In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

Aim To investigate the dynamic changes of neuronal cells at different time points following acute cerebral ischemia-reperfusion injury by establishing a model of brain ischemia-reperfusion injury.Methods Thirty male Sprague-Dawley(SD)rats were ran-domly divided into six groups:sham group and cere-bral ischemia-reperfusion injury(IR)groups at differ-ent time points.Focal cerebral ischemia-reperfusion injury model was established using the middle cerebral artery occlusion(MCAO)technique.The Longa sco-ring method was used to assess neurobehavioral scores in rats.After successful model preparation,routine paraffin sections were made,and TUNEL staining and immunohistochemistry staining with NeuN antibody were performed to observe cell apoptosis and neuronal cell survival,respectively.Immunohistochemistry stai-ning was also performed to investigate the changes in glial fibrillary acidic protein(GFAP)as a marker for astrocytes,ionized calcium-binding adapter molecule 1(IBA-1)as a marker for microglia,and CD31 as a marker for endothelial cells at different time points.Results No significant changes were observed in neu-ronal cells of the sham group at different time points.In the cerebral ischemia-reperfusion injury groups,cell apoptosis was activated at IR3h and increased in quan-tity with morphological damage as time progressed.Ne-uN+neurons showed signs of ischemic injury after IR3h,with abnormal cell morphology.From 12 h,Ne-uN+neurons decreased in a time-dependent manner and reached their peak severity at 24 h.GFAP+astro-cytes decreased significantly after IR3h,while poorly labeled GFAP+astrocytes increased at IR 6 h and al-most disappeared in the infarcted area at 24 h and 48 h.The number of IBA-1+microglia-positive cells de-creased at IR3h,and their volume increased at IR6h.Microglial cell death was observed in the infarcted area at IR12h.CD31+endothelial cells around the infarc-ted cortex and striatum increased significantly after IR3h and persisted until 48 h.Conclusions After cerebral ischemia-reperfusion injury,the number of ap-optotic cells increases with the prolongation of time,and NeuN+neurons exhibit the most severe damage at 24 h.GFAP+astrocytes and microglial cells gradually die over time.The number of CD31+endothelial cells increases significantly around the infarcted cortex and striatum after 3 h of reperfusion and persists until 48 h.

Hydrogen sulfide(H2 S),an endogenous gas trans-mitter involved in the regulation of vascular tone,has a variety of physiological properties,such as antihypertensive,vascular re-laxation,anti-inflammatory and antioxidant potential,and plays an important role in cardiovascular regulation.Chinese scholars call essential hypertension combined with hyperhomocysteinemia(HCY≥10 μmol·L-1)as H-type hypertension.Studies have shown that H2S can antagonized hypertension and hyperhomocys-teinemia,suggesting that H2S may be a potential therapeutic tar-get for H-type hypertension.Therefore,this article briefly sum-marizes the mechanism of H2S on hypertension and homocys-teine.Homocysteine(HCY)is closely related to the occurrence and development of cardiovascular diseases.Hyperhomocysteine-mia(HCY ≥ 10 μmol·L-1)is a risk factor for coronary ath-erosclerotic heart disease,stroke,and other cardiovascular dis-eases,and Chinese scholars define primary hypertension accom-panied by hyperhomocysteinemia as H-type hypertension,which accounts for about 75％of the adult hypertensive patients in Chi-na.The treatment of H-type hypertension should simultaneously reduce blood pressure and plasma HCY levels.Studies have shown that hydrogen sulfide(H2 S)can antagonise hypertension and high HCY,suggesting that H2S may be a potential therapeu-tic target for H-type hypertension.Therefore,this paper summa-rizes the mechanism of action of H2S on hypertension and HCY.

Parkinson's disease is a neurodegenerative disease associated with abnormal copper metabolism in the brain,which leads to misfolding and aggregation of α-synuclein-copper complexes,which is an important pathological sign of Parkinson's disease.Copper metabolism,i.e.,cellular metabolic processes involving copper ions,is closely related to the pathogenesis of α-synuclein aggregation,dopamine metabolism,mitochondrial dysfunction,oxidative stress,and ferroptosis in Parkinson's disease.In this review,we summarize the molecular metabolic mechanism of copper toxicity by studying the pathological role of copper metabolism in Parkinson's disease,to support our further understanding of the mechanism of action and drug development.

Objective:To translate the perceived stressors in intensive care units Scale into Chinese version,and to validate its validity and reliability and in intensive healthcare professionals.Methods:The Perceived Stressors in Intensive Care Units Scale was translated according to the Brislin translation model.After cultural adjustment,495 ICU healthcare professionals were selected to evaluate the validity and reliability of the scale,and univariate analysis was conducted on the scores of the Scale with different characteristics.Results:The Chinese version of the scale re-tained 40 items,and 6 common factors were extracted after exploratory factor analysis.The cumulative variance contribution rate reached 58.21％.Confirmatory factor analysis showed a basic fit of the model(x2/df=2.85,CFI=0.93,TLI=0.93,RMSEA=0.09).The total Cronbach coefficient of the scale was 0.940 and the split-half relia-bility was 0.87.The retest reliability after 2 weeks was 0.92.The item-level content validity index of the Chinese version of The Perceived Stressors in Intensive Care Units Scale was 0.83～1.00,the scale-level content validity index was 0.93,and the average content validity was 0.98.Comparison of the total scores of scale among ICU healthcare professionals with different occupations,professional titles,marital status and working years showed sta-tistically significant differences(P＜0.05).Conclusion:The Chinese version of the Perceived Stressors in Intensive Care Units Scale is proved to be a good instrument with acceptable validity and reliability.

Objective:To explore the effectiveness and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD).Methods:A retrospective analysis was conducted on data of 16 patients who underwent EUS-PD because of endoscopic retrograde pancreatography (ERP) failure, poor effectiveness or anatomical changes and couldn't undergo the routine ERP in Nanjing Drum Tower Hospital from June 2018 to July 2022. The technical success of EUS-PD, clinical efficacy and post-procedure adverse events were analyzed.Results:In the 16 patients, there were 14 males and 2 females, with age of 50.69±12.95 years. A total of 19 times of EUS-PD operations were included, 3 of them were rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), 15 transgastric or transenteric EUS-guided stent placement and 1 was EUS-guided nasopancreatic duct placement. Technical success was achieved in 84.21% (16/19) patients, and among whom 93.75% (15/16) achieved clinical success. The overall incidence of postoperative adverse events was 52.63% (10/19) including 47.37% (9/19) abdominal pain, 15.79% (3/19) fever and 15.79% (3/19) postoperative pancreatitis. All adverse effects were relieved after general conservative treatment and no primary disease or surgery-related death occurred. The mean follow-up was 17.6 (8.2,22.3) months and 93.75% (15/16) of the patients were followed up. By the time of follow-up, 76.92% (10/13) of the patients who had successfully received EUS-PD had no recurrence of abdominal pain or distension.Conclusion:EUS-PD is a safe and effective alternative therapy for those with pancreatic diseases with ERP failure, poor efficacy or anatomical changes.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P＞0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P＜0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P＜0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.

Objective: To analyze the correlation between refractive errors and physical development indicators among primary school students aged 6 to 9, so as to provide a scientific basis for the development of effective prevention and control measures. Methods: A stratified cluster random sampling method was used to recruit 2 833 elementary school students aged 6 to 9 from Guangdong Province for vision screening, ocular biometry, and physical examinations in Octorber, 2020. The Chi square test, t-test, and ANOVA were employed to compare myopia rates and indicator values across different groups. Multiple linear regression models were used to analyze the correlations between height, weight, and body mass index (BMI) with refractive development indicators. Results: The screening myopia rate among primary school students aged 6 to 9 was 16.7%, and the myopia rate increased with age ( χ 2= 51.58 , P <0.01). The height and weight of the myopic group [(126.96±7.41)cm, (26.59±6.45)kg] were higher than those of the non myopic group [(124.76±7.77)cm, (25.42±5.87)kg] ( t =5.84, 3.65, P <0.01). The mean values of spherical equivalent (SE), axial length (AL), anterior chamber depth (ACD), and AL/corneal curvature radius (CR) ratio for students aged 6 to 9 were (-0.17±1.04)D, (22.96±0.78)mm, (3.38±0.24)mm, and (2.95±0.08), respectively, with statistically significant differences across different age and myopia severity groups ( t =37.08, 119.20, 41.54, 133.60; 935.30, 184.10, 73.95, 498.50, P < 0.01). After adjusting for gender, age, and residence, the multiple linear regression model showed that height was positively correlated with AL and CR, weight was positively correlated with ACD, and BMI was positively correlated with AL and ACD ( β = 0.191 , 0.070, 0.035, 0.013, 0.007, P <0.05). When stratified by myopia status, results for the non-myopic group were similar to the overall results, whereas in the myopic group, the correlations between height, BMI, and AL were not statistically significant ( P > 0.05). Conclusions Among primary school students aged 6 to 9, height and BMI are positively correlated with AL in the non myopic group but no similar correlation is observed in the myopic group, indicating that factors other than physical development, such as environmental and behavioral factors, should be considered for their impact on refractive development.

ObjectiveTo use the maternal morbidity WOICE Tool（Chinese version）to investigate the maternal morbidity in Shanghai， and to examine the current situation and associated factors of adverse symptoms and impaired functioning in the third trimester and postpartum period. MethodsPregnant women who made their initial visit and established a medical record at a tertiary obstetrics and gynecology hospital in Shanghai from March to August 2021 were recruited and a baseline survey was completed. The prevalence of maternal morbidity was surveyed in the third trimester and first 6 weeks postpartum. ResultsSelf-reported adverse physical symptoms were observed in 89.8% of women in the third trimester and 86.1% in first 6 weeks postpartum. The prevalence rates of anxiety and depression were 4.1% and 6.2% in the third trimester， and 6.2% and 7.5% in first 6 weeks postpartum， respectively. The proportions of women reporting impaired functioning were 80.3% in the third trimester and 64.1% in first 6 weeks postpartum， respectively. Physical symptoms were associated with parity， education， the newborn’s health status， and risk of experiencing violence. Psychological symptoms were associated with age， household responsibilities， employment status， the newborn’s health status， pre-pregnancy body mass index （BMI）， and risk of experiencing violence. Functionality was associated with the type of registered residence， education level， household responsibilities， and risk of experiencing violence. ConclusionThe physical health status of pregnant and postpartum women in Shanghai is better than that in the middle-income regions abroad， with anxiety and depression at average levels compared to national statistics in China. Physical， psychological， and functional status are affected by multiple factors including personal， health， family， and work conditions. Preventive measures should be taken from various perspectives to mitigate adverse symptoms and impaired functioning， and to improve the positive experience of pregnancy and childbirth.