Effects and mechanism of p53 gene deletion on energy metabolism during the pluripotent transformation of spermatogonial stem cells / 生理学报

Previous studies have shown that long-term spermatogonial stem cells (SSCs) have the potential to spontaneously transform into pluripotent stem cells, which is speculated to be related to the tumorigenesis of testicular germ cells, especially when p53 is deficient in SSCs which shows a significant increase in the spontaneous transformation efficiency. Energy metabolism has been proved to be strongly associated with the maintenance and acquisition of pluripotency. Recently, we compared the difference in chromatin accessibility and gene expression profiles between wild-type (p53+/+) and p53 deficient (p53-/-) mouse SSCs using the Assay for Targeting Accessible-Chromatin with high-throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) techniques, and revealed that SMAD3 is a key transcription factor in the transformation of SSCs into pluripotent cells. In addition, we also observed significant changes in the expression levels of many genes related to energy metabolism after p53 deletion. To further reveal the role of p53 in the regulation of pluripotency and energy metabolism, this paper explored the effects and mechanism of p53 deletion on energy metabolism during the pluripotent transformation of SSCs. The results of ATAC-seq and RNA-seq from p53+/+ and p53-/- SSCs revealed that gene chromatin accessibility related to positive regulation of glycolysis and electron transfer and ATP synthesis was increased, and the transcription levels of genes encoding key glycolytic enzymes and regulating electron transport-related enzymes were markedly increased. Furthermore, transcription factors SMAD3 and SMAD4 promoted glycolysis and energy homeostasis by binding to the chromatin of the Prkag2 gene which encodes the AMPK subunit. These results suggest that p53 deficiency activates the key enzyme genes of glycolysis in SSCs and enhances the chromatin accessibility of genes associated with glycolysis activation to improve glycolysis activity and promote transformation to pluripotency. Moreover, SMAD3/SMAD4-mediated transcription of the Prkag2 gene ensures the energy demand of cells in the process of pluripotency transformation and maintains cell energy homeostasis by promoting AMPK activity. These results shed light on the importance of the crosstalk between energy metabolism and stem cell pluripotency transformation, which might be helpful for clinical research of gonadal tumors.

Neonate-onset ornithine transcarbamylase deficiency / 中国当代儿科杂志

The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed OTC gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.

The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction / 亚洲男科学杂志(英文版)

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

Effects of glucagon-like peptide-1 on male reproductive function / 中华内分泌代谢杂志

With the younger onset of diabetes, the reproductive dysfunction caused by diabetes has received widespread attention. Hyperglycemia and insulin resistance, the main features of diabetes, are high-risk factors for male reproductive dysfunction. Obesity, the common co-morbidity of diabetes, may aggravate the progression of reproductive dysfunction. Glucagon-like peptide-1(GLP-1) and its receptor agonists improve the overall health status by lowering blood glucose, reducing body weight, and inhibiting inflammatory response, which indirectly exerts protective effects on the reproductive system. GLP-1 also protects reproductive function by regulating the neuroendocrine function, and directly acting on the supporting cells and interstitial cells of the testis. However, some studies did not find the protective effects. High-quality clinical studies are needed. GLP-1 receptor agonists may be a therapeutic option to improve reproductive dysfunction in diabetic men.

Rapid identification of chemical constituents in the dried stem bark of Asparagus officinalis L. based on UPLC-Q-TOF-MS/MS / 药学学报

Ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with a molecular network analysis strategy was used to identify the chemical constituents of the stem bark of two kinds of asparagus. The chemical constituents were identified by determining an accurate molecular weight, the fragmentation pathway, and comparison with the mass spectrometry data from the references. A molecular network was established based on the similarity of MS/MS fragmentation patterns. A total of 107 compounds were identified or tentatively deduced, which included 46 saponins, 13 flavonoids, and 48 other compounds. The chemical compounds identified in the stem bark of white and green asparagus differed greatly: the white asparagus was rich in saponins, while the green asparagus was rich in flavonoids. In conclusion, the chemical constituents of asparagus stem bark were characterized rapidly using UPLC-Q-TOF-MS/MS and molecular network analysis, with 10 compounds and 45 targets determined from the HIT 2.0 herbal ingredients' targets platform. This work will provide a theoretical basis for the resource utilization of asparagus.

Protective effects and potential mechanism of the SGLT2 inhibitor on islet β cells / 中华内分泌代谢杂志

Islet β cell protection is one of the key strategies for diabetes treatment. The new antidiabetic drug sodium-glucose cotransporter 2(SGLT2)inhibitor decreases blood glucose by inhibiting glucose reabsorption in the renal tubule, independent of insulin. Various clinical studies have shown that SGLT2 inhibitors improve β cell function. Furthermore, animal experiments have indicated that SGLT2 inhibitors increase β cell mass. SGLT2 inhibitors promote islet regeneration through stimulating β cell proliferation, inhibiting β cell apoptosis and dedifferentiation, enhancing transdifferentiation of α cells to β cells, and initiating progenitor-derived β cell neogenisis. Indirect effects of metabolic improvement(i.e.lowering glucose, losing weight, improving lipid metabolism), inhibiting inflammatory reaction, inducing glucagon-like peptide-1 secreted from α cells, and regulating gene changes might be involved in the β cell protection of SGLT2 inhibitors.

Studies on phenylpropanoids from Eleocharis dulcis and their hepatoprotective activities / 中国中药杂志

To study phenylpropanoids from Eleocharis dulcis and their hepatoprotective activities. The compounds were separated and purified from ethyl acetate part by conventional column chromatography and preparative liquid chromatography, and their structures were identified by various spectral techniques. The HL-7702 cells damage model of hepatocytes induced by APAP was used to screen and evaluate the hepatoprotective activities of these compounds. Sixteen compounds were isolated from ethyl acetate part of E. dulcis, and their structures were identified as 6'-(4″-hydroxy-3″-methoxy-phenylpropenyl)-1-(10-methoxy-phenylacetone)-1'-O-β-D-glucopy-ranoside(1), susaroyside A(2), clausenaglycoside B(3), clausenaglycoside C(4), clausenaglycoside D(5), emarginone A(6), emarginone B(7), thoreliin B(8), 4-O-(1',3'-dihydroxypropan-2'-yl)-dihydroconiferyl alcohol 9-O-β-D-glucopyranoside(9), 2-[4-(3-methoxy-1-propenyl)-2-methoxy-phenoxy]-propane-1,3-diol(10), 6'-O-(E-cinnamoyl)-coniferin(11), methyl 3-(2-O-β-D-glucopyranosyl-3,4,5,6-tetramethoxyphenyl) propanoate(12), clausenaglycoside A(13), 9-O-(E-cinnamoyl)-coniferin(14), 6'-O-(E-cinnamoyl)-syringin(15), 2'-O-(E-cinnamoyl)-syringin(16). Among them, compound 1 was a new compound. Compounds 2-16 were isolated from this plant for the first time. Among them, compounds 2 and 8 showed certain hepatoprotective activities.

Research Progress of Non-coding RNA and Endometrial Receptivity / 中国医学科学院学报

Endometrial receptivity has become the main cause of fertilization and pregnancy outcomes in infertile patients,bringing large psychological damage and economic loss to the patients and their family. In recent years,the role of non-coding RNA has increasingly been recognized. The relationship between non-coding RNA and endometrial receptivity is reviewed in this article.

The correlation between inflammation levels and lung function on patients defined by different TCM syndromes with acute exacerbation of chronic obstructive pulmonary disease / 国际中医中药杂志

Objective:To observe the changes of neutrophil to lymphocyte ratio and lung function of patients defined by different TCM syndromes with acute exacerbation of chronic obstructive pulmonary disease.Methods:A total of 181 patients with acute exacerbation of chronic obstructive pulmonary disease in our hospital from January 2016 to Novenber 2018 were included and divided into 5 groups accoding to different TCM syndromes, which were wind-cold invading lung syndrome (26), external cold and internal fluid syndrome (40), phlegm-heat obstructing lung syndrome (48), phlegm-dampness blocked syndrome (48), an heart spirit confused by phlegm syndrome (19). Then tested the blood for each group, and calculated NLR; tested c-reactive protein, and lung function, and measured with COPD Assessment Test (CAT) and Modified British Medical Research Council (mMRC); conducted 6MWT, then the BODE index and Charlson Comorbidity Index (CCI) scores were calculated.Results:The NLR, CRP level in patients with external cold and internal fluid syndrome and an heart spirit confused by phlegm syndromeby phlegm were significantly higher than those of other syndrome ( P<0.05 or P<0.01), and FEV1% Pred was significantly lower than that of phlegm-dampness blocked syndrome ( P=0.024); the 6-minute walking distance of patients with external cold and internal fluid syndrome was significantly shorter than that of phlegm-heat obstructing lung syndrome and phlegm-dampness blocked syndrome ( P=0.006, P=0.024). The comparison of mMRC grades among the syndromes was statistically significant ( F=26.367, P=0.049). The BODE index of patients external cold and internal fluid syndrome was higher than that of patients phlegm-heat obstructing lung syndrome ( P=0.015), and the CCI score of patients an heart spirit confused by phlegm syndrome was higher than that of patients phlegm-dampness blocked syndrome ( P=0.012). The BODE index of patients with external cold internal fluid syndrome was significantly higher than that of phlegm-heat obstructing lung syndrome ( P=0.015). The CCI score of patients with mental disorder caused by phlegm was significantly higher than that of phlegm-dampness blocked lung syndrome ( P=0.012). Conclusions:There were significantly differences in neutrophil to lymphocyte ratio, CRP and 6-minute walking distance among different TCM syndromes in patients with acute exacerbation of chronic obstructive pulmonary disease. The inflammation in patients with external cold and internal fluid syndrome and mental disorder caused by phlegmare much severe, but there might be no difference in dyspnea and prognosis among TCM syndromes.

Mechanism of Anti-chronic Alcoholic Liver Injury in Rats of Tibetan Medicine Lagotis brachystachys Extracts by TLR2/MyD88/NF-κB and NALP3 Signaling Pathway / 中国实验方剂学杂志

Objective::To established the model of chronic alcoholic liver injury in rats by long-term(8 weeks) alcoholic gavage, to study the effects of Tibetan medicine Lagotis brachystachys extracts on Toll-like receptor(TLR)2/myeloid differentiation factor 88(MyD88)/nuclear factor kappa B (NF-κB)and NOD like receptor protein 3(NALP3) signaling pathways and study preliminary the mechanism of action of chronic alcoholic liver injury. Method::Sixty male Sprague-Dawley rats were randomly divided into normal group, model group, bifendate positive drug group (0.1 g·kg-1) and L. brachystachys low, medium and high-dose groups (0.5, 1, 2 g·kg-1), the corresponding drugs were given at 10 mL·kg-1 in each morning, and the 56 degree Liquor was administered by the afternoon gradient alcoholic gavage method.After 8 weeks, the levels of serum aspartate transaminase (AST), serum alanineaminotransfease(ALT), serum total cholesterol(TC), triglyceride(TG), interleukin-1β(IL-1β), and the liver levels of L-glutathione(GSH)were measured. The expression of TLR2, MyD88, NF-κB and NALP3 protein in liver were detected by Western blot.Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue. Result::Compared with normal group, the serum levels of AST, ALT, TC, TG and IL-1β in model group were significantly increased (P<0.05, P<0.01). Compared with model group, the serum AST, ALT, TC, TG and IL-1β levels were decreased in the various doses of L. brachystachys, and the high dose group was particularly effective (P<0.05, P<0.01). Compared with normal group, the GSH level in the liver homogenate of model group decreased significantly, and the difference was not statistically significant. The levels of TLR2, MyD88, NF-κB and NALP3 in the liver tissue of model group were significantly increased (P<0.05, P<0.01). The GSH levels in the liver and the protein expression of TLR2, MyD88, NF-κB and NALP3 were decreased in L. brachystachys group (P<0.05, P<0.01). The liver pathological section showed that L. brachystachys can improve the pathological changes of rat liver tissue. Conclusion::L. brachystachys can protect liver from alcohol-induced chronic liver injury in rats. The mechanism was related to TLR2/MyD88/NF-κB and NALP3 signaling pathway.

Protective effects and action mechanism of extract from Tibetan medicine Yajima(Chrysosplenium nudicaule) on mice with intrahepatic cholestasis induced by ANIT / 中国中药杂志

Chrysosplenium nudicaule,Tibetan name " Yajima",is recorded as an effective medicine for the treatment of liver and gallbladder diseases by Tibetan Pharmacopoeia published in the past dynasties,but its traditional efficacy has not yet been investigated by means of modern pharmacological research methods. In this paper,the protective effect of extract of C. nudicaule(ECN) on liver injury in mice was observed by using the mice model of intrahepatic cholestasis(IC) induced by α-naphthyl isothiocyanate(ANIT) and the possible mechanism by which ECN work as the therapeutic agent was discussed. The results showed that the serum levels of AST,ALT,ALP,DBIL,TBIL and TBA of the model mice were notably reduced in dose-dependent manner(P<0. 01,P<0. 05). The activity of SOD and GSH-Px in the liver homogenate of mice was increased,while the content of MDA was decreased(P<0. 01,P<0. 05).Pathological examination of liver in mice showed that ECN could improve the pathological changes of liver tissue in mice. The mRNA expression level of genes related to bile acid metabolism were detected by RT-PCR and the results suggested that ECN could significantly increase the expression of genes such as BSEP,FXR and MRP2(P<0. 01,P<0. 05),meanwhile significantly reduce the expression of CYP7 A1(P<0. 01,P<0. 05). These results confirmed the protective effect of ECN on intrahepatic cholestasis-induced liver injury in mice,and indicated that the mechanism may be related to activating FXR and its target genes,reducing bile acid synthesis and increasing bile acid excretion. This study provides a modern pharmacological basis for the clinical application of Yajima in Tibetan medicine.

Effect of Longdan Xiegantang on Serum Inflammatory Factors, Related Proteins and Immune Function in Patients with Secretory Otitis Media / 中国实验方剂学杂志

Objective: To explore the effect of Longdan Xiegantang on serum inflammatory factors, related proteins and immune function in patients of secretory otitis media (SOM) with liver and gallbladder wetness-heat Syndrome. Method:Totally 76 cases of SOM with liver and gallbladder wetness-heat syndrome admitted to our hospital from July 2017 to May 2018 were randomly divided into two groups, with 38 cases in each group. Control group was treated with triamcinolone acetonide and ambroxol. In addition to the therapy of control group, observation group was also treated with Longdan Xiegantang. Immunoglobulin (Ig) A, IgG, IgM, CD3+, CD4+, CD8+and NK, interleukin-1 beta (IL-1β), IL-5, IL-8, tumor necrosis factor-α (TNF-α), platelet activating factor (PAF), calcitonin (PCT) and water channel protein-1 (AQP-1), AQP-4, fiber link protein (Fn) and soluble interleukin-2 receptor (SIL-2R) levels of two groups were observed before and after treatment. Curative effect and adverse reaction were observed. Result:①Curative effect, after treatment, the total effective rate of observation group was 92.11%, which was higher than 76.32% of control group, with statistically significant differences (Z=2.108, Pα, PAF, PCT, IL-1β and IL-8 in observation group were lower than those in control group after treatment (PPP+, IgA, IgG and IgM of observation group were lower than those of control group (P+, CD4+, CD4+/CD8+ and NK were higher than those of control group (PConclusion:Longdan Xiegantang has a remarkable effect in treating patients of secretory otitis media with liver and gallbladder wetness-heat syndrome, and can restore symptoms, inhibit inflammatory response, activate cell and humeral immune system, reduce the secretion of AQP-1, SIL-2R and other proteins, and increase the secretion of AQP-4 and Fn proteins.

Management of an Adult with Goodpasture's Syndrome Following Brain Trauma with Extracorporeal Membrane Oxygenation: A Case Report / 中国医学科学杂志(英文版)

A 22-year-old man suffered from acute pulmonary hemorrhage and deteriorated renal function occurred within 3 days after traumatic brain injury. Mechanical ventilation cannot correct his severe hypoxemia, therefore, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support was initiated and finally resolved his hypoxemia. Concomitantly, continuous renal replacement therapy was performed to improve his kidney function. Although no anti-glomerular basement membrane (anti-GBM) antibody was detected in serum, Goodpasture's syndrome was considered. After treated with methylprednisolone pulse therapy and plasmapheresis, his renal function was significantly improved. ECMO was eventually discontinued after 60 hours of treatment and extubated on day 10. He was discharged home with normal pulmonary and renal functions.

Rapid identification of constituents of Urtica hyperborea using UPLC-ESI-Q-TOF-MS/MS method / 中国中药杂志

This paper deals with the application of ultra-performance liquid chromatography tandem quadrupole time of flight mass spectrometry(UPLC-ESI-Q-TOF-MS/MS) method to rapidly determine and analyze the chemical constituents of methanol extract of Urtica hyperborea. We employed UPLC YMC-Triart C18(2. 1 mm×100 mm,1. 9 μm) column to UPLC analysis with acetonitrile-water(containing 0. 4% formic acid) in gradient as mobile phase. The flow rate was 0. 3 m L·min-1 gradient elution and column temperature was 30℃; the injection volume was 4 μL. ESI ion source was used to ensure the data collected in anegative ion mode. The chemical components of U. hyperborea were identified through retention time,exact relative molecular mass,cleavage fragments of MS/MS and reported data.The results indicated that a total of 31 compounds were identified,including 8 flavonoids,14 phenolic compounds,8 phenylpropanoids(4 coumarins and 4 lignans),and 1 steroidal compound,13 of which were confirmed by comparison. The UPLC-ESI-Q-TOF-MS/MS method could rapid identify the chemical components of U. hyperborea. The above compounds were discovered in U. hyperborea for the first time,which could provide theoretical foundation for further research on the basis of the pharmacodynamics of U. hyperborea.

Analysis of survival and prognostic factors of patients with intracranial ependymoma / 中国肿瘤临床

Objective: To study the factors affecting the survival and prognosis of patients with intracranial ependymoma. Methods:From January 2008 to January 2018, the prognoses of 276 patients with intracranial ependymoma were analyzed using Log-rank and Cox model analysis. The variables included sex, age, tumor location, tumor diameter, resection extent, pathological grade, Ki-67 index, postoperative radiotherapy, and postoperative chemotherapy. Results: Tumor location, resection extent, and postoperative radiothera-py could all affect the overall survival (OS) and progression-free survival (PFS) of patients with intracranial ependymoma (P<0.001) and independently affected the OS (P<0.001, P<0.001, and P=0.002, respectively) and PFS (P<0.001, P<0.001, and P=0.001, respectively). The Ki-67 index was an independent factor affecting PFS in patients with intracranial ependymoma (P<0.001). The supratentorial loca-tion and Ki-67 index≥10% were independent risk factors indicating poor prognosis (P<0.001). Total resection and postoperative radio-therapy were protective factors (P<0.001 and P=0.001, respectively). Conclusions: Tumor location, resection extent, Ki-67 index, and postoperative radiotherapy are independent factors affecting the prognosis of intracranial ependymoma. It is helpful to extend the PFS and OS of patients through complete tumor resection or postoperative radiotherapy.

Study on effect of extract from Tibetan medicine Urtica hyperborean on anti-prostatic hyperplasia / 中国中药杂志

In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.

Glucagon receptor monoclonal antibodies: A new strategy for diabetes pharmacotherapy / 中华内分泌代谢杂志

Glucagon regulates glucolipid metabolism and body weight through binding to and activating glucagon receptor ( GCGR ), which is predominantly expressed in liver and pancreas. In the diabetic state, inappropriately increased glucagon secretion leads to elevated hepatic glucose output, while GCGR blockage restores blood glucose homeostasis. Various approaches including GCGR monoclonal antibodies ( mAbs ), antagonists, antisense oligonucleotides, and gene knockout can block GCGR signaling. It has shown that GCGR mAbs improve hyperglycemia in diabetic mice and humans without severe adverse effects, since they can specifically antagonize the action of glucagon. Therefore, GCGR signaling plays a critical role in the pathophysiology of diabetes and GCGR mAbs represent innovative approaches in the management of diabetes.

Progression of correlation between different Chinese syndromes and laboratory indicators in patients with acute exacerbation of chronic obstructive pulmonary disease / 国际中医中药杂志

This paper analyzed and summarized the correlation between pulmonary function test, inflammatory factors, blood gas analysis and different traditional Chinese medicine syndromes in patients with acute exacerbation of chronic obstructive pulmonary disease. This paper helped to provide a reference for further treatment.

Implication of proinsulin to insulin ratio in the basic and clinical research of diabetes / 中华内分泌代谢杂志

Proinsulin is the precursor of mature insulin.Proinsulin to insulin ratio reflects the degree of pancreatic β-cell dysfunction and the progression of type 2 diabetes, and may predict the risk of diabetes development.Some variants in susceptibility genes of diabetes are associated with the elevation of proinsulin to insulin ratio.Moreover, several antidiabetic drugs are able to decrease the proinsulin to insulin ratio in patients with type 2 diabetes.Therefore, the proinsulin to insulin ratio may act as a simple and useful indicator in the etiological study, risk prediction, disease progression and therapeutical evaluation in type 2 diabetes.