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.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

ObjectiveAutonomic dysfunction is a common and serious complication in patients with early chronic kidney disease （CKD）. Sweat gland dysfunction is an initial sign of autonomic dysfunction. Electrochemical skin conductance （ESC） measurement by reverse iontophoresis and chronoamperometry to assess sweat gland function may detect patients with mild renal insufficiency in healthy population for early intervention and treatment to delay further deterioration of renal function. MethodsAn EZSCAN score （0~100） was calculated using a proprietary algorithm based on the chronoamperometry analysis. A total of 6 661 subjects who received physical examination from the physical examination center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to October 2020 were enrolled， including 2 075 （31.15%） subjects with reduced renal function （eGFR < 90 mL·min^-1·1.73 m^-2） as the case group and 4 586 （68.85%） subjects with normal renal function （90 mL·min^-1·1.73 m^-2≤ eGFR ≤120 mL·min^-1·1.73 m^-2） as the control group. Lasso regression was used to screen covariates， and the relationship between the risk score and eGFR was analyzed by loess curve and logistic regression. ResultsAfter multivariate adjustment， the risk score was correlated with the risk of eGFR decline. Compared with the group with the lowest risk value （Q1<24）， the OR（95%CI ）of Q2 （25-27）， Q3 （28-47）， and Q4 （48-75） were 1.85 （1.55， 2.21）， 2.53 （2.13， 3.00）， 2.49 （2.13， 2.93）， respectively. The maximum area under the ROC curve is 0.75（0.74，0.76）， the sensitivity is 73.98%， the specificity is 63%， the positive predictive value is 47.49%， the negative predictive value is 84.25%， and the Youden index is 0.369 72， the optimal cutoff value is 25. ConclusionsEZSCAN could be a useful screening tool to identify healthy individuals at increased risk of renal function decline， and the one with an EZSCAN score of more than 25% should undergo diagnostic laboratory testing.

Foot-and-mouth disease (FMD) is an acute, severe, and highly contagious infectious disease caused by foot-and-mouth disease virus (FMDV), which seriously endangers the development of animal husbandry. The inactivated FMD vaccine is the main product for the prevention and control of FMD, which has been successfully applied to control the pandemic and outbreak of FMD. However, the inactivated FMD vaccine also has problems, such as the instability of antigen, the risk of spread of the virus due to incomplete inactivation during vaccine production, and the high cost of production. Compared with traditional microbial and animal bioreactors, production of antigens in plants through transgenic technology has some advantages including low cost, safety, convenience, and easy storage and transportation. Moreover, since antigens produced from plants can be directly used as edible vaccines, no complex processes of protein extraction and purification are required. But, there are some problems for the production of antigens in plants, which include low expression level and poor controllability. Thus, expressing the antigens of FMDV in plants may be an alternative mean for production of FMD vaccine, which has certain advantages but still need to be continuously optimized. Here we review the main strategies for expressing active proteins in plants, as well as the research progress on the expression of FMDV antigens in plants. We also discuss the current problems and challenges encountered, with the aim to facilitate related research.
Animals ; Foot-and-Mouth Disease Virus/genetics* ; Foot-and-Mouth Disease/prevention & control* ; Antigens, Viral/genetics* ; Viral Vaccines

OBJECTIVE: To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss. METHODS: A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed. RESULTS: In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss. CONCLUSION In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.
Humans ; Tooth Loss/etiology* ; Periodontitis/complications* ; Tooth ; Periodontal Diseases ; Molar

Breast cancer is the most common cancer among women worldwide, and it seriously threatens women′s life and health. circular RNA (circRNA) play a key role in the development and drug resistance of various cancers, including breast cancer. circRNA is an endogenous RNA molecule with a single-stranded closed structure, which has unique biological characteristics and function, and is a current research hotspot. This article will review circRNA as potential biomarkers to predict breast cancer drug resistance and therapeutic targets.

OBJECTIVE: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. METHODS: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. RESULTS: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. CONCLUSION Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.
Female ; Male ; Humans ; Cross-Sectional Studies ; Sjogren's Syndrome ; Rheumatoid Factor ; Arthritis, Rheumatoid ; Blood Sedimentation ; Phenotype

OBJECTIVE: To investigate clinical outcomes of countertraction method in treating irreducible subcoracoid dislocation of shoulder joint combined with Hill-Sacks injury. METHODS: A total of 56 patients with irreducible subcoracoid dislocation of the shoulder joint combined with Hill-Sacks injury admitted from December 2013 to June 2020 were retrospectively analyzed. Under the anesthesia of shoulder joint cavity injection, the reduction was performed by using anti-traction method (experimental group) and traditional Hippocrates method (control group), 28 cases in each group. There were 11 males and 17 females in experimental group, with an average age of (61.95±19.32) years old, 9 cases on the left side, and 19 cases on the right side. Twelve males and 16 females in control group, with an average age of (63.13±12.75) years old, 11 cases on the left side, 17 cases on the right side. The curative effects between two groups were evaluated before and after operation, including the success rate of reduction, the duration of reduction, the distance from successful reduction to injury, complications and functional rehabilitation(Constant score of shoulder joint). RESULTS: The success rates of reduction in experimental group and control group were 92.86%(26/28) and 67.86% (19/28), respectively, and the difference was statistically significant (P<0.05). The duration of simple reduction was (4.25±2.13) min and ( 6.31±1.69) min, the difference was statistically significant (P<0.05);the time from successful reduction to injury was (9.16±0.94) h and (8.94±1.31) h, respectively, with no significant difference(P>0.05). There were no complications such as vascular nerve injury and fracture in experimental group, 2 cases of axillary nerve injury and 1 case of humeral head fracture in control group. Constant scores of shoulder joint between experimental group and control group were (92.34±5.62) points and (90.91±4.73) points, respectively, with no significant difference (P>0.05). CONCLUSION For patients with irreducible subcoracoid dislocation of the shoulder joint with Hill-Sacks injury, the countertraction method under anesthesia of the shoulder joint cavity achieved a higher success rate and few complications.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Shoulder Joint/surgery* ; Shoulder Dislocation/complications* ; Retrospective Studies ; Shoulder Injuries ; Joint Dislocations/complications* ; Joint Instability/surgery*

This review made a systematic textual research on the historical evolution and changes of the origin， producing areas and quality， harvest time and processing methods， and cultivation technique of Poria in famous classical formulas from the Catalogue of Ancient Famous Classical Formulas （the First Batch） by referring to the literature of ancient materia medica and medical books combining with the modern literature in CNKI， Wanfang Data and other databases， which could provide reference for the development and research of the famous classical formulas containing Poria. According to the research， the origin of Poria in ancient times was the dried sclerotia of Poria cocos. The producing area of Poria is widely distributed in China， mainly produced in Anhui， Hubei， Henan and Yunnan provinces. The quality of Poria from Yunnan is better， and the yield is larger in Anhui and Hubei provinces. The quality evaluation of Poria is basically the same from ancient to modern， which has the characteristics of large block， heavy weight， thin and wrinkled skin， and white and delicate cross section. The harvesting period of Poria is usually in August of the lunar calendar. The initial processing has undergone the evolution from drying in shade in the ancient time to drying in shade after sweating in the modern time. From ancient times to the present， Poria has been processed by cutting to prepare the Fuling lumps and Fuling slices. The cultivation technique has experienced the evolution process of "wild Poria-inoculation of live pine root-basswood cultured". At present， Poria is mainly cultivated by artificial basswood with mature technical methods and abundant yields， which can meet the research and development needs of the famous classical formulas.

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.