Odontogenic and anti-inflammatory effects of magnesium-doped bioactive glass in vital pulp therapy.

This study aimed to investigate the effects of magnesium-doped bioactive glass (Mg-BG) on the mineralization, odontogenesis, and anti-inflammatory abilities of human dental pulp stem cells (hDPSCs). Mg-BG powders with different Mg concentrations were successfully synthesized via the sol-gel method and evaluated using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. Apatite formation was observed on the surfaces of the materials after soaking in simulated body fluid. hDPSCs were cultured with Mg-BG powder extracts in vitro, and no evident cytotoxicity was observed. Mg-BG induced alkaline phosphatase (ALP) expression and mineralization of hDPSCs and upregulated the expression of odontogenic genes, including those encoding dentin sialophosphoprotein, dentin matrix protein 1, ALP, osteocalcin, and runt-related transcription factor 2. Moreover, secretion of inflammatory cytokines (interleukin [IL]-4, IL-6, IL-8, and tumor necrosis factor-alpha) was substantially suppressed by Mg-BG. Collectively, the results of this study suggest that Mg-BG has excellent in vitro bioactivity and is a potential material for vital pulp therapy for inflamed pulps.

Conditional Survival of Patients with Limited-Stage Small Cell Lung Cancer After Surgery: A National Real-World Cohort Study.

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.

Construction and validation of a risk-scoring model to predict lymph node metastasis in T1b-T2 esophageal cancer.

BACKGROUND: Lymph node status is an important factor in determining preoperative treatment strategies for stage T1b-T2 esophageal cancer (EC). Thus, the aim of this study was to investigate the risk factors for lymph node metastasis (LNM) in T1b-T2 EC and to establish and validate a risk-scoring model to guide the selection of optimal treatment options. METHODS: Patients who underwent upfront surgery for pT1b-T2 EC between January 2016 and December 2022 were analyzed. On the basis of the independent risk factors determined by multivariate logistic regression analysis, a risk-scoring model for the prediction of LNM was constructed and then validated. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminant ability of the model. RESULTS: The incidence of LNM was 33.5% (214/638) in our cohort, 33.4% (169/506) in the primary cohort and 34.1% (45/132) in the validation cohort. Multivariate analysis confirmed that primary site, tumor grade, tumor size, depth, and lymphovascular invasion were independent risk factors for LNM (all P < 0.05), and patients were grouped based on these factors. A 7-point risk-scoring model based on these variables had good predictive accuracy in both the primary cohort (AUC, 0.749; 95% confidence interval 0.709-0.786) and the validation cohort (AUC, 0.738; 95% confidence interval 0.655-0.811). CONCLUSION: A novel risk-scoring model for lymph node metastasis was established to guide the optimal treatment of patients with T1b-T2 EC.

The association between histological subtypes and lymph node metastasis and prognosis in early esophageal cancer: a population-based study.

BACKGROUND: There is still a lack of high-level clinical evidence and uniform conclusions on whether there are differences in lymph node metastasis (LNM) and prognosis between early esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). METHODS: Patients with surgically resected, histologically diagnosed, pT1 EAC or ESCC in the Surveillance, Epidemiology and End Results registries database from 2004 to 2015 were included. Multivariable logistic regression, Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the histology and LNM or prognosis. RESULTS: A total of 570 early esophageal cancer patients were included. The LNM rates were 13.8% and 15.1% for EAC and ESCC ( P  = 0.757), respectively. Multivariate logistic regression analysis showed no significant association between histological type and LNM (odds ratio [OR], 1.209; 95% CI, 0.538-2.715; P  = 0.646). Moreover, the prognosis of early EAC and ESCC was shown to be comparable in both multivariate Cox regression (hazard ratio [HR], 1.483; 95% CI, 0.699-3.150; P  = 0.305) and the multivariate competing risk model (subdistribution HR, 1.451; 95% CI, 0.628-3.354; P  = 0.383). After propensity score matching, there were no significant differences between early EAC and ESCC in terms of LNM (10.6% vs.18.2%, P  = 0.215), 5-year CSS (89.8% [95% CI, 81.0%-98.6%] vs. 79.1% [95% CI, 67.9%-90.3%], P  = 0.102) and 5-year cumulative incidence of CSS (10.2% [95% CI, 1.4%-19.0%] vs. 79.1% [95% CI, 9.7%-32.1%], P  = 0.124). CONCLUSION: The risk of LNM and prognosis of early ESCC and EAC are comparable, so the treatment choice for early esophageal cancer does not depend on the histologic type.

Clinical evaluation of a multitarget fecal immunochemical test-sDNA test for colorectal cancer screening in a high-risk population: a prospective, multicenter clinical study.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT (P < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT (P < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.

Immuno-genomic-radiomics to predict response of biliary tract cancer to camrelizumab plus GEMOX in a single-arm phase II trial.

Background & Aims: Immunotherapy is an option for the treatment of advanced biliary tract cancer (BTC), although it has a low response rate. In this post hoc analysis, we investigated the predictive value of an immuno-genomic-radiomics (IGR) analysis for patients with BTC treated with camrelizumab plus gemcitabine and oxaliplatin (GEMOX) therapy. Methods: Thirty-two patients with BTC treated with camrelizumab plus GEMOX were prospectively enrolled. The relationship between high-throughput computed tomography (CT) radiomics features with immuno-genomic expression was tested and scaled with a full correlation matrix analysis. Odds ratio (OR) of IGR expression for objective response to camrelizumab plus GEMOX was tested with logistic regression analysis. Association of IGR expression with progression-free survival (PFS) and overall survival (OS) was analysed with a Cox proportional hazard regression. Results: CT radiomics correlated with CD8+ T cells (r = -0.72-0.71, p = 0.004-0.047), tumour mutation burden (TMB) (r = 0.59, p = 0.039), and ARID1A mutation (r = -0.58-0.57, p = 0.020-0.034). There was no significant correlation between radiomics and programmed cell death protein ligand 1 expression (p >0.96). Among all IGR biomarkers, only four radiomics features were independent predictors of objective response (OR = 0.09-3.81; p = 0.011-0.044). Combining independent radiomics features into an objective response prediction model achieved an area under the curve of 0.869. In a Cox analysis, radiomics signature [hazard ratio (HR) = 6.90, p <0.001], ARID1A (HR = 3.31, p = 0.013), and blood TMB (HR = 1.13, p = 0.023) were independent predictors of PFS. Radiomics signature (HR = 6.58, p <0.001) and CD8+ T cells (HR = 0.22, p = 0.004) were independent predictors of OS. Prognostic models integrating these features achieved concordance indexes of 0.677 and 0.681 for PFS and OS, respectively. Conclusions: Radiomics could act as a non-invasive immuno-genomic surrogate of BTC, which could further aid in response prediction for patients with BTC treated with immunotherapy. However, multicenter and larger sample studies are required to validate these results. Impact and implications: Immunotherapy is an alternative for the treatment of advanced BTC, whereas tumour response is heterogeneous. In a post hoc analysis of the single-arm phase II clinical trial (NCT03486678), we found that CT radiomics features were associated with the tumour microenvironment and that IGR expression was a promising marker for tumour response and long-term survival. Clinical trial number: Post hoc analysis of NCT03486678.

[Recent Research Progress on CircRNA in Hematological Malignancies--Review].

Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.

Survey and analysis of willingness to use mobile medical services and influencing factors of TB patients treated at home.

INTRODUCTION: The objective of this study was to investigate the willingness of patients with tuberculosis (TB) to use mobile medical services (mHealth) and its influencing factors, so as to provide theoretical guidance for optimizing the TB mobile medical platform and improve the willingness of patients to use mHealth. METHODOLOGY: In this cross-sectional study, convenience sampling method was used to investigate patients with TB from the outpatient clinics of two TB specialized hospitals (Beijing Thoracic Tumor and Tuberculosis Hospital and Tuberculosis Prevention and Treatment Hospital of Shaanxi Province) from January to June 2021 using a self-designed questionnaire. RESULTS: Out of 231 patients, only 90 (38.96%) were aware of mHealth services, and 63 (27.27%) had used mHealth services. Among the 63 patients who had used mHealth services, the proportion of mobile medical forms based on WeChat platform was 74.89%. Patients' willingness to use mHealth was scored (11.49 ± 2.53). Univariate analysis showed that the scores of patients' willingness to use mHealth differed by gender and the different ways of affording healthcare (p < 0.05). Regression analysis showed that the influencing factors of willingness to use mHealth in patients with TB included attitude towards use (0.750), health beliefs (0.091) and social impact (0.169) (adjusted R2 = 0.781, p < 0.001). CONCLUSIONS: Patients' awareness of the advantages of the new medical model needs to be improved. Optimized design can improve the willingness of patients to use mHealth services and improve the role of mHealth in patient management.

MicroRNA-494-3p facilitates the progression of bladder cancer by mediating the KLF9/RGS2 axis.

Bladder cancer (BC) is a familiar malignancy with high morbidity and mortality. The effect of treatment is unsatisfactory after the metastasis and invasion of BC. Hence, more studies should be carried out to explore the metastasis of BC. RT-qPCR or/and western blot was conducted to evaluate miR-494-3p, KLF9, and RGS2 expression. Cell proliferation and invasion were estimated by MTT assay and transwell assay, respectively. Cell migration was tested by wound healing assay and transwell assay. Dual-luciferase reporter gene assay was employed to validate the interplay between miR-494-3p and KLF9 mRNA. The interaction between KLF9 and RGS2 promoter was verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. miR-494-3p expression was upregulated, whereas KLF9 and RGS2 were downregulated in BC cells. miR-494-3p inhibition was competent to limit the growth of BC cells. KLF9 knockdown abolished the miR-494-3p depletion-mediated inhibitory growth of BC cells. Mechanistically, we found that KLF9 was a downstream gene of miR-494-3p and could bind to the promoter region of RGS2 to promote the expression of RGS2. Moreover, RGS2 knockdown abrogated the suppressive effects of miR-494-3p knockdown on the proliferation, migration, and invasion of BC cells. Notably, miR-494-3p inhibition obstructed the tumor growth in nude mice. miR-494-3p silencing inhibited the progression of BC by regulating the KLF9/RGS2 axis in vitro and in vivo, which laid the foundation for experiments of miR-494-3p in BC and provided therapeutic targets for BC.

A Metabolic Plasticity-Based Signature for Molecular Classification and Prognosis of Lower-Grade Glioma.

BACKGROUND: Glioma is one of the major health problems worldwide. Biomarkers for predicting the prognosis of Glioma are still needed. METHODS: The transcriptome data and clinic information on Glioma were obtained from the CGGA, TCGA, GDC, and GEO databases. The immune infiltration status in the clusters was compared. The genes with differential expression were identified, and a prognostic model was developed. Several assays were used to detect RPH3A's role in Glioma cells, including CCK-8, colony formation, wound healing, and transwell migration assay. RESULTS: Lower Grade Glioma (LGG) was divided into two clusters. The immune infiltration difference was observed between the two clusters. We screened for genes that differed between the two groups. WGCNA was used to construct a co-expressed network using the DEGs, and four co-expressed modules were identified, which are blue, green, grey, and yellow modules. High-risk patients have a lower overall survival rate than low-risk patients. In addition, the risk score is associated with histological subtypes. Finally, the role of RPH3A was detected. The overexpression of RPH3A in LGG cells can significantly inhibit cell proliferation and migration and regulate EMT-regulated proteins. CONCLUSION: Our study developed a metabolic-related model for the prognosis of Glioma cells. RPH3A is a potential therapeutic target for Glioma.

Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis.

Liver fibrosis is a leading contributor to chronic liver diseases such as cirrhosis and liver cancer, which pose a serious health threat worldwide, and there are no effective drugs to treat it. Qijia Rougan decoction was modified from Sanjiasan, a traditional Chinese medicine (TCM) described in the "Wenyilun" manuscript. Qijia Rougan decoction possesses hepatoprotective and antifibrotic effects for clinical applications. However, its underlying mechanisms remain largely unknown. In this study, fibrotic rats induced by carbon tetrachloride (CCl4) were treated with two doses of Qijia Rougan decoction. Histopathological and serum biochemical analyses were carried out to assess liver structure and function, respectively. High-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) was performed to identify bioactive compositions in Qijia Rougan decoction. Transcriptome analysis using mRNA-sequencing (mRNA-Seq) was used to explore the underlying mechanisms and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Qijia Rougan decoction significantly attenuated CCl4-induced hepatic fibrotic injury, supported by promoted liver function and improved liver fibrosis. Eight main representative components originating from raw materials in the Qijia Rougan decoction were found to possess an antifibrotic role. Mechanistically, Qijia Rougan decoction regulated biological processes such as oxidation-reduction, fatty acid metabolism, cell adhesion, and transforming growth factor beta (TGFß) signaling. We determined that Qijia Rougan decoction reversed the expression of inflammatory cytokines and inhibited the activation of fibrosis-related TGFß signaling. It also reversed the deterioration of liver structure and function in rats induced by CCl4. Overall, Qijia Rougan decoction significantly mediated metabolism-associated processes, inhibited inflammatory reactions, and repressed fibrosis-related TGFß signaling, which prevented liver fibrosis deterioration. Our study deepens our understanding of TCM in the diagnosis and treatment of liver fibrosis.

A nerve conduit filled with Wnt5a-loaded fibrin hydrogels promotes peripheral nerve regeneration.

AIMS: Peripheral nerve injury is a significant clinical problem with a substantial impact on quality of life, for which no optimal treatment has been found. This study aimed to analyze the effect and mechanism of Wnt5a-loaded fibrin hydrogel on a 10-mm rat sciatic nerve defect. METHODS: The Wnt5a-loaded fibrin hydrogel was synthesized by mixing a Wnt5a solution with thrombin and fibrinogen solutions. The loading capacity and release profile of Wnt5a-loaded fibrin hydrogel and the effect of Wnt5a on Schwann cells were evaluated in vitro. We also assessed the in vivo repair status via histological analysis of the regenerative nerve and gastrocnemius muscle, electrophysiological examination, gait analysis, and muscle wet weight. RESULTS: We developed a nerve conduit filled with Wnt5a-loaded fibrin hydrogel (Fn) as a sustained-release system to repair a 10-mm rat sciatic nerve defect. In vitro, Wnt5a could promote SC proliferation and the gene expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and cholinergic neurotrophic factor (CNTF), as well as the protein secretion of VEGF and NGF. In vivo, the Wnt5a/Fn group was superior to the hollow, fibrin hydrogel, and Wnt5a groups in terms of axonal growth, myelination, electrophysiological recovery, target organ innervation, and motor function recovery 12 weeks after the operation. CONCLUSION: The Wnt5a/Fn nerve conduit can promote peripheral nerve defect regeneration, with potential clinical applications. The mechanism for this may be the facilitation of multiple neurotrophin secretion, combining vascularization and neurotrophic growth cues.

Study on Efficacy and Safety of Low-Dose Apatinib Combined with Camrelizumab and SOX Regimen as First-Line Treatment of Locally Advanced and Unresectable Gastric/Gastroesophageal Junction Cancer: A Protocol for an Open-Label, Dose Escalation and Extension Phase Ib Clinical Trial.

BACKGROUND: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8-11 months in the West and 13-17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy. METHODS/DESIGN: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0). DISCUSSION: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy. TRIAL REGISTRATION: ChiCTR.gov.cn: ChiCTR2000034109.

Visualization of the renal vein filled with contrast agent may indicate the renal vein injury during percutaneous nephrolithotomy: two case reports.

BACKGROUND: Intravenous misplacement of a nephrostomy tube is a rare complication of percutaneous nephrolithotomy (PCNL) or percutaneous nephrostomy. The mechanism of misplacement of a nephrostomy tube into the vascular system is seldom investigated. One type of the possible mechanism is that the puncture needle penetrates a major intrarenal tributary of the renal vein and enters the collecting system. However, the guidewire is located outside the collecting system near the large branches of renal vein or perforates into the renal vein. The dilation is performed and causes a large torn injury. Subsequently, the nephrostomy tube is placed inside the vessel when radiological monitoring is not used. However, there is no imaging evidence and the scene of procedure is not demonstrated. This paper reports two cases of visualization of the renal vein filled with contrast agent during PCNL. The findings may be good evidence to support the step of renal vein injury in patients with intravenous nephrostomy tube misplacement. CASE PRESENTATION: We presented two cases with visualization of the renal vein filled with contrast agent during PCNL. In the process of injecting the contrast agent through the puncture needle, we could see the renal vein. Moreover, it was identified that the puncture needle tip was not on the optimal position. The position of puncture needle tip lay outside the collecting system, which was close to the calyceal infundibulum and branches of renal vein. CONCLUSIONS: Visualization of the renal vein filled with contrast agent may be good evidence to verify the renal vein injury in patients with intravenous nephrostomy tube misplacement during PCNL or percutaneous nephrostomy. The suboptimal location of the puncture needle tip and visualization of the renal vein filled with contrast agent indicate the renal vein injury. One type of mechanism of intravenous nephrostomy tube misplacement is as following. Firstly, the guidewire stays outside the collecting system. Subsequently, dilatation directed by the guidewire results in the injury of the vein. Then, the nephrostomy tube migrates into the venous system due to prompt tube inserting and the direction of the sheath and/or the guidewire to the injured vein.

[Clinical Application of Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma--Review].

Diffuse large B-cell lymphoma (DLBCL) as an aggressive lymphoma, there has not a good molecular marker to assess the therapeutic efficacy and prognosis of the disease. As compared with the traditional deteation method, it was found that the circulating tumor DNA (ctDNA) can be used as a non-invasive specific biomarker which can dynamically provide the information about the lymphoma. ctDNA in DLBCL can be obtained by dideoxy chain termination method combined with PCR, so as to detect genetic markers, targeted sequences of gene which is related to lymphoma; the digital PCR (dPCR) for lymphoma somatic mutations and the detection of abnormal methylation; ctDNA is closely related to the diagncsis, therapeutic efficiency and prognosis of DLBCL, thus ctDNA can be used for the early detection, mid-term and prognostic monitoring in DLBCL, which makes ctDNA have a broad clinical applied prospect.

Psoralen, a natural phytoestrogen, improves diaphyseal fracture healing in ovariectomized mice: A preliminary study.

Psoralen is an effective active component extracted from Psoraleacorylifolia, which can promote bone formation in osteoporotic animals. However, to the best of our knowledge, its effect on fracture healing has not yet been examined. In the present study, open femur fractures were created in ovariectomy (OVX)-induced osteoporotic mice. OVX mice were treated with psoralen (psoralen+OVX group) or physiological saline (OVX group) by oral gavage. Radiographic and histological results demonstrated progressed callus consolidation in the psoralen+OVX group compared with the OVX group after 10 and 21 days of treatment. Qualitative histological analysis showed that the number of osteoclasts was significantly reduced in the psoralen+OVX group after treatment. Moreover, reverse transcription-quantitative PCR analysis of callus samples showed increased expression of bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG), and decreased expression of receptor activator of nuclear factor-κB ligand (RANKL) at 10 and 21 days post injury in the psoralen+OVX group compared with the OVX group. Furthermore, western blot analysis showed that psoralen significantly increased the expression of estrogen receptor (ER)-α, but had no effect on ER-ß expression; these results were further confirmed by immunohistochemistry. To conclude, these results indicated that psoralen may promote callus formation and inhibit osteoclast genesis by increasing BMP-2 and ER-α levels, and OPG/RANKL ratio. Consequently, psoralen could be a possible treatment for osteoporotic fracture-related complications.

Current Progress and Future Perspectives of Immune Checkpoint Inhibitors in Biliary Tract Cancer.

Biliary tract cancer (BTC) is an uncommon and aggressive neoplasm, with most patients presenting in an advanced stage. Systemic chemotherapy is the limited treatment available but is unsatisfactory, while targeted therapy is still awaiting validation from clinical trials. Given the potential effect of immune checkpoint inhibitors (ICIs) in the treatment of BTC, this review aims to summarize the evidence-based benefits and predictive biomarkers for using inhibitors of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) ligand, or programmed cell death protein-1 and its ligand (PD-1 and PD-L1) as monotherapy or combined with other anti-tumor therapies, while also pointing out certain pitfalls with the use of ICIs which need to be addressed.

CircRNA_102179 promotes the proliferation, migration and invasion in non-small cell lung cancer cells by regulating miR-330-5p/HMGB3 axis.

Non-small cell lung cancer (NSCLC) accounting for 85 % of all lung cancer was one of the main causes of death worldwide. In this study, we investigated the role of circRNA_102179 in NSCLC development. The levels of circRNA_102179 in NSCLC tissues and cell lines were determined by quantitative real-time PCR assay (qRT-PCR). CCK8 and colony formation assays were applied to explore the effect of circRNA_102179 on the growth of NSCLC cells in vitro. Transwell assay was utilized to analyze the impact of circRNA_102179 on the migration and invasion of NSCLC cells. Target prediction and luciferase reporter assay were used to identify the interacting miRNA of circRNA_102179. The interaction among circRNA_102179/ miR-330-5p/HMGB3 was further validated by colony formation and Transwell invasion assays. Finally, the mouse xenograft NSCLC model was used to explore the role of circRNA_102179 in the tumor growth of NSCLC cells in vivo. CircRNA_102179 was overexpressed in NSCLC tissues and cells compared with normal lung tissues and human bronchial epithelial cells (HBEs). The down-regulation of circRNA_102179 markedly reduced the proliferation, migration, and invasion of NSCLC cells. Moreover, down-expression of circRNA_102179 significantly increased the level of miR-330-5p/HMGB3 in NSCLC cells. Further functional experiments indicated that over-expression of miR-330-5p reversed the inhibitory effect of circRNA_102179 on NSCLC cells growth, migration, and invasion. Our results reveal that circRNA_102179 facilitates the proliferation, migration, and invasion of NSCLC cell via modulating miR-330-5p/ HMGB3 axis in NSCLC cells.