OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Objective: To analyze the trends of overweight and obesity in children and adolescents aged 7-18 in Hainan Province from 2005 to 2019, in order to provide a scientific basis for prevention strategies. Methods: Data were sourced from a total of 42 811 students in Hainan Province in 2005, 2010, 2014 and 2019 for physical fitness and health investigation, according to the criteria of Screening for Overweight and Obesity among School aged Children and Adolescents. The linear trend of overweight and obesity was compared by using the χ 2 test and χ 2 trend test, and with 2005 as the base period, the dynamic analysis was conducted to compare the growth and development rates of overweight and obesity. Results: The detection rates of overweight in children and adolescents aged 7-18 in Hainan Province were 4.7%, 5.1%, 6.7% and 10.8% in 2005, 2010, 2014 and 2019, respectively, while the detection rates of obesity were 2.7%, 2.4%, 2.5% and 6.8%, which showed an overall upward trend by year ( χ 2 trend =370.57 , 313.55, P <0.01). All differences in overweight and obesity detection rates across gender, ethnicity, and age groups were statistically significant for each year ( χ 2=9.56-290.95, P <0.01). And the detection rates of overweight and obesity increased linearly over year in different characteristic groups ( χ 2 trend =29.92-280.11, P <0.01). The annual growth rate of overweight detection rate was higher for girls (6.4%) than for boys (6.1%), higher for ethnic minorities (7.1%) than for Han (5.7%), and higher for the 16- 18 age group (8.4%) than for the 7-9 (3.6%), 10-12 (6.2%), and 13-15 age groups (7.7%). And the annual growth rate of obesity detection rate was higher for boys (8.1%) than for girls ( 5.7% ), higher for ethnic minorities (7.1%) than for Han ( 6.8% ), and higher for the 16-18 age group (77.2%) than for the 7-9 (2.8%), 10-12 (8.2%), and 13-15 (18.7%) age groups. Conclusions The overall prevalence of overweight and obesity among children and adolescents aged 7-18 in Hainan Province continues to increase from 2005 to 2019, with differences in genders, ethnic and ages. Interventions should be implemented to reduce the incidence of overweight obesity in children and adolescents.

Objective: To understand the trends in malnutrition among primary and middle school students of Han nationality in Hainan Province from 2005 to 2019, so as to provide a basis for improving nutrition intervention measures for children and adolescents. Methods: A sample of 32 949 Han nationality primary and middle school students aged 7-18 years old in Hainan Province were investigated in 2005, 2010, 2014 and 2019 based on national survey on student physical fitness and health. The Malnutrition Screening Standard of Schoolage Children and Adolescents was used to screen malnutrition. Statistical analysis was performed using the χ2 test and the χ2trend test. Results: In the four surveys conducted during 2005 to 2019, the prevalence of malnutrition among primary and middle school students were 22.12%, 18.80%, 15.89% and 9.56%, respectively, with an increase of -12.56% and an average annual increase of -5.82%. The decreasing trend of malnutrition by year was statistically significant (χ2trend=600.72, P<0.01), and the proportion of emaciation type was the highest (8.87%-20.15%). The detection rates of malnutrition among all students aged 7 to 18 showed a decreasing trend from 2005 to 2019 (χ2trend=56.44, 60.04, 61.48, 42.49, 51.81, 50.81, 72.86, 101.34, 86.38, 24.81, 17.72, 10.38, P<0.01). From 2005 to 2019, the detection rates of malnutrition in boys were higher than that of girls (in 4 surveys), and that in rural students from 2005 to 2014 of 3 surveys were higher than that in towns (χ2=92.07, 35.16, 25.29, 29.98; 64.35, 4.26, 6.32, P<0.05). Conclusions The malnutrition of Han nationality primary and middle school students aged 7-18 years in Hainan Province show a trend of improvement year by year from 2005 to 2019, despite the overall high detection rate. Wasting is the most common type of malnutrition. The epidemic of malnutrition varies by age, sex and areas. Further targeted measures should be taken to strengthen intervention in the diet of primary and middle school students, to improve the nutritional status of children and adolescents.

Objective To objectively classify cancer-related fatigue(CRF)patients with qi and blood deficiency syndrome;To explore possible enrichment characteristics;To provide ideas for precise population identification.Methods A cross-sectional study was conducted,611 CRF patients with qi and blood deficiency syndrome were included from October 2019 to April 2022.Clinical symptoms of patient were documented,including pale or withered-yellow complexion,shortness of breath with reluctance to talk,dizziness,spontaneous sweating,and palpitations.Additionally,blood routine were conducted,including white blood cell(WBC)count,red blood cell(RBC)count,hemoglobin(HGB),platelet(PLT)count,and neutrophil count(NEUT).The degree of fatigue was assessed using the Piper Fatigue Scale(PFS).Data analysis was performed using R 4.2.0.Clustering analysis was performed using the K-mediods method.Results Through unsupervised clustering analysis,the target population was divided into three categories:qi and blood deficiency syndrome leaning towards qi deficiency,qi and blood deficiency syndrome with mild symptom,qi and blood deficiency syndrome leaning towards blood deficiency.In terms of fatigue severity,the first two groups showed comparable levels,while the third group exhibited the most severe fatigue.Regarding objective indicators,the group leaning towards qi deficiency had the lowest WBC count,NEUT count and PLT count,and the group leaning towards blood deficiency had the lowest HGB count and RBC count.The group of qi and blood deficiency syndrome with mild symptom exhibited the highest level of objective indicators among the three.Conclusion By using clustering analysis methods,the study has preliminarily achieved population enrichment and classification based on syndromes,providing ideas for subsequent information enrichment and accurate identification of populations.Concurrently,the anemia index,WBC count and NEUT count demonstrate a inclination towards blood deficiency syndrome and qi deficiency syndrome,respectively.These findings indicate that these indicators could be incorporated into the syndrome diagnostic criteria for CRF to aid in the classification of the CRF population.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of prurigo nodularis (PN) in the real world.Methods:PN patients who were subcutaneously injected with dupilumab for over 12 weeks were collected from the China Type Ⅱ Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project Database from June 2021 to October 2022. Their clinical data were retrospectively analyzed, which included demographic data, and changes in pruritus numeric rating scale (NRS), investigator global assessment for PN-Stage (IGA PN-S), dermatology life quality index (DLQI) and hospital anxiety and depression scale (HADS) scores before and after treatment. Differences in scores before and after treatment, as well as in efficacy between patients with and without a history of atopic diseases, were analyzed using Wilcoxon signed-rank test, paired t-test or chi-square test. Results:A total of 66 PN patients were collected, including 42 males and 24 females, and they were aged 8 to 89 (44.12 ± 24.17) years. Thirty-six patients had a history of atopic diseases, and 27 had a family history of atopic diseases. After 12-week treatment with dupilumab, the pruritus NRS, IGA PN-S and DLQI scores in the 66 patients significantly decreased from the baseline scores (7.00 [5.00, 8.00], 3.00 [3.00, 4.00], 12.00 [7.75, 20.25], respectively) to 3.00 [2.00, 4.25], 2.00 [2.00, 3.00], 5.00 [1.75, 8.25], respectively (all P < 0.001). Among the 66 patients, 39 continued the regular treatment with dupilumab after 12 weeks and were followed up to 16 weeks; their pruritus NRS and IGA PN-S scores at week 16 further decreased compared with those at week 12 (both P < 0.05). There were no significant differences in the proportion of patients showing an improvement of ≥ 4 points in the NRS score or the proportion of patients achieving IGA 0/1 at week 12 between the patients with history of atopic diseases and those without (both P > 0.05). Before treatment, 32 PN patients were accompanied by mild to severe anxiety and/or depression; after 12-week treatment, the HADS-A scores in the 28 patients with anxiety (HADS-A scores > 7 points) and the HADS-D scores in the 20 patients with depression (HADS-D scores > 7 points) significantly decreased compared with their baseline scores (both P < 0.001) ; 18 (56.52%) patients achieved remission in anxiety and depression (both HADS-A and HADS-D scores < 7 points). Among the 66 PN patients, there were 13 minor patients, including 7 males and 6 females, and they were aged 8 to 17 (13.77 ± 3.09) years; after 12-week treatment, their pruritus NRS, IGA PN-S, and DLQI scores significantly decreased compared with the corresponding baseline scores (all P < 0.05) ; 8 minor patients continued dupilumab treatment for 16 weeks, with a further decrease in the IGA PN-S score compared with that at week 12 ( P < 0.05), but without significant differences between the pruritus NRS and DLQI scores at week 16 and those at week 12 (both P > 0.05). Adverse reactions were observed in 7 adult patients, including eye pruritus, local injection reactions, and systemic erythema accompanied by pruritus on the day of injection. No adverse reactions were reported in minor patients. Conclusion:In the real world, dupilumab could markedly alleviate pruritus, skin lesions, anxiety and depression symptoms in PN, improve the quality of life, and exhibited a good safety profile.

Objective:To explore the association between serum 25-hydroxyvitamin D[25(OH)D]and handgrip strength in middle-aged and elderly people in 5 cities of Western China.Methods:Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023,the relevant demographic characteristics of people were collected by questionnaire,handgrip strength was collected by physical examination,and serum 25(OH)D was detected by HPLC-MS/MS.The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regres-sion and Chi-square test for between-group comparisons models.Results:The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9％and 34.5％,respectively.The people who were older,female,and sampled in winter had lower serum 25(OH)D levels(P＜0.05).The prevalence of loss of handgrip strength among the mid-dle-aged and elderly people was 25.3％.The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency(45.0％)than in those with 25(OH)D insufficiency(32.6％)and 25(OH)D sufficiency(20.6％).The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency(62.1％),followed by the 25(OH)D insufficient group(11.1％,P＜0.05).The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency(OR=2.403,95％CI:1.202-4.804,P=0.013).No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people.For every 5 μg/L increase in total serum 25(OH)D,the risk of handgrip strength loss reduced by 13.1％(OR=0.869,95％CI:0.768-0.982,P=0.025).For every 5 μg/L increase in serum 25(OH)D2,the risk of handgrip strength loss reduced by 24.1％(OR=0.759,95％CI:0.582-0.990,P=0.042).No significant association was found between serum 25(OH)D3 levels and the risk of hand-grip strength loss.The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2％for each incremental increase in the total serum 25(OH)D levels(deficient,insufficient and suf-ficient)(OR=0.748,95％CI:0.598-0.936,P=0.011).The risk of handgrip loss was reduced by 40.0％for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants,and by 80.0％for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants.Conclusion:Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.

Objective To investigate the effect of mogrol on lung injury in rats with severe acute pancreatitis and its possible mechanism.Methods The model of lung injury in rats with severe acute pancreatitis was established by retrograde injection of 4%sodium taurocholate into the biliopancreatic duct,After modeling,they were divided into model group,mogrol low,medium and high dose groups(15,30,60 mg·kg-1),set up another sham operation group,each group containing 12 rats.Intraperitoneal injection,one day once time,a total of 2 times.The pathological changes of pancreas and lung tissues were detected by HE staining;Serum amylase(AMS)and lipase(LPS)levels were detected by biochemical method;The levels of inflammatory cytokines interleukin-1β(IL-1β),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in rat alveolar lavage fluid were determined by ELISA;The activity of Caspase-1 in lung tissue of rats was detected by colorimetry;The expression levels of triggering receptor 1(TREM-1)and pyroptosis related proteins NLRP3,Caspasse-1,Gasdermin D(GSDMD)in lung tissue of rats were detected by Western blot.Results Compared with the sham operation group,the model group showed obvious pathological damage in pancreas and lung tissue.Serum AMS and LPS levels,inflammatory factors IL-1β,IL-18 and TNF-α levels,Caspase-1 activity,and protein expression levels of TREM-1 and NLRP3,Caspasse-1,GSDMD,in lung tissue were significantly increased(P<0.05);Compared with the model group,different doses of mogrol could improve the pathological damage of pancreas and lung tissue in rats,and significantly reduce the levels of serum AMS,LPS,inflammatory factors IL-1β,IL-18 and TNF-α,Caspase-1 activity and the expression levels of TREM-1 and NLRP3,Caspasse-1,GSDMD in lung tissue.Conclusion Mogrol may improve lung injury in rats with severe acute pancreatitis by inhibiting pyroptosis,and its mechanism may be related to the regulation of TREM-1/NLRP3 signaling pathway.

Objective:To summarize the clinical treatment of complete left bundle branch block (CLBBB) after the transcatheter closure of ventricular septal defect (VSD).Methods:A case series study was conducted on the treatments and outcomes of 25 children with CLBBB after transcatheter VSD closure in Guangdong Provincial People′s Hospital from January 2010 to December 2023.Paired sample t test was used to evaluate the effect of occlude removal. Results:Among the 25 patients, 12 were males (48%), and 13 were females (52%).The age at surgery was 3.18 (2.51-3.86) years, the height before surgery was 95.0 (90.0-97.5) cm, and the weight before surgery was 13 (12-15) kg.Fourteen children were early-onset cases (≤ 1 month), while the other 11 were late-onset cases (> 1 month).The mean follow-up time was (6.63±3.93) years.Of the 14 early-onset cases, 6 children underwent occluder removal within 1 month and restored normal heart rhythm or incomplete right bundle branch block; 4 children underwent occluder removal after 1 month, of whom 2 recovered, 1 remained CLBBB, and 1 had complete atrioventricular block (CAVB); the other 4 children received drug treatment, of whom 2 had normal heart rhythm, 1 had left anterior fascicular block, and 1 died of cardiac shock and heart failure.All the 11 late-onset cases were first treated by drugs, of whom 3 recovered, and the other 8 remained CLBBB.One of the 8 cases received occluder removal at 8 months after surgery and recovered, 1 had CAVB, and the other 6 remained CLBBB.Conclusions:For patients with CLBBB after transcatheter closure of VSD, drug therapy is not always effective, and CLBBB is easy to recur.Therefore, occluder removal is recommended to be done immediately after CLBBB is discovered.Patients with persistent CLBBB should be followed up regularly, and pacemaker implantation may be performed if necessary.

Objective To analyze the expressions of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) in peripheral blood of neonates with necrotizing enterocolitis (NEC) and their relationships with the severity of the disease. Methods Ninety-two children with NEC were selected and divided into NEC group, and further divided into mild group (grade Ⅰ, n=60) and severe group (gradeⅡ to Ⅲ, n=32) according to the severity of the disease. Another 60 children with inguinal hernia were selected as control group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expressions of RIPK3 mRNA and MLKL mRNA in peripheral blood. Pearson correlation analysis was used to determine the correlation between RIPK3 mRNA and MLKL mRNA expression in peripheral blood of the NEC group. Western blot was used to detect the expression of RIPK3 and MLKL proteins in ileal tissues of NEC and normal ileal tissues. Multivariate Logistic regression analysis was used to identify independent risk factors for severe NEC. The receiver operating characteristic curve was plotted to analyze the value of peripheral blood RIPK3 mRNA and MLKL mRNA alone and their combination for predicting severe NEC. Results The relative expression levels of RIPK3 mRNA and MLKL mRNA in peripheral blood of the NEC group were significantly higher than those in the control group[(2.41±0.52) versus (1.02±0.21), (3.03±0.64) versus (0.93±0.20), P < 0.001]. The relative gray values of RIPK3 and MLKL proteins in ileal tissues of NEC were significantly higher than those in normal ileal tissues[(1.20±0.21) versus (0.34±0.12), (1.13±0.24) versus (0.32±0.11), P < 0.05]. There was a positive correlation between the relative expression level of RIPK3 mRNA and MLKL mRNA in peripheral blood of children with NEC (r=0.623, P < 0.001). The proportion of children with severe NEC complicated by pneumoperitoneum, multiple organ dysfunction syndrome, and sepsis, as well as the relative expression levels of RIPK3 mRNA and MLKL mRNA were significantly higher in the severe NEC group than in the mild NEC group (P < 0.05). The relative expression levels of RIPK3 mRNA and MLKL mRNA were independent risk factors for severe NEC (P < 0.05). The area under the curve for combined prediction of severe NEC by RIPK3 mRNA and MLKL mRNA in peripheral blood was larger than that for individual prediction (Z=4.127, 4.261, P < 0.05). Conclusion The expression levels of RIPK3 mRNA and MLKL mRNA in peripheral blood are elevated in neonates with NEC, and both are associated with the severity of NEC. The combined detection of RIPK3 mRNA and MLKL mRNA has a higher predictive value for severe NEC.