The Novel Insight of Gut Microbiota from Mouse Model to Clinical Patients and the Role of NF-κB Pathway in Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is a metabolic disorder characterized by hyperandrogenism and related symptoms in women of reproductive age. Emerging evidence suggests that chronic low-grade inflammation plays a significant role in the development of PCOS. The gut microbiota, a complex bacterial ecosystem, has been extensively studied for various diseases, including PCOS, while the underlying mechanisms are not fully understood. This review comprehensively summarizes the changes in gut microbiota and metabolites observed in PCOS and their potential association with the condition. Additionally, we discuss the role of abnormal nuclear factor κB signaling in the pathogenesis of PCOS. These findings offer valuable insights into the mechanisms of PCOS and may pave the way for the development of control and therapeutic strategies for this condition in clinical practice. By bridging the gap between mouse models and clinical patients, this review contributes to a better understanding of the interplay between gut microbiota and inflammation in PCOS, thus paving new ways for future investigations and interventions.

Microdroplets Encapsulated with NFATc1-siRNA and Exosomes-Derived from MSCs Onto 3D Porous PLA Scaffold for Regulating Osteoclastogenesis and Promoting Osteogenesis.

Introduction: Osteoporotic-related fractures remains a significant public health concern, thus imposing substantial burdens on our society. Excessive activation of osteoclastic activity is one of the main contributing factors for osteoporosis-related fractures. While polylactic acid (PLA) is frequently employed as a biodegradable scaffold in tissue engineering, it lacks sufficient biological activity. Microdroplets (MDs) have been explored as an ultrasound-responsive drug delivery method, and mesenchymal stem cell (MSC)-derived exosomes have shown therapeutic effects in diverse preclinical investigations. Thus, this study aimed to develop a novel bioactive hybrid PLA scaffold by integrating MDs-NFATc1-silencing siRNA to target osteoclast formation and MSCs-exosomes (MSC-Exo) to influence osteogenic differentiation (MDs-NFATc1/PLA-Exo). Methods: Human bone marrow-derived mesenchymal stromal cells (hBMSCs) were used for exosome isolation. Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used for exosome and MDs morphological characterization, respectively. The MDs-NFATc1/PLA-Exo scaffold was fabricated through poly(dopamine) and fibrin gel coating. Biocompatibility was assessed using RAW 264.7 macrophages and hBMSCs. Osteoclast formations were examined via TRAP staining. Osteogenic differentiation of hBMSCs and cytokine expression modulation were also investigated. Results: MSC-Exo exhibited a cup-shaped structure and effective internalization into cells, while MDs displayed a spherical morphology with a well-defined core-shell structure. Following ultrasound stimulation, the internalization study demonstrated efficient delivery of bioactive MDs into recipient cells. Biocompatibility studies indicated no cytotoxicity of MDs-NFATc1/PLA-Exo scaffolds in RAW 264.7 macrophages and hBMSCs. Both MDs-NFATc1/PLA and MDs-NFATc1/PLA-Exo treatments significantly reduced osteoclast differentiation and formation. In addition, our results further indicated MDs-NFATc1/PLA-Exo scaffold significantly enhanced osteogenic differentiation of hBMSCs and modulated cytokine expression. Discussion: These findings suggest that the bioactive MDs-NFATc1/PLA-Exo scaffold holds promise as an innovative structure for bone tissue regeneration. By specifically targeting osteoclast formation and promoting osteogenic differentiation, this hybrid scaffold may address key challenges in osteoporosis-related fractures.

Diagnostic value of stimulated urine luteinizing hormone after triptorelin stimulation test in girls with CPP.

OBJECTIVE: To investigate the diagnostic value of urine luteinizing hormone (ULH) after triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). METHODS: The girls with precocious puberty were involved. The triptorelin stimulation test at 8:30 a.m.were performed. Two consecutive 12-hour urine samples were collected after the test, defined as first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development. RESULTS: A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in CPP group were higher than those in PPP group. When first 12-hour ULH/Cr was ≥ 287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When second 12-hour ULH/Cr was ≥ 152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively. CONCLUSION: The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When the compliance of blood sampling in girls with precocious puberty is poor, first 12-hour ULH/Cr ≥ 288 IU/mol (or second 12-hour ≥ 153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP.

N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

Correction: Development of bioactive and ultrasound-responsive microdroplets for preventing ovariectomy (OVX)-induced osteoporosis.

Correction for 'Development of bioactive and ultrasound-responsive microdroplets for preventing ovariectomy (OVX)-induced osteoporosis' by Yi Zhang et al., J. Mater. Chem. B, 2023, 11, 11344-11356, https://doi.org/10.1039/D3TB01726E.

Platelets: A Potential Factor that Offers Strategies for Promoting Bone Regeneration.

Bone defects represent a prevalent category of clinical injuries, causing significant pain and escalating health care burdens. Effectively addressing bone defects is thus of paramount importance. Platelets, formed from megakaryocyte lysis, have emerged as pivotal players in bone tissue repair, inflammatory responses, and angiogenesis. Their intracellular storage of various growth factors, cytokines, and membrane protein receptors contributes to these crucial functions. This article provides a comprehensive overview of platelets' roles in hematoma structure, inflammatory responses, and angiogenesis throughout the process of fracture healing. Beyond their application in conjunction with artificial bone substitute materials for treating bone defects, we propose the potential future use of anticoagulants such as heparin in combination with these materials to regulate platelet number and function, thereby promoting bone healing. Ultimately, we contemplate whether manipulating platelet function to modulate bone healing could offer innovative ideas and directions for the clinical treatment of bone defects.

Therapeutic strategies targeting the NLRP3­mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review).

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD­like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL­1ß and IL­18, as well as gasdermin­D­mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3­mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.

Monolayer Borophene Formation on Cu(111) Surface Triggered by ⟨ 1 1 ¯ 0 ⟩ $\langle {1\bar{1}0} \rangle $ Step Edge.

Borophene, a promising material with potential applications in electronics, energy storage, and sensors, is successfully grown as a monolayer on Ag(111), Cu(111), and Au(111) surfaces using molecular beam epitaxy. The growth of two-dimensional borophene on Ag(111) and Au(111) is proposed to occur via surface adsorption and boron segregation, respectively. However, the growth mode of borophene on Cu(111) remains unclear. To elucidate this, scanning tunneling microscopy in conjunction with theoretical calculations is used to study the phase transformation of boron nanostructures under post-annealing treatments. Results show that by elevating the substrate temperature, boron nanostructures undergo an evolution from amorphous boron to striped-phase borophene (η = 1/6) adhering to the Cu ⟨ 1 1 ¯ 0 ⟩ $\langle {1\bar{1}0} \rangle $ step edge, and finally to irregularly shaped ß-type borophene (η = 5/36) either on the substrate surface or embedded in the topmost Cu layer. dI/dV spectra recorded near the borophene/Cu lateral interfaces indicate that the striped-phase borophene is a metastable phase, requiring more buckling and electron transfer to stabilize the crystal structure. These findings offer not only an in-depth comprehension of the ß-type borophene formation on Cu(111), but also hold potential for enabling borophene synthesis on weakly-binding semiconducting or insulating substrates with 1D active defects.

Development of bioactive and ultrasound-responsive microdroplets for preventing ovariectomy (OVX)-induced osteoporosis.

As a common bone disease in the elderly population, osteoporosis-related bone loss and bone structure deterioration represent a major public health problem. Therapeutic strategies targeting excessive osteoclast formation are frequently used for osteoporosis treatment; however, potential side effects have been recorded. Here, we have developed a novel therapeutic strategy using microdroplets (MDs) encapsulated with NFATc1-siRNA and investigated the role of bioactive MDs-NFATc1 biocompatibility in RAW 264.7 macrophages and human mesenchymal stem cells (hBMSCs), respectively. Its role in regulating osteoclast differentiation and formation was also investigated in vitro. We first fabricated MDs with spherical morphology along with a well-defined core-shell structure. The ultrasound-responsive study demonstrated time-dependent responsive structural changes following ultrasound stimulation. The internalization study into unstimulated macrophages, inflammatory macrophages, and hBMSCs indicated good delivery efficiency. Furthermore, the results from the MTT assay, the live/dead assay, and the cellular morphological analysis further indicated good biocompatibility of our bioactive MDs-NFATc1. Following MDs-NFATc1 treatment, the number of osteoclasts was greatly reduced, indicating their inhibitory effect on osteoclastogenesis and osteoclast formation. Subsequently, osteoporotic rats that underwent ovariectomy (OVX) were used for the in vivo studies. The rats treated with MDs-NFATc1 exhibited significant resistance to bone loss induced by OVX. In conclusion, our results demonstrate that MDs-NFATc1 could become an important regulator in osteoclast differentiation and functions, thus having potential applications in osteoclast-related bone diseases.

Analysis of the Sputum Culture Spectrum of Children with Respiratory Tract Infection in Wuxi Between 2014 and 2021.

Objective: We retrospectively analysed related clinical data to determine the influencing factors to better prevent and treat children's respiratory tract infection. Methods: The study participants were children with respiratory tract infection who had sputum cultured in our hospital between 2014 and 2021. Sputum samples were extracted using negative suction pressure and sent to the hospital microbiological laboratory for testing. The testing results were analysed. Results: A total of 4610 sputum samples were collected, and 508 positive samples were detected. The positive rate of pathogenic bacteria was 11.02%. Escherichia coli infection was more common in male patients (11.11%), whereas Haemophilus influenzae infection was more common in female patients (17.54%); the infection rates of these 2 bacteria are increasing annually. There were 304 (59.84%) strains of gram-negative bacteria, 172 (33.86%) strains of gram-positive bacteria and 32 (6.3%) strains of fungi. In children between 0 and 3 years old, the proportions of gram-negative bacteria were significantly higher than those of gram-positive bacteria in 2016-2017, 2018-2019 and 2020-2021 (p < 0.01). In every age group, the constituent ratio of gram-negative bacteria was significantly higher than that of gram-positive bacteria (p < 0.01) except for the 3-6-year age group. The proportion of Staphylococcus aureus in 2014-2015, 2016-2017, 2018-2019 and 2020-2021 was 25.64%, 25.20%, 22.98% and 16.44%, respectively. The proportion of H. influenzae in 2014-2015 was significantly lower than that in other years (p < 0.01). Haemolyticus staphylococcus and E. coli were more common in newborns, accounting for 19.12%. Conclusion: The pathogens of respiratory tract infection in children change dynamically. There are significant differences in pathogens of respiratory tract infections among different age groups, years and seasons. Clinicians should pay attention to changes in the pathogen spectrum and improve drug resistance monitoring.

Impacts of Ship Emissions on Air Quality in Southern China: Opportunistic Insights from the Abrupt Emission Changes in Early 2020.

In early 2020, two unique events perturbed ship emissions of pollutants around Southern China, proffering insights into the impacts of ship emissions on regional air quality: the decline of ship activities due to COVID-19 and the global enforcement of low-sulfur (<0.5%) fuel oil for ships. In January and February 2020, estimated ship emissions of NOx, SO2, and primary PM2.5 over Southern China dropped by 19, 71, and 58%, respectively, relative to the same period in 2019. The decline of ship NOx emissions was mostly over the coastal waters and inland waterways of Southern China due to reduced ship activities. The decline of ship SO2 and primary PM2.5 emissions was most pronounced outside the Chinese Domestic Emission Control Area due to the switch to low-sulfur fuel oil there. Ship emission reductions in early 2020 drove 16 to 18% decreases in surface NO2 levels but 3.8 to 4.9% increases in surface ozone over Southern China. We estimated that ship emissions contributed 40% of surface NO2 concentrations over Guangdong in winter. Our results indicated that future abatements of ship emissions should be implemented synergistically with reductions of land-borne anthropogenic emissions of nonmethane volatile organic compounds to effectively alleviate regional ozone pollution.

Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS.

Background: Polycystic ovary syndrome (PCOS) is a complex, multifactor disorder in women of reproductive age worldwide. Although RNA editing may contribute to a variety of diseases, its role in PCOS remains unclear. Methods: A discovery RNA-Seq dataset was obtained from the NCBI Gene Expression Omnibus database of granulosa cells from women with PCOS and women without PCOS (controls). A validation RNA-Seq dataset downloaded from the European Nucleotide Archive Databank was used to validate differential editing. Transcriptome-wide investigation was conducted to analyze adenosine-to-inosine (A-to-I) RNA editing in PCOS and control samples. Results: A total of 17,395 high-confidence A-to-I RNA editing sites were identified in 3,644 genes in all GC samples. As for differential RNA editing, there were 545 differential RNA editing (DRE) sites in 259 genes with Nucleoporin 43 (NUP43), Retinoblastoma Binding Protein 4 (RBBP4), and leckstrin homology-like domain family A member 1 (PHLDA) showing the most significant three 3'-untranslated region (3'UTR) editing. Furthermore, we identified 20 DRE sites that demonstrated a significant correlation between editing levels and gene expression levels. Notably, MIR193b-365a Host Gene (MIR193BHG) and Hook Microtubule Tethering Protein 3 (HOOK3) exhibited significant differential expression between PCOS and controls. Functional enrichment analysis showed that these 259 differentially edited genes were mainly related to apoptosis and necroptosis pathways. RNA binding protein (RBP) analysis revealed that RNA Binding Motif Protein 45 (RBM45) was predicted as the most frequent RBP binding with RNA editing sites. Additionally, we observed a correlation between editing levels of differential editing sites and the expression level of the RNA editing enzyme Adenosine Deaminase RNA Specific B1 (ADARB1). Moreover, the existence of 55 common differentially edited genes and nine differential editing sites were confirmed in the validation dataset. Conclusion: Our current study highlighted the potential role of RNA editing in the pathophysiology of PCOS as an epigenetic process. These findings could provide valuable insights into the development of more targeted and effective treatment options for PCOS.

[Research updates of osteoimmunomodulation in osteogenesis].

The gold-standard for bone substitution of large bone defects continues to be autogenous bone graft. Artificial bone substitutes are difficult to replace the autogenous bone grafting due to excessive immune response, fast biodegradation characteristics and inappropriate biocompatibility. Given these drawbacks, osteoimmunology and its advanced functional biomaterials have gained growing attention in recent years. Immune system plays an essential role during bone healing via regulating the shift from inflammatory to anti-inflammation phenotype, and inflammatory cytokines response. The inflammatory reaction mainly include infiltration of immune cells (such as macrophages, neutrophils, T cells, B cells, etc) and release of inflammatory factors (such as IL-1ß, IL-6, TNF-α, etc.) at the bone defects, which subsequently affect the step-wised process of bone healing rejuvenation. Hence, advanced bone biomaterials with immunomodulatory properties is of great significance for the treatment of patients with recalcitrant bone defects, especially for delayed healing or non-union. The reciprocal mechanism of immuno-modulated bone healing, however, is not fully understood and more research is required in the future.

Fabrication of Interleukin-4 Encapsulated Bioactive Microdroplets for Regulating Inflammation and Promoting Osteogenesis.

Background: Despite the inherent regenerative ability of bone, large bone defect regeneration remains a major clinical challenge for orthopedic surgery. Therapeutic strategies medicated by M2 phenotypic macrophages or M2 macrophage inducer have been widely used to promote tissue remodeling. In this study, ultrasound-responsive bioactive microdroplets (MDs) encapsulated with bioactive molecule interleukin-4 (IL4, hereafter designated MDs-IL4) were fabricated to regulate macrophage polarization and potentiate the osteogenic differentiation of human mesenchymal stem cells (hBMSCs). Materials and Methods: The MTT assay, live and dead staining, and phalloidin/DAPI dual staining were used to evaluate biocompatibility in vitro. H&E staining was used to evaluate biocompatibility in vivo. Inflammatory macrophages were further induced via lipopolysaccharide (LPS) stimulation to mimic the pro-inflammatory condition. The immunoregulatory role of the MDs-IL4 was tested via macrophage phenotypic marker gene expression, pro-inflammatory cytokine level, cell morphological analysis, and immunofluorescence staining, etc. The immune-osteogenic response of hBMSCs via macrophages and hBMSCs interactions was further investigated in vitro. Results: The bioactive MDs-IL4 scaffold showed good cytocompatibility in RAW 264.7 macrophages and hBMSCs. The results confirmed that the bioactive MDs-IL4 scaffold could reduce inflammatory phenotypic macrophages, as evidenced by changing in morphological features, reduction in pro-inflammatory marker gene expression, increase of M2 phenotypic marker genes, and inhibition of pro-inflammatory cytokine secretion. Additionally, our results indicate that the bioactive MDs-IL4 could significantly enhance the osteogenic differentiation of hBMSCs via its potential immunomodulatory properties. Conclusion: Our results demonstrate that the bioactive MDs-IL4 scaffold could be used as novel carrier system for other pro-osteogenic molecules, thus having potential applications in bone tissue regeneration.

Advances of Blood Coagulation Factor XIII in Bone Healing.

The biologic process of bone healing is complicated, involving a variety of cells, cytokines, and growth factors. As a result of bone damage, the activation of a clotting cascade leads to hematoma with a high osteogenic potential in the initial stages of healing. A major factor involved in this course of events is clotting factor XIII (FXIII), which can regulate bone defect repair in different ways during various stages of healing. Autografts and allografts often have defects in clinical practice, making the development of advanced materials that support bone regeneration a critical requirement. Few studies, however, have examined the promotion of bone healing by FXIII in combination with biomaterials, in particular, its effect on blood coagulation and osteogenesis. Therefore, we mainly summarized the role of FXIII in promoting bone regeneration by regulating the extracellular matrix and type I collagen, bone-related cells, angiogenesis, and platelets, and described the research progress of FXIII = related biomaterials on osteogenesis. This review provides a reference for investigators to explore the mechanism by which FXIII promotes bone healing and the combination of FXIII with biomaterials to achieve targeted bone tissue repair.

Analysis of risk factors for ulcer recurrence and upper gastrointestinal bleeding in children with peptic ulcer treated with Helicobacter pylori eradication therapy.

Background: The incidence of peptic ulcer disease (PUD) has been increasing yearly, especially in the adolescent population. The eradication of Helicobacter pylori (H. pylori) may reduce recurrence and bleeding to some extent, but it does not completely change the clinical status of PUD. Therefore, this study aims to analyze the risk factors for ulcer recurrence and upper gastrointestinal bleeding after H. pylori eradication therapy in order to provide a reference for reducing the risk of PUD and improving the quality of life of patients. Methods: We retrospectively analyzed 536 adolescent patients who developed peptic ulcer and received H. pylori eradication therapy from June 2016 to July 2021. The relationship between the clinical characteristics of the patients and gastrointestinal bleeding and recurrence was analyzed using the t-test and chi-squared test. Binary logistic regression was used to analyze the independent risk factors for the occurrence of bleeding and recurrence. Results: A total of 536 patients were included in this retrospective study. Gender, history of ulcers, number, size, location and staging of ulcers, and application of nonsteroidal anti-inflammatory drugs (NSAIDs), and other characteristics were significantly different between the bleeding and nonbleeding groups (P<0.05); family history of upper gastrointestinal ulcer, history of ulcers, number and size of ulcers and application of NSAIDs, and other characteristics were significantly different between the recurrent and nonrecurrent groups (P<0.05). Binary logistic regression analysis showed that history of ulcers, number and location of ulcers, coagulation abnormalities, and other characteristics were independent risk factors for the occurrence of bleeding; the occurrence of previous bleeding, number and size of ulcers, and other characteristics were independent risk factors for recurrence. Conclusions: In the clinical treatment of adolescent patients, it is important to pay high attention to clinical characteristics, such as the patient's previous ulcer history, the size, number and location of ulcers, and coagulation function, so as to adopt individualized treatment methods to effectively reduce the harmfulness of the disease in response to the risk factors of ulcer bleeding and recurrence after H. pylori eradication therapy. This can decrease the occurrence of complications and improve the prognosis of patients.

Analysis of risk factors for postoperative bleeding and polyp recurrence in adolescents with gastric polyps treated with endoscopic mucosal resection: a retrospective cohort study.

Background: The incidence of gastric polyps in adolescents has been increasing every year in recent years. Endoscopic mucosal resection (EMR) is one of the most common treatments for adults, but there are few reports on the association between EMR of gastric polyps and the occurrence of bleeding and recurrence after the procedure in adolescents. This study sought to analyze the independent risk factors for postoperative bleeding and polyp recurrence after EMR to provide a reference for reducing the occurrence of postoperative complications. Methods: We retrospectively analyzed the data of 579 adolescent patients who developed gastric polyps from June 2016 to June 2021. Postoperative follow-up was conducted for 1 year by telephone, e-mail, and outpatient review. The general characteristics of the study population were compiled using a general information questionnaire designed by the investigators. The relationship between the patients' clinical characteristics and postoperative bleeding or recurrence was analyzed using the chi-square test. A binary logistic regression analysis was conducted to analyze the independent risk factors for the occurrence of postoperative bleeding and polyp recurrence in patients. Results: The results of the binary logistic regression analysis showed that being female [odds ratio (OR) =0.306, P=0.009], polyps >1 cm in diameter (OR =2.557, P=0.029), polyps in gastric sinus (OR =3.889, P=0.032), sessile lesions (OR =0.398, P=0.036), the need for additional intraoperative sedation (OR =3.469, P=0.005), concurrent diverticulum (OR =3.570, P=0.004), and intraoperative bleeding (OR =4.855, P=0.001) were independent risk factors for postoperative bleeding. We also found that polyps >1 cm in diameter (OR =2.134, P=0.003), multiple polyps (OR =2.117, P=0.005), adenomatous polyps (OR =2.684, P=0.041), combined Helicobacter pylori infection (OR =2.036, P=0.009), the occurrence of postoperative gastrointestinal reflux (OR =1.998, P=0.015), and an operative time ≥40 min (OR =2.021, P=0.010) were independent risk factors for the recurrence of polyps. Conclusions: There is still a high probability of postoperative bleeding and polyp recurrence after EMR in adolescents with gastric polyps. Clinicians should pay close attention to the clinical features of polyps, such as polyp size, number, morphology, and pathological type, to identify the related risk factors as early as possible and reduce the probability of postoperative bleeding and polyp recurrence in patients.

Pharmacokinetics and Bioequivalence of Abiraterone Acetate Tablets in Healthy Chinese Volunteers: An Open, Randomized, Single-Dose, Three-Period, Three-Sequence Crossover Study.

BACKGROUND AND OBJECTIVE: Abiraterone acetate tablet is an inhibitor of androgen synthesis, primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioequivalence and pharmacokinetics of the reference and test formulations of abiraterone acetate tablets in healthy Chinese volunteers. METHODS: A single-center, open, single-dose, randomized, three-period, three-sequence, semi-repeat (only repeated reference formulations), and reference formulation-corrected fasting reference-scaled average bioequivalence test was conducted in 36 healthy volunteers included in this study. Volunteers were randomly assigned to one of three groups in a 1:1:1 ratio. There was a minimum 7-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of abiraterone acetate tablets was determined by liquid chromatography-tandem mass spectrometry, and adverse events were recorded. RESULTS: Under fasting conditions, the maximum plasma concentration (Cmax) was 27.02 ± 14.21 ng/mL, area under the concentration-time curve from time zero to time t (AUCt) was 125.30 ± 82.41 h·ng/mL, and AUC from time zero to infinity (AUC∞) was 133.70 ± 83.99 h·ng/mL. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of AUCt and AUC∞ were in the range of 0.8000-1.2500, and the coefficient of variation (CVWR) of Cmax was more than 30%. The Critbound result was - 0.0522, and the GMR was between 0.8000 and 1.2500. CONCLUSION: Both test and reference formulations of abiraterone acetate tablets were bioequivalent in healthy Chinese subjects under fasting conditions. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04863105, registered 26 April 2021-retrospectively registered ( https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000ARAA&selectaction=Edit&uid=U00050YQ&ts=2&cx=-vbtjri.

The role of autophagy in bone metabolism and clinical significance.

The skeletal system is the basis of the vertebral body composition, which affords stabilization sites for muscle attachment, protects vital organs, stores mineral ions, supplies places to the hematopoietic system, and participates in complex endocrine and immune system. Not surprisingly, bones are constantly reabsorbed, formed, and remodeled under physiological conditions. Once bone metabolic homeostasis is interrupted (including inflammation, tumors, fractures, and bone metabolic diseases), the body rapidly initiates bone regeneration to maintain bone tissue structure and quality. Macroautophagy/autophagy is an essential metabolic process in eukaryotic cells, which maintains metabolic energy homeostasis and plays a vital role in bone regeneration by controlling molecular degradation and organelle renewal. One relatively new observation is that mesenchymal cells, osteoblasts, osteoclasts, osteocytes, chondrocytes, and vascularization process exhibit autophagy, and the molecular mechanisms and targets involved are being explored and updated. The role of autophagy is also emerging in degenerative diseases (intervertebral disc degeneration [IVDD], osteoarthritis [OA], etc.) and bone metabolic diseases (osteoporosis [OP], osteitis deformans, osteosclerosis). The use of autophagy regulators to modulate autophagy has benefited bone regeneration, including MTOR (mechanistic target of rapamycin kinase) inhibitors, AMPK activators, and emerging phytochemicals. The application of biomaterials (especially nanomaterials) to trigger autophagy is also an attractive research direction, which can exert superior therapeutic properties from the material-loaded molecules/drugs or the material's properties such as shape, roughness, surface chemistry, etc. All of these have essential clinical significance with the discovery of autophagy associated signals, pathways, mechanisms, and treatments in bone diseases in the future.Abbreviations: Δψm: mitochondrial transmembrane potential AMPK: AMP-activated protein kinase ARO: autosomal recessive osteosclerosis ATF4: activating transcription factor 4 ATG: autophagy-related ß-ECD: ß-ecdysone BMSC: bone marrow mesenchymal stem cell ER: endoplasmic reticulum FOXO: forkhead box O GC: glucocorticoid HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha HSC: hematopoietic stem cell HSP: heat shock protein IGF1: insulin like growth factor 1 IL1B/IL-1ß: interleukin 1 beta IVDD: intervertebral disc degradation LPS: lipopolysaccharide MAPK: mitogen-activated protein kinase MSC: mesenchymal stem cell MTOR: mechanistic target of rapamycin kinase NP: nucleus pulposus NPWT: negative pressure wound therapy OA: osteoarthritis OP: osteoporosis PTH: parathyroid hormone ROS: reactive oxygen species SIRT1: sirtuin 1 SIRT3: sirtuin 3 SQSTM1/p62: sequestosome 1 TNFRSF11B/OPG: TNF receptor superfamily member 11b TNFRSF11A/RANK: tumor necrosis factor receptor superfamily, member 11a TNFSF11/RANKL: tumor necrosis factor (ligand) superfamily, member 11 TSC1: tuberous sclerosis complex 1 ULK1: unc-51 like autophagy activating kinase 1.

Systematic pan-cancer analysis identifies SLC31A1 as a biomarker in multiple tumor types.

BACKGROUND: Solute Carrier Family 31 Member 1 (SLC31A1) has recently been identified as a cuproptosis-regulatory gene. Recent studies have indicated that SLC31A1 may play a role in colorectal and lung cancer tumorigenesis. However, the role of SLC31A1 and its cuproptosis-regulatory functions in multiple tumor types remains to be further elucidated. METHODS: Online websites and datasets such as HPA, TIMER2, GEPIA, OncoVar, and cProSite were used to extract data on SLC31A1 in multiple cancers. DAVID and BioGRID were used to conduct functional analysis and construct the protein-protein interaction (PPI) network, respectively. The protein expression data of SLC31A1 was obtained from the cProSite database. RESULTS: The Cancer Genome Atlas (TCGA) datasets showed increased SLC31A1 expression in tumor tissues compared with non-tumor tissues in most tumor types. In patients with tumor types including adrenocortical carcinoma, low-grade glioma, or mesothelioma, higher SLC31A1 expression was associated with shorter overall survival and disease-free survival. S105Y was the most prevalent point mutation in SLC31A1 in TCGA pan-cancer datasets. Moreover, SLC31A1 expression was positively correlated with the infiltration of immune cells such as macrophages and neutrophils in tumor tissues in several tumor types. Functional enrichment analysis showed that SLC31A1 co-expressed genes were involved in protein binding, integral components of the membrane, metabolic pathways, protein processing, and endoplasmic reticulum. Copper Chaperone For Superoxide Dismutase, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha and Solute Carrier Family 31 Member 2 were copper homeostasis-regulated genes shown in the PPI network, and their expression was positively correlated with SLC31A1. Analysis showed there was a correlation between SLC31A1 protein and mRNA in various tumors. CONCLUSIONS: These findings demonstrated that SLC31A1 is associated with multiple tumor types and disease prognosis. SLC31A1 may be a potential key biomarker and therapeutic target in cancers.