IGF2BP2 regulates the inflammation of fibroblast-like synoviocytes via GSTM5 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

Exploration of poly (ADP-ribose) polymerase inhibitor resistance in the treatment of BRCA1/2-mutated cancer.

Breast cancer susceptibility 1/2 (BRCA1/2) genes play a crucial role in DNA damage repair, yet mutations in these genes increase the susceptibility to tumorigenesis. Exploiting the synthetic lethality mechanism between BRCA1/2 mutations and poly(ADP-ribose) polymerase (PARP) inhibition has led to the development and clinical approval of PARP inhibitor (PARPi), representing a milestone in targeted therapy for BRCA1/2 mutant tumors. This approach has paved the way for leveraging synthetic lethality in tumor treatment strategies. Despite the initial success of PARPis, resistance to these agents diminishes their efficacy in BRCA1/2-mutant tumors. Investigations into PARPi resistance have identified replication fork stability and homologous recombination repair as key factors sensitive to PARPis. Additionally, studies suggest that replication gaps may also confer sensitivity to PARPis. Moreover, emerging evidence indicates a correlation between PARPi resistance and cisplatin resistance, suggesting a potential overlap in the mechanisms underlying resistance to both agents. Given these findings, it is imperative to explore the interplay between replication gaps and PARPi resistance, particularly in the context of platinum resistance. Understanding the impact of replication gaps on PARPi resistance may offer insights into novel therapeutic strategies to overcome resistance mechanisms and enhance the efficacy of targeted therapies in BRCA1/2-mutant tumors.

From genomic insights to clinical hope: Targeting NEU1 in IgA nephropathy.

BACKGROUND: IgA Nephropathy (IgAN), the primary form of glomerulonephritis, presents significant clinical challenges due to its obscure pathogenesis and lack of targeted treatments. We conducted a proteome-wide Mendelian randomization (MR) study to identify therapeutic targets for IgAN. METHODS: Utilizing a plasma proteome dataset comprising 4907 blood plasma proteins as the exposure variable, and renal biopsy-confirmed IgAN cases as the outcome, this study employed MR to pinpoint proteins potentially pathogenic to IgAN. The robustness of our findings was affirmed through external dataset validation, reverse causation testing, and Bayesian colocalization analysis. Additionally, we conducted phenotypic scanning and analyzed downstream metabolites to investigate candidate proteins's biological function. RESULTS: In our study, a significant association was identified between an increase in neuraminidase 1 (NEU1) expression and the risk of IgAN. Specifically, a one standard deviation increase in NEU1 expression was associated with an odds ratio of 11.80 for the development of IgAN (95% confidence interval: 4.03-34.54). This association was substantiated across various statistical models and external validations. Colocalization analysis indicated a shared causal variant between NEU1 expression and IgAN. Furthermore, an increased influenza risk associated with NEU1 was observed, supporting the therapeutic potential of NEU1 inhibitors for IgAN. However, our study found no significant role for neuraminic acid-related metabolites in IgAN's development, suggesting an independent pathway for NEU1's influence. CONCLUSION: This study identifies NEU1 as a promising therapeutic target for IgAN, backed by robust genetic evidence. Future research should explore NEU1's therapeutic potential in diverse populations and clinical scenarios, further establishing its role in IgAN.

Chk2 Modulates Bmi1-Deficiency-Induced Renal Aging and Fibrosis via Oxidative Stress, DNA Damage, and p53/TGFß1-Induced Epithelial-Mesenchymal Transition.

Renal aging may lead to fibrosis and dysfunction, yet underlying mechanisms remain unclear. We explored whether deficiency of the Polycomb protein Bmi1 causes renal aging via DNA damage response (DDR) activation, inducing renal tubular epithelial cell (RTEC) senescence and epithelial-mesenchymal transition (EMT). Bmi1 knockout mice exhibited oxidative stress, DDR activation, RTEC senescence, senescence-associated secretory phenotype (SASP), and age-related fibrosis in kidneys. Bmi1 deficiency impaired renal structure and function, increasing serum creatinine/urea, reducing creatinine clearance, and decreasing cortical thickness and glomerular number. However, knockout of the serine-threonine kinase Chk2 alleviated these aging phenotypes. Transcriptomics identified transforming growth factor beta 1 (TGFß1) upregulation in Bmi1-deficient RTECs, but TGFß1 was downregulated upon Chk2 knockout. The tumor suppressor protein p53 transcriptionally activated TGFß1, promoting EMT in RTECs. Bmi1 knockout or oxidative stress (induced with H2O2) increased TGFß1 expression, and EMT in RTECs and was partly reversed by p53 inhibition. Together, Bmi1 deficiency causes oxidative stress and DDR-mediated RTEC senescence/SASP, thus activating p53 and TGFß1 to induce EMT and age-related fibrosis. However, blocking DDR (via Chk2 knockout) or p53 ameliorates these changes. Our study reveals mechanisms whereby Bmi1 preserves renal structure and function during aging by suppressing DDR and p53/TGFß1-mediated EMT. These pathways represent potential targets for detecting and attenuating age-related renal decline.

Three-Dimensional Bioprinting of Strontium-Modified Controlled Assembly of Collagen Polylactic Acid Composite Scaffold for Bone Repair.

In recent years, the incidence of bone defects has been increasing year by year. Bone transplantation has become the most needed surgery after a blood transfusion and shows a rising trend. Three-dimensional-printed implants can be arbitrarily shaped according to the defects of tissues and organs to achieve perfect morphological repair, opening a new way for non-traumatic repair and functional reconstruction. In this paper, strontium-doped mineralized collagen was first prepared by an in vitro biomimetic mineralization method and then polylactic acid was homogeneously blended with the mineralized collagen to produce a comprehensive bone repair scaffold by a gas extrusion 3D printing method. Characterization through scanning electron microscopy, X-ray diffraction, and mechanical testing revealed that the strontium-functionalized composite scaffold exhibits an inorganic composition and nanostructure akin to those of human bone tissue. The scaffold possesses uniformly distributed and interconnected pores, with a compressive strength reaching 21.04 MPa. The strontium doping in the mineralized collagen improved the biocompatibility of the scaffold and inhibited the differentiation of osteoclasts to promote bone regeneration. This innovative composite scaffold holds significant promise in the field of bone tissue engineering, providing a forward-thinking solution for prospective bone injury repair.

Activation of CncC pathway by ROS burst regulates ABC transporter responsible for beta-cypermethrin resistance in Dermanyssus gallinae (Acari:Dermanyssidae).

The drug resistance of poultry red mites to chemical acaricides is a global issue in the control of the mites, which presents an ongoing threat to the poultry industry. Though the increased production of detoxification enzymes has been frequently implicated in resistance development, the overexpression mechanism of acaricide-resistant related genes in mites remains unclear. In the present study, it was observed that the transcription factor Cap 'n' Collar isoform-C (CncC) and its partner small muscle aponeurosis fibromatosis (Maf) were highly expressed in resistant strains compared to sensitive strains under the stress of beta-cypermethrin. When the CncC/Maf pathway genes were down-regulated by RNA interference (RNAi), the expression of the ABC transporter genes was down-regulated, leading to a significant increase in the sensitivity of resistant strains to beta-cypermethrin, suggesting that CncC/Maf played a crucial role in mediating the resistance of D.gallinae to beta-cypermethrin by regulating ABC transporters. Furthermore, it was observed that the content of H2O2 and the activities of peroxidase (POD) and catalase (CAT) enzymes were significantly higher in resistant strains after beta-cypermethrin stress, indicating that beta-cypermethrin activates reactive oxygen species (ROS). In ROS scavenger assays, it was found that the expression of CncC/Maf significantly decreased, along with a decrease in the ABC transporter genes. The present study showed that beta-cypermethrin seemed to trigger the outbreak of ROS, subsequently activated the CncC/Maf pathway, as a result induced the ABC transporter-mediated resistance to the drug, shedding more light on the resistance mechanisms of D.gallinae to pyrethroids.

Association of systemic immune-inflammation index (SII) and aggregate index of systemic inflammation (AISI) with thyroid nodules in patients with type 2 diabetes mellitus: a retrospective study.

OBJECTIVE: This retrospective study aimed to investigate the association between TNs and the systemic immune-inflammation index (SII) and the aggregate index of systemic inflammation (AISI) in patients with T2DM. METHODS: A total of 370 T2DM patients, who were admitted to Dongzhimen Hospital between January 2020 and March 2023, were included in this retrospective study. Binary logistic regression models with multivariable adjustment were employed to assess the relationship between SII, AISI quartiles, and TNs. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of SII and AISI in identifying T2DM patients with TNs. RESULTS: Age, diabetes duration, diabetic nephropathy (DN), SII, and AISI demonstrated significant positive associations with TNs. Compared to the first quartile of SII, the second, third, and fourth quartiles showed increased risks of TNs with hazard ratios (HRs) of 1.578 (0.883-2.820), 2.279 (1.257-4.131), and 3.626 (1.931-6.810), respectively (P < 0.001). Similar results were observed for AISI and TNs. ROC curve analysis revealed that SII and AISI exhibited a high discriminatory capability for identifying TNs in the overall and male participant group, whereas the significance among females was not discernible. CONCLUSIONS: This study provides evidence that SII and AISI are independent risk factors for TNs, suggesting that elevated SII and AISI levels may contribute to the development of TNs in patients with T2DM particularly among male individuals.

Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development.

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy. Supplementary Information: The online version contains supplementary material available at 10.1186/s12645-023-00190-x.

Circ_RBM23 knockdown suppresses chemoresistance, proliferation, migration and invasion of sorafenib-resistant HCC cells through miR-338-3p/RAB1B axis.

BACKGROUND: Circular RNA RNA-binding motif protein 23 (circ_RBM23; ID: hsa_circ_0000524) is a novel regulator in hepatocellular carcinoma (HCC). Herein, we planned to investigate its role in sorafenib resistance in HCC. METHOD: Levels of circ_RBM23, microRNA (miR)-338-3p, Ras-related GTPase-trafficking protein (RAB1B), Snail and E-cadherin were detected by real-time quantitative PCR and western blotting. Sorafenib resistant (SR) HCC cells (Huh7/SR and SK-HEP-1/SR) were established by acquisition of sorafenib resistance, and cell functions were measured by MTT assay, Edu assay, colony formation assay, apoptosis assay, transwell assay, and in vivo xenograft formation assay. Crosslink between miR-338-3p and circ_RBM23 or RAB1B was confirmed by bioinformatics analysis and dual-luciferase reporter assay. RESULTS: Circ_RBM23 upregulation was discovered in the tissues of SR patients and SR cells, which was accompanied with miR-338-3p downregulation and RAB1B upregulation. The 50% inhibitory concentration (IC50) of sorafenib in SR cells was greatly suppressed by interfering circ_RBM23 or reinforcing miR-338-3p, allied with this was the inhibition of EdU-positive cell rate, colony formation and migration/invasion abilities under sorafenib treatment, as well as the enhancement of apoptotic rate. Moreover, circ_RBM23 inhibition delayed tumor growth of Huh7/SR cells under sorfanib treatment in vivo. CONCLUSION: Circ_RBM23 promoted chemoresistance, malignant proliferation, migration and invasion of SR HCC cells by modulating miR-338-3p/RAB1B axis.

Function of glycogen synthase kinase3 in embryogenesis of Dermanyssus gallinae.

In the life cycle of Dermanyssus gallinae, the embryo is a developmental stage that does not require blood meals, but needs glucose to produce adenosine triphosphate (ATP) through glycolysis or oxidative phosphorylation, providing energy for embryonic development. Glycogen synthase kinase 3 (GSK3), belonging to the serine/threonine kinase family, is a key enzyme involved in glycogen metabolism in many eukaryotes, but not be described in D. gallinae. The present study was conducted to explore the role of Dg-GSK3 in the embryogenesis of D. gallinae. The results of qPCR showed that Dg-GSK3 mRNA was expressed in different development stages of D. gallinae embryos. RNA interference (RNAi) was performed on the female mites and eggs by immersion, and it was found that lowering GSK3 expression level could significantly decrease the female egg laying rate and egg hatching rate (P < 0.05). Some eggs became shrunken and shriveled in appearance. The fecundity of female D. gallinae obtained from the rDg-GSK3-immunized group of chickens (2.56 ± 0.35 eggs per mite, P < 0.0001) decreased significantly from that of the control group (3.49 ± 0.35). The oviposition rate of rDg-GSK3-immunized group (75.94 ± 7.28 %, P = 0.0003）was significantly lower that of the control group (89.69 ± 2.63 %). In conclusion, Dg-GSK3 is a crucial gene during the embryogenesis of D. gallinae, which can affect both the female fecundity and the egg hatching, which help us understand the function of GSK3 gene in the embryogenesis of mites.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Targeted Deletion of Rictor in BMSCs Reduces the Biological Activity of K7M2 Cells and Mitigates OS-Induced Bone Destruction.

Bone marrow mesenchymal stem cells (BMSCs) are indispensable cells constituting the bone marrow microenvironment that are generally recognized as being involved in the development and progression of osteosarcoma (OS). To explore whether mTORC2 signaling inhibition in BMSCs suppressed OS growth and tumor-caused bone destruction, 3-month-old littermates genotyped Rictorflox/flox or Prx1-cre; Rictorflox/flox (with same gender) were injected with K7M2 cells in the proximal tibia. After 40 days, bone destruction was alleviated in Prx1-cre; Rictorflox/flox mice, as observed on X-ray and micro-CT. This was accompanied by decreased serum N-terminal propeptide of procollagen type I (PINP) levels and reduced tumor bone formation in vivo. Interactions between K7M2 and BMSCs were studied in vitro. Rictor-deficient BMSCs, which were cultured in tumor-conditioned medium (TCM), caused reduced bone proliferation and suppressed osteogenic differentiation. Moreover, compared with the control group, K7M2 cells cultured in BCM (culture medium extracted from Rictor-deficient BMSCs) displayed less proliferation, migration, and invasion, and attenuated osteogenic activity. Forty types of cytokines were then analyzed by mouse cytokine array and decreased levels CCL2/3/5 and interleukin-16 were detected in Rictor-deficient BMSCs. These results suggested that inhibition of mTORC2 (Rictor) signaling pathway in BMSCs exerted anti-OS effects through 2 mechanisms: (1) by suppressing the proliferation and osteogenic differentiation of BMSCs induced by OS to alleviate bone destruction; (2) by reducing the secretion of cytokines by BMSCs, which are closely related to OS cell growth, migration, invasion, and tumorigenic osteogenesis.

Inhibition of Cdc37 Ameliorates Arthritis in Collagen-Induced Arthritis Rats by Inhibiting Synoviocyte Proliferation and Migration Through the ERK Pathway.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to synovial inflammation, pannus formation, cartilage damage, bone destruction, and ultimate disability. Fibroblast-like synoviocytes (FLS) are involved in the pathogenetic mechanism of RA. Cdc37 (cell division cycle protein 37) is regarded as a molecular chaperone involved in various physiological processes such as cell cycle progression, cell proliferation, cell signal transduction, tumorigenesis, and progression. However, the precise role of Cdc37 in the pathogenesis of rheumatoid arthritis (RA) remains uncertain. In our study, we found that Cdc37 expression was upregulated in human rheumatoid synovia in contrast with the normal group. Interestingly, Cdc37 activated the ERK pathway to promote RA-FLS proliferation and migration in vitro. Ultimately, in vivo experiments revealed that silencing of Cdc37 alleviated ankle swelling and cartilage destruction and validated the ERK signaling pathways in vitro findings. Collectively, we demonstrate that Cdc37 promotes the proliferation and migration of RA-FLS by activation of ERK signaling pathways and finally aggravates the progression of RA. These data indicated that Cdc37 may be a novel target for the treatment of RA.

Bone marrow-derived mesenchymal stem cells accelerate angiogenesis in pregnant experimentally induced deep venous thrombosis rat model via up-regulation of pro-angiogenic secretogranin II.

The present study investigated whether bone marrow-derived mesenchymal stem cells (BMMSCs) facilitate angiogenesis and improve outcomes of pregnancy with obstetric deep venous thrombosis (DVT) and explored the underlying mechanism. A pregnant DVT rat model was established using a "stenosis" method on the lower segment of the inferior vena cava (IVC). The extent of vascularization in thrombosed IVC was examined by immunohistochemistry. In addition, the effect of BMMSCs on DVT pregnancy outcomes was evaluated. We also characterized the effect of BMMSC-derived conditioned medium (BM-CM) on the impaired human umbilical vein endothelial cells (HUVECs). Thereafter, transcriptome sequencing was employed to identify the differentially expressed genes in thrombosed IVC tissues of DVT and DVT plus BMMSCs (thrice) groups. Lastly, the candidate gene's role in the promotion of angiogenesis was demonstrated in vitro and in vivo. The DVT model was successfully established using IVC stenosis. The injection of three consecutive BMMSC doses into pregnant SD rats with DVT was demonstrated to be the most effective treatment, which significantly reduced the length and weight of the thrombus, induced the highest level of angiogenesis, and ameliorated the embryo absorption rate. In vitro, BM-CM efficiently increased the abilities of impaired endothelial cells to proliferate, migrate, invade, and form vessel-like tubes, while inhibiting their apoptosis. Transcriptome sequencing revealed that BMMSCs induced a prominent upregulation of a variety of pro-angiogenic genes, including secretogranin II (SCG2). When SCG2 expression was knocked down by lentivirus, the BMMSCs' and BM-CM-induced pro-angiogenic effects on pregnant DVT rats and HUVECs were markedly attenuated. In conclusion, the study results suggest that BMMSCs enhance angiogenesis via up-regulation of SCG2, providing an effective alternative regenerative agent and novel target for the therapy of obstetric DVT.

4-Iodo-6-phenylpyrimidine (4-IPP) suppresses fibroblast-like synoviocyte- mediated inflammation and joint destruction associated with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic immune-mediated inflammatory disease that significantly impacts patients' quality of life. Fibroblast-like synovial cells (FLSs) within the synovial intima exhibit "tumor-like" properties such as increased proliferation, migration, and invasion. Activation of FLSs and secretion of pro-inflammation factors result in pannus formation and cartilage destruction. As an inhibitor of the cytokine, macrophage migration inhibitory factor (MIF), 4-Iodo-6-phenylpyrimidine (4-IPP) has been shown to reduce cell proliferation, migration, invasion, and the secretion of pro-inflammatory mediators in a variety of diseases. However, the usefulness of 4-IPP for RA treatment has not been assessed and was the purpose of this study. In vitro, 4-IPP was demonstrated to inhibit proliferation, migration, and invasion of RA FLSs, as well as the expression of pro-inflammatory cytokines. 4-IPP was also shown to inhibit MIF-induced phosphorylation of ERK, JNK, and p38, as well as reduce expression of COX2 and PGE2. In order to efficiently deliver 4-IPP to anatomical RA sites, we developed lactic-co-glycolic acid (PLGA) nanospheres, which not only protected 4-IPP from degradation but also controlled the release of 4-IPP. 4-IPP/PLGA nanospheres had potent anti-inflammatory activity and a high degree of biosafety. Results showed that local 4-IPP concentration was increased by nanosphere delivery, effectively reducing the inflammatory microenvironment as well as synovial inflammation, joint swelling, and cartilage destruction in a collagen-induced rheumatoid arthritis (CIA) rat model. Therefore, 4-IPP nanospheres are a sustained-release delivery system that may be an effective therapeutic strategy for RA treatment.

Status and related factors of postoperative recurrence of ovarian endometriosis: a cross-sectional study of 874 cases.

PURPOSE: Exploring the status and related factors of postoperative recurrence of ovarian endometriosis. METHODS: This study analyzed the results of questionnaires conducted in 27 hospitals across the country from January 2019 to November 2021. All women were divided into recurrence group and non-recurrence group to analyze the recurrence rate and related factors after ovarian endometriosis surgery. RESULTS: The recurrence rates of ovarian endometriosis within 1 year, 1-2 years, 2-3 years, 3-4 years, 4-5 years and more than 5 years were 6.27%, 35.85%, 55.38%, 65.00% and 56.82%, respectively. Significant differences were found between two groups in terms of age at surgery (OR: 0.342, 95%CI: 0.244-0.481, P < 0.001), presence of dysmenorrhea (OR: 1.758, 95%CI: 1.337-2.312, P < 0.001), presence of adenomyosis (OR: 1.948, 95%CI: 1.417-2.678, P < 0.001) and family history of endometriosis or adenomyosis (OR: 1.678, 95%CI: 1.035-2.721, P = 0.021). The age at surgery (OR: 0.358, 95%CI: 0.253-0.506, P < 0.001), presence of dysmenorrhea (OR: 1.379, 95%CI: 1.026-1.853, P = 0.033) and presence of adenomyosis (OR: 1.799, 95%CI: 1.275-2.537, P = 0.001) were significantly associated with endometrioma recurrence in multivariate analysis. No significant associations were found between the recurrence rate and body mass index (BMI), educational background, age of menarche, gravida, parity, uterine leiomyoma, endometrial polyps or postoperative use of gonadotropin-releasing hormone agonist (GnRH-a). CONCLUSIONS: Dysmenorrhea and presence of adenomyosis are independent risk factors for postoperative recurrence of ovarian endometriosis, and older age is an independent protective factor for postoperative recurrence.

Impact of repeated intravenous infusions of umbilical cord-derived versus bone marrow-derived mesenchymal stem cells on angiogenesis in a pregnant experimentally induced deep venous thrombosis rat model.

Deep venous thrombosis (DVT) therapy during pregnancy warrants special consideration for the woman and the fetus. This study aimed to evaluate the impact of umbilical cord-derived mesenchymal stem cells (UC-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) in terms of pro-angiogenic capacity and amelioration of pregnancy outcomes. The pregnant DVT rat model was successfully established by the "stenosis" method. Three consecutive injections of both UC-MSCs and BM-MSCs improved angiogenesis and ameliorated the embryo absorption rate in pregnant SD rats with DVT, in which UC-MSCs promoted angiogenesis more significantly. Furthermore, the levels of serum vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor (EGF) were significantly higher in the UC-MSC group compared to those of the BM-MSC group. Thereafter, differentially expressed genes (DEGs) in thrombosed inferior vena cava tissues in the UC-MSC and BM-MSC groups were identified using transcriptome sequencing and further assessed by RT-qPCR and western blotting. The bioinformatics analysis indicated that the enriched DEG terms occurred in the cytokine activity, and the DEG pathways were significantly enriched in the cytokine-cytokine receptor interaction. In addition, both the mRNA and protein levels of angiogenic genes and their receptors, including VEGF-A, VEGF receptor-1, EGF, and EGF receptor, were significantly higher in the UC-MSC group. In conclusion, the BM-MSCs and UC-MSCs both significantly stimulate angiogenesis and ameliorate the embryo absorption rate in pregnant SD rats with DVT, but the difference in cytokine secretion causes UC-MSCs to have more potent angiogenic effects than BM-MSCs.

A 3D reconstruction based on an unsupervised domain adaptive for binocular endoscopy.

In minimally invasive surgery, endoscopic image quality plays a crucial role in surgery. Aiming at the lack of a real parallax in binocular endoscopic images, this article proposes an unsupervised adaptive neural network. The network combines adaptive smoke removal, depth estimation of binocular endoscopic images, and the 3D display of high-quality endoscopic images. We simulated the smoke generated during surgery by artificially adding fog. The training images of U-Net fused by Laplacian pyramid are introduced to improve the network's ability to extract intermediate features. We introduce Convolutional Block Attention Module to obtain the optimal parameters of each layer of the network. We utilized the disparity transformation relationship between left- and right-eye images to combine the left-eye images with disparity in HS-Resnet to obtain virtual right-eye images as labels for self-supervised training. This method extracts and fuses the parallax images at different scale levels of the decoder, making the generated parallax images more complete and smoother. A large number of experimental research results show that the scheme can remove the smoke generated during the operation, effectively reconstruct the 3D image of the tissue structure of the binocular endoscope, and at the same time, preserve the contour, edge, detail, and texture of the blood vessels in the medical image. Compared with the existing similar schemes, various indicators have been greatly improved. It has good clinical application prospects.

Comparison of Efficacy and Safety of TACE Combined with Microwave Ablation and TACE Combined with Cryoablation in the Treatment of Large Hepatocellular Carcinoma.

Purpose: To retrospectively evaluate the efficacy and safety of TACE combined with microwave ablation (MWA) and TACE combined with cryoablation (CRA) in the treatment of large hepatocellular carcinoma. Methods: A retrospective analysis was performed on 81 patients with large hepatocellular carcinoma (tumor diameter 5～8 cm cm) who received TACE combined with ablation in our hospital from February 2015 to February 2019. The study patients were divided into TACE combined with MWA group (T-MWA, n = 41) and TACE combined with CRA group (T-CRA, n = 40) according to the treatment plan. Overall survival (OS) and progress free survival (PFS) were compared between the two groups, and complications were observed. Survival curves for OS and PFS were constructed by the Kaplan-Meier method. Differences in overall survival were compared using the log-rank test. Results: There was no statistical difference in general conditions between the two groups of patients. The results showed that 30 (73.2%) patients in T-MWA group achieved objective response (OR) and 39 (95.1%) patients achieved disease control (DC), compared with 24 (60.0%) patients in T-CRA group who achieved objective response (OR) and 37 (92.5%) patients who achieved disease control (DC). The median OS was 19.2 months in the T-MWA group and 18.6 months in the T-CRA group (P=0.64). The median PFS was 9.3 months in the T-MWA group and 12.3 months in the T-CRA group (P=0.6). Univariate and multivariate analysis showed that portal vein tumor thrombus (PVTT), intrahepatic tumor diameter, and the number of tumor lesions were common prognostic factors for OS and PFS. In terms of surgery-related complications and adverse reactions, abdominal pain and gastrointestinal reactions were observed in 13 (31.7%) and 11(26.8%) cases in the T-MWA group, while we observed 4 (10.0%) and 2 (5.0%) cases in the T-CRA group, respectively. The difference between the two was statistically significant (P < 0.05). Conclusion: TACE combined with MWA and TACE combined with CRA were equally effective in the treatment of large hepatocellular carcinoma. TACE-CRA can effectively reduce the incidence of abdominal pain and gastrointestinal reactions in patients. However, compared with TACE-MWA, TACE-CRA is more likely to cause thrombocytopenia.

Boosting the Capacity of Aqueous Li-Ion Capacitors via Pinpoint Surgery in Nanocoral-Like Covalent Organic Frameworks.

Aqueous lithium storage devices are promising candidates for next-generation energy storage applications, featuring low-cost, safety, environmental benignness, and grid-scale merits. Developing reliable anode materials with fast Li+ diffusion is paramount to stimulate their development. Herein, the electrochemical performance and mechanism of a redox-active ß-ketoenamine-linked covalent organic framework (COF) (2,6-diaminoanthraquinone and 2,4,6-triformylphloroglucinol COF, DAAQ-TFP-COF) for lithium storage in aqueous electrolyte are explored for the first time. Systematic studies demonstrate that, by the conversion of neutral COF into anionic COF via a pinpoint surgery on the ß-ketoenamine linkage, the resultative COF shows doubled Li+ storage capacity (132 mAh g-1 at 0.5 A g-1 , 87% of theoretical specific capacity), good rate capability (108 mAh g-1 at 10 A g-1 ), and excellent cyclability in 1000 cycles. This pinpoint surgery can be promising in extending the electrochemical applications of ß-ketoenamine-linked COFs. The Li+ storage mechanism is investigated by ex situ electron paramagnetic resonance, in situ/ex situ Fourier transform infrared investigations, and density functional theory calculations. As a proof of new concept, a novel aqueous lithium-ion capacitor assembled with DAAQ-TFP-COF anode delivers high specific capacitance of 224 F g-1 (0.1 A g-1 ), supercapacitor-level power density (≈4000 W kg-1 ), and long cyclability.