Objective: To detect early subclinical signs of autonomic dysfunction in the cardiovascular system and explore the mechanism of orthostatic hypotension (OH) in patients with multiple system atrophy (MSA). Methods: Eighteen male patients with possible MSA and 10 healthy men were recruited. The hemodynamic responses to head-up tilt and tilt-reversal were studied by an electrically-powered tilt table and a non-invasive cardiac output measurement (NICOM) system. Results: At supine, there was no signifi cant difference in blood pressure, heart rate (HR), stroke volume, cardiac output and total peripheral resistance between MSA patients and healthy controls. During tilting upright, OH developed in 5 MSA patients, with a 23.7±4.8 mmHg drop in systolic blood pressure. Patients with OH were older and exhibited higher scores in unifi ed Multiple System Atrophy Rating Scale part I than patients without OH. The stroke volume, cardiac output and total peripheral resistance did not differ between groups. The controls had the most signifi cant HR elevation (6.5±2.5 bpm) during tiltup, followed by patients without OH (2.8±1.6 bpm) and those with OH (-0.2±2.2 bpm). A similar trend of HR decrease was observed during return to supine posture. The process of tilt-reversal altered HR more signifi cantly than head-up tilt in controls (8.0±2.9 vs 6.5±2.5 bpm; P=0.031) and patients without OH (4.2±2.1 vs 2.8±1.6 bpm; P=0.032), but not in patients with OH (1.2±1.5 vs -0.2±2.2 bpm; P=0.380). Conclusions: The HR change during postural challenge showed signifi cant difference between MSA patients and healthy controls. Impaired HR responsiveness contributed to OH in MSA. Monitoring HR during the tilt table test may be a practical and useful method to detect early autonomic dysfunction in patients with MSA.

The pharmacokinetics of a long-circulating PEGylated Radix Ophiopogonis polysaccharide (ROP) was investigated in rats following i.v. or s.c. administration at three dose levels (9, 20, 50 mg x kg(-1)). A moderate coupling reaction between the hydroxyl-activated ROP and the amino-terminated mPEG was chosen to produce PEGylate ROP. The grafting degree of the prepared conjugate was 1.03, and the molecular mass of mPEG used was 20 kDa. High-performance gel permeation chromatorgraphy with fluorescein isothiocyanate prelabeling was established to determine levels of the conjugate in plasma. The results showed that the elimination half-life of the conjugate following s.c. administration was basically identical to that after iv administration. An accurate linear correlation was observed between administration doses and areas under the curve of plasma conjugate level vs. time profile, regardless of the administration route. The absolute bioavailability of the conjugate following sc administration was approximately 56%, and the mean in vivo residence time was 52.1 h, increased 2.4 times compared to those of iv administration. In general, linear pharmacokinetics was observed for the conjugate within the dose range studied, and sc should be a promising administration route for the conjugate.
Animals ; Area Under Curve ; Biological Availability ; Drug Carriers ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; pharmacokinetics ; Half-Life ; Injections, Intravenous ; Injections, Subcutaneous ; Ophiopogon ; chemistry ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Polyethylene Glycols ; chemistry ; Polysaccharides ; administration & dosage ; chemistry ; isolation & purification ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the prevalence and the clinical characteristics of mitochondrial gene mutation A3243G (mt tRNA(Leu(UUR)) 3243 A-->G) in patients with type 2 diabetes mellitus (DM2) in China.

METHODSFour hundred and twenty-eight cases of DM2 patients were selected randomly. One hundred and eighty-eight individuals were healthy controls. The mutation was assayed by PCR-restriction fragment length polymorphism technique. The target fragments of PCR were digested with restriction endonuclease Apa I.

RESULTSmt tRNA(Leu(UUR)) 3243A-->G gene mutation was found in 2 of 428 patients with DM2, but not found in the controls. Further investigation of the relatives of the 2 patients' families revealed that 3 members were the carriers of mt tRNA A3243G gene mutation and the patients with diabetes. In addition, one proband and her son were characterized with the syndrome of mitochondrial encephalomyopathy with lactic acidosis. The diabetes of these patients is frequently accompanied by hearing impairment or deafness with maternal inheritance.

CONCLUSIONThe prevalence of the mitochondrial gene A3243G mutation is 0.47% in DM2 patients in China. The data acquired in this study suggest that the clinical phenotype of these patients with A3243G should be heterogeneous.

Adult ; Aged ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; RNA, Transfer, Amino Acyl ; genetics

The paper is to report the observation of pharmacokinetic changes of the characteristic ingredients in the combinations of different-dose herbs of Shaoyao-Gancao decoction. After the establishment of HPLC analytical method of plasma effective constituents, rats were orally administered with different-dose herbs of Shaoyao-Gancao decoction. Blood samples at different times after administering these decoctions were collected, and then were analyzed by HPLC fingerprints technology. Pharmacokinetic parameters of characteristic peaks were analyzed by SPSS 15.0 software and DAS 2.0. At last, we looked for the correlation of those pharmacokinetic parameters and the dosage of Gancao. The best dose of Shaoyao-Gancao decoction was at the ratio of 4 to 4, which was consistent with the dose commonly used in ancient times. The absorption of characteristic peaks from Shaoyao-Gancao decoction was related with the dosage of Gancao, and there existed interaction between each characteristic ingredients. There existed the right dose-ratio of Shaoyao and Gancao to get the best effect. The absorptions of effective constitutents were mutual waxing and waning in order to increase biological effects together. It's demonstrated the compatibility connotation at a right dose-ratio of Shaoyao-Gancao decoction through the angle of pharmacokinetics.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; methods ; Dose-Response Relationship, Drug ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Glycyrrhiza uralensis ; chemistry ; Male ; Paeonia ; chemistry ; Plasma ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo provide a mathematical set-based method for evaluating drug release kinetics of multi-component traditional Chinese medicine preparations.

METHODWith Fuzheng Huayu prescription as the study model, a mathematical set-based method for evaluating drug release kinetics was established to guide the preparation of drug release system of Fuzheng Huayu prescription, and a quantitative evaluation was made for its multi-component drug release characteristics. Its accuracy was verified by Kalman filtering method.

RESULTThe comparison between the two showed that the sample No. 4 of Fuzheng Huayu drug release system showed synchronized drug release with its reference preparation Fuzheng Huayu capsules.

CONCLUSIONThe results verified the accuracy and rationality of the evaluation method based on mathematics set. Meanwhile, it displayed the release of target preparations according to asynchronous coefficient (k) and other parameters, and found the orientation of regulating and improving the unit drug release dosage from relevant error parameters of various characteristic peak information, in order to purposefully regulate relevant components, and enable target preparations to meet the synchronized drug release requirements of the reference preparation. Meanwhile, it provided an effective measure for evaluating the quantitative characterization and synchronized release behavior of multi-component traditional Chinese medicines.

Capsules ; Chemistry, Pharmaceutical ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Filtration ; Humans ; Kinetics ; Medicine, Chinese Traditional ; Models, Theoretical

OBJECTIVETo explore the clinical effect and possible mechanism of Shengxueling (SXL), a Chinese medical preparation mainly consisting of ginseng saponins, in treating refractory idiopathic thrombocytopenic purpura (ITP).

METHODSThe selected 69 patients with ITP were randomly assigned to two groups, the 37 patients in the treated group were treated orally by SXL with the dose for adult as 60 mg twice a day for two weeks. Then when no marked rise of platelet count after that, the dose would be doubled and administered for another two weeks. Then the dose could be gradually reduced to the initiative level in patients who responded to the treatment, and if they did not, the treatment was regarded as ineffective and be terminated. The 32 patients in the control group were treated with ampeptide elemente instead of SXL, 0.4 g each time three times a day in the first two weeks, and, if that was ineffective, 0.2 g would be added each time and 1.8 g would be administered a day for two more weeks. Four weeks' treatment was regarded as one therapeutic course for both groups and the observation lasted for two successive courses in patients showing positive reslonse.

RESULTSIn the 37 patients in the treated group, markedly effective was obtained in 7 (19.0%), favorably effective in 15 (40.5%), improved in 5 (13.5%) and ineffective in 10 (27.0%), the total effective rate being 59.5%. The corresponding number in the 32 patients in the control group was 4 (12.5%), 6 (18.8%), 3 (9.4%), 19 (59.4%) and 31.3% respectively. Comparison showed the difference in therapeutic efficacy between the two groups was significant (P<0.05).

CONCLUSIONSXL is a safe and effective preparation for treatment of ITP, showing an immediate effect which is obviously superior to that of ampeptide elemente with less adverse effect.

Administration, Oral ; Adolescent ; Adult ; Amino Acids, Essential ; therapeutic use ; Bone Marrow ; pathology ; physiopathology ; Child ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Megakaryocytes ; pathology ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; blood ; physiopathology ; therapy ; Treatment Outcome

The paper is to report the establishment of an HPLC specific chromatogram of Glycyrrhiza in Sini decoctions and the influence of combination on the specific chromatogram. The RP-HPLC method was used with a Phenomenex Gemini C18 column (250 mm x 4.6 mm ID, 5 microm), and acetonitrile-0.05% trifluoroacetic acid (gradient elution) as mobile phase. Flow rate was 0.8 mL x min(-1) and the detection wavelength was set at 232 nm. The temperature of column was 30 degrees C. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions. Twenty peaks were selected as specific peaks in Sini Decoction with liquiritin peak as the reference peak. Six of them were from Glycyrrhiza and the other 6 peaks were from both Glycyrrhiza and Ganjiangfuzi Decoction. The areas of specific peaks of Sini Decoctions were smaller than those in the chromatogram of Glycyrrhiza. The specific chromatogram of Glycyrrhiza in Sini Decoctions is markedly influenced by Radix Aconiti Carmichaeli and Rhizoma Zingiberis. The areas of the specific peaks in Sini Decoctions were reduced obviously. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions.
Aconitum ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; Flavanones ; chemistry ; Ginger ; chemistry ; Glucosides ; chemistry ; Glycyrrhiza ; chemistry ; Plants, Medicinal ; chemistry ; Reproducibility of Results

Objective To analyze the risk factors affecting pre-eclampsia, to establish a pre-eclampsia risk assessment model, and to assess the risk of pre-eclampsia early. Methods A face-to-face questionnaire survey was conducted for all women who gave birth in the Department of Obstetrics, the First Hospital of Shanxi Medical University from March 2012 to September 2016. A total of 10 319 qualified questionnaires were collected to exclude 9 623 cases of other hypertensive diseases related to pregnancy. A total of 70% of the subjects were randomly selected as training samples to analyze the influencing factors of pre-eclampsia, and a Logistic regression model was established. The remaining 30% of the objects are used as test samples to verify the effect of the model. Results Logistic regression model was established with training samples. Logit P=-2.517-0.696×Pre-pregnancy lean +0.200 ×Pre-pregnancy overweight +0.944×Pre-pregnancy obesity -1.995×Residential in city -0.409×Folic acid supplemented before pregnancy +1.323×Twin and multiple pregnancy +1.708× History of previous pregnancy hypertension. Homer-Lemeshow test P=0.377. Model AUC=0.767 (95%CI:0.747-0.786, P<0.001). Using the test sample to verify the model, the model sensitivity was 81.68%, the specificity was 75.05%, the positive likelihood ratio was 3.27, and the negative likelihood ratio was 0.24. The test sample model AUC = 0.771 (95%CI=0.763-0.790,P<0.001). Conclusion This study establishes a simple and effective pre-eclampsia risk assessment model with controllable factors. The model has good fit and sensitivity and specificity.

OBJECTIVE: To study the gene sequence characteristics of hantavirus in Heilongjiang Province in order to find out the reasons for the changes of clinical characteristics of hemorrhagic fever with renal syndrome in Heilongjiang Province in recent years.METHODS: Totally 110 rat lung specimens,121 blood specimens from patients diagnosed with mild or atypical HFRS and 100 blood specimens from patients diagnosed with typical HFRS in the First Affiliated Hospital of Harbin Medical University and the Seventh Hospital of Qiqihar City from 2005 to 2015 were collected. The gene sequences were obtained by nucleic acid extraction, RT-NestPCR, and gene sequencing. Explore the possible reasons for the changes in clinical characteristics of HFRS by comparing the obtained sequences with previous strains, homology analysis, building phylogenetic trees of M gene, and finding out the law of nucleotide and amino acid loci changes. RESULTS: TM gene of twenty-six mild or atypical HFRS patients were successfully amplified, including 14 cases of HTN type and 12 cases of SEO type; M gene of twenty-two typical HFRS patients were amplified, including 19 cases of HTN type and 3 cases of SEO type. Compared with the standard strain 76-118, the nucleotide homology of hantavirus from mild or atypical HFRS patients, typical HFRS patients and mice was 74.4%-89.2%, 87.4%-90.3% and 88.1%-88.5%. Comparing hantavirus gene sequence from mice and from patients, the nucleotide homology was 79.7-99.1%. Hljh38 and Hljh39 from patients were significantly different from the other strains. They were the same subtype as Amur virus because they had high homology with Amur strains H5 and H8205(94.9%-97.6%). The deduced amino acids showed some variations compared with the standard strains, but no obvious variation law was observed. CONCLUSION: The reason for the changes of clinical characteristics of hemorrhagic fever with renal syndrome in Heilongjiang province is related to the change of viral type. There are also variations of hantavirus and amino acid, but the relationship between specific variation law and clinical manifestations needs to be further verified.

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.