A close relationship between fatty acid metabolism and cancer development is well-established.The hydroxyacyl-coenzyme a dehydrogenase(HADH),a key enzyme in fatty acid beta-oxidation,has recently been identified as an anti-oncogenic factor in various cancers and an oncogenic factor in conditions like acute myeloid leukemia.In cancer cells,HADH not only directly catalyzes fatty acid beta-oxidation but also indirectly influences multiple signaling pathways such as PPAR,TNF-α,JAK-STAT3,PI3K/Akt,IFN-γ,MAPK,and non-canonical Wnt signaling pathways,affecting cancer cell proliferation and migration.HADH shows promise as a potential tumor biomarker for diagnosis,treatment,and prognosis in different cancer types,holding significant clinical value.

Purpose To investigate the effect of CD147 on the proliferation,invasion and migration of cervical cancer cells and its potential molecular mechanism.Methods The expres-sion data of BSG gene(encoding CD147 protein)in cervical cancer samples were downloaded from UCSC database,and the prognosis of different groups of samples was evaluated by Log-rank test.Western blot was used to detect CD147 expression in the Siha and Hela and H8 cells.The expression of CD147 was downregulated by the lentivirus transfection into Hela cells and its transfection efficiency was verified.Western blot was used to detect the expression of p-Akt,p-mTOR,ACC1,FASN,E-cad-herin and N-cadherin in each group.The content of fatty acids in the cells was detected by BODIPY staining and fatty acid kit.Cell proliferation,invasion and migration were detected by CCK-8,plate cloning and Transwell assay.The cell proliferation,in-vasion and migration ability were detected by plate cloning ex-periment and Transwell test.Results The expression of CD147 in cervical cancer tissues was higher than that in normal cervical tissues(P＜0.01).Patients with overexpression of CD147 had poor prognosis.Western blot results showed that compared with H8 cells,the expression of CD147 protein in Siha and Hela cells was increased(P=0.011).After down-regulation of CD147,the protein expression of CD147,ACC1 and FASN in the sh-CD147 group was decreased compared with those in the Hela group(P＜0.001).BODIPY fluorescence staining was weak-ened and fatty acid content was decreased(P＜0.001).The a-bility of cell colony formation,invasion and migration was de-creased.The expression of E-cadherin protein in sh-CD147 group was increased,and the expression of N-cadherin,p-Akt and p-mTOR was decreased.Compared to sh-CD147,after treatment with Akt agonist SC-79(sh-CD147-SC79),the ex-pression of p-Akt,p-mTOR,ACC1,FASN,N-cadherin in cells was increased,and the expression of E-cadherin was decreased,and the results of lipid staining and fatty acid content were con-sistent with the expression of key enzymes(P＜0.01),and the cell proliferation,invasion and migration ability were significant-ly enhanced.Conclusion CD147 through Akt/mTOR signaling pathways regulating the fatty acid synthesis promotes cervical cancer cell proliferation,invasion and migration.

BACKGROUND:Calcium phosphate(CaP)coatings are widely used to improve the integration of titanium implants into bone but these coatings are associated with risks of infection.It is thus desirable to confer antibacterial properties to CaP coatings. OBJECTIVE:To prepare CaP-MgO composite coatings by impregnating magnesium oxide(MgO)sol into CaP coatings and assess the in vitro antibacterial activities and cytocompatibility. METHODS:An electrolyte was determined by titration and used for CaP coating electrodeposition on titanium(referred to as Ti-CaP).MgO was impregnated into the coating by immersing in an MgO sol with different mass fractions(15%,30%,50%)and subsequently calcined to form MgO-CaP composite coatings,which were recorded as Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg,respectively.Microstructure,tensile properties,critical load,and Mg2+ release of coatings in vitro were characterized.Antibacterial activity was assayed using spread plate method by culturing S.aureus on the pure titanium sheet surface and Ti-CaP,Ti-Cap-15mg,Ti-Cap-30mg and Ti-Cap-50mg surfaces for 24 and 48 hours.Mouse osteoblast suspension was inoculated on pure titanium sheets and Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg coated titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay,and cell survival rate was calculated.The morphology of composite coating soaked in DMEM was also observed. RESULTS AND CONCLUSION:(1)Homogeneous,microporous CaP coatings consisting of octacaclium phosphate crystal flakes were prepared on titanium by electrodeposition.After sol impregnation-calcination,MgO aggregates were filled into the inter-flake voids.The extent of MgO filling and Mg concentration in the coating increased with the number of sol impregnation procedures.When immersed in phosphate buffered saline,all composite coatings actively released Mg2+ within 1 day;subsequently,the Mg2+ release slowed down on day 3.A small amount of Mg2+ release was still detected on day 7.The yield strength,tensile strength and fracture growth rate of Ti-CaP-30Mg coated titanium were not significantly different from those of pure titanium(P>0.05).There was no significant difference in the critical load of Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups(P>0.05).(2)Except that pure titanium sheet and Ti-CaP had no antibacterial properties,the other samples had good antibacterial properties,and the antibacterial rate increased with the increase of MgO content in the coating.(3)After 1 and 3 days of co-culture,the cell survival rate of Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups was lower than that of pure titanium group and Ti-CaP group(P<0.05).After 5 and 7 days of culture,there was no significant difference in cell survival rate among five groups(P>0.05).The content of MgO in the coating decreased gradually with the time of immersion in the medium.(4)The MgO sol impregnation added antibacterial properties to the CaP coatings while retained their biocompatibility.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Objective To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer(FET)cycles in patients with polycystic ovary syndrome(PCOS).Methods A retrospective analysis was conducted on patients'data from 882 FET cycles.According to the pregnancy outcome,the patients were divided into non-implantation group(Group A),abortion group(Group B1)and live birth group(Group B2).Clinical data and laboratory parameters were compared among the three groups,and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET.Patients were also divided into four groups(C1-C4)based on the number of high-quality embryos obtained(0-3,4-6,7-10,≥11),and their clinical data and laboratory parameters were compared.Results The clinical pregnancy rate,live birth rate,and miscar-riage rate in the 882 treatment cycles were 71.09%(627/882),61.68%(544/882),and 13.24%(83/627),respectively.Single-factor analysis showed significant differences in body mass index(BMI),infertility type,hu-man chorionic gonadotropin(hCG)day estradiol(E2)level,number of retrieved oocytes,and number of high-quality embryos among Groups A,B1,and B2(P<0.05).Further multiple Logistic regression analysis revealed that BMI(OR=1.046,95%CI:1.001-1.093,P=0.044)and a history of previous pregnancy(OR=1.417,95%CI:1.030-1.950,P=0.032)were independent risk factors for successful FET in PCOS patients,while an in-creased number of high-quality embryos was an independent protective factor for successful pregnancy.Based on the results of Group B2,compared to Group A,OR=0.920,95%CI:0.880-0.962,P=0.000;compared to Group B1,OR=0.923,95%CI:0.862-0.988,P=0.022.Compared with the other three groups(C1-C3),the total amount of gonadotropin(Gn)in the C4 group was the lowest and the number of oocytes obtained was the high-est(P<0.05).Multiple comparisons showed that Group C4 had lower BMI,follicle-stimulating hormone(FSH),very low-density lipoprotein(vLDL)levels,a higher luteinizing hormone and follicle-stimulating hormone(LH/FSH)ratio compared to Group C1(P<0.05).Group C4 had lower fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)levels compared to Group C3,and higher high-density lipoprotein-cholesterol(HDL-C)and apolipoprotein A1(Apo A1)levels compared to Groups C2 and C3(P<0.05).Con-clusion BMI,the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles.Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles.

Objective To investigate the mechanism by which Erastin affects ferroptosis in lung fibroblasts.Meth-ods Mouse lung fibroblasts (C57/B6-L) were treated with varying concentrations of the iron death inducer Eras-tin.Cell viability was assessed using the cell counting Kit-8 (CCK-8) assay.Oxidative stress levels were visualized using a fluorescence microscope, and the expression of proteins related to the mitogen-activated protein kinase (MAPK) signaling pathway was analyzed using Western blot.Additionally, the p38 and extracellular regulated protein kinase (ERK) inhibitors SB203580 and U0126 were employed to further elucidate the mechanism by which Erastin induces iron death in lung fibroblasts.Results At a concentration of 100 μmol/L, Erastin effectively in-duced ferroptosis in lung fibroblasts, leading to an upregulation of oxidative stress.Furthermore, the phosphoryla-tion levels of p38 and ERK proteins in the MAPK pathway were elevated (P<0.05) .The addition of SB203580 and U0126 inhibitors resulted in a significant reduction in oxidative stress levels and a notable increased in cell ac-tivity in lung fibroblasts (P<0.05).Conclusion It can be concluded that Erastin induces ferroptosis in lung fi-broblasts, potentially through the mediation of oxidative stress via the MAPK signaling pathway.

Objective:To quantitatively evaluate the guidelines for hypertensive disorders of pregnancy (HDP) at home and abroad, and to provide a reference for the development of related guidelines in the future.Methods:Guidelines related to HDP published at home and abroad from 1 January 2018 to 31 December 2022 were retrieved from several databases, including CNKI, Wanfang Database, Yiigle, VIP Database, PubMed, Embase, and Web of Science with the terms of "hypertension in pregnancy", "hypertensive disorders of pregnancy", "pre-eclampsia", "eclampsia", and "guidelines". The retrieved guidelines were evaluated with the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) and Scientific, Transparent and Applicable Rankings (STAR) tool. According to the manual of AGREE Ⅱ two researchers graded the retrieved guidelines from six domains: scope and purpose, participants, rigor, clarity, applicability, and independence. Mean standardized score of each domain and the overall score were obtained. STAR tool was used to grade the guidelines by two researchers and one methodologist from 11 domains: registration, protocol, funding, working groups, conflicts of interest, clinical issues, evidence, consensus methods, recommendations, accessibility, and others.Results:A total of 19 related guidelines were included, covering six countries on three continents. The mean standardized scores of the 19 guidelines in the six domains of scope and purpose, participants, rigor, clarity, applicability, and independence using the AGREE II instrument were 73.98%, 63.16%, 59.98%, 66.37%, 56.36%, and 71.93%, respectively. Scores in the 11 domains of registration, protocol, funding, working groups, conflicts of interest, clinical issues, evidence, consensus methods, recommendations, accessibility, and others using the STAR tool were 0.00%, 0.00%, 76.15%, 39.87%, 58.92%, 65.19%, 60.80%, 49.78%, 78.95%, 30.89%, and 42.11%, respectively. According to the overall evaluation results, 12 guidelines were recommended and seven needed further modifications. It was found that most guidelines were unanimous in their recommendations on the prevention of preeclampsia with aspirin, medications for patients with severe hypertension, and the timing of pregnancy termination in preeclampsia patients, with the consensus rates of 10/13, 9/13, and 9/13, respectively. Besides, these recommendations were supported by substantial evidence.Conclusions:The overall quality of guidelines related to HDP at home and abroad is high, but there is still room for improvement. When developing relevant guidelines in the future, statisticians and methodologists should be included in the working groups to improve the evidence-based quality, and much attention should be paid to the disclosure of conflicts of interest guidelines. Registration and protocol are needed before publishing a guideline. The development of multiple versions for different users will conduce to improving the management of HDP.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

Based on the reality that the Health Management Alliance(HMA)has been initially established nationwide as an important component of the integrated health care service system,on the basis of summarizing the evolution process of transaction cost theory,discriminating the essential characteristics of HMA,deconstructing HMA transaction cost and putting forward a quantitative measurement model,the coping strategies of HMA transaction cost are summarized into three levels:"knowing","reducing"and"increasing".It aims to solve the high transaction cost effectively and explore the economic system supply path;correct the deviation of the field of vision which only focuses on the"output orientation"of HMA in the early stage,and arouse the attention and thinking of all parties on the transaction cost of HMA;provide a new position and a new idea for HMA policy research and reform practice in China.

Objective:To explore the mediating role of aging attitude and anxiety in the relationship between self-worth and depression among the elderly.Methods:From July to August 2022, a total of 536 elderly people in Shijiazhuang University for the Elderly were surveyed by the elderly self-worth scale, generalized anxiety disorder-7(GAD-7), attitudes to aging questionnaire(AAQ) and patient health questionnaire(PHQ-9). SPSS 26.0 software was used for descriptive statistics and correlation analysis.AMOS 24.0 was used to construct an intermediation model, and Bootstrap method was used for mediating effect testing.Results:(1)The score of self-worth was 101.00 (92.00, 112.00), the score of aging attitude was 92.00 (83.00, 101.75), the score of anxiety was 2.00(0, 6.00), and the score of depression was 2.00 (0, 5.00). (2)Self-worth was positively correlated with aging attitude ( r=0.67, P<0.01), while negatively correlated with anxiety ( r=-0.45, P<0.01) and depression ( r=-0.48, P<0.01). The aging attitude was negatively correlated with anxiety ( r=-0.41, P<0.01) and depression ( r=-0.41, P<0.01). Anxiety was positively correlated with depression ( r=0.71, P<0.01). (3)The indirect effect of aging attitude between self-worth and depression in the elderly was -0.016, accounting for 19.75% (-0.016/-0.081)of the total indirect effect.The indirect effect of anxiety between self-worth and depression in the elderly was -0.045, accounting for 55.56%(-0.045/-0.081) of the total indirect effect.The chain mediating effect of aging attitude and anxiety between self-worth and depression in the elderly was -0.020, accounting for 24.69%(-0.020/-0.081) of the total indirect effect. Conclusion:Aging attitude and anxiety play a chain mediating role between self-worth and depression in the elderly.