1.Allergy Associated With N-glycans on Glycoprotein Allergens
Yu-Xin ZHANG ; Rui-Jie LIU ; Shao-Xing ZHANG ; Shu-Ying YUAN ; Yan-Wen CHEN ; Yi-Lin YE ; Qian-Ge LIN ; Xin-Rong LU ; Yong-Liang TONG ; Li CHEN ; Gui-Qin SUN
Progress in Biochemistry and Biophysics 2024;51(5):1023-1033
Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.
2.Epidemiological characteristics of early-onset colorectal cancer: a prospective cohort study from a single center
Tian JIN ; Yingshuang ZHU ; Chengcheng LIU ; Xing XU ; Wei LU ; Qian XIAO ; Kefeng DING ; Shu ZHENG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):457-463
Objective:To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC.Methods:Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ 2 tests (categorical variates) were performed to compare differences in epidemiological features. Results:A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ 2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m 2 vs. 22.9 kg/m 2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ 2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ 2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ 2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ 2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher ( P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ 2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ 2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ 2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ 2=46.9, P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850, P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ 2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ 2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions:This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.
3.RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
WEI XINYI ; WANG CONGHUI ; TANG SANGSANG ; YANG QIAN ; SHEN ZHANGJIN ; ZHU JIAWEI ; CHENG XIAODONG ; WANG XINYU ; XIE XING ; XU JUNFEN ; LU WEIGUO
Journal of Zhejiang University. Science. B 2024;25(7):581-593,中插4-中插16
Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely unknown.To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of RAD51B-AS1.Cellular proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry assays.Mouse xenograft models were established for the detection of tumorigenesis.The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues.RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis.Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B.Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1.Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo.Thus,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B expression.RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.
4.Signal interference between drugs and metabolites in LC-ESI-MS quantitative analysis and its evaluation strategy
Jiang FULIN ; Liu JINGYU ; Li YAGANG ; Lu ZIHAN ; Liu QIAN ; Xing YUNHUI ; Zhu JANSHON ; Huang MIN ; Zhong GUOPING
Journal of Pharmaceutical Analysis 2024;14(7):1024-1034
Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.
5.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.
6.Epidemiological characteristics of early-onset colorectal cancer: a prospective cohort study from a single center
Tian JIN ; Yingshuang ZHU ; Chengcheng LIU ; Xing XU ; Wei LU ; Qian XIAO ; Kefeng DING ; Shu ZHENG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):457-463
Objective:To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC.Methods:Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ 2 tests (categorical variates) were performed to compare differences in epidemiological features. Results:A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ 2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m 2 vs. 22.9 kg/m 2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ 2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ 2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ 2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ 2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher ( P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ 2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ 2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ 2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ 2=46.9, P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850, P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ 2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ 2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions:This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.
7.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.
8.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.
9.Association of complement C3 with urine protein level and proteinuria remission status in patients with primary membranous nephropathy
Si CHEN ; Ying PAN ; Yifei LU ; Li QIAN ; Qing LI ; Yili XU ; Suyan DUAN ; Lin WU ; Bo ZHANG ; Changying XING ; Huijuan MAO ; Yanggang YUAN
Chinese Journal of Nephrology 2024;40(9):705-715
Objective:To investigate the correlation between complement C3 and urine protein level and proteinuria remission status in patients with primary membranous nephropathy (PMN), and better guide individualized clinical treatment.Methods:It was a single-center retrospective study. The clinical data of PMN patients who underwent renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2022 were collected. Patients with 24 h urinary protein ≥ 3.5 g were followed up after receiving standard treatment, and the last outpatient or inpatient review was used as the end point of follow-up. 24 h urine protein was collected to evaluate the remission status of proteinuria. Kaplan-Meier method was used to analyze the correlation between serum and renal complements and proteinuria remission. Cox regression analysis method was used to analyze the correlation between serum C3 level and renal tissue C3 deposition and proteinuria remission.Results:This study included 507 PMN patients with 312 (61.54%) males, aged 54 (43, 64) years old. Compared with 24 h urinary protein < 3.5 g group, proportion of males ( χ2=22.479, P<0.001), age ( Z=-2.521, P=0.012), systolic blood pressure ( Z=-4.148, P<0.001), diastolic blood pressure ( Z=-4.084, P<0.001), serum anti-phospholipase A2 receptor (PLA2R) antibody titer ( Z=-7.019, P<0.001), total cholesterol ( Z=-8.796, P<0.001), triglyceride ( Z=-6.158, P<0.001), low density lipoprotein cholesterol ( Z=-8.716, P<0.001), serum creatinine ( Z=-7.368, P<0.001), serum C3 ( Z=-3.663, P<0.001), serum C4 ( Z=-6.560, P<0.001), proportion of glucocorticoid use ( χ2=116.417, P<0.001) and proportion of immunosuppressant use ( χ2=53.839, P<0.001) were all higher, while serum albumin ( Z=12.518, P<0.001), estimated glomerular filtration rate ( Z=6.345, P<0.001) and serum IgG ( Z=7.321, P<0.001) were all lower in 24 h urinary protein ≥3.5 g group. There were 268 patients included in the follow-up cohort with baseline 24 h urinary protein of 7.15 (5.14, 10.24) g, serum anti-PLA2R antibody titer of 61.44 (14.35, 193.24) RU/ml, serum C3 of 1.005 (0.864, 1.150) g/L, and serum C4 of 0.260 (0.214, 0.317) g/L. Kaplan-Meier survival curve showed that the incomplete remission rate of proteinuria in serum C3 > 1.005 g/L group was lower than that in serum C3 ≤ 1.005 g/L group (log-rank χ2=4.757, P=0.029). There was no significant difference in the incomplete remission rate of proteinuria between serum C4 ≤ 0.260 g/L group and serum C4 > 0.260 g/L group (log-rank χ2=3.543, P=0.060). Renal C1q (log-rank χ2=0.167, P=0.683) and C4 (log-rank χ2=1.927, P=0.165) deposition had no significant effects on proteinuria remission in PMN patients. The incomplete remission rate of proteinuria in patients with renal C3 deposition was higher than that in patients without renal C3 deposition (log-rank χ2=7.018, P=0.008). Univariate Cox regression analysis showed that serum C3 level and C3 deposition in renal tissues were influencing factors of incomplete remission of proteinuria (both P<0.05), while adjusting for gender, age, mean arterial pressure, serum anti-PLA2R antibody, serum albumin and 24 h urinary protein, serum C3 ≤ 1.005 g/L ( HR=1.374, 95% CI 1.021-1.849, P=0.036), C3 deposition in renal tissues ( HR=1.949, 95% CI 1.098-3.460, P=0.023), and serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues ( HR=1.472, 95% CI 1.093-1.983, P=0.011) were independent influencing factors of incomplete remission of proteinuria. Conclusions:The serum C3 level and C3 deposition in renal tissues are closely related to urinary protein level and proteinuria remission status in PMN patients. The patients with higher urinary protein have higher serum C3. For patients with massive proteinuria, serum C3 ≤ 1.005 g/L, C3 deposition in renal tissues, serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues are independent risk factors of incomplete remission of proteinuria.
10.Compositional Analysis and Antitumor Activity of Aqueous Extracts of Polygonatum Cyrtonema Hua
Lu SONG ; Chunye GENG ; Chenyu XING ; Qian WANG ; Yaoyao GUO ; Yanjun CHEN ; Fang WANG ; Guosi LI ; Wei WANG ; Leilei GAO ; Dong LIU ; Bangxing HAN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(7):952-962
Objective To analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P<0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P<0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P<0.01,P<0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P<0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.

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