1.Transcriptome sequencing reveals molecular mechanism of seed dormancy release of Zanthoxylum nitidum.
Chang-Qian QUAN ; Dan-Feng TANG ; Jian-Ping JIANG ; Yan-Xia ZHU
China Journal of Chinese Materia Medica 2025;50(1):102-110
The transcriptome sequencing based on Illumina Novaseq 6000 Platform was performed with the untreated seed embryo(DS), stratified seed embryo(SS), and germinated seed embryo(GS) of Zanthoxylum nitidum, aiming to explore the molecular mechanism regulating the seed dormancy and germination of Z. nitidum and uncover key differentially expressed genes(DEGs). A total of 61.41 Gb clean data was obtained, and 86 386 unigenes with an average length of 773.49 bp were assembled. A total of 29 290 DEGs were screened from three comparison groups(SS vs DS, GS vs SS, and GS vs DS), and these genes were annotated on 134 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways. KEGG enrichment analysis revealed that the plant hormone signal transduction pathway is the richest pathway, containing 226 DEGs. Among all DEGs, 894 transcription factors were identified, which were distributed across 34 transcription factor families. These transcription factors were also mainly concentrated in plant hormone signal transduction and mitogen-activated protein kinase(MAPK) signaling pathways. Further real-time quantitative polymerase chain reaction(RT-qPCR) validation of 12 DEGs showed that the transcriptome data is reliable. During the process of seed dormancy release and germination, a large number of DEGs involved in polysaccharide degradation, protein synthesis, lipid metabolism, and hormone signal transduction were expressed. These genes were involved in multiple metabolic pathways, forming a complex regulatory network for dormancy and germination. This study lays a solid foundation for analyzing the molecular mechanisms of seed dormancy and germination of Z. nitidum.
Zanthoxylum/metabolism*
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Plant Dormancy/genetics*
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Seeds/metabolism*
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Gene Expression Regulation, Plant
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Plant Proteins/metabolism*
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Transcriptome
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Gene Expression Profiling
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Germination
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Transcription Factors/metabolism*
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Plant Growth Regulators/genetics*
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Signal Transduction
2.Discovery of highly potent phosphodiesterase-1 inhibitors by a combined-structure free energy perturbation approach.
Zhe LI ; Mei-Yan JIANG ; Runduo LIU ; Quan WANG ; Qian ZHOU ; Yi-You HUANG ; Yinuo WU ; Chang-Guo ZHAN ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2024;14(12):5357-5369
Accurate receptor/ligand binding free energy calculations can greatly accelerate drug discovery by identifying highly potent ligands. By simulating the change from one compound structure to another, the relative binding free energy (RBFE) change can be calculated based on the theoretically rigorous free energy perturbation (FEP) method. However, existing FEP-RBFE approaches may face convergence challenges due to difficulties in simulating non-physical intermediate states, which can lead to increased computational costs to obtain the converged results. To fundamentally overcome these issues and accelerate drug discovery, a new combined-structure RBFE (CS-FEP) calculation strategy was proposed, which solved the existing issues by constructing a new alchemical pathway, smoothed the alchemical transformation, increased the phase-space overlap between adjacent states, and thus significantly increased the convergence and accelerated the relative binding free energy calculations. This method was extensively tested in a practical drug discovery effort by targeting phosphodiesterase-1 (PDE1). Starting from a PDE1 inhibitor (compound 9, IC50 = 16.8 μmol/L), the CS-FEP guided hit-to-lead optimizations resulted in a promising lead (11b and its mesylate salt formulation 11b-Mesylate, IC50 = 7.0 nmol/L), with ∼2400-fold improved inhibitory activity. Further experimental studies revealed that the lead showed reasonable metabolic stability and significant anti-fibrotic effects in vivo.
3.Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment.
Wen-Tao JIA ; Shuang XIANG ; Jin-Bo ZHANG ; Jia-Ying YUAN ; Yu-Qian WANG ; Shu-Fang LIANG ; Wan-Fu LIN ; Xiao-Feng ZHAI ; Yan SHANG ; Chang-Quan LING ; Bin-Bin CHENG
Journal of Integrative Medicine 2024;22(6):696-708
OBJECTIVE:
Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown.
METHODS:
Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR.
RESULTS:
JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment.
CONCLUSION
JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709.
Exosomes/drug effects*
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Animals
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Carcinoma, Hepatocellular/genetics*
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Drugs, Chinese Herbal/pharmacology*
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Liver Neoplasms/pathology*
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Tumor Microenvironment/drug effects*
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Mice
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Humans
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Cell Line, Tumor
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Mice, Inbred BALB C
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Neoplasm Metastasis
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Male
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Mice, Nude
4.Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice.
Mei ZHANG ; Yong ZHANG ; Qian XU ; Joshua CRAWFORD ; Cheng QIAN ; Guo-Hua WANG ; Jiang QIAN ; Xin-Zhong DONG ; Mikhail V PLETNIKOV ; Chang-Mei LIU ; Feng-Quan ZHOU
Neuroscience Bulletin 2023;39(10):1512-1532
The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.
Animals
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Mice
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Enhancer of Zeste Homolog 2 Protein/metabolism*
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Histone Methyltransferases/metabolism*
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Histones/genetics*
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Morphogenesis
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Neuronal Plasticity
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Neurons/metabolism*
5.Reinforced radiculoplasty for the treatment of symptomatic sacral Tarlov cysts: A clinical analysis of 71 cases.
Chao WU ; Bin LIU ; Jing Cheng XIE ; Zhen Yu WANG ; Chang Cheng MA ; Jun YANG ; Jian Jun SUN ; Xiao Dong CHEN ; Tao YU ; Guo Zhong LIN ; Yu SI ; Yun Feng HAN ; Su Hua CHEN ; Xiao Liang YIN ; Qian Quan MA ; Mu Tian ZHENG ; Lin ZENG
Journal of Peking University(Health Sciences) 2023;55(1):133-138
OBJECTIVE:
To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs).
METHODS:
A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery.
RESULTS:
In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred.
CONCLUSION
For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.
Humans
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Tarlov Cysts/epidemiology*
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Retrospective Studies
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Neoplasm Recurrence, Local/complications*
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Cysts/surgery*
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Pain
6. Mechanism of Sophora tonkinensis Gagnep regulating leukocyte transendothelial migration pathway in improving acute pharyngitis based on network pharmacology
Zhao-Yan DANG ; Chang LIU ; Qian-Qian HE ; Ting-Ting FENG ; Wei QUAN ; Ying ZHOU ; Xiu DONG ; Ying ZHOU
Chinese Pharmacological Bulletin 2023;39(2):348-356
Aim To elucidate the molecular mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis based on network pharmacology, animal experiments and quantitative real-time PCR.Methods The active components and targets of Sophora tonkinensis Gagnep were collected from the database of traditional Chinese medicinal systems databases and analysis platform(TCMSP). Targets related to acute pharyngitis were acquired through GeneCards, OMIM, DrugBank and Disgenet databases. After the common targets of the two were screened, the STRING database was used to construct the protein interaction network, and the Metascape platform was used for pathway analysis. At the same time, Cytoscape software was used to construct a network of "herbal-disease-component-target" and "herbal-disease-component-target-pathway" network. The acute pharyngitis models in rats were established to study the effect of water extract of Sophora tonkinensis Gagnep on acute pharyngitis in rats. Quantitative real-time PCR technology was used to study the effect of Sophora tonkinensis Gagnep on key gene targets in key pathways of pharyngeal tissues in rats with acute pharyngitis. Results In this experiment, 509 related targets of 21 active components of Sophora tonkinensis Gagnep were obtained, 2 167 related targets of acute pharyngitis were obtained, and 194 common targets of Sophora tonkinensis Gagnep and acute pharyngitis were obtained. KEGG pathway analysis screened 344 related signaling pathways, indicating that IL-17 signaling pathway, NF-kappa B signaling pathway and leukocyte transendothelial migration pathway might play a key role in the improvement of acute pharyngitis by Sophorae tonkinensis Gagnep. Animal experiments showed that the low dose group of Sophora tonkinensis Gagnep water extract had better therapeutic effect on acute pharyngitis. The results of quantitative real-time PCR showed that the low-dose group of Sophora tonkinensis Gagnep significantly down-regulated the expression levels of ITGB2, PIK3CA, PIK3CD and PTPN11 genes in leukocyte transendothelial migration pathway(P<0.05). Conclusions The above results show that Sophora tonkinensis Gagnep has the characteristics of multi-component, multi-target and multi-pathway synergy in improving acute pharyngitis, which provides a theoretical basis for further study on the complex mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis.
7. Mechanism of Sophorae tonkinensis radix et rhizome-induced nephrotoxicity in rats based on network toxicology and experimental validation
Qian-Qian HE ; Chang LIU ; Wei QUAN ; Ting-Ting FENG ; Jing-Xin DING ; Zhao-Yan DANG ; Ying ZHOU ; Ying ZHOU ; Xiu DONG
Chinese Pharmacological Bulletin 2023;39(4):766-773
Aim To investigate the mechanism of Sophorae tonkinensis radix et rhizome (ST) induced nephrotoxicity based on network toxicology and experimental verification. Methods Through network toxicology the target of toxic components of ST was predicted, nephrotoxicity-related target genes were located, the intersection of targets was taken, the STRING platform was imported to map the target protein interactions, MetaScape database was used for GO and KEGG analysis, BioGPS database for screening the key expressed genes in rat nephrotoxicity and the component-target-pathway network was constructed. The mechanism of ST induced nephrotoxicity was verified through animal experiments, and qRT-PCR was applied to detect mRNA expression level of key genes in kidney tissue. Results Twenty toxic components of ST were screened from network toxicology, mainly including matrine, sophoridine, maackiain. A total of 135 targets were involved, and HSP90AA1, SRC, MAPK1, MAPK3, AKT1 were the main targets. A total of 169 related signaling pathways were yielded by KEGG analysis, and the mechanism of nephrotoxicity might be related to cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway. PPARA, RAF1, MAP2K1, SRC, AKT1 and MAPK3 were screened from BioGPS database. The results of animal experiments showed that BUN and SCr level increased (P <0. 01) in rats with high-dose group, and the kidney tissue was significantly damaged. qRT-PCR results indicated that the expression of PPARA, RAF1, MAP2K1, MAPK3 mRNA increased, the expression of AKT1 mRNA decreased in the high-dose group of ST (P <0. 05). Conclusions The mechanism of Sophorae tonkinensis radix et rhizome induced nephrotoxicity is found to be related to the combined action of multiple components, multiple targets and multiple pathways, which also provides a theoretical basis for the in-depth exploration of the toxicology.
8.Outcomes at discharge of preterm infants born <34 weeks' gestation.
Ning Xin LUO ; Si Yuan JIANG ; Yun CAO ; Shu Jun LI ; Jun Yan HAN ; Qi ZHOU ; Meng Meng LI ; Jin Zhen GUO ; Hong Yan LIU ; Zu Ming YANG ; Yong JI ; Bao Quan ZHANG ; Zhi Feng HUANG ; Jing YUAN ; Dan Dan PAN ; Jing Yun SHI ; Xue Feng HU ; Su LIN ; Qian ZHAO ; Chang Hong YAN ; Le WANG ; Qiu Fen WEI ; Qing KAN ; Jin Zhi GAO ; Cui Qing LIU ; Shan Yu JIANG ; Xiang Hong LIU ; Hui Qing SUN ; Juan DU ; Li HE
Chinese Journal of Pediatrics 2022;60(8):774-780
Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology*
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Gestational Age
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Humans
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Infant
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Infant Mortality/trends*
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Infant, Newborn
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Infant, Premature
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Infant, Premature, Diseases/epidemiology*
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Patient Discharge
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Retinopathy of Prematurity/epidemiology*
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Sepsis/epidemiology*
9.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.
10.Effects of drought stress on physiological and biochemical and chemical components of Cinnamomum cassia seedlings.
Lei ZHONG ; Pei-Ran LIAO ; Chang-Zheng LIU ; Jia-Ping QIAN ; Wan-Cong HE ; Bi LUO ; Quan YANG
China Journal of Chinese Materia Medica 2021;46(9):2158-2166
Six month old Cinnamomum cassia seedlings were used to simulate drought stress with polyethylene glycol(PEG 6000). The physiological indicators(osmotic substances, antioxidant enzymes, etc.) and chemical components of seedlings under different drought levels and the correlation between the two were studied. The results showed that the chlorophyll content and relative water content decreased gradually with the increase of PGE 6000(0, 5%, 10%, 15%) concentration and time(3, 5, 7 d), while the soluble protein content, soluble sugar content and catalase(CAT) activity increased, but the rising rate slowed down with the time. The activities of peroxidase(POD), superoxide dismutase(SOD), malondialdehyde(MDA) and proline content increased at first and then decreased. The content of coumarin, cinnamaldehyde, cinnamic acid and dimethoxycinnamaldehyde decreased, while the content of cinnamyl alcohol continued to increase.Under drought stress, the fluorescence signals of reactive oxygen species and no contents in roots of C. cassia seedlings were significantly stronger than those of the control.Further correlation analysis showed that coumarin content, di-methoxycinnamaldehyde content and osmoregulation substance content were significantly negatively correlated(P<0.05), cinnamic acid content was significantly negatively correlated with POD and SOD activities(P<0.01).It was found that C. cassia seedlings showed a certain degree of drought tolerance under short-term or mild drought stress, but if the drought exceeded a certain degree, the physiological metabolism of the seedlings would be unbalanced.
Catalase
;
Cinnamomum aromaticum
;
Droughts
;
Malondialdehyde
;
Seedlings
;
Stress, Physiological
;
Superoxide Dismutase

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