A landscape of gene expression regulation for synovium in arthritis.

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.

Efficacy of bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed POEMS syndrome patients.

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.

Study of the mechanism of action of sand therapy on atherosclerosis based on the two-phase flow-Casson model.

BACKGROUND: Sand therapy is a non-pharmacological physiotherapy method that uses the natural environment and resources of Xinjiang to treat through the heat transfer and magnetic effects of sand. OBJECTIVE: Employing the two-phase flow-Casson blood flow model, we investigate the mechanism of atherosclerosis prevention via sand therapy, offering a biomechanical theoretical rationale for the prevention of atherosclerosis through sand therapy via the prism of computational fluid dynamics (CFD). METHODS: Sand therapy experiments were conducted to obtain popliteal artery blood flow velocity, and blood was considered as a two-phase flow composed of plasma and red blood cells, and CFD method was applied to analyze the hemodynamic effects of Casson's blood viscosity model before and after sand therapy. RESULTS: (1) The blood flow velocity increased by 0.24 m/s and 0.04 m/s at peak systolic and diastolic phases, respectively, after sand therapy; the axial velocity of blood vessels increased by 28.56% after sand therapy. (2) The average red blood cell viscosity decreased by 0.00014 Pa ⋅ s after sand therapy. (3) The low wall shear stress increased by 1.09 Pa and the high wall shear stress reached 41.47 Pa after sand therapy. (4) The time-averaged wall shear stress, shear oscillation index and relative retention time were reduced after sand therapy. CONCLUSION: The increase of blood flow velocity after sand therapy can reduce the excessive deposition of cholesterol and other substances, the decrease of erythrocyte viscosity is beneficial to the migration of erythrocytes to the vascular center, the increase of low wall shear stress has a positive effect on the prevention of atherosclerosis, and the decrease of time-averaged wall shear stress, shear oscillation index and relative retention time can reduce the occurrence of thrombosis.

Construction of residents' healthy lifestyle cognitive index system in the context of carbon peaking and carbon neutrality / 环境与职业医学

Background Healthy lifestyle is one of the important factors affecting individual health. How to promote residents' cognition of healthy lifestyle has become an urgent practical problem for the whole society. However, there is no residents' healthy lifestyle cognitive indexes available with consideration of carbon peaking and carbon neutrality. Objective To construct a cognitive index system for providing effective assessment on residents' cognition of healthy lifestyle under the background of carbon peaking and carbon neutrality. Methods Based on the health belief model, a preliminary cognitive index system of residents' healthy lifestyle under the background of carbon peaking and carbon neutrality was proposed after literature study and relevant policy review. Then three rounds of indicator importance evaluation and screening by Delphi method were conducted before the index system was finally constructed. The weights of all levels of indicators were determined using analytic hierarchy process. In addition, a self-assessment questionnaire was developed based on the index system. The questionnaire was utilized to conduct a survey among 200 residents by convenience sampling in Shenyang, Liaoning Province from November to December 2021. The survey was used to examine the reliability and validity of the indicator system. Results The effective recovery rates of the three rounds of Delphi method were all 100%. The authority coefficient was 0.84. The Kendall's W consistency test showed good expert consistency (P<0.001). Finally, a cognitive index system of residents' healthy lifestyle under the background of carbon peaking and carbon neutrality was initially constructed, including 4 first-level indicators, 8 second-level indicators, and 35 third-level indicators. Among them, the weights of the first-level indicators were 0.4541 for practice cognition, 0.2248 for benefit and obstacle cognition, 0.1626 for action clue cognition, and 0.1585 for risk cognition, respectively. The correlation coefficients between each indicator were from 0.586 to 0.977 (P<0.01). The overall Cronbach's α coefficient was 0.95, indicating high reliability. Invited experts agreed that the entries were representative and the content validity of the constructed indicator system was good. The factor analysis also showed that the structure validity was good. Conclusion The proposed index system for residents' cognition of healthy lifestyle show good reliability and validity, which can be used as an effective assessment tool for residents' healthy lifestyle cognition under the background of carbon peaking and carbon neutrality. It can provide a scientific and theoretical basis for promoting residents' cognition and practice of healthy lifestyle.

Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children / 中华儿科杂志

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Long non-coding RNA PRR7-AS1 promotes osteosarcoma progression via binding RNF2 to transcriptionally suppress MTUS1.

Introduction: Osteosarcoma is a common bone malignant tumor in adolescents with high mortality and poor prognosis. At present, the progress of osteosarcoma and effective treatment strategies are not clear. This study provides a new potential target for the progression and treatment of osteosarcoma. Methods: The relationship between lncRNA PRR7-AS1 and osteosarcoma was analyzed using the osteosarcoma databases and clinical sample testing. Cell function assays and tumor lung metastasis were employed to study the effects of PRR7-AS1 on tumorigenesis in vivo and in vitro. Potential downstream RNF2 of PRR7-AS1 was identified and explored using RNA pulldown and RIP. The GTRD and KnockTF database were used to predict the downstream target gene, MTUS1, and ChIP-qPCR experiments were used to verify the working mechanismy. Rescue experiments were utilized to confirm the role of MTUS1 in the pathway. Results: Deep mining of osteosarcoma databases combined with clinical sample testing revealed a positive correlation between lncRNA PRR7-AS1 and osteosarcoma progression. Knockdown of PRR7-AS1 inhibited osteosarcoma cell proliferation and metastasis in vitro and in vivo. Mechanistically, RNA pulldown and RIP revealed that PRR7-AS1 may bind RNF2 to play a cancer-promoting role. ChIP-qPCR experiments were utilized to validate the working mechanism of the downstream target gene MTUS1. RNF2 inhibited the transcription of MTUS1 through histone H2A lysine 119 monoubiquitin. Rescue experiments confirmed MTUS1 as a downstream direct target of PRR7-AS1 and RNF2. Discussion: We identified lncRNA PRR7-AS1 as an important oncogene in osteosarcoma progression, indicating that it may be a potential target for diagnosis and prognosis of osteosarcoma.

Indicators and medical tests to identify lower limb swelling causes after total knee arthroplasty: a Delphi study with multidisciplinary experts.

BACKGROUND: Lower limb swelling after total knee arthroplasty (TKA) hinders surgical effectiveness. The poor results of studies on swelling interventions are due to the lack of a classification of swelling causes through appropriate medical tests. A gold standard is missing. This study aimed to clarify the causes of TKA postoperative swelling and how to identify them through indicators and medical tests by consulting a wide range of experts from multiple disciplines. METHOD: The Delphi method was used. A first draft of the index was prepared based on a systematic search of the literature. A total of 11 experts from several disciplines were invited to evaluate the rationality of the indicators and suggest modifications. After two rounds of consultation, the experts reached a consensus, and the consultation was stopped. RESULTS: The response rate of the 11 experts was 100%, and the authoritative Cr was 0.896. Kendall's W values for opinion coordination of the two rounds of consultation were 0.262 and 0.226, respectively (P < 0.001). Among the final indicators, there were 4 primary indicators for swelling cause classification (inflammatory response, poor venous return, joint hematoma, muscle damage, and healing), 19 secondary and 19 tertiary indicators. CONCLUSION: The indications obtained by systematic literature review and multidisciplinary expert consultation are reliable and scientific. Multiple causes of lower extremity swelling after TKA were identified. Blood test indicators can reflect an inflammatory response, suggest poor venous return, and reflect muscle damage and healing progress. Ultrasound scans are needed to identify underlying thrombotic or valvular problems, joint hematomas, and muscle damage. These tests help clinicians and researchers determine the cause of swelling after TKA and take appropriate management.

Behavior analysis and formative assessments in online oral medicine education during the COVID-19 pandemic.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, traditional teaching methods were disrupted and online teaching became a new topic in education reform and informatization. In this context, it is important to investigate the necessity and effectiveness of online teaching methods for medical students. This study explored stomatology education in China to evaluate the development and challenges facing the field using massive open online courses (MOOCs) for oral medicine education during the pandemic. AIM: To investigate the current situation and challenges facing stomatology education in China, and to assess the necessity and effectiveness of online teaching methods among medical students. METHODS: Online courses were developed and offered on personal computers and mobile terminals. Behavioral analysis and formative assessments were conducted to evaluate the learning status of students. RESULTS: The results showed that most learners had already completed MOOCs and achieved better results. Course behavior analysis and student surveys indicated that students enjoyed the learning experience. However, the development of oral MOOCs during the COVID-19 pandemic faced significant challenges. CONCLUSION: This study provides insights into the potential of using MOOCs to support online professional learning and future teaching innovation, but emphasizes the need for careful design and positive feedback to ensure their success.

Exploring expectations of Chinese patients for total knee arthroplasty: once the medicine is taken, the symptoms vanish.

BACKGROUND: Preoperative expectations of total knee arthroplasty (TKA) outcomes are important determinants of patient satisfaction. However, expectations of patients in different countries are affected by cultural background. The general goal of this study was to describe Chinese TKA patients' expectations. METHODS: Patients scheduled for TKA were recruited in a quantitative study(n = 198). The Hospital for Special Surgery Total Knee Replacement Expectations Survey Questionnaire was used for survey TKA patients' expectations. Descriptive phenomenological design was used for the qualitative research. Semi-structured interviews were conducted with 15 TKA patients. Colaizzi's method was used for interview data analysis. RESULTS: The mean expectation score of Chinese TKA patients was 89.17 points. The 4 highest score items were walk short distance, remove the need for walker, relieve pain and make knee or leg straight. The 2 lowest score items were employed for monetary reimbursement and sexual activity. Five main themes and 12 sub-themes emerged from the interview data, including multiple factors raised expectations, expectations of physical comfort, expect various activities back to normal, hope for a long joint lifespan, and expect a better mood. CONCLUSIONS: Chinese TKA patients reported a relatively high level of expectations, and differences across cultures result in different expectation points than other national populations, requiring adjustment of items when using assessment tools across cultures. Strategies for expectation management should be further developed. LEVEL OF EVIDENCE: Level IV.

A retrospective assessment of real-world experience with venetoclax and azacitidine therapy in elderly acute myeloid leukemia.

This study aimed to examine the effect of venetoclax coupled with azacytidine in treating older adults with relapsed and refractory (R/R) acute myeloid leukemia (AML). The clinical data of 10 senior patients with AML over 65 years old who were treated with venetoclax and azacytidine, including six patients with R/R AML, were retrospectively evaluated. This study comprised seven males and three females with a median age of 71 years. Five patients had at least one relapse, and one patient did not achieve remission after four cycles of azacytidine monotherapy, considering it resistant. AML with myelodysplasia-related changes was found in four cases. One of the 10 patients died early after 1-13 cycles of venetoclax plus azacytidine treatment due to a protracted period of neutropenia and severe lung infection induced by medications. Six of the remaining nine patients, including six R/R patients, achieved a complete remission (CR) or a CR with incomplete hematologic recovery (CRi). After two cycles of therapy, one patient did not react. Neutropenia lasted an average of 10.5 (6-15) days in all patients, with the most severe cases occurring in the second and third weeks of therapy. Three patients who tested positive for the TP53 gene mutation had the following outcomes: One relapsed patient has been in progression-free remission (PFS) for the past 24 months, whereas another has been in full remission but relapsed 2 months later. Another patient experienced complete remission in myelology for 4 months, but the variable allele fraction (VAF) value steadily rose, suggesting that the illness was on the verge of progressing. IDH2 gene alterations were found in three of four patients who obtained maintained CR for more than 18 months following recurrence. Venetoclax in combination with azacytidine is a successful and well-tolerated therapy for R/R AML in the elderly. Venetoclax and azacytidine may help patients with TP53 mutations and reduce VAF. The IDH2 mutation might be a good predictor of veneclax sensitivity. A notable adverse response in the treatment phase of the regimen is severe infection induced by neutropenia.

Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.

The timing of pericardial drainage catheter removal and restart of the anticoagulation in patients suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran: Experiences from 20 cases / 中华心血管病杂志

Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.

Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro.@*METHODS@#The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1.@*RESULTS@#Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01).@*CONCLUSION@#Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.

Establishment and validation of a nomograph model for prediction of bronchopulmonary dysplasia in very low birth weight infants born earlier than 32 weeks / 中华围产医学杂志

Objective:To investigate the risk factors of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with gestational age ≤32 weeks within 28 days after birth and to establish and validate the nomogram model for BPD prediction.Methods:We retrospectively chose VLBW infants with gestational age ≤32 weeks who survived to postmenstrual age (PMA) 36 weeks and were admitted to the neonatal intensive care unit of Peking University Third Hospital from January 2016 to April 2020 as the training cohort. BPD was diagnosed in accordance with the 2018 criteria. The clinical data of these infants were collected, and the risk factors of BPD were analyzed by Chi-square test, Mann-Whitney U test, and multivariate logistic regression, and a nomogram model was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive performance. Decision curve analysis (DCA) was constructed for differentiation evaluation, and the calibration chart and Hosmer-Lemeshow goodness of fit test were used for the calibration evaluation. Bootstrap was used for internal validation. VLBW infants with gestational age ≤32 weeks survived to PMA 36 weeks and admitted to Hebei Chengde Maternal and Child Health Hospital from October 2017 to February 2022 were included as the validation cohort. ROC curve and calibration plot were conducted in the validation cohort for external validation. Results:Of the 467 premature infants included in the training cohort, 104 were in the BPD group; of the 101 patients in the external validation cohort, 16 were in the BPD group. Multivariate logistic regression analysis showed that low birth weight ( OR=0.03, 95% CI: 0.01-0.13), nosocomial pneumonia ( OR=2.40, 95% CI: 1.41-4.09), late-onset sepsis ( OR=2.18, 95% CI: 1.18-4.02), and prolonged duration of endotracheal intubation ( OR=1.61, 95% CI: 1.26-2.04) were risk factors for BPD in these groups of infants (all P<0.05). According to the multivariate logistic regression analysis results, a nomogram model for predicting BPD risk was established. The AUC of the training cohort was 0.827 (95% CI: 0.783-0.872), and the ideal cut-off value for predicted probability was 0.206, with a sensitivity of 0.788 (95% CI: 0.697-0.862) and specificity of 0.744 (95% CI: 0.696-0.788). The AUC of the validation cohort was 0.951 (95% CI:0.904-0.999). Taking the prediction probability of 0.206 as the high-risk threshold, the sensitivity and specificity corresponding to this value were 0.812 (95% CI: 0.537-0.950) and 0.882 (95% CI: 0.790-0.939). The Hosmer-Lemeshow goodness-of-fit test in the training and validation cohort showed a good fit ( P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 5%~80% for the training cohort. Conclusion:Low birth weight, nosocomial pneumonia, late-onset sepsis, and prolonged tracheal intubation duration are risk factors for BPD. The established nomogram model has a certain value in predicting the risk of BPD in VLBW less than 32 weeks.

Application of minimally invasive ultrasonic osteotome in robotic-assisted sacral tumor resection / 中华骨科杂志

Sacral tumors are surgically challenging and at a high risk of complications. In recent years, robotic-assisted resection has been gradually applied in sacral tumors, but it is difficult to remove bone tissue by present robotic instruments, which limits the application of surgical robot in sacral tumor. The present study aimed to explore the application range and therapeutic effect of minimally invasive ultrasonic osteotome in robotic-assisted sacral tumor resection. Eighteen patients underwent robotic-assisted sacral tumor resection in the First Affiliated Hospital of Sun Yat-Sen University from May 2015 to March 2021 by the Da Vinci robotic surgical system. Among them three patients who underwent osteotomy with minimally invasive ultrasonic osteotome were enrolled. There were 2 males and 1 female, aged 24, 32, 71 years, respectively. The tumors included 2 schwannomas and 1 ganglioneuroma. The operation time, bleeding volume and postoperative hospitalization days were recorded. The recurrence and complications were evaluated during follow-up. The operative time of the 3 patients was 80, 240 and 300 minutes, and the intraoperative bleeding volume was 30, 30 and 100 ml. Complete resection was performed in 2 cases and intralesional resection in 1 case. The postoperative hospital stay was 5, 3 and 7 days respectively. The follow-up time was 58, 17 and 31 months respectively. No tumor recurrence was found during the follow-up. As regards complications, only one patient had left foot pain after operation, and there were no other intraoperative or postoperative complications. The therapeutic advantages of ultrasonic osteotome combined with the Da Vinci robotic surgical system can achieve precise osteotomy, reduce intraoperative bleeding and accelerate postoperative recovery for certain patients with sacral tumors.

Long-term prognostic analysis of different treatment strategies for T 3-T 4 nasal sinus adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the prognosis and influencing factors of different treatment strategies in T 3-T 4 nasal sinus adenocarcinoma. Methods:The data of 93 cases of T 3-T 4 stage nasal sinus adenocarcinoma diagnosed from 2006 to 2018 were retrospectively analyzed. All patients were divided into combined operation group and non-operation group. The survival status and failure mode after corresponding treatment were analyzed. The enumeration data were analyzed by Chi-square test or Fisher's exact test. Survival analysis was performed by Kaplan-Meier method. Univariate analysis was conducted by log-rank test. Multivariate prognostic analysis was performed by Cox model. Results:The average follow-up time in the whole cohort was 81.3 months (18-156 months). By the end of follow-up, a total of 38.7% (36/93) of patients had local recurrence, 14.0% (13/93) had distant metastasis, 17.2% (16/93) had local recurrence complicated with distant metastasis, and 28.0% (26/93) were stable. The overall 2-, 5-, and 10-year overall survival (OS) and progression free survival (PFS) rates were 83.5%, 59.3%, 31.8% and 73.6%, 40.7% and 25.3%, respectively. In univariate analysis, the PFS and OS of patients aged 46-64 years old (all P<0.001), male ( P=0.022, P=0.001), patients with lesions located in the maxillary sinus ( P=0.001, P<0.001), adenoid cystic carcinoma ( P=0.001, P<0.001), non-invasion of orbital / clivus ( P=0.041, P<0.001), GTV P dose>64 Gy ( P=0.003, P=0.006) and N 1 stage ( P=0.014, P=0.014) were statistically different among different treatment modes. Multivariate analysis showed that age ≥65 years old ( P=0.012, P=0.005), orbital / clival invasion ( P<0.001, P=0.005), and GTV p dose ≤64 Gy ( P<0.001, P=0.011) were the independent adverse prognostic factors affecting PFS and OS in T 3-T 4 stage nasal sinus adenocarcinoma. Conclusions:The local failure rate of T 3-T 4 stage nasal sinus adenocarcinoma is high after treatment. Age, orbital / clival invasion, and GTV p dosage are the independent adverse prognostic factors. Surgery based intervention is superior to other treatment strategies.

The influence of acceptance and commitment therapy on the psychological flexibility, self-compassion, anxiety and depression of the primary caregivers of patients with primary liver cancer / 中国实用护理杂志

Objective:To explore the intervention effect of acceptance and commitment therapy on the psychological flexibility, self-compassion, anxiety and depression of the primary caregivers of patients with primary liver cancer, so as to provide reference for the clinical care of the primary caregivers of cancer patients.Methods:This was a prospective study. A total of 80 primary caregivers of patients with primary liver cancer treated in Tianyou Hospital Affiliated to Wuhan University of Science and Technology from July to December 2021 were selected as the observation objects, and they were randomly divided into the control group and the intervention group according to the random drawing method, with 40 cases in each group. The control group was given routine nursing measures, while the intervention group was given acceptance and commitment therapy on the basis of routine nursing. The intervention effect was evaluated by the Acceptance and Action Questionnaire-2nd Edition (AAQ-Ⅱ), Self-Compassion Scale Short-Form (SCS-SF) and Hospital Anxiety and Depression Scale (HADS) before the intervention, on the day of discharge, and one month after discharge.Results:Finally, 71 primary caregivers completed the intervention and follow-up, 36 in the control group and 35 in the intervention group. Before the intervention, there was no statistically significant difference in the scores of AAQ-Ⅱ, SCS-SF, Anxiety subscale of HADS(HADS-A) and Depression subscale of HADS(HADS-D) between the two groups ( P>0.05). The AAQ-Ⅱscores of the intervention group on the day of discharge and one month after discharge were (19.63±2.59), (19.12 ± 2.20) points, which were significantly lower than those of the control group (23.14 ± 2.49), (22.56 ± 2.40) points. The differences were statistically significant ( t=5.83, 6.25, both P<0.01). The SCS-SF scores of the intervention group on the day of discharge and one month after discharge were (39.34 ± 2.68), (39.89 ± 2.81) points, which were significantly higher than those of the control group (36.69 ± 3.08), (37.72 ± 2.41) points, the differences were statistically significant ( t=-3.86, -3.49, both P<0.01). The HADS-A/HADS-D scores of the intervention group on the day of discharge and one month after discharge were (9.31 ± 1.95), (9.09 ± 1.60) points and (8.80 ± 2.15), (8.54 ± 1.75) points,which were significantly lower than those of the control group(11.42 ± 1.50), (11.03 ± 1.70) points and (10.11 ± 1.92), (10.03 ± 1.84) points, the differences were statistically significant( t values were 2.71-5.10, all P<0.01). The scores of AAQ-Ⅱ, SCS-SF, HADS-A and HADS-D of the two groups were analyzed by repeated measures analysis of variance, and there were significant differences in time effect, inter-group effect and interaction effect ( F vaules were 3.42-37.90, all P<0.05). Conclusions:Acceptance and commitment therapy can improve the self-compassion and psychological flexibility, reduce anxiety and depression of the primary caregivers of patients with primary liver cancer.

Prediction of Responses of Patients with Hepatocellular Carcinoma to Anti-PD-1 Immunotherapy by T-cell Invigoration to Tumour Burden Ratio / 肿瘤防治研究

Objective To explore the predictive value of T cell activation in peripheral blood of patients with hepatocellular carcinoma(HCC) after anti PD-1 therapy and its ratio to tumor burden on the efficacy of immunotherapy. Methods Serum specimens were obtained before and after treatment from 85 patients with HCC who received anti-PD-1 treatment. Indicators such as cell subpopulations and T cell activation were detected by flow cytometry. Combined with imaging analysis, cutoff value was obtained by X-tile software. Survival analysis was used to evaluate patients' outcomes. Results The maximum fold change of Ki-67+/PD-1+/CD8+ T cells in treatment cycles and the tumor burden determined by imaging were associated with prognoses. The ratio of T cell Ki-67+/PD-1+/CD8+ expression to tumor burden ratio greater than 0.6 at the first cycle of anti-PD-1 immunotherapy was associated with improvements in progression-free survival and overall survival (P < 0.05). Conclusion The ratio of activationa in T cells in peripheral blood after immunotherapy to the tumor burden may be related to the clinical efficacy of anti-PD-1 immunotherapy for HCC.

Effects of lentinan on dendritic cell metabolism / 中国药理学通报

Aim To study the effects of lentinan(LNT)on the metabolism of dendritic cells(DCs)by metabonomics, and uncover the potential mechanism of its regulation of DC function. Methods DC2.4 cells were co-incubated with LNT for 24 h, and the activity of the cells was detected by thiazolyl blue tetrazolium bromide(MTT)assay. The contents of interleukin-6(IL-6), tumor necrosis factorα(TNF-α)and interleukin-12(IL-12)in supernatant were detected by enzyme-linked immunosorbent assay(ELISA). The metabolic general changes of DC2.4 cells were detected by Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS), and the differential metabolites were analyzed by multi-distance covariates and bioinformatics, partial least squares-discriminant analysis(PLS-DA). Finally, metabolic pathway analysis was performed by MetaboAnalyst 5.0. Results LNT did not significantly inhibit the activity of DC2.4 cells at the dose of 25100 mg·L-1. LNT(100 mg·L-1)could significantly stimulate the secretion of IL-6, TNF-α and IL-12 in DC2.4 cells. 20 differential metabolites were identified in DC2.4 cells after being stimulated by LNT(100 mg·L-1), which involved 25 metabolic pathways including urea cycle, arginine and proline metabolism. Conclusion The regulation of LNT on DC function involves a variety of amino acid metabolism.

The hippocampal proteomics mechanism of thalidomide in Alzheimer's disease model mice induced by Aβ / 中国药理学通报

Aim To observe the effect of thalidomide on the learning and memory ability and hippocampal tissue proteome of Alzheimer's disease(AD)mice,to screen the differential proteins of thalidomide in preventing and treating AD,the pathways involved in regulation,and to explore its possible mechanism. Methods The experimental mice were randomly divided into blank control group,model group,and thalidomide high and low dose groups. The drugs were administered by gavage every day for 21 days. After the administration,Morris water maze test was used to evaluate the learning and memory abilities of the mice,HE staining and Nissl staining were used to observe the pathological tissue morphology of the mouse hippocampus,ELISA was employed to detect the mitochondrial respiratory chain enzyme complex in mouse brain,and the Label-free proteomics method was used to screen different groups of hippocampal proteome proteins. Results The results of the Morris water maze showed that compared with the model group,the escape latency time of the drug group was significantly reduced,and the number of crossing the platform significantly increased(P<0.05). Thalidomide administration could improve the morphological structure of neurons in hippocampus,and could increase the activity of the mitochondrial respiratory chain complex ,Ⅱ, and of the brain tissues of AD mice(P<0.05). A total of 4 378 differential proteins were identified,which had a significant regulatory effect on the expression of 580 proteins in hippocampus of AD mice(P<0.05). Energy metabolism may jointly participate in the regulation of neurodegeneration pathways-changes in pathways such as various diseases and Alzheimer's disease. Conclusions Thalidomide can significantly improve the learning and memory function of AD model mice induced by Aβ