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.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

Objective To explore the application effect of"Internet + Medical treatment"model in patients with pulmonary rehabilitation after lung cancer surgery.Methods A total of 87 patients with lung cancer who received elective surgery in our hospital from June 2022 to January 2023 were selected and divided into control group(44 cases)and observation group(43 cases)according to random number table method.The control group received routine intervention,and the observation group received intervention based on"Internet + medical treatment"mode.The pulmonary function indexes[forced vital capacity(FVC),first second forced vital capacity(FEV1),respiratory flow(PEF)],cardiorespiratory endurance level[6min walking test(6MWT)],respiratory fatigue and quality of life(WHOQOL-BREF)of the two groups were compared.Results After 6 months of intervention,the scores of FVC,FEV1,PEF,6MWT distance and WHOQOL-BREE in the study group were higher than those in the control group,and the scores of respiratory fatigue were lower than those in the control group,with statistical significance(P<0.05).Conclusion"Internet + Medical treatment"intervention can improve lung function,increase cardiopulmonary endurance,reduce respiratory fatigue and improve quality of life in patients recovering from lung cancer surgery.

Objective:To develop a genotyping method for the Junior blood type and report on a rare blood type with Jr(a-).Methods:Healthy O-type RhD+ volunteer donors of the Shenzhen Blood Center from January to May 2021 ( n=1 568) and a pedigree with difficult cross-matching ( n=3) were selected as the study subjects. Serological methods were used for proband′s blood type identification, unexpected antibody identification, and antibody titer determination. Polymerase chain reaction-sequence specific primer (PCR-SSP) method was used for typing the proband′s RHD gene. ABCG2 gene coding region sequencing and a PCR-SSP genotyping method were established for determining the genotypes of the proband and his family members and screening of Jra antigen-negative rare blood type among the 1 568 blood donors. Results:The proband′s ABO and RhD blood types were respectively determined as B and partial D (RHDDVI.3/RHD01N.01), Junior blood type Jra antigen was negative, and plasma had contained anti-D and anti-Jra. Sequencing of the ABCG2 gene revealed that the proband′s genotype was ABGG201N.01/ABGG201N.01 [homozygous c. 376C>T (p.Gln126X) variants], which is the most common Jr(a-) blood type allele in the Asian population. Screening of the voluntary blood donors has detected no Jr(a-) rare blood type. Statistical analysis of the heterozygotes suggested that the allelic frequency for ABCG2*01N.01 (c.376T) was 0.45%, and the frequency of Jr(a-) rare blood type with this molecular background was about 0.2‰. Conclusion:A very rare case of partial DVI.3 type and Jr(a-) rare blood type has been identified. And a method for identifying the Junior blood type through sequencing the coding regions of the ABCG2 gene and PCR-SSP has been established.

AIM To establish the HPLC fingerprints for freeze-dried powder of Yinhuo Decoction,and to determine the contents of rehmannitin D,methylophiopogonanone A,verbascoside,protocatechuic acid,catalpol,schisandrol A,schisandrin B,schisandrin A.METHODS The fingerprint esablishment was performed on a 30℃thermostatic Supersil AQ18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 230 nm.The UPLC-MS/MS content determination was performed on a 30℃thermostatic Alphasil VC-C18 column(2.1 mm×100 mm,2.5 μm),with the mobile phase comprising of acetonitrile-0.1%formic acid flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS There were 17 common peaks in the fingerprints for 10 batches of freeze-dried powder with the similarities of more than 0.90.and piloside,crystal blue glycoside,deacetylated caryoside schisandrin A were identified.Eight constituents showed good linear relationships within their own ranges(R2＞0.990 6),whose average recoveries were 98.7%-101.1%with the RSDs of 2.0%-5.2%.CONCLUSION The combination of fingerprints and content determination can completely characterize the quality of Yinhuo Decoction reference sample,thus provide a reference for the quality evaluation of its key chemical properties.

OBJECTIVE To develop an individualized medication list for elderly patients by evidence-based pharmacy method， and to support clinical decisions on rational use of METHODS　Firstly， drugs with risk genetic information were screened out by systematically reviewing evidence-based pharmacy information. Secondly， researchers investigated the included drugs in lists from different data E- sources. Drugs included in three or more data sources and drugs proposed by the expert committee were then included in the medication list. Thirdly， for the drugs included in two data sources， researchers designed questionnaires to investigate the necessity of drug-related gene testing. According to the scoring results of the expert questionnaire， drugs with higher scores were included in the list. Data sources included real-world data （list of high frequency medication in hospitals， high frequency medication for elderly outpatients and inpatients in National Health Care Claims Data， drugs related to frequent medication errors and so on） and evidence-based pharmacy evidence （the websites of Clinical Pharmacogenomics Implementation Consortium， Dutch Pharmacogenetics Working Group， Food and Drug Administration and so on）. RESULTS　The study obtain 68 drugs with risk genetic information which were included in three data sources. Combined with 23 drugs proposed by the expert committee， a list containing 74 drugs was preliminarily formed after de-duplication. A total of 37 drugs included in two databases with risk genetic information were scored through the questionnaire survey to form a supplementary list of 26 drugs. This is the final composition of the list of 100 drugs developed in this study. Among them， there are 43 drugs for the central nervous system， 15 drugs for the cardiovascular system， 12 anti-tumor drugs and so on. Twelve drugs were included in six or more data sources， which mainly consisted of drugs for digestive system， all proton pump inhibitors. CONCLUSION　In this study， a list of 100 commonly used drugs which require individualized medication for the elderly was developed by evidence-based pharmacy method. The drug list will be updated in time as available evidence changes， and can provide guidance for rational use of medicines for elderly patients.

Eosinophilic gastroenteritis (EGE) is a gastrointestinal disorder of unclear etiology that is characterized by eosinophilic infiltration of the stomach and small intestine, and consists of mucosal, muscular, and serosal subtypes. Eosinophilic infiltration of the gastrointestinal tract is a fundamental histopathological characteristic of EGE and is driven by several T-helper type 2 (Th2)-dependent cytokines and induced by food allergy. Due to the lack of a diagnostic gold standard, EGE has a high rate of delayed diagnosis or misdiagnosis. However, several new diagnostic strategies have been developed, such as novel genetic biomarkers and imaging tests. Although dietary therapy and corticosteroids remain the common choices for EGE treatment, recent decades have seen the emergence of novel treatment alternatives, such as biologics that target particular molecules involved in the pathogenic process. Preliminary investigations and clinical trials have demonstrated the efficacy of biologics and provided additional insights for the era of refractory or corticosteroid-dependent EGE biologics.
Humans ; Enteritis/drug therapy* ; Gastritis/drug therapy* ; Eosinophilia/therapy* ; Abdomen ; Adrenal Cortex Hormones

Humans ; Bayes Theorem ; Age Factors ; Age Distribution ; Mouth Neoplasms/epidemiology* ; China/epidemiology* ; Mortality

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

Objective To observe the electromyography characteristics of children's handwriting with attention deficit hyperactivity disorder(ADHD),and explore its electrophysiological mechanism,so as to provide an objective basis for developing non-pharmacological treatment for such children.Methods Between September 2021 and April 2022,29 ADHD children were recruited from an ordinary public primary school and the psychiatric clinic of a class-3 grade-A hospital in Beijing.Among them,25 were boys and 4 were girls,with an average age of 8.21±1.78 years.Meanwhile,23 male and 5 fe-male healthy counterparts were selected with the age gap no more than 6 months.The Delsys wireless surface EMG system was used to collect the electromyographic signals of the abductor pollicis breve,the first dorsal interosseous muscle,the flexor radial carpi motor and the extensor finger muscles dur-ing their writing tasks such as tracing trajectories,writing Arabic numerals 0-9,26 small and capital English letters,Chinese characters one to ten and"Yong".The percentage of the averaged electromyog-raphy(AEMG)of a muscle in the sum value of all measured muscles,and the coefficient of differ-ence were selected to evaluate the muscle contribution rate and the consistency of exertion,respective-ly.Moreover,the independent sample t-test was employed to compare the two different groups with the significance set at α=0.05.Results There was a significant difference in the muscle contribution of abductor pollicis breve and first dorsal interosseous muscles when writing Arabic numerals and that of abductor pollicis breve muscles when writing Chinese characters between ADHD children(27.29%,25.58%and 27.53%)and their healthy counterparts(42.87%,19.96%and 37.13%)(P<0.05).Most muscle differentiation coefficients of ADHD children were higher than 100%,with that of the domi-nant hand radial wrist flexor muscle reaching 270%in the trajectory tracing task.Conclusion Accord-ing to the characteristics of EMG signals,school-age ADHD children show an immature writing pat-tern,including poor stability of writing-related muscles,insufficient control of small finger muscle groups,poor control of hand coordination,and insufficient muscle inhibition of non-dominant hand.It is recommended to conduct the electromyoelectric assessment of handwriting movements in ADHD chil-dren,so as to carry out targeted intervention at an early stage.