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 establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.

Objective:To investigate the effects of Zhuanggu Zhitong Capsules on JNK signaling molecules and their phosphorylated proteins in postmenopausal osteoporosis model female mice.Methods:The rats were divided into sham-operation group, blank group, model group, positive drug group, and Zhuanggu Zhitong Capsules group according to the random number table method, with 10 rats in each group. The model group, the positive drug group and the Zhuanggu Zhitong Capsules group were prepared by bilateral ovarian detomy to prepare a female mouse model of postmenopausal osteoporosis. The positive drug group was given 0.9 mg/kg of alendronate sodium, the Zhuanggu Zhitong Capsules group was given was Zhuanggu Zhitong Capsules 1.944 g/kg for gavage, and the blank group, sham-operation group, and model group were given the same volume of normal saline for gavage, once a day for a total of 13 weeks. Rat vaginal exfoliated cells were stained with Wright's staining; serum Omentin-1 and 25(OH)D 3 levels were determined by ELISA; renal tissue and femoral structure were observed by HE staining; JNK and p-JNK protein expressions were detected by immunohistochemical staining; JNK mRNA levels were detected by PCR. Results:Compared with the model group, the serum levels of 25(OH)D3 and Omentin-1 in the Zhuanggu Zhitong Capsules group and the positive drug group increased ( P<0.01), the mean gray values of JNK and p-JNK protein in bone and kidney tissues decreased ( P<0.01), and the mRNA levels of JNK in bone and kidney tissues decreased ( P<0.01). Conclusion:Zhuanggu Zhitong Capsules can effectively improve the bone microstructure of postmenopausal osteoporotic rats, and its mechanism may be related to the regulation of JNK signaling pathway.

AIM To study the chemical constituents from Inula japonica Thunb.and their anti-asthmatic activity.METHODS Separation and purification were performed using silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The effect of compounds on the release rate of β-Hex was evaluated by substrate coloration method.RESULTS Twenty-three compounds were isolated and identified as dehydrodontic acid(1),vitexin(2),alternariol(3),globuxanthone(4),1,3,6,7-tetrahydroxyxanthone(5),hydroxyhydrolapachol(6),isoscopoletin(7),elephanmollen(8),benzoylcholine(9),hoconobiflavone(10),clovandiol(11),hydroxydihydrobovolide(12),5,7-dihydroxycoumarin(13),scopoletin(14),orlichenol glucoside(15),urolignoside(16),9-angeloyloxythymol(17),6,3′,4′-trihydroxyaurone(18),flufuran(19),sweroside(20),guajadial(21),5,7,4′-trimethoxy-4-phenylcoumarin(22),dibutylphthalate(23).After intervention with compounds 9 and 16,the release rates of β-Hex were(56.64±2.37)％and(58.07±2.29)％,respectively.CONCLUSION Compounds 1-23 are isolated from Ⅰ.japonica for the first time.Compounds 9 and 16 have anti-asthmatic activity.

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Aim To investigate the effect of icariin(ICA)on chronic ulcerative colitis(UC)in mice.Methods Male SPF-grade C57BL/6J mice were ran-domly divided into the control group,model group,low-dose ICA group,and high-dose ICA group.Except for the control group,the rest of the mice were established as chronic UC models.Expressions of tight junction proteins,inflammatory factors,fibrosis markers,macro-phage markers,and MAPK signaling pathways in the colonic epithelium of each group were determined by Western blot,qPCR,immunohistochemistry;the degree of intestinal damage and fibrosis was detected by HE and Masson staining;the co-localization of different macrophage markers with related factors was examined by immunofluorescence.Results Treatment of ICA significantly improved the general condition of chronic UC mice,decreased the infiltration of M1-type macro-phages and the secretion of pro-inflammatory factors,inhibited the MAPK signaling pathway,reduced the co-localization expression of M1-type macrophages with the MAPK signaling pathway,and downregulated the infiltration of M2-type macrophages and the secretion of pro-fibrotic factors in the colon.Conclusion ICA mitigates the inflammatory damage and fibrosis of colon in chronic UC mice.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

Objective To establish a method for predicting the risk of endometrial cancer(EC)and endometrial atypical hyperplasia(AH)in women with postmenopausal bleeding(PMB)by collecting clinical data on routine medical history.Methods The clinical data of a total of 408 PMB patients admitted to Fuxing Hospital,Capital Medical University were consecutively collected in this retrospective study from December 2013 to December 2023.According to the results of endometrial pathology,patients were divided into case group and control group.EC and AH were included in the malignant group(case group)and the other endometrial pathologies were included in the non-malignant group(control group).Clinical data,including clinical history,high risk factors,and common gynecological ultrasound measurement indicators,were collected and studied by univariate and multivariate Logistic regression analysis.Results The mean age of 408 patients was(60.4±7.8)years.A total of 74 cases(18.1％)were in case group and 334 cases(81.9％)were in control group.Based on Logistic regression analysis,the best predictors of endometrial malignant lesions were selected to create a"LRDNT"(light bleeding,recurrent bleeding,diabetes,non-uniform echogenicity & thickness)model.LRDNT scores range from 0 to 22.The score of LRDNT ≥15 has the largest Yoden index,and the sensitivity to predict endometrial malignant lesions is 79.73％,the specificity is 80.84％,and the prediction accuracy is 80.64％.Conclusions The risk prediction model LRDNT,which combines clinical information and common gynecological ultrasound measurement indicators of PMB patients,can help clinicians classify patients at high and low risk of endometrial malignant lesions,and optimize the strategy of diagnosis and treatment.

Objective To investigate the influencing factors of pregnancy outcomes after transcervical resection of polyp(TCRP)in infertility patients.Methods The data of 442 patients with infertility complicated with endometrial polyp(EP)underwent TCRP from March 2021 to March 2022 were retrospectively analyzed,and the postoperative follow-up time was 12-24 months,and they were divided into postoperative pregnancy group(pregnancy group)and non-pregnant group(control group).The two groups were compared with age,body mass index(BMI),infertility type,abnormal uterine bleeding,adverse pregnancy history,number of EP,EP size,intraoperative negative pressure uterine aspiration,endometritis,TCRP operation time,and uterine cavity depth,and multivariate analysis was conducted on the influencing factors of pregnancy outcomes after TCRP in infertility patients.Results Among 442 infertility patients with EP,274 cases(62.0%)were in the pregnancy group and 168 cases(38%)in the control group.The factors influencing pregnancy after TCRP were age(OR=0.925,95%CI:0.881-0.972,P<0.05),abnormal uterine bleeding before surgery(OR=0.646,95%CI:0.432-0.967,P<0.05)and primary infertility(OR=2.105,95%CI:1.295-3.423,P<0.05).Conclusion TCRP can improve pregnancy outcomes in infertility patients with EP.Age and abnormal uterine bleeding before operation were the protective factors to increase pregnancy after TCRP in infertility patients.Primary infertility is a risk factor for pregnancy after TCRP in infertility patients.

Objective:To explore the role and mechanism of intestinal endotoxemia in the development of hepatopulmonary syndrome in rats.Methods:Rats were randomly divided into Experimental Group(N=10)and Control Group(N=10),and the rat model of Hepatopulmonary Syndrome was established by common bile duct ligation(CBD),and the contents of endotoxin,TNF-α and IL-6 were measured.Rat lung microvascular endothelial cells were isolated and cultured in vitro.Endotoxin induced the activation and proliferation of these cells,and the levels of TNF-α and IL-6 were detected.Results:The level of endotoxin in rats with hepatopulmonary syndrome was significantly elevated,which induced the production of TNF-α and IL-6,causing pulmonary vasodilation and hypoxemia.Conclusions:Intestinal endotoxemia plays an important role in the development of Hepatopulmonary Syndrome,and its possible mechanism is to induce pulmonary microvascular endothelial cells to produce a variety of inflammatory cytokines and to promote the development of pulmonary vasodilation and Hepatopulmonary Syndrome.It provides key experimental evidence and potential targets for the prevention and treatment strategies of hepatopulmonary syndrome.