Alzheimer's disease(AD) is a common neurodegenerative disease with increasing incidence rate. Up to now,there is no ideal treatment for AD. It has become a public health problem worldwide. Traditional Chinese medicine (TCM) believes that kidney deficiency is the key symptomatic element of deterioration and temporal progression symptoms,accompanied by the AD process. The treatment of tonifying kidneys,supplementing essence and replenishing marrow is the fundamental method for AD in TCM. Clinical studies have shown that kidney-tonifying formula can significantly improve the cognitive function and daily ability of patients with mild and moderate AD and have no obvious adverse reactions. Its mechanism of action may be related to the protection of nerves,reduction of β-amyloid (Aβ) level in the brain,inhibition of inflammatory factors activation and anti-oxidative stress. Besides reviewing the clinical and pharmacological research progress of kidney-tonifying formula for AD,this article also discusses the advantages and shortcomings of kidney-tonifying formula in the prevention and treatment of AD based on TCM theory and modern medical research. The aim of this study is to provide references of kidney nourishing therapy in TCM for the prevention and treatment of neurodegenerative diseases.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective To explore the changes of whole brain white matter ( WM) structural net-work topological property in patients with schizophrenia (SP) and the associations between WM networks to-pological efficiency and clinical variables in patients. Methods Deterministic tractography was used to con-struct the WM networks of 59 patients with SP ( patients group) and 41 age-, handedness-, and gender-matched healthy controls (HCs),and graph theoretical methods were applied to investigate abnormalities in the global and nodal properties of the WM network in these patients. Partial correlation analysis was used to analyze the relationship between global and nodal properties of the WM network and clinical variables in pa-tients with SP. Results Both the patients with SP and HCs showed small-world organization of the WM net-works. However,compared with HCs,the patients with SP exhibited significant abnormal global topology,in-cluding increased shortest path length ( t=7. 95, P=0. 0001) and decreased global efficiency ( 30. 83 ± 16. 08,8. 25±6. 13,t=-9. 81,P=0. 002),clustering coefficiency (0. 03±0. 01,0. 02±0. 01,t=-4. 48,P=0. 0003),the average clustering coefficiency (t=-8. 28,P=0. 002),the small-worldness (3. 92±0. 79,2. 79 ±0. 56,t=-7. 82,P=0. 001) of their WM structural networks(all P<0. 005,FDR corrected). Further,the patients with SP showed a reduction in nodal efficiency predominately in the cingulate gyrus ( t=-4. 11, P=0. 000),superior occipital gyrus ( t=-6. 05, P=0. 002), superior temporal gyrus ( t=-10. 46, P=0. 001),middle temporal gyrus (t=-10. 38,P=0. 000),thalamus (t=-6. 10,P=0. 000) and putamen ( t=-8. 38,P=0. 000) (P<0. 005,FDR corrected). Partial correlation results showed that there was no signifi-cant correlation between global topological properties,node efficiency and clinical symptoms in patients group (Eglob:r=-0. 14,P=0. 279;Eloc:r=-0. 06,P=0. 628;Lp:r=0. 28,P=0. 031;Cp:r=0. 27,P=0. 043;λ:r=-0. 18,P=0. 166;γ:r=-0. 29,P=0. 026;σ:r=0. 26,P=0. 048;nEglob:r=0. 36,P=0. 005;nEloc:r=0. 02,P=0. 901). Conclusions The patients with SP exhibit the abnormal of whole brain WM structural network topological property and the node efficiencies of cortico-striato-thalamo circuitry are significantly re-duced.

Objective To know the prevalence of chronic obstructive pulmonary disease(COPD) in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS) in Kunming Yunnan Province, and the clinical symptom of OS.Methods Retrospective study of 4 636 cases of patients with snoring, excluding COPD in addition to chronic respiratory disease and assess the patient`s condition.The test included AHI, BMI, Epworth sleepiness scale, lung function.The index of OS was confirmed by AHI>5 times/h and FEV1/FVC<70%.Results During the period of 2006 to 2012, he prevalence of COPD in patients with OSAHS was 10.1% [95% confidence interval (CI) 9.1%-11.1%] in Kunming Yunnan Province.And male`s OS prevalence rate is higher than the female(male 10.2%;female 9.7%).The OS patients` average age was 56.9±14.1, the mean AHI was (47.46±26.79) times/h, and the average FEV1/FVC was 60.09%±23.57%.Polysomnographyresults show that patients suffered obvious hypoxiaat night in both OSAHS group and OS group, but it was more significant in OS group.Pulmonary function test showed that OS patients have more serious chronic obstructive pulmonary disease.Conclusions The prevalence of COPD in OSAHS patients was high in Kunming, Yunnan Province, and the prevalence rate in old group reached more than 24%.In addition, the sympotms of patients with OS were more severe than those with only OSAHS or COPD in lung function and hyoxemia.

Objective To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods A total of 41338 women delivered in the 15 hospitals during the 6 months,195 women with PGDM(PGDM group) and 195 women with normal glucose test result(control group)were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups. In the PGDM group, pregnancy outcomes were analyzed in women who used insulin treatment (n=91) and women who did not (n=104). Results (1)The incidence of PGDM was 0.472%(195/41338). Diabetes mellitus were diagnosed in 59 women (30.3%, 59/195) before pregnancy, and 136 women (69.7%,136/195) were diagnosed as PGDM after conceptions. Forty-six women (33.8%) were diagnosed by fasting glucose and glycohemoglobin (HbA1c) screening. (2) The maternal age, pre-pregnancy body mass index (BMI), prenatal BMI, percentage of family history of diabetes, incidence of macrosomia, concentration of low density lipoprotein were significantly higher in PGDM group than those in control group (all P<0.05). Women in PGDM group had significantly higher HbA1c concentration((6.3±1.3)% vs (5.2±0.4)%), fasting glucose [(6.3±2.3) vs (4.8±1.1) mmol/L], oral glucose tolerance test(OGTT)-1 h glucose((12.6±2.9) vs (7.1± 1.3) mmol/L)and OGTT-2 h glucose [(12.0±3.0) vs (6.4±1.0) mmol/L] than those in control group (P<0.01). (3)The morbidity of preterm births was significantly higher (11.3% vs 1.0%, P<0.01), and the gestational age at delivery in PGDM group was significantly smaller [(37.6±2.3) vs (39.2±1.2) weeks, P<0.01]. Cesarean delivery rate in the PGDM group (70.8% vs 29.7%) was significantly higher than the control group (P<0.01). There was significantly difference between PGDM group and control in the neonatal male/female ratio (98/97 vs 111/84, P=0.033). The neonatal birth weight in PGDM group was significantly higher((3159±700) vs (3451±423) g, P<0.01). And the incidence of neonatal hypoglycemia in the PGDM group was higher than the control group (7.7% vs 2.6%, P=0.036).(4)In the PGDM group, women who were treated with insulin had a smaller gestational age at delivery [(36.9±2.9) vs (37.9±2.5) weeks, P<0.01], and the neonates had a higher neonatal ICU(NICU)admission rate (24.2% vs 9.6% , P<0.01). Conclusions The morbidity of PGDM in the 15 hospitals in Guangdong province is 0.472%. The majority of PGDM was diagnosed during pregnancy; HbA1c and fasting glucose are reliable parameters for PGDM screening. Women with PGDM have obvious family history of diabetes and repeated pregnancy may accelerate the process of diabetes mellitus. Women with PGDM have higher risk for preterm delivery and neonatal hypoglycemia. Unsatisfied glucose control followed by insulin treatment may increase the need for NICU admission.

Aim To investigate whether the pain modi-fication by group I metabotropic glutamate receptors (mGluRs)required the involvement of Src homology-2 domain-containing phosphatase-2 (SHP-2 ).Methods Co-immunoprecipitation was performed to examine the possible interaction between SHP-2 and group I mGluRs in spinal cord dorsal horn of mice.By measur-ing the paw withdrawal thresholds,the effects of SHP-2 inhibitor NSC-87877 or its catalytically inactive SHP-2 (C459S ) mutant on allodynia induced by group I mGluRs agonist DHPG (50 nmol)were observed.Re-sults Anti-mGluR5 antibody was able to co-immuno-precipitate SHP-2 from spinal dorsal horn of mice, while no SHP-2 was precipitated by anti-mGluR1 anti-body.Inactivation of SHP-2 by NSC-87877 (6 nmol) or SHP-2 (C459S ) effectively attenuated allodynia caused by DHPG.Conclusion SHP-2 can physically interact with mGluR5.The activation of SHP-2 may be necessary for group I mGluRs to process the nocicep-tive information.

Objective To investigate the susceptibility related sites to schizophrenia through whole genome analysis combined with bioinformatics analysis method.Methods The research was carried out by two stages.In the first stage,300 cases of schizophrenia and 300 healthy controls were enrolled,and 5ml pe-ripheral venous blood was drawn to extract genome DNA.After quality control and concentration adjustment by ultraviolet spectrophotometer,equal mass of DNA was mixed into DNA pooling for case group and control group respectively.Genome-Wide Human SNP Array 6.0 chips were used to detect the polymorphism of the SNP.Plink software was used to locate the differential SNP to genes.GSEA was used to analyze the gene to pathway.Ten loci with the smallest P value of screened pathway were chosen as investigated subjects.In the second stage,240 schizophrenias and 200 healthy controls were collected to gain the genome DNA to verity the genotype of the 10 loci.Results Many single nucleotide polymorphism loci which P<9.2×10-8were found in GWAS.The GSEA pathway analysis showed that the axon guidance pathway was significantly related to the incidence of schizophrenia.The distribution of rs4632195 genotypes involved the distribution of among 10 loci(χ2=11.484,P=0.003)and alleles(χ2=8.824,P=0.009)were statistically significant,and T al-lele was susceptibility genes of schizophrenia(OR=1.537,95%CI:1.157-2.203).Conclusion rs4632195 of DCC gene in the axon guidance pathway is associated with schizophrenia,and the T allele is associated with susceptibility to schizophrenia.

Objective To investigate the association between the patients with schizophrenia and polymorphism in rs2030324 and rs11030101 of brain derived neurotrophic factor(BDNF).Methods 100 patients with schizophrenia and 100 normal controls were enrolled.The BDNF polymorphism (rs2030324 and rs11030101) and allele frequency were genotyped by sequencing the products of PCR.Genotype and allele frequencies were compared between patients and controls.Symptoms were assessed using the PANSS,and the relationship between the score of PANSS and the polymorphism of rs2030324 and rs11030101 was analyzed.Results There was statistically significance between schizophrenic patients and controls in the distribution of allele frequency in rs2030324(x2 =3.888,P=0.049) and rs11030101 (x2 =5.571,P=0.016).There was statistically significance between schizophrenic patients and controls in the distribution of implicit model in rs11030101 (x2=5.230,P=0.022).The score of PANSS negative symptoms of patients with SNPs rs11030101 different genotypes showed that A/T genotype was the highest(34.60±5.63) and T/T genotype was minimum (28.38±9.96),and the difference had statistical significance (F=4.868,P=0.010).Conclusion The polymorphism in rs2030324 and rs11030101 of BDNF is relate to the patients with schizophrenia among Han Chinese and their allele A increases the risk of illness.The SNP of rs11030101 may be associated with the clinical features of schizophrenia.

Objective:To assess the differences among the expressions of p38 mitogen activated protein kinases (MAPK),phospho-p38MAPK and nuclear factor kappa B (NF-κB)in oral lichen planus (OLP)and oral squamous cell carcinoma (OSCC ).Methods:In the study,53 cases of OLP,45 of OSCC,and 18 controls were obtained and 4-μm-thick histological sections were prepared from formalin-fixed paraffin-embedded tissue blocks.The expressions of p38MAPK,phospho-p38MAPK and NF-κB were detected by immunohistochemistry staining.Furthermore,the expressions of p38MAPK and phospho-p38MAPK were detected using Western blotting analyses in the fresh tissues from 1 1 cases of OLP,5 ca-ses of OSCC,and 7 cases of the controls.Results:p38MAPK was over-expressed in the lamina propria, but lowly expressed in the epithelium in OLP group.Phospho-p38MAPK was lower expressed in OLP group than in OSCC and control groups.NF-κB was found over-expressed in the lamina propria in OLP group.p38MAPK was found expressed in all the samples in the 3 groups.The expression of phospho-p38MAPK was observed in 8 (8/11)OLP samples,5 (5/5)OSCC samples and 4 (4/7)controls by Western blotting,but no significant differences were found within the 3 groups.Conclusion:p38MAPK can be detected in normal oral mucosa,OLP and OSCC.phospho-p38MAPK may be related to the onset and progression of OSCC.The role of p38MAPK in OLP is yet to be revealed.