This study established a school-supervisor-postgraduate "three-dimensional interaction" mode of academic norms and ethics education for medical postgraduates based on their training characteristics. The mode was evaluated and improved in practice. The results showed that after the implementation of the mode, graduate students significantly improved their awareness of how to standardize the implementation of experiments [(79.86% vs. 89.47%); P=0.021] and how to write formal experimental records [(84.72% vs. 92.76%); P=0.028]. In addition, there were significant increases in the pass rate of pre defense (85.42% vs. 94.08%; P=0.014) and blind review (84.03% vs. 93.42%; P=0.010). The "three-dimensional interaction" mode truly helps to achieve a win-win-win situation between postgraduate supervisors and the school, and is worth further practice and promotion.

【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Objective To investigate the correlations of serum Apelin-13 and fatty acid binding protein 4 (FABP4) levels with metabolic and bone metabolic indicators in postmenopausal women with different bone mass. Methods A total of 145 postmenopausal women were selected as subjects and divided into three groups based on bone mineral density (BMD) test results: normal bone mass group(49 cases), osteopenia (ON) group(51 cases), and osteoporosis (OP) group(45 cases). Serum Apelin-13, FABP4 levels, bone metabolic indicators, and biochemical indicators were measured and compared among the three groups. Spearman correlation analysis was used to analyze the correlations of Apelin-13, FABP4, and other indicators with BMD. Multivariate Logistic regression analysis was performed to analyze the risk factors for OP, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of serum Apelin-13 for postmenopausal osteoporosis (PMOP). Results The serum Apelin-13 level in the OP group was lower than that in the ON group and the normal bone mass group (P < 0.05). No significant difference in serum FABP4 levels was found among the three groups (P>0.05). The levels of serum parathyroid hormone (PTH), alkaline phosphatase (ALP), type Ⅰ procollagen amino-terminal propeptide (PⅠNP), type Ⅰ collagen cross-linked C-terminal peptide (CTXⅠ), and bone-specific alkaline phosphatase (BALP) in the OP group were higher than those in the ON group and the normal bone mass group (P < 0.05). Lumbar post-menopause BMD was positively correlated with serum Apelin-13 levels (P < 0.05), but had no correlation with serum FABP4 levels (P>0.05). Lumbar BMD was negatively correlated with serum PTH, ALP, PⅠNP, CTXⅠ, BALP, and age (P < 0.05), but positively correlated with body weight, body mass index, T-score, fasting insulin, and insulin resistance index (P < 0.05). Multivariate Logistic regression analysis showed that serum Apelin-13, PTH, ALP, PⅠNP, CTXⅠ, and BALP levels were independent factors influencing the occurrence of OP in postmenopausal women (P < 0.05). ROC curve results showed that the optimal cut-off value of serum Apelin-13 for predicting PMOP was 18.51 pg/mL, with an area under the curve of 0.716, a sensitivity of 70.0%, and a specificity of 64.4%. Conclusion Apelin-13 is lowly expressed in the serum of PMOP patients, and its expression level is closely related to lumbar BMD, which may serve as an early screening indicator and potential therapeutic target for PMOP.

To investigate the clinical manifestations and imaging characteristics of patients with different types of infectious sacroiliitis. Clinical data of 40 patients diagnosed with infectious sacroiliitis were retrospectively analyzed. Among the 40 patients, 16 patients were diagnosed as non-brucellar and non-tuberculous infectious sacroiliitis (ISI), 13 with tuberculous infectious sacroiliitis (TSI), and 11 with brucellar sacroiliitis (BSI). In the ISI and TSI group, female patients accounted for 11/16, 12/13, while the proportion of unilateral involvement was 15/16 and 12/13, respectively. Compared with ISI and TSI group, BSI patients were mainly male (8/11) and presented more bilateral involvement (6/11) ( P<0.05). Bone erosion was more common in ISI and TSI groups than in BSI group (6/15, 7/11 and 2/10), as well as abscess formation (3/15, 4/11 and 1/10, respectively). Symptoms in all patients relieved 1-2 weeks after administration of antibiotics or anti-tuberculosis treatment, but the resolution of the magnetic resonance imaging findings delayed about 6 (3-9) months. ISI and TSI patients with infectious sacroiliitis should be differentiated from spondyloarthritis, with a characteristic of more female patients, unilateral sacroiliitis, bone erosion, soft tissue involvement and abscess formation. However, BSI patients are mainly male, more bilateral involvement and less bone destruction and abscess formation. Antibiotic therapy demonstrates significant therapeutic effects, but resolution of the magnetic resonance imaging findings responses late.

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.
Animals ; Colitis, Ulcerative/microbiology* ; Mice ; Mice, Inbred C57BL ; Porphyromonas gingivalis/pathogenicity* ; Protein-Arginine Deiminases ; Virulence Factors

Objective: To explore the moderated and mediating mechanism between childhood trauma and depressive traits, and to provide a reference for conducting the related research and intervention. Methods: From 2017 to 2018, a cluster sampling method was adopted to select 2 786 freshman. Childhood trauma questionnaire, state-trait depression Scale, the automatic thought questionnaire and trait coping style questionnaire was administered. Results: Regression analysis showed that childhood trauma, automatic thinking and negative coping was positively associated with depressive traits, and positive coping was negatively associated with depressive traits (β=0.12, 0.40, 0.14, -0.33, P<0.05). The mediation analysis showed that automatic thinking mediated the relationship between childhood trauma and depressive traits (95%CI=0.03-0.06). The results of moderation effect showed that negative coping moderated the relationship between childhood trauma and automatic thinking and the relationship between childhood trauma and depressive traits, respectively (P<0.05). Conclusion Childhood trauma affects depressive traits,and its relationship is influenced by boping styles and automatic thinking.

Objective: To explore the relationship between parents’ unstable marital status and offspring’s suicide attempts and the possible mediating factors, and to provide reference for suicide prevention among off spring grom unst able families. Methods: From 2017 to 2018, 2 766 valid questionnaires were collected from freshmen in a university in Hunan province. Students completed questionnaires of childhood trauma and depression traits,and reported their parents’ marital status and suicide attempts etc. Results: Compared to college students with parents of stable marital status,students with parents of unstable marital status showed higher reported rate of suicide attempts and higher scores of depression trait and childhood trauma (t/χ2=2.78, 5.83, 20.30, P<0.05). Controlling possible confounding factors,unconditional Logistic regression showed that childhood trauma,unstable marital status of parents and depressive traits were positively correlated with suicide attempt(OR=1.05, 1.45, 1.08, P<0.05). The 95% confidence interval of the Bootstrapping method with four mediation pathways (parental marital status→childhood trauma→depressive trait,childhood trauma→depressive trait→suicide attempt,parental marital status→childhood trauma→suicide attempt and parental marital status→childhood trauma→depressive trait→suicide attempt) does not include zero. Conclusion Childhood trauma and depressive traits mediate the relationship between parental instable marriage and suicide attempts in off spring.

In recent decades, the research on clinical nursing pathways for breast cancer in China mainly explores their nursing benefits when applied in breast cancer patients who undergo surgery, chemotherapy and radiation therapy. However, there is no official clinical nursing pathway for breast cancer yet in China and the pathway formulation methods and norms are uneven in the existing research. Since the research on the formulation of clinical nursing pathways are relatively lacking in China, this article reviews the domestic and foreign literatures from the formulation and clinical application of clinical nursing pathways for breast cancer, with a view to providing reference for the subsequent research on clinical nursing pathways for breast cancer.

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ²=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors. Conclusion The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.