[Mechanism of aqueous extract of Strychni Semen in improving pain in rats with rheumatoid arthritis based on TLR4/TNF-α/MMP-9 signaling pathway].

This study aims to explore the mechanism of aqueous extract of Strychni Semen(SA) in relieving pain in the rat model of rheumatoid arthritis(RA) via Toll-like receptor 4(TLR4)/tumor necrosis factor-α(TNF-α)/matrix metalloproteinase-9(MMP-9) signaling pathway. Firstly, the main chemical components of Strychni Semen were searched against TCMSP, TCMID, ETCM, and related literature, and the main targets of the chemical components were retrieved from TargetNet and SwissTargetPrediction. The main targets of RA and pain were searched against GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). Venny 2.1.0 was used to obtain the common targets shared by Strychni Semen, RA, and pain, and STRING and Cytoscape 3.6.1 were used to build the protein-protein interaction network. Then, molecular docking was carried out in AutoDock Vina. Finally, the rat model of type Ⅱ collagen-induced arthritis(CIA) was established. The up-down method and acetone method were employed to examine the mechanical pain threshold and cold pain threshold of rats, and the pain-relieving effect of SA on CIA rats was evaluated comprehensively. Hematoxylin-eosin(HE) staining was employed to evaluate the histopathological changes of joints in CIA rats. The expression levels of key target proteins was determined by immunohistochemistry and Western blot, and the mRNA levels of key targets were determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). The results of network prediction showed that Strychni Semen may act on the TLR4/TNF-α/MMP-9 signaling pathway to exert the pain-relieving effect. The results of molecular docking showed that brucine, the main active component of SA, had strong binding ability to TLR4, TNF-α, and MMP-9. The results of animal experiments showed that SA improved the mechanical and cold pain sensitivity(P<0.05, P<0.01) and reduced the joint histopathological score of CIA rats(P<0.01). In addition, medium and high doses of SA down-regulated the protein and mRNA levels of TNF-α, TLR4, and MMP-9(P<0.05,P<0.01). In conclusion, SA alleviated the mechanical pain sensitivity, cold pain sensitivity, and joint histopathological changes in CIA rats by inhibiting the over activation of TLR4/TNF-α/MMP-9 signaling pathway.

Near-infrared imaging of head and neck squamous cell carcinoma using indocyanine green that targets the αvß6 peptide.

Significance: Head and neck squamous cell carcinoma (HNSCC) has a particularly poor prognosis. Improving the surgical resection boundary, reducing local recurrence, and ultimately ameliorating the overall survival rate are the treatment goals. Aim: To obtain a complete surgical resection (R0 resection), we investigated the use of a fluorescent imaging probe that targets the integrin subtype αvß6, which is upregulated in many kinds of epithelial cancer, using animal models. Approach: αvß6 expression was detected using polymerase chain reaction (PCR) and immunoprotein blotting of human tissues for malignancy. Protein expression localization was observed. αvß6 and epidermal growth factor receptor (EGFR) were quantified by PCR and immunoprotein blotting, and the biosafety of targeting the αvß6 probe material was examined using Cell Counting Kit-8 assays. Indocyanine green (ICG) was used as a control to determine the localization of the probe at the cellular level. In vivo animal experiments were conducted through tail vein injections to evaluate the probe's imaging effect and to confirm its targeting in tissue sections. Results: αvß6 expression was higher than EGFR expression in HNSCC, and the probe showed good targeting in in vivo and in vitro experiments with a good safety profile. Conclusions: The ICG-αvß6 peptide probe is an exceptional and sensitive imaging tool for HNSCC that can distinguish among tumor, normal, and inflammatory tissues.

Protein profile analysis of Jilin white goose testicles at different stages of the laying cycle by DIA strategy.

BACKGROUND: Jilin white goose is an excellent local breed in China, with a high annual egg production and laying eggs mainly from February to July each year. The testis, as the only organ that can produce sperm, can affect the sexual maturity and fecundity of male animals. Its growth and development are affected and regulated by a variety of factors. Proteomics is generally applied to identify and quantify proteins in cells and tissues in order to understand the physiological or pathological changes that occur in tissues or cells under specific conditions. Currently, the female poultry reproductive system has been extensively studied, while few related studies focusing on the regulatory mechanism of the reproductive system of male poultry have been conducted. RESULTS: A total of 1753 differentially expressed proteins (DEPs) were generated in which there were 594, 391 and 768 different proteins showing differential expression in three stages, Initial of Laying Cycle (ILC), Peak of Laying Cycle (PLC) and End of Laying Cycle (ELC). Furthermore, bioinformatics was used to analyze the DEPs. Gene ontology (GO) enrichment, Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis were adopted. All DEPs were found to be implicated in multiple biological processes and pathways associated with testicular development, such as renin secretion, Lysosomes, SNARE interactions in vesicle trafficking, the p53 signaling pathway and pathways related to metabolism. Additionally, the reliability of transcriptome results was verified by real-time quantitative PCR by selecting the transcript abundance of 6 selected DEPs at the three stages of the laying cycle. CONCLUSIONS: The funding in this study will provide critical insight into the complex molecular mechanisms and breeding practices underlying the developmental characteristics of testicles in Jilin white goose.

Comparison of rabbit ATLG and ATG for GVHD prophylaxis in hematological malignancies with haploidentical hematopoietic stem cell transplantation.

Rabbit anti-human T lymphocyte globulin (ATLG) and anti-thymocyte globulin (ATG) are commonly used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT). Yet, their efficacy and safety have seldom been compared in hematological malignancies with haploidentical HSCT. A retrospective analysis with 28 ATLG (total dosage, 20-30 mg/kg) and 18 ATG (total dosage, 8-10 mg/kg) patients were performed. The cumulative incidences of chronic GVHD and relapse were comparable between both groups. ATLG showed a trend towards a lower acute GVHD incidence (28.6% vs. 44.4%, P = 0.242) and 3-year non-relapse mortality (10.7% vs. 27.8%, P = 0.160), and had a significantly higher 3-year overall survival (OS, 64.3% vs. 33.3%, P = 0.033) and GVHD-free and relapse-free survival (GRFS, 32.1% vs. 11.1%, P = 0.045) compared with ATG. Multivariate Cox regression analysis demonstrated ATLG was independently associated with a favorable OS (hazard ratio [HR] = 0.37, 95% confidence interval [CI]: 0.16-0.86, P = 0.020) and GRFS (HR = 0.51, 95%CI: 0.26-1.00, P = 0.051). Furthermore, ATLG had a lower risk of fever (25.0% vs. 61.1%, P = 0.014) and hemorrhage cystitis (7.1% vs. 38.9%, P = 0.008) than ATG-T. In conclusion, ATLG confers more survival benefit and a better safety profile than ATG and can be used in hematological malignancies with haploidentical HSCT. Prospective designed trials with a larger sample size are warranted to confirm the results in the future.

Optimizing cervical target volume in patients with nasopharyngeal cancer based on nodal drainage distance.

OBJECTIVES: To determine the potential nodal drainage distances of nasopharyngeal carcinoma (NPC) by investigating spatial distribution of metastatic lymph nodes (LNs). METHODS: NPC patients with at least two ipsilateral metastatic LNs were enrolled. LN spreading distances were analyzed in non-restricted direction, cranial-to-caudal direction, and between the two most caudal LNs. Euclidean distance (ED) and vertical distance (VD) between any two LNs were computed. The nearest-neighbor ED and VD covering 95% of LNs or patients (p95-ED and p95-VD) were considered drainage distances, and were further validated by independent internal and external cohorts with recurrent LNs. RESULTS: In all, 5836 metastatic LNs in 948 patients were contoured. Corresponding to the three scenarios, Per-LN level, the p95-EDs were 2.83, 3.28, and 3.55 cm; and p95-VDs were 2.17, 2.32, and 2.63 cm, respectively. Per-patient level, the p95-EDs were 3.25, 3.95, and 3.81 cm; and p95-VDs were 2.67, 2.81, and 2.73 cm, respectively. In internal validation, over 95% of recurred-LNs occurred within ED of 2.91 cm and VD of 0.82 cm to the neighbor LN, and the corresponding distances in external validation were 2.77 and 0.67 cm, respectively. CONCLUSIONS: In NPC, the maximum LN drainage distance was 3.95 cm without considering the direction. Specifically, in cranial-to-caudal direction, the sufficient vertical drainage distance was 2.81 cm, indicating that a 3-cm extension from the most inferior node may be rational as caudal border of the prophylactic clinical target volume (CTV). These findings promote in-depth understanding of nodal spreading patterns, uncovering paramount evidence for individualized CTV.

miR-140-y targets TCF4 to regulate the Wnt signaling pathway and promote embryonic feather follicle development in Hungarian white goose.

Goose down feather has become one of the most important economical products in the goose breeding industry and it provides several essential physiological roles in birds. Therefore, understanding and regulating the development of skin and feather follicles during embryogenesis is critical for avian biology and the poultry industry. MicroRNAs are known to play an important role in controlling gene expression during skin and feather follicle development. In this study, bioinformatics analysis was conducted to select miR-140-y as a potential miRNA involved in skin and feather follicle development and to predict TCF4 as its target gene. This gene was expressed at significant levels during embryonic feather follicle development, as identified by qPCR and Western blot. The targeting relationship was confirmed by a dual-luciferase assay in 293T cells. Then, the miR-140-y/TCF4 function in dermal fibroblast cells was explored. The results showed that miR-140-y could suppress the proliferation of goose embryonic dermal fibroblast cells (GEDFs) by suppressing the activity of some Wingless-types (Wnt) pathway related genes and proliferation marker genes, while miR-140-y inhibition led to the opposite effect. Similarly, the inhibition of the TCF4 gene results in blocking the proliferation of GEDFs by reducing the activity of some Wnt pathway-related genes. Finally, the co-transfection of miR-140-y inhibitor and siRNA-TCF4 results in a rescue of the TCF4 function and an increase of the Wnt signaling pathway and GEDFs proliferation. In conclusion, these results demonstrated that the miR-140-y-TCF4 axis influences the activity of the Wnt signaling pathway and works as a dynamic regulator during skin and feather follicle development.

Adjuvant activity of cordycepin, a natural derivative of adenosine from Cordyceps militaris, on an inactivated rabies vaccine in an animal model.

Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.

Polarization-separated feedback spectral beam combining source.

A novel, to the best of our knowledge, structure for spectral beam combining (SBC) is proposed, utilizing a polarization-separated feedback (PSF). A polarization separation element is introduced to separate the laser beam into a TE-polarized light and a TM-polarized light. The lower-power light is selected as the external feedback to adjust the resonant wavelength, while the other light is combined spectrally. Compared to the conventional SBC source with a similar feedback, the power and efficiency of the PSFSBC are improved by approximately 20%. Additionally, the beam quality in the non-SBC direction is optimized by 10%, and the power on the output coupler is reduced to nearly one-third. This provides an effective method for achieving an optimized SBC performance.

USP11 promotes glycolysis by regulating HIF-1α stability in hepatocellular carcinoma.

Understanding the mechanisms underlying metastasis in hepatocellular carcinoma (HCC) is crucial for developing new therapies against this fatal disease. Deubiquitinase ubiquitin-specific protease 11 (USP11) belongs to the deubiquitinating family and has previously been reported to play a critical role in cancer pathogenesis. Although it has been established that USP11 can facilitate the metastasis and proliferation ability of HCC, the underlying regulatory mechanisms are poorly understood. The primary objective of this research was to reveal hitherto undocumented functions of USP11 during HCC progression, especially those related to metabolism. Under hypoxic conditions, USP11 was found to significantly impact the glycolysis of HCC cells, as demonstrated through various techniques, including RNA-Seq, migration and colony formation assays, EdU and co-immunoprecipitation. Interestingly, we found that USP11 interacted with the HIF-1α complex and maintained HIF-1α protein stability by removing ubiquitin. Moreover, USP11/HIF-1α could promote glycolysis through the PDK1 and LDHA pathways. In general, our results demonstrate that USP11 promotes HCC proliferation and metastasis through HIF-1α/LDHA-induced glycolysis, providing new insights and the experimental basis for developing new treatments for this patient population.

Long-Term Outcomes of Endoscopic Resection versus Open Surgery for Locally Advanced Sinonasal Malignancies in Combination with Radiotherapy.

Objective Our objective was to compare the long-term outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies (SNMs). Methods Data for continuous patients with sinonasal squamous cell carcinoma and adenocarcinoma who received surgery (endoscopic or open surgery) combined with radiotherapy in our center between January 1999 and December 2016 were retrospectively reviewed. A 1:1 matching with propensity scores was performed. Overall survival (OS), progression-free survival (PFS), and local recurrence rate (LRR) were evaluated. Results We identified 267 eligible patients, 90 of whom were included after matching: 45 patients in the endoscopy group and 45 in the open group. The median follow-up time was 87 months. In the endoscopic group, 84.4% of patients received intensity-modulated radiotherapy (IMRT), with a mean gross tumor volume (GTV) dose of 68.28 Gy; in the open surgery group, 64.4% of patients received IMRT, with a mean GTV dose of 64 Gy. The 5-year OS, PFS, and LRR were 69.9, 58.6, and 24.5% in the endoscopic group and 64.6, 54.4, and 31.8% in the open surgery group, respectively. Multivariable regression analysis revealed that the surgical approach was not associated with lower OS, PFS, or LRR. The overall postoperative complications were 13% in the endoscopic group, while 21.7% in the open group. Conclusion For patients with locally advanced SNMs, minimally invasive endoscopic resection, in combination with a higher radiation dose and new radiation techniques such as IMRT, yields survival outcomes similar to those of open surgery in combination with radiotherapy.

CLAG combined with total body irradiation as intensive conditioning chemotherapy prior to allogeneic hematopoietic stem cell transplantation in patients with refractory or relapsed acute myeloid leukemia.

Refractory or relapsed acute myeloid leukemia (R/R AML) remains the major challenge of AML treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only valid option to achieve cure, but the prognosis is still dismal. We conducted a retrospective analysis for the feasibility of CLAG regimens (cladribine, cytarabine, and granulocyte colony-stimulating factor) combined with total body irradiation (TBI) as new intensive conditioning chemotherapy prior to HSCT in R/R AML. A total of 70 patients, including 21 primary refractory and 49 relapsed AML, were analyzed. Forty-nine (70%) patients had extramedullary diseases, and 54 (77%) patients received haploidentical transplantation. Except for one who died before white blood cell engraftment, all of the 69 evaluable patients achieved measurable residual disease (MRD) negative complete remission. The 3-year overall survival (OS) and relapse-free survival (RFS) rates were 46.0% (95% confidence interval [CI], 33.5-57.7%) and 38.5% (95%CI, 26.8-50.0%). The 1-year cumulative incidences of relapse and non-relapse mortality (NRM) were 38.6% (95%CI, 27.3-49.3%) and 11.6% (95%CI: 5.4-20.3%), respectively. The presence of chronic graft-versus-host disease (cGVHD) showed a trend to be associated with a lower risk of relapse (P = 0.054) and extramedullary diseases with a higher risk of NRM (P = 0.074). Multivariate analyses identified low leukemia burden pre-HSCT (defined as bone marrow blasts ≤ 50%) and cGVHD as independent factors associated with favorable OS and RFS. In conclusion, intensive conditioning with CLAG regimens plus TBI may be an effective and well-tolerated choice for R/R AML patients undergoing allo-HSCT.

Unrevealing the therapeutic benefits of radiotherapy and consolidation immunotherapy using ctDNA-defined tumor clonality in unresectable locally advanced non-small cell lung cancer.

Progression occurs in approximately two-thirds of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving chemoradiation and consolidation immunotherapy. Molecular indicators for outcome prediction are under development. A novel metric, the ratio of mean to max variant allele frequency (mmVAF), was derived from 431 pre-treatment tissue biopsies from The Cancer Genome Atlas and evaluated in serial circulating tumor DNA (ctDNA) from 70 LA-NSCLC patients receiving definitive radiotherapy/chemoradiotherapy (RT/CRT) with/without immunotherapy. High mmVAFs in pre-treatment tissue biopsies, indicating clonal predominant tumors (P < 0.01), were associated with inferior overall survival [OS, hazard ratio (HR): 1.48, 95 % confidence interval (CI): 1.11-1.98]. Similar associations of mmVAF with clonality (P < 0.01) and OS (HR: 2.24, 95 % CI: 0.71-7.08) were observed in pre-treatment ctDNA. At 1-month post-RT, ctDNA mmVAF-high patients receiving consolidation immunotherapy exhibited improved progression-free survival (PFS) compared to those who did not (HR: 0.14, 95 % CI: 0.03-0.67). From the baseline to week 4 of RT and/or 1-month post-RT, survival benefits from consolidation immunotherapy were exclusively observed in ctDNA mmVAF-increased patients (PFS, HR: 0.39, 95 % CI: 0.14-1.15), especially in terms of distant metastasis (HR: 0.11, 95 % CI: 0.01-0.95). In summary, our longitudinal data demonstrated the applicability of ctDNA-defined clonality for prognostic stratification and immunotherapy benefit prediction in LA-NSCLC.

Severe graft-versus-host disease post allogeneic hematopoietic stem cell transplantation due to loss of HLA heterozygosity in recipient lymphocytes after full graft rejection.

Germ cell tumors complicated by hematological malignancy (HM) are a rare clinical phenomenon. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially effective therapy, but graft-versus-host disease (GVHD) is a life-threatening complication. We report a case of a 13-year-old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia. After chemotherapy, she received allo-HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence. However, she developed severe, multiorgan GVHD-like manifestations. DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.

The impact of platelet indices on ischemic stroke: a Mendelian randomization study and mediation analysis.

Introduction: Platelet indices (PIs) are hematological parameters that indicate the number, morphology, and activation of platelets. Although some clinical trials suggest an association between PIs and the risk of stroke, the lack of robust evidence is attributed to confounding effects and reverse causation. Objective: This study aimed to evaluate the association between PIs and stroke risk through Mendelian randomization (MR) while exploring the mediating effect of blood pressure in this association. Methods: We identified genetic variants associated with PIs, including platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), in the UK Biobank (n = 350,474). Relevant genome-wide association studies were utilized to gather summary statistics pertaining to the traits of interest. We primarily used the inverse-variance weighted analysis to obtain estimates for individual causal power. Result: We observed a positive correlation between genetically predicted increases in PCT levels with the stroke onset [PCT: OR (95%CI) = 1.113(1.047, 1.183), p < 0.001]. However, no significant causal relationship was found between PLT, PDW, and MPV and the risk of stroke [PLT: OR (95%CI) = 1.037(0.979, 1.098), p = 0.221; PDW: OR (95%CI) = 0.973(0.923, 1.024), p = 0.294; MPV: OR (95%CI) = 0.990(0.945, 1.038), p = 0.675]. Multivariable MR analyses and mediation analysis found that the proportion mediated by systolic blood pressure (SBP) is 23.71% [95%CI (10.85-33.31%)] and the proportion mediated by diastolic blood pressure (DBP) is 28.09% [95%CI (12.92-39.63%)]. Conclusion: This large MR study presents evidence for the potential causal relationship between the PCT level and the risk of ischemic stroke, which might be mediated by blood pressure.

Network pharmacology-based research on the effect of Scutellaria baicalensis on osteosarcoma and the underlying mechanism.

To explore the anti-tumor effects of Scutellaria baicalensis on osteosarcoma and its mechanism. Network pharmacology and molecular docking techniques were applied to investigate the effect and mechanism of Scutellaria baicalensis on osteosarcoma (OS). We analyzed the protein-protein interaction (PPI) network for potential targets of Scutellaria baicalensis for treating osteosarcoma and identified hub targets. We used KM curves to screen for hub targets that could effectively prolong the survival time of OS patients. We systematically performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the Scutellaria baicalensis potential targets and predicted the Scutellaria baicalensis molecular mechanism and function in treating osteosarcoma. Through molecular docking, the binding process between the hub targets, which could prolong the survival time of sarcoma patients, and Scutellaria baicalensis was simulated. PPI network analysis of potential therapeutic targets discriminated 12 hub targets. The KM curves of the hub targets showed that upregulation of RXRA, RELA, ESR1, TNF, IL6, IL1B, and RB1 expression, and downregulation of MAPK1, VEGFA, MAPK14, CDK1, and PPARG expression were effective in improving the 5-year survival rate of OS patients. GO and KEGG enrichment demonstrated that Scutellaria baicalensis regulated multiple signaling pathways of OS. Molecular docking results indicated that Scutellaria baicalensis could bind freely to the above hub target, which could prolong the survival time of sarcoma patients. Scutellaria baicalensis acted on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Scutellaria baicalensis appears to have the potential to serve as a therapeutic drug for osteosarcoma and to prolong the survival of OS patients.

Astragaloside IV Protects Against IL-1ß-Induced Chondrocyte Damage via Activating Autophagy.

BACKGROUND: Osteoarthritis (OA) is a chronic inflammatory condition that affects the articular cartilage. Astragaloside IV (AS-IV) constitutes the primary active component of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV demonstrates anti-inflammatory and anti-apoptotic attributes, exhibiting therapeutic potential across various inflammatory and apoptosis-related disorders. Nevertheless, its pharmaceutical effects in OA are yet to be fully defined. OBJECTIVES: This study aimed to investigate the protective impact of AS-IV on rat chondrocytes treated with IL-1ß and ascertain whether autophagy plays a role in this effect. METHODS: Chondrocytes were isolated and cultivated from the knee joints of neonatal SD mice. The study included the blank control group, the model group, and the AS-IV concentration gradient group (50, 100, 200 µmol/L) to intervene with chondrocytes. The MTT assay was employed to assess cell viability at varying culture periods, enabling the determination of suitable concentration and duration. Subsequently, chondrocytes were treated with the optimal AS-IV concentration and divided into three groups: the model group replicated IL-1ß-induced inflammatory chondrocyte injury, the AS-IV group received a co-culture of AS-IV and IL-1ß, and a blank control group was established. Changes in cell morphology and structure were observed using ghost pen cyclic peptide staining. ELISA was used to measure TNF-α and GAG levels in cell supernatants. RT-qPCR assessed p62 and LC3 mRNA expression, while Western Blot evaluated p62 and LC3Ⅱ/Ⅰ protein expression. RESULTS: AS-IV promoted chondrocyte proliferation and concurrently inhibited cell apoptosis. An optimal AS-IV dose of 200 µmol/L and a suitable reaction time of 48 h were identified. Ghost pen cyclic peptide staining indicated that the model group's cytoskeleton exhibited fusiform changes with reduced immunofluorescence intensity, as opposed to the blank control group. The AS-IV group displayed more polygonal cytoskeletal morphology with increased immunofluorescence intensity. AS-IV reduced TNF-α levels and elevated GAG levels in the culture supernatant. Additionally, AS-IV lowered p62 mRNA and protein expression while increasing LC3 mRNA expression in cultured chondrocytes. CONCLUSION: Our findings suggest that AS-IV mitigates inflammatory chondrocyte injury, safeguarding chondrocytes through a potential autophagy suppression mechanism. These results imply that AS-IV could offer preventive advantages for OA.

Clinical Characteristics and Long-Term Outcomes following Surgery Combined with Adjuvant Radiotherapy for Patients with Frontal Sinus Malignancies.

Objectives Primary frontal sinus malignancies (FSMs) are the rarest sinonasal cancers. This study aimed to determine clinicopathologic characteristics of primary FSMs and provide long-term survival outcomes. Design This study is a retrospective review. Setting The study was conducted at a tertiary medical center. Participants Patients who participated in this study were diagnosed with primary FSMs. Main Outcome Measures Median survival time is the primary outcome measure of this study. Results In this series, the median age was 48 years (30-53 years) and all patients were male. There were five cases with squamous cell carcinoma and one with osteosarcoma. All cases presented with locally advanced disease without regional lymphatic metastasis, including five cases of stage III and one case of stage II. The two most common pathways of tumor invasion were as follows: local tumor broke posteriorly through bone wall and invaded dura mater, followed by frontal lobe; local tumor infiltrated downward through the floor of frontal sinus into ethmoid sinus, thereafter invaded laterally orbit and orbital contents. All patients received surgery followed by postoperative radiotherapy at the total doses of 50 to 75.95 Gy. Among them, only one patient underwent R0 resection, the rest of patients underwent R1/R2 resection. With a median survival time of 56 months (32-76 months), two patients receiving R1/R2 resection developed treatment failure and died within 5 years, including one case with local recurrence and one with local recurrence, thereafter distant metastasis. Conclusion The majority of FSMs presented with peripherally invasive progression lesions which led to a high ratio of R1/R2 resection. Surgery combined with postoperative radiotherapy might result in satisfactory efficacy.