OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues（MCACs） and investigate the activities of them against breast cancer. METHODS The analogues F1， F2， and F3 were obtained by aldol condensation reaction， and their antitumor activities（including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549） were detected by MTT assay [evaluated with half inhibitory concentration（IC50）]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1， F2 and F3 acting on breast cancer， and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high， medium and low concentrations （16， 8， 4 μmol/L） of F1， F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1， F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin， IC50 of analogues F1， F2 and F3 to A549 and MCF-7 cells（except for IC50 of analogue F2 to A549 cells） were decreased significantly（P＜ 0.05 or P＜0.01）； among them， IC50 of analogue F2 to MCF-7 cell was the lowest， being（9.67±1.27） μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1， F2 and F3 with the first core target epidermal growth factor receptor （EGFR）， protein kinase B （AKT） and AKT were 5.909 2， 8.402 5 and 6.486 6， respectively； high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells（P＜0.01）， while low， medium， and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells（P＜0.05 or P＜0.01）. Medium concentration of F1， F2， and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells（P＜0.01）. CONCLUSIONS Designed and synthesized MCACs F1， F2 and F3 all have good anti- breast cancer activity， and F2 has better anti-breast cancer activity.

BackgroundPreventing and intervening in adolescent gaming disorder is of significant practical importance. Gaming motivation is strongly linked to gaming addiction and serves a key function in comprehending and addressing addictive gaming behaviors. However， the relationship between components of gaming motivation and symptoms of gaming disorder remains unclear. ObjectiveTo explore the relationship between components of gaming motivation and symptoms of gaming disorder among adolescents， so as to provide references for the prevention and intervention of gaming disorder in this population. MethodsFrom January to February 2024， a cluster sampling method was employed to select 1 414 adolescents from four middle schools in Sichuan Province and Chongqing Municipality as participants in the study. Online Game Motivation Scale （OGMS） and Gaming Disorder Scale for Adolescents （GADIS-A） were administered. Network analysis methods were utilized to investigate the relationships between components of gaming motivation and symptoms of gaming disorder. ResultsThe network edge weights revealed that achievement motivation was positively correlated with impaired game control ability， continued gaming despite negative consequences and the frequency of symptom occurrence （r=0.115， 0.050， 0.076， P<0.05）. Social motivation was negatively correlated with negative consequences （r=-0.054， P<0.05），while immersion motivation was positively correlated with continued gaming despite negative consequences （r=0.032， P<0.05）. Achievement motivation exhibited the highest strength centrality （1.157） among the three components of gaming motivation. ConclusionThe connections between components of gaming motivation and symptoms of gaming disorder exhibit distinct patterns， with each motivational component influencing gaming disorder through specific symptom pathway. Among these components， achievement motivation plays the most critical role in the interplay between gaming motivation and symptoms of gaming disorder. ［Funded by Chongqing Science and Health Joint Medical Science and Technology Innovation Projects General Projects （number， 2023MSXM133）］

Objective: To investigate the characteristics of AHFtest-based HIV antibody self-testing among male adolescents at ages of 15 to 24 years, so as to provide insights into the promotion of HIV antibody self-testing. Methods: Data were collected from male adolescents at ages of 15 to 24 years that applied for HIV antibody self-testing in the AHFtest platform from 2019 to 2021, with mailing address showing as Zhejiang Province, and demographics, applying cause and testing results were analyzed. Results: A total of 268 male adolescents were enrolled, with a median age of 22.00 (interquartile range, 3.00) years. There were 160 cases with an educational level of junior college/bachelor (59.70%), 147 students (54.85%), 175 men who had sex with men (65.30%), and 126 cases with a history of previous HIV antibody self-testing (47.01%). The main causes for applying for HIV antibody self-testing through AHFtest were "easy to operate" (259 cases, 96.64%) and "privacy protect" (102 cases, 38.06%). There were 203 subjects that applied once HIV antibody self-testing (75.75%), and 65 subjects that applied multiple self-testing (24.25%). There were 123 subjects that uploaded their test results (45.90%), including 3 cases with HIV antibody positive, and 125 subjects that did not tell others the self-testing results (46.64%). Conclusions Among male applicants at ages of 15 to 24 years in Zhejiang Province from 2019 to 2021, students are predominant occupation. Easy to operate and privacy protect are the main cause for the application, but the proportion of detection results uploading is relatively low.

Objective: To investigate the late identification and its influencing factors of newly reported HIV/AIDS cases in Shangcheng District, Hangzhou City, so as to provide insights into the development of strategies for early detection and identification of HIV/AIDS cases. Methods: Basic information, identification routes and CD4+T lymphocyte counts among newly reported HIV/AIDS cases in Shangcheng District from 2013 to 2022 were collected through the Chinese Disease Prevention and Control Information System. The proportion of late identification of newly reported HIV/AIDS cases was analyzed, and factors affecting late identification was analyzed by a multivariable logistic regression model. Results: Totally 1 052 HIV/AIDS cases were newly reported in Shangcheng District from 2013 to 2022, including 1 011 males (96.10%), and had a mean age of (32.90±12.39) years. There were 333 cases with late identification, accounting for 31.65%. The proportions of late identification have no significant changing trend from 2013 to 2022 (P>0.05). Multivariable logistic regression analysis showed that HIV/AIDS cases aged 25 years and older (25 to 49 years, OR=1.894, 95%CI: 1.350-2.658; 50 years and older, OR=3.010, 95%CI: 1.838-4.928) had a higher risk of late identification, while HIV/AIDS cases with college degree and above (OR=0.655, 95%CI: 0.459-0.936) and identified by voluntary counseling and testing (OR=0.542, 95%CI: 0.380-0.772) had a lower risk of late identification. Conclusions The proportion of late identification of newly reported HIV/AIDS cases in Shangcheng District from 2013 to 2022 was 31.65%. Age, educational level and identification route were important factors affecting late identification of HIV/AIDS cases in Shangcheng District.

Objective:To study the effects and mechanisms of activation of human lung fibroblasts (MRC-5) by exosomal RNA hsa _ circ _ 0006357 (circEZH2) derived from non-small cell lung cancer.Methods:Western blot was used to detect exosome molecular markers, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and cell invasion assays to detect the effect of non-small cell lung cancer-derived exosomes on MRC-5 activation. A circRNA microarray analysis was performed in serum exosomes from patients with non-small cell lung cancer (collected at Ningbo University People's Hospital, September 2023), and levels of circEZH2 were measured in serum exosomes from non-small cell lung cancer by RT-qPCR analysis. The effects of circEZH2 on MRC-5 activation were explored using wound healing assays, Transwell assays, RT-qPCR, cellular immunofluorescence, and western blot. The regulatory effect of circEZH2 on miR-495-3p/TPD52 axis and NF-κB pathway through dual-luciferase assay, immunofluorescence, and western blot.Results:Exosomes derived from non-small cell lung cancer cells were shown to promote MRC-5 cell invasiveness, the number of cells invaded in co-culture with exosomes derived from normal human bronchial epithelial cells was (42±5), and the number of cells invaded in co-culture with exosomes derived from non-small cell lung cancer cells (SPC-A1, H1299, A549 cells) was (246±7), (89±4), (69±14), expression of markers of fibroblast activation (α-SMA, FAP), and cytokines (IL-6, IL-8, P＜0.05). CircEZH2 expression was significantly upregulated in the serum exosomes of non-small cell lung cancer ( P＜0.01). Alternatively, co-culture of exosomes derived from non-small cell lung cancer cells with MRC-5 cells promoted circEZH2 expression ( P＜0.05). Functionally, overexpression of circEZH2 promoted MRC-5 cell migration and invasion [the cell migration rates were (30.81±2.54)% and (60.29±8.34)%, respectively, and the cell invasion numbers were (48.00±13.58) and (115.00±9.50), respectively, P＜0.05]. RT-qPCR, western blot, and immunofluorescence assays demonstrated a significant increase in the expression of the pro-inflammatory genes IL-6 and IL-8 in MRC-5 cells as well as the activation markers α-SMA and FAP in fibroblasts ( P＜0.05) following the expression of circEZH2. Mechanistically, circEZH2 may function as ceRNA to regulate miR-495-3p, promote the expression of TPD52, and activate the NF-κB pathway to promote the activation of MRC-5. Conclusion:Exosomal circEZH2, derived from non-small cell lung cancer, may promote the activation of fibroblasts by activating the NF-κB pathway through the miR-495-3p/TPD52 axis.

Objective:To study the effects and mechanisms of activation of human lung fibroblasts (MRC-5) by exosomal RNA hsa _ circ _ 0006357 (circEZH2) derived from non-small cell lung cancer.Methods:Western blot was used to detect exosome molecular markers, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and cell invasion assays to detect the effect of non-small cell lung cancer-derived exosomes on MRC-5 activation. A circRNA microarray analysis was performed in serum exosomes from patients with non-small cell lung cancer (collected at Ningbo University People's Hospital, September 2023), and levels of circEZH2 were measured in serum exosomes from non-small cell lung cancer by RT-qPCR analysis. The effects of circEZH2 on MRC-5 activation were explored using wound healing assays, Transwell assays, RT-qPCR, cellular immunofluorescence, and western blot. The regulatory effect of circEZH2 on miR-495-3p/TPD52 axis and NF-κB pathway through dual-luciferase assay, immunofluorescence, and western blot.Results:Exosomes derived from non-small cell lung cancer cells were shown to promote MRC-5 cell invasiveness, the number of cells invaded in co-culture with exosomes derived from normal human bronchial epithelial cells was (42±5), and the number of cells invaded in co-culture with exosomes derived from non-small cell lung cancer cells (SPC-A1, H1299, A549 cells) was (246±7), (89±4), (69±14), expression of markers of fibroblast activation (α-SMA, FAP), and cytokines (IL-6, IL-8, P＜0.05). CircEZH2 expression was significantly upregulated in the serum exosomes of non-small cell lung cancer ( P＜0.01). Alternatively, co-culture of exosomes derived from non-small cell lung cancer cells with MRC-5 cells promoted circEZH2 expression ( P＜0.05). Functionally, overexpression of circEZH2 promoted MRC-5 cell migration and invasion [the cell migration rates were (30.81±2.54)% and (60.29±8.34)%, respectively, and the cell invasion numbers were (48.00±13.58) and (115.00±9.50), respectively, P＜0.05]. RT-qPCR, western blot, and immunofluorescence assays demonstrated a significant increase in the expression of the pro-inflammatory genes IL-6 and IL-8 in MRC-5 cells as well as the activation markers α-SMA and FAP in fibroblasts ( P＜0.05) following the expression of circEZH2. Mechanistically, circEZH2 may function as ceRNA to regulate miR-495-3p, promote the expression of TPD52, and activate the NF-κB pathway to promote the activation of MRC-5. Conclusion:Exosomal circEZH2, derived from non-small cell lung cancer, may promote the activation of fibroblasts by activating the NF-κB pathway through the miR-495-3p/TPD52 axis.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

With the continuous improvement of medical information and intelligence, multi-modal data fusion technology is increasingly widely used in the medical field. Multi-modal data not only has a large quantity, but also has rich information content, which can provide strong support for clinical nursing decision-making. However, due to the uneven level of informatization and intelligence development among medical institutions, the development and application of nursing decision support system is still in a fragmented state. Based on this, this study explores in depth the current application status and challenges faced by multi-modal data fusion in nursing decision support systems, with the aim of providing reference for the design and improvement of nursing decision support system at all levels of medical institutions in the future.

Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.423), conceived by assisted reproductive technology ( B=－0.803), male fetus ( B=－0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.415), conceived by assisted reproductive technology ( B=－0.585), male fetus ( B=－0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.