1.Visualization Analysis of Artificial Intelligence Literature in Forensic Research
Yi-Ming DONG ; Chun-Mei ZHAO ; Nian-Nian CHEN ; Li LUO ; Zhan-Peng LI ; Li-Kai WANG ; Xiao-Qian LI ; Ting-Gan REN ; Cai-Rong GAO ; Xiang-Jie GUO
Journal of Forensic Medicine 2024;40(1):1-14
Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.
2.Urine Metabolites Changes in Acute Myocardial Infarction Rats via Metabolomic Analysis
Nian-Nian CHEN ; Jiao-Fang YU ; Peng WU ; Li LUO ; Ya-Qin BAI ; Li-Kai WANG ; Xiao-Qian LI ; Zhan-Peng LI ; Cai-Rong GAO ; Xiang-Jie GUO
Journal of Forensic Medicine 2024;40(3):227-236
Objective To screen biomarkers for forensic identification of acute myocardial infarction (AMI) by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI.Methods The rat models of the sham surgery group,AMI group and hyperlipidemia+acute myocardial infarction (HAMI) group were established.Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the changes of urine metabolic spectrometry in AMI rats.Principal compo-nent analysis,partial least squares-discriminant analysis,and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites.The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites.Results A total of 40 and 61 differential metabolites associated with AMI and HAMI were screened,respec-tively.Among them,22 metabolites were common in both rat models.These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways.Within the 95% confidence in-terval,the area under the curve (AUC) values of receiver operator characteristic curve for N8-acetyl-spermidine,3-methylhistamine,and thymine were greater than 0.95.Conclusion N8-acetylspermidine,3-methylhistamine,and thymine can be used as potential biomarkers for AMI diagnosis,and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI.This study can provide reference for the mechanism and causes of AMI identification.
3.Rapid detection of zearalenone in Coicis Semen based on ELISA.
Yun-Xiang LIU ; Peng-Chao GAO ; Zhi-Lai ZHAN ; Li-Ping KANG ; Tie-Gui NAN ; Yuan YUAN
China Journal of Chinese Materia Medica 2023;48(11):2919-2924
Zearalenone(ZEN) is a toxic metabolite produced by Fusarium culmorum, F. graminearum, F. tricinctum, and other fungi, with estrogenic characteristics. Exposure to or ingestion of ZEN during pregnancy can cause reproductive dysfunction, miscarriage, stillbirth, and malformation, and seriously endanger human life and health. The detection methods for ZEN in the Chinese Pharmacopoeia(2020 edition) are liquid chromatography(LC) and liquid chromatography-mass spectrometry(LC-MS), and it is stipulated that ZEN should not exceed 500 μg in 1 000 g of Coicis Semen. Although these detection methods by instruments can achieve the qualitative and quantitative analysis of ZEN in Coicis Semen, their high detection cost and long periods hinder the rapid screening of a large number of samples in the field. In this study, the synthesized ZEN hapten was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) to obtain the complete ZEN antigen. By virtue of antibody preparation techniques, ZEN monoclonal antibody 4F6 was prepared, which showed 177.5%, 137.1%, and 109.7% cross-reactivity with ZEN structural analogs zearalanol, zearalenone, and α-zearalenol, respectively, and no cross-reactivity with other fungal toxins such as aflatoxin. Direct competitive enzyme-linked immunosorbent assay(dcELISA) based on ZEN monoclonal antibody 4F6 was developed for the determination of ZEN in Coicis Semen with an IC_(50) of 1.3 μg·L~(-1) and a detection range of 0.22-21.92 μg·L~(-1). The recoveries were 83.91%-105.3% and the RSD was 4.4%-8.0%. The established dcELISA method was used to determine the ZEN residuals in nine batches of Coicis Semen samples, and the results were validated by LC-MS. The correlation between the two detection methods was found to be 0.993 9, indicating that the established dcELISA could be used for the rapid qualitative and quantitative detection of ZEN residuals in Coicis Semen.
Humans
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Female
;
Pregnancy
;
Zearalenone
;
Coix
;
Enzyme-Linked Immunosorbent Assay
;
Mycotoxins
;
Antibodies, Monoclonal
4.A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression.
Ling XIN ; Qian WU ; Chongming ZHAN ; Hongyan QIN ; Hongyu XIANG ; Min GAO ; Xuening DUAN ; Yinhua LIU ; Jingming YE
Chinese Medical Journal 2023;136(24):2967-2973
BACKGROUND:
In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.
METHODS:
Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors.
RESULTS:
In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%.
CONCLUSION:
Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.
REGISTRITATION
ChiCTR.org.cn, ChiCTR2100046766.
Humans
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Female
;
Breast Neoplasms/diagnosis*
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Ki-67 Antigen
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Receptor, ErbB-2
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Prognosis
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Thrombosis
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Receptors, Progesterone
5.An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.
Zezhong LIU ; Wei XU ; Zhenguo CHEN ; Wangjun FU ; Wuqiang ZHAN ; Yidan GAO ; Jie ZHOU ; Yunjiao ZHOU ; Jianbo WU ; Qian WANG ; Xiang ZHANG ; Aihua HAO ; Wei WU ; Qianqian ZHANG ; Yaming LI ; Kaiyue FAN ; Ruihong CHEN ; Qiaochu JIANG ; Christian T MAYER ; Till SCHOOFS ; Youhua XIE ; Shibo JIANG ; Yumei WEN ; Zhenghong YUAN ; Kang WANG ; Lu LU ; Lei SUN ; Qiao WANG
Protein & Cell 2022;13(9):655-675
New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2
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Antibodies, Neutralizing
;
Antibodies, Viral
;
COVID-19
;
Epitopes
;
Humans
;
SARS-CoV-2/genetics*
;
Spike Glycoprotein, Coronavirus/genetics*
6.China experts' consensus on preventive and interceptive orthodontic treatments of malocclusions of children.
Xiao-Bing LI ; Quan-Fu YE ; Hong HE ; Hai-Ping LU ; Min ZHU ; Ruo-Ping JIANG ; Shu-Juan ZOU ; Xiang-Long HAN ; Li ZHOU ; Ke CHEN ; Xiao YUAN ; Jun-Mei ZHANG ; Li-Jun TAN ; Chang YIN ; Zhou HE ; Ang LI ; Bin CHENG ; Wen-Hua RUAN ; Fang HUANG ; Juan LIU ; Lan MA ; Rui ZOU ; Fang YANG ; Wei-Bing ZHANG ; Yu-Lou TIAN ; Bei-Zhan JIANG ; Lin-Qin SHAO ; Yang HUANG ; Li-Qin TANG ; Li GAO ; Chen-Chen ZHOU
West China Journal of Stomatology 2021;39(4):369-376
Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child
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China/epidemiology*
;
Consensus
;
Dental Care
;
Humans
;
Malocclusion/prevention & control*
;
Orthodontics, Interceptive
7.Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.
Jie WU ; Shu-Wei DUAN ; Hong-Tao YANG ; Yue-Yi DENG ; Wei LI ; Ya-Ni HE ; Zhao-Hui NI ; Yong-Li ZHAN ; Shan LIN ; Zhi-Yong GUO ; Jun ZHU ; Jing-Ai FANG ; Xu-Sheng LIU ; Li-Hua WANG ; Rong WANG ; Nian-Song WANG ; Xiao-Hong CHENG ; Li-Qun HE ; Ping LUO ; Shi-Ren SUN ; Ji-Feng SUN ; Ai-Ping YIN ; Geng-Ru JIANG ; Hong-Yu CHEN ; Wen-Hu LIU ; Hong-Li LIN ; Meng LIANG ; Lu MA ; Ming CHEN ; Li-Qun SONG ; Jian CHEN ; Qing ZHU ; Chang-Ying XING ; Yun LI ; Ji-Ning GAO ; Rong-Shan LI ; Ying LI ; Hao ZHANG ; Ying LU ; Qiao-Ling ZHOU ; Jun-Zhou FU ; Qiang HE ; Guang-Yan CAI ; Xiang-Mei CHEN
Journal of Integrative Medicine 2021;19(2):111-119
BACKGROUND:
Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.
OBJECTIVE:
This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTION:
This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m
MAIN OUTCOME MEASURES:
The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.
RESULTS:
A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.
CONCLUSION:
SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.
TRIAL REGISTRATION NUMBER
NCT02063100 on ClinicalTrials.gov.
8.Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats.
Qi-Juan LI ; Zhan-Guo WANG ; Yu XIE ; Qiao LIU ; Hui-Ling HU ; Yong-Xiang GAO
Chinese Journal of Natural Medicines (English Ed.) 2020;18(1):47-56
KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg·kg), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg, respectively) plus indomethacin, and sucralfate (1.71 mL·kg) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E (PGE) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL·kg) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin).
9. Effect of Pinelliae Rhizoma Praeparatum Cum Alumine Polysaccharides on MUC5AC mRNA in Lung Tissues of Allergic Asthma Model Rats
Cong HUANG ; Wei PENG ; Da-neng WEI ; Zhan-qiong ZHONG ; Mao-ting MOU ; Shu-jun WEI ; Yong-xiang GAO ; Chun-jie WU
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(22):15-21
Objective: To observe the effect of Pinelliae Rhizoma Praeparatum Cum Alumine polysaccharides(PRPCAP)on airway mucus secretion in rats with allergic asthma, in order to study the material basis of the "macromolecule" component of the polysaccharides as the original medicinal materials. Method: The 60 SPF-grade Wistar rats were induced by intraperitoneal injection of chicken ovalbumin (OVA) and aluminum-magnesium adjuvant, except for the normal control group. The OVA solution was aerosolized to establish a rat model of allergic asthma. After successful modeling, the rats were randomly divided into 5 groups, namely allergic asthma model group, positive drug group (montalurast sodium,5 mg·kg-1), high-dose PRPCAP group (400 mg·kg-1), middle-dose PRPCAP group (200 mg·kg-1) and low-dose PRPCAP group (100 mg·kg-1). The contents of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum and bronchoalveolar lavage fluid (BALF) supernatant were determined by enzyme-linked immunosorbent assay (ELISA), and the count of eosinophils (EOS) was detected by BALF sediment. The histopathological changes were observed by hematoxylin-eosin (HE) staining in lung tissue. The mRNA expression of mucin 5AC (MUC5AC) was detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR). Result: Compared with the normal control group, serum IL-4 level in the allergic asthma model group was significantly increased (P<0.01), IFN-γ level was significantly decreased (P<0.01), and EOS counts in BALF were significantly increased (P<0.01). Compared with the allergic asthma model group, the positive drug group, and high, middle, and low-dose PRPCAP groups could significantly reduce the serum IL-4 content (P<0.01), while high and middle-dose PRPCAP groups could significantly reduce the content of IL-4 in BALF (P<0.05, P<0.01), the middle-dose PRPCAP group could significantly increase the content of IFN-γ in serum (P<0.05), EOS counts in BALF were significantly lower in the positive drug group and all of PRPCAP groups (P<0.01). HE staining showed the pathological changes in the lung tissue of the allergic asthma model group and a mitigating effect in the positive drug group and all of PRPCAP groups. Compared with the normal control group, the expression of MUC5AC mRNA in the lung tissue of rats with allergic asthma was significantly increased (P<0.01). Compared with the model group of allergic asthma rats, the positive drug group and all of PRPCAP groups showed significant decrease in MUC5AC mRNA (P<0.01). Conclusion: The "macromolecule" component of polysaccharides in the Pinelliae Rhizoma Praeparatum Cum Alumine may be the material basis for the efficacy of eliminating dampness and eliminating phlegm.
10.Research rules of famous veteran traditional Chinese medicine practitioners in treating infertility.
Xiang-Jun QI ; Zhao-Ping ZHANG ; Hao-Zhan ZHANG ; Jian-Min LI ; Rui-Lan HUANG ; Qi-Lin LI ; Hong-Kai LIN ; Yi-Qian LU ; Guo-Ming CHEN ; Gao-Pi DENG
China Journal of Chinese Materia Medica 2019;44(7):1491-1496
To explore the medication rules of famous veteran traditional Chinese medicine practitioners in treating infertility based on medical cases of infertility collected from book series of Hundred Traditional Chinese Medicine Clinicians of Hundred Years in China and Prescription Proven by Traditional Chinese Medicine Masters. Researchers extracted the information of prescriptions from these cases according to the inclusion and exclusion criteria. Then, Excel 2010, SPSS Clementine(ver.12.0) and SPSS(ver. 22.0) were adopted respectively for frequency analysis, association rules analysis, cluster analysis and factor analysis. Cluster analysis was carried out by Ochiai algorithm of binary variable data, which was a systematic clustering method. And principal component analysis was used for factor analysis. Besides, KMO test and Bartlett spherical test were used for factor adaptation test. Finally, 151 medical cases and 396 prescriptions were included in total. A total of 60 kinds of frequently used herbs were identified according to the results of frequency analysis for medication, they were mainly used for activating blood and resolving stasis, tonifying and clearing heat respectively. The association rules analysis found out 25 drug pair association rules and 14 3-drug combination association rules. A total of 15 medicine groups were extracted by cluster analysis. KMO test and Bartlett spherical test indicated that the method was suitable for factor analysis, and 21 common factors were respectively extracted by factor analysis. Association rules indicated the characteristics of the therapeutic methods, like tonifying Qi and replenishing blood. The famous veteran traditional Chinese medicine practitioners utilized modified Siwu Decoction for tonifying blood and preferred Atractylodis Macrocephalae Rhizoma(Baizhu) for tonifying Qi. The results of both cluster analysis and factor analysis demonstrated the characteristics of the therapies for tonifying kidney, activating blood, tonifying spleen and dispelling dampness. In addition, factor analysis could reflect the therapies for nourishing Yin, tonifying kidney, warming the meridian, dissipating cold, nourishing blood and dispelling blood stasis. These results of analysis comprehensively showed out the medication characteristics of famous veteran traditional Chinese medicine practitioners of strictly following the pathogenesis, making good use of classical formulas and providing proper compatibility. In conclusion, data mining techniques(including frequency analysis, association rules analysis, cluster analysis and factor analysis) were used to comprehensively analyze the medication rules of famous veteran traditional Chinese medicine practitioners in treating infertility, which is helpful for guiding the clinical practice of treating infertility with traditional Chinese medicine.
China
;
Humans
;
Infertility
;
drug therapy
;
Medicine, Chinese Traditional

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