Hysteroscopic Management of Symptomatic Cesarean Scar Diverticulum in Patients Undergoing Frozen-Thawed Embryo Transfer: Impact on Clinical Pregnancy Rates and Pregnancy Complications.

This retrospective cohort study aimed to compare the clinical outcomes of patients with cesarean scar defect (CSD) undergoing frozen embryo transfer (FET) with or without hysteroscopic repair surgery. The study included 82 patients, with 48 patients in surgical group A (undergoing CSD repair) and 34 patients in surgical group B (undergoing hysteroscopic treatment for other uterine lesions). The results showed that patients in group A had a larger CSD volume and a different shape compared to group B. However, there was no significant difference in clinical pregnancy rates between the two groups. Additionally, there were no differences in miscarriage, live birth, or preterm birth rates, and no complications such as scar pregnancy or placental abnormalities were observed in either group. These findings suggest that hysteroscopic treatment of CSD in symptomatic patients undergoing FET does not increase the risk of pregnancy complications and can lead to comparable clinical pregnancy rates with asymptomatic patients. Further studies with larger sample sizes are needed to confirm these results and evaluate long-term reproductive outcomes following CSD repair.

Association of diabetes with cardiovascular calcification and all-cause mortality in end-stage renal disease in the early stages of hemodialysis: a retrospective cohort study.

BACKGROUND: The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis. METHODS: A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves. RESULTS: Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds. CONCLUSIONS: In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis.

A universal packaging substrate for mechanically stable assembly of stretchable electronics.

Stretchable electronics commonly assemble multiple material modules with varied bulk moduli and surface chemistry on one packaging substrate. Preventing the strain-induced delamination between the module and the substrate has been a critical challenge. Here we develop a packaging substrate that delivers mechanically stable module/substrate interfaces for a broad range of stiff and stretchable modules with varied surface chemistries. The key design of the substrate was to introduce module-specific stretchability and universal adhesiveness by regionally tuning the bulk molecular mobility and surface molecular polarity of a near-hermetic elastic polymer matrix. The packaging substrate can customize the deformation of different modules while avoiding delamination upon stretching up to 600%. Based on this substrate, we fabricated a fully stretchable bioelectronic device that can serve as a respiration sensor or an electric generator with an in vivo lifetime of 10 weeks. This substrate could be a versatile platform for device assembly.

Associations of phosphorus concentrations with medial arterial calcification in lower-extremity arteries and diabetic foot in people with diabetes: a retrospective cross-sectional study.

BACKGROUND: The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks. METHODS: We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019-2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97-3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09-2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees. CONCLUSIONS: Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications.

Circular RNA Gtdc1 Protects Against Offspring Osteoarthritis Induced by Prenatal Prednisone Exposure by Regulating SRSF1-Fn1 Signaling.

Chondrodysplasia is closely associated with low birth weight and increased susceptibility to osteoarthritis in adulthood. Prenatal prednisone exposure (PPE) can cause low birth weight; however, its effect on offspring cartilage development remains unexplored. Herein, rats are administered clinical doses of prednisone intragastrically on gestational days (GDs) 0-20 and underwent long-distance running during postnatal weeks (PWs) 24-28. Knee cartilage is assayed for quality and related index changes on GD20, PW12, and PW28. In vitro experiments are performed to elucidate the mechanism. PPE decreased cartilage proliferation and matrix synthesis, causing offspring chondrodysplasia. Following long-distance running, the PPE group exhibited more typical osteoarthritis-like changes. Molecular analysis revealed that PPE caused cartilage circRNomics imbalance in which circGtdc1 decreased most significantly and persisted postnatally. Mechanistically, prednisolone reduced circGtdc1 expression and binding with Srsf1 to promote degradation of Srsf1 via K48-linked polyubiquitination. This further inhibited the formation of EDA/B+Fn1 and activation of PI3K/AKT and TGFß pathways, reducing chondrocyte proliferation and matrix synthesis. Finally, intra-articular injection of offspring with AAV-circGtdc1 ameliorated PPE-induced chondrodysplasia, but this effect is reversed by Srsf1 knockout. Altogether, this study confirms that PPE causes chondrodysplasia and susceptibility to osteoarthritis by altering the circGtdc1-Srsf1-Fn1 axis; in vivo, overexpression of circGtdc1 can represent an effective intervention target for ameliorating PPE-induced chondrodysplasia.

Outbreak of piglet diarrhea associated with a new reassortant porcine rotavirus B.

Rotavirus B (RVB) is a causative agent leading to acute viral gastroenteritis diarrhea in both children and young animals, and has been commonly detected in piglets. In order to determine the causative agent of diarrheal outbreak occurring in December 2022 in piglets from a pig herd in Luoyang, Henan province of China, four common viral pathogens causing piglet diarrhea-three coronaviruses and rotavirus A (RVA) were first tested and found negative, therefore metagenomic sequencing was performed to explore other potential pathogens in the diarrheal samples. Unexpectedly, the most abundant viral reads mapped to RVB, and were de novo assembled to complete 11 viral gene segments. Sequence comparisons revealed that 5 gene segments encoding VP1, VP2, VP3, NSP3 and NSP4 of RVB strain designated as HNLY-2022 are most closely related to RVB strains derived from herbivores with low nucleotide similarities of 65.7-75.3%, and the remaining segments were relatively close to porcine RVB strains with the VP4 gene segment showing very low nucleotide identity (65.0%) with reference strains, indicating HNLY-2022 is a new reassortant RVB strain. Based on the previously proposed genotype classification criterion, the genotype constellation of RVB strain HNLY-2022 is G6-P[6]-I4-R6-C6-M6-A7-N5-T7-E5-H4 with more than half of the genotypes (P[6], R6, C6, M6, T7 and E5) newly reported. Therefore, the new reassortant RVB strain is the likely causative agent for the diarrheal outbreak of piglets occurred in China and more epidemiological studies should be conducted to monitor the spread of this newly identified porcine RVB strain.

Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.

Anti-inflammatory effect and component analysis of Chaihu Qingwen granules.

ETHNOPHARMACOLOGICAL RELEVANCE: As prevalent acute respiratory condition in clinical practice, acute lung injury has a quick start and severe symptoms which can harm patients physically. Chaihu Qingwen granules (CHQW) is a classic formula for the treatment of respiratory diseases. Clinical observation shows that CHQW has good efficacy in treating colds, coughs, and fevers. AIM OF THE STUDY: The aim of this study was to investigate the anti-inflammatory effect of CHQW on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats and to explore its potential mechanism, as well as to clarify its substance composition. MATERIALS AND METHODS: Male SD rats were randomly divided into the blank group, the model group, the ibuprofen group, the Lianhua Qingwen capsule group and the CHQW group (2, 4 and 8 g/kg, respectively). The LPS-induced acute lung injury (ALI) model in rats was established after pre-administration. The histopathological changes in the lung and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum of ALI rats were observed. The inflammation-related proteins toll-like receptor 4 (TLR4), inhibitory kappa B alpha (IκBα), phospho-IκBα (p-IκBα), nuclear-factor-kappa B (NF-κB), and NLR family pyrin domain containing 3(NLRP3) expression levels were measured by western blotting analysis and immunohistochemical analysis. The chemical composition of CHQW was identified by liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS). RESULTS: CHQW significantly ameliorated lung tissue pathological injury in LPS-induced ALI rats and decreased the release of inflammatory cytokines (interleukin-1ß, interleukin-17 and tumor necrosis factor-α) in BALF and serum. In addition, CHQW decreased the expression of TLR4, p-IκBα and NF-κB proteins, increased the level of IκBα, regulated the TLR4/NF-κB signaling pathway, and inhibited the activation of NLRP3. The chemical components of CHQW were analyzed by LC-Q-TOF-MS, and a total of 48 components were identified by combining information from the literature, mainly flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides. CONCLUSION: The results of this study showed that the pretreatment of CHQW had a strong protective effect on LPS-induced ALI in rats, reducing lung tissue lesions and decreasing inflammatory cytokines released in BALF and serum. The protective mechanism of CHQW may be related to the inhibition of the TLR4/NF-κB signaling pathway and NLRP3 activation. The main active ingredients of CHQW are flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides.

Transforming growth factor-ß receptor 1: An intervention target for genetic poor cartilage quality induced by prenatal dexamethasone exposure.

INTRODUCTION: Fetal-originated osteoarthritis is relative to poor cartilage quality and may exhibit transgenerational genetic effects. Previous findings revealed prenatal dexamethasone exposure (PDE) induced poor cartilage quality in offspring. OBJECTIVES: This study focused on further exploring molecular mechanism, heritability, and early intervention of fetal-originated osteoarthritis. METHODS: Pregnant rats (F0) were segregated into control and PDE groups depending upon whether dexamethasone was administered on gestational days (GDs) 9-20. Some female offspring were bred with healthy males during postnatal week (PW) 8 to attain the F2 and F3 generations. The F3-generation rats were administrated with glucosamine intragastrically at PW12 for 6 weeks. The knee cartilages of male and female rats at different time points were harvested to assay their morphologies and functions. Furthermore, primary chondrocytes from the F3-generation rats were isolated to confirm the mechanism and intervention target of glucosamine. RESULTS: Compared with the control, female and male rats in each generation of PDE group showed thinner cartilage thicknesses; shallower and uneven staining; fewer chondrocytes; higher Osteoarthritis Research Society International scores; and lower mRNA and protein expression of SP1, TGFßR1, Smad2, SOX9, ACAN and COL2A1. After F3-generation rats were treated with glucosamine, all of the above changes could be reversed. In primary chondrocytes isolated from the F3-generation rats of PDE group, glucosamine promoted SP1 expression and binding to TGFßR1 promoter to increase the expression of TGFßR1, p-Smad2, SOX9, ACAN and COL2A1, but these were prevented by SB431542 (a potent and selective inhibitor of TGFßR1). CONCLUSIONS: PDE induced chondrodysplasia in offspring and stably inherited in F3-generation rats, which was related to decreased expression of SP1/TGFßR1/Smad2/SOX9 pathway to reduce the cartilage matrix synthesis, without major sex-based variations. Glucosamine could alleviate the poor genetic cartilage quality in offspring induced by PDE by up-regulating SP1/TGFßR1 signaling, which was prevented by a TGFßR1 inhibitor. This study elucidated the molecular mechanism and therapeutic target (TGFßR1) of genetic chondrodysplasia caused by PDE, which provides a research basis for precisely treating fetal-originated osteoarthritis.

Identification and genomic characterization of a novel porcine parvovirus in China.

Porcine parvoviruses (PPVs) are a group of small non-enveloped viruses with seven species (porcine parvovirus 1-7, PPV1-7) have been identified. In this study, a novel porcine parvovirus, provisionally named porcine parvovirus 8 (PPV8), was initially identified via high-throughput sequencing (HTS) in porcine reproductive and respiratory syndrome virus-positive samples collected from swine herds in Guangdong province, 2021. The nearly full-length genome of PPV8 strain GDJM2021 is 4,380 nucleotides in length with two overlapping open ORFs encoding NS1 and VP1 respectively. Sequence analysis indicated that PPV8 shared 16.23-44.18% sequence identity at the genomic levels to PPV1-7 with the relatively highest homology to PPV1. PPV8-GDJM2021 shared 31.86-32.68% aa sequence identity of NS1 protein with those of PPV1 and porcine bufavirus (PBuV), and formed an independent branch neighboring to those formed by members of the genus Protoparvovirus. Of the 211 clinical samples collected from 1990 to 2021, 37 samples (17.5%) distributed over 12 regions in China were positive for PPV8 with time spanning 24 years (1998-2021). To our knowledge, this is the first report on the genomic characterization of the novel PPV8 and its epidemiological situations in China.

BMSC-derived exosomes promote tendon-bone healing after anterior cruciate ligament reconstruction by regulating M1/M2 macrophage polarization in rats.

BACKGROUND: Recent studies have shown that bone marrow stromal cell-derived exosomes (BMSC-Exos) can be used for tissue repair. However, whether the BMSC-Exos can promote tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is still unclear. In this study, we observed in vivo and in vitro the effect of rat BMSC-Exos on tendon-bone healing after ACLR and its possible mechanism. METHODS: Highly expressed miRNAs in rat BMSC-Exos were selected by bioinformatics and verified in vitro. The effect of overexpressed miRNA in BMSC-Exos on M2 macrophage polarization was observed. A rat model of ACLR was established. The experimental components were divided into three groups: the control group, the BMSC-Exos group, and the BMSC-Exos with miR-23a-3p overexpression (BMSC-Exos mimic) group. Biomechanical tests, micro-CT, and histological staining were performed for analysis. RESULTS: Bioinformatics analysis showed that miR-23a-3p was highly expressed in rat BMSC-Exos and could target interferon regulatory factor 1 (IRF1, a crucial regulator in M1 macrophage polarization). In vitro, compared with the control group or the BMSC-Exos group, the BMSC-Exos mimic more significantly promoted the polarization of macrophages from M1 to M2. In vivo, at 2 weeks, the number of M2 macrophages in the early local stage of ACLR was significantly increased in the BMSC-Exos mimic group; at 4 and 8 weeks, compared with the control group or the BMSC-Exos group, the bone tunnels of the tibia and femur sides of the rats in the BMSC-Exos mimic group were significantly smaller, the interface between the graft and the bone was narrowed, the bone volume/total volume ratio (BV/TV) increased, the collagen type II alpha 1 level increased, and the mechanical strength increased. CONCLUSIONS: BMSC-Exos promoted M1 macrophage to M2 macrophage polarization via miR-23a-3p, reduced the early inflammatory reaction at the tendon-bone interface, and promoted early healing after ACLR.

Modified Double-Row and Double-Pulley Technique for the Treatment of Type Ia Scapular Glenoid Fractures.

OBJECTIVE: To evaluate the efficacy of the double-row and double-pulley technique in treating anterior shoulder glenoid fracture (Ideberg type Ia) using shoulder arthroscopy. METHODS: Thirty-six patients with Ideberg type Ia admitted from March 1, 2017, to March 1, 2020, were retrospectively reviewed. Data of the patients' history included age, sex, side of the affected arm, the mean time from injury to surgery, the surgical duration, the average blood loss, and the average total duration of hospital stay. The double-row and double-pulley technique was used to repair the scapular glenoid fracture under arthroscopy. Computed tomography (CT) was used to evaluate fracture healing after surgery. The American Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) shoulder joint scoring system, and the Constant-Murley shoulder function score were used to assess the function of the affected shoulder. RESULTS: The surgical duration was 90-150 min, with a mean of 127 min. The average blood loss was 90 mL (range, 60-120 mL), and the average total duration of hospital stay was 9.2 days (range, 3 to 14 days). At 9 months after surgery, the CT results showed that all fractures healed, and all patients returned to their previous levels of activity and regained an excellent range of motion. The visual analog scale (VAS) score was 7.55 ± 1.32 before surgery, and the VAS score significantly decreased to 1.24 ± 0.72 at 12 months after the operation (p < 0.05). The Constant, ASES, and UCLA shoulder function scores were 44.38 ± 2.16, 43.47 ± 12.76, and 21.80 ± 1.16 before the surgery, respectively, which improved to 93.52 ± 2.82, 91.34 ± 8.28, and 33.24 ± 1.64, respectively, in the following 12 months. One patient experienced fat liquefaction. However, no cases of deep venous thrombosis, iatrogenic neurovascular compromise, wound infection, or neurovascular injury were identified. CONCLUSION: The double-row and double-pulley technique for treating Ideberg type Ia under shoulder arthroscopy has minor surgical trauma, reliable fracture reduction and fixation, less postoperative pain, and fewer postoperative complications and significantly improves the patient's shoulder joint function.

Increased co-expression of MEST and BRCA1 is associated with worse prognosis and immune infiltration in ovarian cancer.

OBJECTIVE: The crosstalk between tumor microenvironment (TME) and cancer cells plays a critical role in the occurrence and development of ovarian cancer. Imprinted gene MEST is a tumor-promoting factor that modulates several carcinogenic signaling pathways. This study aimed to investigate the expression pattern of MEST and its association with immune cell infiltration. METHODS: The transcriptome data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database was utilized, and the expression and immune characteristics of MEST were verified by immunohistochemistry of ovarian cancer specimens. Kaplan-Meier Plotter was used to assess the prognostic value in patients with ovarian cancer. RESULTS: We found that high expression of MEST was associated with diminished immune cell infiltration and worse prognosis of ovarian cancer patients in independent cohorts. There was a positive correlation between MEST and BRCA1 expression. The MESThighBRCA1high ovarian cancer group was correlated with lower infiltration of CD4+ cells, CD57+ cells, CD68+ cells and MPO+ cells, had worse overall survival (OS) in TCGA (HR = 1.57, p = 0.0004) and GSE27651 (HR = 4.27, p = 0.0002) cohorts, and predicted poor progress free survival (PFS) in GSE9891 (HR = 1.76, p = 0.0098) and GSE15622 (HR = 4.80, p = 0.0121) cohorts. Moreover, the expression of PD-L1 predicted unfavorable OS (HR = 2.48, p = 0.0415) and PFS (HR = 2.36, p = 0.0215) in MESTlowBRCA1low ovarian cancer group in GSE9891 cohort. CONCLUSION: These findings suggest that the co-expression of MEST and BRCA1 may be an ideal combination for predicting the prognosis and response to immunotherapy in patients with ovarian cancer.

Glucocorticoid caused lactic acid accumulation and damage in human chondrocytes via ROS-mediated inhibition of Monocarboxylate Transporter 4.

Osteoarthritis (OA) is a common joint disease lacking effective treatments. Dexamethasone (Dex) is often used to relieve joint pain. However, the adverse effects of Dex on cartilage can't be ignored. This study aimed to investigate the effect of Dex on articular cartilage and its mechanism by in vitro and in vivo experiments. The results showed that intra-articular injection with Dex damaged the matrix synthesis of cartilage. In vitro, Dex induced human chondrocytes mitochondrial dysfunction and increased reactive oxygen species (ROS) level, while down-regulated or unchanged key glycolysis genes, but increased lactic acid (LA) concentration. It was showed that high concentrations of LA induced chondrocytes apoptosis. Mechanistically, monocarboxylate transporter 4 (MCT4) was inhibited by Dex and had a significant negative correlation with ROS level. Further results showed that the trimethyl-histone H3-K4 (H3K4me3) level of MCT4 was reduced by Dex, and the ROS scavenger N-Acetyl-L-cysteine (NAC) and α-ketoglutarate (α-KG) alleviated the Dex-induced obstruction of matrix synthesis and high level of ROS by up-regulating the H3K4me3 level of MCT4 and its expression. In conclusion, Dex exhibited harm to cartilage, shown as mitochondrial dysfunction and increased ROS. The latter further caused LA accumulation in chondrocytes via decreasing the H3K4me3 level of MCT4 and its expression, which may account for the long-term side effects of Dex on chondrocytes. And α-KG may be used as an auxiliary drug to weaken the toxic effect of Dex on cartilage.

Low expression of NR1H3 correlates with macrophage infiltration and indicates worse survival in breast cancer.

Background: Nuclear receptor NR1H3 is a key regulator of macrophage function and lipid homeostasis. Here, we aimed to visualize the prognostic value and immunological characterization of NR1H3 in breast cancer. Methods: The expression pattern and prognostic value of NR1H3 were analyzed via multiple databases, including TIMER2, GEPIA2 and Kaplan-Meier Plotter. TISIDB, TIMER2 and immunohistochemical analysis were used to investigate the correlation between NR1H3 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB and GeneMANIA were used to visualize the functional enrichment of NR1H3 and signaling pathways related to NR1H3. Results: We demonstrated that the expression of NR1H3 was significantly lower in breast cancer compared with adjacent normal tissues. Kaplan-Meier survival curves showed shorter overall survival in basal breast cancer patients with low NR1H3 expression, and poorer prognosis of relapse-free survival in breast cancer patients with low NR1H3 expression. NR1H3 was mainly expressed in immune cells, and its expression was closely related with infiltrating levels of tumor-infiltrating immune cells in breast cancer. Additionally, univariate and multivariate analysis indicated that the expression of NR1H3 and the level of macrophage infiltration were independent prognostic factors for breast cancer. Gene interaction network analysis showed the function of NR1H3 involved in regulating of innate immune response and macrophage activation. Moreover, NR1H3 may function as a predictor of chemoresponsiveness in breast cancer. Conclusion: These findings suggest that NR1H3 serves as a prognostic biomarker and contributes to the regulation of macrophage activation in breast cancer.

The psychological impact of COVID-19 outbreak on medical staff and the general public.

To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the pandemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Among the 1493 questionnaires completed, 827 (55.39%) of these were men, and 422 (28.27%) of these were medical personnel. The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

Hyperglycemia-induced accumulation of advanced glycosylation end products in fibroblast-like synoviocytes promotes knee osteoarthritis.

Osteoarthritis (OA) is significantly associated with diabetes, but how hyperglycemia induces or aggravates OA has not been shown. The synovium plays a critical role in cartilage metabolism and substance exchange. Herein, we intended to investigate whether and how hyperglycemia affects the occurrence and progression of OA by influencing the synovium. In patients with knee OA and diabetes (DM OA), we found a more severe inflammatory response, higher endoplasmic reticulum stress (ERS) levels, and more advanced glycosylation end products (AGEs) accumulation in the synovium than in patients without diabetes. Subsequently, we found similar results in the DM OA group in a rat model. In the in vitro cocultivation system, high glucose-stimulated AGEs accumulation, ERS, and inflammation in rat fibroblast-like synoviocytes (FLSs), which resulted in chondrocyte degeneration due to inflammatory factors from FLSs. Furthermore, in the synovium of the DM OA group and FLSs treated with high glucose, the expression of glucose transporter 1 (GLUT1) and its regulatory factor hypoxia-inducible factor (HIF)-1α was increased significantly. Inhibitors of HIF-1α, GLUT1 or AGEs receptors attenuated the effect of high glucose on chondrocyte degradation in the FLS-chondrocyte coculture system. In summary, we demonstrated that hyperglycemia caused AGEs accumulation in FLSs via the HIF-1α-GLUT1 pathway, which increases the release of inflammatory factors from FLSs, subsequently inducing chondrocyte degradation and promoting OA progression.

Clinicopathological and immunological characterization of RNA m6 A methylation regulators in ovarian cancer.

BACKGROUND: N6 -methyladenosine (m6 A) modification is one of the critical gene regulatory mechanisms implicated in cancer biology. However, the roles of m6 A regulators in ovarian cancer are still poorly understood. METHODS: We integrated multiple databases including Gene Expression Omnibus (GEO), ROC Plotter, Kaplan-Meier Plotter, and Tumor Immune Estimation Resource (TIMER) to explore clinicopathological significance of m6 A regulators in ovarian cancer. RESULTS: We showed that alterations in the expression of m6 A regulators were related to the malignancy and poor prognosis of ovarian cancer. We found decreased YTHDC1 and increased RBM15 expressions were associated with ovarian cancer cell metastases and HNRNPC was a predictor of paclitaxel resistance. Moreover, dysregulated m6 A regulators were enriched in the activation of cancer-related pathways. Our results further demonstrated that the level of immune cell infiltration and the expression of various immune gene markers were closely associated with the expressions of specific m6 A regulators (RBM15B, ZC3H13, YTHDF1, and IGF2BP1). CONCLUSIONS: Our study establishes a new prognostic profile of ovarian cancer patients based on m6 A regulators, and highlights the potential roles of m6 A regulators in ovarian cancer development.