Virtual surgical planning is a useful tool in the surgical management of mandibular condylar fractures.

PURPOSE: The aim of this study is to evaluate the application value of virtual surgical planning in the management of mandibular condylar fractures and to provide a reliable reference. METHODS: This was a prospective randomized controlled study and recruited 50 patients requiring surgical treatment for their mandibular condylar fractures. The inclusion criteria were patients (1) diagnosed with a condylar fracture by two clinically experienced doctors and required surgical treatment; (2) have given consent for the surgical treatment; and (3) had no contraindications to the surgery. Patients were excluded from this study if: (1) they were diagnosed with a non-dislocated or only slightly dislocated condylar fracture; (2) the comminuted condylar fracture was too severe to be treated with internal reduction and fixation; or (3) patients could not complete follow-up for 3 months. There were 33 male and 17 female patients with 33 unilateral condylar fractures and 17 bilateral condylar fractures included. The 50 patients were randomly (random number) divided into control group (25 patients with 35 sides of condylar fractures) and experimental group (25 patients with 32 sides of condylar fractures). Virtual surgical planning was used in the experimental group, but only clinical experience was used in the control group. The patients were followed up for 1, 3, 6 and 12 months after operation. Variables including the rate of perfect reduction by radiological analysis, the average distance of deviation between preoperative and postoperative CT measurements using Geomagic software and postoperative clinical examinations (e.g., mouth opening, occlusion) were investigated for outcome measurement. SPSS 19 was adopted for data analysis. RESULTS: The average operation time was 180.60 min in the experimental group and 223.2 min in the control group. One week postoperatively, CT images showed that the anatomic reduction rate was 90.63% (29/32) in the experimental group and 68.57% (24/35) in the control group, revealing significant difference (X2 = 4.919, p = 0.027). Geomagic comparative analysis revealed that the average distance of deviation was also much smaller in the experimental group than that in the control group (0.639 mm vs. 0.995 mm; t = 3.824, p < 0.001). CONCLUSION: These findings suggest that virtual surgical planning can assist surgeons in surgical procedures, reduce operative time, and improve the anatomic reduction rate & accuracy, and thus of value in the diagnosis and treatment of condylar fractures.

Mini suture anchor: An effective device for reduction and fixation of displaced temporomandibular joint disc with intracapsular condylar fracture.

PURPOSE: The main aim is to provide clinical reference for the application of mini suture anchor in the reduction and fixation of displaced temporomandibular joint (TMJ) disc with intracapsular condylar fracture. METHODS: From October 2018 to October 2019, 21 patients (31 sides) with intracapsular condylar fractures and articular disc displacement from West China Hospital of Stomatology, Sichuan University were included. The selection criteria were: (1) mandibular condylar fractures accompanied by displacement of the TMJ disc, confirmed by clinical examination, CT scan and other auxiliary examinations; (2) indication for surgical treatment; (3) no surgical contraindications; (4) no previous history of surgery in the operative area; (5) no facial nerve injury before the surgery; (6) informed consent to participate in the research program and (7) complete data. Patients without surgical treatment were excluded. The employed patients were followed up at 1, 3, 6 and 12 months after operation. Outcomes were assessed by success rate of operation, TMJ function and radiological examination results at 3 months after operation. Data were expressed as number and percent and analyzed using SPSS 19.0. RESULTS: All the surgical procedures were completed successfully and all the articular discs were firmly attached to the condyles. The articular disc sufficiently covered the condylar head after the fixation. The fixation remained stable when the mandible was moved in each direction by the surgeons. No complications occurred. The functions of the TMJ were well-recovered postoperatively in most cases. CT scan revealed that the screws were completely embedded in the bone without loosening or displacement. CONCLUSION: Mini suture anchor can provide satisfactory stabilization for the reduced articular disc and also promote the recovery of TMJ functions.

Targeting GRP78 enhances the sensitivity of HOS osteosarcoma cells to pyropheophorbide-α methyl ester-mediated photodynamic therapy via the Wnt/ß-catenin signaling pathway.

Photodynamic therapy (PDT), which is a new method for treating tumors, has been used in the treatment of cancer. In-depth research has shown that PDT cannot completely kill tumor cells, indicating that tumor cells are resistant to PDT. Glucose regulatory protein 78 (GRP78), which is a key regulator of endoplasmic reticulum stress, has been confirmed to be related to tumor resistance and recurrence, but there are relatively few studies on the further mechanism of GRP78 in PDT. Our experiment aimed to observe the role of GRP78 in HOS human osteosarcoma cells treated with pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPα-PDT) and to explore the possible mechanism by which the silencing of GRP78 expression enhances the sensitivity of HOS osteosarcoma cells to MPPα-PDT. HOS osteosarcoma cells were transfected with siRNA-GRP78. Apoptosis and reactive oxygen species (ROS) levels were detected by Hoechst staining and flow cytometry, cell viability was detected by Cell Counting Kit-8 assay, GRP78 protein fluorescence intensity was detected by immunofluorescence, and apoptosis-related proteins, cell proliferation-related proteins, and Wnt pathway-related proteins were detected by western blot. The results showed that MPPα-PDT can induce HOS cell apoptosis and increase GRP78 expression. After successful siRNA-GRP78 transfection, HOS cell proliferation was decreased, and apoptosis-related proteins expressions was increased, Wnt/ß-catenin-related proteins expressions was decreased, and ROS levels was increased. In summary, siRNA-GRP78 enhances the sensitivity of HOS cells to MPPα-PDT, the mechanism may be related to inhibiting Wnt pathway activation and increasing ROS levels.

Protective effect of Qingre Huoxue decoction against myocardial infarction via PI3K/Akt autophagy pathway based on UPLC-MS, network pharmacology, and in vivo evidence.

CONTEXT: Qingre Huoxue (QRHX) decoction, a traditional Chinese medicine, has been widely used to prevent and treat myocardial infarction (MI). OBJECTIVE: This study elucidates the possible mechanisms of QRHX in preventing or treating MI in a rat model. MATERIALS AND METHODS: The chemical constituents of QRHX were identified by UPLC-MS. Sprague-Dawley rats were randomly divided into the Sham (normal saline), Model (normal saline), QRHX-L, QRHX-M and QRHX-H group (n = 10 per group). QRHX decoction was administered by gavage to the rats for 14 days (5, 10 and 20 g/kg/day). The left anterior descending ligation method was performed to develop MI in Model and QRHX groups, and the same surgical procedures excluding ligation sutures were performed for the sham group. Finally, we evaluated cardiac function, myocardial fibrosis degree, serum inflammatory factors, autophagy levels and verified the signalling pathways in vivo. RESULTS: A total of 68 active components of QRHX corresponding to 223 active targets were obtained and 2558 MI-related disease targets were collected. After integration, 123 QRHX anti-MI targets were obtained, and 70 signalling pathways, such as PI3K/Akt, were identified by enrichment analysis. In vivo experiments suggest that QRHX could reduce the degree of myocardial fibrosis, downregulate serum inflammatory factors, and promote autophagy in MI rats. DISCUSSION AND CONCLUSIONS: QRHX plays a protective role in the myocardium by mediating PI3K/Akt signalling pathway to activate autophagy and inhibiting inflammatory factor expression. These findings provide a scientific basis for further research and validation of QRHX as a potential therapeutic for MI.

Cardiolipin-Dependent Mitophagy Guides Outcome after Traumatic Brain Injury.

Mitochondrial energy production is essential for normal brain function. Traumatic brain injury (TBI) increases brain energy demands, results in the activation of mitochondrial respiration, associated with enhanced generation of reactive oxygen species. This chain of events triggers neuronal apoptosis via oxidation of a mitochondria-specific phospholipid, cardiolipin (CL). One pathway through which cells can avoid apoptosis is via elimination of damaged mitochondria by mitophagy. Previously, we showed that externalization of CL to the mitochondrial surface acts as an elimination signal in cells. Whether CL-mediated mitophagy occurs in vivo or its significance in the disease processes are not known. In this study, we showed that TBI leads to increased mitophagy in the human brain, which was also detected using TBI models in male rats. Knockdown of CL synthase, responsible for de novo synthesis of CL, or phospholipid scramblase-3, responsible for CL translocation to the outer mitochondrial membrane, significantly decreased TBI-induced mitophagy. Inhibition of mitochondrial clearance by 3-methyladenine, mdivi-1, or phospholipid scramblase-3 knockdown after TBI led to a worse outcome, suggesting that mitophagy is beneficial. Together, our findings indicate that TBI-induced mitophagy is an endogenous neuroprotective process that is directed by CL, which marks damaged mitochondria for elimination, thereby limiting neuronal death and behavioral deficits.SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) increases energy demands leading to activation of mitochondrial respiration associated with enhanced generation of reactive oxygen species and resultant damage to mitochondria. We demonstrate that the complete elimination of irreparably damaged organelles via mitophagy is activated as an early response to TBI. This response includes translocation of mitochondria phospholipid cardiolipin from the inner membrane to the outer membrane where externalized cardiolipin mediates targeted protein light chain 3-mediated autophagy of damaged mitochondria. Our data on targeting phospholipid scramblase and cardiolipin synthase in genetically manipulated cells and animals strongly support the essential role of cardiolipin externalization mechanisms in the endogenous reparative plasticity of injured brain cells. Furthermore, successful execution and completion of mitophagy is beneficial in the context of preservation of cognitive functions after TBI.

miR-194-5p inhibits LPS-induced astrocytes activation by directly targeting neurexophilin 1.

Astrocytes are vitally involved in the development of neurodegenerative diseases and brain cancers. In this work, we investigated the potential ameliorative role of microRNA-194-5p (miR-194-5p) against lipopolysaccharide (LPS)-induced astrocytes activation and the mechanism underneath. Astrocytes were transfected with miR-194-5p mimic or inhibitor and subsequently induced with LPS. Cell proliferation was measured using MTT assay while Transwell assay was used for assessing cell migration. The concentrations of cyclooxygenase 2 (COX2) and cytokines (tumor necrosis factor-α (TNF-α), transforming growth factor ß (TGF-ß), interleukin (IL)-1ß and IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Gene expression was assessed by quantitative reverse transcription PCR (RT-qPCR) while western blotting was used for quantifying relative protein expression. We found that miR-194-5p, downregulated in LPS-induced astrocytes, significantly inhibited LPS-induced cell proliferation and migration. In addition, miR-194-5p inhibited the release of COX2 and pro-inflammatory cytokines (TNF-α, TGF-ß, IL-1ß and IL-6). Moreover, the silencing of neurexophilin 1 (NXPH1), an in silico and mechanistically confirmed direct target of miR-194-5p, reverted the anti-inflammatory, anti-proliferative and anti-migratory effects of miR-194-5p. We anticipated that miR-194-5 inhibits the proliferation, invasion, and inflammatory reaction in LPS-induced astrocytes by directly targeting NXPH1. These findings hinted that miR-194-5p/NXPH1 axis exerts vital functions in astrocytes activation and neuroinflammation-associated diseases. This finding will open novel avenues for biomedical and neuroscience research.

A newly synthesized oleanolic acid derivative inhibits the growth of osteosarcoma cells in vitro and in vivo by decreasing c-MYC-dependent glycolysis.

Osteosarcoma (OS) is the primary malignant bone tumor with a peak incidence in children and adolescents. However, the little molecular mechanism of pathogenesis has been known and it is urgent to develop new therapeutical strategies to improve outcomes for patients. CDDO-NFM (N-formylmorpholine substituent of CDDO) is a newly synthesized triterpenoid, which is a derivative of oleanolic acid. In this study, we explored whether CDDO-NFM possesses a potential antitumor effect and revealed its molecular mechanism. We found that CDDO-NFM efficiently inhibited cell growth of OS cells and this inhibitory effect was independent of apoptosis-related and cell-cycle-related proteins. CDDO-NFM could decrease the level of glucose uptake, the generation of lactate, and the production of adenosine triphosphate to block the process of glycolysis. In vitro and in vivo cell-based assays showed that CDDO-NFM inhibited glycolysis via degradation of c-MYC rather than activating peroxisome proliferator-activated receptor gamma. Finally, CDDO-NFM could reduce tumor volume and weight with low toxicity, and down-regulate the expression of glycolysis-related enzymes in nude mice. Taken together, these results showed that CDDO-NFM might be a promising antitumor compound.

Ezrin mediates both HGF/Met autocrine and non-autocrine signaling-induced metastasis in melanoma.

Aberrant HGF/Met signaling promotes tumor migration, invasion, and metastasis through both autocrine and non-autocrine mechanisms; however, the molecular downstream signaling mechanisms by which HGF/Met induces metastasis are incompletely understood. We here report that Ezrin expression is stimulated by HGF and correlates with activated HGF/Met, indicating that HGF/Met signaling regulates the expression of Ezrin. We show that HGF/Met signaling activates the transcription factor Sp1 through the MAPK pathway, and activated Sp1 can in turn directly bind to the promoter of Ezrin gene and regulate its transcription. Notably, knockdown of Ezrin expression by shRNAs inhibits the metastasis induced by either HGF/Met autocrine or non-autocrine signaling in syngeneic wildtype and HGF transgenic mouse hosts. We also used small molecule drugs in preclinical mouse models to confirm that Ezrin is one of the downstream molecules mediating HGF/Met signaling-induced metastasis in melanoma. We conclude that Ezrin is a key downstream factor involved in the regulation of HGF/Met signaling-induced metastasis and demonstrate a link between Ezrin and HGF/Met/MAPK/Sp1 activation in the metastatic process. Our data indicate that Ezrin represents a promising therapeutic target for patients bearing tumors with activated HGF/Met signaling.

The C-reactive protein/albumin ratio predicts overall survival of patients with advanced pancreatic cancer.

Recent studies have demonstrated the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in cancer. However, the role of the CRP/Alb ratio in advanced pancreatic cancer (PC) has not been examined. A retrospective study of 233 patients with advanced PC was conducted. We investigated the relationship between the CRP/Alb ratio, clinicopathological variables, and overall survival (OS). The optimal cutoff point of the CRP/Alb ratio was 0.54. A higher CRP/Alb ratio was significantly associated with an elevated neutrophil-lymphocyte ratio (NLR) (P < 0.001) and higher modified Glasgow prognostic score (mGPS) (P < 0.001). Using univariate analyses, we found that the age (P = 0.009), disease stage (P < 0.001), NLR (P < 0.001), mGPS (P < 0.001), and CRP/Alb ratio (P < 0.001) were significant predictors of OS. Patients with a higher CRP/Alb ratio had a worse OS than patients with a lower CRP/Alb ratio (hazard ratio (HR) 3.619; 95 % CI 2.681-4.886; P < 0.001). However, the CRP/Alb ratio was identified as the only inflammation-based parameter with an independent prognostic ability in the multivariate analyses (P < 0.001). The pretreatment CRP/Alb ratio is a superior prognostic and therapeutic predictor of OS in advanced PC.

[Correlation between cyclin-dependent kinase inhibitor p27kip1 and trastuzumab-resistance in gastric cancer].

OBJECTIVE: To investigate the correlation between cyclin-dependent kinase inhibitor p27kip1 and trastuzumab-resistance in gastric cancer.
 METHODS: We selected HER2-overexpressed human gastric cancer cell line NCI-N87 to establish trastuzumab-resistant NCI-N87/TR cell line by stepwise exposure to different doses of trastuzumab. The 50% inhibitory concentration (IC(50)) of trastuzumab and resistance index (RI) were calculated or analyzed by MTT assay. The expression levels of cdk2 and p27kip1 were detected by Western blot. After the treatment with cdk2 inhibitor (Purvalanol A), the expression levels of relevant proteins in NCI-N87/TR cells were detected by Western blot, and the sensitivity to trastuzumab was analyzed by MTT assay. 
 RESULTS: Compared with NCI-N87 cells, the expression of cdk2 was significantly increased in NCI-N87/TR cells (P<0.001), while the expression of p27kip1 showed a significant decrease (P<0.001). Restoration of the p27kip1 protein expression by cdk2 inhibitor (Purvalanol A) increased the sensitivity of NCI-N87/TR to trastuzumab.
 CONCLUSION: Down-regulation of p27kip1 might be a mechanism for triggering trastuzumab resistance to gastric cancer cell line NCI-N87.

Trichosporon asahii infection after total knee arthroplasty: A case report and review of the literature.

Reports of fungal infection after total knee arthroplasty are extremely rare. In most reports, the infecting organism is a Candida species. The present report describes a case involving a 73-year-old immunocompetent woman who underwent total knee arthroplasty and presented one month later with signs of prosthetic infection. She underwent joint debridement and the fluid was sent for culture and sensitivity testing. The culture showed growth of Trichosporon asahii. The patient was administered intravenous and intra-articular injections of amphotericin B, followed by antifungal treatment with voriconazole for one year. At 26 months of follow-up, there was no evidence of infection and the patient was ambulating with a walker. To the authors' knowledge, the present case is the first report of T asahii infection following knee replacement. Early detection, prompt institution of the appropriate antibiotics and regular follow-up are recommended.

Les rapports d'infection fongique sont d'une extrême rareté après une arthroplastie totale du genou. Dans la plupart des rapports, l'organisme infectant fait partie des espèces à Candida. Le présent rapport décrit le cas d'une femme immunocompétente de 73 ans qui a subi une arthroplastie totale du genou et qui, un mois plus tard, a consulté en raison de signes d'infection prosthétique. Elle a subi un débridement articulaire, et le liquide a été envoyé pour mise en culture et test de sensibilité. La culture a révélé une croissance de Trichosporon asahii. La femme a reçu des injections intraveineuses et intra-articulaires d'amphotéricine B, puis un traitement antifongique au voriconazole pendant un an. Après 26 mois de suivi, elle n'avait plus de traces d'infection et pouvait se déplacer avec un déambulateur. En autant que le sache les auteurs, ce cas est le premier rapport d'infection à T asahii après une arthroplastie du genou. Ils recommandent le dépistage précoce, l'amorce rapide des antibiotiques pertinents et un suivi régulier.

[Research on the dynamics of ion debris from Sn plasma by use of dual laser pulses].

Extreme ultraviolet lithography is one of the most promising technologies on the next generation of high-capacity integrated circuit manufacturing. However, techniques for ion debris mitigation have to be considered in the application of extreme ultraviolet source for lithography. In our paper the dynamics of ion debris from Sn plasma by using dual ns laser pulses were investigated. The results show that debris from plasma greatly depends on the energy of pre-pulse and the delay time between the two laser pulses. The energy of Sn ions debris was efficiently mitigated from 2. 47 to 0. 40 keV in the case of dual laser pulses, up to 6. 1 times lower than that by using single laser pulse. We also found that Sn ions debris can be mitigated at all angles by using the dual laser pulses method.

XB130 promotes proliferation and invasion of gastric cancer cells.

BACKGROUND: XB130 has been reported to be expressed by various types of cells such as thyroid cancer and esophageal cancer cells, and it promotes the proliferation and invasion of thyroid cancer cells. Our previous study demonstrated that XB130 is also expressed in gastric cancer (GC), and that its expression is associated with the prognosis, but the role of XB130 in GC has not been well characterized. METHODS: In this study, we investigated the influence of XB130 on gastric tumorigenesis and metastasis in vivo and in vitro using the MTT assay, clonogenic assay, BrdU incorporation assay, 3D culture, immunohistochemistry and immunofluorescence. Western blot analysis was also performed to identify the potential mechanisms involved. RESULTS: The proliferation, migration, and invasion of SGC7901 and MNK45 gastric adenocarcinoma cell lines were all significantly inhibited by knockdown of XB130 using small hairpin RNA. In a xenograft model, tumor growth was markedly inhibited after shXB130-transfected GC cells were implanted into nude mice. After XB130 knockdown, GC cells showed a more epithelial-like phenotype, suggesting an inhibition of the epithelial-mesenchymal transition (EMT) process. In addition, silencing of XB130 reduced the expression of p-Akt/Akt, upregulated expression of epithelial markers including E-cadherin, α-catenin and ß-catenin, and downregulated mesenchymal markers including fibronectin and vimentin. Expression of oncoproteins related to tumor metastasis, such as MMP2, MMP9, and CD44, was also significantly reduced. CONCLUSIONS: These findings indicate that XB130 enhances cell motility and invasiveness by modulating the EMT-like process, while silencing XB130 in GC suppresses tumorigenesis and metastasis, suggesting that it may be a potential therapeutic target.

Does trade policy uncertainty hurt renewable energy-related sustainable development goals in China?

Trade policy uncertainty might hamper trade flow, including the trade of green and renewable energy technologies. Therefore, this study aims to examine the asymmetric effects of trade policy uncertainty (TPU) on renewable energy consumption (REC) in China. To calculate the short- and long-term relationships between REC, TPU, national income, carbon footprints, and financial development, we used the nonlinear QARDL technique. The estimates reveal that an upsurge in TPU hurts REC in the short and long run. Conversely, a stable trade policy or a reduction in TPU increases REC in the long run. In the short run, a fall in TPU exerts no influence on REC. The findings further imply that various factors, including GDP, CO2 emissions, and financial development, contribute to long-term improvements in REC in China, both in the short and long run.

The use of intramedullary reduction techniques in the treatment of irreducible intertrochanteric femoral fractures with negative medial cortical support.

Objective: To explore the clinical efficacy of intramedullary reduction techniques for irreducible intertrochanteric femoral fractures with negative medial cortical support. Methods: A retrospective analysis was conducted on 69 patients with irreducible intertrochanteric femoral fractures with negative medial cortical support treated in the Department of Orthopedics at Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University) from July 2019 to December 2021. Patients were divided into Group A and Group B. Group A (experimental group) consisted of 36 cases with an average age of 76.2 ± 5.9 years, while Group B (control group) comprised 33 cases with an average age of 76.6 ± 6.3 years. Group A received treatment using intramedullary reduction techniques, while Group B received treatment using traditional extramedullary reduction techniques. Both groups achieved anatomic reduction of the medial cortex or slight positive support. Surgical duration, intraoperative fracture reduction time, intraoperative bleeding, intraoperative fluoroscopy time, fracture reduction quality, fracture healing, postoperative neck-shaft angle loss, femoral neck shortening, and hip joint functional recovery score (FRS) were compared between the two groups. Results: All patients were followed up for an average of 13.8 months. Group A showed superior outcomes compared to Group B in surgical duration, intraoperative fracture reduction time, intraoperative bleeding, intraoperative fluoroscopy time, fracture reduction quality, fracture healing, postoperative neck-shaft angle loss, and femoral neck shortening (P < 0.05). Hip joint function assessed by functional recovery score was better in Group A than Group B at 1 and 3 months postoperatively (P < 0.05), with no significant statistical difference at other time points (P > 0.05). Conclusion: For irreducible intertrochanteric femoral fractures with negative medial cortical support, intramedullary reduction techniques used during surgery demonstrated simplicity, significant reduction in surgical duration, decreased intraoperative bleeding, fewer amounts of intraoperative fluoroscopy, improved fracture reduction quality, and reduced surgical complexity. Further clinical research and application are warranted.

Grinding siderite with ferric sulfate to generate an active ferrous source for Cr(VI) reduction.

Activated siderite, endowed with excellent properties, was simply prepared by co-grinding with Fe sulfate to enhance its high reducing ability for Cr(VI). Batch experiments were conducted to investigate the main affecting parameters, such as material ratio, pH, temperature, etc. The removal of Cr(VI) by activated siderite was completed within 4 h of the reaction. The activated siderite maintained a high removal effect of Cr(VI) within a wide pH range (3-9). Various analytical methods, including XRD, SEM/EDS, XPS, etc., were employed to characterize the samples and discover variations before and after the reaction. The Fe (Ⅱ) in activated siderite becomes highly active, and it can even be released from the solid phase in the mildly acidic liquid phase to efficiently reduce Cr(VI) and mitigate its toxicity. These findings introduce an innovative approach for activating various minerals widely distributed in nature to promote the recovery of the ecological system.

Correlation of Eosinophils and Type 2 Inflammatory Mediators with Osteitis in Chronic Rhinosinusitis with Nasal Polyps.

Objective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP. Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated. Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P<0.001), periosteal proteins (P<0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P<0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively. Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.

Baicalin inhibits IL-1ß-induced ferroptosis in human osteoarthritis chondrocytes by activating Nrf-2 signaling pathway.

BACKGROUND: Osteoarthritis (OA) is a common degenerative disease involving articular cartilage, in which ferroptosis of chondrocytes plays an important role. Baicalin (BAI) exerts regulatory effects in a wide range of orthopedic diseases including OA, but its effect on ferroptosis of chondrocytes (CHs) is still unclear. The purpose of this study was to determine the effect of BAI on ferroptosis in human OA chondrocytes (OACs), and to explore its possible mechanism. METHODS: CHs were treated with IL-1ß (10 ng/mL) to simulate inflammation in vitro. Immunofluorescence, quantitative RT-PCR, Western blotting and cell viability assay were performed to evaluate the impacts of BAI on Fe2+ level, mitochondrial dysfunction, ferroptosis-related proteins, oxidative stress and cytotoxicity in CHs. Additionally, siRNA was made use of to knock out nuclear factor E2-related factor 2 (Nrf2) to analyze the role played by Nrf2 in BAI-induced CH ferroptosis. RESULTS: BAI eliminated IL-1ß-induced Fe2+ accumulation, changes in mitochondrial membrane potential and ferroptosis-related protein GPX4, SLC7A11, P53 and ACSL4 levels, as well as reactive oxygen species (ROS), lipid peroxidation (LPO) and malondialdehyde (MDA) accumulation in CHs. Besides, BAI reversed IL-1ß-induced decrease of Collagen II and increase of MMP13 in CHs. Meanwhile, BAI attenuated IL-1ß-induced CH toxicity and promoted Nrf2 antioxidant system activation. When Nrf2 was knocked down by siRNA, the effects of BAI on IL-1ß-induced ferroptosis-related proteins and antioxidant stress in CHs were significantly weakened. CONCLUSIONS: This study demonstrates that IL-1ß can induce CH ferroptosis. BAI is able to inhibit IL-1ß-induced CH ferroptosis and ECM degradation, and the specific mechanism may be that it can inhibit IL-1ß-induced CH ferroptosis by activating Nrf2 antioxidant system to attenuate the accumulation of intracellular ROS and lipid ROS.

Cinobufacini enhances the therapeutic response of 5-Fluorouracil against gastric cancer by targeting cancer stem cells via AKT/GSK-3ß/ß-catenin signaling axis.

BACKGROUND: Gastric cancer stem cells (GCSCs) play crucial role in the development, recurrence, and resistance of gastric cancer (GC). Cinobufacini, a traditional Chinese medicine, offers significant advantages in improving tumor therapy. However, pre-clinical investigation into the antitumor effect and mechanism of Cinobufacini on GC is still lacking. Additionally, it has not been reported whether Cinobufacini is related to cancer stem cells (CSCs). METHODS: The CCK-8, clone formation, EdU staining, transwell and wound healing experiments were performed to assess the cell toxicity of Cinobufacini and demonstrate the preventive effects of Cinobufacini on proliferation, invasion, and migration of GC cells. Elucidating the underlying mechanism of Cinobufacini in GC based on the transcriptome sequencing. Flow cytometry assays, sphere formation assays, subcutaneous xenograft model in nude mice, and immunofluorescent staining have been used to investigate whether the anti-GC effect of Cinobufacini is associated with GCSCs and enhancing therapeutic response to 5-Fluorouracil (5-FU). RESULTS: Cinobufacini exerts minimal impact on normal human gastric epithelium cell GES-1, while significantly suppressing the proliferation, invasion, and migration of GC cell lines. Additionally, Cinobufacini attenuates the stemness of GCSCs by disrupting the AKT/GSK-3ß/ß-catenin signaling cascade. Moreover, Cinobufacin enhances the anti-tumor effects of 5-FU against GCSCs by reducing in vitro sphere formation and inhibiting subcutaneous graft tumor growth in vivo. CONCLUSIONS: Cinobufacini enhances the therapeutic response of 5-FU against GC by targeting CSCs via AKT/GSK-3ß/ß-catenin signaling axis. Our findings offer a crucial insight into the molecular mechanism of Cinobufacini's anticancer activity in GC.

Molecular mechanisms of transmitted endoplasmic reticulum stress mediating immune escape of gastric cancer via PVR overexpression in TAMs.

Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Due to the complex tumor microenvironment (TME), the efficacy of immunotherapy in GC has not met expectations. Malignant changes in the TME induce endoplasmic reticulum stress (ERS). ERS can be transmitted between tumor cells and tumor-associated macrophages (TAMs), promoting tumor immune escape, but the specific mechanism in GC remains unclear. We established a TAM model of transmitted ERS (TERS), and iTRAQ proteomic analysis identified overexpressed proteins. The overexpression of poliovirus receptor (PVR) was screened while flow cytometry and ELISA showed that PVR mediated the immunosuppressive function of TAMs by downregulating the proliferative activity and cytotoxicity of cocultured CD8+ T lymphocytes. With EMSA and dual-luciferase reporter assays, we confirmed that erythropoietin-producing hepatocellular receptor A2 (EphA2) affected PVR expression by increasing the transcriptional activity of activator protein-1 (AP-1). MFC cells were mixed with EphA2 knockdown or control RAW264.7 cells to establish subcutaneous tumor models with or without tunicamycin treatment in vivo. The vivo experiments revealed that ERS promoted subcutaneous xenograft growth, which was reversed by EphA2 knockdown. Clinically, GC patients with high expression of PVR and EphA2 tended to have an immunosuppressive TME, which were determined by immunohistochemical and immunofluorescence analyses. In conclusion, the transcriptional activity of AP-1 is upregulated in ERS-transmitted TAMs through EphA2 to increase PVR expression, which promotes immune escape in GC. Our study provides a new perspective on the role of ERS in tumor immunity.