Clinical manifestations and outcomes of otitis media with effusion in adult patients following Omicron infection in China.

This study investigates the clinical features and therapeutic outcomes of otitis media with effusion (OME) in adults following infection with the Omicron variant of coronavirus disease 2019 (COVID-19), in the context of China ending its "Zero-COVID-19" policy. Conducted as a multicenter, retrospective analysis at two medical institutions in Eastern China from December 2022 to February 2023, the study included patients with confirmed Omicron infection who were diagnosed with OME within two months, adhering to guidelines from the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF). Data on demographics, time from infection to OME manifestation, associated symptoms, and treatment outcomes were collected. Among 68 patients (73 affected ears) with OME post-Omicron infection, common symptoms included cough and nasal obstruction (69.1%). All reported ear fullness, with 86.8% experiencing hearing loss. Tympanic bullae were observed in 72.6% during otoscopy, and most tympanometry results showed a B-type tympanogram (80.0%). An integrated treatment strategy led to an 83.6% cure rate, although 8.2% experienced relapse within 2-3 months. Our findings highlight OME as a prevalent ear complication associated with COVID-19 during the Omicron pandemic, underscoring the necessity for further investigation into its complexities. While the integrated treatment approach proved effective, the 8.2% post-treatment recurrence rate underscores the importance of ongoing monitoring and signals an urgent need for more comprehensive research.

Two-Dimensional Biodegradable Black Phosphorus Nanosheets Promote Large Full-Thickness Wound Healing through In Situ Regeneration Therapy.

Large full-thickness skin lesions have been one of the most challenging clinical problems in plastic surgery repair and reconstruction. To achieve in situ skin regeneration and perfect clinical outcomes, we must address two significant obstacles: angiogenesis deficiency and inflammatory dysfunction. Recently, black phosphorus has shown great promise in wound healing. However, few studies have explored the bio-effects of BP to promote in situ skin regeneration based on its nanoproperties. Here, to investigate whether black phosphorus nanosheets have positive bio-effects on in situ skin repair, we verified black phosphorus nanosheets' positive effects on angiogenic and anti-inflammatory abilities in vitro. Next, the in vivo evaluation performed on the rat large full-thickness excisional wound splinting model more comprehensively showed that the positive bio-effects of black phosphorus nanosheets are multilevel in wound healing, which can effectively enhance anti-inflammatory ability, angiogenesis, collagen deposition, and skin re-epithelialization. Then, multiomics analysis was performed to explore further the mechanism of black phosphorus nanosheets' regulation of endothelial cells in depth. Molecular mechanistically, black phosphorus nanosheets activated the JAK-STAT-OAS signaling pathway to promote cellular function and mitochondrial energy metabolism in endothelial cells. This study can provide a theoretical basis for applying two-dimensional black phosphorus nanosheets as nanomedicine to achieve in situ tissue regeneration in complex human pathological microenvironments, guiding the subsequent optimization of black phosphorus.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma.

Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.

Reduction-responsive nucleic acid nanocarrier-mediated miR-22 inhibition of PI3K/AKT pathway for the treatment of patient-derived tumor xenograft osteosarcoma.

miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.

Kinome-wide CRISPR-Cas9 knockout screens revealed PLK1 as a therapeutic target for osteosarcoma.

Osteosarcoma is the most common malignant bone tumor, tending to be aggressive and recurrent. The therapeutic development for treating osteosarcoma has been largely hampered by the lack of effective and specific targets. Using kinome-wide CRISPR-Cas9 knockout screens, we systematically revealed a cohort of kinases essential for the survival and growth of human osteosarcoma cells, in which Polo-like kinase 1 (PLK1) appeared as a specific prominent hit. PLK1 knockout substantially inhibited proliferation of osteosarcoma cells in vitro and the tumor growth of osteosarcoma xenograft in vivo. Volasertib, a potent experimental PLK1 inhibitor, can effectively inhibit the growth of the osteosarcoma cell lines in vitro. It can also disrupt the development of tumors in the patient-derived xenograft (PDX) models in vivo. Furthermore, we confirmed that the mode of action (MoA) of volasertib is primarily mediated by the cell-cycle arrest and apoptosis triggered by DNA damage. As PLK1 inhibitors are entering phase III clinical trials, our findings provide important insights into the efficacy and MoA of the relevant therapeutic approach for combating osteosarcoma.

Do green innovation, I.C.T., and economic complexity matter for sustainable development of B.R.I. economies: moderating role of higher education.

The research intends to enlarge the environmental economics literature by displaying the probable mechanisms between green innovation, higher education, and sustainable development. In the context of a new era, sustainability faces challenging obstacles. Many studies have looked at fundamental factors affecting CO2 emissions, while the impact of green innovation and higher education is essential but mostly ignored. This study looked at 60 Belt and Road Initiative (B.R.I.) economies to see how factors, including green innovation, economic complexity index, I.C.T., and higher education, affect carbon emissions in the presence of sustainable development using annual data from 2000-2020. In order to calculate the persistence of the connection between the factors, this research uses the CS-ARDL. The results' robustness and reliability were examined using PMG estimation. The results indicate that the economic complexity index and urbanization positively impact carbon emission (CO2). Higher education (E.D.U.) has a significant positive impact in the short run and a negative effect in the long run-on carbon emissions. Similarly, information and communication technology (I.C.T.) and green innovation have a negative impact on carbon emission (CO2). Moreover, the results indicate that the moderate effect of green innovation with economic complexity index, information and communication technology, and higher education has a negative impact on carbon emission. The estimated coefficients also provide significant policy implications for the chosen and the other developing markets in designing an adequate route ahead to a sustainable environment.

IL-11Rα-targeted nanostrategy empowers chemotherapy of relapsed and patient-derived osteosarcoma.

Osteosarcoma (OS) is a rare but frequently lethal bone malignancy in children and adolescents. The adjuvant chemotherapy with doxorubicin (Dox) and cisplatin remains a mainstream clinical practice though it affords only limited clinical benefits due to low tumor deposition, dose-limiting toxicity and high rate of relapse/metastasis. Here, taking advantage of high IL-11Rα expression in the OS patients, we installed IL-11Rα specific peptide (sequence: cyclic CGRRAGGSC) onto redox-responsive polymersomes encapsulating Dox (IL11-PDox) to boost the specificity and anti-OS efficacy of chemotherapy. Of note, IL-11Rα peptide at a density of 20% greatly augmented the internalization, apoptotic activity, and migration inhibition of Dox in IL-11Rα-overexpressing 143B OS cells. The active targeting effect of IL11-PDox was supported in orthotopic and relapsed 143B OS models, as shown by striking repression of tumor growth and lung metastasis, and substantial survival benefits over free Dox control. We further verified that IL11-PDox could effectively inhibit patient-derived OS xenografts. IL-11Rα-targeted nanodelivery of chemotherapeutics provides a potential therapeutic strategy for advanced osteosarcoma.

Application of Smartphone Otoscope in Telemedicine in Rural Medical Consortium in Eastern China in the COVID-19 Era.

Purpose: This study aimed to evaluate the effectiveness of smartphone otoscope telemedicine in the rural medical consortium in East China in the COVID-19 era. Methods: This prospective study was conducted within a rural medical consortium that provides health care services by integrating medical resources in the same area. When a patient visited primary health care (PHC) for ear diseases, the PHC provider used a smartphone otoscope to examine the patient's external ear canal and eardrum, and then sent photos or videos of the patient's ear to the otolaryngologist at the lead hospital via WeChat group. The otolaryngologist provided remote diagnosis and management recommendations to the PHC provider. The following data were recorded: age and gender, outpatient diagnosis, disease duration, sides, duration of treatment, telemedicine visits, treatment outcomes, patient satisfaction, and PHC providers' self-evaluation score. Results: A total of 83 patients were included in the study, including 43 males and 40 females, with a mean age of 44.6 ± 19.7 years (range 3-83 years). The duration of treatment for these patients was 14.0 (7,14) days. PHC visits were 2.2 ± 1.1 times (range: 1-7 times). Telemedicine visits ranged from 1 to 5, with a mean of 1.8 ± 0.9. Among of patients, 62 (74.7%) were cured, 21 (25.3%) improved, and 0 (0%) were ineffective. Sixty-five patients (78.3%) were very satisfied, 16 (19.3%) patients were somewhat satisfied, and two patients (2.4%) were dissatisfied. Based on the self-reported helpfulness, the primary health care providers assessed telemedicine as very helpful (n = 63, 75.9%), helpful (n = 20, 24.1%), and unhelpful (n = 0, 0%). Conclusions: Smartphone otoscope telemedicine in the medical consortium can effectively improve the ability of rural PHC providers to diagnose and treat ear diseases, save time and costs for patients, and improve patient satisfaction.

Osteoconductive and osteoinductive biodegradable microspheres serving as injectable micro-scaffolds for bone regeneration.

There are intensive needs for scaffolds with new designs to meet the diverse requirements of bone repairing. Biodegradable microspheres are highlighted as injectable micro-scaffolds thanks to their advantages in filling irregular defects via a minimally invasive surgery. In this study, microspheres with surface micropores were made via the W1/O/W2 double emulsion method using amphiphilic triblock copolymers (PLLA-PEG-PLLA) composed of poly(L-lactide) (PLLA) and poly(ethylene glycol) (PEG) segments. When the PEG fraction was controlled as 10 wt.%, the microspheres demonstrated higher cell affinity than the smooth-surfaced PLLA microspheres. After being further functionalized with polydopamine coating and apatite deposition, the PLLA-PEG-PLLA microspheres could up-regulate the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) significantly. Before subcutaneous implantation, bone morphogenetic protein-2 (BMP-2) was adsorbed onto the biomineralized microspheres by taking advantages of the strong affinity of apatite to BMP-2. The resulted microspheres induced ectopic osteogenesis efficiently without causing biocompatibility problems. In summary, this study provided a simple strategy to prepare functionalized microspheres with osteoconductivity and osteoinductivity, which showed great potential in promoting bone regeneration as injectable micro-scaffolds.

Building Osteogenic Microenvironments With Strontium-Substituted Calcium Phosphate Ceramics.

Bioceramics have experienced great development over the past 50 years. Modern bioceramics are designed to integrate bioactive ions within ceramic granules to trigger living tissue regeneration. Preclinical and clinical studies have shown that strontium is a safe and effective divalent metal ion for preventing osteoporosis, which has led to its incorporation in calcium phosphate-based ceramics. The local release of strontium ions during degradation results in moderate concentrations that trigger osteogenesis with few systemic side effects. Moreover, strontium has been proven to generate a favorable immune environment and promote early angiogenesis at the implantation site. Herein, the important aspects of strontium-enriched calcium phosphate bioceramics (Sr-CaPs), and how Sr-CaPs affect the osteogenic microenvironment, are described.

Nano-Hydroxyapatite Modulates Osteoblast Differentiation Through Autophagy Induction via mTOR Signaling Pathway.

Hydroxyapatite (HAP) plays an important role in skeleton formation and bone remodeling. Synthetic HAP is similar to naturally occurring HAP and has been widely used in orthopedic and dental implantation. While it is known nano-HAP easily aggregates at high concentrations, the intracellular fate and mechanisms-of-action of dispersed nano-HAP in osteoblast differentiation remain to be fully elucidated. In the present study, we treated the osteoblast cell line MC3T3E1 with autoclaved nano-HAP and added sodium hexametaphosphate to control nanoparticle agglomeration. Dispersed nano-HAP promoted osteoblast differentiation in a dose-dependent manner. Our findings further revealed that the internalized nano-HAP particles were located in typical autophagic vacuoles and increased the ratio of LC3II/LC3I, indicating nano-HAP induced cell autophagy. Moreover, the induction of autophagy by nano-HAP was via mTOR signaling pathway which also concentration dependent. Collectively, these results reveal nano-HAP modulates osteoblast differentiation by mediating autophagy in a dose-dependent manner.

Characterization of hepatitis B virus (HBV) preS/S gene mutations in blood donors with occult HBV infection in the Baoji area of North China.

BACKGROUND: Occult hepatitis B virus (HBV) infection (OBI) in blood donors was investigated in the Baoji area of North China, and OBI-related viral mutations in donors were characterized. STUDY DESIGN AND METHODS: In total, 110,843 blood donor samples that were consecutively collected from December 2011 to March 2015 at the Baoji Blood Center were examined. Hepatitis B surface antigen-negative and HBV DNA-positive OBI samples were amplified for sequence analysis of OBI-related mutations in the HBV preS/S region. HBV genomes from 108 adult patients with chronic hepatitis B from North China were used as controls. RESULTS: OBI was detected in 60 (1:1847) individual blood donors. All OBI samples were negative for hepatitis B e-antigen, and 55 were positive for anti-hepatitis B core antigen. The preS/S genes were successfully sequenced for 43 OBI samples. OBI-related S gene mutations in the major hydrophilic region were detected more frequently in blood donors with OBI than that in controls (51.16 vs. 12.96%; p < 0.01). Specifically, the incidence of five OBI-related major hydrophilic region mutations (sS117T, sT118K, sT131N, sT134Y/L, and sD144E) was significantly higher in blood donors with OBI than in controls. In addition, the coexistence of multiple OBI-related mutations in the major hydrophilic region was detected more frequently in donors than in controls (30.23 vs. 1.85%; p < 0.01), and preS deletions greater than 33 base pairs also were detected more frequently in blood donors with OBI than in controls. CONCLUSION: OBI in blood donors should be addressed attentively in the Baoji area of North China, and HBV preS/S gene mutations may play an important role in OBI prevalence in the area.

[Effects of immunosuppressants on proliferation of pheochromocytoma 12 and L929 cells].

OBJECTIVE: To explore the effects of several immunosuppressants on the proliferation of pheochromocytoma 12 (PC12) and L929 cells. METHODS: Different concentrations of methylprednisolone (10(-3), 10(-4), 10(-6) and 10(-8) mol/L), cyclosporin A (CsA, 10(-5), 10(-6), 10(-7) and 10(-8) mol/L) and FK506 (10(-6), 10(-7), 10(-8) and 10(-9) mol/L) were administrated to the PC12 and L929 cells, while control group was given no drugs. At 24, 48 and 72 hours after administration, the cell proliferation was measured with MTT methods respectively. The results were compared and analyzed statistically. RESULTS: High concentration methylprednisolone (10(-3) mol/L) and low concentration CsA (10(-8)-10(-7) mol/L) could promote the proliferation of PC12 cells within 48 hours after administration, after that, the proliferation effects were no longer significant. There were no promotion effects for different concentrations of FK506. Under high concentrations, both CsA (10(-6)-1 x 10(-5) mol/L) and methylprednisolone (10(-3) mol/L) could significantly inhibit the proliferation of L929 cells after 24 hours of administration. And high concentration (10(-6) mol/L) FK506 could promote the proliferation of L929 cells transitorily (only for 48 hours after administration). CONCLUSION: 10(-3) mol/L methylprednisolone and 10(-8)-10(-7) mol/L CsA can promote the proliferation of PC12 cells for a short period of time. Both 10(-3) mol/L methylprednisolone and 10(-6)-10(-5) mol/L CsA can significantly inhibit proliferation of L929.

[Effects of immunosuppressants on cultured rat macrophages and Schwann's cells].

OBJECTIVE: To explore the effects of several immunosuppressants on the cell numbers of cultured rat macrophages and Schwann's cells. METHODS: The macrophages and Schwann's cells were cultured from the new-born Wistar rats. Different concentrations of methylprednisolone (10(-3), 10(-4), 10(-6) and 10(-8) mol/L), CsA (10(-5), 10(-6), 10(-7) and 10(-8) mol/L) and FK506 (10(-6), 10(-7), 10(-8) and 10(-9) mol/L) were administrated to the cells, while control group was given no drugs. Twenty-four, 48 and 72 hours after administration, the cells from different concentrations were measured with MTT methods respectively. The results were compared and analyzed statistically. RESULTS: Only high concentration methylprednisolone (10(-4) mol/L) and a certain range of concentrations of CsA (10(-6), 10(-7) and 10(-8) mol/L) and FK506 (10(-7), 10(-8) and 10(-9) mol/L) can provide protection to cultured rat macrophages. Under most concentrations, CsA and FK506 had no effects on the cell number of cultured rat Schwann's cell. Only with high concentration CsA (10(-5) mol/L) and methylprednisolone (10(-3) mol/L) could significantly decreased the cell number of Schwann's cell. Long time (72 hours) and low dosage (10(-8) mol/L) administration of methylprednisolone could significantly protect Schwann's cell. CONCLUSION: High concentration methylprednisolone and some certain concentration CsA and FK506 can protect cultured rat macrophages. But high concentration CsA and methylprednisolone prohibit the proliferation of Schwann's cells. Only long time and low dosage methylprednisolone can protect cultured rat Schwann's cells.