Large-vessel vasculitis (LVV) encompasses Takayasu arteritis (TAK) and giant cell arteritis (GCA), both characterized by granulomatous inflammation of large arteries. While these diseases have distinct clinical features, the emergence of large-vessel GCA (LV-GCA) highlights an area of overlap with late-onset TAK. Although T cell- and macrophage-driven inflammation represents a shared hallmark, the contribution of B cells and autoantibodies remains less clearly defined. This review comparatively summarizes B cell mediated responses and autoantibody involvement in TAK and GCA. TAK demonstrates significant B cell activity, evidenced by B cell infiltration and the presence of tertiary lymphoid organs (TLOs) within the arterial wall. Importantly, specific autoantibodies, such as anti-endothelial protein C receptor (EPCR) and anti-scavenger receptor class B type I antibodies, have been identified. Anti-EPCR antibodies specifically associate TAK with coexisting ulcerative colitis, suggesting a shared aberrant immune pathway. In contrast, cranial GCA is primarily T cell-driven and contains relatively few B cells. However, aortic lesions in LV-GCA exhibit extensive B cell and plasma cell infiltration, including TLOs, indicating that this subtype shares key B cell mediated responses with TAK. Despite this immunological convergence, the specific autoantibody profiles appear distinct and remain incompletely characterized. Taken together, B cell and autoantibody responses are more pronounced and functionally relevant in TAK, show intermediate involvement in LV-GCA, and are least prominent in cranial GCA. These differences provide critical insights for LVV subtyping and underscore the need for further elucidation of the pathomechanisms underlying TAK, late-onset TAK, LV-GCA, and cranial GCA to enable personalized therapeutic strategies.

This study investigates the expression patterns of lncRNA differentiation antagonizing non-protein coding RNA (DANCR) and microRNA (miR)-185-5p, and their potential roles in the pathogenesis of polycystic ovary syndrome (PCOS). Involved 100 patients with PCOS as the case group and 80 non-PCOS patients with fallopian tube diseases as the control group. The relative levels of serum DANCR and miR-185-5p were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Pearson’s method was performed to estimate the correlation between DANCR and abnormal indicators in the PCOS group. The effects of DANCR and miR-185-5p on cell viability and apoptosis were evaluated by Cell Count Kit (CCK)-8 assay and flow cytometry. The target relationship between DANCR and miR-185-5p was verified via a luciferase reporter assay. Compared with the control group, DANCR expression was elevated, while miR-185-5p levels were reduced in the serum of patients with PCOS. When further grouped, patients with PCOS and insulin resistance (IR) showed higher DANCR levels and lower miR-185-5p levels than those without IR. Receiver operator characteristic (ROC) curve analysis displayed that the sensitivity and specificity of DANCR to distinguish PCOS from control groups were 74.0% and 88.7%, respectively. In KGN cells, down-regulation of DANCR expression enhanced cell viability and suppressed cell apoptosis by elevating miR-185-5p levels. Luciferase reporter gene assays confirmed that miR-185-5p directly targeted DANCR and was negatively regulated by DANCR. Our findings suggest that dysregulated upregulation of DANCR might promote granulosa cell apoptosis and impair cell viability by repressing miR-185-5p, thereby exacerbating POCS progression.

Femoral shaft fractures are high-energy injuries to the femur that have a probability of delayed union. Prolonged fracture healing time can cause more pain and financial burden to the patient. miR-378a-3p has been reported to be the promoter of bone formation. This study thus investigated the association between miR-378a-3p and femoral shaft fracture delayed union, as well as the underlying mechanism. This study aimed to provide valuable information on treating femoral shaft fracture and preventing its delayed union. Serum samples were obtained from femoral shaft fracture delayed or normal-union patients to investigate the expression level of miR-378a-3p. Cell experiments were conducted using the MC3T3-E1 cell line to explore the underlying mechanism. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of microRNA (miRNA) and gene. To estimate the effect of miR-378a-3p and Zinc Finger Protein, FOG Family Member 2 (ZFPM2) on osteoblast proliferation, Cell Counting Kit-8 (CCK-8) was chosen in this study. The mechanism was investigated using dual luciferase reporter assay. miR-378a-3p was downregulated in femoral shaft fracture patients with delayed union. The miR-378a-3p downregulation was found as an independent risk factor for the delayed union of femoral shaft fracture. miR-378a-3p could facilitate osteoblast proliferation and differentiation. miR-378a-3p affected osteoblast activities by targeting ZFPM2. In conclusion, the miR-378a-3p downregulation was an indicator of delayed union of femoral shaft fracture. miR-378a-3p played a crucial role in the fracture healing process. ZFPM2 mediated the effect of miR-378a-3p on the fracture healing process.

A six-year-old girl was diagnosed with Turner syndrome (TS), monosomy X, based on results of amniotic fluid and leukocyte karyotyping. It is well known that most patients with TS are infertile due to premature ovarian insufficiency before puberty. The patient and her parents desired fertility preservation (FP) through ovarian tissue cryopreservation (OTC), which is the only option for FP in prepubertal patients, to prepare for future loss of fertility. OTC was performed after the physician provided sufficient information to the patient, and informed consent and assent were obtained. The girl’s right ovary was removed in a Shiga University of Medical Science hospital and her father transported it for about 3.5 hours to a cryopreservation facility, HOPE in Tokyo. The removed ovary, measuring 3.0 cm × 1.2 cm and weighing 0.96 g, appeared striated. It was divided into 4 pieces and cryopreserved by slow freezing method. Pathology specimen examination showed no primordial follicles, but calcein-AM staining performed prior to cryopreservation detected 6 viable follicles. This report is valuable as we succeeded in cryopreserving autologous gametes in non-mosaic TS patients using calcein-AM staining, which made it possible to detect follicles with certainty in all samples. Although there has been insufficient evidence regarding the subjects and efficacies of FP for genetic and chromosomal disorders, earlier FP should be considered because individuals may lose their fertility prematurely. OTC may be a promising option to preserve fertility for girls with TS as well as childhood cancer patients.

Sufentanil exhibits potent analgesic efficacy with a prolonged duration of action, making it a frequently utilized agent for labor analgesia. This study aimed to investigate the association between SLC6A4 rs1042173 polymorphisms and the efficacy of sufentanil epidural analgesia during labor in primiparous women. This study enrolled 288 full-term primiparas eligible for vaginal delivery. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to detect the SLC6A4 rs1042173 polymorphism. The Hardy-Weinberg equilibrium test was conducted to assess the representativeness of the samples relative to the population. Logistic regression analysis was performed to examine the association between the SLC6A4 rs1042173 polymorphism and labor analgesia, as well as to identify independent influencing factors. The pharmacokinetics of sufentanil in pregnant women were significantly influenced by the SLC6A4 rs1042173 polymorphism. The Visual Analogue Scale (VAS) indicated that the SLC6A4 rs1042173 genotype significantly influenced the analgesic response patterns in pregnant women. In the early stages of drug action, the TT and TG genotypes exhibited higher sensitivity (P < 0.001). Regarding specific adverse reactions, significant differences were noted in the incidences of nausea, urinary retention, and abnormal fetal heart rate monitoring among pregnant women with different genotypes (P < 0.05). Logistic regression analysis revealed significant correlations between the rs1042173 polymorphism and both the VAS score at 2 hours (P = 0.014) post-administration and the Activity, Pulse, Grimace, Appearance, Respiration (Apgar) scores at 1 minute (P < 0.001) of newborns. SLC6A4 rs1042173 gene polymorphisms were significantly associated with the analgesic efficacy of sufentanil epidural anesthesia in primiparas.

Diminished ovarian reserve (DOR) is a critical challenge in reproductive health, leading to reduced fertility and hormonal imbalances. Current treatments such as assisted reproductive technologies and hormone replacement therapy often have limited success and adverse effects. Progesterone receptor membrane component 2 (PGRMC2) is a protein essential for various reproductive processes and is involved in ovarian folliculogenesis, with its increased expression associated with DOR. This study investigates the protective mechanisms of total flavonoids from Semen Cuscutae (TFSC) on ovarian reserve through PGRMC2 modulation and T helper 17 cell (Th17)/regulatory T cell (Treg) immune balance in a DOR rat model. DOR was induced in rats by administering 50 mg/kg tripterygium glycosides (TG) via intragastric administration once daily for 15 days. Various analytical techniques were used to assess the effects of TFSC, including immunohistochemistry for ovarian tissue analysis, Western blotting to measure PGRMC2 protein expression, flow cytometry for evaluating Th17/Treg ratio, and Enzyme-linked immunosorbent assay (ELISA) to quantify serum cytokine levels. Results demonstrate that TFSC enhances ovarian function, up-regulates PGRMC2 expression, and restores immune homeostasis, highlighting its potential as an alternative therapeutic strategy. By elucidating TFSC’s role in immune modulation and ovarian function, this study paves the way for developing targeted therapies to improve outcomes for women with DOR.

Hyponatremia was defined as a serum sodium level below 136 mmol/L. The current classification identified serum sodium level below 120 mmol/L as high-risk patients, which ignored the impact of comorbidities on outcomes. We aim to develop a novel classification based on the integration of serum sodium level and comorbid conditions to aid precise clinical management. Data were collected from patients admitted to Peking Union Medical College Hospital. Non-supervised machine learning method TwoStep and k-means analysis were used to classify patients into homozygous clusters. Decision tree modelling derived a clinical classifier from the novel classification, which was further validated in an internal dataset. During the development of novel classification based on serum sodium level Integrated with comorbid conditions (BASIC), TwoStep and k-means analysis yielded similar results. Cluster analysis identified 5 stable and replicable clusters which had distinct clinical characters: (i) mild hyponatremia and at least one comorbidity; (ii) mild hyponatremia and high prevalence of cancer; (iii) younger patients with mild hyponatremia; (iv) mild hyponatremia, poor renal function, and high prevalence of chronic kidney disease; (v) moderate and severe hyponatremia patients with other characters similar to Cluster 1. BASIC is a machine learning originated best cluster. However, it lacked specific classification criteria. Therefore, we developed a simple and practical classifier, BASIC-C, which assigned patients to their corresponding subgroups with a combined accuracy of 93.1% (95% CI: 91.5%-94.7%) in the validation cohort. The outcomes of identified subgroups were similar to their corresponding clusters in BASIC. We proposed BASIC, a novel classification of hyponatremia via data-driven cluster analysis, and derived a practical clinical classifier, BASIC-C. Our results revealed that serum sodium of 130-135 mmol/L increased in-hospital mortality when patients were combined with cancer or chronic kidney disease, and it was necessary to provide careful management.

Microspheres based transarterial chemoembolization is important for liver cancer treatment. UniPearls^® is a novel product of microspheres featuring a uniform particle size and independently developed in China. This study aimed to investigate the physical properties, drug loading and releasing ability, and biocompatibility of UniPearls^®. Various experiments were performed including: compression rupture, suspendability, simulated use, drug loading, drug releasing, cytotoxicity, mouse lymphoma assay (MLA), muscle implant, intradermal reaction, guinea pig maximization test (GPMT), and systemic toxicity. UniPearls^® or UniPearls^® extraction liquid was set as experimental group(s), while HepaSphere^® or related extraction liquid was set as control group(s). UniPearls^® showed no microsphere rupture after compression to 1 μm for 10 or 20 min, but some ruptures for 30 min, and microspheres were successfully suspended in a short time. In a 3-dimensional (3D) hepatic artery model, UniPearls^® exhibited no microsphere break, delivery block, shape change or unexpected catheter outflow during simulated experiment. The maximum loading rates of 40-100 mg doxorubicin and irinotecan were 100% and 97.4% by UniPearls^®, respectively; then the releasing rates at plateaus with different-dose doxorubicin and irinotecan ranged 34.0%-46.5% and 85.6%-91.8%, respectively. In vitro experiments revealed no cytotoxicity or impact on inducing gene mutation by UniPearls^®. In vivo experiments disclosed no local reaction, skin sensitization, obvious acute/subchronic systemic toxicity symptoms by UniPearls^®. Besides, the above indexes were not different between UniPearls^® and controls (HepaSphere^® or related extraction liquids). UniPearls^® serves as a good product of microspheres, benefiting from its satisfied physical properties, drug loadability, releasing ability and biocompatibility.

To examine the diagnostic value and mechanism of action of serum linc00893 in patients with diabetic retinopathy (DR), 209 diabetic patients, including 106 patients with DR, were included in the study. ROC curves assessed the clinical value of linc00893 in predicting DR, and logistic analyzed the factors affecting DR. RT-qPCR detected serum linc00893 and miR-107 expression, CCK8 measured cell proliferation, flow cytometry documented apoptosis, and ELISA detected the inflammatory factor. Dual luciferase reporter assay and RIP assay verified the interactions between linc00893 and miR-107. Biochemical indicators are more severe in DR than in diabetes alone, and linc00893 expression was notably down-regulated in DR patients. linc00893 is an influential factor in the promotion of DR and has diagnostic value for it. Transfection of linc00893 enhanced the proliferative capacity of high-glucose (HG) cells, reduced apoptosis, and lowered the levels of inflammatory factors (VEGF, IL-1β, IL-18). The results also demonstrated that miR-107 is a target gene of linc00893 and the two can directly bind. miR-107 was markedly up-regulated in DR patients and had a clear negative correlation with linc00893 expression. miR-107 overexpression inhibited HG cell proliferation and increased apoptosis and inflammatory. linc00893 is lowly expressed in DR patients, and it has the diagnostic value of predicting DR. miR-107 is involved in the DR mechanism as linc00893, which is manifested by low-linc00893 promoting miR-107 induced slowing down of cell proliferation, increasing apoptosis and inflammation level, which triggers DR.

Women with diminished ovarian reserve (DOR) have reduced fertility, but the mechanisms regulating ovarian function remain unclear. This study aims to explore the mechanism by which FOXO1 regulates ovarian granulosa cell function. The ovarian granulosa cell line KGN was cultured and transfected with FOXO1 and LHX8 vectors. Cell proliferation and apoptosis were assessed using CCK-8 and flow cytometry, respectively. mtROS content was determined by immunofluorescence. ATP was detected using an assay kit. E2 was detected by ELISA. ChIP was used to detect the binding of FOXO1 to the LHX8 promoter. Luciferase reporter genes were used to analyze the regulation of FOXO1 on LHX8 promoter activity. RT-qPCR was performed to measure the expression of FOXO1 mRNA, LHX8 mRNA, ND1, and β-globin. Western blotting was used to detect FOXO1, LHX8, and aromatase proteins.FOXO1 knockdown or LHX8 overexpression promoted proliferation, inhibited apoptosis, reduced mitochondrial ROS, and increased ATP, mtDNA, E2, and aromatase levels in KGN cells. FOXO1 overexpression or LHX8 knockdown produced the opposite regulatory effects. FOXO1 bound to the LHX8 promoter and reduced its activity. LHX8 overexpression eliminated FOXO1-induced KGN cell damage. In conclusion, FOXO1 reduces viability and promotes apoptosis in granulosa cells by inhibiting LHX8 transcription to induce mitochondrial dysfunction, which may contribute to DOR.

Currently, the pathogenesis of sepsis has not been fully elucidated. This study aimed to explore the role of cytochrome P450 oxidoreductase (POR) in this disease. Specifically, two-sample Mendelian randomization, multivariate Mendelian randomization, and summary data-based Mendelian randomization methods were employed to assess the genetic impact of peripheral POR protein and POR genes from multiple tissue sources on the risk of streptococcal sepsis (ICD-10 A40) and other sepsis (ICD-10 A41). Subsequently, a mouse model of sepsis (based on lipopolysaccharide) was constructed, and the expression of POR was specifically upregulated and downregulated through AAV9-mediated overexpression and shRNA interference, respectively. Various methods were used to evaluate physiology, liver and kidney function, peripheral inflammation, and oxidative stress levels of the mice. The results of Mendelian randomization analysis showed that elevated levels of peripheral POR protein and POR genes from multiple tissues were associated with a reduced risk of other sepsis, but not with the risk of streptococcal sepsis. Animal experiments demonstrated that specific upregulation of POR expression improved the moving distance, heart rate, blood pressure, liver and kidney functions, peripheral inflammation, and oxidative stress levels in septic mice, while specific downregulation of POR expression exacerbated the above indicators. In conclusion, evidence from both genetic and animal studies indicates that POR may play an important protective role in the occurrence and development of sepsis (excluding streptococcal sepsis).

Laryngeal squamous cell carcinoma (LSCC) ranks first in mortality among head and neck tumors. MicroRNA (miR)-324-3p has a dual role depending on the tumor type. Currently, biological significance of miR-324-3p in LSCC needs to be validated. The study attempts to make clear whether miR-324-3p modulates cell malignancy by interacting with tumor-associated macrophages in LSCC. THP-1-differentiated macrophages were co-cultured with LSCC cells to mimic tumor microenvironment in vitro. The viability, migration, and invasion of LSCC cells were assessed by cell counting, wound-healing, and transwell invasion assays. Evaluation of the expression of CD163, CD206, and miR-324-3p was undertaken by quantitative polymerase chain reaction. Determination of CD163 and CD206 protein levels was done by western blot. The release of Transforming growth factor-beta (TGF-β) and interleukin-10 were detected by enzyme-linked immunosorbent assay. Higher expression of miR-324-3p was observed in LSCC cells. The polarization of Macrophage type 2 (M2-type) macrophages was promoted and the viability, migration, and invasion of TU177 cells were strengthened in the co-culture system. Furthermore, miR-324-3p silencing decreased the polarization of M2-type macrophages, along with reduced viability, migration, and invasion of TU177 cells. Conversely, miR-324-3p overexpression drove the polarization of M2-type macrophages, accompanied by elevated malignant behaviors of TU686 cells. Interestingly, dysregulation of miR-324-3p did not affect the viability, migration and invasion of LSCC cells in the absence of co-incubation with macrophages. The miR-324-3p facilitates malignant behaviors of tumor cells by promoting M2 macrophage polarization in LSCC, suggesting that miR-324-3p may be a promising target for LSCC treatment by mediating the tumor microenvironment.

Osteoarthritis (OA) is a chronic musculoskeletal disorder, characterized by the chronic and progressive degenerative illness of articular cartilage that leads to tenacious joint pain and inflammation as well as functional disability, impairing the life quality in elderly people. Unfortunately, there is no regenerative therapy for treating osteoarthritis. Curcumin (diferuloylmethane), a hydrophobic polyphenol compound isolated from curcuma longa rhizome, has been broadly employed as a safe supplement traditionally. Despite great beneficial impacts, achieving the desired pharmacological effects of curcumin has shown limitations because of its low systemic bioavailability. It has been found that biological activities and bioavailability of curcumin could be efficiently enhanced using nanoscale drug carriers. The current literature review aimed to discuss nanoscale delivery systems that have been constructed to improve the bioavailability and therapeutic efficacy of curcumin for treating osteoarthritis. In brief, various delivery systems composed of polymer, metal, or emulsion nanocarriers have been manufactured to improve the bioavailability and therapeutic efficacy of curcumin in the treatment of osteoarthritis. Intra-articular injection of curcumin nanoparticles could induce chondrogenesis, inhibit degradation of articular cartilage, and reverse abnormalities in joint structure and smooth surface of articular cartilage in knee osteoarthritis, thus preventing osteoarthritis development, mechanistically, through anti-inflammatory and anti-oxidative activities of curcumin. In conclusion, nano-formulations of curcumin have been found to enhance the therapeutic efficacy of curcumin for treating osteoarthritis and introduce a promising therapeutic alternative to current therapies, however, future clinical investigations are warranted to approve their application in humans.