and EAA, including body mass index, body fat percentage, and waist circumference. No evidence for reverse causality and pleiotropy were detected (p > 0.05). Conclusions Our findings supported the causal effects of genetic liability for denture wearing on epigenetic aging, with partial mediation by obesity. More attention should be paid to the obesity-monitoring and management for slowing EAA among denture wearers.

Abstract Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia.

Abstract Background The role of thyroid health in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder, such as hypothyroidism or hyperthyroidism, is destructive in TMDs. This study aims to investigate the overall and specific causal effects of various thyroid conditions on TMDs. Methods Mendelian randomization (MR) studies were performed using genetic instruments for thyrotropin (TSH, N = 119,715), free thyroxine (fT4, N = 49,269), hypothyroidism (N = 410,141), hyperthyroidism (N = 460,499), and TMDs (N = 211,023). We assessed the overall effect of each thyroid factor via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Additionally, multivariable MR was conducted to evaluate the direct or indirect effects of hypothyroidism on TMDs whilst accounting for TSH, fT4 and hyperthyroidism, and vice versa. Results Univariable MR analyses revealed a causal effect of hypothyroidism on an increased risk of TMDs (IVW OR: 1.12, 95% CI: 1.05–1.20, p = 0.001). No significant association between genetically predicted hyperthyroidism, TSH, or fT4 and TMDs. In the multivariable MR analyses, the effects of hypothyroidism on TMDs occurrence remained significant even after adjSusting for TSH, fT4 and hyperthyroidism (multivariable IVW OR: 1.10, 95% CI: 1.03–1.17, p = 0.006). No pleiotropy and heterogeneity were detected in the analyses (p > 0.05). Conclusions Hypothyroidism might causally increase the risk of TMDs through a direct pathway, highlighting the critical role of managing thyroid health in the prevention of TMDs. Clinicians should give heightened attention to patients with hypothyroidism when seeking medical advice for temporomandibular discomfort. However, caution is warranted due to the potential confounders, pleiotropy, and selection bias in the MR study.

BackgroundThe role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs.MethodsGenetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves’ disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren’s syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality.ResultsUnivariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p < 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including “CD25++ CD8+ T cell % CD8+ T cell” (mediation proportion: 6.2%) and “CD3 on activated CD4 regulatory T cell” (5.4%). Additionally, “CD127 on granulocyte” mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p > 0.05).ConclusionThis MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.

Summary: Maternal-to-zygotic transition (MZT) is central to early embryogenesis. However, its underlying molecular mechanisms are still not well described. Here, we revealed the expression dynamics of 5,000 proteins across four stages of zebrafish embryos during MZT, representing one of the most systematic surveys of proteome landscape of the zebrafish embryos during MZT. Nearly 700 proteins were differentially expressed and were divided into six clusters according to their expression patterns. The proteome expression profiles accurately reflect the main events that happen during the MZT, i.e., zygotic genome activation (ZGA), clearance of maternal mRNAs, and initiation of cellular differentiation and organogenesis. MZT is modulated by many proteins at multiple levels in a collaborative fashion, i.e., transcription factors, histones, histone-modifying enzymes, RNA helicases, and P-body proteins. Significant discrepancies were discovered between zebrafish proteome and transcriptome profiles during the MZT. The proteome dynamics database will be a valuable resource for bettering our understanding of MZT.

Background: Though anterior cruciate ligament (ACL) tear has been widely accepted as an important accelerator for knee osteoarthritis (KOA), the role of intrinsic ACL degeneration in developing KOA has not been fully investigated. Purpose: To determine whether ACL degeneration, in the absence of ACL tear, is associated with incident KOA over 4 years. Study design: Cohort study; Level of evidence, 2. Methods: Participants’ knees in this nested case–control study were selected from the Osteoarthritis Initiative (OAI) study, with Kellgren–Lawrence grading (KLG) of 0 or 1 ​at baseline (BL). Case knees which had incident KOA (KLG ≥2) over 4 years, were matched 1:1 with control knees by gender, age and radiographic status. ACL signal intensity alteration (0–3 scale) and volume were assessed as compositional feature and morphology of ACL degeneration, using knee MRI at P0 (time of onset of incident KOA), P-1 (1 year prior to P0) and baseline. Conditional logistic regression was applied to analyze the association between measures of ACL degeneration and incident KOA. Results: 337 case knees with incident KOA were matched to 337 control knees. Participants were mostly female (68.5%), with an average age of 59.9 years old. ACL signal intensity alterations at BL, P-1 and P0 were significantly associated with an increased odds of incident KOA respectively (all P for trend ≤0.001). In contrast, ACL volumes were not significantly associated with incident KOA at any time points. Conclusions: ACL signal intensity alteration is associated with increased incident KOA over 4 years, whereas ACL volume is not.The translational potential of this article: This paper focused on ACL signal intensity alteration which could better reflect ACL degeneration rather than ACL tear during the progression of KOA and explored this topic in a nested case–control study. Utilizing MR images from KOA participants, we extracted the imaging features of ACL. In addition, we established a semi-quantitative score for ACL signal intensity alteration and found a significant correlation between it and KOA incidence. Our findings confirmed that the more severe the ACL signal intensity alteration, the stronger relationship with the occurrence of KOA. This suggests that more emphasis should be placed on ACL degeneration rather than ACL integrity in the future.

The development of appropriate and effective periodate (PI) activation technology is currently a popular research area. This study presents a novel efficient photocatalytic activation approach of PI for pollutant degradation based on carbon nitride (g-C3N4) and visible light (Vis). The results show that the system can remove 92.3% of acid orange 7 (AO7) within 60 min under the g-C3N4/PI/Vis reaction system. The degradation rate constant (kobs) reached 4.08 × 10−2 min−1, which is 4.21, 5.16 times, and 51.3 times higher than that of the g-C3N4/Vis system (9.7 × 10−3 min−1), PI/Vis system (7.9 × 10−3 min−1) and the g-C3N4/PI system (7.96 × 10−4 min−1), respectively. Clearly, the addition of PI significantly enhances the degradation efficiency of AO7 in the system. Additionally, under the same reaction conditions, the presence of PI showed excellent oxidation capacity in the photoactivation process compared with other common oxidants, such as peroxymonosulfate, peroxydisulfate, and H2O2. Moreover, the g-C3N4/PI/Vis system showed excellent removal of AO7 across a wide range of pH levels and in the presence of various anions. Electron paramagnetic resonance (EPR) and quenching experiments suggested that the superoxide anions (•O2−) and singlet oxygen (1O2) dominated in the oxidation of pollutants in the g-C3N4/PI/Vis system. In addition, the catalyst showed relative stability during cyclic testing, although a slight reduction in degradation efficiency was observed. In brief, the g-C3N4/PI/Vis system is highly efficient and environmentally friendly, with significant application potential in wastewater treatment.

Abstract Objective This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). Methods BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles. Results A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The “has-miR-424-5p/lncRNA PVT1” was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes. Conclusion IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.