BACKGROUND:Nano-zirconium dioxide has good application potential in the field of bone tissue repair.Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects. OBJECTIVE:To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. METHODS:Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured,and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay.The biosafety concentration was selected according to the cytotoxicity,and the cells were randomly divided into a control group,a nano-zirconium dioxide group,and a nano-hydroxyapatite group.Osteogenic differentiation of cells was directionally induced in each group.On day 7 of induced differentiation,alkaline phosphatase staining was performed.qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers(Runx2 and Osx).On day 21 of induced differentiation,alizarin red staining was conducted.qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers(OPN and OCN). RESULTS AND CONCLUSION:(1)The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL.In the experiment,the mass concentration of 200 μg/mL was selected for intervention.Zirconium dioxide had no significant effect on the proliferation of the cells.(2)Compared with the control group,the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher,but there was no significant difference compared with the nano-hydroxyapatite.(3)Compared with the control group,the expression of bone-related genes and proteins increased significantly,but there was no significant difference compared with nano-hydroxyapatite.(4)The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.This promoting effect is equivalent to that of nano-hydroxyapatite.

Objective:To investigate the protein expression characteristics of bone metastatic breast cancer cells and the underlying molecu-lar mechanism driving bone metastasis.Methods:A firefly luciferase-overexpressing human breast cancer cell line,MCF-7-luc,and its bone metastasis subline,MCF-7-BOM-luc,were established.Additionally,a nude mouse model of breast cancer bone metastasis was established by injecting the aforementioned cells into the left ventricle.Bone metastasis and trabecular changes were assessed using micro-computed tomography(Micro-CT).Cell migration,and invasion were evaluated using the Transwell assays.Differential protein expression and epithelial-mesenchymal transition(EMT)were analyzed using proteomics,Western blot,and reverse transcription-quantitative PCR(qPCR).We meas-ured the glucose uptake,L-lactic acid content,and cell energy metabolism parameters using 2-NBDG,ELISA,and a Seahorse energy metabol-izer.Results:MCF-7-BOM-luc cells exhibited stronger migration,invasion,and EMT characteristics as well as more pronounced bone meta-stasis capabilities than the MCF-7-luc cells.Proteomic analysis revealed increased S100 calcium-binding protein A(S100A4)expression in MCF-7-BOM-luc cells,with other differentially expressed proteins being primarily involved in metabolic pathways.Additionally,MCF-7-BOM-luc cells displayed increased expression of E-box binding homeobox 1/2(zinc finger E-box binding homeobox 1/2,ZEB1/2)and Vimentin and reduced E-cadherin expression.MCF-7-BOM-luc cells also exhibited enhanced glucose uptake,L-lactic acid production,and glycolysis rates as well as increased phosphorylation levels of extracellular signal-regulated kinases 1/2(ERK1/2)and signal transducer and activator of tran-scription 3(STAT3).Conclusions:MCF-7-BOM-luc cells promote S100A4 expression through ERK1/2 and STAT3 signaling pathway activation,which in turn enhances the EMT process and glycolysis rate,thereby contributing to malignant bone metastasis.Proteomic analysis of breast cancer bone metastasis-related protein characteristics could offer potential targets for the diagnosis,prevention,and treatment of breast cancer bone metastasis.

Objective To investigate serum levels of soluble apoptosis-related factor ligand(sFasL)and stromal cell derived factor 1(SDF-1)in patients with aplastic anemia(AA)and their correlation with immunosuppressive treatment.Methods Forty-three AA patients who received immunosuppressive therapy for half a year were selected as the observation group,and another 43 healthy subjects at the same period were selected as the control group.Patients in the observation group received immunosuppressive therapy and hematopoietic propoietic therapy,and patients were divided into the ineffective group and the effective group according to the efficacy.Clinical data of patients were collected,and serum levels of sFasL,SDF-1,tumor necrosis factor-α(TNF-α)and interleukin-8(IL-8)were detected by enzyme-linked immunosorbent assay.The correlation between serum sFasL and SDF-1 levels was analyzed.Multivariate Logistic regression analysis was conducted to analyze influencing factors of immunosuppressive treatment in AA patients.The predictive values of serum sFasL and SDF-1 on immunosuppressive treatment were analyzed by receiver operating characteristic(ROC)curve.Results Serum levels of sFasL and SDF-1 were higher in the observation group than those in the control group(P＜0.05).Serum levels of TNF-α,IL-8,sFasL and SDF-1 were higher in the ineffective group than those in the effective group(P＜0.05).Serum sFasL level was positively correlated with SDF-1 level in AA patients(r=0.534,P＜0.001).Increased serum sFasL and SDF-1 levels were independent risk factors for ineffective immunosuppressive therapy in AA patients(P＜0.05).The area under the curve(AUC)of serum sFasL and SDF-1 combined to predict the immunosuppressive treatment effect of AA patients was 0.973(95%CI:0.872-0.999),which was better than that of single diagnosis(P＜0.05),and its sensitivity and specificity were 94.44%and 96.00%,respectively.Conclusion Serum levels of sFasL and SDF-1 are significantly increased in patients with AA.The combined detection of sFasL and SDF-1 has high predictive value for the immunosuppressive treatment effect of AA.

Objective To investigate the expression and prognostic significance of serum protease C1 inhib-itor(SERPING1)and plasminogen activator inhibitor type 1(SERPINE1)in patients with sepsis.Methods A total of 132 patients with sepsis treated in the hospital from March 2018 to March 2020 were se-lected as the sepsis group.According to whether they died within 28 days of admission,they were divided into a death group(n=34)and a survival group(n=98).Enzyme linked immunosorbent assay was used to detect the expression of serum SERPING1 and SERPINE1.Multivariate Logistic regression model and receiver oper-ating characteristic curve were used to study the value of serum SERPING1 and serpine1 in evaluating the prognosis of patients'death.Results[Compared with the control group,serum SERPING1(331.12±51.80 ng/L vs.639.04±91.12 ng/L)was lower and serum serpine1(412.67±64.84 ng/L vs.42.33±10.32 ng/L)was higher in the sepsis group,and the differences were statistically significant(P＜0.05).[Compared to the survival group,the levels of serum SERPINE1,procalcitonin,C-reactive protein,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score in the death group were higher,while serum SERPING1 was lower,and the differences were statistically significant(all P＜0.05).Serum SERPING1 showed negative correlation with APACHE Ⅱ and SOFA scores(r=-0.779,-0.653,P＜0.05),while serum SERPINE1 showed positive correlation with APACHE Ⅱ and SO-FA scores(r=0.740,0.685,P＜0.05).APACHE Ⅱ score,SOFA score,and serum SERPINE1 were risk fac-tors affecting the prognosis of sepsis patients,while serum SERPING1 was a protective factor.The area under the curve of serum SERPING1 and SERPINE1 combined for the evaluation of the death in sepsis patients was 0.938(95％CI:0.893-0.968),which was significantly higher than 0.860(95％CI:0.812-0.899)and 0.838(95％CI:0.781-0.868)of the single detection,and the differences were statistically significant(Z=3.861,4.015,P＜0.001).Conclusion The elevated levels of serum SERPING1 and SERPINE1 in patients with sepsis are related to the severity of the patient's condition.The combination of the two has high prognos-tic value for sepsis patients.

This study included 116 professional postgraduate students majoring in clinical surgery who rotated in the Department of Breast and Thyroid Surgery of The First Affiliated Hospital of Army Medical University from 2019 to 2022. The students were provided with open online courses on precision medicine to build a strong theoretical foundation for evidence-based medicine; subsequently, precision medicine courses focusing on thyroid surgery were offered; and multidisciplinary team rounds for typical and difficult-to-diagnose cases were organized. Taking thyroid cancer as an example, questionnaire surveys and typical clinical case assessment were conducted to compare the scientific research and professional competencies of the students before and after evidence-based medicine education. The results showed that the students had significantly improved ability to use academic databases to acquire professional knowledge and solve problems, and showed increased enthusiasm in class, believing that the teaching content was easy to absorb and moderate in difficulty and the teaching effect was good.

Objective:To understand the level of self-advocacy in young female breast cancer patients and analyze its influencing factors, so as to provide reference for clinical intervention.Methods:A total of 250 young female breast cancer patients from Puyang People′s Hospital and Puyang Oilfield General Hospital from May 2021 to June 2022 were selected as research objects by convenience sampling method. A cross-sectional survey was conducted using the general information questionnaire, Female Self-Advocacy in Cancer Survivorship, Cancer Distress Scales for Adolescent and Young Adults and Family Resilience Assessment Scale. Multiple stepwise linear regression was used to analyze the influencing factors of self-advocacy in young women with breast cancer.Results:A total of 235 young female breast cancer patients completed the survey. The total score for self-advocacy was (77.04 ± 12.76) points, the total score of psychological distress was (108.25 ± 18.36) points, and the total score of family resilience was (112.93 ± 25.20) points. Self-advocacy was negatively correlated with psychological distress ( r=-0.548, P<0.001), and positively correlated with family resilience ( r=0.596, P<0.001). Education level, personality type, family monthly income, perceived economic pressure, work status, fertility, intimate relationship, diagnosis time, psychological distress and family resilience were the influencing factors of self-advocacy of young female breast cancer patients ( R2=0.595, F=35.31, P<0.01). Conclusions:The level of self-advocacy of young female breast cancer patients should be further improved. Medical staff should take targeted measures according to influencing factors to improve their self-advocacy level.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders.Impaired social functioning is a core characteristic of individuals with ASD.Social attention deficits are important manifestation of their impaired social functioning.And it mainly reflected in the gaze on faces and social interactions.Eye movement technology is an objective and sensitive non-invasive measurement tool.Its application makes the measurement of individual core characteristics of ASD more accurate and objective.A review of recent studies revealed that the type of eye-movement stimuli for social attention in patients with AD gradually shifted from face image processing to social interaction scenes, and developed from static presentation to dynamic presentation.Dimensional embodiment of the progress of eye-movement studies of social attention in individuals with ASD.These studies suggest that individuals with ASD are less likely to gaze at the face region and the eye region of the face.More studies are currently using eye-tracking technology, and the analysis of emotional face gaze reveals that, the reduction in eye gaze in individuals with ASD is due to the discomfort associated with threatening faces.These findings validate the " gaze aversion" hypothesis regarding impaired social attention in individuals with ASD.Related neural mechanism studies have found a general lack of attention to social cues in the environment in individuals with ASD.Brain regions such as the amygdala, cingulate gyrus, superior temporal sulcus and anterior insula are associated with social attention in individuals with ASD.Especially with the superior temporal sulcus, the dorsal and ventral sides of the anterior insula, and so on.Future research should explore the cognitive neural mechanisms of social attention deficits in ASD, and the application of advanced information technology, such as eye-tracking technology, in the rehabilitation of patients with ASD.

Background and Objectives: Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. Methods: and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). Conclusions Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.

Objective To investigate the epidemiological features and antiviral response of patients with genotype 6 chronic hepatitis C (CHC) in Guangxi, China. Methods A total of 97 patients with genotype 6 CHC who were admitted to The First Affiliated Hospital of Guangxi Medical University from December 2012 to December 2020 were enrolled, among whom 62 patients were given antiviral therapy. The 62 patients receiving antiviral therapy were divided into interferon group with 22 patients and direct-acting antiviral agent (DAA) group with 40 patients. Related data were collected, including general demographic data, HCV RNA, liver function, routine blood test results, and renal function. The chi-square test was used for comparison of categorical data between groups. Results Among the 97 patients, there were 69 male patients (71.1%) and 28 female patients (28.9%), with a mean age of 41.97±10.12 years, and the patients aged 30-40 years accounted for 47.4% (46/97). Of all 97 patients, 95 (97.9%) had genotype 6a, 1 had genotype 6e, and 1 had genotype 6xa. Among the 65 patients with a definite route of infection, 41 (63.1%) had intravenous drug use, 14 had medical-related operations, 9 had blood transfusion, and 4 had sexual contact as the route of infection. For the interferon group, the rapid virologic response (RVR) rate at week 4 was 81.8% (18/22), the rate of undetectable virus at the time of drug withdrawal (Epoint) was 86.4% (19/22), the rate of sustained virologic response at 12 weeks after drug withdrawal (SVR12) was 81.8%, and the rate of sustained virological response at 24 weeks after drug withdrawal (SVR24) was 81.8%; 1 patient in this group experienced recurrence. All 40 patients in the DAA group were previously untreated patients (33 patients without liver cirrhosis and 7 patients with compensated liver cirrhosis), with an overall RVR rate of 87.5%(35/40), an Epoint rate of 100%, and an SVR12 rate of 100%, and there was no treatment failure or recurrence. Although different DAA regimens had different RVR rates, they all had a SVR12 rate of 100%. The patients with compensated liver cirrhosis and other diseases had a SVR12 rate of 100%. Conclusion Intravenous drug addiction is the main route of infection for patients with genotype 6 CHC in Guangxi, and CHC is more common in men, with genotype 6a as the main subtype. DAA treatment has a higher virologic response rate than interferon treatment, with an SVR12 rate of 100%. There is no significant difference in SVR12 rate between the patients with compensated liver cirrhosis and those without liver cirrhosis.

Objective:To evaluate the relationship between preoperative widespread pain and chronic post-surgical pain (CPSP) following total knee arthroplasty (TKA) in the patients with knee osteoarthritis.Methods:Two hundred American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients with knee osteoarthritis, aged 40-70 yr, undergoing elective the first unilateral primary TKA under general anesthesia, were enrolled.The widespread pain index, visual analogue scale score, Hospital Anxiety and Depression Scale and Central Sensitization Inventory scores were recorded at 1 day before surgery.The patients were divided into CPSP-positive group and CPSP-negative group according to visual analogue scale score at 6 months after surgery.Risk factors for CPSP were analyzed by logistic regression.Results:The results of logistic regression analysis showed that increased preoperative widespread pain index score, Central Sensitization Inventory score and Hospital Anxiety and Depression Scale score and female were risk factors for CPSP after TKA.Conclusions:Preoperative widespread pain is a risk factor for CPSP following TKA in the patients with knee osteoarthritis.