Isolated non-immune mediated second-degree atrioventricular block in fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To uncover the clinical course of fetal isolated non-immune mediated second-degree AVB and determine the factors associated with the spontaneous recovery for fetal non-immune second-degree atrioventricular block (AVB). METHODS: A total of 20 fetuses with isolated, non-immune mediated second-degree AVB were prospectively recruited between 2014 and 2022. These fetuses were divided into the spontaneous recovery group (n=12) and the non-spontaneous recovery group (n=8). Maternal and fetal basic characteristics, intrauterine and postnatal outcomes were compared between groups. RESULTS: Twelve fetuses restored 1:1 atrioventricular conduction in utero and did not recur during the postnatal follow-up period. The residual eight fetuses maintained as second-degree AVB and six of them were aborted due to parental request in utero. Of the two live children with second-degree AVB, one of them progressed to complete AVB at the latest follow up at the age of 34 months, but without any symptoms, heart enlargement or dysfunction. The residual one progressed to complete AVB and was finally diagnosed with type 2 long-QT syndrome. Fetuses in the spontaneous recovery group presented with earlier gestational age at diagnosis (20.0[17.0-26.0] vs. 24.5[18.0-35.0] weeks, p=0.004) and higher atrial rate (147[130-160] vs 138.00[125.00-149.00] bpm, p=0.006) in comparison with the non-spontaneous recovery group. A cut-off value of 22.5 weeks of gestational age and 144 bpm of atrial rate at diagnosis could predict the failure of spontaneous recovery, with sensitivities of 87.5%, 75%, and specificities of 92.0%, 87.5%, respectively. CONCLUSIONS: The outcome of fetal non-immune second-degree AVB was favorable. Earlier gestational age at diagnosis and higher atrial rate were related to spontaneous reversion for isolated non-immune-mediated second-degree AVB. However, prenatal gene test should be performed for those with persistent AVB to exclude the heritable disorders including LQTS. These findings may provide important references for clinical management and prenatal counseling. This article is protected by copyright. All rights reserved.

Remarkable undercooling capability and metastable thermophysical properties of liquid Nb84.1Si15.9 alloy revealed by electrostatic levitation in outer space.

The stable manipulation, high undercooling, and thermophysical property measurement of the liquid Nb84.1Si15.9 refractory alloy were successfully achieved by the electrostatic levitation technique on board the China Space Station. By controlling the superheating temperature, a maximum liquid undercooling up to 421 K (0.18 TL) was obtained in the space environment, and two distinct solidification paths with different recalescence features were realized at metastable undercooled states. The liquid density and the ratio of specific heat to emissivity were measured in a wide temperature range from 1841 to 2346 K, which displayed linear and quadratic relations vs temperature, respectively. The liquid emissivity was further deduced from the specific heat of the liquid alloy calculated by molecular dynamics simulation. In addition, both the density and structural characteristics of the undercooled liquid alloy were also analyzed by MD calculations.

[Research status of potential therapeutic targets for thyroid-associated ophthalmopathy].

Thyroid-associated ophthalmopathy (TAO) is an autoimmune eye disease that affects visual function and appearance, involving pathological remodeling processes of orbital tissue such as inflammatory reaction, oxidative stress, lipogenesis, and fibrosis. Current clinical first-line treatment options cannot be effective for all patients. This article summarizes the research on potential therapeutic targets of TAO at home and abroad in recent years, including receptor protein targets, immune cell targets, fat suppression targets, anti-fibrosis targets, transcription factor targets, and metabolic regulatory enzyme targets. Both non-natural compounds and natural compounds are introduced, with a view to providing clinical researchers with reference and ideas in the treatment of TAO and promoting the clinical application of new therapeutic drugs.

[THRIVE combined with i-gel laryngeal mask for prolonging apneic oxygenation time in retrograde intrarenal surgery].

OBJECTIVE: To explore the effect of THRIVE combined with i-gel laryngeal mask on the safety of oxygen therapy in apnea and surgical precision of retrograde intrarenal surgery. METHODS: A total of 120 patients undergoing retrograde intrarenal surgery under general anesthesia with laryngeal mask were randomized into 3 groups (n=40), and after the flexible ureteroscope entered the renal pelvis and located the stones, the patients received assisted ventilation in APPV mode (control group), ventilation with small tidal volume and high respiratory rate (group H), or THRIVE combined with laryngeal mask for oxygen supply without using the ventilator (THRIVE group). The time for lithotripsy by the surgeons, surgeons' satisfaction, diaphragm mobility, and times of urinary tract mucosal injury were recorded, and arterial blood pressure, heart rate, SpO2, PaO2, PaCO2, and pH value were measured before, during and after lithotripsy. RESULTS: Among the 3 groups, THRIVE group had the shortest time for lithotripsy, best satisfaction of the surgeons, the lowest diaphragmatic mobility of the patients, and the smallest number of mucosal injuries. The arterial blood pressure, heart rate, and SpO2 of the patients did not differ significantly among the 3 groups. At 20 min and 30 min after the start of lithotripsy, PaO2 decreased significantly in group H and THRIVE group; in THRIVE group, PaCO2 increased and pH decreased significantly at 10, 20 and 30 min after the start of lithotripsy. No significant difference was found in oxygenation indicators among the 3 groups upon discharge from the PACU. CONCLUSION: In retrograde intrarenal surgery, THRIVE combined with i- gel laryngeal mask for oxygen therapy during the anaerobic period can improve the surgical accuracy and maintain the patient's oxygenation index in a controllable range within 30 min.

[Alveolar nitric oxide concentration has a potential value in the diagnosis and differential diagnosis of interstitial lung diseases].

OBJECTIVE: To investigate the value of exhaled nitric oxide (eNO) in the diagnosis and differential diagnosis of interstitial lung disease (ILD). METHODS: This study was conducted among 45 patients with interstitial lung disease, including 18 with connective tissue disease-related ILD (CTD-ILD) and 27 with non-CTD-ILD, with 68 healthy subjects as the control group. According to European Respiratory Association Guidelines, alveolar nitric oxide (CaNO) concentration and fractional exhaled nitric oxide (FeNO) level were measured at the flow rates of 50 and 200 mL/s. The predictive level of CaNO was analyzed using receiver-operating characteristic curve (ROC), and the correlations between CaNO and pulmonary function indicators were examined in the patients with ILD. RESULTS: CaNO, FeNO50, and FeNO200 levels were significantly higher in patients with ILD than in the healthy controls. Logistic regression analysis showed that lowered levels of CaNO and FeNO200 were risk factors for ILD. ROC curve analysis showed that the area under the curve (AUC) of CaNO combined with FeNO200 was 0.829 (95% CI: 0.752-0.906) for the diagnosis of ILD. In patients with ILD, CaNO levels were negatively correlated with DLCO%pred (r=-0.471, P < 0.05). Subgroup comparison showed a significantly higher CaNO level in CTD-ILD group than in non-CTD-ILD group. The AUC for CaNO to discriminate CTD-ILD from non-CTD-ILD was 0.725 (95% CI: 0.576 to 0.875). CONCLUSION: CaNO has a potential value in the diagnosis of ILD and differential diagnosis of CTD-ILD.

Release of Interface Confined Water Significantly Improves Dentin Bonding.

Water residue and replacement difficulty cause insufficient adhesive infiltration in demineralized dentin matrix (DDM), which produces a defective hybrid layer and thus a bonding durability problem, severely plaguing adhesive dentistry for decades. In this study, we propose that the unique properties of a highly hydrated interface of the porous DDM can give rise to 1 new type of interface, confined liquid water, which accounts for most of the residue water and may be the main cause of insufficient infiltration. To prove our hypothesis, 3 metal ions with increasing binding affinity and complex stability (Na+, Ca2+, and Cu2+) were introduced respectively to coordinate negatively charged groups such as -PO43-, -COO- abundant in the DDM interface. Strong chelation of Ca2+ and Cu2+ rapidly released the confined water, significantly improving penetration of hydrophobic adhesive monomers, while Na+ had little effect. A significant decrease of defects in the hybrid layer and a much decreased modulus gap between the hybrid layer and the adhesive layer greatly optimized the microstructure and micromechanical properties of the tooth-resin bonding interface, thus improving the effectiveness and durability of dentin bonding substantially. This study paves the way for a solution to the core scientific issue of contemporary adhesive dentistry: water residue and replacement in dentin bonding, both theoretically and practically.

[Levofloxacin combined with cellulase can eradicate bacille Calmette-Guerin biofilm infection].

OBJECTIVE: To investigate the inhibitory effects of levofloxacin (LEV) combined with cellulase against bacille CalmetteGuerin (BCG) biofilms in vitro. METHODS: The mature growth cycle of BCG biofilms was determined using the XTT method and crystal violet staining. BCG planktonic bacteria and BCG biofilms were treated with different concentrations of LEV and cellulose alone or jointly, and the changes in biofilm biomass were quantified with crystal violet staining. The mature BCG biofilm was then treated with cellulase alone for 24 h, and after staining with SYTO 9 and Calcofluor White Stain, the number of viable bacteria and the change in cellulose content in the biofilm were observed with confocal laser scanning microscopy. The structural changes of the treated biofilm were observed under scanning electron microscopy. RESULTS: The MIC, MBC and MBEC values of LEV determined by broth microdilution method were 4 µg/mL, 8 µg/mL and 1024 µg/mL, respectively. The combined treatment with 1/4×MIC LEV and 2.56, 5.12 or 10.24 U/mL cellulase resulted in a significant reduction in biofilm biomass (P < 0.001). Cellulase treatments at the concentrations of 10.24, 5.12 and 2.56 U/mL all produced significant dispersion effects on mature BCG biofilms (P < 0.001). CONCLUSION: LEV combined with cellulose can effectively eradicate BCG biofilm infections, suggesting the potential of glycoside hydrolase therapy for improving the efficacy of antibiotics against biofilmassociated infections caused by Mycobacterium tuberculosis.

[Efficacy of one-stage total spondylectomy and circumferential reconstruction for axial tumors through a combined anterior retropharyngeal-posterior approach].

Objective: To elucidate the safety and efficacy of one-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach for axial tumors. Methods: A total of 20 patients with axial tumor who received total spondylectomy through a combined anterior retropharyngeal-posterior approach in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from February 2006 to December 2018 were retrospectively analyzed. Anterior reconstruction was performed with a special-shaped titanium mesh or three-dimensional printed (3DP) implants. The degree of local pain and neurological function was assessed by the visual analogue scale (VAS) and Frankel classification systems, respectively. Status of internal fixation and local recurrence was analyzed by radiological examination during follow-up. Results: Among the 20 patients, 12 were male and 8 were female with a mean age of (59.1±11.0) years (31 to 72 years). The mean operation time was (605.0±60.1) minutes (430 to 700 minutes) with a mean intraoperative blood loss of (1 250±347) ml (800 to 2 400 ml). The mean postoperative hospital stay was (13.2±2.8) days (8 to 20 days), and mean follow-up duration was (37.2±14.2) months(14 to 66 months). Anterior reconstructions were performed with a special-shaped titanium mesh in 14 patients and with 3DP implants in another 6 patients. Posterior occipital-cervical fixation was performed in 5 patients, while cervical fixation only in another 15 patients. The mean VAS score of pain at the last follow-up decreased significantly when compared with that before operation (1.6±0.6 vs 7.1±1.1, P<0.001). Nine patients with neurological deficits indicated significant improvement by at least 1 level at the last follow-up; among them, 2 cases of Frankel B improved to Frankel C and D, respectively; 3 cases of Frankel C all improved to Frankel D, and 4 cases of Frankel D improved to Frankel E. The perioperative complications included: 2 cases of vertebral artery injury, 2 cases of dysphagia, 3 cases of hoarseness and cough, 2 cases of cerebrospinal fluid leakage, and 1 case of greater occipital neuralgia. At the last follow-up, 5 patients died and 3 patients relapsed. Only 1 case suffered fixation failure due to local recurrence at the last follow up. Conclusions: One-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach is safe and effective for axial tumors with favorable clinical outcomes and minor complications. Circumferential reconstruction with special-shaped titanium mesh or 3DP implant and posterior fixation can effectively reconstruct mechanical stability.

A spectral CT-based nomogram for predicting the response to induction chemotherapy in nasopharyngeal carcinoma.

AIM: To establish a spectral computed tomography (CT)-based nomogram for predicting the response to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-four patients with NPC who underwent spectral CT examination before ICT were enrolled prospectively. Patients were assigned to response and non-response groups according to response evaluation. The predictive indicators were spectral CT parameters of venous phase, including iodine concentration (IC), normalised IC (NIC), slope of the spectral attenuation curve in Hounsfield units (λHU), effective atomic number (Eff-Z), and water concentration. Multivariate logistic regression was used to construct a predictive model. The receiver operating characteristic (ROC) and calibration curves were used to evaluate the robustness of model, while the bootstrap method was used for internal validation. The Hosmer-Lemeshow test was used to test the goodness of fit of the discriminant model. RESULTS: Multivariate logistic regression analysis showed that NIC, λHU, and Eff-Z were the potential predictors, and the three indicators were further used to establish a predictive model. The nomogram was evaluated to have good predictive performance, the area under the ROC curve was 0.909 (95% confidence interval [CI]: 0.799-0.970), and the model was well calibrated (χ2 = 8.149, p=0.419). CONCLUSIONS: The spectral CT nomogram has potential clinical value in predicting response to ICT in NPC and may help guide individualised treatment decisions.

[Expert consensus on measurement and clinical application of serum HBV RNA in patients with chronic HBV infection].

Since the discovery of circulating hepatitis B virus (HBV) RNA in the peripheral blood of patients with chronic hepatitis B in 1996, a growing number of studies have focused on clarifying the biological characteristics and clinical application value of serum HBV RNA. This consensus mainly summarizes the research progress of serum HBV RNA existing profiles, quantitative detection methods, and current clinical applications. In order to better apply this indicator for the clinical management of patients with chronic HBV infection, recommendations on quantitative detection target regions, detection results, and clinical applications are put forward.

Immunogenicity of the mRNA-1273 and ChAdOx1 nCoV-19 vaccines in Asian patients with autoimmune rheumatic diseases under biologic and/or conventional immunosuppressant treatments.

OBJECTIVE: Nucleic acid-based vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are effective in the general population. However, it is unknown whether this is true in Asian patients with autoimmune rheumatic diseases (ARDs) who have received various combinations of disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We designed a large prospective observational study recruiting 228 patients with ARDs in a tertiary rheumatology centre in Taiwan. Altogether, 142 received biological or targeted synthetic DMARDs and 86 received only conventional synthetic (cs) DMARDs. Serum levels of immunoglobulin G antibody against SARS-CoV-2 spike proteins were measured 2-6 weeks after COVID-19 vaccination with mRNA-1273 (Moderna®) or ChAdOx1 nCoV-19 (Oxford/AstraZeneca®). The immunomodulatory therapies were not modified before or after vaccination. RESULTS: Overall, 194 patients (85.09%) exhibited antibodies (758.33 ± 808.43 ng/mL) but 34 patients did not (103.24 ± 41.08 ng/mL). Patients with systemic lupus erythematosus or rheumatoid arthritis had significantly lower humoral responses to COVID-19 vaccination than those with other ARDs (p < 0.05). There was no significant difference in immunogenicity among patients on different csDMARD treatments. Compared to patients treated with only csDMARDs, those on rituximab or abatacept therapy had significantly lower immune response to the vaccination (p = 0.008 and p = 0.035, respectively). Patients who were treated with anti-tumour necrosis factor-α or interleukin-6 inhibitor exhibited higher titres of vaccination antibodies than those treated with direct lymphocyte inhibitors. CONCLUSIONS: mRNA-1273 and ChAdOx1 nCoV-19 vaccines were immunogenic in the majority of ARD patients. Rituximab and abatacept were associated with significantly diminished COVID-19 vaccination immunogenicity.

[The dual mTORC1/2 inhibitor AZD2014 inhibits acute graft rejection in a rat liver transplantation model].

OBJECTIVE: To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation. METHODS: Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema. RESULTS: Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ2=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01). CONCLUSIONS: AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.

[Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis].

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 µmol/L vs. 17.9 µmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

A multimodality intervention to improve musculoskeletal health, function, metabolism, and well-being in spinal cord injury: study protocol for the FIT-SCI randomized controlled trial.

BACKGROUND: A spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual's health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI. METHODS: This single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant's home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety. DISCUSSION: We anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI. TRIAL REGISTRATION: ClinicalTrials.gov :  ( NCT03576001 ). Prospectively registered: July 3, 2018.

[Navigation-guided nasal endoscopy for removal of the cavernous hemangioma of the orbital apex through the sphenoid approach].

Objective: To explore the feasibility of navigation-guided nasal endoscopy for removal of the cavernous hemangioma of the orbital apex through the sphenoid approach. Methods: Retrospective case series study. From May 2012 to December 2019, 12 patients (12 eyes) with imaging findings of cavernous hemangioma in the orbital apex were collected at the Eye Hospital Affiliated to Nanchang University, including 3 males and 9 females aged 32 to 59 years. All patients underwent navigation-guided sinusoscopy through the sphenoid approach to remove the cavernous hemangioma of the orbital apex (video attached). Changes of visual function and complications after operation were analyzed. Results: In 3 patients without visual impairment, the postoperative visual function was still normal. Among the remaining 9 patients with preoperative visual impairment, visual function was fully recovered in 3 patients after operation, was improved in 2 patients, and had no change in 4 patients. There were no complications in 3 of the 12 patients, and 9 patients had transient, mildly limited intraocular rotation with diplopia after operation, which all returned to normal within 1 month. Conclusion: Navigation-guided sinus endoscopy through the sphenoid approach is effective and feasible in the removal of the cavernous hemangioma of the orbital apex. (Chin J Ophthalmol, 2021, 57: 837-843).

[Antitumor effects of AZD2014, a dual mTORC1/2 inhibitor, against human hepatocellular carcinoma xenograft in nude mice].

OBJECTIVE: To investigate the antitumor effects of AZD2014 (a dual mTORC1/2 inhibitor) against human hepatocellular carcinoma (HCC) xenograft in mice. METHODS: HCCLM3 cells were injected subcutaneously in the right flank of nude mice, and when the tumors were macroscopic, the mice were randomized into 2 groups for daily intraperitoneal injection of AZD2014 (5 mg/kg, n=5) or vehicle (5 mL/kg, n=5) for 24 days. Tumor growth was assessed using calipers every 4 days and the tumor growth curve was drawn. After the final injection, the mice were euthanized and the tumors were dissected for measuring tumor weight and histopathological analysis with HE staining. Immunohistochemical staining was used to detect the expressions of Ki-67, cleaved caspase-3, CD31, and the epithelial-mesenchymal transition (EMT)-related proteins (Ecadherin, N-cadherin, and vimentin) in the tumor tissue. RESULTS: Daily treatment with AZD2014 significantly suppressed HCC growth as compared with the control group. HE staining showed significantly increased tumor necrosis in AZD2014-treated mice. AZD2014 treatment inhibited tumor cell proliferation, angiogenesis and EMT progression as shown by decreased expressions of Ki-67, CD31, N-cadherin, and vimentin and increased expression of E-cadherin in the tumor tissue, and significantly promoted tumor cell apoptosis as shown by an increased expression of cleaved caspase-3 in AZD2014-treated mice. CONCLUSIONS: AZD2014 is a highly potent antitumor agent for HCC in nude mice bearing HCC xenografts. AZD2014 can effectively inhibit tumor proliferation, angiogenesis and EMT progression and induce tumor cell necrosis and apoptosis.

[Research advances on platelet-rich blood products combined with biological materials in wound repair].

The efficient management of wounds is the focus of current research. In addition to conventional wound management and necessary surgery, the role of pro-healing drugs in wound treatment has gradually been emphasized. Platelet-rich blood products that is rich in a variety of biologically active molecules are considered as a low-cost and safe therapy in promoting tissue healing, and have great development prospects in the field of regenerative medicine. However, due to the lack of standard preparation and management and the unstable activities of the biomolecules in them, the therapeutic effects of platelet-rich blood products are uneven. In order to solve these problems, researches related to the protection and delivery of biologically active molecules in platelet-rich blood products by biomaterials have gradually increased in recent years, which is also one of the latest trends in wound treatment research. This article first briefly introduces the types of platelet-rich blood products, then outlines the latest research progress achieved by their combination with biomaterials, and finally summarizes the research progress and future research directions of the combination approach in wound treatment.

CircTP53 promotes the proliferation of thyroid cancer via targeting miR-1233-3p/MDM2 axis.

BACKGROUND: Follicular cells give rise to thyroid cancer. Worldwide thyroid cancer incidence continues to rise in recent decades but the mortality rate remains at a stable level. The discovery of novel molecular mechanisms in the pathogenesis of thyroid cancer will promote new diagnostic or therapeutic strategies. Circular RNA (circRNA) is a type of noncoding RNA which is characterized by the covalently closed loop and non-protein coding capacity. The abnormal expression of circRNAs is an important part during the pathogenesis and development of thyroid cancer. CircTP53 is a novel circRNA, and we aimed to investigate its function in the pathogenesis of thyroid cancer and to further demonstrate the underlying molecular mechanism. METHODS: The levels of circTP53, miR-1233-3p, and other relative mRNA were analyzed by qRT-PCR. Protein levels were shown by Western blot. RNA-pulldown assay and luciferase assay were employed to examine the interaction between circTP53 and miR-1233-3p. Cell proliferation was analyzed by the MTT assay. RESULTS: CircTP53 was a circRNA highly expressed in thyroid cancer tissues. CircTP53 promoted cell proliferation and cell viability of TPC-1 cells. Knockdown of circTP53 inhibited the expression of Mouse double minute 2 (MDM2) and increased the protein level of p53. CircTP53 acted as a target of miR-1233-3p to increase MDM2 expression. p53 expression in thyroid cancer tissue exhibited a negative correlation with circTP53 expression. CONCLUSION: In thyroid cancer, overexpressed circTP53 decreased the protein level of p53 via targeting miR-1233-3p/MDM2 axis and promoted cancer cell proliferation.