Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

【Objective】 To explore the diagnosis, treatment and prognosis of renal cell carcinoma (RCC) patients with Stauffer syndrome. 【Methods】 The clinicopathological and follow-up data of 17 RCC patients with Stauffer syndrome who underwent operation during Sep.2014 and Aug.2019 were retrospectively analyzed. The survival was analyzed with Kaplan-Meier curve and log-rank, and related factors affecting the prognosis were determined with univariate and multivariate Cox regression model. 【Results】 The pathological results included clear cell RCC in 14 cases, papillary RCC in 2 cases, and poorly differentiated tissue in 1 case. The liver function recovered within 3 months after operation in 5 cases, within 6 months in 3 cases, within 1 year in 4 cases, and did not recover in 3 cases. During the follow up of 6 to 72 (average 54.1) months, the 1-, 3-, and 5-year survival rates were 88.2% (15/17), 76.5% (13/17) and 52.9% (9/17), respectively. Survival analysis showed that the cancer-specific survival (CSS) of RCC patients with Stauffer syndrome was low, and tumor size, AJCC stage, lymph node metastasis and Stauffer syndrome were predictors of poor prognosis. 【Conclusion】 The prognosis of RCC patients with Stauffer syndrome is poor, and early surgical intervention should be conducted. The liver function of most patients can return to normal gradually after surgery. Continuous examination of liver function has significant meaning for tumor recurrence, metastasis and prognosis.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

To compare the performance of generalized additive model (GAM) and long short-term memory recurrent neural network (LSTM-RNN) on the prediction of daily admissions of respiratory diseases with comorbid diabetes. Daily data on air pollutants, meteorological factors and hospital admissions for respiratory diseases from Jan 1st, 2014 to Dec 31st, 2019 in Beijing were collected. LSTM-RNN was used to predict the daily admissions of respiratory diseases with comorbid diabetes, and the results were compared with those of GAM. The evaluation indexes were calculated by five-fold cross validation. Compared with the GAM, the prediction errors of LSTM-RNN were significantly lower [root mean squared error (RMSE): 21.21±3.30 vs. 46.13±7.60, <0.01; mean absolute error (MAE): 14.64±1.99 vs. 36.08±6.20, <0.01], and the value was significantly higher (0.79±0.06 vs. 0.57±0.12, <0.01). In gender stratification, RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting female admission (all <0.05), but there were no significant difference in predicting male admission between two models (all >0.05). In seasonal stratification, RMSE and MAE of LSTM-RNN were lower than those of GAM in predicting warm season admission (all <0.05), but there was no significant difference in value (>0.05). There were no significant difference in RMSE, MAE and between the two models in predicting cold season admission (all >0.05). In the stratification of functional areas, the RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting core area admission (all <0.05). has lower prediction errors and better fitting than the GAM, which can provide scientific basis for precise allocation of medical resources in polluted weather in advance.
Beijing/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Hospitalization ; Humans ; Male ; Memory, Short-Term ; Neural Networks, Computer

Objective:To explore the influencing and prognosis factors of emphysematous urinary tract infection (EUTI).Methods:The baseline clinical data of the patients admitted to Shandong University Qilu Hospital (Qingdao) from December 2013 to June 2020 and diagnosed with EUTI were analyzed retrospectively. The patients with non-EUTI (NEUTI) during the same period were selected as the control group. The baseline characteristics between the two groups were compared. Logistic regression analysis method was used to analyze the influencing factors of EUTI.Results:(1) 24 EUTI patients and 53 NEUTI patients were included in the present study. Compared with the NEUTI group, the hemoglobin level was lower ( t=-5.245, P<0.001) and the levels of blood urine nitrogen ( Z=-4.361, P<0.001), serum creatinine (Scr, Z=-4.543, P<0.001), blood glucose ( Z=-2.608, P=0.009), and triacylglycerol ( Z=-2.408, P=0.016) were higher in the EUTI group. The proportions of diabetes mellitus ( χ2=13.453, P<0.001) and chronic kidney disease ( χ2=17.936, P<0.001) in the EUTI group were higher than those in the NEUTI group. Increasing Scr was the risk factor of EUTI in patients with urinary tract infection ( OR=1.011, 95% CI 1.001-1.020, P=0.025). (2) Escherichia coli ( E.coli, 14 cases, 58.3%) was the most common causative organism. The other causative organisms included Klebsiella pneumoniae (2 cases, 8.3%), Enterococcus faecium (1 case, 4.2%), Pantoea (1 case, 4.2%), and mixed bacteria of E.coli and Enterococcus faecium (1 case, 4.2%). Ten cases of E.coli were extended-spectrum β-lactamases (ESBL)-positive. (3) Of the 24 patients with EUTI, 4 patients had adverse outcomes. The length of stay ( Z=-2.457, P=0.014), blood urea nitrogen ( t=2.432, P=0.024), shock ( P=0.002), autoimmune disease ( P=0.022), and white blood cell count ( Z=-2.091, P=0.036) were statistically different between good prognosis group ( n=20) and poor prognosis group ( n=4). However, logistic regression analysis results showed that neither was the influencing factor of poor prognosis of EUTI. Conclusions:The elevated Scr level is the independent influencing factor of EUTI among urinary infection patients. E.coli is the most common pathogenic bacteria, and ESBL-positive bacteria are common.

Background Zinc is a trace element essential for normal fetal heart development, and excess zinc can be toxic. The relationship between maternal and fetal zinc levels and the development of congenital heart disease (CHD) in the offspring is unclear. Objective To study the effects of maternal and neonatal zinc exposure levels on the risk of developing CHD in the offspring. Methods The data and biological samples of the study subjects were derived from the birth cohort established by Gansu Provincial Maternity and Child Care Hospital in Lanzhou from 2010 to 2012. Questionnaire surveys were conducted at baseline in the first trimester and at follow-up visits in the second trimester, the third trimester, and 42 d after delivery. Maternal venous blood during the third trimester and neonatal umbilical venous blood at delivery were collected, and information on their birth outcomes was extracted from medical records. Ninety-seven children with CHD diagnosed by echocardiography at birth and confirmed at the follow-up after 42 d were selected as the case group, and 194 healthy full-term infants were selected as the control group, 1∶2 matched for maternal age and geographical location from the database. The zinc concentrations in whole blood of pregnant mothers and umbilical cord blood of fetuses in both groups were measured by inductively coupled plasma mass spectrometry. According to the quartiles P₂₅ and P₇₅ of zinc levels in the whole blood of pregnant mothers and neonatal cord blood in the control group, zinc exposure was divided into three groups: low, medium, and high. After adjusting for maternal vaginal bleeding in early pregnancy, pre-pregnancy folic acid and vitamin supplementation, birth weight, and umbilical cerclage confounders, a multiple conditional logistic regression model was applied to analyze the associations between maternal whole blood and fetal umbilical cord blood zinc levels and the risk of CHD in the offspring, and a further subgroup analysis was performed by disease classification. Results The medians (P₂₅, P₇₅) of maternal whole blood zinc levels in the case group and the control group were 5.034 (3.456, 6.644) and 4.693 (3.411, 5.646) mg·L⁻¹, respectively, with significant differences between the two groups (P=0.029). The medians (P_25, P₇₅) of neonatal cord blood zinc level was 2.153 (1.479, 2.405) mg·L⁻¹ in the case group and 1.636 (1.304, 1.979) mg·L⁻¹ in the control group, with significant differences between the two groups (P<0.001). The zinc levels of maternal whole blood and neonatal cord blood in the simple CHD group were significantly higher than those in the control group (P<0.05). The multiple conditional logistic regression model showed that compared with the maternal medium zinc exposure level group (3.41-5.65 mg·L⁻¹), the risk of offspring CHD was 2.225 times of the high exposure level group (>5.65 mg·L⁻¹) (OR=2.225, 95%CI: 1.017-4.868). Compared with the neonatal medium zinc exposure level group (1.30-1.98 mg·L⁻¹), the neonatal high exposure level group (>1.98 mg·L⁻¹) also had an increased risk of CHD (OR=4.132, 95%CI: 1.801-9.480). The subgroup analysis results showed that compared with corresponding medium exposure level groups, the risk of simple CHD in the offspring of the maternal high zinc exposure level group was increased (OR=4.081, 95%CI: 1.427-11.669), and the risks of simple CHD (OR=7.122, 95%CI: 2.126-23.854) and complex CHD (OR=5.165, 95%CI: 1.859-14.346) of neonates of the neonatal high zinc exposure level group were increased. Conclusion Under the exposure levels of the study population, high concentrations of zinc exposure in pregnant mothers and neonates may be associated with the incidence of CHD.

BACKGROUND: Aurora kinases (AURKs) family plays a vital role not only in cell division but also in tumorigenesis. However, there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer (BC). Systematic bioinformatics analysis was conducted to explore the biological role, prognostic value, and immunologic function of AURKs family in BC. METHODS: The expression, prognostic value, and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals: ONCOMINE Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, Metascape, GeneMANIA, and LinkedOmics; and the result was verified using human tissues. RESULTS: The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage (all P   <  0.05). BC patients with high AURKA and AURKB expression had a worse overall survival, relapse-free survival, and distant metastasis-free survival (all P   <  0.05). Verification experiment revealed that AURKA and AURKB were upregulated in BC ( P  < 0.05). AURKA and AURKB were specifically associated with several tumor-associated kinases (polo-like kinase 1 and cyclin-dependent kinase 1), miRNAs (miR-507 and miR-381), and E2F transcription factor 1. Moreover, AURKA and AURKB were correlated with immune cell infiltration. Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway, platinum drug resistance signaling pathway, ErbB signaling pathway, Hippo signaling pathway, and nucleotide-binding and oligomerization domain-like receptor signaling pathway. CONCLUSIONS Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.
Humans ; Female ; Aurora Kinase A/metabolism* ; Aurora Kinase B/metabolism* ; Prognosis ; Breast Neoplasms/genetics* ; Neoplasm Recurrence, Local ; MicroRNAs

To implement the fundamental task of the Ministry of Education on carrying out curriculum ideological and political education and promoting colleges and universities to implement the morality education, this study tried to carry out ideological and political education for medical students in "medical functional science experimental course", and organically integrated the ideological and political elements of "loving experimental animals and reverencing for life" into the teaching of this course. This paper explored the implementation process and effect evaluation of ideological and political courses from the aspects of teaching objects, design, objectives, in-class and off-class practical activities, and analyzed the current problems and future directions. In order to provide beneficial ideas for the ideological and political construction of college curriculum and help cultivate excellent and innovative medical talents with warmth and feelings.

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.