1. Exploring mechanism of hypolipidemic effect of total Ligustrum robustum (Roxb. ) Blume on hyperlipidemic golden hamsters based on intestinal flora
Chen-Xi XU ; Rui-Le PAN ; Meng-Chen DONG ; Zhi-Hong YANG ; Xiao-Ya LI ; Wen JIN ; Run-Mei YANG
Chinese Pharmacological Bulletin 2024;40(3):476-483
Aim To evaluate the hypolipidemic effect of the total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) on hyperlipidemic golden hamsters and explore its regulatory effect on intestinal flora. Methods Sixty hamsters were randomly divided into a control group, a model group, a positive drug group, LRTPG-L group, LRTPG-M group, and LRTPG-H group. After the successful induction of the model by high-fat diet, the animals were continuously administered for four weeks, and their blood lipids and liver lipids were detected. The formed feces from the colorectal region of the hamsters in the control group, model group and LRTPG-H group were collected for 16S rDNA sequencing. Results LRTPG reduced serum TG, TC, LDL-C and liver TG, TC concentrations significantly in hyperlipidemic hamsters. The results of the intestinal microbiota sequencing showed that compared to the control group, LRTPG significantly decreased the relative abundance of the phylum Firmicutes and increased the relative abundance of the phylum Bacteroidetes and Verrucomicrobia (P < 0.01) at the phylum level. At the family level, LRTPG significantly increased the relative abundance of Christensenellaceae, Peptococcaceae, and Verrucomicrobiaceae (P < 0.05 or P < 0.01). At the genus level, LRTPG significantly increased the relative abundance of Oscillospira, Oscillibacter, Flavonifractor and Akkermansiaceae (P < 0.05 or P < 0.01). These changes in the flora were beneficial to the hypolipidemic effect of LRTPG. Conclusion LRTPG may exert its hypolipidemic effect by improving the intestinal flora disorder caused by a high-fat diet in golden hamsters.
2.Predictive Ability of Hypertriglyceridemic Waist,Hypertriglyceridemic Waist-to-Height Ratio,and Waist-to-Hip Ratio for Cardiometabolic Risk Factors Clustering Screening among Chinese Children and Adolescents
Li Tian XIAO ; Qian Shu YUAN ; Yu Jing GAO ; S.Baker JULIEN ; De Yi YANG ; Jie Xi WANG ; Juan Chan ZHENG ; Hui Yan DONG ; Yong Zhi ZOU
Biomedical and Environmental Sciences 2024;37(3):233-241
Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.
3.Interpretation of specification for service of cancer screening for workers
Hongda CHEN ; Bin LU ; Ying ZHENG ; Peng DU ; Xiao QI ; Kai ZHANG ; Yuying LIU ; Junli WEI ; Donghua WEI ; Jiyong GONG ; Yunchao HUANG ; Zhenya SONG ; Xi CHU ; Dong DONG ; Wenjing ZHENG ; Min DAI
Chinese Journal of Epidemiology 2024;45(4):486-489
As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.
4.Effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in a rat model of cardiac hypertrophy
Hao ZHANG ; Xiao-Yun DING ; Hu WANG ; Ting-Ting LI ; Yu-Mei QIU ; Meng-Die XIE ; Wei DONG ; Yi-Xin SHEN ; Xi-Lan TANG
Chinese Traditional Patent Medicine 2024;46(11):3594-3602
AIM To investigate the effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in isoproterenol(ISO)-induced rat heart tissue and primary myocardial cells of neonatal rats.METHODS The SD rats were randomly divided into the normal group,the model group,the Xinyue Capsules intervention group and Xinyue Capsules control group,with 8 rats in each group.The rat model of cardiac hypertrophy was established by 14 days consecutive intraperitoneal injection of ISO(30 mg/kg).Prior to the modeling,once daily administration of 0.393 g/kg Xinyue Capsules was given by gavage from 3 days in advance to the end of the experiment.After the last administration,the procurement of blood from abdominal aorta,the left and right ventricles were processed.And the rats had their indices levels of the heart,the left ventricle and the right ventricle measured;their pathomorphological changes of myocardial tissue observed using HE staining;their expressions of cardiac hypertrophy-related myocardial embryonic genes ANP,β-MHC and α-SKA mRNA detected using RT-qPCR method;and their serum TC,TG,LDL-C and HDL-C levels detected by biochemical method.In in vitro experiment,the neonatal rat model of myocardial hypertrophy was induced by exposure to ISO 1 μmol/L for 24 h.The investigation of the effect of Xinyue Capsules 12.5 μg/mL on ISO-induced myocardial hypertrophy was conducted by detection of myocardial cell area,embryo genes related to cardiac hypertrophy and myocardial cells protein cuntent.The further anti-cardiac hypertrophy mechanism of Xinyue Capsules research was conducted using RT-qPCR and Western blot to detect the gene and protein expressions of phospholipase A2(PLA2G6),phospholipase A1 member A(PLA1A)and lecithin cholesterol acyltransferase(LCAT)in left ventricle tissue and myocardial cells of each group.RESULTS The in vivo experimental result showed that compared with the normal group,the model group displayed increased indices levels of the heart,the left ventricle and the right ventricle and cross-sectional area of left ventricular myocytes(P<0.05);and up-regulated expressions of ANP,β-MHC,α-SKA mRNA and PLA2G6,PLA1A and LCAT mRNA and proteins in the left ventricle(P<0.05);and increased levels of serum TC,TG and LDL-C(P<0.05);and decreased HDL-C level(P<0.05).However,the intervention of Xinyue Capsules inhibited the changes of the aforementioned indices(P<0.05).The in vitro experimental result revealed that Xinyue Capsules inhibited the ISO-induced increases of myocardial cell surface area and myocardial cell protein level,the up-regulation of ANP,β-MHC,α-SKA mRNA expressions and the PLA2G6,PLA1A,LCAT mRNA and protein expressions as well(P<0.05).CONCLUSION Xinyue Capsules can improve the ISO-induced cardiac hypertrophy in rats,and its mechanism may be associated with its regulation upon the expressions of glycerophospholipid metabolism-related enzymes PLA2G6,PLA1A and LCAT.
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.Expression and diagnostic value of serum free light chain in lung cancer
Xi XIAO ; Li ZHENG ; Hua ZENG ; Dan CHEN ; Liqin LIU ; Caimei DONG ; Yanping ZHANG
Journal of Central South University(Medical Sciences) 2024;49(6):914-920
Objective:The expression of serum free light chain(FLC)is abnormal in various diseases,but its role in lung cancer remains unclear.This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer. Methods:A total of 80 lung cancer patients treated at Xiangdong Hospital,Hunan Normal University from January to December 2021 were selected as the lung cancer group.Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group.General information and serum κFLC and λFLC levels were collected for all subjects.Clinical indicators such as serum carcinoembryonic antigen(CEA),cytokeratin fragment antigen 21-1(CYFRA21-1)levels,tumor diameter,histological type,TNM stage,and lymph node metastasis status were recorded for lung cancer patients.The expression levels of serum FLC[κFLC,λFLC,and FLC(κ+λ)]were compared between the lung cancer group and the control group.Lung cancer patients were grouped based on gender,age,smoking history,tumor diameter,TNM stage,histological type,and lymph node metastasis to compare differences in serum κFLC and λFLC levels.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer. Results:The expression levels of serum FLC(κ+λ)and κFLC were significantly higher in the lung cancer group than those in the control group(both P<0.001),while there was no significant difference in serum λFLC levels between the 2 groups(P>0.05).There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters,histological types,or TNM stages(all P>0.05);however,serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without,with statistical significance(P=0.033).There were no significant differences in serum λFLC levels based on tumor diameter or histological type(both P>0.05),but serumλFLC levels were higher in stage Ⅲ+Ⅳ and lymph node metastatic lung cancer patients compared to stage Ⅰ+Ⅱ and non-metastatic patients,with statistical significance(P=0.033 and P=0.019,respectively).The area under the curve(AUC)for κFLC and CEA in diagnosing lung cancer showed no significant difference(P=0.333).The combination ofκFLC+CYFRA21-1 had the highest diagnostic efficacy(AUC=0.875)and sensitivity(71.3%).The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915(95%CI 0.860 to 0.953,P<0.001). Conclusion:Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis.Serum FLC,particularly κFLC,has diagnostic value for lung cancer,and the combined detection of FLC,CEA,and CYFRA21-1 offers the best diagnostic efficacy.
7.Research progress of histone deacetylase and its inhibitors in osteogenesis and odontogenic differentiation of odontogenic stem cells
Dong-Yu LI ; Xiao-Miao ZHU ; Ji-Rong ZHAO ; Wen-Xi HE
Medical Journal of Chinese People's Liberation Army 2024;49(4):468-474
Histone deacetylases(HDACs)can deacetylate histones,leading to tighter DNA binding,and thereby playing a role in inhibiting gene transcription.On the contrary,histone deacetylase inhibitors(HDACis)can promote chromatin relaxation,enabling various transcription factors to bind specifically to DNA and activate transcription genes.Dental stem cells(DSCs)are human adult stem cells.These cells have the characteristics of less damage and low immune rejection during sampling,and are especially important seed cells in the process of osteogenesis,odontogenesis and other differentiation.A large number of experimental studies have shown that HDACs and HDACis together play important roles in cell division and differentiation,signal transduction,regulation of cellular inflammation and other life processes.This review summarizes the research progress of HDACs and HDACis in regulating osteogenic and odontogenic differentiation of DSCs,aiming to provide insights into the study of the interaction between HDACs and HDACis,and potentially guide clinical application of DSCs in the treatment of tooth and bone injury.
8.The therapeutic effect of Qingjie Huagong decoction on acute lung injury in rats with severe acute pancreatitis model and its mechanism
Min-Chao FENG ; Fang LUO ; Xi-Ping TANG ; Kai LI ; Xiao-Dong ZHU ; Bing-Yu ZHANG ; Guo-Zhong CHEN
Chinese Pharmacological Bulletin 2024;40(5):975-983
Aim To investigate the possible mechanism of action of Qingjie Huagong decoction(QJHGD)on acute lung injury(ALI)associated with severe acute pancreatitis(SAP)using network pharmacology,and to verify it by animal experiments.Methods The TC-MSP,BATMAN-TCM,ETCM,and SwissTargetPredic-tion databases were searched to obtain the action tar-gets of the blood-entering active ingredients of each drug in the QJHGD.The GeneCard database was searched to obtain SAP-ALI disease targets.The drug targets and disease targets were intersected to obtain common targets.Subsequently,the common targets were analyzed by STRING database and Cytoscape 3.7.1 software for protein interaction network analysis.GO and KEGG enrichment analysis was performed with the help of DAVID database.Finally,the key signa-ling pathways were verified by animal experiments.Results A total of 28 active ingredients were screened out for the treatment of SAP-ALI with 42 common tar-gets.PPI network analysis showed that STAT3,IL-6,and TGFB1 might be core targets;GO and KEGG en-richment analysis mainly involved cell proliferation,PI3K/AKT signaling pathways,etc.Animal experi-ments confirmed that QJHGD could improve the pathol-ogy of pancreas and lung tissues in SAP-ALI rat mod-el,down-regulate the expression levels of α-amylase,lipase,IL-1 β,IL-6,and TNF-α in serum,and down-regulate the expression levels of proteins and mRNAs related to PI3K/AKT1 signaling pathway in lung tis-sues.Conclusion QJHGD synergistically treats SAP-ALI through multi-component,multi-target,and multi-pathway,with a mechanism that may be related to the inhibition of PI3K/AKT signaling pathway activation.
9.Effect of Qingjie Huagong decoction on pancreatic necrotic apoptosis in rats with severe acute pancreatitis based on RIPK1/RIPK3/MLKL signaling pathway
Xiao-Dong ZHU ; Min-Chao FENG ; Kun-Rong LIU ; Ying BAN ; Xi-Ping TANG ; Guo-Zhong CHEN
Chinese Pharmacological Bulletin 2024;40(8):1489-1494
Aim To explore the therapeutic effect of Qingjie Huagong decoction in regulating RIPK1/RIPK3/MLKL signaling pathway on pancreatic necrotic apoptosis in rats with severe acute pancreatitis(SAP)and the underlying mechanism.Methods The SAP rat model was established by retrograde pancreaticobili-ary injection of sodium taurocholate,and the sham-op-eration group,the model group,the group with differ-ent dosages of Qingjie Huagong decoction and the posi-tive control group were set up respectively.The group with different dosages of Qingjie Huagong decoction was given low,medium and high dosages of traditional Chinese medicine in the gastric gavage,the positive control group was given ulinastatin drug intervention,and the sham-operation and the model group were giv-en physiological saline in the gastric gavage;HE stai-ning was applied to observe pancreatic pathology;ELISA was used to measure the serum levels of α-am-ylase,IL-1β,IL-6,and TNF-α;immunohistochemis-try and Western blot were employed to determine the RIPK1,RIPK3,MLKL protein expression in rat pan-creatic tissue;and qRT-PCR was utilized to detect the transcription levels of R1PK1,RIPK3 and MLKL mR-NA in rat pancreatic tissue.Results Compared with the sham-operated group,the model group showed dif-fuse necrosis of pancreatic acinar cells,obvious inter-lobular septal edema,inflammatory cell infiltration,significantly higher levels of α-amylase,IL-1β,IL-6,and TNF-α(P<0.01),and significantly higher ex-pression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P<0.01)in the model group;com-pared with the model group,the Qingjie Huagong de-coction dose groups and positive control group signifi-cantly improved pancreatic histopathology,reduced pancreatic tissue necrosis and apoptosis,lowered the expression levels of α-amylase,IL-1 β,IL-6 and TNF-α(P<0.01),and reduced the expression levels of RIPK1,RIPK3,and MLKL proteins and mRNAs(P<0.01).Conclusions Qingjie Huagong decoction may improve the necrotic apoptosis of pancreatic tissue by regulating the RIPK1/RIPK3/MLKL signaling path-way,thus playing a role in protecting pancreatic tissue and slowing down the progression of the disease.
10.Advances in the development of novel E3 ubiquitin ligase ligands
Chen-xi WANG ; Yang LU ; Xiao-wu DONG ; Jin-xin CHE
Acta Pharmaceutica Sinica 2024;59(11):2926-2940
The ubiquitin-proteasome system (UPS) is responsible for protein degradation in both normal and pathological states. E3 ligases selectively attach ubiquitin to specific substrates, which is essential for regulating cellular homeostasis. The function of E3 ligases has been associated with a variety of diseases, such as cancer and cardiovascular disease. The discovery of E3 ligands can help regulate E3 ligases, thus expanding new ideas for disease treatment. Targeted protein degradation (TPD) drugs, including proteolysis targeting chimera (PROTAC), have become increasingly popular in recent years due to their dependence on E3 ligands. In this paper, we review the discovery techniques of E3 ligands, including activity-based protein mapping, fragment-based drug discovery, and library-based methods, and briefly introduce the protein interaction detection techniques involved in the ligand discovery techniques, in the hope of providing certain ideas for the future discovery of E3 ligands as well as the treatment of diseases.

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