Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis.

M1 macrophage polarization and synovitis play an important role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Reduced molecular weight of hyaluronic acid (HA) in synovial fluid of patients with TMJOA. In addition, high molecular weight hyaluronic acid (HMW-HA) is often used clinically to treat TMJ inflammation. As a pattern recognition receptor of the cytoplasm, ALPK1 was found to be pro-inflammatory in a variety of diseases. However, the relationship of ALPK1, HA and M1 macrophage polarization in TMJ synovitis remains unclear. We aimed to investigate the role of ALPK1 and HA in macrophage polarization and TMJ synovitis and the underlying mechanisms. The results demonstrated that ALPK1 was highly upregulated in the synovial macrophages in the inflamed TMJ synovium of patients. Low molecular weight hyaluronic acid (LMW-HA) promoted the expression of ALPK1 and M1 macrophage-associated genes. Besides, rhALPK1 promoted the expression of M1 macrophage-associated factors and the nuclear translocation of PKM2. Furthermore, ALPK1 knockout mice exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage-associated genes in CFA-induced TMJ synovitis. While HMW-HA inhibited the expression of ALPK1 and M1 macrophage polarization. Our results elucidated that ALPK1 promoted TMJ synovitis by promoting nuclear PKM2-mediated M1 macrophage polarization, whereas HMW-HA inhibited the expression of ALPK1 as well as M1 macrophage polarization.

Macrophage Activation in Synovitis and Osteoarthritis of Temporomandibular Joint and Its Relationship with the Progression of Synovitis and Bone Remodeling.

This study investigates the regulatory mechanisms of synovial macrophages and their polarization in the progression of temporomandibular joint osteoarthritis (TMJOA). Macrophage depletion models were established by intra-articular injection of clodronate liposomes and unloaded liposomes. TMJOA was induced by intra-articular injection of 50 µL Complete Freund's Adjuvant and the surgery of disc perforation. The contralateral joint was used as the control group. The expression of F4/80, CD86, and CD206 in the synovium was detected by immunofluorescence staining analysis. Hematoxylin and eosin staining and TMJOA synovial score were detected to show the synovial changes in rat joints after TMJOA induction and macrophage depletion. Changes in rat cartilage after TMJOA induction and macrophage depletion were shown by safranin fast green staining. The bone-related parameters of rats' joints were evaluated by micro-computed tomography analysis. The TMJOA model induced by Complete Freund's Adjuvant injection and disc perforation aggravated synovial hyperplasia and showed a significant up-regulation of expression of F4/80-, CD86-, and CD206-positive cells. F4/80, CD86, and CD206 staining levels were significantly decreased in macrophage depletion rats, whereas the synovitis score further increased and cartilage and subchondral bone destruction was slightly aggravated. Macrophages were crucially involved in the progression of TMJOA, and macrophage depletion in TMJOA synoviocytes promoted synovitis and cartilage destruction.

Synthesis and In Vivo Antiarrhythmic Activity Evaluation of Novel Scutellarein Analogues as Voltage-Gated Nav1.5 and Cav1.2 Channels Blockers.

Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated from Scutellaria altissima L., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4'-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves' amplitude. The most promising compound 10e showed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound 10e was able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound 10e even showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound 10e did not block the hERG potassium channel which highly associated with cardiotoxicity.

Progress in animal models of trigeminal neuralgia.

OBJECTIVE: This review aims to systematically summarize the methods of establishing various models of trigeminal neuralgia (TN), the scope of application, and current animals used in TN research and the corresponding pain measurements, hoping to provide valuable reference for researchers to select appropriate TN animal models and make contributions to the research of pathophysiology and management of the disease. DESIGN: The related literatures of TN were searched through PubMed database using different combinations of the following terms and keywords including but not limited: animal models, trigeminal neuralgia, orofacial neuropathic pain. To find the maximum number of eligible articles, no filters were used in the search. The references of eligible studies were analyzed and reviewed comprehensively. RESULTS: This study summarized the current animal models of TN, categorized them into the following groups: chemical induction, photochemical induction, surgery and genetic engineering, and introduced various measurement methods to evaluate animal pain behaviors. CONCLUSIONS: Although a variety of methods are used to establish disease models, there is no ideal TN model that can reflect all the characteristics of the disease. Therefore, there is still a need to develop more novel animal models in order to further study the etiology, pathological mechanism and potential treatment of TN.

Clinical Application of CAD/CAM-Guided Modified Dautrey's Procedure in Recurrent Temporomandibular Joint Luxation.

This study aimed to introduce the clinical application of the CAD/CAM-guided modified Dautrey's procedure in recurrent anterior temporomandibular joint luxation and evaluate its clinical effects. Four selected patients were treated by the CAD/CAM-guided modified Dautrey's procedure and were followed-up to access their curative effect. Joint pain and sound, recurrence rate, mandibular function, maximum mouth opening (MMO), symptoms of facial nerve injury, and changes in zygomatic facial appearance were observed in postoperative follow-up. The followed-up period ranged from 3 months to 1 year with an average time of 7.5 months. There was no recurrence in all 4 patients, and no symptoms of facial nerve injury and zygomaticofacial appearance changes were found. All patients showed improvement in MMO, with a mean preoperative and postoperative MMO of 4.74 and 3.74 cm, respectively. All of them showed relief of joint pain or sound 3 months or more after the operation and could exercise mandibular normally. This results showed that the CAD/CAM-guided modified Dautrey's procedure was effective in the treatment of recurrent temporomandibular joint luxation and could be used as a good alternative treatment for it.

The Long-Term Clinical Outcomes of Selectively Extracranial Radiofrequency Thermocoagulation for Trigeminal Neuralgia Guided by Three-Dimensionally Printed Personalized Template.

ABSTRACT: The purpose of this study was to assess the long-term pain relief and the complications of selectively extracranial radio-frequency thermocoagulation (RFT) for trigeminal neuralgia (TN) guided by a three-dimensionally (3D) printed personalized template. The authors conducted a retrospective study of 117 TN patients, who were treated with selectively extracranial RFT under 3D printed personalized template guidance between September 2014 and January 2019. The mean follow-up duration was 42.8 months (range: 28-83 months). Favorable pain relief of patients was 100% at discharge, 86.3% at 1 year, 80.3% at 2 years, 78.6% at 3 years, and 75.4% at 5 years. No complication associated with a puncture or intracranial complication was observed during or after RFT. Postoperative complications included facial numbness in 91 patients (77.8%), masticatory muscle weakness in 15 patients (12.8%), ear paresthesia in 3 patients (2.6%), limited mouth opening in 2 patients (1.7%), and taste hypesthesia in 2 patients (1.7%). Most of these symptoms were improved during the visits and their life was not severely affected. Selectively extracranial RFT guided by a 3D printed personalized template is a clinically practical, effective, and safe approach for TN patients.

The surgical management of osteoid osteoma: A systematic review.

Background: Osteoid osteoma (OO) comprises approximately 11%-14% of benign bone tumors. The main symptom of OO is localized pain accompanied by nighttime aggravation. Surgical treatment is frequently used in clinic, including open surgery and percutaneous ablation, the latter including radiofrequency ablation, cryoablation, and microwave ablation, but there is no consensus on when and how to choose the best treatment for OO. Purpose: We did a systematic review of the literature on existing surgical treatments of OO to assess the safety and efficacy of surgical treatments of OO and to evaluate the surgical options for different locations of OO. Methods: The inclusion criteria in the literature are 1. Patients diagnosed with osteoid osteoma and treated surgically; 2. Include at least five patients; 3. Perioperative visual analogue scale (VAS), postoperative complications, and recurrence were recorded; 4. Literature available in PubMed from January 2014 to December 2021. Results: In the cohort, 1565 patients (mainly adolescents) with OO received 1615 treatments. And there are 70 patients with postoperative recurrence and 93 patients with postoperative complications (minor: major=84:9). The results of Kruskal-Wallis examination of each experimental index in this experiment were clinical success rate H=14.818, p=0.002, postoperative short-term VAS score H=212.858, p<0.001, postoperative long-term VAS score H=122.290, p<0.001, complication rate H=102.799, p<0.001, recurrence rate H=17.655, p<0.001, the technical success rate was H=45.708, p<0.001, according to the test criteria of α=0.05, H0 was rejected. The overall means of the outcome index in each group were not completely equal. Conclusion: Percutaneous ablation and open surgery are safe and reliable for OOs, and the technical success rate of percutaneous ablation is higher than that of open surgery. Open surgery and cryoablation can be selected for OOs close to the nerve and atypical sites, while radiofrequency ablation and microwave ablation can be selected for OOs in most other sites.

Nickel-catalyzed decarboxylative cross-coupling of indole-3-acetic acids with aryl bromides by convergent paired electrolysis.

Herein, nickel-catalyzed decarboxylative cross-coupling of indole-3-acetic acids with aryl bromides by convergent paired electrolysis was developed in an undivided cell. This protocol features good functional group tolerance, and is chemical redox agent- and sacrificial electrode-free. Mechanistic studies indicated that the base was crucial for the decarboxylation step and a NiI/NiIII catalytic cycle was involved in this transformation.

Overexpression of Ubiquilin4 is associated with poor prognosis in patients with cervical cancer.

BACKGROUND: Ubiquilins (UBQLNs) are important factors for cell proteostasis maintenance. UBQLNs are involved in the modulation of the cell cycle, as well as in apoptosis, membrane receptors regulation, DNA repair, epithelial-mesenchymal transition, and miRNA activities. They also affect the selection of double-strand break repair pathways. Abnormal UBQLNs expression can lead to many diseases, including cancer. Studies have found that the expression of Ubiquilin4 (UBQLN4) is associated with the development of several tumor types. However, the association between UBQLN4 and cervical cancer has not been examined yet. AIM: To investigate the expression of UBQLN4 in cervical cancer and to evaluate its correlation with disease prognosis. METHODS: Immunohistochemistry was performed to examine the expression of UBQLN4 in 117 cervical cancer tissues and 32 matching pericervical tissues. Paired t-test (two-tailed) was used to compare the differences between groups. We collected patients' clinical characteristics, including age, histological grade, pathologic type, lymph node metastasis, and FIGO stage (2018) and compared them by chi-square test. All patients were followed for 5.5 to 6.8 years. Kaplan-Meier method and log-rank test were used to compare the differences in the overall survival (OS) and progression-free survival (PFS) among the different groups. RESULTS: Overexpression of UBQLN4 was observed in 70.9% (83/117) of all cervical cancer tissues and in 15.6% (5/32) of the paired parauterine tissues. The expression of UBQLN4 was associated with lymph node metastasis, poor differentiation, and advanced stage, but the difference was not significant. Kaplan-Meier and log-rank test results suggested the high expression of UBQLN4 was associated with short OS and PFS. Regardless of UBQLN4 expression, the patient age and FIGO stage were also associated with disease prognosis. The statistically significant variables obtained from univariate the Kaplan-Meier analysis were subjected to Cox multivariate survival regression analysis, which showed that, in addition to the FIGO stage and age, UBQLN4 was also an independent prognostic marker for OS and PFS (P = 0.011 and P = 0.024, respectively). CONCLUSION: The overexpression of UBQLN4 was associated with poor prognosis in cervical cancer. Our study proposed a novel prognostic factor and improved the existing understanding of the pathogenesis of cervical cancer.

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Bronchopulmonary dysplasia (BPD) is a chronic lung disease due to impaired pulmonary development and is one of the main causes of respiratory failure in preterm infants. Preterm infants with BPD have significantly higher complication and mortality rates than those without BPD. At present, comprehensive management is the main intervention method for BPD, including reasonable respiratory and circulatory support, appropriate enteral nutrition and parenteral nutrition, application of caffeine/glucocorticoids/surfactants, and out-of-hospital management after discharge. The continuous advances in stem cell medicine in recent years provide new ideas for the treatment of BPD. Various pre-clinical trials have confirmed that stem cell therapy can effectively prevent lung injury and promote lung growth and damage repair. This article performs a comprehensive analysis of the mechanism of mesenchymal stem cells in the treatment of BPD, so as to provide a basis for clinical applications.

Standard orthodontic treatment after condylectomy for patients with active unilateral condylar hyperplasia.

INTRODUCTION: Unilateral condylar hyperplasia (UCH) is a progressive, nonneoplastic overgrowth of the condyle of the temporomandibular joint. For treating active UCH, a popular method combines orthognathic surgery with high condylectomy and orthodontic treatment. The goal of this study was to introduce a new method to correct asymmetry for active UCH. METHODS: Retrospectively, 47 patients with active UCH were divided into horizontal-type, vertical-type, and combined-type. All patients were treated with condylectomy plus postsurgery standard orthodontics (CPSO) with applied miniscrews implanted in infrazygomatic crest and hard palate to intrude affected side of maxillary molars and apply intermaxillary traction for contralateral molars. Cone-beam computed tomography was taken at presurgery, postsurgery, and the end of orthodontics (T3). RESULTS: In the vertical (n = 10) and combined (n = 28) types, deviation of the chin and the canting of the mandible and maxillary occlusal plane were significantly reduced at T3. A difference in the torque of bilateral maxillary first molar (U6) and bilateral mandibular first molar (L6) was significantly reduced at T3. The anterior, superior, and posterior joint spaces in the vertical-type and combined-type were significantly decreased at T3 compared with postsurgery. In contrast, in the horizontal-type group (n = 9), the deviation of the chin was corrected; however, the canting of the mandible and maxillary occlusal plane was significantly increased at T3 compared with presurgery. CONCLUSIONS: CPSO restored facial and occlusal symmetry for vertical-type and combined-type active UCH and returned affected-side condyle to the glenoid fossa. However, CPSO was not suitable for treating the horizontal-type UCH.

The Regrowth of Mandibular Coronoid Process After Coronoidectomy: A Retrospective Analysis of 57 Cases.

PURPOSE: Coronoidectomy is carried out frequently as a part of the cranial-maxillofacial surgery procedure. There are few articles on the fate of coronoid process after coronoidectomy, except that several case reports mentioned that coronoid process had regenerated. This study aimed to radiographically access the anatomic outcomes of coronoid process and investigate which factors were associated with the outcomes after coronoidectomy. MATERIALS AND METHODS: A retrospective cohort study included patients undergoing coronoidectomy over a 7-year period. The primary outcome variable was the new coronoid process occurrence (yes/no). Secondary outcome variable was the type of the new coronoid process by evaluating its size, shape and position. Radiograph at 1-year postoperative visit was used to determine the outcomes. The predictor variables included age, sex, surgical purpose, surgical side, surgical approach and the maximal interincisal opening. Appropriate statistics were analyzed by SPSS version 22. χ2 test and binary logistic regression were used to assess the association between predictor factors and anatomic outcomes (P <.05). RESULTS: The study sample included 57 patients. In total, 96 coronoidectomies were performed. Seventy-four coronoid processes (77.1%) showed complete (n = 44, 45.8%), nonunion (n = 19, 19.8%) or partial (n = 11, 11.5%) regrowth, whereas no evidence of regeneration in 22 sites was observed radiographically at 1-year postoperative visit. Binary logistic regression showed that a young age (odds ratio 0.704; 95% confidence interval 0.562-0.882; P = .002) was significantly associated with regeneration of coronoid process. CONCLUSIONS: Coronoid process can mostly regenerate after coronoidectomy. A young age may contribute to regrowth of coronoid process.

Astragaloside prevents UV-induced keratinocyte injury by regulating TLR4/NF-κB pathway.

BACKGROUND: Ultraviolet (UV) radiation is a key risk factor of environment to contribute photoaging and skin cancer through production of reactive oxygen species (ROS) and inflammatory responses. Astragaloside IV (AS-IV) is an active component from Astragalus membranaceus, and shows various pharmacological effects on inflammation, oxidative stress and apoptosis. However, whether AS-IV shows protective effect on UVB-induced injury in epidermal keratinocytes remain unknown. AIMS: To explored the effects of AS-IV on UVB-induced oxidative injury and inflammatory response in human epidermal keratinocytes. METHODS: HaCaT keratinocytes were exposed to UVB irradiation, followed by AS-IV incubation. The cell viability, intracellular ROS level, oxidative stress, and apoptosis were determined. The regulatory effects of AS-IV on toll-like receptor 4 (TLR4) pathway in UVB-exposed HaCaT cells were also investigated. RESULTS: Astragaloside IV pretreatment (10, 25, 50, 100 and 150 µM) increased cell viability in UVB-exposed HaCaT cells. AS-IV (50 µM) significantly reduced intracellular ROS level and lipid oxidation product malondialdehyde (MDA) content, and increased a ROS-scavenging enzyme superoxide dismutase (SOD) in HaCaT cells with UVB irradiation. In addition, AS-IV pretreatment suppressed apoptosis, increased Bax protein, caspase-3 and 9, and decreased BCL-2 protein in contrast to HaCaT cells with UVB-irradiation. AS-IV suppressed proinflammatory cytokine production, inhibited TLR4 and its downstream signaling molecules NF-κB, iNOS and cyclooxygenase-2 (COX-2) protein expression. We also found that the effects of AS-IV on cell viability and TLR4 expression was reversed by NAC. The protective of AS-IV on UVB-induced damage and TLR4 expression was dependent on ROS, as the increase in viability and decrease in TLR4 protein by AS-IV was significantly attenuated by ROS scavenger NAC (1 mM). CONCLUSION: Astragaloside IV prevent UVB-induced oxidative damage and inflammation by inhibiting TLR4 expression.

Clinical guidelines for microwave ablation of spinal metastases.

Spinal metastases are the most common source of morbidity in patients with cancer. Recently, microwave ablation has produced satisfactory results in the management of spinal metastases. However, there is still controversy in terms of clinical treatment, such as indication, power, time, and temperature. To standardize the application of microwave ablation technology and reduce the risk of surgical-related complications in spinal metastases, in this report, we aimed to summarize the current evidence and clinical experience of microwave ablation and developed a clinical guideline, initiated by the Musculoskeletal Tumor Group of the Committee for Minimally Invasive Therapy in Oncology of the Chinese Anti-Cancer Association. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used in to rate the quality of evidence and the strength of recommendations, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist was strictly followed to report the guideline. Finally, 15 evidence-based recommendations were formulated based on the 15 most concerned clinical questions among orthopedic surgeons, oncologists, and interventional radiologists in China. This guideline aims to promote the science-based normalization of microwave ablation for the treatment of spinal metastases.

A retrospective clinical study of patients with pregnancy-associated breast cancer among multiple centers in China (CSBrS-008).

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a special type of breast cancer that occurs during pregnancy and within 1 year after childbirth. With the rapid social development and the adjustment of reproductive policies in China, the average age of females at first childbirth is increasing, which is expected to lead to an increase in the incidence of PABC. This study aimed to accumulate clinical experience and to investigate and summarize the prevalence, diagnosis, and treatment of PABC based on large multicenter samples in China. METHODS: According to the Chinese Society of Breast Surgery, a total of 164 patients with PABC in 27 hospitals from January 2016 to December 2018 were identified. The pregnancy status, clinicopathological features, comprehensive treatment methods, and outcomes were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method. RESULTS: A total of 164 patients of PABC accounted for 0.30% of the total number of cases in the same period; of which, 83 patients were diagnosed during pregnancy and 81 patients during lactation. The median age of PABC was 33 years (24-47 years). Stage I patients accounted for 9.1% (15/164), stage II 54.9% (90/164), stage III 24.4% (40/164), and stage IV 2.4% (4/164). About 9.1% (15/164) of patients were luminal A. Luminal B patients accounted the most (43.3% [71/164]). About 15.2% (25/164) of patients were human epidermal growth factor receptor 2 (Her-2) overexpression and 18.9% (31/164) of patients were triple-negative breast cancer. For pregnancy breast cancer, 36.1% (30/83) of patients received direct surgery and 20.5% (17/83) received chemotherapy during pregnancy. About 31.3% (26/83) chose abortion or induction of labor. The median follow-up time was 36 months (3-59 months); 11.0% (18/164) patients had local recurrence or distant metastasis and 3.0% (5/164) died. CONCLUSIONS: It is safe and feasible to standardize surgery and chemotherapy for PABC.

Circular RNA BMI1 Serves as a Potential Target for Diagnosis and Treatment in Esophageal Cancer.

AIMS: Previous studies have confirmed that BMI1 is elevated in esophageal cancer, which is a potential therapeutic target for esophageal cancer. However, the clinical significance of circular RNA BMI1 (circ-BMI1) in esophageal cancer is not yet clear. Herein, we revealed the clinical implication of circ-BMI1 in esophageal cancer, and provided a theoretical basis for molecular diagnosis and potential targeted therapy of esophageal cancer. METHODS: Firstly, 10 fresh paired esophageal cancer tissues and paracancer tissues, 49 esophageal cancer serum samples and 28 healthy control serum samples were involved in our study. Differential expression and clinical significance of circ-BMI1 in esophageal cancer patients and healthy controls were evaluated by quantitative Real-time RT-PCR (RT-qPCR). Secondly, effects of circ-BMI1 differential expression on biological function of esophageal cancer cell line Eca109 were analyzed. Effects of circ-BMI1 on cell proliferation, migration and colony forming ability were evaluated by CCK-8, wound healing, and colony-forming assay. Cell apoptosis, drug sensitivity tests were also be conducted. Finally, influence of Eca109 cells differentially expressed by circ-BMI1 on tumorigenicity in nude mice was studied. RESULTS: Expression of circ-BMI1 in serum and tissues of esophageal cancer patients was significantly decreased compared to controls (P < 0.001 and P = 0.003, respectively). Area under the receiver operating characteristic curve (ROC) was 0.726. Cell proliferation, migration and colony forming ability of circBMI1-Eca109 cells were obviously decreased than that of NC-Eca109 cells (P < 0.05). circBMI1-Eca109 cells were more sensitive to 5-fluorouracil and cisplatin, and tumor volume of nude mice in circBMI1-Eca109 group was smaller (P < 0.05). CONCLUSIONS: The study indicated that expression of circ-BMI1 was significantly down-regulated in esophageal cancer. Overexpression of circ-BMI1 inhibited proliferation, migration, colony formation of Eca109 cells, and tumor growth of Eca109 cells in nude mice. circ-BMI1 may be a potential target for diagnosis and treatment in esophageal cancer.

Anthracycline-free or short-term regimen as adjuvant chemotherapy for operable breast cancer: A phase III randomized non-inferiority trial.

BACKGROUND: De-escalating anthracycline is gaining popularity for breast cancer patients. We aim to evaluate the non-inferiority of an anthracycline-free or short-term regimen to the standard anthracycline-based regimen for operable patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: It is a prospective, open-label, phase 3, randomized non-inferiority trial from June 1, 2010 to June 1, 2017. Follow-up had been kept until July 2019. This trial was conducted at Fudan University Shanghai Cancer Center. Patients with pT1-3N+ or pT2-3N0 but high-risk (grade II/III, lymphovascular invasion, ≤35 years of age or hormone-receptor negative) HER2-negative operable breast cancer were eligible and stratified by age, pathological tumour stage, pathological node status and hormone-receptor status. Patients were randomized to 6 cycles of docetaxel and cyclophosphamide (TC, n = 524), 3 cycles of cyclophosphamide/epirubicin/fluorouracil followed by 3 cycles of docetaxel (CEF-T, n = 523) or epirubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 12 weeks (EC-P, n = 524) as the intention-to-treat population. Of these patients, 94% completed allocated therapy. Difference in disease-free survival (DFS) compared to EC-P. The prespecified non-inferiority margin was 4.5%, corresponding to the hazard ratio (HR) of 1.44 (one-sided α = 0.05), with an assumed 5-year DFS of 89% for EC-P. FINDINGS: Included in the intention-to-treat population were 1571 patients (median [IQR] age, 50 [45-57] years; 92% estrogen receptor [ER]-positive; 59% pN+). Through a median follow-up of 5.5 years, HR for TC versus EC-P was 1.05 (5-year DFS: 85.0% vs. 85.9%; 90% confidence interval [CI]: 0.79-1.39, non-inferior P = 0.048) and for CEF-T versus EC-P, 0.99 (5-year DFS: 85.1% vs. 85.9%; 90% CI: 0.75-1.30, non-inferior P = 0.045). Grade 3 or 4 adverse events for TC included rash (3.9%) and peripheral neuropathy (2.8%) and for CEF-T and EC-P diarrhea and nausea/vomiting were predominant. Results of per-protocol analyses were similar. INTERPRETATION: Both TC and CEF-T are non-inferior adjuvant regimen to EC-P mainly in patients with ER+HER2- breast cancer. TC is a safe regimen that avoids anthracycline-related side effects. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (Grants 81672600, 81722032, 82072916, and 91959207), the 2018 Shanghai Youth Excellent Academic Leader, the Fudan ZHUOSHI Project, the Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals (grant SHDC12010116), the Cooperation Project of Conquering Major Diseases in the Shanghai Municipality Health System (grant 2013ZYJB0302), the Innovation Team of the Ministry of Education (grant IRT1223), and the Shanghai Key Laboratory of Breast Cancer (grant 12DZ2260100) and the National Cancer Institute (grant P30 CA16058).

[Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion].

OBJECTIVES: To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells. METHODS: A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. SCC-25 cells were cultured and divided into the CyPA interference sequence group, negative control group, and blank group. The expression levels of CyPA mRNA and protein in cells were detected by using real-time fluorescent quantitative polymerase chain reaction and Western blot, respectively. Cell proliferation was detected by using methyl thiazolyl tetrazolium and plate colony formation assays. Cell invasion was detected by using Transwell assay. RESULTS: The positive expression rate of CyPA protein in OSCC tissues was 76.62%, which was higher than that in adjacent tissues (P<0.05). The positive expression rate of CyPA protein in TNM stage T3+T4, clinical stage Ⅲ+Ⅳ, moderately or poorly differentiated lymph node metastasis was increased (P<0.05). Compared with the negative control and blank groups, the CyPA interference sequence group had decreased relative expression levels of CyPA mRNA and protein (P<0.05); optical density va-lues of cells at 24, 48, 72, and 96 h (P<0.05); and number of cell colonies and invasive cells (P<0.05). CONCLUSIONS: The CyPA protein is highly expressed in OSCC tissues, and the downregulation of CyPA gene expression in SCC-25 cells can reduce cell proliferation and inhibit cell invasion.