BACKGROUND/OBJECTIVES: Deoxyshikonin (DSK) has been reported to inhibit tumor growth in various types of cancers, but its roles and action mechanisms in breast cancer (BC) are unclear. This study examined the anti-cancer function and mechanism of DSK in BC.MATERIALS/METHODS: MDA-MB-231 and BT549, human BC cells, were used. The cell viability and apoptosis levels were examined using Cell Counting Kit-8 experiments and flow cytometry, respectively. The expression of apoptosis-related factors (Ki-67, Bax, and Bcl-2), CD206, CD168, and proteins involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)uclear factor (NF)-κB pathway was evaluated by Western blot analysis. The cell invasion ability was determined using the Transwell experiment. The levels of interleukin (IL)-10 and transforming growth factor (TGF)-β were detected using an enzyme-linked immunosorbent assay. The in vivo functions of DSK were assessed using a xenograft mouse model. RESULTS: DSK inhibited cell proliferation, enhanced cell apoptosis, and reduced the cell invasion of MDA-MB-231 and BT549 cells. DSK also reduced the levels of CD206 and CD168 proteins, as well as IL-10 and TGF-β in phorbol 12-myristate 13-acetate-induced THP-1 cells.DSK downregulated the expression of the phosphorylated (p)-PI3K, p-AKT, and p-NF-κB proteins in cells. These effects were reversed by 740 Y-P (PI3K/AKT activator). In addition, DSK significantly reduced the tumor volume and weight in a xenograft mouse model. DSK increased the level of cell apoptosis and decreased the expression of Ki-67 and CD206 in subcutaneous tumor tissue. DSK also inactivated the PI3K/AKT/NF-κB pathway proteins. CONCLUSION DSK inhibits the proliferation, invasion, and tumor immune microenvironment of BC cells by inactivating the PI3K/AKT/NF-κB pathway, indicating that DSK may be a potential therapeutic option for BC treatment.

Objective: To explore the influencing factors of blood transfusion volume in obstetric patients based on the national health development strategy, and to provide evidence for clinical transfusion management and maternal and infant safety. Methods: A total of 1 203 obstetric patients who received blood transfusion in a tertiary hospital in Beijing from 2013 to 2023 were enrolled retrospectively. Seventeen indicators including age, body mass index (BMI), hemoglobin and prothrombin time were selected as research variables. Descriptive analysis was conducted firstly. Scatter plot matrix was used to analyze the correlation between continuous variables and transfusion volume, and box plots were used to analyze the relationship between categorical variables and transfusion volume. Linear regression, logistic regression and random forest models were established for empirical analysis, and ROC curves and AUC values were compared to evaluate model performance. Results: Descriptive analysis showed that the distribution of obstetric blood transfusion volume was right-skewed, and multiple indicators were significantly correlated with transfusion volume. Linear regression indicated that 9 variables such as age, BMI and hemoglobin had linear correlation with transfusion volume. Logistic regression confirmed that 7 variables including BMI and hemoglobin were statistically correlated with the probability of massive blood transfusion. Random forest model screened the core influencing factors, which were ranked by importance: hemoglobin, prothrombin time, hematocrit, BMI, activated partial thromboplastin time, platelet count and age. The AUC values of logistic regression and random forest were 0.78 and 0.81 respectively, and the latter had better predictive performance. Conclusion: Prenatal anemia, coagulation disorders, advanced age, obesity, gestational hypertension, placental abnormalities and organ damage can increase the risk of massive blood transfusion in obstetric patients. The random forest model has better analytical and predictive ability in this study. The results can provide reference for accurate blood transfusion and risk prediction in obstetrics.

Objective:To summarize the theoretical basis and practical experience of the hospital where the author works, in actively promoting the interdisciplinary integration of ″Medicine+ ″, and provide reference for hospitals of the same type.Methods:Based on the Resource-Based View framework, this study analyzed the core dimension heterogeneous resources including organizational capital, physical and financial capital, and human capital through a case study of Zhongnan Hospital of Wuhan University, systematically examining its interdisciplinary research promotion strategies.Results:The hospital had created a strong interdisciplinary atmosphere. Its scientific research and innovation capabilities had been significantly enhanced. High-quality interdisciplinary academic achievements had emerged continuously. And its academic influence has continued to expand.Conclusions:Interdisciplinary integration is a systematic project that requires organized implementation and a ″multi-pronged approach″: coordinating and innovating the organizational management system, conducting comprehensive resource inventorying and ensuring sustainable provision, making overall plans for talent introduction and cultivation, and adhering to the clinical-problem-oriented approach in carrying out interdisciplinary integration.

OBJECTIVE To investigate the relationship between 23-site chip genetic screening failures and the results of newborns hearing screening,and to provide clinical reference for the diagnosis and treatment of genetic screening failures.METHODS There were 1 916 newborns born in the Beijing area from November 2022 to May 2024,who did not pass the 23-site chip genetic screening tests and underwent newborn hearing screening with definite initial screening results.Chi-square test was used to analyze the relationship between different mutation types and genotypes and the initial hearing screening results.RESULTS The overall neonatal hearing screening failure rate was 5.27%(101/1 916),with a higher failure rate of 61.54%(56/91)for homozygous and compound heterozygous mutations than the failure rate of 2.54%(45/1 772)for heterozygous mutations,0%(0/34)for digenic gene heterozygous mutations,and 0(0/19)for mtDNA 12S rRNA mutations,with a statistically significant difference(P<0.001).Among the homozygous and compound heterozygous mutations,the failure rates of homozygous and compound heterozygous for GJB2 gene and SLC26A4 gene were 59.76%(49/82)and 77.78%(7/9),respectively,with no statistically significant difference between the two groups(P=0.488).The homozygous and compound heterozygous for GJB2 gene were divided into three groups based on genotype:c.109G>A homozygous mutations,c.109G>A compound heterozygous mutations,and other homozygous and compound heterozygous mutations.The hearing screening failure rates of the three groups,from highest to lowest,were as follow:other homozygous and compound heterozygous mutations(88.89%,8/9),c.109G>A homozygous mutations(65.12%,28/43),and c.109G>A compound heterozygous mutations(43.33%,13/30),with a statistically significant difference(P=0.029).The failure rates of heterozygous for GJB2 gene,SLC26A4 gene and GJB3 gene were 2.86%(40/1 398),1.25%(4/321)and 1.89%(1/53),respectively,with no statistically significant difference among the three groups(P=0.241).The failure rate of hearing screening for individuals with GJB2 heterozygotes of different genotypes and individuals with SLC26A4 heterozygotes of different genotypes did not show statistically significant differences.CONCLUSION The failure rate of newborn hearing screening for homozygous and compound heterozygous mutation of 23-site chip genetic screening is higher than that of other mutation types,verifying the effectiveness of the newborn hearing screening program.Some newborns of homozygous and compound heterozygous mutation can pass the hearing screening,especially those with the c.109G>A homozygous and compound heterozygous mutation,who need clinical follow-up.

Objective:To find out whether the performance of a China-made high performance human centrifuge can satisfy the need of high G training by conducting physiological experiments.Methods:The dynamic physical performance of the anti-G equipment with the human centrifuge was tested before 5 subjects underwent the gradual-onset rate (GOR) run and rapid onset rate (ROR) run experiments. The G onset rate of GOR was 0.1 G/s. The relaxed G-tolerance under GOR (GOR tolerance 1) and the anti-G straining maneuver aided G-tolerance under GOR (GOR tolerance 2) were tested respectively. The G onset rate of ROR was 3 G/s, and the closed-loop mode and pre-programed mode were employed respectively. The closed-loop mode involved 5 G 10 s and 8 G 10 s, where the subjects were required to manipulate the joystick to ensure that the real-time curve of the load matched the target curve. In the pre-programmed mode, the subjects were exposed to 8 G 10 s passively, without any operation requirements. A subjective evaluation form was filled out by subjects after the experiments, in which the 14 indexes for evaluation were about the gondola facilities and environment, running processes, medical monitoring and overall assessment.Results:Both the oxygen mask and anti-G suit achieved full pressurization within 2.0 s. The GOR tolerance 1 was [4.0(3.8, 4.6)] G while the GOR tolerance 2 was (6.2±0.5) G, suggesting a statistically significant difference ( Z=-2.63, P=0.008). The HP anti-G straining maneuver effect was (2.0±0.6) G. All the 5 subjects finished the 5 G 10 s experiment in a closed-loop mode. Three of them attempted 8 G 10 s in the closed-loop mode (1 subject achieved only 7.6 G peak acceleration, and the other 2 achieved full 8 G 10 s exposure), while the remaining 2 completed the 8 G 10 s in the pre-programmed mode. In the closed-loop mode, it was found that the stick force was too strong, the guiding G and real time G curve were not easy to distinguish for some of the subjects because the curve colors were similar, and that the subjects could not see the G curves clearly in case of a grayout. Both seat comfort and the voice quality of communication got the highest subjective assessment score [5.0(4.0, 5.0)] while the sensation of tumble got the lowest score (2.8±0.8). The median or mean scores of other subjective evaluation indexes ranged from 3.0 to 4.6 points. The overall score of subjective assessment was [4.0(3.5, 4.0)] points. Conclusions:The China-made high performance human centrifuge can meet the requirements of 8.0 G high G training, which can be made more effective and comfortable if the strong stick force and feeling of tumble during stop running are overcome.

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

Objective:To find out whether the performance of a China-made high performance human centrifuge can satisfy the need of high G training by conducting physiological experiments.Methods:The dynamic physical performance of the anti-G equipment with the human centrifuge was tested before 5 subjects underwent the gradual-onset rate (GOR) run and rapid onset rate (ROR) run experiments. The G onset rate of GOR was 0.1 G/s. The relaxed G-tolerance under GOR (GOR tolerance 1) and the anti-G straining maneuver aided G-tolerance under GOR (GOR tolerance 2) were tested respectively. The G onset rate of ROR was 3 G/s, and the closed-loop mode and pre-programed mode were employed respectively. The closed-loop mode involved 5 G 10 s and 8 G 10 s, where the subjects were required to manipulate the joystick to ensure that the real-time curve of the load matched the target curve. In the pre-programmed mode, the subjects were exposed to 8 G 10 s passively, without any operation requirements. A subjective evaluation form was filled out by subjects after the experiments, in which the 14 indexes for evaluation were about the gondola facilities and environment, running processes, medical monitoring and overall assessment.Results:Both the oxygen mask and anti-G suit achieved full pressurization within 2.0 s. The GOR tolerance 1 was [4.0(3.8, 4.6)] G while the GOR tolerance 2 was (6.2±0.5) G, suggesting a statistically significant difference ( Z=-2.63, P=0.008). The HP anti-G straining maneuver effect was (2.0±0.6) G. All the 5 subjects finished the 5 G 10 s experiment in a closed-loop mode. Three of them attempted 8 G 10 s in the closed-loop mode (1 subject achieved only 7.6 G peak acceleration, and the other 2 achieved full 8 G 10 s exposure), while the remaining 2 completed the 8 G 10 s in the pre-programmed mode. In the closed-loop mode, it was found that the stick force was too strong, the guiding G and real time G curve were not easy to distinguish for some of the subjects because the curve colors were similar, and that the subjects could not see the G curves clearly in case of a grayout. Both seat comfort and the voice quality of communication got the highest subjective assessment score [5.0(4.0, 5.0)] while the sensation of tumble got the lowest score (2.8±0.8). The median or mean scores of other subjective evaluation indexes ranged from 3.0 to 4.6 points. The overall score of subjective assessment was [4.0(3.5, 4.0)] points. Conclusions:The China-made high performance human centrifuge can meet the requirements of 8.0 G high G training, which can be made more effective and comfortable if the strong stick force and feeling of tumble during stop running are overcome.

Objective:To summarize the theoretical basis and practical experience of the hospital where the author works, in actively promoting the interdisciplinary integration of ″Medicine+ ″, and provide reference for hospitals of the same type.Methods:Based on the Resource-Based View framework, this study analyzed the core dimension heterogeneous resources including organizational capital, physical and financial capital, and human capital through a case study of Zhongnan Hospital of Wuhan University, systematically examining its interdisciplinary research promotion strategies.Results:The hospital had created a strong interdisciplinary atmosphere. Its scientific research and innovation capabilities had been significantly enhanced. High-quality interdisciplinary academic achievements had emerged continuously. And its academic influence has continued to expand.Conclusions:Interdisciplinary integration is a systematic project that requires organized implementation and a ″multi-pronged approach″: coordinating and innovating the organizational management system, conducting comprehensive resource inventorying and ensuring sustainable provision, making overall plans for talent introduction and cultivation, and adhering to the clinical-problem-oriented approach in carrying out interdisciplinary integration.

Objective To investigate the sequencing results of the SLC26A4 gene in 34 nuclear families and the genetic diagnosis on the offspring in the nuclear families who have been screened for SLC26A4 gene single-allele mutation in the deafness genetic screening,to provide a basis for genetic consulting.Methods A retrospective anal-ysis was performed on the results of SLC26A4 gene testing in 34 nuclear families,in which the offspring with SLC26A4 gene single-allele mutation in deafness genetic screening of each nuclear family.The offspring of 34 nucle-ar families with the second mutation site detected by sequencing,their audiological results were included in the anal-ysis;and if they suffered from hearing loss,the results of temporal bone CT or inner ear MRI were also included in the analysis.Results The sequencing results of 34 nuclear families showed that there were 23 offsprings(67.65％,23/34)with SLC26A4 gene single-allele mutation,and one parent was SLC26A4 gene single-allele mutation.There were 11 offsprings(32.35％,11/34)with second site,among which 7 offsprings(63.64％,7/11)with SLC26A4 gene complex heterozygous mutations,and their parents were SLC26A4 gene single-allele mutations.Among the 7 offsprings with SLC26A4 gene complex heterozygous mutation,3 cases were with hearing loss,all of which were diagnosed as large vestibular aqueduct syndrome,and the other 4 cases were normal.While 4 offsprings(36.36％,4/11)with SLC26A4 gene double heterozygous mutation(cis mutation),and one parent was SLC26A4 gene double heterozygous mutation.The hearing 4 offsprings with SLC26A4 gene double heterozygous mutations were normal.Among the 34 nuclear families,3 pairs of parents were SLC26A4 gene single-allele mutation,and both mutation sites were pathogenic,risk of reproducing children with hereditary hearing loss was 25％.Conclusion The detec-tion sites of deafness gene chip are limited.Using gene sequencing technology to sequence the nuclear family can fur-ther clarify the gene mutation type in offspring and provide guidance for parents to reproduce.