Clinical Researches on Chinese Patent Drug for Diabetes： A Scoping Review / 中国实验方剂学杂志

ObjectiveTo review the drug information and clinical researches on Chinese patent drug in Pharmacopoeia of the People's Republic of China，National Essential Drugs List and Medicine List for National Basic Medical Insurance，Employment Injury Insurance and Maternity Insurance. MethodSearch Chinese patent medicine，which can reduce blood sugar in the three major catalogues above. CNKI，VIP，Wanfang，Embase and PubMed were searched from their inception dates to August 14th，2021 for the clinical researches on Chinese patent drug. A database was established based on the collected Chinese patent drug for the treatment of diabetes. And then，descriptive analysis was performed to analyze the general condition of clinical researches． ResultFrom the three catalogues above，28 kinds of Chinese patent drugs were retrieved， and Supplementing Qi and Nourishing Yin was the basic effect of 22 kinds of Chinese patent drugs. A total of 1 069 clinical researches published and peaked in 2017 before August 14th，2021 were included. Clinical studies have been carried out and published in all 30 provinces and autonomous regions，and the province with the largest number of published literature was Henan.What's more，16.65% of the projects were supported by government funding. The number of research to Shenqi Jiangtang tablets/granules/capsules was the largest，among the 28 kinds of Chinese patent drugs.Besides，the most frequent type of interventions in the 958 two-arm trials was the load test，accounting for 78.91%.Most types of diabetes，including type 1 diabetes，type 2 diabetes and its complications，gestational diabetes，other types of diabetes and pre-diabetes，were covered in in this study. And the results showed that different drugs with different suitable crowd. ConclusionA summary of the current status of clinical research on Chinese patent drug by means of scoping review can provide direction for the next research.

Treatment of thyroid nodules based on Chaihu constitution / 国际中医中药杂志

Thyroid nodule is a common endocrine system disease in clinic. Its onset is mostly related to affect-mind internal damage. The core pathogenesis is dysfunction of the liver and liver-qi stagnation, and the main pathological changes are qi stagnation, phlegm turbidity and blood stasis. Constitution is inherited from the natural factors and nourished from the postnatal factors, which is closely related to the occurrence of diseases, the transformation of syndromes and the transmission of diseases. Chaihu constitution refers to the type of constitution suitable for long-term use of Bupleuri Radix and prescriptions about Bupleuri Radix. The characteristics of patients with Chaihu constitution are similar to those of patients with thyroid nodules in clinic, and the risk of developing thyroid nodules is higher. Chaihu constitution is the internal basis of thyroid nodules. When treating thyroid nodule patients with Chaihu constitution, the dominant position of Bupleuri Radix should be highlighted, and Bupleuri Radix and prescriptions about Bupleuri Radix should be used flexibly. The dosage of Bupleuri Radix is mostly between 6-15 g, and according to the change of pathogenesis, it is often combined with Chinese materia medica with the efficacy of soothing liver and promoting qi, resolving phlegm and removing turbidity, promoting blood circulation and removing blood stasis, in order to prevent the occurrence and development of thyroid nodules.

The rules of Traditional Chinese Medicine compounds for diabetes based on the National Patent Database / 国际中医中药杂志

Objective:To analyze the rules of Traditional Chinese Medicine (TCM) for treating diabetes based on the National Patent Database.Methods:In the patent search and analysis platform of the China National Intellectual Property Administration, search the invention patents of the TCM compounds for treating diabetes during January 1,2016-December 31,2020. The Ancient and Modern Medical Records Cloud Platform (V2.3.5) was used to conduct the statistics of Chinese materia medica frequency, the nature and meridian entry, and the analysis of association rules. The cluster analysis and factor analysis were carried out with the SPSS 25.0.Results:A total of 490 TCM compound patents were included, which involve 791 kinds of Chinese materia medica. For each patent, the number of the Chinese materia medica types was rough 13-14 in average. Remarkably, thirty kinds of Chinese materia medica with high frequencies were obtained, where tonic Chinese materia medica accounted for the largest number, followed by the heat-clearing Chinese materia medica. Among these Chinese materia medica the categories of nature are mainly flat, cold and slightly cold, while the flavors are mostly sweet, bitter and pungent, which mainly belongs to the three meridians of lung, kidney and spleen. As for the results of statistical analysis, the association rule analysis indicated that there were 17 effective kinds of Chinese materia medica pairs, such as Rhizoma Dioscoreae-Astragalus Membranaceus and Radix Rehmanniae Recen-Astragalus Membranaceus. Seven Chinese materia medica groups were derived by the cluster analysis, and 11 common factors were extracted through factor analysis. Conclusions:The TCM compounds for treating diabetes are based on clearing heat and moisturizing dryness, nourishing yin and fluid, supplemented by invigorating spleen and removing dampness, dispelling phlegm and dissolving blood stasis, purging fire and detoxification. Notably, in clinical application, phlegm, blood stasis, heat toxin and other pathological products are supposed to be the focus, must identifying the both symptoms and root causes.

Effect of Shenqi Pills （肾气丸） on Cognitive Function and Hippocampal Glucose Energy Metabolism in Type 2 Diabetes Mellitus Model Mice / 中医杂志

ObjectiveTo explore the effect and possible mechanism of Shenqi Pills （肾气丸） on cognitive impairment and hippocampal glucose energy metabolism in type 2 diabetes mellitus （T2DM）. MethodsSixty C57BL/6 mice were randomly divided into control group， model group， rosiglitazone group and Shenqi Pills low-， medium- and high-dose groups， with 10 mice in each group. T2DM model was induced by a high-fat diet combined with intraperitoneal injection of streptozotocin in all the groups except for the control group. After successful modeling， the high-， medium-， and low-dose Shenqi Pills groups were given 2.08， 1.04， and 0.52 g/（kg·d） of Shenqi Pills granules by gavage respectively， while the rosiglitazone group was given 3 mg/（kg·d） of rosiglitazone tablets by gavage， and the control group and model group were gavaged with 10 ml/（kg·d） of distilled water， all for 8 consecutive weeks. The body weight and fasting blood glucose （FBG） level were recorded every two weeks. The Morris water maze test was performed on the 8th week of medication. After 8-week medication， oral glucose tolerance test （OGTT） and fasting insulin level were measured， hippocampal glucose energy metabolism-related products were quantitatively detected by liquid chromatography tandem mass spectrometry， and KEGG annotation analysis was performed. ResultsCompared to those measured at the same timepoints in the control group， the body mass on week 6 and 8， as well as the FBG level on week 2， 4， 6 and 8 in the model group increased； the blood glucose level at 0， 30， 60 and 120 minutes of the OGTT test increased， while fasting insulin level after 8-week medication decreased. The escape latency of the model group was significantly prolonged on the 3rd and 4th days， and the escape latency time increased， while the total swimming distance， platform quadrant residence time and the number of platform crossings decreased （P＜0.05 or P＜0.01）. Compared to those measured at the same timepoints in the model group， the body mass on week 6 in the low-dose Shenqi Pills group， on week 6 and 8 in the medium- and high-dose groups， and on week 8 in the rosiglitazone group were significantly reduced； the FBG levels in all the Shenqi Pills groups and rosiglitazone group on week 6 and 8 decreased， while fasting insulin levels increased. In the OGTT test， blood glucose in the medium-dose group of Shenqi Pills at all timepoints decreased； in the Morris water maze test， the escape latency period of the medium- and high-dose Shenqi Pills groups was shortened on the 3rd and 4th days， while the escape latency time was reduced， and the total swimming distance， platform quadrant residence time， and number of platform crossings increased in the medium-dose Shenqi Pills group （P＜0.05 or P＜0.01）.The medium-dose Shenqi Pills showed best effect， therefore it was selected for the targeted quantitative detection of metabolites. The medium-dose Shenqi Pills group could regulate the disorder of glucose metabolism in the hippocampus of T2DM mice， and 13 differential metabolites were found，up-regulating α-ketoglutarate and 3-phosphoglyceric acid， and down-regulating fumaric acid， glutamatic acid， lactatic acid， inosine， malic acid， adenine， fructose 1,6-diphosphate and others. KEGG annotation of differential metabolites suggested that Shenqi Pills was closely related to the regulation of glucose metabolism disorder and insulin resistance in the hippocampus region of T2DM model mice， as well as neurodegenerative diseases and ABC transport， hypoxia-inducible factor 1 （HIF）， forkhead transcription factor （FoXO） and cyclic adenosine monophosphate （cAMP） signaling pathways. ConclusionShenqi Pills can improve learning and memory abilities and cognitive impairment in T2DM mice， and may act its role by regulating glucose energy metabolism in the hippocampus of T2DM.

Oral Chinese Patent Medicines for Hyperlipidemia： A Scoping Review of Clinical Evidence / 中国实验方剂学杂志

To summarize the status quo of clinical evidence on oral Chinese patent medicine in the treatment of hyperlipidemia through scoping review and thereby provide a reference for clinical application and decision-making in health care. Proprietary Chinese medicines for the treatment of hyperlipidemia （dyslipidemia） were retrieved from relevant catalogs and then screened based on their instructions. Articles on the selected Chinese patent medicines were searched from Chinese and english electronic databases and screened according to the inclusion criteria， followed by data extraction and analysis. The results were described with text and graphs. ①A total of 32 Chinese patent medicines and 1 010 related articles were screened out. ②All the included Chinese patent medicines were made from Chinese medicinal materials， of which 5 were Chinese medicinal extracts，and the remaining 27 were pure Chinese medicinal preparations （the compositions of 1 prescription is confidential）. ③As indicated in the instructions， all the 32 Chinese patent medicines can be used to treat hyperlipidemia with the main syndrome of combined phlegm and blood stasis， and the main effect of them is activating blood and resolving stasis. ④Among the 32 medicines， Xuezhikang tablets （Capsules） and Gypenosides Tablets have the lowest price. ⑤For the 328 key clinical studies， 248 were randomized controlled trials and 80 non-randomized controlled trials. ⑥As for the sample size， randomized controlled trials generally included 28-579 cases， and non-randomized controlled trials 24-152 cases. Clinical studies with more than 200 cases accounted for 9.3% （12/129）. ⑦The most common method was the comparison of the intervention effect of Chinese patent medicine and western medicine （36.5%） and Atorvastatin Calcium Tablets was the preferred western medicine control. The observation duration was generally 56 days （8 weeks）. ⑧In clinical practice， the absolute value of blood lipid decrease and （total） effective rate were often used to evaluate the efficacy， and the effective rate was generally determined based on Clinical Guidelines for New Chinese Medicines. The overall quality of clinical studies on oral Chinese patent medicines is uneven and there is a lack of high-quality clinical evidence. Moreover，there are the risks of unreasonable use and uneasy use of Chinese patent medicine.It is recommended that researchers on proprietary Chinese medicine should further broaden the research ideas，focus on the top-level design of the research plan， and standardize the research process，thereby provide high-quality research evidence for the clinical use of proprietary Chinese medicine. Moreover， more efforts should be made to establish a sound mechanism for information collection and feedback of proprietary Chinese medicine， so as to reduce the risk of uneasy use.We hope that in-depth investigation and discussion should be launched by price， economy， quality evaluation， and other departments headed by the supervision department to make the price of Chinese patent medicine reasonable and fair， thereby promoting the rational use of Chinese patent medicine.

Expert consensus statement on treatment of type 2 diabetes with Xiaoke Pills in clinical practice / 中国中药杂志

Xiaoke Pills are Chinese and Western medicine compound preparations with effects of nourishing kidney and Yin,and supplementing Qi and promoting fluid. It is widely used in clinical treatment of type 2 diabetes( Qi and Yin deficiency syndrome),and continuously included in 2010,2013 and 2017 editions of Chinese prevention guide for type 2 diabetes. For the purpose of accurate positioning and rational use in clinic,it is necessary to further define the curative effect,indications,medication precautions and contraindications of Xiaoke Pills,in order to improve medication safety. This consensus was reached by reference of international clinical guidelines and expert consensus approach based on clinical evidence-based evidence,expert experience and standard specification. The evidence-based evaluation was oriented to clinical problems summarized by no less than 200 front-line clinical physicians in two rounds.GRADE system was adopted for quality classification and evaluation of the evidences,and then the nominal group method was used to form consensus recommendations or suggestions. This consensus defined the curative effect advantages,target users,dosage,administration method,contraindications and precautions of Xiaoke Pills,and provided valuable reference for the clinical use of the drug. Thisconsensus still needs to be updated and revised based on new clinical problems and evidence-based evidence in practical application in the future.

Application of classical formula in treatment of diabetes / 中国中药杂志

The application of classical formula in the treatment of diabetes has a long history. Zhang Zhongjing set up a special chapter on consumptive thirst in Synopsis of the Golden Chamber,listing Baihu Jia Renshen Decoction for exuberant heat in the lung and stomach,dual deficiency of Qi and Yin syndrome,and Shenqi Pills for kidney Qi deficiency syndrome. However,the clinical application is not limited to them. In this study,formulas of Huanglian,Dahuang,Chaihu,Gualougen,Lingzhu,Huangqi and Dihuang are listed as the main therapeutic methods for diabetes mellitus,with effects in clearing heat,dredging the bowels and purging turbid,clearing depression and dispersing knots,nourishing Yin and quenching thirst,invigorating spleen and draining dampness,supplementing Qi and tonifying deficiency,nourishing Yin and tonifying kidney,which have the advantages for the treatment of diabetes and its complications. Based on accurate differentiation of symptoms and signs,consideration shall be given to both " of diseases and syndromes",while emphasis shall be given to the " main symptoms",so as to flexibly apply classical formula and expand the scope of application.

Effect of inhibitor of differentiation 1 deficiency on ocular neovascularization / 上海交通大学学报（医学版）

Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over-expression of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determined by immunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1-/-) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. In order to explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models (P＜0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the expression of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury.

LC-MS analysis of sintilimab as an anti-PD-1 therapeutic mab for its improved hinge stability study / 药学学报

Monoclonal antibodies (mAbs) have been widely used as therapeutic drugs for treating diseases such as cancers and auto-immune diseases. When using an IgG4 isotype, one of the challenges is the instability of its hinge which is prone to Fab-arm exchange (FAE). The hinge sequence of a wild type IgG4 is -CPSC-, however, a single point mutation S228P from -CPSC- to -CPPC- can effectively diminish FAE, thereby improving hinge stability of the IgG4 molecule. Sintilimab is the fully human anti-PD-1 monoclonal antibody designed and developed for immuno-oncology, in which serine 228 in the hinge was engineered to proline to mitigate FAE. In this study, LC-MS is used to study hinge stability of sintilimab in both in vitro (PBS and human serum) and in vivo (SCID mouse) studies. The studies demonstrate that LC-MS is a fast and simple way to monitor for the occurrence of FAE in vitro and in vivo, and FAE can be eliminated by antibody engineering with a single point mutation.

Determination of Hydroxyl Radical in Atmosphere by Molecularly Imprinted Electrochemical Sensor / 分析化学

p-Hydroxybenzoic acid can be oxidized by hydroxyl radicals ( · OH) to produce electroactive 3,4-dihydroxybenzoic acid (3,4-DHBA). Therefore, it can be used as a probe to detect ·OH. In this work, 3,4-DHBA/ PPy / TiO2 molecularly imprinted polymer film was prepared for indirect determination of ·OH based on its recognition ability for 3,4-DHBA. The sensor was constructed by using pyrrole as the functional monomer and 3, 4-DHBA as the template molecule. The sensor was characterized by scanning electron microscope and different electrochemical methods. The preparation and determination conditions, such as the electropolymerization cycle number, pH value in the electropolymerization process, and elution time, were optimized. Under the optimal conditions, a linear range of 1. 0×10-8-1. 0×10-6 mol/ L was obtained for 3,4-DHBA and the detection limit was down to 4. 2×10-9 mol/ L (S / N = 3). This new approach was of low cost and convenience, and was successfully applied to measure the concentration of ·OH in the atmosphere.

Clustering of Non-communicable Diseases Risk Factors in Healthy Adults Aged 35 Years and Older in Shenzhen, China / 生物医学与环境科学（英文）

We assessed the prevalence of non- communicable diseases (NCDs) risk factors with a focus on their clustering among healthy adults in Shenzhen, China. Data from the 2011 China Health and Nutrition Survey, comprising a regionally representative sample of 806 healthy adults aged 35 years or older, were obtained to determine the prevalence of five risk factors for NCDs. The prevalence of current smoking, central obesity, impaired fasting glucose, borderline hypertension, and borderline high total cholesterol was 19.97%, 28.29%, 4.47%, 10.55%, and 36.10%, respectively. A total 63.77% of participants had at least one risk factor. Upon examination of risk factor clustering, we observed that 7.57% of participants had at least three risk factors. Using this threshold as a cutoff, clustering of risk factors was associated with sex [odds ratio (OR) = 3.336, 95% confidence interval (CI): 1.782 to 6.246], physical activity (OR = 1.913, 95% CI: 1.009 to 3.628), and BMI (OR = 7.376, 95% CI: 3.812 to 14.270). The prevalence of risk factors for NCDs is fairly high among healthy adults in Shenzhen, with a clustering tendency.

Report of three death cases of imported falciparum malaria in Wenzhou City / 中国血吸虫病防治杂志

The three death cases of falciparum malaria in Wenzhou City were all imported from Africa. One patient died on 10 January 2007 because of severe clinical symptoms after hospitalization. The second case was initially misdiagnosed as influen-za in primary health and medical institution. The patient's condition quickly worsened and died of Plasmodium falciparum infec-tion on 5 March 2011. The third patient belonged to"non-identity"person,and there were no detailed information and epidemio-logical history on admission,which resulted in the delayed diagnosis,disease exacerbation and death. In conclusion,the health education should be provided to the people who return from Africa and also to medical workers in order to reduce the mortality of falciparum malaria.

Operation time and curative effect on acute gallstone pancreatitis / 国际外科学杂志

Objective To analyse and summarise of the clinical effect and operative opportunity laparoscopic cholecystectomy for acute mild unobstructed gallstone pancreatitis.Methods Fify-four gallstone pancreatitis patients were treated as observation group in the first people's hospital of yangzhou from December 2012 to September 2015,which were treated with laparoscopic cholecystectomy after two weeks,while 53 patients which were treated with laparoscopic cholecystectomy after three months were treated as control group.The treatment effect,operation time,hospitalization time and total cost.Results There were no deaths,no bile duct injury and biliary fistula,the total hospitalization time [(19.8 ±2.6)d vs (26.5 ±3.5) d],the total cost [(2.6282 ± 0.2451) vs (3.2892 ± 0.3982)],recurrent pancreatitis rate (0) were lower than the control group(9.4％),the recovery rate of liver function were higher than the control group,there was significant difference between two groups(P ＜ 0.05),however,there was no significant difference between two groups for postoperative complications and operation time (P ＞ 0.05).Conclusions For acute mild unobstructed gallstone pancreatitis patients,the safe and feasible operative opportunity was recommended two weeks after the symptoms were completely improved,Laparoscopic cholecystectomy in the treatment of acute gallstone pancreatitis can promote recovery,shorten the hospitalization time.

Bromelain and cardiovascular risk factors in diabetes: An exploratory randomized, placebo controlled, double blind clinical trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess whether the dietary supplement (bromelain) has the potential to reduce plasma fibrinogen and other cardiovascular disease (CVD) risk factors in patients with diabetes.</p><p><b>METHODS</b>This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain (1,050 mg/day) on plasma fibrinogen. This randomized controlled trial (RCT) recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years (standard deviation (SD), 12.62 years)] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg (3×350 mg) of either bromelain or starch-filled placebo capsules, two to be taken (2×350 mg) after breakfast and another (350 mg) after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks.</p><p><b>RESULTS</b>The change in the fibrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L (standard deviation (SD) 0.86g/L) compared with the mean reduction of 0.36 g/L (SD 0.96 g/L) for the placebo group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups (mean difference=0.23g/L (SD 0.22 g/L), =0.291). Similarly, the difference in mean change in other CVD risk factors (blood lipids, blood pressure), blood glucose, C-reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Statistical differences in fibrinogen between bromelain and placebo groups before the trial despite randomization may have influenced the results of this study.</p><p><b>CONCLUSION</b>This RCT failed to show a beneficial effect in reducing fibrinogen or influencing other selected CVD risk factors but suggests other avenues for subsequent research on bromelain.</p>

HER-2 promotes breast cancer cell epithelial-mesenchymal transition by regulating ZEB1 / 中国癌症杂志

Background and purpose:Human epidermal growth factor receptor-2 (HER-2), a member of epidermal growth factor receptor family, initiates a diverse set of signaling pathways that ultimately affect such fun-damental processes as cell proliferation, cell motility and cell apoptosis. It is reported that HER-2 was associated with epithelial-mesenchymal transition (EMT) process. However, the mechanism needs further investigation. The purpose of this study was to investigate the mechanism of HER-2 on regulating EMT process.Methods:Transwell assay was used to determine the motility of breast cancer cells; Real-time lfuorescence quantitative polymerase chain reaction (RT-FQ-PCR) was employed to determine the expression of genes of interest, and reactive oxygen species production was measured by reactive oxygen species detection kit.Results:HER-2 overexpression in breast cancer cells could promote cell migration and invasion. Mechanistic study showed that HER-2 overexpression could upregulate ZEB1 expression. ZEB1 silencing by siRNA reduced cell motility of HER-2-overexpressing breast cancer cells. Furthermore, reactive oxygen species produced in HER-2-overexpressing breast cancer cells were less than those produced in corresponding control cells.Conclusion:Our study demonstrated that HER-2 overexpression endowed breast cancer cells with EMT related properties by upregulating ZEB1 expression. ZEB1 could be a candidate target for further study of the relation-ship between HER-2 and EMT.

Effect of Vascular Cell Adhesion Molecule -1 Overexpression on Adipogenic Differentiation of Murine Mesenchymal Stem Cells and Its Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of vascular cell adhesion molecule-1 (VCAM-1) gene overexpression on adipogenic differentiation of mouse mesenchymal stem cells(MSC) and explore its molecular mechanism.</p><p><b>METHODS</b>VCAM-1 overexpression MSC (MIGR1-VCAM-1/MSC) and the empty plasmid transfection MSC (MIGR1/MSC) were induced to adipogenic differentiation, oil-red-O staining and real-time PCR were used to detect the adipogenic differentiation ability and the mRNA expression level of key transcription factors C/EBP α and PPAR γ. The activation of P38, ERK and JNK pathways were analyzed by Western blot. Furthermore, the specific chemical inhibitors of MAPK pathway (SB203580, PD98059 and JNK inhibitor II) were added to the induced culture system and the alteration of the MSC adipogenic differentiation ability were evaluated.</p><p><b>RESULTS</b>no matter in self or induced differentiation groups, the lipid droplets in MIGR1-VCAM-1/MSC became larger, the amount of adipocyte increased than that in MIGR1/MSC (P<0.01), the mRNA expression level of C/EBPα and PPARγ were upregulated, and JNK pathway were down-regulated while the P38 and ERK pathway were significantly up-regulated. The inhibition of JNK pathway of MIGR1-VCAM-1/MSC could lead to increased mRNA expression level of C/EBP α and PPAR γ, the amount of adipocytes increased (P<0.01), however, the inhibition of the P38 and ERK pathway of MIGR1-VCAM-1/MSC could lead to decreased mRNA expression level of C/EBP α and PPAR γ, and the lipid droplets and the number of adipocytes became smaller and less.</p><p><b>CONCLUSION</b>The overexpression of VCAM-1 may promote MSC to differentiate into adipocytes through inhibiting JNK signaling pathway, activating P38 and ERK pathways.</p>

Effect of Knockdown of Vascular Cell Adhesion Molecule-1 on the Immunologic Regulation Capacity of Murine Mesenchymal Stem Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish the stably lower expression of vascular cell adhesion molecule-1 (VCAM-1) in MSC cell line (C3H10T1/2) by siRNA technology, and explore the effect of knockdown of VCAM-1 on the immunologic regulation capacity of murine MSC.</p><p><b>METHODS</b>The mouse GV118-VCAM-1-RNAi retrovirus vector was constructed by gene recombination technology. The recombinant plasmid was identified by restriction analysis and sequencing, and then the recombinant plasmid GV118-VCAM-1-RNAi was transfected into 293 cells by Lipofectamine, and the supernatant was collected to transfect C3H10T1/2. Moreover, the VCAM-1 lower expression on MSC was evaluated by flow cytometry and fluorescent microscopy. The knockdown VCAM-1 MSC was sorted by flow cytometry. Furthermore, the inhibitory effect of the knockdown VCAM-1 MSC on lymphocyte proliferation was tested by lymphoblast transformation assay (LTT) and mixed lymphocyte reaction assay(MLR).</p><p><b>RESULTS</b>The recombinant retroviral vector of knockdown VCAM-1 (GV118-VCAM-1-RNAi) was successfully constructed and transfected into mouse MSC cell line C3H10T1/2. The knockdown VCAM-1/MSC was obtained by flow cytometric sorting. The LTT and MLR assay showed that the immunosuppressive effect of MSC lower-expressing VCAM-1 dramatically decreased (P<0.05).</p><p><b>CONCLUSION</b>Knockdown VCAM-1 in MSC can significantly down-regulate the inhibitory capability of MSC on the proliferation of T-cells. The data of this study laid an experimental foundation for studying effect of VCAM-1 transfecting into MSC on immune function.</p>

Study on TCM syndromes of Type 2 diabetic encephalopathy by data mining / 国际中医中药杂志

Objective To explore characteristics of the elements of syndrome, the disease position and the relationship between chemical indicators and TCM syndromes of type 2 diabetic encephalopathy. Methods 2 501 cases of type 2 diabetes clinical data were collected from Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing University of Chinese Medicine, Dongzhimen Hospital, Dongfang Hospital, etc. in nearly 3 years, among which, 342 cases were type 2 diabetic encephalopathy. The original clinical data were double entried in epidata by two people, establishment forms in excel, factor analysis and Bayesian networks were used as data mining research methods. Results 20 elements which characteristic root more than 1 were derived by factor analysis, 68.4% were covered. Of all 20 elements, five factors belong to Yin, five factors belong to blood stasis; lassitude, shortness of breath, stool frequency were appeared when fasting glucose abnormalities; lassitude, hemiplegia were appeared when 2-hour postprandial blood glucose abnormalities;lassitude, feverish palms and soles, stool frequency, more nocturnal enuresis when glycated hemoglobin abnormalities by Bayesian networks. Conclusion The Elements of the syndrome of type 2 diabetes encephalopathy were deficiency of Yin and blood stasis; and the main positions for diabetic patients were liver, spleen and kidney. Patients with impaired fasting glucose were Qi deficiency; Patients with impaired 2-hour postprandial glucose were Qi deficiency or pathogenic wind attacking collaterals; Patients with abnormal hemoglobin were Qi deficiency and Yin deficiency.

Experimental study on pharmacokinetics of Reduning Injection in human body / 中草药

Objective: To establish a high performance liquid chromatography/mass spectrometry (HPLC-MS/MS) for the simultaneous determination of the concentration in plasma of chlorogenic acid, new chlorogenic acid, cryptochlorogenic acid, gardenia component geniposide, shanzhiside, and genipin gentian diglucoside from Lonicerae Flos in Reduning Injection iv dripped in healthy human body. Methods: Sixteen healthy subjects were iv infused of Reduning Injection with 2 ampoules, a total of 20 mL diluted with 5% glucose injection to 250 mL, iv injection time was set for 90 min, venous blood was measured at the different time points before, during, and after infusion, respectively. The conditions of determination for chlorogenic acid and other ingredients were as follows: Inertsil ODS-2 chromatographic column (150 mm × 2.1 mm, 5 μm), mobile phase (acetonitrile, 0.1% formic acid), rolling gas 137.9 kPa (20 psi), collision gas 56.16 kPa (8 psi), spray voltage -4 500 V. The LC-MS/MS conditions for determination of shanzhiside, geniposide and genipin gentian diglycoside were as follows: Ecosil C18 (150 mm × 4.6 mm, 5 μm), the mobile phase (methanol, 20 mmol/L ammonium formate, 0.1% formic acid, and 10% methanol), rolling gas 96.53 kPa (14 psi), collision gas 56.16 kPa (8 psi), spray voltage 4 500 V. Results: The tmax of neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid were 1.31, 1.38, and 144 h; Cmax were 1 241, 329 4, and 2 121 ng/mL; AUC0~t were 1 972, 5 351, and 3 596 ng·h/mL; MRT0~t were 0.708, 0.790, and 0.899 h; CL were 10.3, 385, and 5.73 L/h; Vd were 16.7, 766, and 10.7 L; t1/2 were 1.13, 1.36, and 1.27 h, respectively. The tmax of geniposide, shanzhiside, and genipin gentian diglucoside were 1.41, 1.47, and 1.47 h; Cmax were 4.49, 0.288, and 0.541 μg/mL; AUC0~t were 7.41, 0.671, and 1.22 μg·h/mL; MRT0~t were 0.856, 1.59, and 152 h; CL were 2.74, 30.0, and 16.6 L/h; Vd were 5.63, 60.9, and 35.2 L; t1/2 were 1.42, 1.42, and 1.47 h. Conclusion: The method is simple, accurate, and can be used for in vivo pharmacokinetic study on Reduning Injection.

Protection and mechanism of shenqi compound for diabetic angiopathy model rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats.</p><p><b>METHODS</b>Totally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot.</p><p><b>RESULTS</b>Compared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05).</p><p><b>CONCLUSIONS</b>Shenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.</p>