BACKGROUND:Inflammation affects the osteogenic differentiation of periodontal ligament stem cells,and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related.However,there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation. OBJECTIVE:To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions. METHODS:Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured,and underwent Vimentin,pan-CK,and Stro-1 fluorescence staining.At 3,7,and 14 days of osteogenic differentiation,western blot assay was used to detect the protein expression levels of alkaline phosphatase,LC3B,Beclin1,and ATG5 in normal and inflammatory periodontal ligament stem cells.The mRNA expression levels of alkaline phosphatase,bone sialoprotein,osteocalcin,Runx2,LC3B,Beclin1,and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION:(1)Stro-1 was positive,Vimentin was positive,and pan CK was negative in periodontal ligament stem cells.(2)At 3,7,and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced(P<0.01);the expression of alkaline phosphatase protein and mRNA was significantly lower(P<0.05);the mRNA expression levels of bone sialoprotein,osteocalcin,and Runx2 were significantly decreased(P<0.05).(3)At 7 and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the expression levels of ATG5,LC3B,and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated(P<0.05).These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation.

Objective:To analyze the clinical characteristics of patients with inflammatory bowel disea-ses(IBD)in pre-pregnancy,pregancy and loctation.Methods:The clinical data of pregnancy compli-cated with IBD in Department of Obstetrics and Gynecology of Peking University Third Hospital and deli-very from September 2011 to June 2022 were collected.The clinical characteristics of the patients were analyzed retrospectively.According to the state of diseases during pre-pregnancy,pregnancy and lactation,the patients were divided into active and remission group,and the two groups were compared interms of pre-pregnancy counseling,nutritional status,pregnancy and delivery complications,gestational week,mode of delivery,and neonatal outcome.Results:A total of 33 pregnant women with IBD were included in this study,of which 7 delivered a second child,for a total of 40 deliveries,with 36 natural pregnan-cies(90.0％)and 4 assisted reproductions(10.0％).Among the 40 cases,21 cases(52.5％)were sustained in remission in pre-pregnancy,pregnancy and lactation,and 19 cases(47.5％)in disease ac-tivity,of which 8 cases(42.1％)were due to self-withdrawal of drugs or failure to take medicine regu-larly.Compared with the activity group,the disease remission group had a higher rate of pre-pregnancy counseling(57.1％vs.15.8％,P=0.010),and higher levels of hemoglobin[(112.67±8.53)g/L vs.(102.84±5.23)g/L,P＜0.001],serum total protein[(66.58±6.34)g/L vs.(60.83±6.25)g/L,P=0.006],serum albumin[36.4(35.1,38.3)g/L vs.34.3(31.1,35.6)g/L,P=0.006],se-rum calcium[(2.25±0.10)μmol/L vs.(2.13±0.15)μmol/L,P=0.004],but a lower incidence of gestational hypertensive disorders(0 vs.31.6％,P=0.007).In 40 deliveries,there were 27 cases of vaginal delivery(67.5％),13 cases of cesarean section(32.5％).The analysis of neonatal outcomes showed 38 full-term deliveries and 2 preterm deliveries;1 case of macrosomia,1 case of small-for-gesta-tional-age,1 case of low birth weight and 3 cases of birth defects.There were 10 newborns admitted to neonatal intensive care unit,including 4 cases of neonatal infections and 2 cases of neonatal jaundice.Conclusion:Pre-pregnancy counseling and evaluation of IBD patients are very important,and good preg-nancy outcomes can be obtained through careful management during pregnancy in the most of the pa-tients.

Objective:To evaluate the curative effects of 3D printed microporous titanium (tantalum) prosthesis in reconstruction of large segmental bone defects caused by lower extremity osteomyelitis.Methods:A retrospective study was conducted to analyze the clinical data of 18 patients who had been treated for large segmental bone defects caused by lower extremity osteomyelitis between January 2020 to May 2022 at Department of Orthopaedics, The 920th Hospital of Joint Logistics Support Force. There were 10 males and 8 females with an age of (45.3±14.1) years. The defects were at the left side in 13 cases and at the right side in 5 cases, at the femur in 11 cases and at the tibia in 7 cases. The duration of osteomyelitis was 1.0 (1.0, 3.5) years. The length of bone defects was 8.35 (6.50, 9.84) cm. Their bone defects were repaired by an individually 3D printed microporous titanium (tantalum) prosthesis after operative removal of osteomyelitis lesions. The wound healing was observed after surgery. The clinical efficacy was comprehensively evaluated by the Paley grading for bone defect healing, visual analog scale (VAS), lower extremity functional scale (LEFS), and imaging examination.Results:The postoperative follow-up period for the 18 patients was (12.2±0.3) months. Wound infection occurred 2 months after surgery in one patient who was treated with Ilizarov bone transfer after removal of the microporous titanium prosthesis. The remaining 17 patients had good postoperative wound healing. At the last follow-up, the 18 patients had a VAS pain score of 2.0(1.0, 4.0) points, significantly lower than the preoperative one [(6.1±2.3) points], and a LEFS score of 54.00(34.50, 69.25) points, significantly higher than the preoperative one [18.50(9.00, 26.50) points] ( P<0.05). At the last follow-up, according to the Paley grading, the bone union was rated as excellent in 16 patients, as good in 1 patient and as poor in 1 patient. The integration of femoral fractures with 3D printed microporous titanium prostheses was fine. Conclusion:In reconstruction of large segmental bone defects caused by lower extremity osteomyelitis, implantation of a 3D printed microporous titanium (tantalum) prosthesis is feasible and effective, not only reducing pain but also restoring the limb function.

Objective:To explore the current status of barriers to participation in phaseⅡcoronary artery bypass grafting (CABG) patients and the factors influencing them, and to provide new ideas for reducing barriers to participation in rehabilitation and improving the participation rate in cardiac rehabilitation.Methods:For this study, a cross-sectional survey research method was utilized. The study included 334 patients who underwent CABG and were admitted to the Second Hospital of Hebei Medical University between June 2022 and May 2023. These patients were selected using the convenience sampling method. A General Information Questionnaire, the Cardiac Rehabilitation Barriers Scale (CRBS-C/M), and a Questionnaire on the Knowledge of Information Related to Cardiac Rehabilitation were used to conduct the survey. Multiple linear regression was used to analyze the independent influencing factors on barriers to participation in phase Ⅱ cardiac rehabilitation in post-CABG patients.Results:Out of 334 patients, 248 were males and 86 were females with age (54.74 ± 7.61) years old. The total average score of CRBS-C/M in patients after CABG surgery was 3.20 ± 0.43, with the highest external logistic factors score of 3.42 ± 0.58. The knowledge status score of information related to cardiac rehabilitation was 42.11 ± 7.94. Multiple linear regression analysis revealed that the following factors independently influenced post-CABG patients′ barriers to participating in phaseⅡcardiac rehabilitation: marital status, whether or not they had completed phase I cardiac rehabilitation,number of other comorbidities, knowledge of cardiac rehabilitation information. All of these differences were statistically significant ( t values were -4.87-3.35, all P<0.05). Conclusions:The barriers to participation in phase Ⅱ cardiac rehabilitation in post-CABG patients are at an intermediate to high level, and healthcare professionals should emphasize the assessment of barrier factors in these patients, and target the development and implementation of phase Ⅱ cardiac rehabilitation in terms of the influencing factors.

Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.

Based on the theoretical reflection on the reflective function of medical records,the important findings in the practice of medical records writing in the field of palliative care,and conceptual analysis of narrative medicine tools,combined with empirical investigation materials and analysis,this paper focused on the practice of medical records writing for reflection and research.The main contents include defining the concept of narrative medical records,which are medical records used in clinical practice that incorporate narrative content;clarifying their characteristics and functions at different levels;and exploring practical paths for their application in clinical practice.Based on an in-depth exploration of the uniqueness of narrative medicine practice at Peking Union Medical College,it also emphasized the necessity of writing medical records with narrative thinking.Specifically,it focused on using narrative thinking and forms to enhance the improvement of current medical records writing,and further sought a general framework and multiple possibilities for narrative medicine clinical pathways.

Background:There is a link between dysbiosis or disorder of gut microbiota and brain and liver diseases,and gut microbiota may affect the occurrence and development of primary biliary cholangitis(PBC)and depression through the gut-liver-brain axis.Aims:To analyze the gut microbiota in PBC mice associated with depression by using 16S rRNA gene sequencing technology.Methods:Twelve female mice were randomly divided into control group,cholestasis group,cholestasis+depression group and treatment group.Mice in the control group were given normal feed and water.Mice in the cholestasis group were fed with a feed containing 0.1%DDC for 2 weeks to establish cholestasis model.Mice in the cholestasis+depression group were stimulated with chronic mild unpredictable stress for 2 weeks,followed by 2 weeks of 0.1%DDC-containing feed to establish cholestasis+depression model.Mice in the treatment group were injected intraperitoneally with clomipramine hydrochloride(7.5 mg·kg-1·d-1)for 2 weeks based on the construction of cholestasis+depression model.During the modeling period,the behavioral changes of the mice were observed.After the modeling,the body weight was recorded,and the weight-bearing swimming test,forced swimming test,tail suspension test and HE staining of liver tissue were performed.The fresh feces were collected,and the changes of gut microbiota were analyzed by 16S rRNA gene sequencing technology.Results:Compared with the control group,the body weight of mice in cholestasis group and cholestasis+depression group was significantly decreased(P<0.05),and the depression-like behavior was significantly aggravated(P<0.05);compared with the cholestasis+depression group,the body weight of mice in treatment group was significantly increased(P<0.05),and the depression-like behavior was significantly ameliorated(P<0.05).Various degrees of cholestatic injury of the liver tissue were observed in the cholestasis group,cholestasis+depression group and treatment group.Compared with the cholestasis+depression group,the pathological injury of the liver tissue in treatment group was significantly reduced.After sequencing and flattening,5 491 operational taxonomic units(OTUs)were obtained in fecal samples.There were 162 common OTUs among the 4 groups.The microbial diversity and community composition of the control group,cholestasis group,cholestasis+depression group and treatment group were significantly different.At the phylum level,the abundance of Firmicutes in the cholestasis group was significantly increased;the abundance of Proteobacteria in the cholestasis+depression group was significantly increased;the abundance of both Firmicutes and Proteobacteria was significantly increased in the treatment group,while the abundance of Bacteroidetes was significantly decreased.LEfSe analysis was performed in species with significant differences among the groups,and the results showed that there were 38 microbial groups with LDA value>4.Conclusions:Significant changes are observed in gut microbiota composition and diversity in mice with PBC associated with depression.Antidepressant treatment can improve the abundance and diversity of gut microbiota,and regulating gut microbiota may become a new treatment strategy for PBC associated with depression.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To systematically evaluate the qualitative research on human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients′experience of participating in advance care planning (ACP), so as to provide reference for the application of ACP in HIV/AIDS patients.Methods:Computer searched qualitative studies on HIV/AIDS patients′participation in ACP experience in Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, Wanfang, VIP, China Biomedical Literature Database. The search time limit was from inception to December 1, 2023, and the research results were integrated using Meta integration method after quality evaluation.Results:A total of 10 articles were included, and 58 research results were extracted, forming 12 new categories, and 4 integrated results were obtained: HIV/AIDS patients′understanding of ACP; attitudes of HIV/AIDS patients towards ACP; the influencing factors of HIV/AIDS patients′participation in ACP; suggestions for implementing ACP for HIV/AIDS patients.Conclusions:Medical staff should promptly identify the needs of HIV/AIDS patients for ACP, help them increase their awareness and acceptance of ACP. At the same time, based on China′s unique cultural background and healthcare system, relevant laws and regulations should be continuously improved to promote the development and improvement of ACP in China.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.