Objective:To standardize the management of Investigator-Initiated Trials(IITs) and improve the quality of research projects, this study takes a tertiary hospital in Beijing as an example to analyze the key risk points in the implementation process of IITs and proposes countermeasures based on the issues identified during the management process.Methods:The study analyzed the IITs conducted at in the hospital from 2022 to 2023, focusing on 4 aspects: project classification evaluation and management (risk management), project implementation quality (process management), collaboration and support conditions(contract review and execution), and participant protection (medical ethics). It examined the key points and difficulties in project process management to standardize the quality management of IITs.Results:The implementation process management of IITs in medical institutions was an essential component for standardized clinical research management and an effective means to ensure the scientific nature of clinical research and the quality of data.Conclusions:Medical institutions should establish an effective and feasible IIT quality management system to comprehensively enhance the quality of IIT project, aiming to produce high-quality clinical research outcomes.

Objective:To standardize the management of Investigator-Initiated Trials(IITs) and improve the quality of research projects, this study takes a tertiary hospital in Beijing as an example to analyze the key risk points in the implementation process of IITs and proposes countermeasures based on the issues identified during the management process.Methods:The study analyzed the IITs conducted at in the hospital from 2022 to 2023, focusing on 4 aspects: project classification evaluation and management (risk management), project implementation quality (process management), collaboration and support conditions(contract review and execution), and participant protection (medical ethics). It examined the key points and difficulties in project process management to standardize the quality management of IITs.Results:The implementation process management of IITs in medical institutions was an essential component for standardized clinical research management and an effective means to ensure the scientific nature of clinical research and the quality of data.Conclusions:Medical institutions should establish an effective and feasible IIT quality management system to comprehensively enhance the quality of IIT project, aiming to produce high-quality clinical research outcomes.

BACKGROUND:Although traditional therapies,including drugs and surgery,cannot repair the damaged myocardial tissue,the mortality rate of myocardial infarction remains high.Stem cells provide the possibility to solve this problem due to their self-renewal and multi-directional differentiation potential. OBJECTIVE:To analyze the research progress of stem cell therapy for myocardial infarction in recent ten years by bibliometric analysis. METHODS:The related articles on stem cells and myocardial infarction published in SCI-E and SSCI from January 1,2012 to December 1,2022 in the Web of Science database were searched.EXCEL,CiteSpace and VOSviewer software were used to make statistical and visualization analyses of the data such as the number of publications,authors,institutions,journals,countries and keywords. RESULTS AND CONCLUSION:A total of 3 210 core articles were published,and the total number increased year by year.hausenloy,derek j.is the author with the largest number of publications,China is the country with the largest number of publications,and the Fourth Military Medical University is the institution with the largest number of publications.The research hotspots in this field are changing from cell experiments and animal experiments to clinical trials.In the past ten years,research in this field has been highly popular and still has great development prospects.It is necessary to promote international and inter-agency exchange and learning,and further explore the role of stem cells in the treatment of myocardial infarction.

Traumatic cataract is relatively common in clinical practice. Typically, non-metallic foreign bodies entering the eye do not cause intraocular reactions, manifesting only as traumatic cataract, while metal foreign bodies entering the eye are more likely to cause complications. Foreign bodies entering the eye can be detected through ophthalmic examination or found during cataract surgery. However, a very small number of patients may experience missed diagnosis in clinical practice. This article reported a case of traumatic cataract with disappearance of intraocular metal foreign body, presenting with a history and signs of ocular trauma and foreign body entry into the eye, but no foreign body was found before, during or after surgery. The reasons for the disappearance of the metal foreign body were also analyzed.

FLASH radiotherapy (FLASH-RT) is a treatment modality that delivers ultra-high dose rate and ultra-fast radiation for cancer treatment. Compared to conventional dose rate radiotherapy, FLASH-RT can yield similar efficacy for tumors and achieve normal tissue protection, translating to an increased therapeutic window. Due to this unique feature, FLASH-RT is attracting increasing attention from the radiotherapy community, both academia and industry. Due to its unique Bragg peak as well as intrinsic high dose rate, application of FLASH has more value and profound significance in proton therapy while achieving highly conformal dose deposition simultaneously. This article reviews research progress on FLASH-RT, relevant cell and animal studies, experimental conditions and results. Moreover, this article also investigates the potential biological mechanisms, technical challenges for implementation and potential clinical applications of FLASH-RT.

Objective:To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant.Methods:Participants were from the Ma’anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants’ neurobehavioral development.Results:A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants’ neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M ( P25, P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant’s development of social behavior [β (95% CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with β (95% CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion:BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.

Objective:To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant.Methods:Participants were from the Ma’anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants’ neurobehavioral development.Results:A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants’ neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M ( P25, P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant’s development of social behavior [β (95% CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with β (95% CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion:BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.

Objective: To explore the role of β-catenin in distraction osteogenesis of new bone formation, the expression of β-catenin in the distraction gap callus was detected during rabbit mandibular distraction osteogenesis. Methods: 26 New-Zealand rabbits were randomly divided into 3 groups. Group A is a normal control group with 2 rabbits, group B is the mandibular defect control group, and group C is the distraction group. Group B and C with 12 rabbits, respectively. The two rabbits in group A without surgery, their mandibles are normal control. In group B, vertical osteotomy was performed between the first molar and the mental foramen on the mandibles bilaterally, followed by rigid internal fixation with titanium plates and screw with 5 mm gap immediately. In group C, after the same osteotomy was performed, the fragments of mandibles were reduced and fixed with mandibular distractors bilaterally. On the fourth day postoperatively, the distraction started at a rate of 0.8 mm/d and lasted for 7 days, followed by consolidation period. Two rabbits of group B and C were sacrificed at 6th, 10th, 17th, 24th, 31st, 38th day postoperatively, respectively. The newly formed callus in the distraction gap of mandibles was harvested for Western blotting and immunohistochemistry examination to detect the distribution and expression of β-catenin. The experimental data were analyzed by SPSS 22.0 statistical software using Spearman function. Results: The result of Western blotting showed that the expression of β-catenin gradually increased at distraction period(6-10 days after surgery) and reached the peak at the end of the distraction period(10th day postoperatively), it gradually decreased during the consolidation period. However, the expression of β-catenin in group C was higher than that of group B. Immunohistochemistry stain showed that the expression of β-catenin mainly located in inflammatory cells(eg. monocyte), fibroblast of the granulation tissue, the osteoblasts, osteocyte on the surface of new formed trabecular, and the connective tissues surrounding the new bone in the new formed callus. Cytoplasmic and nuclear staining were positive. In group C, the expression of β-catenin was strong (3.245 8±0.132 3) after distraction (6th day postoperatively), and reached a peak (4.602 8±0.021 9) on the 10th day postoperatively. With the disappearance of the distraction stress, the expression of β-catenin gradually decreased since17th day postoperatively(3.639 8±0.125 5), but the staining was still positive. In group B, the strong positive staining of β-catenin on the 6th day after surgery (2.734 0±0.134 7), the strongest staining on the 10th day after surgery (3.101 3±0.104 8), and the expression of β-catenin on the 17th day after surgery (2.542 8±0.211 1) was weaker than that on the 10th day after surgery. At each time point, the expression of β-catenin in group C was significantly higher than that in group B, and the difference was statistically significant (r=0.943, P=0.005 6). Conclusions During mandibular distraction osteogenesis, the distraction stress activates the Wnt signal pathway to enhance the expression of β-catenin, it suggests that β-catenin plays an important role in the transformation of the mechanical signal to chemical signals during the process of distraction osteogenesis, and participates in the regulation of new bone formation during distraction osteogenesis.

Objective To investigate the expression of Wnt/β-catenin signal antagonist DKK1 protein in callus of distraction gap during mandibular distraction osteogenesis (MDO).Methods Twenty four healthy New Zealand rabbits were randomly divided into distraction group,fracture control group,with twelve rabbits each,respectively.In distraction group,bilateral mandibular distraction models were established.In control group,after bilateral mandibular osteotomy,the two bone fragments were fixed by titanium plate and screws with a 5 mm gap.The expression of DKK1 in the distracted calluses was analyzed by cell digital imaging software.Results Expression of DKK1 was colocalized in the nucleus and cytoplasm of osteoblasts,fibroblasts,cartilageand newly embedded osteocytes.The expression of DKK1 increased following distraction activated after surgery,peaked at 10 days after surgery,the population of cells that stained for DKK1 decreased gradually.At 31 to 38 days postoperatively,DKK1 expression reduced gradually,mainly located in the osteocyte,and both nucleus and cytoplasm were positive staining.At each time point,the expression of DKK1 in distraction group was higher than that in the control group and the difference was statistically significant (P＜0.05).Conclusions During MDO,the Wnt/β-catenin pathway is activated due to the distraction and mechanical strain on the bone.With the increased expression of Wnt-related factors,the endogenous negative feedback is enhanced to induce DKK1 expression and to regulate the activated Wnt/β-catenin pathway.This would be beneficial to the new bone formation and remodeling in the distraction gap.

Objective: To investigate the association between the internal exposure levels of phthalic acid esters (PAEs) and executive function (EF) of preschool children. Methods: Between October 2008 and October 2010, pregnant women who accepted pregnancy health care services in four municipal medical and health institutions in Ma'anshan city, Anhui Province, were recruited as study objects. A total of 5 084 pregnant women and 4 669 singleton live births were enrolled in this cohort. The follow-up study was conducted from April 2014 to April 2015. A total of 3 725 data-completed preschool children aged 3 to 6 years older entered in this study. The method of analysis seven metabolites of phthalates in urine was high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and divided objects into low (P₀-P₂₄), medium (P₂₅-P₇₄) and high (P₇₅-P₁₀₀) groups according to their exposure concentrations. To investigate the executive function of preschool children, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the etiology association between the phthalate metabolites levels and preschool children's executive function. Results: In this study, 53.6% (1 997/3 725) of preschoolers were boys, children's age was (51.5±5.6) months. The detection rates of seven phthalate esters were: mono-n-methyl phthalate (MMP) was 99.89% (3 721/3 725); mono-ethyl phthalate (MEP) was 99.97% (3 724/3 725); mono-benzyl phthalate (MBzP) was 69.10% (2 574/3 725); mono-butyl phthalate (MBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 100.00% and mono-ethylhexyl phthalate (MEHP) was 99.95% (3 723/3 725). The median concentrations of the seven phthalate metabolites were: 17.71, 15.36, 0.07, 155.24, 10.73, 14.67, 3.59 µg/L, respectively. The median concentrations corrected by urinary creatinine were 29.65, 26.65, 0.12, 257.73, 17.94, 24.80, 6.27 µg/g Cr, respectively. The P₂₅ and P₇5 concentration of the total PAEs metabolites corrected by urinary creatinine were 1.20 µmol/g Cr and 3.04 µmol/g Cr. After adjusted the relevant demographic information: children sex, children age in month, maternal age, parental education levels, household exposure to secondhand smoke and whether the child is the only child as confounds, multivariate logistic regression model showed that the risk of inhibitory self-control index (ISCI) dysplasia in MEHHP high concentration group and MEOHP high concentration group were 1.71 and 1.54 times (OR=1.71, 95% CI: 1.11-2.62; OR=1.54, 95% CI: 1.01-2.34) than in low concentration group. The risk of ISCI dysplasia in total PAEs metabolites high concentration group was 1.55 times (OR=1.55, 95% CI: 1.00-2.38) than in low concentration group. Conclusion Phthalates exposure may damage the executive function of preschool children.