1.Mechanism of action of D-limonene on steatosis in primary hepatocytes based on AMPK/ACC/CPT1A signaling pathway
Qian-jun REN ; Su LI ; Yu-qing CHEN ; Yin-ying LIAO ; Chun-ni LIANG ; Rui-chao FANG ; Xu-dong LIU ; Xiao-fang ZHAO
Chinese Pharmacological Bulletin 2025;41(9):1665-1672
Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.
2.Mechanism of action of D-limonene on steatosis in primary hepatocytes based on AMPK/ACC/CPT1A signaling pathway
Qian-jun REN ; Su LI ; Yu-qing CHEN ; Yin-ying LIAO ; Chun-ni LIANG ; Rui-chao FANG ; Xu-dong LIU ; Xiao-fang ZHAO
Chinese Pharmacological Bulletin 2025;41(9):1665-1672
Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.
3.Changing resistance profiles of Enterobacter isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Shaozhen YAN ; Ziyong SUN ; Zhongju CHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yi XIE ; Mei KANG ; Fengbo ZHANG ; Ping JI ; Zhidong HU ; Jin LI ; Sufang GUO ; Han SHEN ; Wanqing ZHOU ; Yingchun XU ; Xiaojiang ZHANG ; Xuesong XU ; Chao YAN ; Chuanqing WANG ; Pan FU ; Wei JIA ; Gang LI ; Yuanhong XU ; Ying HUANG ; Dawen GUO ; Jinying ZHAO ; Wen'en LIU ; Yanming LI ; Hua YU ; Xiangning HUANG ; Bin SHAN ; Yan DU ; Shanmei WANG ; Yafei CHU ; Yuxing NI ; Jingyong SUN ; Yunsong YU ; Jie LIN ; Chao ZHUO ; Danhong SU ; Lianhua WEI ; Fengmei ZOU ; Yan JIN ; Chunhong SHAO ; Jihong LI ; Lixia ZHANG ; Juan MA ; Yunzhuo CHU ; Sufei TIAN ; Jinju DUAN ; Jianbang KANG ; Ruizhong WANG ; Hua FANG ; Fangfang HU ; Yunjian HU ; Xiaoman AI ; Fang DONG ; Zhiyong LÜ ; Hong ZHANG ; Chun WANG ; Yong ZHAO ; Ping GONG ; Lei ZHU ; Jinhua MENG ; Xiaobo MA ; Yanping ZHENG ; Jinsong WU ; Yuemei LU ; Ruyi GUO ; Yan ZHU ; Kaizhen WEN ; Yirong ZHANG ; Chunlei YUE ; Jiangshan LIU ; Wenhui HUANG ; Shunhong XUE ; Xuefei HU ; Hongqin GU ; Jiao FENG ; Shuping ZHOU ; Yan ZHOU ; Yunsheng CHEN ; Qing MENG ; Bixia YU ; Jilu SHEN ; Rui DOU ; Shifu WANG ; Wen HE ; Longfeng LIAO ; Lin JIANG
Chinese Journal of Infection and Chemotherapy 2024;24(3):309-317
Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5%in all clinical isolates amd 5.7%in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7%(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)%,followed by secretions/pus(16.4±2.3)%and urine(16.0±0.9)%.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9%),and only(7.1±0.8)%of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)%compared to the inpatients in any other departement.Overall,≤ 7.9%of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6%of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7%vs 3.9%).Overall,≤8.1%of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5%of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0%over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.
4.Genomic and cellular infection characteristics of a newly isolated Mangshi virus in China
Heng YANG ; Zhan-Hong LI ; Lei XIAO ; Zhuo-Ran LI ; Jia-Rui XIE ; De-Fang LIAO ; Lin GAO ; Hua-Chun LI
Chinese Journal of Zoonoses 2024;40(6):504-511,528
The genomic characteristics and cellular tropism of a Mangshi virus(MSV)isolated in China were investigated,thereby establishing a robust foundation for further research on the evolution and pathogenicity of MSV.The genome sequence of MSV strain V301/YNJH/2019 was obtained by next-generation sequencing,followed by phylogenetic tree construction and rearrangement assessment using software IQtree,RPD4,and Simplot.Viral proliferation was assessed in C6/36(Aedes albop-ictus),Vero(African green monkey kidney),and BHK(baby hamster kidney)cells.An initial epidemiological investigation of MSV in local cattle and goats was conducted using the serum neutralization test.The genome of MSV strain V301/YNJ H/2019 was 20623 bp in length,encompassing 12 segments of double-stranded RNA(Seg-1 to Seg-12).Sequence analysis confirmed genomic rearrangement of the Seg-1 and Seg-11 sequences,ex-hibiting high similarity to MSV isolated from lake sediment in China in 2022,while Seg-2 to Seg-10 and Seg-12 were most closely related to a MSV strain isolated from mosquitoes in China in 2013.The virus efficiently proliferated and induced sig-nificant cytopathic effects(CPE)in both C6/36 and BHK cells,but limited replication and no observable CPE in Vero cells.No detectable neutralizing antibodies against MSV were detected in 20 goat serum samples collected in Mangshi,while 2 of 20 bo-vine serum samples were positive with neutralizing antibody titers of 1:128 and 1:54.Whole genome sequencing revealed re-assortment events of the V301/YNJH/2019 strain,which is capable of infecting C6/36,BHK,and Vero cells.MSV infection was confirmed in cattle in Mangshi.
5.A Family with Congenital Dysfibrinogenemia and Blood Transfusion.
Xiang-Cheng LIAO ; Shan-Shan ZHANG ; Zi-Ji YANG ; Chun-Li ZHU ; Hui-Ni HUANG ; Rui-Xian LUO ; Si-Na LI ; Hui-Qiong XIE ; Hai-Lan LI ; Zhu-Ning MO
Journal of Experimental Hematology 2023;31(5):1469-1474
OBJECTIVE:
To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.
METHODS:
Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations.
RESULTS:
The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery.
CONCLUSION
Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans
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Child
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Female
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Fibrinogen/genetics*
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Pedigree
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Afibrinogenemia/genetics*
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Mutation
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Blood Transfusion
6.Clinical Study of Modified Chaihu Guizhi Decoction in Treating Stable Angina Pectoris of Coronary Heart Disease with Anxi-ety/Depression of Qi Stagnation and Blood Stasis Type
Hai-Quan HUANGFU ; Hui-Chun HUANG ; Hai-Rui YU ; Xiao-Ming SHANG ; Wei-Qian LIAO
Journal of Nanjing University of Traditional Chinese Medicine 2023;39(11):1122-1128
OBJECTIVE To observe the clinical efficacy of modified Chaihu Guizhi Decoction in treating stable angina pectoris with anxiety/depression in patients with coronary heart disease of qi stagnation and blood stasis type.METHODS 60 patients with stable angina pectoris and anxiety/depression caused by qi stagnation and blood stasis type of coronary heart disease were included in the study.They were randomly divided into a control group(n=30)and a treatment group(n=30).Both groups of patients received health education,psychological counseling,and routine treatment for coronary heart disease angina pectoris.The control group received droperidol melitracin tablets in addition to basic treatment,while the treatment group received modified Chaihu Guizhi Decoction in ad-dition to basic treatment for 4 weeks.The efficacy of traditional Chinese medicine(TCM)syndrome,total score of traditional Chinese medicine syndrome,angina symptom score,electrocardiogram treadmill exercise test,nitroglycerin withdrawal rate,self-rating anxiety scale(SAS),self-rating depression scale(SDS),and Seattle angina questionnaire(SAQ)scores between the two groups of patients were compared before and after treatment.At the same time,peripheral blood lipids and IL-6 levels were measured.RESULTS Af-ter treatment,the TCM syndrome score,angina symptom score,SAS,SDS score of both groups of patients decreased(P<0.01),and the scores of various dimensions of SAQ increased(P<0.01).The occurrence time of ST segment depression of 1mm in treadmill exer-cise test was prolonged,the occurrence time of angina was prolonged,and the recovery time of ST segment was shortened(P<0.01),and TC,TG,LDL-C,IL-6 were significantly reduced(P<0.05,P<0.01).Moreover,the treatment group was superior to the con-trol group in improving TCM syndrome scores,angina symptom scores,SAS,SDS scores,PL and TS scores in SAQ,apparent effective rate of TCM syndrome,nitroglycerin cessation rate,blood lipids(TC,LDL-C),and serum IL-6(P<0.05,P<0.01).CONCLU-SION Modified Chaihu Guizhi Decoction can significantly improve the clinical symptoms,anxiety and depression status of patients with stable angina pectoris and anxiety/depression of qi stagnation and blood stasis type of coronary heart disease,improve quality of life,reduce blood lipids and IL-6 levels.
7.A 10-year retrospective analysis of spectrums and treatment options of orthostatic intolerance and sitting intolerance in children.
Ya Xi CUI ; Jun Bao DU ; Qing You ZHANG ; Ying LIAO ; Ping LIU ; Yu Li WANG ; Jian Guang QI ; Hui YAN ; Wen Rui XU ; Xue Qin LIU ; Yan SUN ; Chu Fan SUN ; Chun Yu ZHANG ; Yong Hong CHEN ; Hong Fang JIN
Journal of Peking University(Health Sciences) 2022;54(5):954-960
OBJECTIVE:
To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options.
METHODS:
The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed.
RESULTS:
A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4-18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ2= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS.
CONCLUSION
POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.
Child
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Electrolytes
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Female
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Humans
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Male
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Metoprolol
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Midodrine
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Orthostatic Intolerance/therapy*
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Postural Orthostatic Tachycardia Syndrome/diagnosis*
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Retrospective Studies
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Salts
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Sitting Position
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Syncope, Vasovagal/diagnosis*
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Tilt-Table Test
8. Mitochondrial Fission Protein 1 (FIS1) Overexpression in Human Cervical Cancer Cells Promotes Mitochondrial Fission and Reduces Cell Proliferation and Migration Capacity
Rui CONG ; Xing-Yu LI ; Nan HUO ; Xiang ZHU ; Chun-Yuan XUE ; Liao-Xin FANG ; Xiao-Feng KANG ; Jun-Wen ZHU ; Yi-Meng DU ; Xiao-Jie XU
Chinese Journal of Biochemistry and Molecular Biology 2022;38(7):926-935
Mitochondria are dynamic organelles that continuously divide and fuse. In recent years, in addition to the studies related to mitochondrial metabolism, the unique dynamics of mitochondria have gradually attracted researchers' attention. A growing body of research has revealed that mitochondrial dynamics are related to the biological behavior of tumor cells. Mitochondrial fission proteins (mitochondrial fission protein 1, FIS1) mediate the assembly of mitochondrial fission complexes and participate in the execution of mitochondrial fission. They are important proteins in the process of mitochondrial fusion and fission. However, few studies have revealed the expression and role of FIS1 in human cervical cancer. In this study, the expression level of FIS1 in human cervical cancer tissues and paracancer tissues were compared. The results showed that the level of FIS1 mRNA in human cervical cancer tissues was significantly lower than that in paracancer tissues (P<0. 01). Further KEGG pathway and GO Term-BP pathway analysis showed that the differential genes are mainly related to mitochondrial biological functions. Subsequently, HeLa cells with overexpressed FIS1 were investigated for their proliferation, migration, mitochondrial fission and ROS levels. The experimental results showed that FIS1 overexpression decreased HeLa cell proliferation and migration ability, enhanced mitochondrial fission and higher ROS levels. In conclusion, the expression of FIS1 in human cervical cancer cells was attenuated, while overexpression of FIS1 resulted in a series of abnormal biological functions in human cervical cancer cells. Further studies can be carried out to investigate the role of FIS1 in the treatment of human cervical cancer.
9.Effects of Temperature on Outpatient Visits for Urticaria among Lanzhou Residents Based on Distributed Lag Non-linear Model.
Jing ZHANG ; Chun-Rui SHI ; Bei LIAO ; Lei HAN ; Ya-Juan PAN ; Zhi-Cheng LUO ; Qun XI ; Lin HE ; Rui WANG
Acta Academiae Medicinae Sinicae 2021;43(5):727-735
Objective To evaluate the influence of temperature on the outpatient visits for urticaria in Lanzhou City and its hysteresis and to find out the sensitive populations by sex and age stratification.Methods We collected the urticaria outpatient data in three grade A class three hospitals as well as the meteorological data and air pollutant data in Lanzhou from January 2011 to December 2017.The distributed lag non-linear model(DLNM)was employed to analyze the influence of daily mean temperature on the outpatient visits for urticaria.Stratification analysis was performed for different age groups(0-14,15-59,≥60 years)and different sex populations.Results Temperature had a non-linear relationship with the outpatient visits for urticaria,and there existed hysteresis.During the research period,the average daily outpatient visits for urticaria at the three hospitals in Lanzhou was 25,ranging from 1 to 76.With the rise in the daily mean temperature within 0-10 ℃,the risk of outpatient visits for urticaria first increased and then decreased.When the daily mean temperature was 2 ℃,hysteresis occurred on the 18th day,and the relative risk(
Adolescent
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Air Pollutants/analysis*
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Child
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Child, Preschool
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China/epidemiology*
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Female
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Humans
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Infant
;
Infant, Newborn
;
Middle Aged
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Nonlinear Dynamics
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Outpatients
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Temperature
;
Urticaria/epidemiology*
10.Formulation regularity and thinking of adjuvant sleep-improving Chinese medicinal health products.
Er Xun Re-Yi-la TU ; Yan LIAO ; Na YUE ; Rui ZHANG ; Chun WANG ; Jian-Jun ZHANG
China Journal of Chinese Materia Medica 2021;46(13):3228-3233
To summarize and analyze the current adjuvant sleep-improving Chinese medicinal health products,this study retrieved the information on health products with the sleep-improving effect published by the Department of Special Food Safety Supervision and Management,State Administration for Market Regulation( SMAR),which was statistically analyzed with Microsoft Excel and TCMISS for the characteristics of formulations. A total of 435 sleep-improving health products were collected,including 344 ones containing Chinese herbal medicines. Among them,413 health products were not suitable for adolescents,neither 194 for pregnant women. Ten Chinese herbal medicines showed a frequency of use ≥40,with 1 095 times( 73. 1%) in use. Through unsupervised hierarchical entropy-based clustering of the above Chinese herbal medicines of health products( degree of support of 45 and confidence coefficient of0. 7),12 new formulas were obtained. The composition of Chinese herbal medicines was consistent with the principles of improving sleep in traditional Chinese medicine( TCM) theories,i. e.,replenishing the heart and spleen,nourishing blood,calming the nerves,nourishing Yin,reducing internal heat,communicating the heart and kidney,replenishing Qi,relieving convulsions,clearing heat,resolving phlegm,regulating the middle warmer,soothing the liver,relieving heat,and calming the heart. According to TCM theories,syndrome differentiation was performed based on the existing sleep-improving health products,followed by data mining and analysis according to the formulation regularity,aiming to provide new ideas for the development of new Chinese medicinal health products. In particular,attention should be attached to the requirements of special populations to provide a basis for follow-up studies,exert the advantages of TCM,and lay a foundation for Chinese medicinal health products to service the public.
Adolescent
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China
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Data Mining
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Drugs, Chinese Herbal
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Female
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Humans
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Medicine, Chinese Traditional
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Pregnancy
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Sleep

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