Critical Values of Daily Sedentary Time and Its Longitudinal Association with Mild Cognitive Impairment Considering APOE ε4: A Prospective Cohort Study.

BACKGROUND: Long sedentary time and physical inactivity are negatively related to cognition, but the cut-off value remains unclear, and apolipoprotein E polymorphism ε4 (APOE ε4) is a known genetic risk factor of mild cognitive impairment (MCI). OBJECTIVES: To explore longitudinal association of sedentary time and MCI, and to identify a cutoff value that increases the risk of developing MCI, taking into account APOE ε4 stratification and its interactions. DESIGN: A prospective cohort study. SETTING: Population-based study. PARTICIPANTS: We included 4932 older adults from Tianjin Elderly Nutrition and Cognition (TENC) cohort study recruited from March 2018 to June 2021 with 3.11 years of median follow-up time. MEASUREMENTS: The primary outcome was newly diagnosed MCI, which was diagnosed by a modified version of the Petersen's criteria. The information of sedentary time (hours/day) and physical activity (MET-h/week) were obtained by questionnaire. Cox proportional hazard regression models and restricted spline curve were conducted. RESULTS: A total of 4932 participants were included (mean [SD] age, 67.85 [4.96] years; 2627 female [53.3%] and 2305 male [46.7%]), 740 newly onset MCI patients were identified. Longer sedentary time was associated with higher risk of MCI for all participants (HR:1.069, 95%CI: 1.034, 1.105), especially in APOE ε4 non-carriers (HR:1.083, 95%CI: 1.045, 1.123) whether adjusted potential confounders. Sedentary time had synergistic interactions with APOE ε4 (ß:1.503, 95%CI: 1.163, 1.942) and physical activities (ß: 1.495, 95%CI: 1.210, 1.846). Restricted spline curve showed a cut-off value of 3.03 hours/day. CONCLUSIONS: Long sedentary time (≥3.03 hours/day) could increase MCI risk, especially in APOE ε4 non-carriers, people with higher PA, aged 65 and above.

Identification of potential candidate genes for the Houyan trait in developing Wulong goose embryos by transcriptomic analysis.

1. The Wulong goose is a Chinese breed and a source of high-quality meat and eggs. A characteristic of the Wulong goose is that a proportion of the birds do not have eyelids, known as the Huoyon trait.2. Wulong geese exhibiting the Huoyan trait at embryonic stages of 9 days (E9), 12 days (E12) and 14 days (E14) were selected alongside those with normal eyelids for comprehensive transcriptome sequencing. Differentially expressed gene (DEG) and functional enrichment analyses were performed and finally, eight DEG were chosen to verify the accuracy of qPCR sequencing.3. Overall, 466, 962 and 550 DEG were obtained from the three control groups, D9 vs. N9, D12 vs. N12 and D14 vs. N14, respectively, by differential analysis (p < 0.05). CDKN1C, CRH, CROCC and TYSND1 were significantly expressed in the three groups. Enrichment analysis revealed the enrichment of CROCC and TYSND1 in pathways of cell cycle process, endocytosis, microtubule-based process, microtubule organising centre organisation, protein processing and protein maturation. CDKN1C and CRH were enriched in the cell cycle and cAMP signalling pathway.4. Some collagen family genes were detected among the DEGs, including COL3A1, COL4A5, COL4A2 and COL4A1. FREM1 and FREM2 genes were detected in both Huoyan and normal eyelids. There was a significant difference (p < 0.01) in FREM1 expression between ED9 and ED14 in female embryos, but this difference was not observed in male embryos.

[α2-macroglobulin alleviates glucocorticoid-induced avascular necrosis of the femoral head in mice by promoting proliferation, migration and angiogenesis of vascular endothelial cells].

OBJECTIVE: To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. METHODS: In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX; 10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. RESULTS: In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). CONCLUSION: A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

[Therapeutic potential of EAE mice with sodium oligomannate and effects of intestinal flora and microglia polarization].

Objective: To investigate the therapeutic effect of sodium oligomannate on experimental autoimmune encephalomyelitis (EAE) mice and its effect on intestinal flora and microglia polarization. Methods: Fifty female C57BL/6 mice were randomly divided by the random number table method into the control group, EAE model group and low-dose, medium-dose and high-dose group of sodium oligomannate with 10 mice each. The EAE model group and each dose group of sodium oligomannate were induced by subcutaneous multi-point injection of MOG35-55 peptide for the EAE model. Mice in the low-dose, medium-dose and high-dose group of sodium oligomannate were gavaged sodium oligomannate 40, 80, and 160 mg/kg twice a day, respectively, starting from the day after modeling. The intervention continued until the mice were euthanized. Observe the incidence of disease, infiltration of inflammatory cells in spinal cord tissue, and demyelination in each group of mice.. The mice feces were collected and tested for intestinal flora by 16S rRNA sequencing. Immunofluorescence staining was used to observe the expression of Iba-1 protein, an activation indicator of microglia, in spinal cord tissue. The protein levels of M1 type markers iNOS, CD16, and M2 type markers Arg1 and CD206 were tsested in the spinal cord by Western blotting and immunofluorescence staining. Results: None of the mice in the control group developed any disease, while the mice in other groups showed varying degrees of disease, including tail sag, unstable walking, and hind limb weakness. Compared with the EAE model group, the incubation period was prolonged, the peak was delayed and the peak neurological dysfunction score was reduced (3.6±0.6 vs 3.0±0.6, 2.8±0.5, 1.8±0.6, P<0.05) in all sodium oligomannate groups, with milder symptoms at higher doses. The differences in pairwise comparisons between the groups were all statistically significant (all P<0.05). In the control group, no inflammatory cell infiltration or demyelinating changes were observed in spinal cord tissue. In the EAE model group, inflammatory cell infiltration and demyelination changes were evident in the spinal cord tissues at the onset peak. Compared with the EAE model group, inflammatory cell infiltration and demyelination were ameliorated in all sodium oligomannate groups. Compared with the control group, the relative abundance of Bacteroidota decreased and that of Firmicutes increased in the EAE model group. Compared with the EAE model group, the relative abundance of Bacteroidota increased and that of Firmicutes decreased, the ratio of Bacteroidetes to Firmicutes increased (0.20±0.05 vs 0.37±0.02,0.61±0.03,0.91±0.08,P<0.01) in the respective dose groups. The difference in pairwise comparison between groups was statistically significant (P<0.01), with greater changes at higher doses. Compared with the control group, the levels of Iba-1、CD16 and iNOS increased, while the levels of Arg-1 and CD206 decreased in the EAE model group. Compared with the EAE model group, the levels of Iba-1、CD16 and iNOS decreased, while the levels of Arg-1 and CD206 increased in all sodium oligomannate groups(P<0.01), with greater changes at higher doses. The difference between groups was statistically significant (P<0.01). Conclusions: Sodium oligomannate has a therapeutic effect on EAE and is dose-dependent. Its mechanism of action may be related toimproving intestinal microecology and the modulation of microglial polarization.

[Retrospective analysis of diagnosis and treatment of tuberculosis in designated medical institutions in China from 2017 to 2022].

Objective: To understand the status of tuberculosis diagnosis and treatment capacity and the development and changes of tuberculosis diagnosis and treatment in provincial and municipal designated medical institutions in China from 2017 to 2022, so as to provide a basis for the formulation of relevant policies for the improvement and development of designated medical institutions for tuberculosis and the tuberculosis prevention and treatment service system, and to provide reasonable support for further strengthening the capacity of designated medical institutions for tuberculosis. Methods: This study was initiated and carried out by Beijing Chest Hospital affiliated to Capital Medical University/Clinical Center for Tuberculosis Prevention and Control of China CDC (hereinafter referred to as "Clinical Center") by means of questionnaire survey, and the investigation was carried out from March to November 2023. During this period, the clinical center distributed questionnaires to the hospital member units of "Beijing Tuberculosis Diagnosis and Treatment Technology Innovation Alliance", retrospectively collected their tuberculosis-related diagnosis and treatment data from 2017 to 2022, and used descriptive statistical methods to analyze the number of tuberculosis beds, outpatients and hospitalizations in medical institutions. The results were expressed in absolute numbers (percentages), and three-line tables, bar charts and line charts were drawn to describe the analysis results and changing trends. Results: The 54 medical institutions surveyed in this survey included 21 provincial-level designated medical institutions and 33 prefecture-level designated medical institutions. Most medical institutions have set up clinical departments, auxiliary departments and functional departments to undertake public health tasks of infectious diseases. The tuberculosis laboratory in the hospital has a comprehensive ability and has the detection technology needed for most tuberculosis diagnosis; The number of tuberculosis beds, children's tuberculosis beds and ICU beds all showed an increasing trend from 2017 to 2022. The proportion of tuberculosis beds in the hospital decreased slightly, from 39.31% in 2017 to 34.76% in 2022, showing a slight downward trend. Compared with the hospital surveyed, the number of tuberculosis outpatients in 2019 was 562 029, and the number of outpatients in 2020-2022 was 462 328, 519 630 and 424 069 respectively, which was significantly lower than that in 2019. The number of tuberculosis outpatients in medical institutions decreased significantly from 2020 to 2022. By analyzing the proportion of patients with different types of tuberculosis, the proportion of sensitive tuberculosis outpatients in 2017-2022 decreased from 84.49% in 2017 to 78.05% in 2022, showing a downward trend year by year. The proportion of patients with multidrug-resistant/ rifampin-resistant tuberculosis increased from 2.03% in 2017 to 7.18% in 2022. From 2017 to 2019, the total number of inpatients with tuberculosis showed an upward trend. Compared with 2019, the number of inpatients in 2020, 2021 and 2022 showed a downward trend, and the decline in 2020 was large (down 14.94% compared with 2019). Among the inpatients, the absolute number and proportion of patients with sensitive pulmonary tuberculosis remained relatively stable, and the number and proportion of inpatients with multidrug-resistant/rifampin-resistant pulmonary tuberculosis increased year by year. Conclusions: Most medical institutions have the capacity to carry out routine diagnosis and treatment of tuberculosis, but the public health function needs to be strengthened. The transformation of medical institutions requires proper guidance and adequate support. During 2019-2022, most medical institutions were affected by the COVID-19 epidemic, and their tuberculosis diagnosis and treatment work also changed to varying degrees. During this period, hospitals took various measures to overcome difficulties and tried their best to maintain the normal development of tuberculosis diagnosis and treatment, and the tuberculosis diagnosis and treatment work of various institutions gradually resumed in 2022.

Microstructural, Micromechanical Atlas of the Temporomandibular Joint Disc.

The temporomandibular joint (TMJ) disc is mainly composed of collagen, with its arrangement responding to efficient stress distribution. However, microstructural and micromechanical transformations of the TMJ disc under resting, functional, and pathological conditions remain unclear. To address this, our study presents a high-resolution microstructural and mechanical atlas of the porcine TMJ disc. First, the naive microstructure and mechanical properties were investigated in porcine TMJ discs (resting and functional conditions). Subsequently, the perforation and tear models (pathological conditions) were compared. Following this, a rabbit model of anterior disc displacement (abnormal stress) was studied. Results show diverse microstructures and mechanical properties at the nanometer to micrometer scale. In the functional state, gradual unfolding of the crimping cycle in secondary and tertiary structures leads to D-cycle prolongation in the primary structure, causing tissue failure. Pathological conditions lead to stress concentration near the injury site due to collagen interfibrillar traffic patterns, resulting in earlier damage manifestation. Additionally, the abnormal stress model shows collagen damage initiating at the primary structure and extending to the superstructure over time. These findings highlight collagen's various roles in different pathophysiological states. Our study offers valuable insights into TMJ disc function and dysfunction, aiding the development of diagnostic and therapeutic strategies for TMJ disorders, as well as providing guidance for the design of structural biomimetic materials.

[Clinical characteristics and prognosis analysis of 17 cases of SMARCA4-deficient chest tumors].

Objective: To analyze the clinical characteristics and prognosis of 17 patients with pathologically confirmed SMARCA4-deficient chest tumors. Methods: Seventeen patients with SMARCA4-deficient thoracic tumors diagnosed by pathology in the Affiliated Hospital of Jining Medical University from September 2021 to January 2023 were collected through Results Query System of Pathology Department, and the patients' general conditions, clinical symptoms, tumor markers, imaging features, treatment and regression were retrospectively analyzed, and literature review was performed. Results: A total of 17 patients were included in this study. Their clinical characteristics were characterized as follows: male/female=16/1, age 42-74 years, mean (64.0±5.7)years. Only 1 female had no clear smoking history, and 16 males had a smoking history, of whom 1 had 5 smoking pack-years, and the remaining 15 case had a smoking history of 20-100 smoking pack-years, with a mean of (68.5±44.5) smoking pack-years. Clinical symptoms were mainly cough and sputum, followed by chest tightness, hemoptysis and chest pain. Tumor markers CYFRA19-9 was elevated in 9 cases (3.79-16.61 ng/ml), CEA was elevated in 8 cases (5.37-295.93 ng/ml), and NSE was elevated in 6 cases (17.18-70.37 ng/ml). Imaging manifestations were intrapulmonary or mediastinal mass shadows, and the tumor involved the mediastinum in 9 cases, the upper lobe of the right lung in 6 cases, the upper lobe of the left lung in 5 cases, the lower lobe of the right lung in 3 cases, the lower lobe of the left lung in 3 cases; cervical or supraclavicular lymph node metastasis in 8 cases, pleural metastasis in 4 cases, hepatic metastasis in 3 cases, cerebral metastasis in 3 cases, bone metastasis in 2 cases, and subcutaneous metastasis in 1 case. Combining immuno-histochemistry and pathology, there were 6 cases of SMARCA4-deficient NSCLC and 11 cases of SMARCA4-deficient undifferentiated tumor. Eight patients were treated with platinum-contained chemotherapy agents, four of which were combined with immune checkpoint inhibitors, and one was treated with enzatinib; only one of the 9 patients achieved partial remission after treatment, and the remaining eight had progression of the tumors on chest CT after treatment. Five patients abandoned the treatment, and died in 6-month of follow-up. Three patients underwent surgery for resection, and there was no significant progression in the three patients in the 6 months of follow-up. Conclusions: Clinically, middle-aged and elderly men with a history of heavy smoking should be given high priority, especially in patients whose imaging mostly showed intrapulmonary, especially in upper lobes, and/or mediastinal masses, rapid lesion progression, and early distant metastasis, and who should be alerted to the possibility of SMARCA4-deficient thoracic tumors. Late clinical stage is a high risk factor for poor overall patient survival, and platinum-containing chemotherapy agents combined with immune checkpoint inhibitor therapy may be effective, and early surgery may improve patient prognosis.

[Diagnostic value of whole blood cell parameters logistic regression model for radiation injury on radiation workers].

Objective: To explore the diagnostic value of whole blood cell parameters logistic regression model for radiation injury on radiation workers by comparing the differences of whole blood cell parameters between occupational radiation injury population and occupational health examination population. Methods: In February 2023, 184 radiation workers who received occupational health examinations in our hospital and occurrenced chromosome aberration from July 2021 to July 2022 were retrospectively selected as the radiation injury group. And other 184 radiation workers encountered in the same period without chromosome aberration occurrence were selected as the control group. Collected whole blood cell parameters from two groups of research subjects, conducted comparative analysis, constructed a logistic regression model, and evaluated the diagnostic value of the logistic regression model for radiation injury on radiation workers by receiver operating characteristic curve (ROC) and area under curve (AUC) . In addition, with the same standard, 60 radiation workers with chromosome aberration and 60 radiation workers without chromosome aberration from August 2022 to January 2023 were included in the validation queue to validate the logistic regression model. Results: Neu_X, Neu_Y, Neu_Z, Lym_X, Lym_Y, Lym_Z, Mon_X, Mon_Y, Mon_Z, Micro, MCHC in the radiation injury group were significantly higher than those in the control group, and the difference was statistically significant (P<0.05) . And MCV and Macro in the radiation injury group were lower than those in the control group, and the difference was statistically significant (P<0.05) . Moreover, logistic regression analysis showed that Lym_X, Lym_Y, Lym_Z, MCHC, Micro were all independent risk factors for diagnosing radiation injury on radiation workers (OR=1.08、1.02、0.99、1.06、51.32, P<0.05) . ROC curve analysis showed that the AUC, sensitivity, specificity, and accuracy of the logistic regression model based by Lym_X, Lym_Y, Lym_Z, MCHC and Micro in diagnosing radiation injury on radiation workers were 0.80, 85.9%, 65.8% and 75.9% respectively. The validation queue verified the logistic regression model and the AUC, sensitivity, specificity, and accuracy of the logistic regression model were 0.80, 81.7%, 71.7% and 76.7% respectively, the model fitted well. Conclusion: Radiation damage can cause changes in multiple whole blood cell parameters of radiation workers. The logistic regression model based by Lym_X, Lym_Y, Lym_Z, MCHC and Micro showed good diagnosis ability and can be used for the screening of radiation injury on radiation workers.

[Epidemiological characteristics and genotype trends of rotavirus diarrhea in China from 2009 to 2020].

Objective: To investigate the epidemiological characteristics and genotype trends of rotavirus infection among the population with diarrhea in China, from 2009 to 2020 and provide evidence for strategic surveillance and prevention. Methods: Surveillance data on diarrhea syndrome from 252 sentinel hospitals across 28 provinces (municipalities, autonomous regions) were obtained from the information management system of the Infectious Disease Surveillance Technology Platform of the National Science and Technology Major Project. Descriptive epidemiological methods were employed to analyze the distribution of rotavirus diarrhea cases in different climatic zones, populations, and times from 2009 to 2020, as well as the genotyping characteristics and changing trends of group A rotavirus diarrhea cases. Results: From 2009 to 2020, a total of 114 606 diarrhea cases were tested for rotavirus, and the positive rate was 19.1% (21 872/114 606); group A rotavirus was dominant (98.2%, 21 471/21 872). The positive rate of rotavirus was the highest in 2009 (36.9%, 2 436/6 604) and 2010 (30.6%, 5 130/16 790), fluctuated between 14.0% to 18.0% from 2011 to 2017, raised slightly in 2018 (20.3%, 2 211/10 900), and declined continuously in the following two years (15.5%, 2 262/14 611 and 9.5%, 470/4 963). The positive rate of males (20.2%, 13 660/67 471) was significantly higher than that of females (17.4%, 8 212/47 135). Children under five had the highest positive rate (28.4%, 18 261/64 300), more than four times that of adults. The positive rate peaked from December to February in the mediate temperate zone, warm temperate zone, and subtropical zone, while there were two peaks from November to January and May to June in the frigid zone of the plateau. The dominant genotype of group A rotavirus gradually changed from G3P[8] and G1P[8] to G9P[8] during 2009-2020. Conclusions: The overall rotavirus infection rate in China was on a downward trend. Meanwhile, significant variations of positive rates were observed in seasonal epidemics and different age groups from 2009 to 2020. Rotavirus diarrhea in children was still a prominent concern. Vaccination of rotavirus vaccine should be promoted, and the epidemiological characteristics and genotypes of rotavirus diarrhea should be continuously monitored.

Standardization of a silver stain to reveal mesoscale myelin in histological preparations of the mammalian brain.

BACKGROUND: The brain is built of neurons supported by myelin, a fatty substance that improves cellular communication. Noninvasive magnetic resonance imaging (MRI) is now able to measure brain structure like myelin and requires histological validation. NEW METHOD: Here we present work in small and large biomedical model mammals to standardize a silver impregnation method as a high-throughput histological myelin visualization procedure. Specifically, we built a new staining well plate to increase batch size, and then systematically varied the staining and clearing cycles to describe the staining response curve across taxa and conditions. We compared tissues fixed by immersion or perfusion, mounted versus free-floating, and cut as thicker or thinner slices, with two-weeks of post-fixation. RESULTS: The staining response curves show optimal staining with a single exposure across taxa when incubation and clearing epochs are held to within 3-9 min. We show that clearing was slower in mounted vs free-floating tissue, and that staining was faster and caused fracturing earlier in thinner sliced and smaller volumes of tissue. COMPARISON WITH EXISTING METHODS: We developed a batch processing approach to increase throughput while ensuring reproducibility and demonstrate the optimal conditions for fine myelinated fiber morphology visualization with short cycles (<9 minutes). CONCLUSIONS: We present our optimized protocol to reveal mesoscale neuroanatomical myelin content in histology across mammals. This standard staining procedure will facilitate multiscale analyses of myelin content across development as well as in the presence of injury or disease.

[Real-time localization for port-implanted catheter tip by echocardiographic guidance].

The clinical data of 23 patients undergoing real-time echocardiography-guided infusion port implantation in the Breast Center of Tsinghua Changgung Hospital in Beijing from January to July 2021 were analyzed. The length of catheter insertion L1 was initially estimated using surface measurement method in all patients. Intraoperatively, transthoracic echocardiography was applied using the parasternal four-chamber view to visualize the catheter image within the right atrium, and the length of catheter insertion L2 was recorded under the guidance of echocardiography. Postoperatively, chest radiographs were taken in the upright position to observe the position of the catheter tip. According to chest CT scans, the ideal length (L) for catheter tip placement was calculated when it was located at the junction of superior vena cava and right atrium. Bland-Altman scatter plot analysis and linear regression fitting test were used on L1 and L2 respectively with L to evaluate the consistency. A total of 23 patients were included in this study, among which one case of left breast cancer patient undergoing breast-conserving surgery had difficulty in identifying the catheter tip position due to residual pleural effusion obscuring the imaging of the cardiac apex four-chamber view. In 22 patients, the results of intraoperative ultrasound imaging were good, including 1 case of catheter ectopic to azygos vein, and 21 cases of right atrial catheter could be detected by ultrasound. Statistical analysis showed that there was a good consistency between L1 and L, L2 and L, and the difference between them was d=0.28 cm (95%CI:-1.76-2.31 cm) and d=0.20 cm(95%CI:-0.84-1.23 cm), respectively, with no statistical significance (P>0.05). In the linear regression model, L2 and L had a higher fit than L1, and the difference was statistically significant (R²=0.954, P<0.001). This study found that real-time echocardiographic localization technique can be applied in adult port surgery to replace X-ray-guided real-time catheter tip detection and adjustment to the optimal position.

[Analysis of factors influencing the efficacy and prognosis of surgical treatment for primary malignant pelvic bone tumors].

Objective: To analyze the prognostic factors and the influence of surgical margin to prognosis. Methods: A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models. Results: There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection (P＜0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection (P＜0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection (P＜0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions: The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.

[Efficacy analysis of 7 cases of mixed neuroendocrine-nonneuroendocrine neoplasm of the duodenal papilla].

The clinical data of 7 patients diagnosed with mixed neuroendocrine-nonneuroendocrine neoplasm were analyzed in the Department of Hepatobiliary Surgery of Hunan Provincial People's Hospital from January 2016 to December 2022. Among the 7 patients, 5 were male and 2 were female, with an average age of 59.3 years. Its clinical characteristics are similar to malignant ampulla tumors, and it is difficult to differentiate them. The preoperative puncture biopsy positivity rate is low, making it difficult to diagnose preoperatively, and the prognosis is worse.Comprehensive treatment including surgery, chemotherapy, and radiotherapy can be the preferred treatment option for this disease.

A high-density and high-confinement tokamak plasma regime for fusion energy.

The tokamak approach, utilizing a toroidal magnetic field configuration to confine a hot plasma, is one of the most promising designs for developing reactors that can exploit nuclear fusion to generate electrical energy1,2. To reach the goal of an economical reactor, most tokamak reactor designs3-10 simultaneously require reaching a plasma line-averaged density above an empirical limit-the so-called Greenwald density11-and attaining an energy confinement quality better than the standard high-confinement mode12,13. However, such an operating regime has never been verified in experiments. In addition, a long-standing challenge in the high-confinement mode has been the compatibility between a high-performance core and avoiding large, transient edge perturbations that can cause very high heat loads on the plasma-facing-components in tokamaks. Here we report the demonstration of stable tokamak plasmas with a line-averaged density approximately 20% above the Greenwald density and an energy confinement quality of approximately 50% better than the standard high-confinement mode, which was realized by taking advantage of the enhanced suppression of turbulent transport granted by high density-gradients in the high-poloidal-beta scenario14,15. Furthermore, our experimental results show an integration of very low edge transient perturbations with the high normalized density and confinement core. The operating regime we report supports some critical requirements in many fusion reactor designs all over the world and opens a potential avenue to an operating point for producing economically attractive fusion energy.

[High expression of UBE2S promotes progression of hepatocellular carcinoma by increasing cancer cell stemness].

OBJECTIVE: To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma (HCC) microenvironment and its impact on proliferation and stemness of HCC cells. METHODS: TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC. Specific expression patterns of UBE2S, intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website. We further examined UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells using immunohistochemistry and immunofluorescence staining. We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay. RESULTS: Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues (P < 0.001), and its transcriptional level increased with tumor grades. The methylation level of UBE2S promoter was significantly decreased in HCC (P < 0.001), and its transcription level increased obviously in HCC with TP53 mutation (P < 0.001). Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues (P < 0.001). Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis (P < 0.001). Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells, epithelial cells and fibroblasts in HCC microenvironment. Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells. In HCC-LM3 and HepG2 cells, UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation (P < 0.05). CONCLUSION: UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis. High UBE2S expression promotes the stemness of HCC cells.

The factors influencing the occurrence of post-ischemic stroke depression and its relationship with the burden score of cerebral small vessel disease.

OBJECTIVE: This study explored the determinants of post-stroke depression (PSD) in ischemic stroke (AIS) patients and its association with the burden score of cerebral small vessel disease (CSVD). PATIENTS AND METHODS: We analyzed 374 AIS patients treated between January 2020 and January 2022. Patients were categorized into 90 with PSD and 284 without PSD, enabling an investigation into PSD risk factors and the CSVD-PSD relationship. RESULTS: There was no significant difference in health factors between PSD and non-PSD patients (p>0.05). However, significant disparities were noted in age, gender, initial Barthel Index (BI), Mini-Mental State Examination (MMSE) score, plasma fibrinogen, homocysteine, red cell distribution width, National Institutes of Health Stroke Scale (NIHSS) score, and CSVD burden score (p<0.05). Regression analysis indicated that these variables were pivotal PSD predictors (OR>1, p<0.05). Surprisingly, a positive correlation with PSD occurrence was found for age, NIHSS score, plasma fibrinogen, homocysteine levels, red cell distribution width, CSVD burden score (r=0.565, 0.615, 0.482, 0.514, 0.572, 0.608, respectively; p<0.05). Meanwhile, the MMSE score and BI index were inversely related to PSD onset (r=-0.604, -0.590; p<0.05). The ROC curve analysis of the combination model based on MMSE, NIHSS and CSVD score revealed an AUC of 0.926 and Youden's index of 0.744. CONCLUSIONS: Age, MMSE score, BI index, NIHSS score, plasma fibrinogen concentration, homocysteine level, red blood cell distribution width, and CSVD burden score are all major influencing factors in the occurrence of PSD. The combination model based on MMSE, NIHSS, and CSVD scores presented a valuable approach to predicting PSD.

[Clinical outcome of posterior lumbar interbody fusion combined with Ponte osteotomy for reconstruction of coronal sagittal plane balance in degenerative scoliosis].

Objective: To evaluate the clinical efficacy of posterior lumbar interbody fusion combined with Ponte osteotomy in the treatment of patients with degenerative scoliosis. Methods: The medical records and imaging data of degenerative scoliosis in department of orthopedics, Peking Union Medical College Hospital from 2013 to 2022 were retrospectively collected, and the shortest follow-up time was 1 year. A total of 38 patients were included, including 13 males and 25 females, aged 50-87(65.6±10.9) years old.The follow-up was12-119(43±20) months. Standing position full spine anteroposterior lateral X-ray examinations were performed on all patients preoperatively, postoperatively, and at latest follow-up. The length of hospital stay, complications, operation time, blood loss, instrumented segment, fusion segmen were recorded. The clinical scores and coronasagittal imaging indicators at three time points were compared. Results: The operation time was (274.5±70.5)min, and intraoperative blood loss was (619.2±93.5)ml. The coronal vertical axis was improved from (2.9±1.8)cm preoperatively to (1.2±1.0)cm postoperatively. The preoperative coronal Cobb angle was 16.6°±9.9° and the immediate postoperative correction was 6.4°±4.0°(t=-6.83, P<0.001). The difference was statistically significant (t=-6.12, P<0.001). The coronal Cobb Angle at the last follow-up was 5.7°±3.7°, and there was no significant orthopaedic loss at the last follow-up (t=-6.12, P<0.001).The sagittal vertical axis decreased from (5.6±3.9)cm preoperatively to (3.2±2.5) cm immediately after operation (t=-6.83,P<0.001), and was well maintained at the last follow-up[(2.7±1.8) cm,t=-7.77,P<0.001]. Lumbar lordosis increased from 21.8°±10.2° preoperatively to 35.8°±8.3° postoperatively(t=12.01, P<0.001)and 40.1°±8.6° at last follow-up(t=-10.21, P<0.001). Oswestry disability score (ODI score), visual analogue score (VAS) low back pain score and VAS leg pain score were also lower after surgery than before surgery (all P<0.05). Conclusion: Posterior lumbar interbody fusion combined with Ponte osteotomy can significantly improve the coronal and sagittal plane deformity and postoperative functional score in adult patients with degenerative scoliosis.

[Primary cardiac synovial sarcoma: a clinicopathological analysis of five cases].

Objective: To assess the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of primary cardiac synovial sarcoma (PCSS). Methods: Five cases of PCSS were collected at Guangdong Provincial People's Hospital from 2008 to 2023, and their clinicopathological features were summarized. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and relevant literatures were reviewed. Results: The cases were found in four males and one female, ranging in ages from 16 to 51 years (median 30 years). Two cases were located in the pericardium, two in the right ventricle, and one in the left ventricle. Follow-up data were available in four cases. All the four patients died of disease at 3, 7, 13 and 26 months, respectively, after diagnosis. The tumor maximum diameter ranged from 6.0 to 14.0 cm in (mean 10.0 cm). Microscopically, three cases were monophasic and two cases were biphasic. Immunohistochemically, all cases were immunoreactive for EMA, vimentin, bcl-2 and CD56. The tumor cells were variably positive for pan-cytokeratin, SS18-SSX, SOX2, TLE1, CD99, synaptophysin, calretinin and calponin. FISH showed the presence of SS18 rearrangement in all the cases. NGS detected SS18-SSX gene fusion in three cases (SS18-SSX1 in one and SS18-SSX2 in two). Conclusions: PCSS is an exceedingly rare neoplasm, and should be distinguished from other various malignant epithelial and mesenchymal tumors. The clinical history, histopathological and immunohistochemical features, and molecular findings are all essential to the definitive diagnosis of PCSS.