Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Rehmanniae Radix is a common medicine of traditional Chinese medicine， which has the function of nourishing Yin and tonifying the kidney， and has a long application history of processing. This medicine was first recorded in Synopsis of Golden Chamber （《金匮要略》）， which was mainly produced by steaming and boiling. Its processing materials were diverse. In addition to rice wine， honey， Amomi Fructus， milk， Aquilariae Lignum Resinatum， and Carthami Flos were also recorded in ancient books， but with the evolution of time， the characteristic excipients gradually disappeared. Based on this， starting with different excipients， the author consulted the classics of materia medica and processing specifications in various regions， sorted out the historical evolution of Rehmanniae Radix processing， and explored new methods and new ideas to exert the maximum efficacy on this basis. At the same time， the effects of different processing excipients on the chemical components and pharmacodynamic effects of Rehmanniae Radix were analyzed. After literature review， it was found that Rehmanniae Radix mainly had the effects of clearing heat and cooling blood， nourishing Yin and generating fluid. Its traditional processing excipients generally used rice wine， Carthami Flos and others. After processing with different excipients， there was different effects on the chemical components and pharmacological effects of Rehmanniae Radix. In summary， this paper can provide useful reference for standardized research on different processed products of Rehmanniae Radix.

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.
BRCA1 Protein/genetics* ; BRCA2 Protein/genetics* ; Breast Neoplasms/pathology* ; Cross-Sectional Studies ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Mutation ; Recombinational DNA Repair ; Triple Negative Breast Neoplasms/pathology*

This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.
Drugs, Chinese Herbal/chemistry* ; Excipients ; Furaldehyde/analogs & derivatives* ; Iridoid Glucosides ; Plant Extracts ; Rehmannia/chemistry* ; Sugars ; Technology ; Water

【Objective】 We sought to compare ultrasound superb micro- vascular imaging （SMI） and contrast- enhanced ultrasound（CEUS）in the evaluation of carotid plaque neovascularization，and to understand the feasibility of SMI as a method to screen neovascularization of plaque.【Methods】A total of 60 cases，with a total of 109 plaques underwent SMI and CEUS to detect neovascularization of plaque.【Results】SMI and CEUS examination results were consistent in 101 of 109 plaques. The cost of SMI was less than CEUS（￥150 vs. ￥900）. There was significant difference in examination time between SMI and CEUS［（5.0 ± 1.4 vs. 18.5 ± 2.2）min，P < 0.05］.【Conclusion】Preliminary results showed that these two methods have good consistency. SMI also has advantages ：simple ，less time-consuming ，cheap and low risk. It indicates that SMI may be an effective screening method for neovascularization in plaques.

Dihydrochelerythrine was isolated from the ethanol extract of Corydalis yanhusuo by chromatographic and recrystallization techniques. To our knowledge, this is the first report that dihydrochelerythrine was found to be unstable. The NMR, HPLC, and LC-MS were applied to monitor the structural conversion process of dihydrochelerythrine. The results showed that when dissolved in polar deuteration solvent (e.g., DMSO-₆ & MeOD), dihydrochelerythrine is directly converted to chelerythrine gradually. However, if used non-polar reagent (e.g.,CD₂Cl₂), the sample of dihydrochelerythrine undergoes the formation of pseudobase, chelerythrine, and bimolecular ether then followed by oxidation to oxychelerythrine as the major final product. Which leads to this phenomenon maybe is that the C-6 in dihydrochelerythrine is highly reactive to nucleophiles, and is easily converted to different derivatives in different solvents attributed to the solvent effect. This finding will contribute to the extraction and isolation, bioactivity screening, and quality evaluation of medicinal materials containing dihydrochelerythrine and other similar derivatives.

OBJECTIVETo investigate the protective effect and mechanism of curcumin derivatives B06 on myocardium from type 2 diabetic rats.

METHODSThirty-five male SD rats were randomly divided into 5 groups, normal control group (NC group), high fat group (HF group), high fat treatment group (FT group), diabetes mellitus group (DM group) and diabetes treatment group (DT group) (n = 7). The late four groups were fed with high fat food, after four weeks of high fat feeding, the rats from DM group and DT group were injected with low dosage of streptozocin intraperitoneally to induce diabetes mellitus, FT group and DT group were gavaged with curcumin derivatives B06 at the dosage of 0.2 mg/kg x d. The blood glucose and lipid were detected biochemically, blood insulin was assayed by ELISA and the insulin resistance index was calculated, the morphology of myocardium was observed by light and transmission electron microscopy, the protein expression of AMP-activated protein kinase alpha (AMPKalpha) and phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) in myocardium were tested by Western blot.

RESULTSThe level of blood glucose, lipid, insulin and the insulin resistance index were increased in HF group and DM group, but they were decreased after the treatment with B06. The expression of AMPKalpha and p-AMPKalpha were decreased, but they became increased after the treatment of B06. There were increased collagen fibers in interstitium and expansion of mitochondria in cytoplasm of myocardium from DM group, but they were ameliorated in B06 treatment group.

CONCLUSIONIt is suggested that B06 may relieve the damage of myocardium from type 2 diabetic rats and the increased expression of AMPKalpha and p-AMPKalpha may be involved in it.

AMP-Activated Protein Kinases ; metabolism ; Animals ; Blood Glucose ; Curcumin ; pharmacology ; Diabetes Mellitus, Experimental ; physiopathology ; Heart ; drug effects ; Insulin Resistance ; Male ; Myocardium ; pathology ; Rats ; Rats, Sprague-Dawley ; Streptozocin

BACKGROUNDTrabeculectomy has become a mainstream treatment in intraocular pressure (IOP) reduction for primary angle-closure glaucoma (PACG); combined trabeculectomy and cataract surgery was reported to reduce IOP and simultaneously improve vision for patients with PACG and coexisting cataract. This study was specialized to compare the efficacy and safety of combined phacotrabeculectomy with that of trabeculectomy only in the treatment of PACG with coexisting cataract.

METHODSThis is a comparative case series study. Thirty-one patients (31 eyes) with PACG and coexisting cataract were enrolled. Of these, 17 underwent phacotrabeculectomy and 14 underwent trabeculectomy alone. IOP, filtering blebs, and complications were compared at the final follow-up. Complete success was defined as a final IOP less than 21 mmHg without IOP-lowering medication.

RESULTSAfter 10 months of postoperative follow-up, the phacotrabeculectomy and trabeculectomy groups showed no significant differences regarding IOP reduction ((20.59 ± 7.94) vs. (24.85 ± 14.39) mmHg, P = 0.614), complete success rate (88% vs. 71%, P = 0.370), formation rate of functioning blebs (65% (11/17) vs. 93% (13/14), P = 0.094), and complications (41% (7/17) vs. 57% (8/14), P = 0.380). IOP-lowering medication was not required for most of the patients in both groups. Additional surgery interventions, including anterior chamber reformation and phacoemulsification, were needed in the trabeculectomy group, whereas no surgery was needed postoperatively in the phacotrabeculectomy group.

CONCLUSIONPhacotrabeculectomy and trabeculectomy treatments exhibit similar IOP reduction, successful rates, and complications when it comes to treating PACG patients with coexisting cataract, although additional surgery intervention may be needed for a few cases with cataract and complications after trabeculectomy.

Aged ; Cataract Extraction ; Female ; Glaucoma, Angle-Closure ; physiopathology ; surgery ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Phacoemulsification ; adverse effects ; methods ; Postoperative Complications ; etiology ; Trabeculectomy ; adverse effects ; methods ; Visual Acuity

OBJECTIVETo study the HIV incidence and risk factors among sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province.

METHODSA cohort of sero-negative spouses of the HIV patients had been developed and followed up since November, 2005. HIV new infections and related behaviors had been investigated every six months.

RESULTSBy the end of June, 2008, 790 sero-negative spouses of HIV patients had been recruited, of whom 702 were followed-up for at least one time. During the total 1202.35 person-years, 31 new HIV infections were identified, with an overall incidence of 2.58/100 person-years. The HIV incidence rates were 2.22/100 person-years in 2006, 2.95/100 person-years in 2007 and 2.74/100 person-years in 2008. Data from the Cox proportional hazard regression model indicated that those who resided in Yingjiang county [hazard ratio (HR) = 4.37, 95%CI: 1.48 - 12.90, P = 0.008], ever using drugs (HR = 3.49, 95%CI: 1.09 - 11.18, P = 0.035), or having an HIV-infected spouse who never exposed to antiretroviral treatment (HR = 3.60, 95%CI: 1.41 - 9.16, P = 0.007) were at higher risk for HIV infection.

CONCLUSIONSero-negative spouses of HIV patients in Dehong prefecture of Yunnan province had a relatively high incidence of HIV new infection during 2006-2008. More efforts should put on those people living in these areas, having a history of drug use or having an HIV-infected spouse who had never been exposed to antiretroviral treatment.

Adolescent ; Adult ; China ; epidemiology ; Female ; HIV Infections ; epidemiology ; HIV Seronegativity ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Sexual Behavior ; Spouses ; Young Adult

Objective To study the HIV incidence and risk factors among sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province. Methods A cohort of sero-negative spouses of the HIV patients had been developed and followed up since November, 2005.HIV new infections and related behaviors had been investigated every six months. Results By the end of June, 2008, 790 sero-negative spouses of HIV patients had been recruited, of whom 702 were followed-up for at least one time. During the total 1202.35 person-years, 31 new HIV infections were identified, with an overall incidence of 2.58/100 preson-years. The HIV incidence rates were 2.22/100person-years in 2006, 2.95/100 person-years in 2007 and 2.74/100 person-years in 2008. Data from the Cox proportional hazard regression model indicated that those who resided in Yingjiang county [hazard ratio (HR) =4.37, 95% CI: 1.48-12.90, P=0.008] , ever using drugs (HR=3.49, 95% CI:1.09-11.18, P=0.035) , or having an HIV-infected spouse who never exposed to antiretroviraltreatment (HR=3.60, 95% CI: 1.41-9.16, P=0.007) were at higher risk for HIV infection.Conclusion Sero-negative spouses of HIV patients in Dehong prefecture of Yunnan province had a relatively high incidence of HIV new infection during 2006-2008. More efforts should put on those people living in these areas, having a history of drug use or having an HIV-infected spouse who had never been exposed to antiretroviral treatment.