Etiology and clinical features of children with bronchiectasis in China: A 10-year multicenter retrospective study.

INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children. METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed. RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive. CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.

A New Three-Dimensional Classification of Proximal Tibiofibular Fractures: A Multicenter Study.

OBJECTIVES: To propose an updated definition of proximal tibia and fibula fracture (PTFF) and establish a three-dimensional (3D) structure-based classification of PTFF. METHODS: In total, 1358 adult patients (837 males and 521 females; 43.61 ± 15.13 years， 1364 affected knees) who were diagnosed with PTFF at the departments of orthopaedic surgery of four hospitals from January 2010 to December 2019 were enrolled. The new classification of PTFF, termed Wu classification, included three parts: classification of columns in the horizontal plane, regions in the frontal plane, and segments in the sagittal plane. All PTFFs were classified according to Schatzker, Luo, and Wu classification systems. Additionally, the incidence and characteristics of PTFFs were analyzed. RESULTS: The major internal structural fractures of PTFF were tibial plateau fracture (TPF) only (725, 53.15%), TPF and proximal fibular fracture (274, 20.09%), and isolated avulsion fracture of the posterior cruciate ligament (PCL) (189, 13.86%). Approximately a quarter of PTFF cases could not be classified using Schatzker or Luo classifications, but all PTFF cases could be classified using Wu classification. The most frequent PTFFs included all four columns in region IV, segment 2 (235, 17.23%); the posterolateral and posteromedial columns in region II, segment 2 (191, 14.00%); and the lateral and posterolateral columns in region IV, segment 2 (136, 9.97%). Isolated avulsion fracture of the anterior cruciate ligament (ACL) was categorized as three injury types, most of which involved the lateral and medial columns in region II, segment 1 (40/63, 64%). More than 97% of cases of isolated fractures of the PCL involved the posterolateral and posteromedial columns in region II, segment 2. The most frequent combined avulsion fracture of the ACL and PCL included all four columns in region II, segment 2 (18/24, 75%). All of the isolated avulsion fractures of the ACL were located in segment 1, and all those of the PCL in segment 2. The most common type of isolated proximal fibular fracture involved the posterolateral column in region III, segment 2 (23/26, 88%). The most frequent combined TPF and proximal fibular fracture involved all four columns in region IV, segment 2 (107/274, 39.05%). CONCLUSIONS: All cases of PTFF could be classified by the new 3D Wu classification which should be beneficial for clinical diagnosis, guidance of treatment, statistical analysis, academic communication, and prognosis, and the most frequent PTFF involved all four columns in region IV, segment 2.

A MnO2-coated multivariate porphyrinic metal-organic framework for oxygen self-sufficient chemo-photodynamic synergistic therapy.

Lately, chemotherapy and photodynamic therapy (PDT) synergistic therapy has become a promising anti-cancer treatment mean. However, the hypoxia in tumor leads to huge impediments to the oxygen-dependent PDT effects. In this work, a multifunctional nanoplatform (TUDMP) based on a multivariable porphyrin-nMOFs core and a manganese dioxide (MnO2) shell was prepared for relieving tumor hypoxia and enhancing chemo-photodynamic synergistic therapy performance. The obtained TUDMP nanoplatform could effectively catalyze the hydrolysis of hydrogen peroxide to generate oxygen and also lead to consumption of antioxidant GSH, thereby facilitating the production of cytotoxic reactive oxygen species (ROS) by photosensitizer under laser irradiation. More importantly, the decomposition of the MnO2 shell would further promote the release of the loaded doxorubicin (DOX), and thus an efficient chemo-PDT synergistic therapy was realized. Both in vitro and in vivo experimental results demonstrated the oxygen self-sufficient multifunctional nanoplatform could exhibit significantly enhanced anticancer efficiencies compared with chemotherapy or PDT alone.

Population Pharmacokinetics of High-Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia.

High-dose methotrexate (HD-MTX) is widely used in pediatric acute lymphoblastic leukemia (ALL) treatment regimens. In this study, we aimed to develop a population pharmacokinetic (PK) model of HD-MTX in Chinese pediatric patients with ALL for designing personalized dosage regimens. In total, 4,517 MTX serum concentration data for 311 pediatric patients with ALL, aged 0.75-15.2 years and under HD-MTX treatment, were retrospectively collected at a tertiary Children's Hospital in China. The non-linear mixed-effect model was used to establish the population PK model, using NONMEM software. The potential covariate effects of age, body weight, and biochemical measurements (renal and liver function) on MTX PK disposition were investigated. The model was then evaluated using goodness-of-fit, visual predictive check. MTX PK disposition was described using a three-compartment model reasonable well. Body weight, implemented as a fixed allometric function on all clearance and volume of distribution parameters, showed a substantial improvement in model fit. The final population model demonstrated that the MTX clearance estimate in a typical child with body weight of 19 kg was 6.9 L/h and the central distribution of volume estimate was 20.7 L. The serum creatinine significantly affected the MTX clearance, with a 0.97% decrease in clearance per 1 µmol/L of serum creatinine. Other covariates (e.g., age, sex, bilirubin, albumin, aspartate transaminase, concomitant medication) did not significantly affect PK properties of MTX. The proposed population PK model could describe the MTX concentration data in Chinese pediatric patients with ALL. This population PK model combined with a maximum a posteriori Bayesian approach could be used to estimate individual PK parameters, and optimize personalized MTX therapy in target patients, thus aiming to reduce toxicity and improve treatment outcomes.

A versatile nanoplatform based on multivariate porphyrinic metal-organic frameworks for catalytic cascade-enhanced photodynamic therapy.

In recent years, the antitumor application of photodynamic therapy (PDT) has gained widespread interest in treating solid tumors. Due to the hypoxic environment in tumors, the major limit of PDT seems to be the source of oxygen. In this work, we attempted to relieve hypoxia and enhance photodynamic therapy, and therefore, designed and assembled a catalytic cascade-enhanced PDT multifunctional nanoplatform. The mentioned platform termed UIO@Ca-Pt is based on porphyrinic metal-organic framework (UIO) combination, which is simultaneously loaded by CaO2 NPs with polydopamine (PDA) and then the Pt raw material to further improve biocompatibility and efficiency. In a tumor microenvironment, CaO2 could react with water to generate calcium hydroxide and hydrogen peroxide, which was further decomposed by Pt nanoparticles to form oxygen, thereby facilitating the generation of cytotoxic singlet oxygen by photosensitizer TCPP under laser irradiation. Both in vitro and in vivo experiment results confirmed the excellent oxygen production capacity and enhanced PDT effect of UIO@Ca-Pt. With guaranteed safety in PDT, the oxygen-supplying strategy might stimulate considerable interest in the development of various metal-organic materials with multifunctionality for tumor diagnosis and therapy.

Manganese dioxide (MnO2) based nanomaterials for cancer therapies and theranostics.

Today, cancer still poses a serious threat to human, but there is no exact cure. Therefore, exploring to accomplish high therapeutic performance is a challenging and urgent task. Since the nanoparticles unique properties were discovered, they have displayed promising potential for more effective therapies and have been widely used in photodynamic therapy (PDT) and radiation therapy (RT). However, some special properties of the tumour microenvironment (TME) have seriously affected the therapeutic outcomes, so the modulation of the TME becomes critical. Manganese dioxide (MnO2), as a transition metal oxide, has been widely used in biomedical fields with special physical and chemical properties, especially in regulating the TME. Furthermore, MnO2 has widely applications in various cancer treatments, such as PDT, chemodynamic therapy (CDT), immunotherapy, and some specific collaborative treatment. Herein, we reviewed the recent applications of MnO2 modified nanomaterials in tumour therapies and theranostics, including TME regulation, controlled drug loading/delivery/release, and imaging.

Recent Research on Methods to Improve Tumor Hypoxia Environment.

Cancer is a major disease burden worldwide. In recent years, in addition to surgical resection, radiotherapy and chemotherapy are recognized as the most effective methods for treating solid tumors. These methods have been introduced to treat tumors of different origins and stages clinically. However, due to insufficient blood flow and oxygen (O2) supply in solid tumors, hypoxia is caused, leading to decreased sensitivity of tumor cells and poor therapeutic effects. In addition, hypoxia will also lead to resistance to most anticancer drugs, accelerate malignant progress, and increase metastasis. In solid tumors, adequate O2 supply and adequate delivery of anticancer drugs are essential to improve radiotherapy and chemotherapy sensitivity. In recent decades, the researches on relieving tumor hypoxia have attracted researchers' extensive attention and achieved good results. However, as far as we know, there is no detailed review of the researches on alleviating tumor hypoxia. Therefore, in this contribution, we hope to give an overview of the researches on methods to improve tumor hypoxia environment and summarize their effect and application in tumor therapy, to provide a methodological reference for the research and development of new antitumor agents.

Case Report: Adult Retinoblastoma Progression in 19 Months.

SIGNIFICANCE: Retinoblastoma is the most common intraocular malignancy in childhood, comprising 4% of all pediatric cancers. Adult onset is extremely rare. Enucleation is usually performed in adult cases because of the atypical presentations and malignant features of the tumor, which lead to misdiagnosis. PURPOSE: We report a case of a 34-year-old woman who presented with an intraocular mass that was present for 19 months without any treatment before enucleation. CASE REPORT: A 34-year-old woman with a history of a dark shadow in her right eye for 2 weeks presented with a whitish-pink mass in the nasal superior retina. Angiography revealed leakage of vessels on the surface of the tumor. Ultrasound showed a midrange echogenic mass in the right eye. The patient denied treatment and was not seen again until 19 months after her first visit. B-scan ultrasound showed enlargement of intraocular growth without calcification. The patient subsequently underwent enucleation, and retinoblastoma was confirmed with histopathology of the enucleated eye. CONCLUSIONS: Retinoblastoma in adulthood is very rare. It has different clinical characteristics that need to be differentiated from other retinal tumors, such as primitive neuroectodermal tumor. They can develop very fast, but needle biopsy is not recommended. Eye care practitioners should be aware of the possibility of this malignancy in adults.

Oxygen Self-Sufficient Core-Shell Metal-Organic Framework-Based Smart Nanoplatform for Enhanced Synergistic Chemotherapy and Photodynamic Therapy.

The abnormal angiogenesis and insufficient oxygen supply in solid tumors lead to intratumoral hypoxia, which severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a multifunctional nanoplatform (ZDZP@PP) based on a zeolitic imidazolate framework-67 (ZIF-67) core as a hydrogen peroxide catalyst, a zeolitic imidazolate framework-8 (ZIF-8) shell with a pH-responsive property, and a polydopamine-poly(ethylene glycol) (PDA-PEG) layer for improving the biocompatibility is fabricated for not only relieving tumor hypoxia but also enhancing the efficacy of combination chemo-photodynamic therapy. The chemotherapy drug doxorubicin (DOX) and photosensitizer protoporphyrin IX (PpIX) are encapsulated in different layers independently; thus, a unique two-stage stepwise release becomes possible. Moreover, the nanoplatform can effectively decompose hydrogen peroxide to produce oxygen and thus relieve tumor hypoxia, which further facilitates the production of cytotoxic reactive oxygen species (ROS) by PpIX under laser irradiation. Both in vitro and in vivo experimental results confirm that the combination chemo-photodynamic therapy with the ZDZP@PP nanoplatform can provide more effective cancer treatment than chemotherapy or PDT alone. Consequently, the oxygen self-sufficient multifunctional nanoplatform holds promising potential to overcome hypoxia and treat solid tumors in the future.

Ras pathway mutation feature in the same individuals at diagnosis and relapse of childhood acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, while relapse and refractory ALL remains a leading cause of death in children. However, paired ALL samples of initial diagnosis and relapse subjected to next-generation sequencing (NGS) could construct clonal lineage changes, and help to explore the key issues in the evolutionary process of tumor clones. Therefore, we aim to analyze gene alterations during the initial diagnosis and relapse of ALL patients and to explore the underlying mechanism. METHODS: Targeted exome sequencing technology was used to detect molecular characteristic of initial diagnosis and relapse of ALL in 12 pediatric patients. Clinical features, treatment response, prognostic factors and genetic features were analyzed. RESULTS: In our 12 paired samples, 75% of pre-B-cell acute lymphoblastic leukemia (B-ALL) patients had alterations in the Ras pathway (NRAS, KRAS, NF1, and EPOR), and Ras mutation are very common in patients with ALL relapse. TP53 mutations mainly existed in the primary clones and occurred at the initial diagnosis and relapse of ALL. Relapse-associated genes such as NT5C2 and CREBBP were observed in patients with ALL relapse; however, all patients included in this study had gene abnormalities in the Ras pathway, and NT5C2 and CREBBP genes may collaboratively promote ALL relapse. CONCLUSIONS: Among the 12 ALL patients, Ras pathway mutations are common in ALL relapse and may be associated with other recurrence-related genes alterations. The study with paired samples could improve the understanding of ALL relapse.

Retrospective study of 213 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis from China.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial. METHODS: A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG). RESULTS: The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection. CONCLUSION: The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.

Prostate-specific membrane antigen expression in hepatocellular carcinoma, cholangiocarcinoma, and liver cirrhosis.

BACKGROUND: Primary liver cancer includes three subtypes: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and combined hepatocellular carcinoma. Patients with primary liver cancer experienced poor prognosis and high mortality, so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer. Prostate-specific membrane antigen (PSMA) expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently, but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited. AIM: To study the expression of PSMA in HCC, CCA, and liver cirrhosis. METHODS: A total of 446 formalin-fixed paraffin-embedded (FFPE) liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital. Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens (213 HCC, 203 CCA, and 30 liver cirrhosis). The tumor compartment and the associated neovascular endothelium were separately analyzed. PSMA expression was examined by two certified pathologists, and the final results were presented in a 4-point scoring system (0-3 points). Correlation between PSMA expression and clinicopathological information was also assessed. RESULTS: PSMA was expressed primarily in the neovascular endothelium associated with tumors. The positive rate of PSMA staining in HCC was significantly higher than that in CCA (86.8% vs 79.3%; P = 0.001) but was only 6.6% in liver cirrhosis (P = 0.000). HCC cases had more 3-score PSMA staining than CCA had (89/213, 41.8% vs 35/203, 17.2%; P = 0.001). PSMA expression correlated positively with the stage and grade of HCC and CCA. In both liver cancer subtypes, there were more PSMA+ cases in stages III-V diseases than in stages I and II. High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage. There was no significant association of PSMA expression with sex, age, region, α-fetoprotein, hepatitis B surface antigen, or tumor size in both tumor subtypes. CONCLUSION: Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.

Circular RNAs: from biogenesis and function to diseases.

OBJECTIVE: Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases. DATA SOURCES: The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science. STUDY SELECTION: The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type. RESULTS: CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5' and 3' ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases. CONCLUSIONS: Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient's body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.

Genetic variants and clinical significance of pediatric acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by molecular aberrations. Recently, genetic profiling has been fully investigated on ALL; however, the interaction between its genetic alterations and clinical features is still unclear. Therefore, we investigated the effects of genetic variants on ALL phenotypes and clinical outcomes. METHODS: Targeted exome sequencing technology was used to detect molecular profiling of 140 Chinese pediatric patients with ALL. Correlation of genetic features and clinical outcomes was analyzed. RESULTS: T-cell ALL (T-ALL) patients had higher initial white blood cell (WBC) count (34.8×109/L), higher incidence of mediastinal mass (26.9%), more relapse (23.1%), and enriched NOTCH1 (23.1%), FBXW7 (23.1%) and PHF6 (11.5%) mutations. Among the 18 recurrently mutated genes, SETD2 and TP53 mutations occurred more in female patients (P=0.041), NOTCH1 and SETD2 mutants were with higher initial WBC counts (≥50×109/L) (P=0.047 and P=0.041), JAK1 mutants were with higher minimal residual disease (MRD) level both on day 19 and day 46 (day 19 MRD ≥1%, P=0.039; day 46 MRD ≥0.01%, P=0.031) after induction chemotherapy. Multivariate analysis revealed that initial WBC counts (≥50×109/L), MLLr, and TP53 mutations were independent risk factors for 3-year relapse free survival (RFS) in ALL. Furthermore, TP53 mutations, age (<1 year or ≥10 years), and MLLr were independently associated with adverse outcome in B-cell ALL (B-ALL). CONCLUSIONS: MLLr and TP53 mutations are powerful predictors for adverse outcome in pediatric B-ALL and ALL. Genetic profiling can contribute to the improvement of prognostication and management in ALL patients.

Nanoscale Metal-Organic-Frameworks Coated by Biodegradable Organosilica for pH and Redox Dual Responsive Drug Release and High-Performance Anticancer Therapy.

Responsive nanocarriers with biocompatibility and precise drug releasing capability have emerged as a prospective candidate for anticancer treatment. However, the challenges imposed by the complicated preparation process and limited loading capacities have seriously impeded the development of novel multifunctional drug delivery systems. Here, we developed a novel and dual-responsive nanocarrier based on a nanoscale ZIF-8 core and an organosilica shell containing disulfide bridges in its frameworks through a facile and efficient strategy. The prepared ZIF-8@DOX@organosilica nanoparticles (ZDOS NPs) exhibited a well-defined structure and excellent doxorubicin (DOX) loading capability (41.2%) with pH and redox dual-sensitive release properties. The degradation of the organosilica shell was observed after 12 h incubation with a 10 mM reducing agent. Confocal imaging and flow cytometry analysis further proved that the nanocarriers can efficiently enter cells and complete intracellular DOX release under the low pH and high glutathione concentrations, which resulted in an enhanced cytotoxicity of DOX for cancer cells. Meanwhile, subcellular localization experiments revealed that the ZDOS NPs entered cells mainly by endocytosis and then escaped from lysosomes into the cytosol. Moreover, in vivo assays also demonstrated that the ZDOS NPs exhibited negligible systemic toxicity and significantly enhanced anticancer efficiencies compared with free DOX. In summary, our prepared pH and redox dual-responsive nanocarriers provide a potential platform for controlled release and cancer treatment.

Advances in the treatment of rhegmatogenous retinal detachment.

The pathogenesis of rhegmatogenous retinal detachment depends on three factors, namely, retinal rupture, vitreous liquefaction and traction causing the retina to separate from the pigment epithelium, among which retinal rupture is the most important. Retinopathy is caused by a gap between the neurosensory retina and the retinal pigment epithelium, which severely damages the visual function of the patient. Therefore, early clinical discovery, prevention and selection of an appropriate treatment are important. This article reviews progress in the treatment of retinal detachment.

Design, synthesis and biological evaluation of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy.

A series of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy were designed, synthesized and biologically evaluated. Among them, compound 7l displayed the most potent inhibitory against COX-2 (IC50 = 0.82 µM) and antiproliferative activities against Hela cells (IC50 = 0.34 µM) compared with Celecoxib (IC50 = 0.38 and 7.91 µM). The further mechanistic studies revealed that 7l could induce apoptosis of Hela cells by mitochondrial depolarization and the antiproliferative activities of 7l were positively correlated with the levels of intracellular NO release in Hela cells. Most notably, 7l could dramatically suppress tumor growth in Hela cells xenografted mouse model. In summary, compound 7l may be promising candidates for cancer therapy.

Design and biological evaluation of novel hybrids of 1, 5-diarylpyrazole and Chrysin for selective COX-2 inhibition.

The overexpress of COX-2 was clearly associated with carcinogenesis and COX-2 as a possible target has long been exploited for cancer therapy. In this work, we described the design and synthesis of a series of diarylpyrazole derivatives integrating with chrysin. Among them, compound e9 exhibited the most potent inhibitory activity against COX-2 and antiproliferative activity against Hela cells with IC50 value of 1.12 µM. Further investigation revealed that e9 could induce apoptosis of Hela cells by mitochondrial depolarization and block the G1 phase of cell cycle in a dose-dependent manner. Besides, molecular docking simulation results was further confirmed that e9 could bind well with COX-2. In summary, compound e9 may be promising candidates for cancer therapy.

Circulating MicroRNA-21, MicroRNA-23a, and MicroRNA-125b as Biomarkers for Diagnosis and Prognosis of Burkitt Lymphoma in Children.

BACKGROUND The aim of this study was to investigate the diagnostic and prognostic value of microRNA (miRNA)-21, miRNA-23a, and miRNA-125b in Burkitt lymphoma (BL) in children. MATERIAL AND METHODS We recruited 41 children with BL for the case group, 56 children with lymph node inflammation for the positive control group, and 60 healthy children for the negative control group. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was conducted for detection of circulating miRNA-21, miRNA-23a, and miRNA-125b. A receiver operating characteristic (ROC) curve was drawn to compare the diagnostic value of miRNA-21, miRNA-23a, and miRNA-125b. Kaplan-Meier method and log-rank test were used for prognostic analyses. RESULTS MiRNA-21 and miRNA-23a had significantly higher expression in cases than in positive and negative controls (all P<0.05). Overexpression of miRNA-21 and miRNA-23a were associated with staging, WBC, upregulated serum lactate dehydrogenase (LDH) level, presence of lymphoma size ≥6 cm, and cluster of differentiation 10 (CD10) expression, while miRNA-125b expression had an association with staging and upregulated serum LDH level (both P<0.05). ROC curves of miRNA-21, miRNA-23a, and miRNA-125b presented an area under curve (AUC) of 0.759, 0.853 and 0.615, respectively. MiRNA-21 and miRNA-23a in combination had an AUC of 0.869. After treatment, both miRNA-21 and miRNA-23a expression were significantly decreased (both P<0.05). Advanced clinical stage, upregulated LDH, and lymphoma size of ³6 cm were related to low complete remission rate (all P<0.05). CONCLUSIONS Patients with high expression of miRNA-21 and miRNA-23a had significantly lower complete remission rates and survival rates than those with low expression. Expression of miRNA-21 and miRNA-23a may serve as useful diagnostic and prognostic biomarkers in children with BL.

[Application of a self-made steel wire guide in the treatment of avulsion fractures of tibial posterior cruciate ligament].

OBJECTIVE: To explore the effect of a self-made guiding needle of steel wire in guiding the wire through the tibial tunnel for the treatment of avulsion fractures of tibial posterior cruciate ligament with open reduction and wire fixation. METHODS: From February 2011 to June 2014, a total of 22 patients with avulsion fractures of tibial posterior cruciate ligament underwent surgical treatments were analyzed, including 14 males and 8 females with an average age of 35.6 years old (ranged, 17 to 63 years old). According to Meyers classification, 9 patients were classified as type II, 13 patients were classified as type III. All the patients underwent open reduction and wire fixation with medial knee "L" shape approach. A wire guiding needle was used to guide the wire through the tibial tunnel during operation. RESULTS: With the assistance of wire guidance needles, wires passed through the tibial tunnel rapidly during the operation in all the 22 patients. All the patients were followed up, X-ray imagings 6 months after operation showed the fractures healed well. The average follow-up time in all patients was 6 months (ranged, 6 to 12 months). The averaged Lysholm knee score in 22 knee was 92.7 +/- 3.4. All patients' posterior drawer test were negative. CONCLUSION: Self-made wire guiding needle can simplify the operation procedures in which the wires pass through the tibial tunnel, shorten the operation time, reduce the surgical trauma and complications, and be worthy of clinical application.