Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective To construct a comorbidity network for medical expenses by analyzing the rele-vant medical records,and to construct a deep learning prediction model by combining with the disease net-works and long short-term memory neural networks in order to improve the accuracy of individual medical ex-pense prediction and provide the assistance for optimizing the medical policies and enhancing the patient health management level.Methods Based on the medical records of Taiwan,China Health Insurance Research Data-base during 2000-2013,the data of 5.84 million visits from 9 963 patients were analyzed,and a comorbidity network of medical expenses for 104 common diseases was constructed.The network structure was analyzed and the potential comorbidity was predicted,and the deep learning model of individual medical cost was con-structed by combining the input of patient's gender,age,medical history and other information.Results The constructed medical cost comorbidity network consists of 104 nodes,3 390 edges and 6 modules,and is a high-ly connected network with nodes,indicating that the medical costs possesses the high correlation between dis-eases.The constructed deep learning prediction model significantly improves the prediction accuracy compared to the traditional regression models and deep learning models that do not fully consider the comorbidity infor-mation.Conclusion The constructed model provides a new theoretical perspective for understanding the co-morbidity of diseases,as well as an effective tool for accurately predicting medical costs,optimizing medical re-source allocation and achieving the personalized medical services.

Objective Port-wine stains are a kind of dermatological disease of congenital capillary malformation.Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration,we intend to construct a nanodrug co-loaded with rapamycin(RPM),an anti-angiogenesis drug,and photochlor(HPPH),a photosensitizer,and integrate the nanodrug with dissolvable microneedles(MN)to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains.Methods First,RPM and HPPH co-loaded nanoparticles(RPM-HPPH NP)were prepared by the emulsification solvent-volatilization method,and its ability to generate reactive oxygen species(ROS)was investigated under 660 nm laser irradiation.Mouse hemangioendothelioma endothelial cells(EOMA)were used as the subjects of the study.The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry.The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays(with free RPM serving as the control).Then,hyaluronic acid(HA)dissolvable microneedles loaded with RPM-HPPH NP(RPM-HPPH NP@HA MN)were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method.The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine.The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment.Results The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation.At the cellular level,RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner.The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation.Under laser irradiation,RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant(P＜0.05).The height of the needle tip of RPM-HPPH NP@HA MN was 600 μm and the mechanical property of a single needle was 0.75048 N.Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum.Conclusion RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy,providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.
Humans ; Transcription Factors/metabolism* ; Nuclear Proteins/metabolism* ; Histones ; Cell Cycle Proteins/metabolism* ; Neoplasms/metabolism* ; Protein Domains

Rheumatoid arthritis (RA) is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS). The up-regulated cellular membrane expression of G protein coupled receptor kinase 2 (GRK2) of FLS plays a critical role in RA progression, the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor (EP4) signaling and FLS abnormal proliferation. Recently, although our group found that paeoniflorin-6'-

Objective To explore the effect of decreased air pollutants concentrations on the incidence of Type 2 Diabetes Mellitus (T2DM). Methods A prospective cohort was designed in Tianjin where the air quality gradually improved from 2014 to 2018. A total of 5 077 community residents (18-90 years old) were recruited as the baseline population from 2013 to 2014. From 2014 to 2018 follow-up was carried out year by year to observe the new incidence of T2DM in the cohort. The HR and 95%CI (95% confidence interval) were calculated with the multiple Cox proportional hazard regression model to evaluate the effect of the decrease in the concentrations of SO₂, NO₂, and particulate matters with diameters <10μm and <2.5μm (PM₁₀, PM_2.5) on the incidence of T2DM. Results The cohort was followed up year by year from 2014 to 2018, with a cumulative follow-up of 25 385 person-years over the 5 years. At the same time, the air quality of Tianjin was significantly improved. Statistical analysis results after covariate adjustment revealed that the risk of T2DM in the population decreased by 0.172, 0.124, and 0.210 times, for a decrease of 10 μg/m³ in the annual average concentrations of SO₂, PM₁₀, and PM_2.5 each, respectively (SO2：HR=0.828，95%CI=0.757-0.907；PM₁₀：HR=0.876，95%CI=0.816-0.941；PM_2.5：HR=0.790，95%CI=0.694-0.899). Conclusion The implementation of environmental protection measures to improve air pollution could reduce the risk of T2DM in the population and control the increasing prevalence.

OBJECTIVE: To observe the clinical effect of platelet rich plasma (PRP) combined with β tricalcium phosphate bioceramic bone in the treatment of non traumatic necrosis of the femoral head in ARCO stageⅡ. METHODS: From January 2017 to December 2018, 100 patients (160 hips) with ARCO stageⅡnon traumatic necrosis of the femoral head were divided into PRP group and control group. In PRP group, 50 patients (80 hips), 22 males and 28 females, aged from 18 to 65 (43.47± 7.23) years, with a course of 4 to 18 (15.8±2.9) months, underwent core decompression and bone grafting combined with PRP implantation. There were 50 cases (80 hips) in the control group, including 27 males and 23 females, aged 20 to 63 (45.72± 7.43) years, and the course of disease was 6 to 19 (14.9±3.8) months. Hip X-ay film was followed up after operation. Harris score and VAS score were used to evaluate the curative effect, and the survival rate of hip joint was recorded. RESULTS: All patients had good wound healing, no infection, thrombosis and other complications. All patients were followed up for 12 to 14 (12.0±0.4) months. Twelve months after operation, the image expression of PRP group was better than that of control group( CONCLUSION Platelet-rich plasma(PRP) combined with artificialbone for core decompression and bone grafting can change the situation of simple artificial bone implantation and uncertain curative effect, improve the success rate of this operation, effectively reduce the collapse rate of femoral head necrosis in the early and middle stage, delay or even avoid hip replacement.
Adolescent ; Adult ; Aged ; Artemisinins ; Bone Transplantation ; Decompression, Surgical ; Female ; Femur Head/surgery* ; Femur Head Necrosis/surgery* ; Humans ; Male ; Middle Aged ; Naphthoquinones ; Platelet-Rich Plasma ; Treatment Outcome ; Young Adult

Objective: To investigate the value of means of surfaces with nonhomogeneity (MSN) in esti-mating the incidence of pneumoconiosis. Methods: Based on the principal component analysis, all counties (districts) of Hebei Province, China, were divided into three categories according to the degree of pneumoconiosis hazards and the MSN model was used to estimate the incidence rate of pneumoconiosis and the number of pneu-moconiosis cases using the data of the incidence of pneumoconiosis in 2010. Results: With reference to the appli-cation requirements of the MSN model, results of the principal component analysis, and expert experience, the 172 counties (districts) in Hebei Province were divided into three categories with mild, moderate, and severe pneumoconiosis hazards. There were 74, 61, and 49 counties in the above categories, respectively, and 12, 12, and 25 counties were selected from them, respectively. The estimated number of pneumoconiosis cases in Hebei Province was 2105, and the incidence rate was 261.5 per hundred thousand, with a standard error of esti-mation of 389.9 per hundred thousand. Conclusion The MSN model provides a new thought and method for es-timating the number of pneumoconiosis cases.

BACKGROUND:The establishment of a standardized clinical liver transplantation specimen bank is the primary condition for scientific research in this field, which can help to provide a qualified sample resource platform for research. OBJECTIVE:To primarily establish biological specimen bank of hepatocelular carcinoma for liver transplantation, to explore the standardized procedures of specimen colection, processing and preservation of hepatocelular carcinoma for liver transplantation, and to establish the sound and comprehensive information management system of clinical information of colected specimens. METHODS: In accordance with standardized procedures to establish biological specimen banks, the operational processes and quality control system were formulated. Liver tissue and blood samples of hepatocelular carcinoma recipients undergoing liver transplantation were regularly colected, managed and stored. Simultaneously, liver tissue and blood samples of benign liver disease in liver transplant recipients and of healthy donor were colected as controls. A systematic management was conducted in colected specimens and corresponding clinical information. RESULTS AND CONCLUSION:From August 2009, tissue and blood samples of 501 cases of receipts and donors undergoing liver transplantation with complete clinical information were colected from the specimen bank, including 203 hepatocelular carcinoma specimens, 214 benign liver disease specimens and 84 healthy donor specimens. These specimens included tumor tissue, adjacent tissues and distal non-cancerous tissue specimens, totaly 1 773. A total of 45 specimens were randomly selected for quality monitoring. The colected specimens had a high quality. Specimen information data computer management system was developed. This study initialy established a standardized research-based clinical transplantation specimen bank, which is helpful to elevate sample quality and has a good manipuility.

Objective PB840 ventilator to explore non-invasive ventilation (NIV) in the ICU of the application,efficacy and safety.Methods Application PB840 Ventilator-Non-invasive mechanical ventilation in the treatment of the seven cases of different causes of respiratory failure patients,non-invasive ventilation in the treatment of 4 h,the blood gas (PaO2,PaCO2 and pH value) analysis and analysis of clinical symptoms to improve the situation.Results Patient before and after treatment of PaO2,PaCO2 and pH compared to the value there is significant difference.Target to improve the blood after treatment significantly (P<0.05),reduce or alleviate the symptoms of sick;cyanosis improved.However,leakage is still a major disadvantage,some patients can not tolerate when there is need to immediately replace invasive mechanical ventilation.Conclusion PB840 ventilator mode non-invasive ventilation can improve the patient′s respiratory failure and clinical symptoms of blood-gas target,but most critically ill patients should be carefully applied.