OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Fe-based γ-cyclodextrin nanoparticles(Fe-γ-CD)with peroxidase-like activity were successfully synthesized through a solvothermal approach for establishing a simple and sensitive sarcosine(SAR)assay method.Fe-γ-CD could catalyze the oxidation of colorless 3,3′,5,5′-tetramethylbenzidine(TMB)to blue oxidized TMB(oxTMB)in the presence of H2O2,accompanied by a characteristic absorption peak centered at 652 nm.The effects of reaction conditions were investigated,and the catalytic mechanism as well as the steady-state kinetics were analyzed.Fe-γ-CD could catalyze H2O2 to generate hydroxyl radical,singlet oxygen and superoxide radical,these reactive oxygen species with robust oxidizability further oxidized TMB.This process followed a typical Michaelis-Menten kinetic model.With the assistance of sarcosine oxidase(SOx),SAR was hydrolyzed into H2O2 to trigger Fe-γ-CD catalyzed chromogenic reaction,resulting in deepened color and increased absorbance.The degree of colorimetric signal change was related to SAR concentration and thus SAR could be quantitatively detected.The linear range and detection limit were 1.0-70.0 μmol/L and 0.46 μmol/L,respectively.Typical amino acids and metal ions had no obvious interference on SAR detection,indicating a good selectivity.The method was successfully applied to determination of SAR level in serum with satisfactory results.

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 investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the expression of CD123 in children with acute lymphoblastic leukemia(ALL)and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia(B-ALL).Methods A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology,Children's Hospital of Kunming Medical University,from December 2019 to June 2022.According to the expression of CD123 at initial diagnosis,the children were divided into CD123+group and CD123-group,and the two groups were compared in terms of clinical characteristics and treatment outcome.The factors influencing the prognosis were analyzed.Results Among the 251 children with ALL,there were 146 children(58.2%)in the CD123+group.The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group(P<0.05).Compared with the CD123-group,the CD123+group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years,with a relatively low proportion of children with E2A-PBX1 fusion gene(P<0.05).The multivariate Cox proportional-hazards regression model analysis showed that compared with the>10 years group,the 1-10 years group had a significantly higher overall survival rate(P<0.05),and compared with the high risk group,the moderate risk group had a significantly higher event-free survival rate in children with B-ALL(P<0.05).Conclusions CD123 is widely expressed in children with B-ALL,and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL,which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Objective To investigate the preliminary clinical effect of closed reduction and cannulated nail internal fixa-tion for femoral neck fracture assisted by robot navigation and positioning system.Methods From July 2019 to January 2020,16 cases of femoral neck fracture(navigation group)were treated with closed reduction and internal fixation guided by robot system,including 7 males and 9 females,aged 25 to 72 years old with an average of(53.61±5.45)years old;Garden classification of fracture:3 cases of type Ⅰ,3 cases of type Ⅱ,8 cases of type Ⅲ,2 cases of type Ⅳ.Non navigation group(control group):20 cases of femoral neck fracture were treated with closed reduction and hollow nail internal fixation,8 males and 12 females,aged 46 to 70 years old with an average of(55.23±4.64)years old;Garden type Ⅰ in 2 cases,type Ⅱ in 4 cases,type Ⅲ in 11 cases,type Ⅳ in 3 cases.The operation time,fluoroscopy times,guide needle drilling times,screw adjustment times,intraoperative bleeding volume and other indicators of two groups were evaluated.Results Both groups were followed up for 12 to 18 months with an average of(15.6±2.8)months.The fractures of both groups were healed without delayed union and nonunion.There was no significant difference in healing time between two groups(P=0.782).There was no significant differ-ence in Harris scores between two groups at the last follow-up(P=0.813).There was no significant difference in operation time between two groups(P＞0.05).There were significant differences between two groups in fluoroscopy times,guide needle drilling times,hollow screw replacement times,and intraoperative bleeding volume(P＜0.05).Conclusion Closed reduction and hollow screw internal fixation assisted by robot navigation system for femoral neck fracture has the advantages of minimally invasive operation,precise screw placement,and reduction of X-ray radiation damage during operation.

Objective To develop a catalytic hairpin assembly(CHA)-based fluorescent assay for the detection of the target RNA of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),so as to realize the rapid nucleic acid testing of SARS-CoV-2.Methods A 24-nt segment of the SARS-CoV-2 nucleocapsid protein gene(N gene,NC_045512.2)was chosen as the target RNA and the hairpin motif 1(H1)and hairpin motif 2(H2)were designed based on the principle of CHA reaction.The H1 motif was labelled with a fluorophore group as well as a quencher group.When the target RNA was added to the hairpin motifs,CHA reaction was triggered at room temperature(25℃),which led to the amplification of fluorescence signal,thereby enabling the rapid detection of the target RNA.After the optimization of the hairpin motifs and the experimental conditions,the sensitivity and the specificity of the testing method were measured to evaluate its performance.Results We successfully constructed a CHA-based fluorescent assay specifically for the target RNA of SARS-CoV-2.With this method,testing could be completed at room temperature within 30 min.This testing method exhibited excellent specificity and could be used to accurately distinguish the perfectly-matched target RNA from the target RNA with single-base mutations.In addition,the testing method demonstrated good sensitivity,with a detection limit of 50 pmol/L.Conclusion The proposed assay enables the simple and rapid detection of the SARS-CoV-2 target RNA with excellent sensitivity and specificity,showing great promise for further optimization and subsequent clinical application for the rapid detection of SARS-CoV-2 nucleic acid.

Objective    To explore the treatment outcome of carotid endarterectomy combined with vertebral artery transposition in patients with severe stenosis to occlusion of the vertebral artery V1 segment and the ipsilateral carotid artery. Methods    From June 2017 to September 2020, patients with severe stenosis to occlusion of the vertebral artery V1 segment and the ipsilateral carotid artery treated with carotid endarterectomy combined with vertebral artery transposition in Fuwai Hospital were retrospectively analyzed. Results    Finally 12 patients were enrolled, including 10 males and 2 females with an average age of 67.8±6.0 years. Twelve patients were successfully operated and the follow-up time was 1-3 years. The stenosis degree of the V1 segment of the vertebral artery decreased from 83.5%±11.8% to 24.9%±14.3% (P<0.001). The stenosis degree of carotid artery decreased from 85.6%±11.0% to 0% (P<0.001). Postoperative follow-up showed that the symptoms of symptomatic patients before surgery improved. The 1-year and 3-year patency rates were 100.0%, and there were no peripheral nerve injury complications, perioperative deaths or strokes. Conclusion    Carotid endarterectomy combined with vertebral artery transposition can treat ipsilateral carotid artery  stenosis and vertebral artery stenosis at the same time, improve blood supply to the brain, improve patients' symptoms and has high promotion value.

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.