The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

The effect of mindfulness-based stress reduction on renal function and quality of life in uremic hemodialysis patients / 中国实用护理杂志

Objective:To construct a mindfulness-based stress reduction (MBSR) intervention program suitable for uremic hemodialysis patients, and analyze the impact of the program on renal function and quality of life in uremic hemodialysis patients.Methods:This was a randomized controlled trial. The convenience sampling method was used to select 92 uremic patients who underwent hemodialysis in the First People's Hospital of Lianyungang City from March 2018 to March 2019. They were divided into routine group (46 cases, routine care) and MBSR group (46 cases, MBSR of face-to-face guidance combined with WeChat platform supervision) by random number table method. Both groups were intervened for 8 weeks. The Chinese version of the European Five-Dimensional Scale (EQ-5D-3L) was used to evaluate the quality of life of the patients, and the quality of life of the two groups before and after the intervention was compared; and the blood creatinine (Scr) and estimated glomerular filtration rate (eGFR), urea nitrogen (BUN), cystatin C (CysC) levels of the two groups before and after the intervention were analyzed.Results:Before the intervention, there was no significant difference in the levels of Scr, eGFR, BUN, and CysC between the two groups ( P>0.05); after 8 weeks of intervention, the levels of Scr, eGFR, BUN, and CysC were (201.81±14.77) μmol/L, (35.30 ± 2.02) ml/min and (11.47 ± 2.66) mmol/L, (2.41 ± 0.28) mg/L in the MBSR group, (218.37 ± 14.90) μmol/L, (33.99 ± 1.95) ml/min, (12.50 ± 0.76) mmol/L, (2.76 ± 0.30) mg/L in the routine group, the differences were statistically significant between the two groups ( t values were 2.53-5.79, all P<0.05). Before the intervention, there was no significant difference in EQ-5D-3L scores between the two groups ( P>0.05); after 8 weeks of intervention, the pain (discomfort), anxiety (depression), Vasual Analogue Scale (VAS) scores were (1.17 ± 0.34), (1.02 ± 0.35), (88.57 ± 20.28) points in the MBSR group, and (1.46 ± 0.63), (1.30 ± 0.32), (62.69 ± 18.79) points in the routine group, the differences were statistically significant between the two groups ( t=2.75, 4.00, 6.35, all P<0.05). Scr level was negatively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were -0.481 - -0.214, all P<0.05); eGFR level was positively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were 0.199-0.492, all P<0.05). But BUN and CysC levels were not correlated with EQ-5D-3L score (all P>0.05). Conclusions:MBSR can effectively improve the renal function and quality of life of uremic hemodialysis patients, and it is worthy of clinical application.

Overview of systematic reviews of acupuncture for vascular cognitive impairment / 中国针灸

OBJECTIVE@#To overview the methodological quality, report quality and evidence quality of the systematic review (SR) of acupuncture for vascular cognitive impairment ( VCI ).@*METHODS@#The SRs regarding acupuncture for VCI were searched in PubMed, Cochrane Library, EMbase, CNKI, SinoMed, Wanfang and VIP databases. The retrieval period was from the establishment of the database to September 24, 2020. The report quality, methodological quality and evidence quality of the included SRs were evaluated by PRISMA statement, the AMSTAR 2 tool and the GRADE system.@*RESULTS@#A total of 22 SRs were included, including 102 outcome indexes. The methodological quality was generally low, with low scores on items 2, 5, 7, 10, 14, 15 and 16. The report quality was good, with scores ranging from 19 points to 24.5 points. The problems of report quality were mainly reflected in the aspects of structural abstract, program and registration, other analysis and funding sources. The level of outcome indexes of SRs was mostly low or very low, and the main leading factor was limitation, followed by inconsistency and inaccuracy.@*CONCLUSION@#Acupuncture for VCI is supported by low quality evidence of evidence-based medicine, but the methodological quality and evidence body quality of relevant SRs are poor, and the standardization is needed to be improved.

Mechanism of Action of Traditional Chinese Medicine Against Prostatic Carcinoma： A Review / 中国实验方剂学杂志

Prostatic carcinoma （PCa） is one of the most common male malignancies， accounting for 10% of all male cancers， and has become a global health problem. At present， it is mainly tackled with radical prostatectomy and endocrine therapy. However， most patients will develop drug resistance， allowing the progression of PCa into castration-resistant prostate cancer （CRPC）. Guided by the principles of holism and treatment based on syndrome differentiation， traditional Chinese medicine （TCM） alleviates cancer pain， regulates immune balance， and improves the quality of life of patients via multiple targets， multiple pathways， and multiple mechanisms without inducing obvious side effects， thus better exerting the preventive and therapeutic effects against PCa. This paper retrieved relevant articles concerning PCa intervention with TCM published in recent five years from PubMed and China National Knowledge Infrastructure （CNKI）， and summarized the molecular mechanism of PCa， its etiology and pathogenesis in TCM， and TCM interventions. The findings showed that the active ingredients of Chinese medicinals， single Chinese medicinals and Chinese medicinal compounds inhibited PCa by interfering with not only the classical pathways of PCa such as androgen receptor（AR）， Wnt/β-catenin， PI3K/Akt/mTOR， and NF-κB but also other pathways like ERS/UPR， RIPK， CIP2A/PP2A/ERK， EGFR， etc. The intervention of active ingredients from Chinese medicinals in PCa has been explored extensively， but there are fewer studies on single Chinese medicinals and Chinese medicinal compounds that can better reflect the unique advantages of TCM. Further research is needed to provide an important theoretical and experimental basis for the development of novel anti-PCa Chinese medicinal products and their clinical application.

Formation of neutrophil extracellular traps and their effects on autoimmune diseases / 中国中药杂志

Neutrophil extracellular traps(NETs) are networks of extracellular fibers primarily composed of DNA, histones, granular proteins, and cytoplasmic proteins and released to the outside of cells by neutrophils under the stimulation of bacteria, fungi, viruses, parasites, etc. NETs are generated in two forms, suicidal NETs and vital NETs, according to different stimuli. NETs have both anti-inflammatory and pro-inflammatory effects. On the one hand, they can play the anti-microbial role to resist inflammation by capturing, fixing, and killing invading pathogens, which is a special way for neutrophils to exert host defenses. On the other hand, in case of excessive formation or insufficient elimination, they can cause tissue damage directly, and also promote the release of inflammatory factors by recruiting other pro-inflammatory cells or proteins to further expand the inflammatory response, which is related to the pathologies of many diseases. In autoimmune diseases, NETs as important sources of autoantigens, can act as danger-associated molecular patterns( DAMPs) and activate the nucleotide-binding oligomerization domain leucine-rich repeats containing pyrin domain 3(NLRP3) inflammasome and complement system, thereby breaking self-tolerance and accelerating autoimmune inflammation. In addition, NETs can also activate other immune cells(such as B cells, antigen-presenting cells, and T cells) and regulate the acquired immune response. The present study reviewed the correlation of NETs with diseases such as systemic lupus erythematosus(SLE), rheumatoid arthritis(RA), and gouty arthritis(GA) to reveal the effect of dynamic balance between formation and clearance of NETs in autoimmune diseases and provide a theoretical basis for the investigation of underlying mechanisms and targeted therapies of traditional Chinese medicine.

Mechanism of Sanhuang Decoction in alleviating dextran sulfate sodium induced ulcerative colitis in mice with Candida albicans colonization:based on high-throughput transcriptome sequencing / 中国中药杂志

This study explored the mechanism of Sanhuang Decoction(SHD) in treating dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice with Candida albicans(Ca) colonization via high-throughput transcriptome sequencing. Specifically, the animal model was established by oral administration of 3.0% DSS for 7 days followed by intragastrical administration of Ca suspension at 1.0 × 10~8 cells for 4 days and then the mice were treated with SHD enema for 7 days. Afterwards, the general signs were observed and the disease activity index(DAI) was recorded every day. After mice were sacrificed, colon length and colon mucosa damage index(CMDI) were determined and the histomorphology was observed with the HE staining method. The fungal loads of feces were detected with the plate method. Anti-saccharomyces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, and IL-6 in serum and colon were detected by ELISA. High-throughput RNA sequencing method was adopted to identify transcriptome of colon tissues from the control, model and SHD(15.0 g·kg~(-1)) groups. Differentially expressed genes(DEGs) among groups were screened and the GO and KEGG pathway enrichment analysis of the DEGs was performed. The expression levels of NLRP3, ASC, caspase-1, and IL-1β genes related to the NOD-like receptor signaling pathway which involved 9 DEGs, were examined by qRT-PCR and Western blot. The results demonstrated that SHD improved the general signs, decreased DAI and Ca loads of feaces, alleviated colon edema, erosion, and shortening, and lowered the content of β-1,3-glucan in serum and TNF-α, IL-1β, and IL-6 in serum and colon tissues of mice. Transcriptome sequencing revealed 383 DEGs between SHD and model groups, which were mainly involved in the biological processes of immune system, response to bacterium, and innate immune response. They were mainly enriched in the NOD-like signaling pathway, cytokine-cytokine interaction pathway, and retinol metabolism pathway. Moreover, SHD down-regulated the mRNA and protein levels of NLRP3, caspase-1, and IL-1β. In a word, SHD ameliorates DSS-induced UC in mice colonized with Ca, which probably relates to its regulation of NOD-like receptor signaling pathway.

Effect of Shenling Baizhusan on Protein and mRNA Expression of NF-κB p65，IκBα，IκKβ in Ulcerative Colitis Rats with Syndrome of Dampness Stagnancy Due to Spleen Deficiency / 中国实验方剂学杂志

Objective:To observe the effect of Shenling Baizhusan on the protein and mRNA expression of inhibitor of nuclear factor kappa B kinase (IκK)/inhibitor of nuclear factor kappa B(IκB)/nuclear factor kappa B(NF-κB) signaling pathway in the colon of rats with ulcerative colitis (UC) of spleen deficiency and dampness stagnation type, and to explore the mechanism of Shenling Baizhusan in the treatment of UC. Method:The 48 Wistar rats were randomly divided into normal group, model group, Shenling Baizhusan group (15.6 g·kg-1) and osalazine sodium group (0.68 g·kg-1), 12 rats in each group. The model of UC with spleen deficiency and dampness stagnation was reproduced by trinitrobenzene sulfonic acid (TNBS)/ethanol enema combined with environment and diet intervention.Serum levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β(IL-1β) were determined by enzyme-linked immunosorbent assay（ELISA）. The expression of NF-κB p65, IκBα, IκKβ protein in colon tissue was measured by Western blot and immunohistochemical method, and the mRNA expression of NF-κB p65, IκBα and IκKβ in colon tissue of rats in each group was detected and compared by real time polymerase chain reaction (Real-time PCR). Result:Compared with normal group,the levels of TNF-α,IL-6 and IL-1β in the serum, the protein and mRNA expression of NF-κB p65, IκKβ in colon tissue of the model group was significantly higher than that of normal group (P<0.01), and the protein and mRNA expression of IκBα was significantly lower than that of normal group (P<0.01). Compared with model group,the protein and mRNA expression of NF-κB p65, IκKβ in colon tissue of the Shenling Baizhusan group and osalazine sodium group were significantly decreased (P<0.01), and the protein and mRNA expression of IκBα was significantly increased (P<0.01). Conclusion:Shenling Baizhusan can obviously down regulate the protein and mRNA expression of NF-κB p65, IκKβ,up regulate the expression of IκBα in colon tissue of UC rats with spleen deficiency and dampness stagnation. The inhibition of IκK/IκB/NF-κB signal pathway activation by Shenling Baizhusan is an important mechanism of its role in protecting intestinal mucosa.

Anti-diabetic effects of the fraction of alkaloids from Ramulus Mori, an innovative Sangzhi alkaloids as an α-glucosidase inhibitor / 药学学报

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC50 was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism / 生物医学与环境科学（英文）

OBJECTIVE@#We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats.@*METHODS@#In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw).@*RESULTS@#In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity.@*CONCLUSION@#These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.

Effect of Autophagy in Treatment of Tumors with Traditional Chinese Medicine / 中国实验方剂学杂志

The cure of tumors is a difficulty in the world, and both the quality of life and the survival rate of patients remain low. Therefore, it is very meaningful to find a drug target to inhibit the occurrence and development of tumors. In recent years, autophagy or self-phagocytosis has become a hotspot of medical research. It can remove damaged or excess organelles from cells, be survived from external environmental pressures, and affect the survival, metabolism, differentiation, aging and death of tumor cells. The biological behavioral process plays important roles in remodeling and maintaining the dynamic balance of cell survival, especially in close relations to tumor development. Autophagy is also a double-edged sword in effect on a single tumor cell and the entire tumor. When the autophagy of the tumor cells is abnormal, or the cells are unable to remove the damaged substances in time under the conditions of hypoxia and nutrient deficiency, autophagy is beneficial to the proliferation and survival of the tumor cells. Contrarily, moderate autophagy acts as an inhibitor of tumors and has an anti-tumor effect. Traditional Chinese medicine (TCM) has a long history of controlling tumors, with the advantages of low toxicity and multiple targets. Through overall and local therapies, it has a comprehensive therapeutic effect in cancer. With the deepening of tumor autophagy research, in addition to western medicine researches on tumor autophagy, there are also domestic and foreign researches on the autophagy in single herb and TCM compounds. The latest insights into the molecular mechanism of autophagy have led to the discovery of potential drug targets. At the same time, TCM researches have made some progress in tumor autophagy. The authors review the research progress of autophagy in TCM and the research progress of effect of TCM in regulating tumor autophagy, in the hopes to provide useful reference for effect of TCM in the treatment of autophagy.

Biopharmaceutics classification system of Chinese materia medica of berberine in Gegen Qinlian decoction / 中国中药杂志

One of the top-level researches of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is the study on single component in compound Chinese medicine. The medicines shall be classified according to its solubility and intestinal permeability, as well as the ascending degree in multicomponent environment. Based on above, we chose berberine as the main object to explore the change rules of its solubility and intestinal permeability in Gegen Qinlian decoction. Shaking flask-HPLC was used to detect the solubility changes of berberine in compounds. The qualitative investigation of berberine in intestinal absorption was measured by everted gut sac, and the quantitative research of berberine in intestinal absorption was measured by single-pass intestinal perfusion experiment, while the qualitative and quantitative research of berberine absorption into blood was measured by in intestinal perfusion with venous sampling experiment.

Overall intestinal permeability of multiple components in lotus leaves / 中国中药杂志

In the study of biopharmaceutics classification system of Chinese materia medica (CMMBCS), the interactions of multiple components in the absorption should be taken into consideration in simultaneous multi-component determination. To investigate the absorption of multiple components, the in vitro everted gut sac model was used in this study, wtih lotus leaves as the research object. Aquantitative analysis was also carried out for the known components in this study. Totally 19 components in lotus extracts were absorbed by the intestinal tract, the Papp levels of the known components were nuciferine (1×10⁻⁵-1×10⁻⁶ cm•s⁻¹), rutin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹), hyperoside (1×10⁻⁶ cm•s⁻¹), isoquercitrin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹) and astragalin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹), respectively. These components showed a low permeability under a multi-component environment. This study was carried out to lay a foundation for further relevant target studies for different categories of components.

Water extract from Codonopsis thalictrifolia wall affects the reproductive system of male infant rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the impact of the water extract from Codonopsis thalictrifolia Wall (CTW) on the reproductive</p><p><b>METHODS</b>We divided 32 male SD infant rats into four groups of equal number to be treated intragastrical-system of male infant rats. ly with distilled water (control) and CTW at 10 g/kg (low dose) , 20 g/kg (medium dose), and 40 g/kg (high dose), respectively, twice a day for 2 weeks. Then we killed the rats, measured the levels of testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the serum, obtained the testis weight, body weight, testis visceral coefficient and sperm concentration, and detected sperm viability, sperm motility and the level of cyclic adenosine monophosphate (cAMP) in the Leydig cells, followed by</p><p><b>RESULTS</b>Compared with the control group, the low-dose, me-analysis of differences among different groups using the SPSS software. Medium-dose and high-dose CTW groups showed significant decreases in the serum T level ([3.09 +/-0.42] vs [1.22 +/-0. 32] , [1.06 +/- 0.29] and [0.57 +/-0.18] nmol/L, P<0.01), testis weight ([1.40 +/-0.16] vs [0.96 +/-0.09], [0.92 +/-0.11] and [0.91 +/- 0.08] g, P <0.01), and sperm concentration ([1.03 +/-0.16] vs [0.19 +/-0.07], [0.17 +/-0.08] and [0.16 +/-0.07] x 10(6)/ml, P <0.01), but a dramatic elevation in the testis visceral coefficient ([42.22 +/- 3.02] vs [51.39 +/- 3.09], [52.28 +/- 4.86] and [54.13 +/-6.06] mg/10 g, P <0.01); the medium- and high-dose CTW groups exhibited remarkable increases in the levels of serum LH ([13.62+/-0.89] vs [14.69 +/-0.12] and [14.93 +/-0.28] ng/L, P<0.01) and FSH ([4.32 +/-0.18] vs [4.77 +/-0.23] and [4.89 +/-0. 38] IU/L, P <0.05); all the three CTW groups showed markedly inhibited serum T secretion ([1.85 +/- 0.18] vs [1.42 +/-0.15], [1.12+/-0.18] and [0.88 +/-0.21] nmol/L, P<0.01) and intracellular cAMP ([5.51 +/-0.12] vs [4.39+/-0.06], [4.28 +/-0.07] and [4.11 +/- 0.10] nmol/L, P <0.01) in the Leydig cells.</p><p><b>CONCLUSION</b>The water extract from CTW may reduce the synthesis of testosterone in the serum of male infant rats through the PKA pathway and consequently inhibit their testicular development and sperm production and affect the development of their reproductive system.</p>

Effect of Mudan Granule on islets beta cell function in monosodium glutamate induced obese mice with insulin resistance: an experimental study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR).</p><p><b>METHODS</b>MSG obese mice were induced by subcutaneous injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group (Con), the low dose MD group, the high dose MD group, and the Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and p-NF-kappaB p65 in the pancreas were tested.</p><p><b>RESULTS</b>Compared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con group, the aforesaid indices could be improved in the Met group (P < 0.05, P < 0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously increased (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>MD could significantly improve IR and functional disorder of 3 cells in MSG obese mice, which might be associated with lowering inflammatory reaction in the pancreas.</p>

Cytogenetic analysis of childhood acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To characterize the genetic aberrations in pediatric acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>Ninety ALL cases were enrolled in the study from January 2009 to November 2011. Chromosome banding analysis and fluorescence in situ hybridization (FISH) were used to detect genetic aberrations.</p><p><b>RESULTS</b>(1) Chromosome analysis: 35 (53.0%) of 66 cases who had metaphase were abnormal, and 24 cases had no metaphase. (2) FISH analysis: among the 31 cases who had normal karyotypes and 24 who had no metaphase detected by chromosome banding technique, 7 (22.6%) and 14 (58.3%) cases were abnormal detected by FISH, respectively. There were no statistically significant differences compared with chromosome analysis (P = 0.655). Among these 55 ALL cases TEL/AML1, bcr-abl and MLL fusion genes were observed in 16 (29.1%), 3(5.5%) and 2(3.6%) cases, respectively. (3) Cytogenetic aberration was observed in 56 of total 90 ALL cases (62.2%).</p><p><b>CONCLUSIONS</b>Cytogenetic changes are common in childhood ALL. Conventional cytogenetic study could reliably detected chromosomal abnormalities for ALL with assessable metaphase. FISH should be used as a complementary method for ALL patients who have poor chromosomal morphology or no metaphase cells, and combination of both methods can improve the detection rate of genetic abnormalities in childhood leukemia.</p>

Professor LI Ding's understanding on the eight extra meridians / 中国针灸

Through his long-term acupuncture-moxibustion teaching and academic research, professor LI Ding from Shanghai University of TCM had conducted a profound research on the theory of the eight extra meridians, named Governor Vessel, Conception Vessel, Thoroughfare Vessel, Belt Vessel, Link Vessels and Heel Vessels, as well as their relationship with the regular meridians. He rectified the miss-understanding on the courses of Governor Vessel and Conception Vessel determined by the ancient medical masters, and had a further analysis on some different views, such as the running course of Governor Vessel and the flowing direction of meridian qi in Governor Vessel and Conception Vessel. He proposed that the nutrient qi flew up to down in Governor Vessel and down to up in Conception Vessel. His research and discovery much perfected the theory of the eight extra meridians and provided a significant instruction for the research on the eight extra meridians in the later generations.

Effect of lactuside B on the expression of bcl-2 and bax mRNA and their protein in rats' cerebral cortex after cerebral ischemia-reperfusion injury / 药学学报

This study is to investigate the effect of the major chemical composition in rhizome of Pterocypsela elata, lactuside B, on expression of bcl-2, bax mRNA and their protein in rats' cerebral cortex after cerebral ischemia-reperfusion injury. First, middle cerebral artery ischemia-reperfusion injury model was established, and each group was treated with the corresponding medicines. Animals were separately sacrificed at 24 h and 72 h. The brain infarct volumes were detected by TTC dye, bcl-2 and bax mRNA expression was checked by RT-PCR, and the proteins of bcl-2 and bax were explored by two-step immunohistochemistry in cerebral cortex of rats. Lactuside B can reduce brain infarct volume of cerebral cortex of rats, increase the expression of bcl-2 mRNA and decrease that of bax mRNA. Moreover, the ratio of bcl-2 to bax mRNA is higher in 12.5 and 25 mg kg(-1) dose group, respectively, which is significantly different from that of model group (P < 0.05 or P < 0.01). Generally, either 12.5 or 25 mg kg(-1) dose group is better than positive control medicine nimodipine (P < 0.05 or P < 0.01). In addition, the expression of bcl-2 and bax protein is consistent with their gene expression. Infarct volume and the ratio of bcl-2 to bax mRNA expression are significantly different (P < 0.05 or P < 0.01) between 72 h and 24 h group. The results demonstrated that lactuside B could play a good role in resisting cerebral ischemia by upregulating the expression of bcl-2 mRNA and protein and downregulating that of bax mRNA and protein.

Investigation of the alterations in cellular electrophysiology underlying ventricular arrhythmia in dogs with the multiple organ dysfunction syndrome.

BACKGROUND: Multiple organ dysfunction syndrome (MODS)-specific cellular electrophysiological changes have so far not been reported and it seemed unlikely that they were related to arrhythmogenesis. METHODS AND RESULTS: Twelve dogs, weight 12 +/- 2 kg, were divided into a control group (n = 6) and an MODS group (n = 6). MODS lasting for 72 h was induced by the 'two-hit' method in 6 dogs. Ventricular myocytes were enzymatically isolated. Early afterdepolarizations (EADs), action potential duration (APD) and L-type calcium currents (ICa,L) were assessed. Sinus arrhythmias in all MODS dogs (100%; 6 of 6) and premature ventricular beats in 4 MODS dogs (66%; 4 of 6) were recorded, while no arrhythmias were found in the control animals. The prolongation of the APD was associated with a decreased ICa,L, and frequently provoked EADs were the typical electrophysiological alterations in the myocytes of MODS dogs. The action potential prolongation was shortened, the ICa,L blocked and EAD suppressed by using verapamil (100 micromol/l) in the myocytes of MODS dogs (66%; 4 of 6). CONCLUSION: The changes in cellular electrophysiology within 72 h in the heart of MODS dogs are APD prolongation, markedly decreased ICa,L as well as frequently provoked EAD, the most common types of arrhythmia being sinus arrhythmia and premature ventricular beats. This study suggests that verapamil appears to be an effective agent in reversing alterations in cellular electrophysiology at the early stage of MODS.

DOU Han-qing's academic thought of acupuncture and moxibustion / 中国针灸

DOU Han-qing's academic thought of acupuncture and moxibustion are analyzed, which include "eight confluence points", sensation of qi arrival, 14 manipulations for promotion of qi sensation, point selection, needling technique and observation of the psychological condition of patients. DOU's inheritance and development of Huangdi Neijing (Internal Classic) and Nanjing (Classics on Medical Problems) as well as his influences on the later schools are approved to have great value and significance on the enhancement of clinical effect and development of acupuncture and moxibustion sciences.

The influence of fluoride on expression of OPGL and M-CSF genes and their proteins in rats with experimental fluorosis and the therapeutic effect of Danlan Xianpeng Liaofu caspule / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate mRNA and protein expressions of OPGL and M-CSF mRNA in bones of rats with experimental fluorosis induced by intake of fluoride in the drinking water, and to study the antagonizing effects of Danlan Xianpeng Liaofu capsules on the gene expression.</p><p><b>METHODS</b>Totally 72 SD rats were randomly assorted into 6 groups including the control group, the fluoride group, the high-dosage (0.8 g/kg×d), mid-dosage (0.4 g/kg×d) and low dosage (0.2 g/kg×d) medication groups and the borax group (borax, 0.8 g/kg×d). The distribution of female and male rats in each group was divided up on a fifty-fifty basis. Except the control group, a NaF containing water (NaF 50 mg/L in concentration) was supplied as the drinking water for all the experimental rats in order to establish experimental fluorosis. The thickness and density of trabecula and the thickness of bone cortex were measured by light microscopy. The fluoride content in urine and bone were analyzed by using fluoride ion selective electrode method. Expressions of OPGL and M-CSF mRNA and protein were studied using RT-PCR and immuno-histochemistry, respectively.</p><p><b>RESULTS</b>(1) 10/12 of the experimental fluorosis rats developed dental fluorosis, and 2/12 of dental fluorosis rats occurred in the low-dosage medication group. Fluoride content in urine and bone of the fluorosis rats increased (P<0.05). (2) Compared with that of the control rats, the bone trabecular depth, cortical thickness and trabecular density in experimental fluorosis rats were remarkably reduced. (3) Compared with that of the control group, mRNA expression of both OPGL and M-CSF was increased in the fluoride group rats. The difference was statistically significant (P<0.05). (4) Compared with that of the fluoride group animals, the expression intensity of OPGL mRNA decreased in animals of the control group, the high, mid- and low- dosage medication groups and the borax group. Among them, except the low-dosage group, the difference between all the other groups and the fluoride group was statistically significant, respectively (P<0.05). There was also a decrease of M-CSF mRNA in all the 3 medication groups and the borax group animals in comparing with that of the fluoride group and the difference was also statistically significant (P<0.05), respectively. (5) Compared with that of the control group. There were an increase of OPGL and a decrease of M-CSF protein expression; and in addition, there were a decrease of OPGL and an increase of M-CSF protein expression in all 3 medication groups and the borax group in comparing with that of the fluoride group anima (P < 0.05).</p><p><b>CONCLUSIONS</b>Excessive fluoride induces an accelerated bone turnover and may promote the absorption activity of osteoclasts by increasing the expression of OPGL and M-CSF. Danlan Xianpeng Liaofu capsule may be capable of regulating bone remodeling through a down-regulation on OPGL and M-CSF expression.</p>