Emerging Roles of Circular RNA in Macrophage Activation and Inflammatory Lung Responses.

Circular RNA (circRNA) is a type of single-stranded RNA that forms a covalently closed continuous loop, unlike linear RNA. The expression of circRNAs in mammals is often conserved across species and shows tissue and cell specificity. Some circRNA serve as gene regulators. However, the biological function of most circRNAs is unclear. CircRNA does not have 5' or 3' ends. The unique structure of circRNAs provides them with a much longer half-life and more resistance to RNase R than linear RNAs. Inflammatory lung responses occur in the pathogenesis and recovery of many lung diseases. Macrophages form the first line of host defense/innate immune responses and initiate/mediate lung inflammation. For example, in bacterial pneumonia, upon pro-inflammatory activation, they release early response cytokines/chemokines that recruit neutrophils, macrophages, and lymphocytes to sites of infection and clear pathogens. The functional effects and mechanisms by which circRNAs exert physiological or pathological roles in macrophage activation and lung inflammation remain poorly understood. In this article, we will review the current understanding and progress of circRNA biogenesis, regulation, secretion, and degradation. Furthermore, we will review the current reports on the role of circRNAs in macrophage activation and polarization, as well as in the process of inflammatory lung responses.

Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence.

The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.

From Hit to Lead: Discovery of First-In-Class Furanone Glycoside D228 Derived from Chimonanthus salicifolius for the Treatment of Inflammatory Bowel Disease.

TNFα and related inflammatory factor antibody drugs have been orchestrated for the treatment of inflammatory bowel disease (IBD). However, antibody drugs elicited inevitable disadvantages and small molecule drugs are in an urgent need. Herein, we described the discovery, design, synthesis, and SAR studies from furanone glycoside compound Phoenicein (hit) isolated from Chimonanthus salicifolius to D228 (lead). Remarkably, D228 exhibited good inhibitory activity on B and T lymphocyte and excellent anti-IBD efficacy in vivo. Mechanistically, D228 alleviated the inflammation response by downregulating the MyD88/TRAF6/p38 signaling. Importantly, the relationship of D228, Phoenicein, and their aglycone 7a was deduced: D228 could be considered as a prodrug and metabolized to intermediate Phoenicein. In turn, Phoenicein released their shared active aglycone 7a. Additionally, D228 demonstrated good and balanced profiles of safety and efficacy both in vitro and in vivo. These results suggested that D228 could be used as an ideal lead and potentially utilized for IBD chemotherapy.

The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: Pathogenesis and therapeutic strategies.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common and debilitating joint disorders affecting millions of individuals worldwide. Despite their distinct pathological features, both conditions share a crucial role of macrophages in disease progression. Macrophages exhibit remarkable plasticity, polarizing into pro-inflammatory M1 or anti-inflammatory M2 phenotypes in response to environmental cues. An imbalance in macrophage polarization, particularly a shift towards the M1 phenotype, contributes to chronic inflammation and joint damage in RA and OA. This review explores the complex interplay between macrophages and various cell types, including T cells, B cells, synovial fibroblasts, osteoclasts, chondrocytes, and adipocytes, in the pathogenesis of these diseases. We discuss the current understanding of macrophage polarization in RA and OA, highlighting the molecular mechanisms involved. Furthermore, we provide an overview of potential therapeutic strategies targeting macrophage polarization, such as disease-modifying anti-rheumatic drugs, traditional Chinese medicine, nanomedicines, proteins, chemical compounds, and physical therapies. By elucidating the precise mechanisms governing macrophage polarization and its interactions with other cells in the joint microenvironment, researchers can identify novel therapeutic targets and develop targeted interventions to alleviate disease progression and improve patient outcomes in RA and OA.

Estrogen receptor is involved in the osteoarthritis mediated by Atg16L1-NLRP3 activation.

OBJECTIVES: This study aims to explore the mechanisms of dual regulation of osteoarthritis (OA) progression by the involvement of estrogen receptor (ER) in autophagy and inflammation. MATERIALS AND METHODS: Bioinformatics methods were used to explore the relationship among associated genes. Western blot assays were used to detect related protein expression of OA in C28I2 and induced OA cellular model. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect OA related gene expression in C28I2 and induced OA cellular model. Co-immunoprecipitation (CO-IP) analysis were used to verify the direct interaction between ER and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). RESULTS: The C28I2 cellular model of OA was induced by interleukin-1ß (IL-1ß). The small interfering ribonucleic acid (SiRNA)-mediated knockdown of autophagy-related 16 like 1 (ATG16L1) in C28I2 decreased the expression of MAP1LC3B (LC3B) and NLRP3. Besides, ER-beta (ERß) agonist changed the gene expression of NLRP3 and ATG16L1. Moreover, CO-IP analysis indicated the direct interaction between ER and NLRP3. CONCLUSION: Our study results revealed that ATG16L1, NLRP3, and IL-1ß interacted closely and ERß was involved in OA process by affecting autophagy and inflammatory activation.

Evaluating enrollment and representation in COVID-19 and HIV vaccine clinical trials.

Background: Vaccine clinical trials should strive to recruit a racially, socioeconomically, and ethnically diverse range of participants to ensure appropriate representation that matches population characteristics. Yet, full inclusion in research is often limited. Methods: A single-center retrospective study was conducted of adults enrolled at Brigham and Women's Hospital (Boston, MA) between July 2020 and December 2021. Demographic characteristics, including age, race, ethnicity, ZIP code, and sex assigned at birth, were analyzed from both HIV and COVID-19 vaccine trials during the study period, acknowledging the limitations to representation under these parameters. We compared the educational attainment of vaccine trial participants to residents of the Massachusetts metropolitan area, geocoded participants' addresses to their census block group, and linked them to reported median household income levels from publicly available data for 2020. Frequency and quartile analyses were carried out, and spatial analyses were performed using ArcGIS Online web-based mapping software (Esri). Results: A total of 1030 participants from four COVID-19 vaccine trials (n = 916 participants) and six HIV vaccine trials (n = 114 participants) were included in the analysis. The median age was 49 years (IQR 33-63) and 28 years (IQR 24-34) for the COVID-19 and HIV vaccine trials, respectively. Participants identifying as White were the majority group represented for both the COVID-19 (n = 598, 65.3%) and HIV vaccine trials (n = 83, 72.8%). Fewer than 25% of participants identified as Hispanic or Latin. Based on ZIP code of residence, the median household income for COVID-19 vaccine clinical trial participants (n = 846) was 102,088 USD (IQR = 81,442-126,094). For HIV vaccine clinical trial participants (n = 109), the median household income was 101,266 USD (IQR 75,052-108,832). Conclusion: We described the characteristics of participants enrolled for HIV and COVID-19 vaccine trials at a single center and found similitude in geographical distribution, median incomes, and proportion of underrepresented individuals between the two types of vaccine candidate trials. Further outreach efforts are needed to ensure the inclusion of individuals from lower educational and socioeconomic brackets. In addition, continued and sustained efforts are necessary to ensure inclusion of individuals from diverse racial and ethnic backgrounds.

First-principles calculations to investigate the impact of fluorine doping on electrochemical properties of Li-rich Li2MnO3 layered cathode materials.

Li-rich layered oxides are promising candidates for high-capacity Li-ion battery cathode materials. In this study, we employ first-principles calculations to investigate the effect of F doping on Li-rich Li2MnO3 layered cathode materials. Our findings reveal that both Li2MnO3 and Li2MnO2.75F0.25 exhibit significant volume changes (greater than 10%) during deep delithiation, which could hinder the cycling of more Li ions from these two materials. For Li2MnO3, it is observed that oxygen ions lose electrons to compensate for charge during the delithiation process, leading to a relatively high voltage plateau. After F doping, oxidation occurs in both the cationic (Mn) and anionic (O) components, resulting in a lower voltage plateau at the beginning of the charge, which can be attributed to the oxidation of Mn3+ to Mn4+. Additionally, F doping can somewhat suppress the release of oxygen in Li2MnO3, improving the stability of anionic oxidation. However, the increase of the activation barriers for Li diffusion can be observed after F doping, due to stronger electrostatic interactions between F- and Li+, which adversely affects the cycling kinetics of Li2MnO2.75F0.25. This study enhances our understanding of the impact of F doping in Li2MnO3 based on theoretical calculations.

Predicting incident radiographic knee osteoarthritis through quantitative meniscal lesion parameters: data from the osteoarthritis initiative.

BACKGROUND: This study investigates the potential of novel meniscal parameters as predictive factors for incident radiographic knee osteoarthritis (ROA) over a span of four years, as part of the Osteoarthritis Initiative (OAI) study. OBJECTIVES: Quantitative measurements of meniscal parameters alteration could serve as predictors of OA's occurrence and progression. METHODS AND MATERIALS: A nested matched case-control study design was used to select participants from OAI study. Case knees (n = 178) were defined as those with incident ROA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline (BL), evolving into KLG 2 or above by year 4). Control knees were matched one-to-one by sex, age and radiographic status with case knees. The mean distance from medial-to-lateral meniscal lesions [Mean(MLD)], mean value of tibial plateau width [Mean(TPW)] and the mean of the relative percentage of the medial-to-lateral meniscal lesions distance [Mean(RMLD)] were evaluated through coronal T2-weighted turbo spin echo (TSE) MRI at P-0 (visit when incident ROA was found on radiograph), P-1(one year prior to P-0) and baseline, respectively. Using the imaging data of one patient, the mechanism was investigated by finite element analysis. RESULTS: Participants were on average 60.22 years old, predominantly female (66.7%) and overweight (mean BMI: 28.15). Mean(MLD) and Mean(RMLD) were significantly greater for incident knees compared to no incident knees at baseline, P-1 and P-0. [Mean(MLD), Mean(RMLD); (42.56-49.73) mean ± (7.70-9.52) mm SD vs. (38.14-40.78) mean ± (5.51-7.05)mm SD; (58.61-68.95) mean ± (8.52-11.40) mm SD vs. (52.52-56.35) mean ± (6.53-7.85)mm SD, respectively]. Baseline Mean(MLD) and Mean(RMLD), [Adjusted OR, 95%CI: 1.11(1.07 to 1.16) and 1.13(1.09 to 1.17), respectively], were associated with incident ROA during 4 years, However, Mean(TPW) [Adjusted OR, 95%CI: 0.98(0.94 to 1.02)] was not associated with incident ROA during 4 years. While Mean(TPW) at P-1 and P-0 was not associated with the risk of incident ROA, Mean(MLD) and Mean(RMLD) at P-1 and P-0 were significantly positively associated with the risk of incident ROA. CONCLUSIONS: The meniscal parameters alteration could be an important imaging biomarker to predict the occurrence of ROA.

The mitochondrial genome of a social wasp, Vespula rufa (Linnaeus, 1758) (Hymenoptera: Vespidae).

For an ongoing systematic study of Korean Vespidae, we analyzed the complete mitochondrial genome of a social wasp, Vespula rufa (Linnaeus 1758), from the South Korea. The mitogenome is 17,521 bp in length, comprising 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. The nucleotide composition is 40.5% adenines, 43.0% thymines, 6.0% guanines, and 10.5% cytosines. The GC content is 16.5%. A maximum-likelihood analysis was conducted to understand phylogenetic relationships, based on 13 complete mitogenome sequences of Vespinae species. We recognized that V. rufa is being placed basal within the genus Vespula. The complete mitochondrial genome of V. rufa provides useful genetic information for further studies.

Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication.

The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/ß-catenin pathway modulation to suppress liver cancer.

BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.

Analytical method for studying acoustic fields radiated by general spherical sound sources in thermoviscous fluids.

The study of acoustic radiation from spherical sound sources plays a crucial role in understanding the thermoviscous effects in practical acoustic problems. However, finding a general solution of acoustic radiation from spherical sound sources in thermoviscous fluids remains a formidable challenge. To advance this issue, an analytical method is developed in this paper to calculate the acoustic field radiated by spherical sound sources with the isothermal boundary condition and arbitrary velocity boundary condition. The developed method is utilized to present the solutions of the acoustic field generated by an oscillating sphere and a general spherical sound source, and the accuracy and validity of these solutions are verified through analytical and numerical methods.

Scalp Reconstruction With Free Tissue Transfer Using Descending Branch of Lateral Circumflex Femoral Vessels as Interposition Graft.

Despite the rich blood supply to the scalp, postoperative skin necrosis at the surgical site sometimes occurs, and unresolved defects often present a significant challenge for the surgeon. When planning a free flap for scalp reconstruction, distant anastomoses may be necessary if local recipient vessels are unavailable due to previous surgery. This study presents the authors' treatment strategy, which includes extending the pedicle length with arteriovenous bundle interposition grafts. Two patients who experienced surgical wound necrosis after bypass surgery for moyamoya disease underwent reconstruction for skin and soft tissue coverage. To evaluate the altered anatomical structures after the previous surgery, three-dimensional computed tomography angiography was performed, and preoperative photos were taken to accurately measure the expected defect. The surgical strategy was designed to accommodate their unique conditions, utilizing an arteriovenous interposition graft, which included 2 stages of microvascular anastomoses, for pedicle lengthening. The procedure successfully bridged the gap between distant recipient vessels and the extensive defect, and the wounds healed without major complications such as venous congestion or total flap loss. Both patients were satisfied with the surgical outcomes. Arteriovenous bundle interposition grafts can be a useful option for patients with complex scalp defects who lack local recipient vessels. The use of an anterolateral thigh flap with artery-to-artery anastomosis, utilizing the lateral circumflex femoral artery from the opposite side in this study, offers many advantages compared with traditional pedicle lengthening tools utilizing vein-to-artery anastomosis.

Association Between the Timing of Atrial Fibrillation Detection and Functional Outcome Following Mechanical Thrombectomy.

BACKGROUND: Atrial fibrillation detected after stroke (AFDAS) refers to the identification of newly diagnosed atrial fibrillation (AF) following an ischemic stroke in patients without known AF (KAF). The objective of this study was to compare the functional outcomes of patients diagnosed with AFDAS and those with KAF who underwent mechanical thrombectomy. METHODS AND RESULTS: We conducted a retrospective analysis of patients who underwent mechanical thrombectomy and with either new AF diagnosed during hospitalization or KAF. We compared the baseline characteristics, clinical, and procedure-related variables between those with AFDAS and KAF. The primary outcome was the achievement of functional independence, defined as a modified Rankin Scale score of 0 to 2, at 3 months after stroke. Of the 252 patients, 101 (40.1%) were classified into the AFDAS group. The KAF group exhibited a higher rate of stroke history compared with the AFDAS group (32.5% versus 13.9%; P=0.001). Tandem occlusion was more common in the KAF group (13.2% versus 5.9%), while M2 occlusion was more common in the AFDAS group (11.3% versus 20.8%). The proportion of patients who achieved functional independence was higher in the AFDAS group (37.7% versus 52.5%; P=0.029). Multivariable analysis showed that AFDAS was associated with a favorable functional outcome (odds ratio, 2.67 [95% CI, 1.39-5.14]; P=0.003). CONCLUSIONS: AFDAS demonstrated a positive association with functional independence in patients with stroke who underwent mechanical thrombectomy and were finally diagnosed to have AF during hospitalization. The observed disparities in occlusion site, intractable thrombus, and history of previous stroke may have contributed to these findings.

Retinal light damage: From mechanisms to protective strategies.

Visible light serves as a crucial medium for vision formation.;however, prolonged or excessive exposure to light is recognized as a significant etiological factor contributing to retinal degenerative diseases. The retina, with its unique structure and adaptability, relies on the homeostasis of cellular functions to maintain visual health. Under normal conditions, the retina can mount adaptive responses to various insults, including light-induced damage. Unfortunately, exposure to intense and excessive light triggers a cascade of pathological alterations in retinal photoreceptor cells, pigment epithelial cells, ganglion cells, and glial cells. These alterations encompass disruption of intracellular REDOX and Ca²âº homeostasis, pyroptosis, endoplasmic reticulum stress, autophagy, and the release of inflammatory cytokines, culminating in irreversible retinal damage. We first delineate the mechanisms of retinal light damage through 4 main avenues: mitochondria function, endoplasmic reticulum stress, cell autophagy, and inflammation. Subsequently, we discuss protective strategies against retinal light damage, aiming to guide research toward the prevention and treatment of light-induced retinal conditions.

Comparative efficacy of 0.1% and 0.15% Sodium Hyaluronate on lipid layer and meibomian glands following cataract surgery: A randomized prospective study.

PURPOSE: To compare the efficacy of a 0.15% HA with that of 0.1% HA eye drops for DES after cataract surgery. METHODS: This study was double blinded, randomized and prospective study, and conducted in 69 participants (70 eyes) from Pusan National University Yangsan Hospital and executed from February 1, 2022 to November 30, 2022. Participants were adult cataract patients with normal lid position, not suffering from any other ocular disease and not meet the exclusion cirteria of clinical trial. Participants were randomly divided into two groups: 35 participants (17 males and 18 females) in the 0.1% HA group and 34 participants (19 males and 15 females) in the 0.15% HA group, receiving treatment six times daily for 6 weeks following cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits, including ocular surface disease index score, tear break up time, corneal staining score, Schirmer's I test score, lipid layer thickness), meiboscore, and biochemical analysis of the eye drops. RESULTS: Throughout the study, the postoperative ocular surface disease index score was significantly lower in the group receiving 0.15% hyaluronic acid than in the group receiving 0.1% hyaluronic acid. Additionally, the postoperative ocular surface disease index score showed a significant positive correlation with the postoperative use of 0.15% hyaluronic acid and the preoperative Schirmer's I test score. In multivariate analysis, treatment with 0.15% hyaluronic acid and the preoperative ocular surface disease index score were significant independent parameters affecting the postoperative ocular surface disease index score. CONCLUSION: The use of 0.15% hyaluronic acid is recommended for its potential advantages in alleviating symptoms following cataract surgery, making it a viable alternative to traditional 0.1% hyaluronic acid treatment. TRIAL REGISTRATION: ISRCTN95830348.

Risk factors for benign paroxysmal positional vertigo and construction of a nomogram predictive model.

BACKGROUND: To analyze the risk factors for benign paroxysmal positional vertigo (BPPV) and to construct a predictive nomogram model. METHODS: In this retrospective study, 312 participants were enrolled, including 164 BPPV patients and 148 healthy subjects without BPPV. Risk predictors for BPPV were identified using univariate and multivariate analyses, and a clinical nomogram was constructed. The predictive accuracy was assessed by unadjusted concordance index (C-index) and calibration plot. RESULTS: Univariate and multivariate regression analysis identified stroke (95% CI, 0.575-5.954; P=0.022), hyperlipidemia (95% CI, 0.471-4.647; P=0.003), chronic suppurative otitis media (95% CI, 1.222-45.528; P=0.005), cervical spondylosis (95% CI, 1.232-3.017; P=0.005), and osteoporosis (95% CI, 1.130-3.071; P=0.001) were the independent risk factors for BPPV. These risk factors were used to construct a clinical predictive nomogram. The regression equation was: logit (P) = -6.820 + 0.450 * stroke + hyperlipidemia * 0.312 + chronic suppurative otitis media * 0.499 + cervical spondylosis * 0.916 + osteoporosis * 0.628. The calibration curves demonstrated excellent accuracy of the predictive nomogram. Decision curve analysis showed that the predictive model is clinically applicable when the threshold probability was between 20% and 60%. CONCLUSIONS: Stroke, hyperlipidemia, chronic suppurative otitis media, cervical spondylosis and osteoporosis are independent risk predictors for BPPV. The developed nomogram is useful in predicting the risk of BPPV.

Integrating network pharmacology with experimental validation to investigate the mechanism of Wuwei Zishen formula in improving perimenopausal syndrome.

OBJECTIVES: To investigate the role of the Wuwei Zishen formula (WWZSF) in treating and preventing perimenopausal syndrome (PMS) and to understand its mechanism. METHODS: Network pharmacology and molecular docking was used to predict active compounds, potential targets, and pathways for PMS treatment using WWZSF. Female Sprague-Dawley (SD) rats were induced with D-galactose (D-gal) to establish a PMS model and treated with Kunbao pill (KBP) and WWZSF. Estrus cycles were observed using vaginal smears. Serum sex hormones were measured using the enzyme-linked immunosorbent assay (ELISA). Histological changes in the uterus and ovaries were evaluated using hematoxylin-eosin staining (HE). Western blot was used to assess the protein expression levels of Cleaved Caspase-3, p62, BAX/Bcl-2, p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR in the uterus and ovaries. RESULTS: A total of 70 active compounds and 440 potential targets were screened out. Important targets and pathways, including AKT1, Bcl-2, Caspase-3, mTOR, and the PI3K/AKT/mTOR pathways, and molecular docking verified their high affinities to key WWZSF components. In vivo experiments showed that WWZSF can ameliorate the morphological abnormalities of the uterus and ovaries, increase sex hormone levels and organ index, and restore the estrus cycles in PMS rats. Moreover, the western blot results showed decreased Cleaved Caspase-3 and BAX/Bcl-2 protein levels in the ovarian and uterine tissues after WWZSF therapy. Concurrently, there was an increase in the expression of p62 and the ratios of p-AKT/AKT, p-mTOR/mTOR, and p-PI3K/PI3K. CONCLUSION: The PI3K/AKT/mTOR signaling pathway-mediated apoptosis and autophagy pathways may be how WWZSF efficiently reduces PMS.

Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging.

The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.