Objective To study the value of contact heat evoked potentials (CHEPs) for the early diagnosis of diabetic peripheral polyneuropathy. Methods Seventy-five diabetic patients were examined by conventional nerve conduction velocity studies and then divided into 2 groups: diabetics with normal nerve conduction and diabetics with abnormal nerve conduction. Thirty-three normal subjects were used as controls. Toronto Clinical Neuropathy Sco-ring System was used to evaluate the patients. CHEPs were recorded using different stimulation intensities at different temperatures. Results The peak latencies of 45℃ , 50℃, 53℃ in diabetics with normal nerve conduction group were longer than those in normal control group, with a significant difference between the 2 groups(P<0.05). The peak latencies of diabetics were positively related to Toronto scores. Conclusion CHEPs could detect the impair-ment of diabetic peripheral nerve and reveal the impairment earlier than conventional nerve conduction velocity exami-nation, The prolongation of peak latency in diabetics group was significantly and positively related to clinical condi-tion.

BACKGROUND: Studies have demonstrated that intermittent high glucose can have a more severe impact on vascular endothelial function in comparison with persistent hyperglycemia.OBJECTIVE: To investigate the effect of intermittent high glucose on the proliferation and apoptosis of endothelial progenitor cells (EPCs) from human peripheral blood in vitro as well as the production of malondialdehyde (MDA) and antioxidant. METHODS: Total mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation and then the cells were placed on fibronectin-coated culture dishes. After 7 days of culture, the adherent cells were identified as EPCs by laser scanning confocal microscope. The cells were synchronized and then stimulated with glucose 5.5 mmol/L (normal control group), 20 mmol/L (constant high glucose group), and 5.5/20 mmol/L (intermittent high glucose group, 5.5 and 20 mmol/L glucose culture solution was changed every 8 hours) for 72 hours. EPCs proliferation and apoptosis was measured by MTT assay and flow cytometry, respectively. The content of MDA and the activity of superoxide dismutase (SOD) in culture solution were detected with colorimetry.RESULTS AND CONCLUSION: After EPCs were exposed to constant high glucose (20 mmol/L) and intermittent high glucose (5.5/20 mmol/L) for 72 hours, proliferated cells were significantly reduced and the apoptosis rate was significantly increased compared with those exposed to normal glucose (P < 0.01). Furthermore, there was a significant increase in MDA contents as well as a significant reduce in SOD activities in the constant high glucose and intermittent high glucose group (P < 0.01), especially in the latter group. These findings indicated that both intermittent high glucose and constant glucose could inhibit the proliferation and promote the apoptosis of EPCs; however, intermittent high glucose appears to worsen the effects on EPCs. This is maybe due to the increased oxidative stress.

It is an obvious contradiction between the shortage of kidney donors and the increasing demand for kidney transplantation.Living- related donor kidney transplantation may be a proper resolution,which has been academically proved to be superior to cadaveric kidney transplantation.However,there are still many ethical problems unsolved.Based on ethical theory and the"Seven Principles",we explore possible solutions to the ethical problems of living - related donor kidney transplantation.

At present, majority of the small molecular drugs used in clinics target proteins, they exert the efficacy through the binding to specific sites on the target protein. However, the "druggable" protein targets account for a small portion of the total number of proteins, and "non-druggable" proteins account for 80%, because of not having suitable drug binding sites. In the central rule, RNA is located in the upstream of proteins and controls the transcription of proteins. The research of small molecule drugs targeting RNA can solve the problem of protein "undruggable proteins" in some extent. This review summarizes the representative research achievements of small molecular drugs targeting RNA in recent years, and the screening methods applied to this field, with the focuses on the latest progress of small molecular drugs targeting novel coronavirus RNA.

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

Adult ; Air Pollutants ; adverse effects ; Humans ; Male ; Military Medicine ; Monitoring, Physiologic ; Noise, Occupational ; adverse effects

China ; Female ; Gynecology ; trends ; Humans ; Physical Examination ; statistics & numerical data ; Rural Health ; statistics & numerical data ; Rural Population

Objective:To investigate the correlation between the breast cancer MRI schedule of reinforcement and the shrinkage pattern of tumor after neo-adjuvant chemotherapy, and its clinical significance in the guidance of formulating operation plan. Methods:Dynamic contrast-enhanced MRI scan was performed before chemotherapy and before surgery after a whole-range N-Acety-L-Cysteine (NAC) treatment in 55 patients with loco-regionally advanced breast cancer who received the neo-adjuvant chemotherapy. MRI sched-ule of reinforcement and the shrinkage pattern of tumor after neo-adjuvant chemotherapy were obtained in the treatment, and the corre-lation between the two was analyzed. Results:Of the 55 patients, the unilateral breast mass was found in 54 and the bilateral lesion in 1. There were 56 neo-plastic foci in these patients. The mass-like enhanced image was seen in 24 of the total cases (43%), of which 23 presented with a centripetal shrinkage, 1 with an annular decline, (P<0.01). Multifocal mass-like enhancement image was found in 13 of the total cases, (23%), of which 2 centripetal shrinkages were the singular mass, 11 remained a multifocal lesion after the tumor shrinkage (P<0.01). The mass with peripheral non-tumor-like enhancement image was seen in 8 of the total cases (14%), of which 4 showed a centripetal shrinkage and another 4 a honeycombed multifocal decline (P>0.05). There were 11 of the total cases with non-tu-mor-like enhancement (20%), in which 4 assumed a centripetal shrinkage and 7 a honeycombed multifocal shrinkage (P<0.01). Conclu-sion:The tumor shrinking pattern and its accurate radiological image evaluation are the keys to the selection of breast-conserving sur-gery and the control of local recurrence after treatment of NAC regimen. We can predict the shrinking pattern through the type of the le-sion on baseline before NAC, which is important for the patients and surgeon to get a reasonable expectation in the subsequent treat-ments.

Objective To investigate whether a novel long-acting tumor necrotic factor (TNF) antagonist (soluble TNF receptor:IgG Fc [sTNFR:IgG-Fc]) can protect hepatocyte damage against liver failure caused by drugs in immunity-induced cirrhotic rats.Methods Wistar rats were repeatedly sensitized by human serum albumin (HSA) emulsified in complete freud adjuvant.The blood was collected at day 10 after the final sensitization.If anti-albumin antibody was positive,the rats were intravenously injected with HSA twice a week.After six weeks,liver cirrhosis was induced by immunity.All the model rats were divided into three groups with 15 each.Liver failure was induced with D-galactosamine/ lipopolysaccharide (LPS) intraperitoneal injection in the rats with liver cirrhosis in model group.The rats in pretreatment group were intraperitoneally injected with long-acting soluble TNF receptor p55 18 h before D-galactosamine/LPS injection.The control group were injected with 0.9％ sodium chloride.General condition,survival rate,liver function and pathological changes were all examined.Serum levels of interleukin (IL)-6,IL-22 and intrahepatic level of IL-6 were detected by enzyme linked immunosorbent assay (ELISA).The activity of Caspase 3 in hepatocyte lysis solution was measured by spectrophotography.Real-time polymerase chain reaction (PCR) was used to detect mRNA expressions of proliferating cell nuclear antigen (PCNA),bcl-2,bax and IL-22 receptor.Data were analyzed by variance analysis among groups.Results Rats in model group were dispirited with poor response after 12 hours and only 3 survived,compared with soluble TNF receptor p55 pre-treated group rats,in which all survived (P=0.029 8) with flexible response.Serum alanine aminotransferase levels in these two groups were (6 533± 360) and (105 ± 7) U/L,respectively.Hepatic regenerative nodule developed massive or submassive necrosis with septal fibrosis in model group,whereas soluble TNF receptor p55 alleviated the inflammatory and necrosis reaction of hepatic tissue.Serum IL-6 levels in model group and pretreatment group were (842.0±12.9) and (91.9±1.6) pg/mL,respectively (F=380.30,P＜0.01).Intrahepatic levels of IL-6 in these two groups were (26.2±1.2) and (11.1±0.8) pg/mL,respectively (F=176.90,P＜0.01),and serum IL-22 levels were (167.0±27.8) and (988.0±109.6) pg/mL,respectively (F=37.91,P＜0.01).Hepatic Caspase-3 activity was reduced by almost 60％ by soluble TNF receptor p55 pretreatment (F=303.70,P＜0.01) and bax expression reduced by 22％ (F=108.80,P＜0.01),while bcl-2 and PCNA expressions were up-regulated by 3.6-folds and 23.0-folds,respectively (F=115.60,P＜0.01; F=594.20,P＜0.01).Conclusions Long acting soluble TNF receptor p55 could improve survival rate,liver function and reduce inflammatory reaction of rats with liver failure induced by drugs on the basis of liver cirrhosis caused by immunity,which indicates that this drug may process a potential therapeutic value.