Objective To explore the clinical curative effect of pidotimod on patients with respiratory tract infection and effect on immune function. Methods 120 children with recurrent respiratory tract infection in the Third Hospital of Qinhuangdao,the Third Staff Hospital of Baogang Group,the Third Hospital of Wulanchabu were selected,and were divided into two groups according to random number table.60 cases in control group were treated with routine treatment of anti-infection,relieving cough,eliminating phlegm,antipyretic;60 cases in experimental group were treated with pidotimod on the basis of routine treatment,oral with boiled water,0.4g per times,2 times a day,with a course of 60 days.Clinical curative effect after treatment and serum immunoglobulin (IgG,IgA,IgM)levels,T lymphocyte subsets (CD3+,CD4+,CD8+)levels and NK cells relative activities before and after treatment were compared between two groups.Results After treatment,the total effective rate of experimental group (95.00%)was significantly higher than that of control group (81.67%),and the difference was statistically significant (P<0.05);the immune indexes before treatment had no significant difference,and levels of serum immunoglobulin and T lymphocyte subsets were improved,and levels of serum immunoglobulin (IgG,IgA,IgM)and T lymphocyte subsets (CD3+,CD4+,CD8+)of experimental group were more higher than those of control group,and the difference was statistically significant (P<0.05 );relative activity of NK cells in both groups improved after treatment,but relative activity of NK cells in experimental group was significantly higher than that in control group,and the difference was statistically significant (P<0.05 );adverse reactions according minor rashes and anemia were observed in two groups,and there was no significant differece in the incidence of adverse reactions,and ADR was tolerable after symptomatic treatment.Conclusion Pidotimod could significantly improve the clinical curative effect of patients with respiratory tract infections and effectively improve the immune function of patients with recurrent respiratory tract infections with high security,which has a clinical significance.

Objective To investigate the expression of transforming growth factor beta (TGF-β) and Smad signaling in ankylosing spondylitis (AS) and to explore their roles in the pathogenesis. Methods Fiftythree patients with AS were included in the study. In these 53 cases, 30 patients were performed computed tomography-guided needle biopsy in sacroiliac joint. Serum TGF-β_1 was determined by enzyme-linked immunosorbent assay (ELISA). Immunohistological studies were performed with the streptavidin-peroxidase conjugated methods to assess the expression of TGF-β_1, p-smad3 and Smad7 in sacroiliac joint tissue sample.One-way ANOVA, two independent samples t test and kolmogoorov-Simimov test were used to do statistical analysis. Results In 53 cases patients with AS, 20 cases were with high level Erythro-cyte sedimentation rate(ESR) and C-reactive protein (CRP), while those of the other 33 cases were normal. Serum average TGF-β_1level [ (15.9±5.6) ng/ml ], in patients with high level ESR/CRP [(5.4±5.8) ng/ml ] was significantly increased as compared to the controls and patients with normal ESR/CRP [(4.1±3.6) ng/ml] (P<0.05). There was no expression of TGF-β_1 could be detected in the pannus and bone marrow in SI joints tissue of 30 cases with AS, while decreased level of smad7 expression was detected. In addition, p-smad3 expression was found in the nuclear. Conclusion TGF-β_1 signaling may play an important role in the inflammatory erosion and cartilage fibrosis of sacrojlitis in AS.

Objective To investigate the expression of connective tissue growth factor(CTGF),coll agen I and collagen Ⅲ in sacroiliac joint(SIJ)of patients with spondyloarthropathy(SpA).Methods Thirty patients with SpA,including 17 patients with grade Ⅱ saeroiliitis and 13 patients with grade Ⅰ sacroiliitis,were performed on CT guided needie biopsy of SIJ.After sacroiliitis were confirmed by staining with hematoxylin and eosin in sacroiliac joint tissue sample,immunohistochemical assay was performed to determine the expression of CTGF,collagen Ⅰ and collagen Ⅲ in sacroiliac ioint tissue.Univariate Chi-square test was used for data comparison between multiple groups and t-test was used for two group data comparison.Results Contrast to healthy controls,CTGF were found upexpressed on the cytoplasm of inflammatory cells in pannus and bone marrow of sacroiliac tissue samples of patients with SpA,while collagen I and collagen Ⅲ were found up-expressed in bone,cartilage and ligament tissue[(57.9±42.4)/HP vs(2.7±2.5)/HP P<0.05,0.298±0.080 vs 0.044±0.024 and 28.254±41.165 vs 0.105±0.054.P<0.05 respectively].Conclusion CTGF,collagen Ⅰ and collagen Ⅲ are up-expressed in SIJ of SpA patients.CTGF may play an important role in articular cartilage fibrosis and ossification of SpA.

Objective:To explore the feasibility of using Double FLASH coronary CTA (CCTA) to evaluate myocardial blood perfusion based on the original Patlak Plots.Methods:A total of 50 subjects with non-ischemic heart disease were prospectively included in the study who received dynamic myocardial CT perfusion (CTP) and Double FLASH CTA scans in General Hospital of Tianjin Medical University from January 2018 to January 2020 due to coronary heart disease or suspected coronary heart disease. The age of the enrolled patients was at least 18 years old and there was no moderate or above stenosis on CTA. The dynamic CTP images were analyzed by using CTP analysis software on FRONTIER platform to calculate the CTP derived MBF (MBF CTP). While the CTA derived MBF (MBF CTA) was calculated from the CT attenuation values of both aorta and myocardium segments on two scanning time set of Double FLASH CTA which were measured by two independent radiologists. Pearson correlation and Bland-Altman analysis were used to compare the results of MBF CTP and MBF CTA. Results:There was a strong linear correlation between MBF CTP and MBF CTA measurements. In the mid anteroseptal level: MBF CTA=0.936MBF CTP-11.999, r2=0.600, P<0.01. In the mid anterolateral level: MBF CTA=1.010MBF CTP-9.206, r2=0.448, P<0.01. In the apex: MBF CTA=0.822MBF CTP+16.904, r2=0.375, P<0.01. Bland-Altman analysis also showed there were no significant differences between MBF CTP and MBF CTA measurements. Compared with dynamic CTP scan, Double FLASH CTA mode significantly reduced the radiation dose [(4.33±1.89) mSv vs. (1.38±0.19) mSv, t=4.378, P=0.030]. Conclusions:This study validated the feasibility and accuracy of the MBF CTA measurement based on the theory of Patlak Plots only using Double FLASH CTA images. This method might have the potential to expand the clinical application of one-stop CTP examination for simultaneously evaluating coronary artery and myocardial ischemia in the clinic.

Objective To understand the cognition ,attitudes and needs of the science and technology achievement trans-formation policies among the medical personnel of 21 tertiary hospitals in Shanghai .Methods Convenient sampling method was used .The self-designed questionnaires were used to survey 420 personals in 21 tertiary hospitals in Shanghai ,and 411 valid questionnaires were responded with a valid rate of 97 .86％ .Results The cognition of science and technology achievement transformation policies of the respondents was low ,and the degree of cognition was related to the professional titles ( P<0 .05) .While the recognition degree of some policies was high ;40 .47％ agreed that enterprises could be the decision-maker during the transformation process ;85 .99％ agreed that it is OK to hire the Technology intermediary service agencies to evalu-ate the achievements value ,confirmed that need such agencies to provide the services of information collection and screening . Conclusions More Policy publicity should be enhanced among the medical personnel ,communications about their needs and suggestions on the science and technology achievement transformation should be carried out to further update related policies , as well as improve the transformation of science and technology achievements in health system .

Objective:To deliver understanding of the latest research progress on clinical trials and approval of dermatological drugs in China in 2020.Methods:A registration and information disclosure platform for drug clinical studies and a query system for domestic and imported drugs in the National Medical Products Administration of China were searched for registered clinical trials and approved dermatological drugs, respectively. The number and stages of clinical trials, indications and classification of involved products, and listed dermatological drugs in 2020 were summarized and depicted.Results:There were 157 dermatological drug trials registered in China in 2020, accounting for 6.16% of all the 2 548 clinical drug trials, including 127 (80.9%) initiated by Chinese pharmaceutical enterprises and 25 (15.9%) international multicenter trials. Among the 127 drug trials initiated by Chinese pharmaceutical enterprises, bioequivalence trials were mostly common, accounting for 55.9% (71/127) . Compared with global pharmaceutical enterprises, domestic pharmaceutical companies initiated significantly decreased proportions of international multicenter trials (1.9% [3/157] vs. 14.0% [22/157], P < 0.001) , but significantly increased proportions of phaseⅠclinical trials and bioequivalence trials (24.4% [31/127] vs. 10.0% [3/30], 55.9% [71/127] vs. 0, respectively, both P < 0.001) . Totally, 90 kinds of dermatological drug were involved in all the trials, psoriasis, atopic dermatitis and melanoma were the most common indications, and innovative drugs accounted for 53.3% (48/90) ; the proportion of innovative drugs was significantly lower in domestic pharmaceutical companies than in global pharmaceutical companies (43.2% [32/74] vs. 16/16, P < 0.001) . In addition, 28 dermatological drugs developed by 22 pharmaceutical companies were approved in China in 2020, of which 21 drugs were developed by domestic pharmaceutical companies. Conclusion:Clinical drug trials carried out by domestic pharmaceutical companies mostly focus on generic drugs, and it is still necessary for domestic pharmaceutical companies to further improve the innovation ability.

Objective:To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019.Methods:Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020.Results:A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism ( P>0.05). Conclusions:During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

Objective:To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019.Methods:Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020.Results:A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism ( P>0.05). Conclusions:During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*