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Abstract Background Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. Method Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. Results In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. Conclusion In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.

The pathogenesis of rheumatoid arthritis (RA) remains elusive. The initiation of joint degeneration is characterized by the loss of self-tolerance in peripheral joints. Ferroptosis, a form of regulated cell death, holds significant importance in the pathophysiology of inflammatory arthritis, primarily due to iron accumulation and the subsequent lipid peroxidation.The present study investigated the association between synovial lesions and ferroptosis-related genes using previously published data from rheumatoid patients. Transcriptome differential gene analysis was employed to identify ferroptosis-related differentially expressed genes (FRDEGs). To validate FRDEGs and screen hub genes, we used weighted gene co-expression network analysis (WGCNA) and receiver operating characteristic (ROC) curves. Subsequently, immune infiltration analysis and single cell analysis were conducted to investigate the relationship between various synovial tissues cells and FRDEGs. The findings were further confirmed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemical staining, and immunofluorescence techniques.Upon intersecting DEGs with ferroptosis-related genes, we identified a total of 104 FRDEGs. Through the construction of a protein-protein interaction (PPI) network, we pinpointed the top 20 most highly concentrated genes as hub genes. Subsequent analyses using ROC curve and WGCNA validated eight FRDEGs: TIMP1, JUN, EGFR, SREBF1, ADIPOQ, SCD, AR, and FABP4. Immuno-infiltration analyses revealed significant infiltration of immune cell in RA synovial tissues and their correlations with the FRDEGs. Notably, TIMP1 demonstrated a positive correlation with various immune cell populations. Single-cell sequencing date of RA synovial tissue revealed predominant expression of TIMP1 is in fibroblasts. RT–qPCR, immunohistochemistry, and immunofluorescence analyses confirmed significant upregulation of TIMP1 at both mRNA and protein levels in RA synovial tissues and fibroblast-like synoviocytes (FLS).The findings provide novel insights into pathophysiology of peripheral immune tolerance deficiency in RA. The dysregulation of TIMP1, a gene associated with ferroptosis, was significantly observed in RA patients, suggesting its potential as a promising biomarker and therapeutic target.

Chouioia cunea are known to exploit in varying degrees a wide range of lepidopteran species and its offspring development may vary with host species. This study examined its preimaginal development and larval gut microbiota in parasitizing five folivorous lepidopteran hosts including Hyphantria cunea (referred to thereafter as CcHc), Antherea pernyi (CcAp), Helicoverpa armigera (CcHa), Spodoptera exigua (CcSe), and Spodoptera frugiperda (CcSf). Though rates of parasitism and offspring eclosion did not change with host species, the development period and number of offspring eclosed varied with hosts, with the shortest period in CcSf and the highest number from CcAp. For offspring larval gut microbiota, though phylum Proteobacteria was dominant for attacking CcAp, Firmicutes was so for the other hosts. All microbial genera except Enterococcus were less abundant for CcSf than the other hosts. The database-based predictions indicate a significant positive correlation between Cutibacterium and Aureimonas with the relative number of wasp emergence, while Blastomonas exhibits a strong positive association with the developmental period. Our results imply the potential relevance of the gut microbial community in offspring larvae to host species attacked by C. cunea.

BackgroundThis meta-analysis investigated the influence of exercise on cognitive function in people living with diabetes.MethodsStringent criteria for literature inclusion and exclusion were defined. Searches were conducted across four English databases to gather randomized controlled trials investigating exercise interventions for cognitive function in people living with diabetes. Outcome indicators from 1193 subjects across 12 articles were analyzed using RevMan 5.4 software.ResultsExercise intervention demonstrated the ability to mitigate cognitive decline in people living with diabetes, with a combined effect size (standardized mean difference) of 0.91, 95% CI: 0.28, 1.54, P < 0.00001. The intervention effect showed significant modulation by intervention content (I2 = 95%), intervention duration (I2 = 95%), intervention frequency (I2 = 95%), and intervention cycle (I2 = 96%). Among these factors, multi-component exercise, sessions >40 minutes, exercise frequency >4 times per week, and sustained exercise for >6 months were paramount, all with P < 0.05.ConclusionExercise intervention emerges as a viable strategy for delaying cognitive decline in people living with diabetes. Its efficacy is subject to modulation by various variables. Optimal intervention includes multi-component exercise, individual sessions lasting 40-60 minutes, exercising >4 times a week, and continuous exercise for over 6 months.

Based on the land economic density of 892 town units, the spatial pattern of the land economic density in Zhejiang Province is analyzed using the coefficient of variation, spatial classification, and spatial correlation methods, and the influencing factors are analyzed using a spatial regression model. The results are as follows: (1) The coefficients of variation were 2.6 and 3.1 in 2014 and 2019, respectively, indicating that the degree of imbalance of the town's industrial economy at the county level increased. (2) The distribution of the high-level agglomeration areas was characterized by one core area and two sub-core areas. The main core area was located at the junction of Hangzhou City, Shaoxing City, and Jiaxing City, and the two sub-core areas were located in Yuyao City and the main urban area of Ningbo City. In addition, several small-scale agglomeration areas composed of medium and high-level units were distributed in Wenzhou City. (3) The high-value agglomeration and low-value agglomeration distribution in the spatial correlation patterns was identified using the spatial auto-correlation method. The hot spots and sub-hot spots were distributed in Northern Zhejiang, and the cold spots formed a large-scale agglomeration in Quzhou City, Lishui City, Taizhou City, and several other cities in Southern Zhejiang. (4) Compared with the county scale, the spatial scope of the high-level areas in Northern Zhejiang shrunk significantly at the township scale, and the high-level agglomeration areas along the southeast coast changed into a cluster of several townships. (5) According to the geographically weighted regression (GWR) model, the importance of influencing factors is as follows: population density > regional area > industrial output value per capita > total population > proportion of secondary and tertiary personnel > total employees.

BackgroundArtificial forest can have great potential in serving as habitat to wildlife, depending on different management methods. As the state-owned forest farms now play a new role in ecological conservation in China, the biological richness of this kind of land-use type is understudied. Once owned by a mining company, a largest state-owned forest farm, Jingxi Forest Farm, has been reformed to be a state-owned forest farm with the purpose of conservation since 2017. Although this 116.4 km2 forest farm holds a near-healthy montaine ecosystem very representative in North China, a large proportion of artificial coniferous forest in the forest farm has been proven to hold less biodiversity than natural vegetation. This situation, however, provides a great opportunity for ecological restoration and biodiversity conservation. Therefore, from November 2019 to December 2020, we conducted a set of biodiversity surveys, whose results will serve as a baseline for further restoration and conservation.New informationHere, we report the result of a multi-taxa fauna diversity survey conducted in Jingxi Forest Farm mainly in year 2020 with explicit spatial information. It is the first survey of its kind conducted in this area, revealing a total of 19 species of mammals, 86 birds, four reptiles, two amphibians and one fish species, as well as 101 species of insects. Four species of mammals are identified as data-poor species as they have less than 100 occurrence records with coordination in the GBIF database. One species of insect, representing one new provincial record genus of Beijing, is reported.

BackgroundSmad7 is protective in a mouse model of rheumatoid arthritis. Here we investigated whether Smad7-expressing CD4+ T cells and the methylation of Smad7 gene in CD4+ T cells contribute to the disease activity of RA in patients.MethodsPeripheral CD4+ T cells were collected from 35 healthy controls and 57 RA patients. Smad7 expression by CD4+ T cells were determined and correlated with the clinical parameters of RA including RA score and serum levels of IL-6, CRP, ESR, DAS28-CRP, DAS28-ESR, Swollen joints and Tender joints. Bisulfite sequencing (BSP-seq) was used to determine the DNA methylation in Smad7 promoter (-1000 to +2000) region in CD4+ T cells. In addition, a DNA methylation inhibitor, 5-Azacytidine (5-AzaC), was added to CD4+ T cells to examine the possible role of Smad7 methylation in CD4+ T cell differentiation and functional activity.ResultsCompared to the heath controls, Smad7 expression was significantly decreased in CD4+ T cells from RA patients and inversely correlated with the RA activity score and serum levels of IL-6 and CRP. Importantly, loss of Smad7 in CD4+ T cell was associated with the alteration of Th17/Treg balance by increasing Th17 over the Treg population. BSP-seq detected that DNA hypermethylation occurred in the Smad7 promoter region of CD4+ T cells obtained from RA patients. Mechanistically, we found that the DNA hypermethylation in the Smad7 promoter of CD4+ T cells was associated with decreased Smad7 expression in RA patients. This was associated with overreactive DNA methyltransferase (DMNT1) and downregulation of the methyl-CpG binding domain proteins (MBD4). Inhibition of DNA methylation by treating CD4+ T cells from RA patients with 5-AzaC significantly increased Smad7 mRNA expression along with the increased MBD4 but reduced DNMT1 expression, which was associated with the rebalance in the Th17/Treg response.ConclusionDNA hypermethylation at the Smad7 promoter regions may cause a loss of Smad7 in CD4+ T cells of RA patients, which may contribute to the RA activity by disrupting the Th17/Treg balance.

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease. We previously revealed that the natural compound artemisitene (ATT) exhibits excellent broad anticancer activities without toxicity on normal tissues. Nevertheless, the effect of ATT on RA is undiscovered. Herein, we aim to study the effect and potential mechanism of ATT on RA management. Methods A collagen‐induced arthritis (CIA) mouse model was employed to confirm the anti‐RA potential of ATT. Cell Counting Kit‐8 (CCK‐8) and 5‐ethynyl‐2'‐deoxyuridine (EdU) assays, cell cycle and apoptosis analysis, immunofluorescence, migration and invasion assays, quantitative real‐time PCR (RT‐qPCR), Western blot, RNA‐sequencing (RNA‐seq) analysis, plasmid construction and lentivirus infection, and methylated RNA immunoprecipitation and chromatin immunoprecipitation assays, were carried out to confirm the effect and potential mechanism of ATT on RA management. Results ATT relieved CIA in mice. ATT inhibited proliferation and induced apoptosis of RA‐fibroblast‐like synoviocytes (FLSs). ATT restrained RA‐FLSs migration and invasion via suppressing epithelial–mesenchymal transition. RNA‐sequencing analysis and bioinformatics analysis identified intercellular adhesion molecule 2 (ICAM2) as a promoter of RA progression in RA‐FLSs. ATT inhibits RA progression by suppressing ICAM2/phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/p300 pathway in RA‐FLSs. Moreover, ATT inhibited methyltransferase‐like 3 (METTL3)‐mediated N6‐methyladenosine methylation of ICAM2 mRNA in RA‐FLSs. Interestingly, p300 directly facilitated METTL3 transcription, which could be restrained by ATT in RA‐FLSs. Importantly, METTL3, ICAM2 and p300 expressions in synovium tissues of RA patients were related to clinical characteristics and therapy response. Conclusions We provided strong evidence that ATT has therapeutic potential for RA management by suppressing proliferation, migration and invasion, in addition to inducing apoptosis of RA‐FLSs through modulating METTL3/ICAM2/PI3K/AKT/p300 feedback loop, supplying the fundamental basis for the clinical application of ATT in RA therapy. Moreover, METTL3, ICAM2 and p300 might serve as biomarkers for the therapy response of RA patients.

Abstract Background Rheumatoid arthritis is a progressive and systemic autoimmune disease seriously compromises human health. Fibroblast like synoviocytes are the major effectors of proliferation and inflammation in rheumatoid arthritis synovial tissue. Shikonin has anti-inflammatory and immunomodulatory activities. But, its role on synovitis of rheumatoid arthritis is unknown. Methods The DBA/1 male mice were randomly divided into the following three groups (n = 6): (1) the normal control group of mice, (2) the CIA (collagen-induced arthritis) group in which mice suffered from arthritis induced by collagen, (3) the SKN (shikonin) group of mice which got arthritis and given intragastrically with shikonin 4 mg/kg per day continuously for 20 days,(4) the MTX (methotrexate) group of mice which got arthritis and orally administration with shikonin 0.5 mg/kg once two days continuously for 20 days. The therapeutic effect of shikonin on collagen induced arthritis mice was tested by arthritis incidence rate, arthritis score and inflammatory joint histopathology. The invasion, adhesion and migration of fibroblast like synoviocytes induced by tumor necrosis factor-α were applied to measure the anti-synovitis role of shikonin. The effect of shikonin on expression of interleukin-6, interleukin-1β and tumor necrosis factor-α was measured by enzyme linked immunosorbent assay. The interaction between shikonin and suppressor of cytokine signaling 1 was verified by molecular docking. The signaling pathways activated by shikonin were measured by western blot. Results Shikonin decreased the arthritis score and arthritis incidence, and inhibited inflammation of inflamed joints in collagen induced arthritis mice. And shikonin reduced the number of vimentin+cells in collagen induced arthritis mice inflamed joints. Meanwhile, shikonin suppressed tumor necrosis factor-α-induced invasion, adhesion and migration of fibroblast like synoviocytes and reduced the expression of interleukin-6, interleukin-1β and tumor necrosis factor-α. And we found that shikonin targeted suppressor of cytokine signaling 1. More interestingly, shikonin blocked the phosphorylation of Janus kinase 1/signal transducer andactivator of transcription 1/signal transducer andactivator of transcription 6 in synovial tissues and in fibroblast like synoviocytes. Conclusion Shikonin represents a promising new anti-rheumatoid arthritis drug candidate that has anti-synovitis effect in collagen induced arthritis mice and inhibits tumor necrosis factor-α-induced fibroblast like synoviocytes by targeting suppressor of cytokine signaling 1/ Janus kinase/signal transducer andactivator of transcription signaling pathway. These findings demonstrate that shikonin has anti-synovitis effect and has great potential to be a new drug for the treatment of rheumatoid arthritis.

Objective: The purpose of this study was to evaluate the therapeutic effects and mechanism of Qufeng Zhitong (QFZT)capsule for the treatment of osteoarthritis (OA) in a rat model. Methods: 8-10-week-old male Sprague–Dawley rats were randomly divided into the sham group (vehicle-treated), OA group (vehicle-treated), high-dose, middle-dose, low-dose of QFZT capsule-treated groups. OA was induced by transecting the medial collateral ligament and the medial meniscus in the right limb. The Sprague–Dawley rats were treated daily for 12 weeks with different concentrations of QFZT capsule: low (QFZT-L, 128 ​mg/kg), medium (QFZT-M, 256.5 ​mg/kg), and high (QFZT-H, 513 ​mg/kg) by gavage administration for a period of 4 and 12 weeks respectively. Vehicle-treated rats served as controls and administered 0.5% Carboxymethyl Cellulose Sodium (CMC-Na) by gavage on the same schedule. Weekly measurement of dynamic weight-bearing capacity, grip strength, joint swelling was were performed to monitor the progression of disease for 3 weeks. After euthanasia, the knee joints were articular cartilage changes. Pro-inflammatory gene expression in synovial joints was examined to assess the bone and cartilage changes. Gene expression of pro-inflammatory cytokines in synovial joints was measured to determine the therapeutic effect of QFZT. Results: 2 weeks after the treatment, the grip strength and weight-bearing capacity were significantly increased in the QFZT-M and QFZT-H groups, compared with the OA group. The joint widths were decreased significantly in the QFZT-L and QFZT- H groups, compared with the OA group as well. The mRNA level in the articular cartilage of knee joint of IL-1β in the QFZT-L group and IL-6 in the QFZT-H group was significantly suppressed at week 4, compared with the OA group. The radiology score was significantly decreased in the QFZT-H group compared with the OA group 12 weeks after treatment. Furthermore, the rats on QFZT treatment decreased the progression of OA, which was characterised by decreased cartilage degradation. However, the bone changes were no different in OA group and QFZT groups. Conclusion: In a rat model of OA, QFZT capsule shows the tendency to reduce the destruction of cartilage, joint swelling and bone erosion which provides new evidence for the therapeutic potential of QFZT capsule in the treatment of OA in clinics. The translational potential of this article: The QFZT capsule can improve the symptoms of the OA in rodent animal rats by attenuating pain and retarding cartilage damage. This study indicated that the QFZT capsule has the potential clinical application of in OA therapy.

Rheumatoid arthritis (RA) is the most common type of autoimmune arthritis. Hypoxia-inducible factor-1α (HIF-1α) as a transcription factor in response to hypoxia suggests that it could be a potential therapeutic target for the treatment of RA. In this study, we assessed whether the HIF pathway blockade attenuates the manifestations of RA in the collagen-induced arthritis (CIA) rat model. We constructed a short hairpin RNA (shRNA) lentiviral expression vector targeting HIF-1α (pLVX-shRNA-HIF-1α) and to achieve HIF-1α RNA interference. Quantitative RT-PCR, immunofluorescence staining, and western blot were used to detect the expressions of HIF-1α, vascular endothelial growth factor (VEGF), phsopho (p)-p65, and p-IКBɑ mRNA and protein, respectively. Micro-computed tomography was used to investigate joint morphology at different time points after CIA induction. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to monitor the expression of inflammatory cytokines. In vitro analyses revealed that pLVX-shRNA-HIF-1α effectively inhibited the expression of HIF-1α and VEGF and led to the activation of p-65 and p-IКBɑ, as well as decreased proinflammatory cytokine expression in cell culture. Inhibition of HIF-1α in rats decreased signs of a systemic inflammatory condition, together with decreased pathological changes of RA. Moreover, downregulation of HIF-1α expression markedly reduced the synovitis and angiogenesis. In conclusion, we have shown that pharmacological inhibition of HIF-1 may improve the clinical manifestations of RA. Keywords: lentivirus, rheumatoid arthritis, HIF-1α, shRNA

Purpose: To evaluate the difference of the lens nuclear density measured before and after mydriasis by using the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany) and the Pentacam Scheimpflug imaging (Pentacam HR, Oculus Incorporation, Wetzlar, Germany) and investigate the relationship between the measurement data and the phacoemulsification parameters.Methods: Patients with age-related nuclear cataracts diagnosed on the slit-lamp examination were enrolled in the age range of 53–76 years. No patient had a history of ocular surgery, laser treatment, or general disorders affecting vision. The mean optical density (OD) was measured by the IOLMaster 700 by using the Image-Pro® Plus software before and after mydriasis. The Pentacam nucleus densitometry (PND) was obtained automatically from the Pentacam Scheimpflug imaging and compared with OD. The correlation between OD and effective phacoemulsification time (EPT), PND, and EPT were analyzed, respectively.Results: In this study, 53 eyes of 52 patients were evaluated. Before and after mydriasis, the mean OD values were 64.34 ± 23.31 and 63.81 ± 23.21 pixel units, respectively; the mean PND values were 28.51 ± 11.42 and 25.41 ± 11.31, respectively; and the mean EPT value was 6.24 ± 3.49. The Bland–Altman analysis showed that the lens nuclear densities of the two devices were highly consistent. There was no significant difference in the OD values (t = 0.455, p > 0.05) before and after mydriasis, but the difference has existed in the PND values (t = 2.509, p < 0.05). The OD and PND values were positively correlated with EPT before and after mydriasis (rOD−Before = 0.604, rOD−After = 0.593, rPND−Before = 0.701, and rPND−After = 0.891, p < 0.01).Conclusion: The combination of the IOLMaster 700 and the Image-Pro® Plus software can quantitatively evaluate the degree of the cataract lens opacification. It has good consistency with the Pentacam and is positively correlated with the phacoemulsification parameters. It is expected to become a new method to predict the phacoemulsification parameters before and during cataract surgery.

Abstract Background To evaluate the effects of anterior capsular opening size on deviation from predicted refraction and the effective position of the intraocular lens (ELP) in cataract surgery. Methods Nonrandomized clinical trial. Eighty patients (80 eyes) with simple age-related cataracts were treated from May 2018 to September 2018 at the Fourth Affiliated Hospital of China Medical University. All patients undergoing phacoemulsification received intraocular lens based on the voluntary principle. Forty eyes were implanted with the C-loop haptic intraocular lens (AMO Tecnis ZCB00) while the other 40 eyes were implanted with the plate haptic intraocular lens (CT ASPHINA 509 M). Follow-up visits were conducted postoperatively at 1 week, 1 month, and 3 months during which patients underwent refraction and data collection after pupil dilation, which included anterior segment photography and Scheimpflug imaging by Pentacam. The area, horizontal and vertical diameter of the capsulorrhexis, circularity, decentration, and package were analysed using the image analysis software Image-Pro-Plus 6.0,then evaluated the relationship between the different shapes of capsulorrhexis with deviation from predicted refraction and ELP in cataract surgery. Results Deviation from predicted refraction and all of the parameters of capsulorrhexis were not correlative in the 509 M IOL group, however, in the Tecnis IOL group, while the deviation from predicted refraction and all of the capsulorrhexis parameters were not correlative at 1 week, the deviation from predicted refraction did correlate with capsulorrhexis area, horizontal diameter at 1 month (P = 0.029, P = 0.048), and with capsulorrhexis area, vertical diameter at 3 months (P = 0.03, P = 0.017). The ELP correlated with package in both groups postoperatively (r > 0, P 0.05). For the Tecnis IOL group, the ELP and capsulorrhexis area were correlated at 1 week and 1 month, while the ELP and horizontal diameter, the ELP and vertical diameter were correlated at 1 week, but did not correlate with the other capsulorrhexis parameters in the Tecnis IOL group (all P > 0.05). Conclusions The shape of the capsulorrhexis has an effect on postoperative refractive outcomes and the effective position of the intraocular lens in cataract surgery, and plate haptic intraocular lenses have better refractive stability than C-loop haptic intraocular lenses. Trial registration ChiCTR1800015638,2018-04-12.

Aim. To observe the clinical efficacy and safety of phacoemulsification surgery combined with intravitreal injection of conbercept in cataract patients with DME. Methods. This is a prospective clinical cohort study. Thirty-five cataract patients (49 eyes) with DME were divided into two groups. The observation group (23 eyes) underwent a cataract phacoemulsification surgery combined with intravitreal injection of conbercept 0.5 mg; the control group (26 eyes) underwent a cataract phacoemulsification surgery only. The visual acuity, central macular thickness (CMT), IOP, and anterior chamber flare were examined before surgery and 1 week and one month after surgery. Results. The UCVA and BCVA in Log MAR in the observation group were lower than those in the control group at 1 week (p=0.032; p=0.041) and 1 month (p=0.035; p=0.039), respectively, after the surgery. The CMT of the observation group changed from 492.7 ± 32.2 μm before surgery to 341.6 ± 59.9 μm one week after surgery and 374.8 ± 48.3 μm one month after surgery. The CMT of control group increased after surgery. There was no significant difference in IOP and flare between the two groups at all following times. Conclusion. In patients with DME, undergoing a cataract surgery combined with intravitreal injection of conbercept is safe and effective for visual improvement and CMT declination with relatively fewer IOP and flare fluctuation.

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclastogenesis. Targeting RANKL signaling pathways has been an encouraging strategy for treating lytic bone diseases such as osteoporosis and rheumatoid arthritis (RA). Sinomenine (SIN), derived from Chinese medicinal plant Sinomenioumacutum, is an active compound to treat RA, but its effect on osteoclasts has been hitherto unknown. In the present study, SIN was found to ameliorate M. tuberculosis H37Ra (Mt)-induced bone loss in rats with a decreased serum level of TRACP5b and RANKL, and an increased level of osteoprotegerin (OPG). In vitro study also showed that SIN could inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, MMP-9, TRACP were inhibited by SIN in a dose dependent manner. Signal transduction studies showed that SIN could obviously reduce the expression of RANK adaptor molecule TRAF6 and down-regulate RANKL-induced NF-κB activation. It decreased the RANKL-induced p38, JNK posphorylation but not ERK1/2 posphorylation. SIN could also reduce RANKL-mediated calcium influx which is associated with TRAF6/c-Src complex. Finally, SIN suppressed RANKL induced AP-1 and NFAT transcription, as well as the gene expression of NFATc1 and AP-1 components (Fra-1, Fra-2, c-Fos). The protein expression of c-Fos and TRAF6 were also inhibited by SIN after RANKL stimulation. Taken together, SIN could attenuate osteoclast formation and Mt-induced bone loss by mediating RANKL signaling pathways.

Purpose: The effect of soy products on prostate cancer (PCA) remains a topic of debate. This study aimed to investigate the association between soy products consumption and the incidence of PCA. Materials and Methods: A search was conducted in the PubMed, EBSCO, Web of Science, and Cochrane Library databases up to December 2023. The adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) were used to assess the association. Results: A total of 22 articles, comprising 1,409,213 participants, were included for this meta-analysis. The results indicate that soy products reduce the risk of PCA (OR=0.94, 95% CI=0.91–0.97, p

Abstract Objective Rheumatoid arthritis (RA) is a prevalent autoimmune disorder that leads to chronic joint inflammation, deformity, disability, and systemic complications. This study aimed to analyze the clinical characteristics and synovial pathology of RA patients with synoviocyte detachment, and explore the factors associated with this phenomenon. Methods This was a retrospective cohort study included RA patients who underwent synovial biopsy at our center from April to September 2023. Demographic, clinical, laboratory, and synovial histological data were retrospectively collected from medical records at the time of joint synovial biopsy in patients. Microscopic examination of hematoxylin and eosin (HE)-stained synovial tissue sections categorized the samples into synoviocyte detachment and no-synoviocyte detachment groups. Clinical characteristics and synovial pathological changes were compared between the two groups, and the factors associated with synoviocyte detachment were explored through logistic regression analysis. Results Fifty-five RA patients were enrolled; 45 were females, and the mean age was 53.4 ± 11.8 years. Nine RA patients exhibited synoviocyte detachment. A total of 46 RA patients in the no-synoviocyte detachment group (15 with a normal lining layer and 31 with synovial cell proliferation) were included. Compared with the no-synoviocyte detachment group, the synoviocyte detachment group presented higher RF, ESR, CRP and DAS28-CRP levels (P

Background/purpose: External root resorption is a main side effect of orthodontic treatment and is more likely to occur on the pression side than the tension side. To explore the potential protective mechanisms on the tension side, this study investigated the influence of mechanical tension on cementoblast mineralization and elucidated the role of autophagy in mediating this process. Materials and methods: Mechanical tension was applied to cementoblasts using iStrain. The expression of mineralization-related and autophagy-related markers was detected by qRT-PCR, Western blot analysis, and immunofluorescence staining. RNA sequencing identified key regulators. Immunohistochemical staining assessed related markers expression in in vivo experiments. Results: Applying tension to cementoblasts increased mineralization-related gene expression in a force-dependent and time-dependent manner. The immunohistochemical staining result of in vivo experiments supported these findings, demonstrating elevated expression of mineralization markers under tension. Mechanical tension also enhanced autophagic activity in cementoblasts, which was demonstrated by the results of qRT-PCR, Western blot analysis, immunofluorescence staining, and in vivo experiments. Suppression of autophagy with chloroquine attenuated the mineralization of cementoblasts induced by tension stimulus. RNA-seq identified Postn as a key regulator, and the knockdown of Postn impaired the mechanical tension-promoted mineralization of cementoblasts. Conclusion: This study proposed the tension-induced promotion in mineralization of cementoblasts and emphasized the mediating role of autophagy in this process. Postn, a mediator connecting autophagy and mineralization, was identified as a key regulator. These discoveries helped elucidate orthodontic-related microprocesses on tooth roots and offer potential targets for therapeutic interventions to prevent and restore external root resorption clinically.

Abstract Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Abstract Treatment strategies for hard tissue defects aim to establish a mineralized microenvironment that facilitates tissue remodeling. As a mineralized tissue, cementum shares a similar structure with bone and exhibits an excellent capacity to resist resorption under compression. Macrophages are crucial for mineralized remodeling; however, their functional alterations in the microenvironment of cementum remain poorly understood. Therefore, this study explores the mechanisms by which cementum resists resorption under compression and the regulatory roles of cementoblasts in macrophage functions. As a result, extracellular vesicles from compression‐loaded cementoblasts (Comp‐EVs) promote macrophage M2 polarization and enhance the clearance of apoptotic cells (efferocytosis) by 2‐ to 3‐fold. Local injection of Comp‐EVs relieves cementum destruction in mouse root resorption model by activating the tissue repair function of macrophages. Moreover, Comp‐EV‐loaded hydrogels achieve significant bone healing in calvarial bone defect. Unexpectedly, under compression, EV secretion in cementoblasts is reduced by half. RNA‐Seq analysis and verification reveal that Rab35 expression decreases by 60% under compression, thereby hampering the release of EVs. Rab35 overexpression is proposed as a modification of cementoblasts to boost the yield of Comp‐EVs. Collectively, Comp‐EVs activate the repair function of macrophages, which will be a potential therapeutic strategy for hard tissue repair and regeneration.

Orthodontic treatment in adults is often related to longer treatment time as well as higher periodontal risks compared to adolescents. The aim of this review is to explore the influence of age-related chages on orthodontic tooth movement (OTM) from macro and micro perspectives. Adults tend to show slower tooth movement speed compared to adolescence, especially during the early phase. Under orthodontic forces, the biological responses of the periodontal ligament (PDL) and alveolar bone is different between adult and adolescents. The adult PDL shows extended disorganization time, increased cell senescence, less cell signaling and a more inflammatory microenvironment than the adolescent PDL. In addition, the blood vessel surface area is reduced during the late movement phase, and fiber elasticity decreases. At the same time, adult alveolar bone shows a higher density, as well as a reduced osteoblast and osteoclast activation, under orthodontic forces. The local cytokine expression also differs between adults and adolescents. Side-effects, such as excessive root resorption, greater orthodontic pain, and reduced pulpal blood flow, also occur more frequently in adults than in adolescents.

Abstract Background To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment. Methods We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors. Results The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group. Conclusions For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Background Artificial forest can have great potential in serving as habitat to wildlife, depending on different management methods. As the state-owned forest farms now play a new role in ecological conservation in China, the biological richness of this kind of land-use type is understudied. Once owned by a mining company, a largest state-owned forest farm, Jingxi Forest Farm, has been reformed to be a state-owned forest farm with the purpose of conservation since 2017. Although this 116.4 km forest farm holds a near-healthy montaine ecosystem very representative in North China, a large proportion of artificial coniferous forest in the forest farm has been proven to hold less biodiversity than natural vegetation. This situation, however, provides a great opportunity for ecological restoration and biodiversity conservation. Therefore, from November 2019 to December 2020, we conducted a set of biodiversity surveys, whose results will serve as a baseline for further restoration and conservation. New information Here, we report the result of a multi-taxa fauna diversity survey conducted in Jingxi Forest Farm mainly in year 2020 with explicit spatial information. It is the first survey of its kind conducted in this area, revealing a total of 19 species of mammals, 86 birds, four reptiles, two amphibians and one fish species, as well as 101 species of insects. Four species of mammals are identified as data-poor species as they have less than 100 occurrence records with coordination in the GBIF database. One species of insect, representing one new provincial record genus of Beijing, is reported. [ABSTRACT FROM AUTHOR]

BackgroundThe effect of polyphenol subclasses on prostate cancer (PCA) is controversial. Therefore, the purpose of this study was to investigate the relationship between polyphenol subclasses and PCA incidence.MethodsFrom the establishment of the database to December 2023, a systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library to identify relevant observational studies. The adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI) were used to assess the association.ResultsA total of 38 studies (11 were cohort studies and 27 were case–control studies), composing 824,933 participants, were included in this meta-analysis after excluding irrelevant records. The findings of the study revealed that men who consumed dietary polyphenols had a significantly higher risk of PCA compared to those who never or rarely consumed dietary polyphenols (OR = 1.01, p = 0.023), especially dietary flavonol (OR = 1.05, p = 0.042), flavanol (OR = 1.03, p = 0.026) and anthocyanin (OR = 1.06, p = 0.001). Neither total nor subclasses of dietary polyphenols have an effect on non-localized or high-grade PCA (OR = 1.01, p = 0.518). Dietary isoflavones tended to reduce the incidence of local or low-grade PCA, although there was no statistically significant difference (OR = 1.00, p = 0.081). Regarding serum/plasma polyphenol, total polyphenol (OR = 0.95, p = 0.002), genistein (OR = 0.92, p = 0.029) and enterolactone (OR = 0.92, p = 0.022) can reduce the incidence of PCA. No association was observed between total/subclasses of urinary polyphenols and PCA risk.ConclusionPolyphenols seem to generally increase the risk of PCA in the male population. The effect of polyphenols on PCA is affected by factors such as polyphenol subclasses, their forms (serum/plasma, urinary, dietary), and PCA-related factors (like PCA stage).Systematic review registrationidentifier: CRD42022322699.

Objective: To examine the clinical features and synovial pathologies in rheumatoid arthritis (RA) patients across varying titers of circulating anti-citrullinated protein antibodies (ACPA). Methodology: We devised a negative pressure suction and rebound synovial biopsy tool to enhance the yield of synovial biopsies, noted for its ease and safety of use. This research involved a retrospective examination of 60 active RA patients who underwent synovial biopsies with this tool from June to November 2013 at our institution. A range of disease activity markers were collected, including DAS28-CRP, ESR, CRP, count of swollen and tender joints, VAS pain scale, and so forth. Synovial tissue underwent HE staining and immunohistochemistry, including synovitis grading (GSS) and counting of B cells (CD20), T cells (CD3), macrophages (CD68), and plasma cells (CD138). Participants: were categorized into three groups as per ACPA titers: ACPA-negative (0–5U/mL), low-titer (5–20U/mL), and high-titer (above 20U/mL). The study compared the clinical features and synovial pathologies across these groups. Results: Of the 60 RA patients, they were segregated into three groups based on ACPA titers: 20 in ACPA-negative, 9 in the low-titer group, and 31 in the high-titer group. No significant differences were observed in GSS scores, synovial cell proliferation and loss, matrix activation, inflammatory infiltration, and neovascularization among these groups (P > 0.05). The high-titer ACPA group demonstrated significantly increased counts of CD3+ T cells, CD20+ B cells, and CD68+ macrophages in synovial tissues compared to the ACPA-negative and low-titer groups (p

Electrocatalytic treatment of chemical saline wastewater showed great technical advantages due to its characteristics of simple operation, high catalytic efficiency and little secondary pollution. The review takes the classification and composition of titanium-based anodes as the starting point. Typical studies of wastewater treatment by electrocatalytic technology based on free radicals and non-free radicals were also discussed. Combined with the previous researches about electrocatalytic mechanisms in recent years, the mechanisms of titanium-based anodes were analyzed in terms of ·OH, active chlorine and others. The studies on titanium-based anodes in chemical wastewater containing different salt concentrations, such as dye wastewater, coal chemical wastewater, landfill leachate wastewater, fertilizer and pesticide production wastewater, etc., were thoroughly examined. According to the amount of electricity required for the removal of organic matter per unit, the energy consumption of titanium-based anodes for wastewater treatment by electrochemistry was described. The review would provide theoretical basis and technical support for electrocatalytic treatment of chemical saline wastewater.