1.Development and validation of a prognostic nomogram model for patients with the lower third and abdominal oesophageal adenocarcinoma
Zhengshui XU ; Dandan LIU ; Jiantao JIANG ; Ranran KONG ; Jianzhong LI ; Yuefeng MA ; Zhenchuan MA ; Jia CHEN ; Minxia ZHU ; Shaomin LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):201-207
Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.
2.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
3.Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism.
Dandan XIAO ; Wenguang CHANG ; Xiang AO ; Lin YE ; Weiwei WU ; Lin SONG ; Xiaosu YUAN ; Luxin FENG ; Peiyan WANG ; Yu WANG ; Yi JIA ; Xiaopeng TANG ; Jianxun WANG
Acta Pharmaceutica Sinica B 2025;15(3):1589-1607
Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER T2 /Parkin fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.
4.Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer.
Dandan LING ; Xueli JIA ; Ke WANG ; Qiucheng YAN ; Bochuan YUAN ; Lina DU ; Miao LI ; Yiguang JIN
Acta Pharmaceutica Sinica B 2024;14(1):365-377
Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.
5.Current Situation, Challenges and Suggestions for the Development of Primary Health Care Services in China in the Post Pandemic Era
Dandan KE ; Nan JIA ; Puan CUI ; Zhong HE
Medical Journal of Peking Union Medical College Hospital 2024;15(1):45-51
Primary health care institutions should be the main force of China's medical and health service system and the cornerstone of the national health care system. During the COVID-19 pandemic, China's primary health care institutions played a critical role, but many deficiencies and weaknesses were also highlighted. Through systematic literature search and analysis, this article finds that China's primary health care institutions have some problems such as low demand for patient care, weak integration of the health system, weak service foundation, and insufficient emergency response capacity for public health emergencies. Accordingly, we put forward a strategy for the construction of primary health care institutions based on the "Three Forces Theory", which aims to improve the primary medical and health care service system, upgrade the capacity of primary medical and health care services, and better fulfill the strategic goal of "Healthy China 2030".
6.Using allostatic load as a tool for evaluating aging of male SD rats and the intervention effects of Zuogui Pill
Yuxin JIA ; Xiaohong DENG ; Leifeng SUN ; Dandan CHEN ; Xianjun SUN ; Xiaohong DUAN ; Shikai YAN ; Jianhua HUANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(6):753-761
Objective Using the concept of allostatic load(AL)to evaluate aging of male SD rats and the effectiveness of Zuogui Pill in naturally aging rats.Methods Naturally aging male SD rats were tested at the ages of 2,5,8,14,18,and 21 months.They were divided into an elderly control group,low-dose Zuogui Pill group,and high-dose Zuogui Pill group.Intervention with Zuogui Pill was trialed for 3 months.Blood samples were taken from the tails of rats each month,and the number of T lymphocytes and rate of apoptosis were measured by flow cytometry.Low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),triglycerides(TG),total cholesterol(TC),free fatty acids(FFA),25 hydroxyvitamin D(25-OH-D),corticosterone(CORT),C-reactive protein(CRP),and interleukin-6(IL-6)were detected in rat sera.By identifying the collinearity between indicators and professional considerations,LDL-c,TC,HDL-c,FFA,TG,CORT,IL-6,CRP,25-OH-D,CD3+T cell count,and CD3+T cell apoptosis rate were included in the AL scoring.The threshold for each indicator was established with data from 5-month-old rats,and the score was 1 point below or/and above the threshold.Results The serum levels of LDL-c,TG,TC,25-OH-D,CRP,and IL-6 of rats showed significant changes with age,although the patterns of change differed.The CD3+T lymphocyte count significantly decreased with age(P<0.01),while the apoptosis rates of CD3+,CD4+,and CD8+T lymphocytes significantly increased with age(P<0.01).Zuogui Pill significantly increased serum CORT levels in elderly rats(P<0.01)and reduced the apoptosis rate of CD8+T lymphocytes(P<0.05).The AL score began to increase in rats at 5 months of age and reached its peak in those of 18 months of age.Conclusions AL can better characterize the aging process compared to a single indicator.Zuogui Pill can improve the stress response ability of aging rats and alleviate immunosenescence.
7.The diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system in adult goiter
Zexu ZHANG ; Zongyu YUE ; Honglei XIE ; Yue SU ; Haowen PAN ; Jia LI ; Wenjing CHE ; Xin HOU ; Meng ZHAO ; Lanchun LIU ; Dandan LI ; Xian XU ; Weidong LI ; Fangang MENG ; Lijun FAN ; Lixiang LIU ; Ming LI ; Peng LIU
Chinese Journal of Endemiology 2024;43(11):922-927
Objective:To study the diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system (hereinafter referred to as intelligent ultrasound system) in adult goiter.Methods:In June 2022 and March 2023, two phases of thyroid disease survey were carried out in 4 cities in Anhui Province. One village was selected in each city, and 250 adults were selected as survey subjects in each village. Adult bilateral thyroid area was scanned by both intelligent ultrasound system and conventional ultrasound scanning equipment, and the effectiveness of intelligent ultrasound system in the diagnosis of goiter was analyzed based on the results of conventional ultrasound examination. Receiver operating characteristic (ROC) curve was drawn, and Kappa test was used to analyze the consistency between intelligent ultrasound system and conventional ultrasound examination in the diagnosis of goiter. At the same time, Spearman correlation analysis and Bland-Altman method were used to evaluate the consistency of the two methods in measuring thyroid volume.Results:After screening and removing outliers and missing values, a total of 910 adults were included, including 253 males (27.80%) and 657 females (72.20%). The age was (45.92 ± 10.20) years old, ranging from 18 to 60 years old. The sensitivity, specificity, and accuracy of the intelligent ultrasound system for diagnosing adult goiter were 80.00%, 99.67%, and 99.56%, respectively. The area under the ROC curve (AUC) was 0.996, which was consistent with the results of conventional ultrasound examination for diagnosing goiter ( κ = 0.67, P < 0.001). After controlling for variables such as gender, thyroid function, and thyroid nodules, the intelligent ultrasound system showed good consistency with conventional ultrasound examination in the diagnosis of goiter in females, adults with thyroid dysfunction, and adults without thyroid nodules ( κ = 0.66, 0.80, 0.80, P < 0.001). The consistency in the diagnosis of goiter in adults with thyroid nodules was moderate ( κ = 0.56, P < 0.001). Spearman correlation analysis showed a highly positive correlation between the measurement results of adult thyroid volume by intelligent ultrasound system and conventional ultrasound examination ( r = 0.88, P < 0.001). The Bland-Altman method results showed that only 4.62% (42/910) of points in adults were outside the 95% consistency limit, indicating good consistency between intelligent ultrasound system and conventional ultrasound examination in measuring thyroid volume (< 5%). The proportion of points outside the 95% consistency limit in males, adults with thyroid dysfunction, and adults with thyroid nodules was 6.72% (17/253), 5.83% (12/206), and 6.45% (12/186), respectively. Conclusions:The intelligent ultrasound system has certain diagnostic value for adult goiter and has good consistency with conventional ultrasound examination for thyroid volume measurement. However, the accuracy of diagnosis for males and adults with thyroid nodules still needs to be improved.
8.Improvement of image quality in portal vein dual-low CT venography with CE-Boost technique
Dandan NIU ; Yuqing SUN ; Nannan SUN ; Yancui BI ; Min ZHANG ; Ying LI ; Zhuangfei MA ; Shouqiang JIA
Journal of Practical Radiology 2024;40(6):990-993
Objective To explore the image quality improvement of portal vein computed tomography venography(CTV)using CE-Boost technique with low dose and low contrast media usage.Methods A total of 50 patients with suspected portal vein disorders who underwent abdominal non-contrast and biphasic contrast-enhanced CT scans using the Canon 320-row CT machine were retrospectively selected.Images of portal venous phase(PVP)were postprocessed with CE-Boost technique.The CT values of each area,standard deviation(SD)values of the paraspinal muscles,volume CT dose index(CTDIvol),and dose length product(DLP)before and after CE-Boost were measured and recorded.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),effective dose(ED)of each blood vessel before and after CE-Boost were calculated.Subjective image quality was analyzed by two senior radiologists using a five-point scale in a double-blinded method.Statistical analysis was performed using paired t-test and Wilcoxon test.Results The CT values of each area with CE-Boost images were significantly higher than those without CE-Boost images(P<0.001).SNR and CNR of each blood vessel with CE-Boost images were significantly higher than those without CE-Boost images(P<0.001).The subjective scores of both images were above 3 points,which met the requirements of clinical diagnosis with good consistency(Kappa=0.772,0.697).The median subjective scores of images with CE-Boost were 5(5,5),which were significantly higher than those without CE-Boost images 5(5,4),(P=0.002).CTDIvol,DLP and ED were(1.85±1.12)mGy,(94.66±44.68)mGy·cm and(1.42±0.67)mSv,respectively.Conclusion CE-Boost technique can significantly improve the image quality of portal vein CTV with low dose and low contrast media usage.
9.The relationship between comorbidity factors and in-hospital mortality in patients with carbapenem-resistant Klebsiella pneumoniae pneumonia
Yan WANG ; Jia CUI ; Dandan WANG ; Chunyue GE ; Yunjian HU ; Xiaoman AI
Chinese Journal of Preventive Medicine 2024;58(11):1705-1710
This study aimed to explore the relationship between comorbidity factors and in-hospital mortality related to factors in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia. This study collected clinical data from 218 patients with CRKP pneumonia in Beijing hospital from November 2011 to December 2023, analyzed the number of comorbidities carried by CRKP pneumonia patients, comorbidity patterns, Charlson Comorbidity Index (CCI) scores, and comorbidity of underlying diseases, and explored the relationship between various indicators and comorbidity factors and in-hospital mortality in CRKP pneumonia patients. The Ward.D cluster analysis was performed on the comorbidities of patients and used to draw heatmaps. Using a multiple logistic regression model, a nomogram model was constructed to predict in-hospital mortality in patients with CRKP pneumonia. This study included 218 patients with CRKP pneumonia. The results showed that there were significant differences in the age ( P=0.003), comorbidities such as heart failure ( P<0.001), arrhythmia ( P=0.002), chronic liver disease ( P=0.003), chronic kidney disease ( P=0.002), CCI score ( P=0.007), total number of comorbidities ( P<0.001), and comorbidity patterns (respiratory/immune/psychiatric disease patterns and cardiovascular/tumor/metabolic disease patterns, P=0.003) between the survival and death groups of CRKP pneumonia patients. The multiple logistic regression showed that cardiovascular/tumor/metabolic disease patterns ( P=0.030), CCI score ( P=0.040), concomitant heart failure ( P=0.011), and concomitant arrhythmia ( P=0.025) were independent risk factors for in-hospital mortality in patients with CRKP pneumonia. The nomogram model for predicting the risk of in-hospital mortality in patients with CRKP pneumonia, constructed based on the identified risk factors, had an area under the ROC curve of 0.758. Both the ROC curve and validation curve indicated that the nomogram model had stable performance in predicting in-hospital mortality in patients with CRKP pneumonia. In summary, comorbidity factors are risk factors for predicting in-hospital mortality in patients with CRKP pneumonia, and the role of comorbidity factors in in-hospital mortality in patients with CRKP pneumonia should be taken seriously.
10.The relationship between comorbidity factors and in-hospital mortality in patients with carbapenem-resistant Klebsiella pneumoniae pneumonia
Yan WANG ; Jia CUI ; Dandan WANG ; Chunyue GE ; Yunjian HU ; Xiaoman AI
Chinese Journal of Preventive Medicine 2024;58(11):1705-1710
This study aimed to explore the relationship between comorbidity factors and in-hospital mortality related to factors in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia. This study collected clinical data from 218 patients with CRKP pneumonia in Beijing hospital from November 2011 to December 2023, analyzed the number of comorbidities carried by CRKP pneumonia patients, comorbidity patterns, Charlson Comorbidity Index (CCI) scores, and comorbidity of underlying diseases, and explored the relationship between various indicators and comorbidity factors and in-hospital mortality in CRKP pneumonia patients. The Ward.D cluster analysis was performed on the comorbidities of patients and used to draw heatmaps. Using a multiple logistic regression model, a nomogram model was constructed to predict in-hospital mortality in patients with CRKP pneumonia. This study included 218 patients with CRKP pneumonia. The results showed that there were significant differences in the age ( P=0.003), comorbidities such as heart failure ( P<0.001), arrhythmia ( P=0.002), chronic liver disease ( P=0.003), chronic kidney disease ( P=0.002), CCI score ( P=0.007), total number of comorbidities ( P<0.001), and comorbidity patterns (respiratory/immune/psychiatric disease patterns and cardiovascular/tumor/metabolic disease patterns, P=0.003) between the survival and death groups of CRKP pneumonia patients. The multiple logistic regression showed that cardiovascular/tumor/metabolic disease patterns ( P=0.030), CCI score ( P=0.040), concomitant heart failure ( P=0.011), and concomitant arrhythmia ( P=0.025) were independent risk factors for in-hospital mortality in patients with CRKP pneumonia. The nomogram model for predicting the risk of in-hospital mortality in patients with CRKP pneumonia, constructed based on the identified risk factors, had an area under the ROC curve of 0.758. Both the ROC curve and validation curve indicated that the nomogram model had stable performance in predicting in-hospital mortality in patients with CRKP pneumonia. In summary, comorbidity factors are risk factors for predicting in-hospital mortality in patients with CRKP pneumonia, and the role of comorbidity factors in in-hospital mortality in patients with CRKP pneumonia should be taken seriously.

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