The ripe dried fruit of citron(Citrus medica) is one of the important sources of Chinese herb Citri Fructus. At the same time, it is also grown for edible and ornamental uses. There are many species and abundant genetic variation. To clarify the intraspecific variation and resource distribution of citron, this study investigated the variation in 11 citron fruits, basically covering the main species in China, including Xiaoguo citron(C. medica var. ethrog), Goucheng(C. medica var. yunnanensis), Muli citron(C.medica var. muliensis), Dehong citron(C.medica×Citrus spp.), Fuzhou citron(C.medica×C.grandis?), Mawu(C.medica×C.grandis?), Cangyuan citron, Binchuan citron, Sweet citron, Big citron, and Small citron. The natural communities of citron were proved to be mainly distributed in the southwestern and western Yunnan and southeastern Tibet of China, with Yunnan, Sichuan, Guangxi, Chongqing, Hubei, and Zhejiang identified as the main production areas. Citron has also been widely grown in India, the Mediterranean region, and the Caribbean coast countries. The field investigation revealed the large-scale intraspecific variation of citron fruits. Most of the fruits are oval-like or sphere-like in shape. The fruits are green when raw and yellow when ripe, with oil cell dots on the skin, stripe-likes running from top to bottom, and bulge at the top. Usually, in the smaller citron fruits, the pulp and juice vesicles are better developed and the central columella is tighter. By contrast, the juice vesicles and central columella in larger fruits became more vacant, with carpels visible, and the apex segregation and development of the carpels is one of the reasons for variation. These variations should be given top priority in the future variety selection and breeding, and the quality differences of different citron species and their mechanisms should be further studied. In particular, variety selection and classification management according to their medicinal or edible purposes will provide scientific and technological supports for the orderly, safe, and effective production of citron products consumed as food and medicine.
China ; Citrus ; Fruit ; Taste ; Tibet

OBJECTIVE: To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML). METHODS: A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. The risk stratification of patients was poor or very poor, according to IPSS-R score. The treament results of decitabine combined with CEG and decitabine combined with CAG were compared. RESULTS: The comparison of the two regiem showed that the DCEG regimen had advantages on total effective rate (ORR, 86.4% vs 47.8%, respectively), overall survival time (OS) (10.0 months vs 6.0 months, respectively) and progression-free survival time (PFS) (9.0 months vs 3.0 months, respectively). About 50% of MDS patients treated by DCEG regimen achieved PR or CR, with a median OS of 31 months. Multivariate analysis showed that patients with PR or CR after induction therapy and DCEG regimen had longer survival time (31months). The incidence of bone marrow suppression, infection and treatment-related mortality rate were similar between the two groups. CONCLUSION Decitabine combined with CEG regimen could improve the survival of patients with high-risk MDS and MDS-transformed AML. The conclusion of the reaserch needs to be validated by a larger prospective randomized clinical trial.
Aclarubicin ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine/therapeutic use* ; Cytarabine/therapeutic use* ; Decitabine/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Myelodysplastic Syndromes/drug therapy* ; Patients ; Prospective Studies ; Treatment Outcome

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.

This paper explored the background, framework and approach, contents and implementation of WHO Rehabilitation in Health System using approaches of ICF and WHO Handbook for Guideline Development. The actions and significances of implementations of seven recommendations and one good practice statements on assistive products had been discussed.

Objective To use World Health Organization Family International Classifications (WHO-FICs) to explore the framework and approaches of development and research of guidelines of rehabilitation at levels of policies, community and services.Methods The important documents and tools of rehabilitation at international level, including United Nations Convention on the Rights of Persons with Disabilities, WHO World Report on Disability, Community-based Rehabilitation Guideline, Rehabilitation in Health Service System, and International Classification of Diseases (ICD), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHI) of WHO-FICs, had been discussed.Results The framework, classifications, diagnosis and description of diseases and functioning, coding, intervention and functioning evaluation based on ICD-11, ICF and ICHI-β-2 had been established for development and implementation of rehabilitation guidelines and Cochrane rehabilitation.Conclusion The framework and systematic approaches of ontology, classification, terminology, coding, diagnosis and description of diseases and functioning, interventions and evaluations for the development and implementation of rehabilitation guidelines had been developed.

Objective:To analyze the results of Grading of Recommendations Assessment, Development and Evaluation (GRADE) for clinical practice guidelines of rehabilitation. Methods:Clinical practice guidelines of rehabilitation were systematically retrieved from PubMed, EMBASE, CNKI, China Biology Medicine disc, Wanfang database and the guideline-related websites until January 11, 2020. Two researchers independently screened guidelines using Grading of Recommendations Assessment, Development and Evaluation (GRADE), and extracted and analyzed the results. Results:A total of 83 clinical practice guidelines of rehabilitation were included, in which 46 (55.4%) applied grading systems. Only four (4.8%) guidelines applied GRADE, including 44 recommendations, in which 39 guidelines (88.6%) had quality of evidence. Among the evidences citied in the recommendations, low quality evidences were the most (34.1%); among the recommendations, weak recommendations were more (56.8%). The quality of strong recommendation supporting evidence was higher than that of weak recommendation (χ² = 8.218,P < 0.05). Conclusion:The application of the GRADE grading system in clinical practice guidelines of rehabilitation remains to be improved. It is proposed for guideline makers to further implement the methodology of guidelines and GRADE to improve the reliability and applicability of the clinical practice guidelines of rehabilitation more effectively.

To study the binding capacity of active ingredients of Daidai lipid-lowering flavonoid extract and plasma protein,investigate the ways to improve the traditional formula for calculating protein binding rates based on ultrafiltration,and increase the stability and reliability of the experimental results. UPLC-MS/MS was used to establish a quantitative analysis method for simultaneous determination of active ingredients( neohesperidin and narngin) in ultrafiltrate. The protein binding rates were calculated by the traditional ultrafiltration formula. The correction factors( F) were introduced later,and the binding rates calculated with the correction factors were compared with those without the correction factors. The binding capacity of the extract and plasma protein was evaluated. The quantitative analysis method established by UPLC-MS/MS had a good specificity. The standard curve and linear range,method accuracy,precision and lower limit of quantitation all met the requirements. The method met the requirement for quantitative detection of the active ingredients in ultrafiltrate after the rat plasma was filtrated in the ultrafiltration tube. Under the experimental conditions,the binding rates of both active ingredients( neohesperidin and narngin) were higher than 90%. The active ingredients and rat plasma protein were bound in a concentration-dependent manner,with statistically significant differences( P<0. 01). There was no statistically significant difference between the protein binding abilities of the two active ingredients with rat plasma protein. Therefore,the active ingredients of Daidai lipid-lowering flavonoid extract had a relatively strong binding strength with rat plasma protein,and they were bound in a concentration-dependent manner. Additionally,when calculating protein binding rates by the traditional ultrafiltration formula,the correction factors could be introduced to effectively reflect the errors of multiple ingredient groups in traditional Chinese medicine extracts.This correction method could provide a reference thinking and practical reference for the improvement of the determination method of the traditional Chinese medicine plasma protein binding ability based on ultrafiltration.
Animals ; Blood Proteins ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacology ; Flavonoids ; pharmacology ; Hypolipidemic Agents ; pharmacology ; Lipids ; Rats ; Reproducibility of Results ; Tandem Mass Spectrometry

Objective: To study on the physical and chemical properties of dichroa alkali hydrochloride and to establish a method for the determination of entrapment efficiency of dichroa alkali hydrochloride liposomes. Method: HPLC was used to determine the content of dichroa alkali hydrochloride with mobile phase of acetonitrile-water-triethylamine-glacial acetic acid(9:91:0.35:0.75) and detection wavelength at 265 nm.The oil-water partition coefficient of this compound in different pH range was measured by shake flask method.The stability of the dichroa alkali hydrochloride in phosphate buffer solution with different pH after sterilization at 125℃ for 30 min was investigated.Ammonium sulfate gradient method was used to prepare dichroa alkali hydrochloride liposomes.The microcolumn was prepared by dextran gel and cation exchange resin,respectively.Then the free drug and liposome were separated by centrifugation,the drug content was measured,and the encapsulation efficiency was calculated.The t-test was performed using SPSS 20.0 software,the differences between these two methods were compared. Result: In the pH 6-9,the oil-water partition coefficient of dichroa alkali hydrochloride increased with increasing of pH,which was between 0.016 and 1.44;the recovery rate of dichroa alkali hydrochloride after sterilization was 37.16%-57.91%.Between the dextran gel microcolumn centrifugation and the cation exchange resin microcolumn centrifugation,there was no significant difference in the entrapment efficiency of the liposomes. Conclusion: Dichroa alkali hydrochloride is suitable for preparation of liposomes.However,its stability is not ideal,so the experimental temperature should be strictly controlled in the preparation process.Dextran gel microcolumn centrifugation and cation exchange resin microcolumn centrifugation can be used to determine the entrapment efficiency of dichroa alkali hydrochloride liposomes,and the cation exchange resin microcolumn centrifugation is suggested after comparison.

The paper studies and compares the metabolic difference of active ingredients of lipid-lowering flavonoid extract of Daidai in rat livers and intestinal microsomes,in order to explore the phase Ⅰ metabolism characteristics of active ingredients in livers and intestines. UPLC-MS/MS was used to establish a quantitative analysis method for active ingredients,neohesperidin and narngin,in a phase Ⅰ metabolism incubation system of liver and intestinal microsomes. Differential centrifugation was used to make liver and intestinal microsomes of rats. A phase Ⅰ metabolism incubation system was established,and the concentrations of the residual at different incubation time points were analyzed. Graphs were plotted to calculate the metabolic elimination half-life of the main active parts,with the natural logarithm residual percentage values ln( X) at different time points as the y axis,and time t as the x axis. The metabolism characteristics of the active ingredients were compared. The established UPLC-MS/MS quantitative analysis method has a good specialization,standard curve and linear range,accuracy and precision,with a satisfactory lower quantitative limit. The method allows quantitative detection of the active ingredients in a phase Ⅰ metabolism incubation system of liver and intestinal microsomes of rats. In the rats liver microsomes incubation system,the metabolic elimination half-life of neohesperidin and narngin were( 2. 20 ± 0. 28) h and( 1. 97±0. 28) h respectively. The elimination half-life of neohesperidin was larger than that of narngin,but with no statistically significant difference. In the rats intestinal microsomes incubation system,the metabolic elimination half-lives of neohesperidin and narngin were( 3. 68±0. 54) h and( 2. 26±0. 13) h respectively. The elimination half-life of neohesperidin was larger than that of narngin,with statistically significant differences( P<0. 05). The elimination half-lives of the active ingredients in liver microsomes were smaller than those in intestinal microsomes. The experiment results showed that the active ingredients of lipid-lowering flavonoid extract of Daidai had different elimination half-lives in phase Ⅰ rats liver and intestinal microsomes incubation system. This implied that they had different metabolic characteristics in rats liver and intestine,and liver may be the main metabolism site of the active ingredients. The phaseⅠ metabolism of narngin was stronger than that of neohesperidin. The differences between their metabolic characteristics may be related to the binding sites of B-ring hydroxyl in flavonoid glycosides and the number of methoxyl group. The results provided an important experimental basis for further development and clinical application of lipid-lowering flavonoid extract preparation of Daidai.
Animals ; Chromatography, Liquid ; Citrus sinensis ; Flavonoids ; Intestines ; Lipids ; Liver ; Microsomes, Liver ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

OBJECTIVETo compare the expression of DKKL1 in ejaculated spermatozoa of normal fertile men and men with asthenospermia and investigate the role of DKKL1 in the pathogenesis of asthenospermia.

METHODSThe characteristics of semen samples collected from normal fertile men and men with asthenospermia were analyzed using computer-assisted sperm analysis according to WHO criteria. The ejaculated sperms were isolated by Percoll discontinuous density gradients to detect the expression of DKKL1 mRNA and protein using real-time PCR and Western blotting.

RESULTSThe expression of DKKL1 mRNA was significantly down-regulated by 11.1 times in asthenospermic men as compared with that in normal fertile men (P<0.01). Western blotting showed that the expression of DKKL1 protein was down-regulated by 2.4 times in asthenospermic men compared to normal fertile men.

CONCLUSIONThe expression of DKKL1, which may play an important role in sperm motility,is significantly decreased in ejaculated spermatozoa of men with asthenospermia.