Objective To propose a deep learning neural network approach for transforming megavoltage computed tomography(MVCT)images of cervical cancer into pseudo kilovoltage computed tomography(kVCT)images with high signal-to-noise ratio and contrast-to-noise ratio,thus providing three-dimensional anatomical images and localization information required for adaptive radiotherapy of cervical cancer,and guiding the accelerator to achieve precise treatment.Methods The MVCT and kVCT images of 54 patients treated with cervical cancer radiotherapy were collected,with 44 cases randomly selected as the training set,and the remaining 10 cases as the test set.A cyclic generative adversarial network with gating mechanism and multi-channel data input was used to synthesize pseudo-kVCT images from MVCT images.The network training results were evaluated with imaging quality evaluation parameters,such as mean absolute error(MAE),peak signal-to-noise ratio(PSNR),and structural similarity index(SSIM).Results The MAE,PSNR,and SSIM of MVCT imagesvspseudo-kVCT(5:5)images were(24.9±0.7)HUvs(17.8±0.3)HU,(29.8±0.2)dBvs(30.7±0.2)dB,and 0.841±0.007 vs 0.898±0.003,respectively.Conclusion The generated pseudo-kVCT images have advantages in noise reduction and contrast enhancement,and can reduce the need for additional MV-kVCT electron density calibration in dose calculations.The dose calculation ability of pseudo-kVCT is comparable to that of MVCT,providing a possibility for the application of pseudo-kVCT images in image-guided adaptive radiotherapy.

Objective To investigate the role of Taraxasterol(TAR)on ferroptosis in chondrocytes induced by Erastin.Methods The C28/I2 chondrocyte line was treated with Erastin to construct the ferroptosis model of chon-drocytes in vitro and the experiments were divided into Control,Erastin,TAR,and TAR+Erastin groups.Cell via-bility was detected by the CCK-8 assay.Cytotoxicity was detected by the lactate dehydrogenase(LDH)kit and the Calcein/PI cytokinesis kit.Flow cytometry was used to detect lipid reactive oxygen species(ROS).The intracellular glutathione(GSH)content was detected by GSH kit.Mitochondrial membrane potential was detected by JC-1 stai-ning and RH123 staining.ACSL4 and GPX4 protein expression and the key indicators of ferroptosis were detected by Western blot.Results TAR restored the decreased cell viability of C28/I2 chondrocytes induced by Erastin treatment as well as reduced Erastin-induced cytotoxicity(P＜0.01).Compared with the control group,the level of intracellular lipid ROS increased(P＜0.01)and the content of GSH decreased(P＜0.01)after treatment with Erastin,while TAR could reduce the production of lipid ROS(P＜0.01)and increase the content of GSH(P＜0.01).TAR restored mitochondrial membrane potential in C28/I2 chondrocytes ferroptosis,decreased ACSL4 pro-tein expression(P＜0.01)and increased GPX4 protein expression(P＜0.01).In addition,TAR restored the re-duced cell viability caused by IL-1 β treatment.Conclusion TAR can inhibit Erastin induced ferroptosis in C28/I2 chondrocytes,which may be related to the regulation of ACSL4 and GPX4 protein expression.

Objective:To investigate the pathway of self-disclosure to posttraumatic growth in patients after cervical cancer surgery, and to provide reference for improving the level of posttraumatic growth in patients.Methods:A convenient sampling method was used to investigate 300 patients with cervical cancer after surgery in Shandong Provincial Hospital Affiliated to Shandong First Medical University from June to November 2022 by using general data questionnaire, Distress Disclosure Index (DDI), Connor-Davidson Resilience Scale (CD-RISC), the Shortened Chinese Version of the Family Resilience Assessment Scale (FRAS-C) and the Posttraumatic Growth Inventory (PTGI) in a cross-section study.Results:A total of 290 valid questionnaires were collected, with an effective recovery rate of 96.7%. The patients were aged 23-70(48.13 ± 10.39) years. The scores of self-disclosure, resilience, family resilience and posttraumatic growth were (46.41 ± 9.82), (67.06 ± 14.63), (108.18 ± 11.06) and (58.24 ± 17.86) respectively. The results of pathway analysis showed that self-disclosure could not only directly predict posttraumatic growth, but also indirectly predict posttraumatic growth through the mediating role of resilience and family resilience, and the chain mediating role of resilience and family resilience, respectively. The direct effect of self-disclosure on posttraumatic growth was 0.236(95% CI 0.138-0.335), and the chain mediating effect of family resilience and resilience between self-disclosure and posttraumatic growth was 0.036(95% CI 0.018-0.060). Conclusions:Medical staff should not only consider the direct influence of self-disclosure on posttraumatic growth, but also pay attention to improve the resilience and family flexibility of patients after cervical cancer surgery, so as to promote their posttraumatic growth.

Objective To investigate the role and possible mechanism of curcumin(Cur)regulating Peroxiredoxin-6(Prdx6)expression in inhibiting Erastin-induced ferroptosis in C28/I2 chondrocytes.Methods Safranin O/Fast Green and hematoxylin-eosin(HE)staining were performed to observe the pathological changes in the knee joint of rats with osteoarthritis(OA).The expression levels of Prdx6 and GPX4 proteins in cartilage tissues with OA were detected by immunohistochemistry and Western blot.C28/I2 chondrocytes were treated with different concentrations of Cur,cell viability was detected by thiazolyl blue tetrazolium bromide(MTT)assay and cytotoxicity was measured by lactic dehydrogenase(LDH)assay.The production of lipid reactive oxygen species(ROS)in chondrocytes was detected by flow cytometry,and the total glutathione(GSH)assay kit was used to detect the GSH level in chondro-cytes.Western blot was performed to detect the expression level of Prdx6 and ferroptosis-related proteins in chon-drocytes.The interaction between the Cur molecule and Prdx6 was analyzed through the molecular docking tech-nique.Results During the OA progression,OA rats and OA patients showed pathological changes such as damage to the cartilage and a decrease in the number of chondrocytes.The expression levels of Prdx6 and GPX4 were re-duced in the cartilage tissues of OA patients compared with healthy people.Further study revealed that the treat-ment of Erastin-induced ferroptosis in C28/I2 chondrocytes in a mouse model with 20 μmol/L of Cur could improve cell viability,decrease cytotoxicity,inhibit lipid ROS production,and increase the level of intracellular GSH.Western blot results showed decreased expression of Prdx6,SLC7A11,FTH,and GPX4 and increased expression of ACSL4.In addition,Cur molecules interacted with Prdx6 protein by van der Waals forces and π bond.Conclu-sion Cur may inhibit Erastin-induced ferroptosis in C28/I2 chondrocytes by upregulating the Prdx6 expression lev-el.

IL-34 can promote osteoclast differentiation and activation, which may contribute to steroidinduced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.

Objective Breast cancer is one of the deadliest malignancies in the world. ebracteolatain A (EA) is a kind of acetylphloroglucinol extracted from ebracteolatain. To explore the specific mechanism of EA inhibiting the proliferation of breast cancer cell MCF-7, so as to provide a new approach for the clinical treatment of breast cancer. Methods EA with different concentrations were added to breast cancer cell MCF-7 to detect changes in PKD1 protein expression. The plasmid with overexpressed PKD1 was constructed and transfected into cells, and the mRNA and protein expression levels of PKD1 were detected by real-time fluorescence quantitative PCR and Western Blot assay. CCK-8 assay was used to detect changes in cell proliferation capacity. Western Blot assay was used to detect the expression level of PKD1 and its related signaling pathways. Results EA inhibited the expression of PKD1 protein in breast cancer cells with a dose-dependent manner (P< 0.05). When transfected with the overexpressed plasmid, PKD1 was significantly increased in mRNA and protein levels (P<0.001). At the same time, PKD1 overexpression significantly reversed inhibition of EA on MCF-7 proliferation (P<0.001). It was confirmed by signaling pathway analysis that EA might affect the proliferation ability of breast cancer cells by inhibiting PKD1-mediated MEK/ERK and PI3K/AKT signaling activity (P<0.05). Conclusion EA could inhibit the proliferation of breast cancer cells by regulating PKD1-mediated MEK/ERK and PI3K/AKT signaling pathways.

Objective To investigate the association between serum total testosterone (TT ) levels and type 2 diabetes(T2DM )and any gender differences in elderly patients. Methods Based on the Aging Health database built from 2008 to 2012 ,935 elderly individuals over 60 years old with a mean age of 65.8 years receiving physical examinations were included.According to the 1999 WHO criteria for diabetes ,participants were assigned into four groups :a T2DM group(n＝298) ,an impaired fasting glucose(IFG)group(n＝26) ,an impaired glucose tolerance(IGT)group(n＝121) ,and a normal glucose regulation(NGR)group(n ＝ 490).We measured serum TT by ELISA and analyzed the distribution patterns in the groups.Furthermore ,we examined the gender-specific correlation of TT with T2DM and homeostasis model assessment of insulin resistance (HOMA-IR). Results The prevalence of T2DM in the participants was 31.9%(298/935).One-way ANOVA analysis showed that the TT level was higher in the NGR group than in the T2DM and IGT groups (PANOVA＝ 0.001) . Logistic regression analysis indicated a significant protective association between TT and T 2DM in the elderly.Every one unit of increase in the SD of the TT level was accompanied by a 23% reduction in the risk for T2DM (P＝ 0.001).Further gender-stratification analysis suggested that the protective role of TT against T2DM only existed in males (OR＝ 0.55 ,95% CI :0.44-0.68 ;P＜ 0.001).After adjustment for age ,blood pressure ,blood lipids ,and waist circumference ,the protective role of TT against T2DM in males still remained (OR ＝ 0.68 ,95% CI :0.53-0.86 ;P ＝ 0.002 ).Pearson correlation analysis also indicated a significant negative correlation between TT and HOMA-IR in older males(P＝0.002).As for older females ,no significant correlation of TT with T2DM and HOMA-IR was found. Conclusions The serum TT level might be an independent protective factor for T 2DM in older males ,as evidenced by its correlation with improved insulin resistance status ,which is not present in older females.

Objective To conduct mutation screening of SCN1A 3′ untranslated region (UTR) on Dravet syndrome (DS) patients without mutations in the SCN1A coding region and promoter region, and functional analysis of the variant from DS patients.Methods Twenty-eight DS patients without mutations in the SCN1A coding region and promoter region were screened for SCN1A 3′ UTR mutations using PCR and direct sequencing.Functional analysis of the detected mutation was done via luciferase assay, mRNA stability analysis and RNA electrophoretic mobility shift assay (RNA-EMSA).Results A novo variant (c.*20A>G) in SCN1A 3′ UTR was found in one DS patient.The variant (c.*20A>G) reduced the luciferase gene xpression by 30% through increasing the affinity of pluripotent embryonal carcinoma cell line NT2/cytoplasmic protein binding and reducing luciferase gene mRNA stability (t=8.5,P<0.01).Conclusions A functional variant was detected from one patient with DS.This variant negatively regulated the gene expression by increasing the affinity of pluripotent embryonal carcinoma cell line NT2/cytoplasmic protein binding and reducing mRNA stability.

Objective To explore the clinical value of MRI in diagnosing and treating cesarean scar pregnancy (CSP).Methods A retrospective analysis was conducted on the clinical manifestations of 54 patients diagnosed with CSP between January 2009 to January 2013 in Peking University Third Hospital.Based on the patients' MRI image and other clinical datas,we did transvaginal operation on patients with CSP1,and transvaginal combined with abdominal operations on patients with CSP2.The intraoperative blood loss,operation time,postoperative hospital stay,and the length of time required for of serum hCG dropping to normal of the patients were analyzed.Results The average age of the 54 patients was (34±5) years and the average duration of gestation was (56± 16) days,all patients' vital sign were stable,the hCG level was 23-142 962 U/L before treatment.Twelve patients were diagnosed with CSP1 by MRI,and 5 of them had focus of 1-2 cm in diameter,the 5 patients' serum hCG level was 436-1 159 U/L and 23-32 days after drug administration,their hCG level returned to normal; the other 7 patients had focus of 2.0-4.4 cm in diameter,and their hCG level was 2 218-63 446 U/L,lesion resection was done on the 7 patients by hysteroscope or under B-uhrasound monitor.Forty-two patients were diagnosed with CSP2,and their focus were 1.0-7.1 cm in diameter,and serum hCG level were 23-142 962 U/L.We did bilateral uterine artery occlusion by laparoscope or laparotomy during operation for 22 patients or bilateral uterine artery embolization (UAE) before operation for 20 patients,then we did lesion resections.The blood loss during operation of CSP1 or CSP 2 was 50.1,267.2 ml; operation time was 30,128 minutes; postoperative hospital stay was 4.6,6.7 days;their serum hCG returned to normal 13-30 days after the surgery.All the 54 patients' uterus were preserved,and the patients undergoing operations were all cured without the second operation.Conclusion MRI is an effective method to conduct clinical treatment in CSP.

Objective To identify drug resistance status of Mycobacterium tuberculosis (MTB) strains by the GenoType MTBDRplus line-probe assay (LPA),compare its performance with traditional drug susceptibility testing (DST),and to assess its predictive value for the prognosis of patients with drug resistance tuberculosis.Methods Pulmonary tuberculosis patients who visited Zhuji People's Hospital,Zhejiang Province during February 2011 and January 2012 with a positive result of sputum smear at baseline were all recruited.A total of 275 culture positive specimens were collected,then isolated and cultured for Mycobacterium tuberculosis in the laboratory.DST were performed,meanwhile,GenoType MTBDRplus were also applied to detect resistance to isoniazid (INH) and rifampin (RMP).All the tuberculosis patients who were recruited were followed,including sputum culture and chest radiography.Results There were 192 strains showing drug resistance both by DST and MTBDRplus LPA.Fourteen multidrug resistant (MDR),21 INH mono-resistant and 2 RMP mono-resistant strains were detected by DST.As for GenoType MTBDRplus LPA,MDR,INH mono-resistant and RMP mono-resistant strains were 14,18 and 2,respectively.Taken DST as the gold standard,LPA was more accurate in the detection of resistance to RMP,while it failed to detect 23.8％ (5/21) of the INH-resistant strains.We analyzed the prognosis of patients with drug resistance by GenoType MTBDRplus LPA,the rates of treatment success were 84 ％ (110/131),9/15,3/11 in patients infected with susceptible,INH mono-resistant and MDR strains,respectively.For the 2 cases of RMP mono-resistanee,one was cured and the other failed.The predictive value of molecular drug resistance test for treatment failure in INH mono-resistant patients was 40.0 ％,while that was 83.5 ％ for treatment success in INH susceptible patients.The predictive value for treatment failure in RMP mono-resistant patients was 50.0％,while that was 81.5％ for treatment success in RMP susceptible patients.The predictive value for treatment failure in MDR patients was 72.7％,while that was 81.1％ for treatment success in patients without MDR.Conclusion The GenoType MTBDRplus LPA assay is a rapid and reliable diagnostic test for resistance of MTB,which can be used to predict the prognosis of drug resistant tuberculosis in the clinical practice.