1.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
2.Co-infection of Chlamydia pneumoniae and SARS-CoV-2 and its effect on the secretion of inflammatory cytokines
Jia-Yan LI ; Li-Ping YUAN ; Qing-Kai LUO ; Ye-Fei LEI ; Yuan LI ; Feng-Hua ZHANG ; Li-Xiu PENG ; Yu-Qi OUYANG ; Shi-Xing TANG ; Hong-Liang CHEN
Chinese Journal of Infection Control 2024;23(11):1391-1397
Objective To explore characteristics of co-infection of Chlamydia pneumoniae(Cpn)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and identify their effect on SARS-CoV-2-induced inflammatory response.Methods Patients with coronavirus disease 2019(COVID-19)who received treatment in a hospital in Chenzhou City from December 20,2022 to February 20,2023 were selected.According to the severity of COVID-19,severe and critical cases were classified as the severe symptom group,while mild and moderate cases were classified as the mild symptom group.Meanwhile,according to the age of patients(≥18 years old as adults,<18 years old as juveniles),they were divided into the adult severe symptom group,adult mild symptom group,juvenile severe symptom group,and juvenile mild symptom group.Propensity score was adopted to match age,gender,and under-lying diseases of patients in severe symptom and mild symptom group in a 1∶1 ratio.Bronchoalveolar lavage fluid(BALF),throat swabs,and serum specimens of patients were collected.Cpn IgG/IgM antibody was detected by enzyme-linked immunosorbent assay(ELISA),levels of 12 common cytokines(including interleukin-8[IL-8])in BALF were detected by flow cytometry,differences among groups were compared.Results A total of 102 patients were included,with 61 severe and critical(severe symptom)patients,as well as 41 mild and moderate(mild symp-tom)patients.There were 71 patients aged ≥18 years and 31 juvenile patients aged<18 years.There were 39 pa-tients in the adult severe symptom group and 32 in the adult mild symptom group,and 30 pairs were successfully matched through propensity score analysis.There were 22 patients in the juvenile severe symptom group and 9 in the juvenile mild symptom group,and 8 pairs were successfully matched through propensity score analysis.Among COVID-19 patients,the positive rates of Cpn IgG and IgM were 36.27%(n=37)and 8.82%(n=9),respective-ly,with 1 case positive for both Cpn IgG and IgM.The level of interferon(IFN)-α in serum specimens from adult patients with severe symptom combined with positive Cpn IgG was higher than that of IgG negative patients(P=0.037).There was no statistically significant difference in the levels of other cytokines in BALF and serum speci-mens between the two groups of patients(all P>0.05).The levels of IL-8 and IL-17 in serum specimens of patients with positive Cpn IgG in the adult mild symptom group were both higher than those in Cpn IgG negative patients(both P<0.05).The levels of IL-8 in both BALF and serum specimens from Cpn IgM positivity patients in the ju-venile mild symptom group were higher than those from patients with negative Cpn IgM(both P<0.05).Logistic regression analysis results showed that Cpn IgG and IgM positivity were not risk factors for the development of se-vere COVID-19.Conclusion Combined Cpn infection is not a risk factor for the development of severe symptom in COVID-19 patients,and Cpn infection has limited impact on the secretion of inflammatory factors caused by SARS-CoV-2.
3.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
4.Study of phenylpropanoids from Tripterygium hypoglaucum
Zhi-qi LIN ; Hong-bo ZHU ; Tang ZHOU ; Ji WANG ; Rong-ping ZHANG ; Xing-long CHEN
Acta Pharmaceutica Sinica 2024;59(6):1730-1740
This paper aimed to study phenylpropanoids of
5.The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis.
Si Jin ZHONG ; Jun Jun GAO ; Ping TANG ; Yue Ping LIU ; Shu Lian WANG ; Hui FANG ; Jing Ping QIU ; Yong Wen SONG ; Bo CHEN ; Shu Nan QI ; Yuan TANG ; Ning Ning LU ; Hao JING ; Yi Rui ZHAI ; Ai Ping ZHOU ; Xin Gang BI ; Jian Hui MA ; Chang Ling LI ; Yong ZHANG ; Jian Zhong SHOU ; Nian Zeng XING ; Ye Xiong LI
Chinese Journal of Oncology 2023;45(2):175-181
Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans
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Aged
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Treatment Outcome
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Retrospective Studies
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Combined Modality Therapy
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Chemoradiotherapy/methods*
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Urinary Bladder Neoplasms/radiotherapy*
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Neoplasm Staging
6.Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China.
Hui XI ; Qin LIU ; Dong Hua XIE ; Xu ZHOU ; Wang Lan TANG ; De Guo TANG ; Chun Yan ZENG ; Qiong WANG ; Xing Hui NIE ; Jin Ping PENG ; Xiao Ya GAO ; Hong Liang WU ; Hao Qing ZHANG ; Li QIU ; Zong Hui FENG ; Shu Yuan WANG ; Shu Xiang ZHOU ; Jun HE ; Shi Hao ZHOU ; Fa Qun ZHOU ; Jun Qing ZHENG ; Shun Yao WANG ; Shi Ping CHEN ; Zhi Fen ZHENG ; Xiao Yuan MA ; Jun Qun FANG ; Chang Biao LIANG ; Hua WANG
Biomedical and Environmental Sciences 2023;36(2):127-134
OBJECTIVE:
This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.
METHODS:
We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.
RESULTS:
The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.
CONCLUSION
Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans
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beta-Thalassemia/genetics*
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alpha-Thalassemia/genetics*
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Hemoglobinopathies/genetics*
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China/epidemiology*
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High-Throughput Nucleotide Sequencing
7.Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version).
Wei-An YUAN ; Jun-Hua ZHANG ; Jian-Ping LIU ; Zhong-Qi YANG ; Jun-Ling CAO ; Xing LIAO ; Xiao-Yu XI ; Mei HAN ; Wen-Yuan LI ; Zhen-Wen QIU ; Shi-Yin FENG ; Yuan-Yuan GUO ; Lu-Jia CAO ; Xiao-Hong LIAO ; Yan-Ling AI ; Ju HUANG ; Lu-Lu JIA ; Xiang-Fei SU ; Xue WU ; Ze-Qi DAI ; Ji-Hua GUO ; Bing-Qing LU ; Xiao-Xiao ZHANG ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2023;48(1):256-264
Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional
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Nonprescription Drugs
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Consensus
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China
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Reference Standards
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Drugs, Chinese Herbal
8.Free PSA performs better than total PSA in predicting prostate volume in Chinese men with PSA levels of 2.5-9.9 ng ml-1.
Ma-Ping HUANG ; Ping TANG ; Cliff S KLEIN ; Xing-Hua WEI ; Wei DU ; Jin-Gao FU ; Tian-Hai HUANG ; Hui CHEN ; Ke-Ji XIE
Asian Journal of Andrology 2023;25(1):82-85
This study investigated whether free prostate-specific antigen (fPSA) performs better than total PSA (tPSA) in predicting prostate volume (PV) in Chinese men with different PSA levels. A total of 5463 men with PSA levels of <10 ng ml-1 and without prostate cancer diagnosis were included in this study. Patients were classified into four groups: PSA <2.5 ng ml-1, 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1. Pearson/Spearman's correlation coefficient (r) and receiver operating characteristic (ROC) curves were used to evaluate the ability of tPSA and fPSA to predict PV. The correlation coefficient between tPSA and PV in the PSA <2.5 ng ml-1 cohort (r = 0.422; P < 0.001) was markedly higher than those of the cohorts with PSA levels of 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1 (r = 0.114, 0.167, and 0.264, respectively; all P ≤ 0.001), while fPSA levels did not differ significantly among different PSA groups. Area under ROC curve (AUC) analyses revealed that the performance of fPSA in predicting PV ≥40 ml (AUC: 0.694, 0.714, and 0.727) was better than that of tPSA (AUC = 0.545, 0.561, and 0.611) in men with PSA levels of 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1, respectively, but not at PSA levels of <2.5 ng ml-1 (AUC: 0.713 vs 0.720). These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the ''gray zone'' (PSA levels of 2.5-9.9 ng ml-1), but its performance was similar to that of tPSA at PSA levels of <2.5 ng ml-1.
Male
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Humans
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Prostate-Specific Antigen
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Prostate
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East Asian People
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Prostatic Neoplasms/diagnosis*
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ROC Curve
9.Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.
Zekai WU ; Yuan SHI ; Yueli CUI ; Xin XING ; Liya ZHANG ; Da LIU ; Yutian ZHANG ; Ji DONG ; Li JIN ; Meijun PANG ; Rui-Ping XIAO ; Zuoyan ZHU ; Jing-Wei XIONG ; Xiangjun TONG ; Yan ZHANG ; Shiqiang WANG ; Fuchou TANG ; Bo ZHANG
Protein & Cell 2023;14(5):350-368
Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans
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Mice
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Rats
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Cell Proliferation
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Heart/physiology*
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Mammals
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Myocardial Infarction/metabolism*
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Myocytes, Cardiac/metabolism*
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Pericardium/metabolism*
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Single-Cell Analysis
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Zebrafish/metabolism*
10.Mechanism of Wuling Capsules against hepatic fibrosis based on network pharmacology and animal experiments.
Nan LI ; Su-Juan REN ; Rui ZHOU ; Zhong-Xing SONG ; Yan-Ru LIU ; Zhi-Shu TANG ; Jian-Ping ZHOU ; Zhao-Jun CAO
China Journal of Chinese Materia Medica 2023;48(19):5365-5376
The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.
Animals
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Rats
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Interleukin-6
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Network Pharmacology
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Animal Experimentation
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Tumor Necrosis Factor-alpha
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Molecular Docking Simulation
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Liver Cirrhosis/genetics*
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Medicine, Chinese Traditional
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Capsules
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Class I Phosphatidylinositol 3-Kinases
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Collagen
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Drugs, Chinese Herbal/pharmacology*

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