To investigate the effect of Ginkgo biloba extract (GBE) on lipids accumulation and the progression of atherosclerosis(AS), ApoE-/- mice fed with HFD were injected i.g. with two different doses of GBE (GBE-L 50 mg/(kg·d) or GBE-H 150 mg/(kg·d)) for 9 weeks. The core targets and potential mechanisms of GBE therapy for AS were investigated using network pharmacological target prediction. Subsequently, oxidized low-density lipoprotein (ox-LDL)-induced THP-1 was used to investigate the effect of GBE on foam cell formation through oil red staining and Dil-oxLDL fluorescent staining. The mRNA alterations in cholesterol uptake and efflux receptors were detected by real-time quantitative PCR. Finally, the impact of GBE on the expression of PPARγ as the core target was assessed through Western blot and immunofluorescence. It was found that GBE improved serum lipid profile, reduced necrotic cores and lipid deposition in aortic root plaques, and decreased the level of inflammatory factors in serum of ApoE-/- mice. Moreover, GBE treatment reduced the level of intracellular lipid accumulation and inhibited cholesterol uptake and efflux to alleviate foam cell formation. GBE activated PPARγ to enhance ABCA1/ABCG1-induced cholesterol efflux in THP-1. These results suggest that GBE can suppress lipid accumulation and alleviate foam cell formation by activating PPARγ pathway.

To analyze the current quality of treatment for hospitalized cancer patients in Beijing, identify major issues in treatment practices, and propose improvements.

Objective:To revise the Chinese version of the Coparenting Inventory for Parents and Adolescents(CI-PA)in middle school students and their parents to test the validity and reliability.Methods:Totally 691 middle school students were tested with the adolescent version of CI-PA,924 parents were tested with the parents'version of CI-PA.The sample was split randomly in half,and item analysis and exploratory factor analysis,confirmatory factor analysis,criterion validity analysis and convergent validity test were performed respectively.The Achenbach Youth Self-Report(YSR)and marital satisfaction subscale(MSS)of Olson Enrich Marital Inventory(ENRICH)were used to test the validity of the criterion.Totally 62 students and 70 parents were followed to complete the Chi-nese version of CI-PA 4 weeks after the first investigation.Results:Exploratory factor analysis showed that there were 37 and 25 items in the adolescent version and the parents'version respectively,3 factors were extracted,inclu-ding 3 dimensions of cooperation,triangulation and conflict.The factor loadings of each item ranged from 0.60 to 0.95,and the subscales explained the total variance ranged from 64.56％to 74.06％.Confirmatory factor analysis showed that all the 3 factors models fitted well in adolescent version(x2/df=1.32,1.30,1.41;CFI=0.99,0.99,0.99;TLI=0.99,0.99,0.98;RMSEA=0.03,0.03,0.03)and the parents'version(x2/df=1.20,1.33;CFI=0.99,0.99;TLI=0.99,0.99;RMSEA=0.02,0.03).Cooperation scores of the adolescent version were negatively correlated with the YSR scores(ICC=-0.18--0.27,Ps＜0.01),triangulation and conflict scores of the adoles-cent version were positively correlated with the YSR scores(ICC=0.15-0.34,Ps＜0.01).Cooperation scores of the parents'version were positively correlated with the MSS scores(ICC=0.52,0.47,Ps＜0.01),triangulation and conflict scores of the parents'version were negatively correlated with the MSS scores(ICC=-0.28--0.47,Ps＜0.01).The Cronbach's α of 3 dimensions were all above 0.72,the retest reliabilities(ICC)were all a-bove 0.54.Conclusion:The Chinese version of Coparenting Inventory for Parents and Adolescents(CI-PA)is valid and reliable in measuring the coparenting in Chinese adolescence families.

Adenomyosis(AM)is characterized by the benign invasion of endometrial tissue and stroma into the myometrium,resulting in diffuse or localized pathological changes.Typical symptoms include increased menstrual volume,prolonged menstrual periods,and progressive dysmenorrhea.In severe cases,AM can lead to infertility.Endometrial receptivity(ER)plays a crucial role in facilitating adhesion,penetration,and implantation required for successful embryo implantation and pregnancy outcome.The impairment of ER due to AM-related factors involves complex mechanisms.This article aims to provide a comprehensive review of recent research findings on the mecha-nisms underlying ER injury caused by AM over the past three years while highlighting the latest advancements in treatment strategies.

Objective:To explore the efficacy and safety of the modified VIALE-A regimen in the treatment of elderly (>75 years old) patients with intermediate or high risk myelodysplastic syndromes (MDS).Methods:A retrospective case series analysis was conducted. Clinical data were collected from 7 MDS patients aged >75 years who were continuously treated with the modified VIALE-A regimen (azacytidine 75 mg/m 2 per day from day 1 to day 7 + venetoclax 200 mg per day from day 8 to day 28) from May 2021 to August 2023, and the patients were diagnosed according to the World Health Organization 2016 staging criteria and were determined to be at intermediate or high risk according to the revised International Prognostic Scoring System. The patients' efficacy and common adverse reactions were analyzed, and the Kaplan-Meier method was used for survival analysis. Results:Of the 7 patients, 5 were female and 2 were male; the median age [ M ( Q1, Q3)] was 84 years old (80 years old, 90 years old). One patient failed the initial treatment, and the remaining 6 achieved complete remission or complete remission in bone marrow after induction therapy with the modified VIALE-A regimen in 1-2 courses. By the follow-up cut-off date of December 31st, 2023, the median follow-up was 10 months (5 months, 18 months) and the median overall survival time was 18 months (95% CI: 0-39 months). Grade 3-4 myelosuppression occurred in all 7 patients during the induction phase, with granulocytopenia lasting 7-10 d; Of the 64 courses of maintenance treatment, 54 (84%) had grade 1-3 myelosuppression; non-hematologic adverse reactions were mild; no treatment interruptions occurred in the cumulative 73 courses. Conclusions:The modified VIALE-A regimen is moderately efficacious in elderly patients with intermediate or high risk MDS, with controllable adverse reactions.

Objective To explore the effect of physical exercise on semen quality in order to provide basic data and theoretical basis for the improvement of male reproductive health.Methods A cross-sectional study was conducted on 1 059 males who visited the Reproductive Medicine Center of Shandong Maternal and Child Health Hospital for medical treatment and physical examination during July 2022 and April 2023.Their demographic data and physical exercise data were surveyed with questionnaires.Total sperm count,sperm concentration,total sperm motility,forward movement and normal sperm morphology were analyzed with computer aided analysis.Logistic regression model and multiple linear regression model were applied to analyze the effects of physical exercise on semen quality.Results After adjustment for confounding factors such as age,body mass index,alcohol consumption and smoking,logistic regression analysis showed that the risk of abnormal semen quality was increased in patients with moderate and heavy exercise intensity(OR=2.103,OR=2.229).Compared with the participants with physical exercise ≤10 min per session,those with＞20 min per session had a lower risk of abnormal semen quality(OR=0.357,0.256,0.289 for exercise time for＞20～30,＞30～60,＞60 min,respectively).There was no statistical significance between physical exercise frequency and semen quality(P＞0.05).The participants having exercise well were at a lower risk for abnormal semen quality(OR=0.711).Multiple linear regression analysis revealed that the frequency of physical exercise was an influencing factor of sperm concentration(β=7.474,95％CI:4.800～10.149,P＜0.05);the time of physical exercise per session was an influencing factor for total sperm count(β=20.632,95％CI:7.634～33.629);the intensity of physical exercise(β=-1.461,95％CI:-2.392～-0.530)and time of physical exercise per session(β=2.608,95％CI:1.404～3.812,P＜0.05)were influencing factors for percentage of forward motility sperm(P＜0.05);and physical exercise intensity(β=-1.934,95％CI:-3.238～-0.630),time of physical exercise per session(β=4.211,95％CI:2.525～5.897)and frequency of physical exercise(β=-2.008,95％CI:-3.480～-0.536)were influencing factors of total sperm motility(P＜0.05).Conclusion Physical exercise may affect semen quality,greater intensity of physical exercise may be a risk factor for abnormal semen quality,and longer physical exercise time may be related to improving semen quality.Therefore,proper physical exercise can help improve semen quality.

Objective To express recombinant Burkholderia pseudomallei(B.pseudomallei)type Ⅲ secretion system BipD protein,prepare its polyclonal antibodies and verify their immunological traits.Methods The recombinant pET-28a-BipD plasmid was generated,and the pET-28a-BipD-carried E.coli BL21(DE3)bacteria were induced with isopropyl-β-d-thiogalactoside(IPTG)to express recombinant BipD(rBipD)protein.The rBipD was obtained by affinity chromatography using His Trap column,then mixed with Fredrick's adjuvant to immunize BALB/c mice by intraperitoneal injection in order to obtain anti-rBipD polyclonal antibodies.The immunoreactivity of rBipD was detected by Western blot assay using rabbit anti-melioidosis serum and the serum from melioidosis patients.The immunogenicity of rBipD was evaluated using Western blotting and immunofluorescence staining.Finally,rBipD was used to establish an indirect ELISA to detect serum antibodies of clinical melioidosis patients.Results The recombinant plasmid pET-28a-BipD was successfully constructed and transformed into E.coli BL21(DE3)to induce rBipD expression with IPTG treatment.The obtained rBipD had a relative molecular weight of 36×103 and a purity of 95.4％,and had good immunogenicity and immunoreactivity.It could induce the production of specific antibodies after immunizing mice,and mouse polyclonal antibodies against rBipD were prepared with the titer of 1∶512 000.rBipD of 5.0 μg/mL produced specific immune response with the serum of melioidosis patients,but had no specific reaction with the serum of tuberculosis patients,with statistical difference(P＜0.01).Conclusion rBipD with immunological activity is successfully prepared and purified,and its polyclonal antibodies are also developed,which provide a good tool for clinical immunological diagnosis and study of immune mechanism of B.pseudomallei infection.

Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei(B.pseudomallei)mediates the formation of multinucleated giant cells(MNGCs)when host cells are infected by the bacterium.Methods The mutant strain(BPC006 Δhcp1)and complementation strain(BPC006 Δhcp1::hcp1)were constructed by homologous recombination and plasmid complement technology,respectively.After RAW264.7 cells were infected with B.pseudomallei,the localization of Hcp1 in host cells was analyzed by immunofluorescence staining.The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1.The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining.Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1,while BPC006 Δhcp1::hcp1 restored Hcp1 expression.The above results proved that the mutant and complement strains were successfully constructed.Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes.Last but not least,compared with the control group,anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC(P＜0.01).Conclusion Hcp1 protein in type Ⅵ secretion system of B.pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.

Objective To explore the role and mechanism of RNA demethylase fat mass and obesity-associated protein(FTO)in the ferroptosis in testicular interstitial cells induced by di(2-ethylhexyl)phthalate(DEHP).Methods Forty 3-week-old C57BL/6 male mice were randomly divided into a control group(corn oil)and 3 dosed DEHP treatment groups(5,250 and 500 mg/kg),and received an intragastric infusion of corresponding agents for 35 d,respectively.After mouse testicular interstitial TM3 cells was treated with 0,100,200 and 400 μmol/L mono-2-ethylhexyl phthalate(MEHP)for 24 h,corresponding plasmids were transfected to construct Fto overexpressing TM3 cells.Serum testosterone level was detected by ELISA,expression of testicular proteins was detected with immunohistochemical assay,and contents of Fe2+,malondialdehyde(MDA)and lipid peroxides in the testicle were detected by colorimetry.Methylated RNA immunoprecipitation,RT-PCR,and Western blotting were used to detect the level of N6-methyladenosine(m6A)modification.Results In the mice exposed to 250 and 500 mg/kg DEHP,the serum testosterone level was significantly reduced(P＜0.01),contents of Fe2+,MAD and lipid peroxides in testicular tissue were obviously increased(P＜0.01),and protein levels of RNA demethylase FTO,and ferroptosis related molecules ferritin heavy chain 1(FTH1)and glutathione peroxidase 4(GPX4)were significantly down-regulated(P＜0.05),while those of transferrin receptor(TFRC),ferroportin(FPN),cyclooxygenase-2(COX-2),and acyl-CoA synthetase long-chain family member 4(ACSL4)were notably up-regulated(P＜0.05).MEHP treatment for 24 h resulted in remarkably decreased cell viability in the TM3 cells,increased production of intracellular reactive oxygen species(ROS),reduced mitochondrial membrane potential(MMP)(P＜0.01),down-regulated mRNA and protein levels of Fto(P＜0.01),and the changes in other ferroptosis related proteins were consistent with the trend in testicular tissue,indicating ferroptosis in testicular interstitial cells.Intervention with ferroptosis inhibitor Fer-1 or overexpression of Fto significantly inhibited MEHP-induced toxicity and ferroptosis in TM3 cells(P＜0.05),and overexpression of Fto reduced the m6A modification of Gpx4 and Fth1 mRNA(P＜0.05).Conclusion Abnormal m6A modification of Gpx4 and Fth1 caused by inhibiting FTO expression may be the mechanism of ferroptosis in testicular interstitial cells induced by DEHP.

BackgroundCombination of antipsychotic drugs and modified electroconvulsive therapy （MECT） is currently a commonly used method for treating schizophrenia， but its efficacy varies among different patient groups. ObjectiveTo explore the therapeutic effects of MECT on schizophrenia patients living in different urban versus rural environments， so as to provide references for the selection of treatment plans based on patients' residence. MethodsA total of 587 patients hospitalized at Luzhou Mental Health Center， Zigong Mental Health Center and Yibin Fourth People's Hospital from May 2018 to August 2022， who met the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） ，were included in the study. Patients were divided into two groups： medication-only group （n=106） and MECT combined with medication group （n=481）. In MECT combined with medication group， 24 rural patients residing in urban areas were excluded， leaving the remaining patients divided into urban group （n=103） and rural group （n=354） based on their place of residence. Positive and Negative Syndrome Scale （PANSS） was used to assess the severity of symptoms. Clinical efficacy was evaluated using PANSS score reduction rate， and covariance analysis was used to compare the therapeutic effects of different patients. ResultsThe differences of reduction rate of PANSS total score， positive symptom scale score and negative symptom scale score as well as treatment effectiveness rate between MECT combined with medication group and medication-only group were statistically significant （F=11.149， 12.111， 31.725， χ²=14.010， P<0.01）. Statistically significant differences were also observed in reduction rate of PANSS total score and positive symptom subscale score as well as treatment effectiveness rate between urban and rural patients in MECT combined with medication group （F=3.946， 4.523， χ²=4.033， P<0.05）. ConclusionThe efficacy of MECT combined with medication may be superior to medication alone in the treatment of schizophrenia， and the combined therapy may be more effective in urban patients than that in rural patients， with potentially more pronounced improvements in positive symptoms.