Objective: To understand the changing trends and related factors of knowledge, attitude and practice (KAP) regarding the three major infectious diseases (acquired immunodeficiency syndrome, tuberculosis, hepatitis B) among freshmen in Jiangsu from 2019 to 2022, so as to provide a reference basis for the health education of infectious diseases in schools. Methods: From 2019 to 2022, a total of 33 944 freshmen from 20 universities in Jiangsu Province were randomly selected for four consecutive years to investigate their KAP levels online through self designed questionnaires on three major infectious diseases. The multiple linear regression model was used to analyze the changing trends of students KAP levels of the three major infectious diseases, and to explore the influencing factors of KAP. Results: From 2019 to 2022, the knowledge scores(18.0±3.1,18.4±3.2,18.7±3.2,18.8±3.2), related to the three major infectious diseases showed an upward trend ( F=436.50, P <0.01), and the positive attitude reporting rates were 81.77%, 81.46%, 82.68% and 81.74%, respectively. The reporting rates of positive practice were 80.11%, 79.25%, 79.08 % and 79.04%, respectively. Multiple linear regression showed that school type, parental education level, mother s occupation, average income per person in family and living arrangements during high school all had an impact on the knowledge ( β = -1.510 -0.559), attitudes ( β =-0.043-0.065) and practice ( β =-0.028-0.027) of the three major infectious diseases ( P < 0.05 ). The family residence areas only affected the reporting rate of positive attitude scores ( β =0.002-0.065), and whether only children or not affected the reporting rate of positive practice scores ( β =0.009)( P <0.05). The knowledge score showed an upward trend ( β= 0.297, P <0.01), the positive attitude reporting rate showed no statistically significant change ( β=0.001, P =0.22), and the positive practice reporting rate showed a downward trend ( β=-0.005, P <0.01). Conclusions Freshman in Jiangsu Province from 2019 to 2022 have shown a separation in KAP scores regarding the three major infectious diseases. Targeted measures should be taken to improve their health practice level.

ObjectiveTo evaluate the intervention effect of meteorological risk forecasting service on acute onset and medical expenses of chronic obstructive pulmonary disease（COPD） patients， and to provide scientific basis for the establishment of health management model for chronic obstructive pulmonary disease（COPD） patients. MethodsStudy subjects were recruited from chronic obstructive pulmonary patients aged ≥40 in Pudong New Area. Propensity score matching method was used to determine the intervention group and the control group. The control group received regular health education and follow-up management， and the intervention group was provided with meteorological and environmental risk forecasting services through WeChat， mobile phone short message service（SMS）and telephone. Finally， a total of2 589 subjects were included in the analysis， including 1 300 in the intervention group and 1 289 in the control group. General demographic data， past medical history and family history of COPD， COPD related knowledge and practice survey， COPD related symptom assessment， acute onset， health service utilization and medical expenses before and after intervention were collected through questionnaire survey. The differences of acute attack， health service utilization and related medical expenses between the two groups before and after intervention were compared to evaluate the intervention effect. ResultsIn terms of acute attacks， after intervention， the incidence of acute attacks in the intervention group was lower than that before intervention（χ²=52.901， P<0.001）， and the incidence of acute attacks in the groups with different intervention methods was lower than that before intervention （P<0.001）. WeChat had the best effect， decreasing the incidence by 14.4%， followed by mobile phone SMS SMS decreasing by 12.3%. In terms of utilization of health services， the outpatient rate due to acute attack was lower in the intervention group after intervention than that before intervention （χ²=7.129， P=0.008）， and the outpatient rate due to acute attack was lower in the subjects who received the forecast service through mobile phone SMS than that before intervention （χ²=4.675， P<0.001）. In terms of medical expenses， there was no significant difference between control group and intervention group with different intervention methods before intervention （P>0.05）. After intervention， the difference between the control group and the intervention group with different intervention methods was statistically significant （H=11.864， P<0.05）. The results of multiple comparisons showed that compared with the control group， the average annual medical expenses of patients receiving mobile phone SMS and telephone forecasting services after intervention were lower than those of the control group， and the difference was statistically significant （P<0.05）. ConclusionMeteorological risk forecasting service can reduce the acute onset of COPD， reduce the rate of consultation and medical expenses due to acute onset， and provide scientific basis for the basic COPD health management model.

Objective:To explore the efficacy and safety of dual targeted therapy（DTT）in the treatment of refractory inflammatory bowel disease（IBD）in children.Methods:The diagnosis and treatment processes of refractory IBD children treated with DTT in the Department of Gastroenterology,Beijing Children's Hospital Affiliated to Capital Medical University from April 2022 to May 2024 were analyzed retrospectively,and their clinical characteristics were summarized.Results:A total of ten children with refractory IBD were included,including five males and five females,with a median onset age of 12.58 (5.25,13.33) years old,and seven cases of Crohn's disease (CD) and three cases of ulcerative colitis (UC),with a median disease course of 1.25 (0.91,4.00) years，were treated with DTT for a median time of 6.08 (6.00,13.40)months.Two (2/7) cases of CD patients were partially effective with infliximab(IFX) treatment,while five (5/7) cases were partially effective with a combination of IFX and azathioprine treatment.These patients received DTT with UST in addition to continuous using of IFX.When the seven CD patients were treated with DTT for four weeks,12 weeks and 24 weeks,and the clinical remission rates were 42.9%(3/7),71.4%(5/7) and 100%(7/7)，respectively.The pediatric Crohn's disease activity index gradually decreased,which were significantly lower than those before treatment( P<0.05).Fecal calprotectin,C-reactive protein,erythrocyte sedimentation rate,and blood white blood cells all gradually decreased,which were lower than those before treatment,while hemoglobin and serum albumin were higher than those before treatment.Three children with UC were all resistant to glucocorticoids.One case was partially effective with adalimumab treatment,one case was partially effective with IFX combined with immunosuppressive agents,and one case was partially effective with vedolizumab.All the three UC patients received DTT treatment with UST in addition to continuous using of the original biological preparation.When the three UC patients were treated with DTT for four weeks and 12 weeks,one case showed clinical remission,one case showed clinical response,and one case showed no clinical response.After 24 weeks of DTT treatment,two cases achieved clinical remission and one case had no clinical response.Re-examination of colonoscopy showed that one case of clinical remission had mucosal healing and one case had mild disease activity.However,there was a slight improvement in disease activity under endoscopy compared with that before DTT in patient who had no clinical response.During DTT treatment,no adverse events occurred in all patients. Conclusion:DTT is effective and relatively safe for children with refractory IBD,and can be one of the attempts for children with IBD when they are partially effective with one biological agent.

Objective:To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis.Methods:The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children′s Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital.Results:The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up.Conclusions:The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.

Objective:To explore the clinical effect of magnetic resonance imaging (MRI) or ultrasound-guided high intensity focused ultrasound (HIFU) ablation in the treatment of uterine fibroids.Methods:The clinical data of 124 patients with uterine fibroids who received HIFU ablation in the Department of Obstetrics and Gynecology of Xi'an People's Hospital were retrospectively analyzed from April 2020 to February 2023. The patients were divided into an MRI group (58 cases treated with magnetic resonance guided HIFU ablation) and an ultrasound group (66 cases treated with ultrasound guided HIFU ablation) according to different guidance methods. The treatment effects (total effective rate, fibroid ablation volume, fibroid ablation rate), surgical conditions (total energy consumption, total time consumption, energy efficiency factor, irradiation time), incidence of adverse events, ovarian function (follicle stimulating hormone (FSH), inhibin) at 3 months before and after surgery were compared between the two groups. B. Antral follicle count (AFC) and recurrence at 6 and 12 months after surgery. The t-test is used for comparing between groups of metric data that conform to normal distribution, and the chi square test is used for comparing between groups of count data.Results:The total energy consumption, total time consumption and irradiation time in MRI group were longer than those in ultrasound group( (571.68±184.31) kJ vs (494.82±155.03) kJ, (186.21±36.19) min vs (121.63±31.09) min, (26.12±7.93) min vs (22.07±7.46) min), there were have statistical differences( t values were 2.52, 10.69, and 2.93, respectively; P values were 0.013, <0.001, and 0.004, respectively). At 3 months after surgery, the level of FSH in the two groups was risen than that before surgery(MRI group (10.27±1.72) U/L vs (8.67±1.63) U/L, ultrasound group (10.13±1.66) U/L vs (8.46±1.57) U/L), the level of INHB and the number of AFC were declined (MRI group (40.46±5.31) ng/L vs (47.19±4.24) ng/L, (4.22±1.21) vs (6.72±1.48); ultrasound group (39.07±5.12) ng/L vs (48.20±4.77) ng/L, (4.11±1.09) vs (6.63±1.41)) there were have statistical differences ( t values were 5.14, 5.94, 7.54, 9.96, 10.60, and 11.48, respectively; all P<0.001). Conclusion:Both methods of guided HIFU ablation for uterine fibroids can effectively ablate fibroids and improve ovarian function, with safety. Ultrasound guidance has a shorter treatment time and less energy consumption compared to MRI guidance.

Objective:To investigate the utility of cardiac magnetic resonance (CMR) multiparametric imaging in the etiological and differential diagnoses of troponin increase with non-obstructive coronary arteries (TINOCA).Methods:A retrospective analysis was conducted on patients diagnosed with TINOCA and confirmed by coronary angiography in Dongguan Kanghua Hospital from January 2018 to June 2023. CMR examinations were performed within 7 days of onset. The examination sequences included "black blood" single-shot balanced turbo field echo with breath-hold, balanced turbo field echo with breath-hold, T 2-weighted short tau inversion recovery black blood, modified gradient and spin echo black blood with SENSE, dynamic balanced turbo field echo, and phase-sensitive inversion recovery [late gadolinium enhancement (LGE)]. Based on the imaging findings, patients were categorized into 4 groups: myocardial infarction with non-obstructive coronary arteries (MINOCA) group, acute myocarditis group, Takotsubo syndrome group, and CMR negative group. The observed indices included left ventricular function, myocardial edema, first perfusion, and LGE of contrast enhancement. The differences in these parameters among the aforementioned disease groups were statistically compared. The categorical data were analyzed between groups using the chi-square test or Fisher′s exact probability method. The data in line with normal distribution were statistically described by xˉ±s. The independent-sample t test was used to compare the means of the 2 samples. The data with skewed distribution were described by M ( Q1, Q3). The Mann-Whitney U test was used for intergroup analysis. Results:A total of 33 patients were enrolled in this study, the 4 groups comprised 14(42.4%), 12(36.4%), 0, and 7(21.2%) patients, respectively. The positive rate of CMR diagnosis was 78.8%. The onset age in the MINOCA group significantly differed from that in the acute myocarditis group ( Z=3.32, P=0.001). No significant differences were observed in left ventricular function, number of myocardial edema segments, and T 2 value of the diseased myocardium between the 2 groups ( P>0.05), but the number of abnormal first perfusion was significantly distinct ( P<0.001). Significant differences were observed in the quality and volume of LGE between the 2 groups ( P<0.05 for all). Conclusion:CMR multiparameteric imaging technology plays a unique role in the etiological diagnosis of TINOCA, accurately distinguishing TINOCA caused by MINOCA, acute myocarditis, and other cardiac causes.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

It is the current confusion encountered by integrated Chinese and Western medicine that how to find the breakthrough direction of integrating Chinese and Western medicine， from crossover to integration to innovation， and open up a new horizon of integrated Chinese and Western medicine. The progress of Chinese medicine lay in expanding the scope of diagnosis and treatment with the help of modern diagnostic and therapeutic equipments and developing “micro” identification， while the progress of Western medicine lay in looking at “macro” and developing systemic medicine and integrated medicine， both of which are in the direction of each other. The “state-target identification and treatment” may become an important way to build a modern diagnosis and treatment system of integrated Chinese and Western medicine， and the thinking mode of “from target to state” is a further refinement and development on the basis of the theoretical system of “state-target identification and treatment”， which provided a clearer solution for the current stage of the integrated Chinese and Western medicine model， and pointed out the important development direction for the future integrated Chinese and Western medicine. From the perspective of strategic level and diagnosis and treatment practice， it integrated the “target-state” thinking mode into the modern diagnosis and treatment model of the integrated Chinese and Western medicine， i.e.， “Western medicine as the basis and treating with Chinese medicine； Chinese medicine as the basis and treating with Western medicine”. On the one hand， Western medicine should strengthen the reference to the traditional theories and holism of Chinese medicine， and advocate a higher level of education on the integrated Chinese and Western medicine under the guidance of the traditional theories of Chinese medicine. On the other hand， the “from target to state” mode of thinking should be applied to guide the establishment of diagnostic and treatment strategies and clinical selection of medicines in clinical practice， so as to locate the target and adjust the body state in a gradual and orderly manner， and to provide practical methods for the modern clinical work of the integrated Chinese and Western medicines. Chinese and Western medicine systems can learn from each other， combine organically， give full play to their respective strengths， and form an internal law， so as to make breakthroughs and innovations in the integrated Chinese and Western medicine model.

Objective:To investigate the clinical phenotype and prognosis among different genotypes of progressive familial intrahepatic cholestasis(PFIC) by cases analysis.Methods:The PFIC cases diagnosed at Beijing Children′s Hospital from 2015 to 2022 were collected, and the clinical phenotypic characteristics, treatment and prognosis were compared and analyzed.Results:A total of 628 cases of cholestatic liver disease were diagnosed, and 26 cases of PFIC were found, accounting for 4.1%.The number of PFIC 2 were the most, 14(53.8%)cases; three(11.5%) cases were PFIC 1; five(19.2%)cases were PFIC 3; while two(7.7%) cases were PFIC 4 and PFIC 6, respectively, and there was no case of PFIC 5.Type 1, 2, 4, and 6 had early onset ages(2 days to 21 months), while type 3 had a wide range of onset ages(8 to 145 months). The symptoms included jaundice(96.2%), pruritus(42.3%), and mucosal bleeding(15.4%). All three cases of type 1 had extrahepatic manifestations of diarrhea and malnutrition.Two cases of type 3 were found to have end-stage liver disease.Cases of PFIC 3 had increased serum γ-glutamyltransferase(97.2-439.5 U/L), while those of other types were normal.The bile acids were all increased(10.1-599.6 μmol/L). Abdominal ultrasound mainly showed liver enlargement(80.8%)and enhanced echogenicity of liver parenchyma(73.1%), enlargement of the spleen(61.5%). Ultrasound liver elastography ranged from 6.3 kPa to 23.1 kPa, there were 21(80.8%) cases ≥9 kPa.Among 26 cases, one case was lost to follow-up, and 11 cases were effective by oral medication alone.Fourteen children were still suffering from relapse or progress after drug treatment: four cases received liver transplantation (three cases had a good prognosis and one case died), two cases received biliary drainage, six cases were still taking drugs orally, and two cases died without active intervention in disease progress.Conclusion:Type 2 is the most common type in PFIC.The onset of most cases is in infancy.Jaundice, pruritus and hepatosplenomegaly are common clinical manifestations, and extrahepatic manifestations can be seen in type 1 cases.Type 3 cases can start with end-stage liver disease.Bile acid of all cases are increased.Except for type 3, the serum γ-glutamyltransferase of cases are normal.Oral medication has certain effects on some cases, but more than half progress, and some need biliary diversion or liver transplantation.

Objective:To investigate the expression and clinical significance of vitamin D receptor (VDR) and human β-defensin-2(HBD2) in children with Helicobacter pylori (Hp) infection and gastritis.Methods:Eighty-one children who were hospitalized in the Department of Gastroenterology at Beijing Children′s Hospital from January 2021 to June 2023 and underwent endoscopic examination were collected.They were divided into Hp infection group and non-Hp infection group according to whether they were infected with Hp.The expression levels of VDR and HBD2 between two groups, and the correlation between VDR, HBD2 expression levels and gastritis were compared and analyzed.Results:Among 81 cases, 48 cases were Hp positive, including 24 males and 24 females, with an average age of (11.4±2.7) years; 33 cases were Hp negative, including 14 males and 19 females, with an average age of (11.3±2.6) years.There were no significant differences in sex and age between two groups ( P>0.05). The positive rates of VDR and HBD2 expression in gastric mucosa of children with Hp infection were higher than those of children without Hp infection, and the differences were statistically significant (87.5% vs.39.4%, 79.2% vs.63.6%, all P<0.05). The expressions of VDR and HBD2 had no correlation with age and sex ( P>0.05). The expressions of VDR and HBD2 were positively correlated with granular degeneration of gastric mucosa ( r=0.384, P<0.001; r=0.258, P=0.020). The expression of VDR was positively correlated with the degree of gastric inflammation ( r=0.365, P=0.001), while the expression of HBD2 was not correlated with the degree of gastric inflammation ( P>0.05). Conclusion:The expression levels of VDR and HBD2 in gastric mucosa of children infected with Hp are increased.The expression level of VDR is correlated with the degree of gastritis and the granular degeneration of gastric mucosa.The expression level of HBD2 is correlated with the granular degeneration of gastric mucosa.But there is no correlation between the level of HBD2 expression and the degree of gastritis.