Presenilin and Alzheimer's disease: calcium signaling pathway / 中华行为医学与脑科学杂志

Presenilin (PS) is the main pathogenic gene of familial Alzheimer's disease(AD). Mutations of PS gene can promote the processing of amyloid precursor protein (APP) into a toxic form of amyloid beta protein (Aβ), which plays an important role in the pathogenesis of AD.However, the current targeted therapy for Aβ has not yet produced a good effect on AD, suggesting the existence of additional pathogenic mechanisms.In recent years, the abnormal calcium homeostasis and its pathological role in AD have attracted people's attention.The calcium signaling pathway is regulated by presenilin.And the calcium regulation of PS gene mutant neurons is impaired, resulting in reduced ability to deal with oxidative stress, which leads to cell death and promotes the occurrence of AD.In addition, damage to neuronal autophagy induced by PS gene mutations also depends on the ability to partially deplete endoplasmic reticulum calcium content.Recent studies have shown that abnormal Ca 2+ homeostasis caused by PS gene mutations can lead to impaired mitochondrial metabolism and defects in brain network activity.This review will focus on the calcium signaling pathway, and explore the pathogenesis of presenilin in AD through the regulation of calcium signals from the perspectives of impaired autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, apoptosis and defects in brain network activity, so as to provide ideas for the etiology of AD and the discovery of drug targets.

Early / 中南大学学报(医学版)

Alzheimer's disease (AD) is the most common senile neurodegenerative disease characterized by progressive cognitive dysfunction, psychological and behavioral abnormalities, and impaired ability of activities of daily living. A family with a total of 3 patients were admitted to the Department of Neurology of Xiangya Hospital, Central South University in 2018. The proband showed memory decline as the presenting symptoms, and subsequently showed psychological and behavioral abnormalities, personality changes, seizures, and motor retardation. Definite diagnosis of early-onset familial AD (EOFAD) with missense mutation of presenilin 2 (PSEN2) (c.715A>G p.M239V) was established by whole exome sequencing (WES) technology. We reported the mutation in Chinese Han population for the first time, which expanded the mutation spectrum ofPSEN2 gene and aid to enrich the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Patients with early onset age and complex clinical manifestations of AD can be diagnosed with the help of genetic testing to avoid misdiagnosis.

Primary study on the mechanism of ductus arteriosus closure in rats: impact of aging pathway / 中华心血管病杂志

Objective: To explore the role and mechanism of aging pathway in patent ductus arteriosus closure of rats. Methods: Thirty outbreeding Sprague Dawley rats(20 females, 10-15 weeks old, 270-330 g) underwent random mating and conception. The primary Ductus Arteriosus smooth muscle cells (DASMCs) of pregnant 19 days(E19 group), 21 days(E21 group) and newborn(Day0 group) fetus were extracted and cultured. mRNA expression of cell senescence related markers p16, 21 and 53 genes in each group were detected by real-time fluorescent quantitative PCR(RT-PCR) after 48 hours culture. After hypoxic culture on DASMCs for 3 days, the DASMCs were divided into 3 groups: hypoxic control group(G0 group), 3 hours normal oxygen concentration treatment group(G3 group) and 6 hours normal oxygen concentration treatment group(G6 group). After intervention, mRNA expression of p16, 21 and 53 RT-PCR was detected. The DASMCs of newborn rats(Day0 group) were extracted and divided into 3 groups:low-oxygen culture control group, low-oxygen+siRNA culture group and normal oxygen concentration culture group. The DASMCs migration ability was tested experimentally by Transwell method. Result: The mRNA levels of p16, 21 and 53 in DASMCs were higher in E19 group than in Day0 group(all P<0.01), and the mRNA levels of p16, 21 and 53 in DASMCs were also higher in E21 group than those in Day0 group (all P<0.01). The mRNA levels of p16, 21 and 53 in DASMC were all higher in G0 group than those in G3 group (P<0.05 or 0.01), and the mRNA levels of p16, 21 and 53 in DASMCs were all higher in G0 group than those in G6 group (all P<0.01), and the mRNA levels of p16, 21 and 53 in DASMCs were all higher in G3 group than those in G6 group (all P<0.05). DASMCs migration ability of newborn rats was higher in normal oxygen concentration culture group than that in low-oxygen culture group (P<0.01), and DASMCs migration ability of newborn rats was also higher in low-oxygen+siRNA culture group than that in low-oxygen culture group (P<0.01). Conclusion: The expression of senescence marker of DASMCs decreases with the birth in rats during the process of ductal closure, and the aging pathway may affect ductal closure by inhibiting DASMCs migration in rats.

Relationship between fabella and posterolateral knee pain and common peroneal nerve injury / 中国骨伤

OBJECTIVE@#To analyze the incidence and characteristics of fabella in the Chinese population and its correlation with pain in the posterolateral region of the knee joint and common peroneal nerve palsy.@*METHODS@#Total 732 patients including 405 males(450 knees) and 327 females(383 knees) who underwent unilateral or bilateral knee MR imaging from September 2015 to July 2019 were retrospectively evaluated. The basic information of all patients was extracted from the hospital's his system. The patient's medical records were checked by telephone follow-up or his system, and the number of patients with posterolateral knee pain and common peroneal nerve paralysis were recorded.@*RESULTS@#The overall prevalence of fabella was 48.38%, 23.53% in men and 24.85% in women, there was no significant difference between them (@*CONCLUSION@#The prevalence of fabella us in Chinese population is 48.38%. There is no relationship between the incidence of gastrocnemius and gender, but the incidence of fabella is positively correlated with age, pain in the posterolateral region of the knee joint and the occurrence of common peroneal nerve symptoms.

Effects of protein kinase C and motigen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway on mRNA level of inducible nitric oxide synthase in Tca8113 cells / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To explore the regulatory mechanism of inducible nitric oxide synthase (NOS-2) expression related to proliferation of Tca8113 cells.</p><p><b>METHODS</b>RNAi mediated by short hairpin RNAs was utilized to knock down NOS-2, protein kinase C (PKC)-α, PKC-β and PKC-δ. Griess Reagent played a significant role on the detection of NO product after NOS-2 silence. The cell proliferation was determined by CCK8 method. Quantitative real-time polymerase chain reaction (q-PCR) was recruited to check the mRNA level of NOS-2, PKC-α, PKC-β and PKC-δ after treated by a variety of ways. Eventually, the measure of phosphorylation of extracellular regulated protein kinases (ERK)1/2 was performed by Western blotting in PMA-treated Tca8113 cells.</p><p><b>RESULTS</b>The cell viability of Tca8113 decreased obviously after transfected with NOS-2 siRNA (P<0.01). PKC reduced the expression level of NOS-2 mRNA (P<0.05). PKC-α, PKC-β and PKC-δ worked together to regulate the level of NOS-2 mRNA (P<0.01). Motigen-activated protein kinase kinase (MEK)/ERK signaling pathway regulated the level of NOS-2 mRNA negatively (P<0.05). PKC down regulated the level of NOS-2 mRNA through MEK/ERK signaling pathway (P<0.05).</p><p><b>CONCLUSIONS</b>PKC regulates the mRNA level of NOS-2 related to proliferation through MEK/ERK signaling pathway in Tca8113 cells.</p>

Benefit of post-circumcision application of skin wound induction gel in the treatment of phimosis in children / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effects of skin wound induction gel on the glans scabbing rate, class-A wound healing rate, and wound healing time of circumcision for phimosis in pediatric patients.</p><p><b>METHODS</b>We randomly assigned 48 six to thirteen years old children with phimosis to an experimental group (n = 25) and a control group (n = 23) to be treated by circumcision. After surgery, the patients in the experimental group received application of skin wound induction gel while those in the control group received that of povidone iodine only to the glans and incision. We recorded and compared the glans scabbing rate, class-A wound healing rate, and wound healing time between the two groups of patients.</p><p><b>RESULTS</b>Glans scabbing was observed in 3 cases in the experimental group and 17 cases in the control group (12.0% vs 73.9%, P < 0.01). No statistically significant differences were found in the rate of class-A wound healing between the two groups (100% vs 91.3%, P > 0.05). The wound healing time was significantly shorter in the experimental than in the control group ([10.7 ± 1.7] d vs [11.9 ± 2.1] d, P < 0.05).</p><p><b>CONCLUSION</b>Post-circumcision application of skin wound induction gel to the glans and incision can effectively reduce glans secreta, alleviate inflammatory reaction, and shorten the healing time in the treatment of phimosis in children.</p>

Comparative study of sleep quality in ketamine dependent subjects and methamphetamine dependent subjects / 中华行为医学与脑科学杂志

Objective To explore the difference of sleep quality and the influencing factors in ketamine dependent subjects and methamphetamine dependent subjects.Methods 60 ketamine dependent subjects and 60 methamphetamine dependent subjects with Pittsburgh sleep quality index (PSQI),self-rating depression scale (SDS),self-rating anxiety scale (SAS) were tested.Results Methamphetamine dependent subjects was significantly more likely to elicit poor sleep quality than ketamine dependent subjects (P =0.022).The sleep quality of ketamine dependent subjects had a positive correlation with anxiety(P =0.015),depression(P =0.038),the onset age (P =0.029),and the dose of ketamine use in the last three months (P =0.048),while the sleep quality of methamphetamine dependent subjects had a positive correlation with the total time of ketamine use (P =0.038),anxiety (P =0.041),the dose of ketamine use in the last three months (P =0.011).Conclusion Methamphetamine dependent subjects are prone to a more serious poor sleep quality than ketamine dependent subjects.

The effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells.</p><p><b>METHODS</b>RAW2647 mice mononuclear macrophage leukemia cells were observed. The tested group was interfered by Tlr4-mus-1567 RNA which had the best result confirmed by QPCR, cells interfered by Negative Control RNA as NC group, and normal cell as control. We perform the phagocytosis test on each group.</p><p><b>RESULTS</b>The tested group has lower phagocytes percentage than control (17.67% +/- 3.51% vs 32.00% +/- 3.00%, P < 0.01), and lower phagocytic index (46.33% +/- 7.51% vs 82.00% +/- 6.08%, P < 0.01).</p><p><b>CONCLUSIONS</b>Decreased phagocytic activity was observed on Kupffer cells by RNA interference.</p>

Activation of Kupffer cell and related signal pathway proteins in the liver of high fat and high fructose diet induced NAFLD mice / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the expression of F4/80, NF-kappaB, p-AKT, AKT in the liver of nonalcoholic fatty liver disease (NAFLD) mice. To determine the role of Kupffer cells (KCs) in the development of NASH (non-alcoholic steatohepatitis), and understand the pathogenic mechanism of NASH.</p><p><b>METHODS</b>Five C3H/HeN mice fed with normal diet were served as controls, while fifteen fed with high fat, high fructose, high fat combined fructose diet respectively for 16 weeks were as NAFLD mice models. The liver inflammation and hepatic damage were examined, and the expression of F4/80, NF-Kb, p-AKT, AKT and the content of lipid in the liver were also detected.</p><p><b>RESULTS</b>Chronic intake of high fat and 30% fructose solution caused a significant increase in hepatic steatosis in animals in comparison to water controls. Liver F4/80 and NF-kappaB were significantly higher in high fat and high fat combined fructose diet fed mice than that in controls (P < 0.01, P < 0.01), F4/80 protein were higher in high fat diet treated mice than those in fructose and high fat combined fructose groups (P < 0.01, P < 0.01). Markers of insulin resistance (e. g, hepatic phospho-AKT, AKT) were only altered in fructose-fed or high fat combined fructose animals (P < 0.01, P < 0.01).</p><p><b>CONCLUSION</b>High fat and fructose diet may induce NAFLD in C3H/HeN mice. Kupffer cells and signal pathway proteins were activated, and they may play key roles in the initiation and progression of NASH.</p>

Hearing loss may be associated with the novel mitochondrial tRNA(Asp) A7551G mutation in a Chinese family / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>We reported here the clinical and genetic evaluations as well as mutational analysis of mitochondrial DNA(mtDNA) in a Chinese family with maternally transmitted non-syndromic hearing loss and investigated the influence of the mitochondrial tRNA(Asp) A7551G mutation to the phenotypic manifestation of the deafness.</p><p><b>METHODS</b>One Chinese Han pedigrees of maternally transmitted nonsyndromic hearing loss were collected. The proband and family members underwent clinical, genetic, and molecular evaluations, such as audiological examinations, mutational analysis of mitochondrial genome and mutational analysis of GJB2 gene.</p><p><b>RESULTS</b>Six people of this pedigree suffered from hearing loss, including four matrilineal members, and others did not have significant clinical abnormalities. Sequence analysis of the complete mitochondrial genome in the proband showed that there were 28 mtDNA polymorphisms belonging to East -Asian haplogroup A4.In addition to the A7551G homogeneity mutation, there were no other functionally significant variants found in this family. The A7551G mutation located immediately at the three prime end to the anticodon, corresponding with the conventional position 37 of tRNA(Asp), and its' CI value was 100% compared with other 15 primate species. The A7551G mutation was absent in other Chinese controls. The mutations on GJB2 were detected by direct sequence analysis,GJB2 235delC and 299delAT which was associated with hearing loss were found in the genomic DNA of the proband and some matrilineal members. Clinical evaluation showed a variable phenotype of severity, age-at-onset and audiometric configuration of hearing loss in the matrilineal relatives in these families.</p><p><b>CONCLUSIONS</b>The A7551G mutation may modify the secondary structure of the tRNA, and affect the stabilization of tRNA(Asp), produce non-normal functional tRNA(Asp) ultimately. And it may cause the phenotypic manifestation of the deafness that associated with A7551G mutation. Therefore, the mitochondrial tRNA(Asp) A7551G mutation may be a new mitochondrial mutation for hearing loss.</p>

Analysis of genotype-phenotype correlation for GJB2 in 221 non-syndromic deafness probands and their pedigrees / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To assess the possible genotype-phenotype correlation for GJB2.</p><p><b>METHODS</b>Retrospectively analyzed GJB2 gene mutations with non-syndromic hearing impairment (NSHI) patients and their families audiological data. Individuals were grouped, according to non-truncated mutant (non-truncating, NT) and truncating mutations (truncating, T), into T/T group, T/NT group and NT/NT group. And according to whether they carry 235delC, grouped into 235delC/235delC group, 235delC/Non-235del group and Non-235delC/Non-235delC group.</p><p><b>RESULTS</b>Grouped according to whether the truncation mutants:Fisher exact statistical analysis showed that the degree of hearing loss among the three groups did not meet the random distribution (P = 0.003) , T/T group was significantly higher than T/NT group (P = 0.000) and NT/NT group (P = 0.000) on the degree of hearing loss. Grouped according to whether they carry 235delC mutation: degrees of hearing loss among the three groups were statistically significant differences. Respectively pairwise comparisons (Fisher exact test) found 235delC/235delC group was significantly higher than 235delC/Non-235delC on the degree of hearing loss group (P = 0.001) and Non-235delC/Non-235delC group (P = 0.000), 235delC/Non-235delC group higher than Non-235delC/Non-235delC group (P = 0.033). In GJB2 mutations homozygous and compound heterozygous mutation genotype:G109A/G109A, 235delC/512insAACG, 299delAT/G109A and 235delC/G109A degree of hearing loss caused by genotype was significantly lower than 235delC/235delC group.</p><p><b>CONCLUSIONS</b>235delC homozygotes have significantly more hearing impairment, when compared with 235delC/non-235delC compound heterozygotes. People with two non-235delC mutations have even less hearing impairment. Patients with non-truncation mutants (G109A) suffer from lighter hearing loss than truncation mutations(235delC, 299delAT).</p>

Molecular mechanisms underlying function of hair bundle: study on genetic deafness in mouse models / 生理学报

Although the basic principles for the function of peripheral auditory system have been known for many years, the molecular mechanisms which affect deafness are not clear. In recent years, the study of hereditary deafness associated mouse models has revealed the molecular basis which is related with the formation and function of the hair bundle and the mechanosensory organelle of hair cell. This review focused on the role of protein network, which is formed by the proteins encoded by the Usher syndrome type 1 genes, in hair-bundle development and mechanotransducer channel gating. And the review also showed how the stereocilia rootlets contribute to the hair bundle's mechanical properties and how the hair bundle produces suppressive masking. Finally, the review revealed multiple roles of the tectorial membrane and extracellular matrix in the hair bundles stimulating in the cochlea.

Comparative effects of Roux-en-Y gastric bypass procedures preserving different gastric volume on blood glucose in Goto-Kakizaki rats / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the effects of Roux-en-Y gastric bypass (RYGBP)procedures preserving different gastric volume on blood glucose of rats with non-obese type 2 diabetes.</p><p><b>METHODS</b>A total of 36 Goto-Kakizaki rats randomly underwent one of the following procedures: gastric bypass with different types of anastomosis including the Roux-en-Y of total stomach excision(n=12), the Roux-en-Y of partial stomach excision(n=12) and the Roux-en-Y of stomach preservation(n=12). Rats were observed for 24 weeks after surgery. Body weight, food intake and fasting blood glucose level were tested at 0(preoperative), 1, 3, 6, 12, 24 weeks. Hemoglobin A1c(HbA1c) level was measured at 0, 12, 24 weeks and glucose tolerance test (OGTT) was performed in conscious rats before (baseline) and then 30, 60, 120, and 180 minutes. Change of blood glucose over time was depicted. Area under curve(AUC) of glucose tolerance were calculated.</p><p><b>RESULTS</b>Compared with preoperative levels, the weight and food intake of all the rats were significantly decreased at 1 week after surgery(P<0.01). At 3 weeks after operation, the weight and food intake were significantly increased compared with 1 week after operation in the Roux-en-Y of partial stomach excision and the Roux-en-Y of stomach retention(P<0.01). In the Roux-en-Y of total stomach excision, the weight and food intake were significantly lower compared with other two groups(P<0.05). At 24 weeks after operation, the levels of fasting blood glucose were (7.3 ± 1.5), (7.5 ± 2.0) and (8.3 ± 1.3) mmol/L, which were lower than the preoperative levels [(13.2 ± 1.6), (13.6 ± 2.5) and (12.9 ± 2.0) mmol/L, P<0.01] in the three groups. There were no significant differences among the three groups(P>0.05). At 24 weeks after operation, the HbA1c levels were(6.3 ± 1.3)%, (6.4 ± 2.0)% and (7.0 ± 1.3)%, which were lower than the preoperative level[(10.2 ± 2.6)%, (9.6 ± 2.5) and (9.9 ± 2.0)%, P<0.01]. There were no significant differences among the three groups(P>0.05). The trend of the glucose tolerance test and AUC were similar in the three groups after operation.</p><p><b>CONCLUSION</b>Roux-en-Y gastric bypass in non-obese diabetic rats is effective in terms of glucose control and the efficacy of gastric bypass has no obvious association with the stomach volume.</p>

Characterization of two Chinese families with aminoglycoside-induced and nonsyndromic hearing loss both carrying a mitochondrial 12S rRNA 1494C>T mutation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of mitochondrial DNA(mtDNA) secondary mutations, haplotypes, GJB2 gene mutations on phenotype of 1494C>T mutation, and to study the molecular pathogenic mechanism of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.</p><p><b>METHODS</b>Two Chinese Han pedigrees of maternally transmitted aminoglycoside induced and nonsyndromic hearing loss were collected. The two probands and their family members underwent clinical, genetic and molecular evaluations including audiological examinations and mutational analysis of mitochondrial genome and GJB2 gene.</p><p><b>RESULTS</b>Clinical evaluation revealed wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in both families, for which the penetrance of hearing loss was respectively 42.9% and 28.6% when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss were 14.3% and 14.3%. Sequence analysis of mitochondrial genomes identified a known 12S rRNA 1494C>T mutation, in addition with distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroups C4a1a and B4b1c, respectively.</p><p><b>CONCLUSION</b>Mitochondrial 12S rRNA 1494C>T mutation probably underlie the deafness in both families. Lack of significant mutation in the GJB2 gene ruled out involvement of GJB2 in the phenotypic expression. However, aminoglycosides and other nuclear modifier genes may still modify the phenotype of the 1494C>T mutation in these families. The B4b1c is a newly identified haplogroup in aminoglycoside-induced and nonsyndromic hearing loss family carrying the 1494C>T mutation. The 1494C>T mutation seems to have occurred sporadically through evolution.</p>

Mitochondrial 12S rRNA variants studies in 456 subjects with hearing loss in seven schools for deaf and mutes in Zhejiang province / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate mutational spectrum and frequency of the mitochondrial 12S rRNA gene in Chinese subjects with aminoglycoside-induced and non-syndromic hearing loss.</p><p><b>METHODS</b>Total of 456 subjects with non-syndromic hearing loss were recruited from seven schools for deaf-mutes in Zhejiang province. Genomic DNA was extracted from the whole blood, and then the DNA fragment was amplified spanning the 12S rRNA gene, followed by sequencing and analyzed.</p><p><b>RESULTS</b>Thirty-one variants were identified by mutation analysis of 12S rRNA gene in these subjects. The frequency of the known 1555A > G mutation was 4.4% (20/456). Prevalence of other putative deafness-associated mutation at positions 961 and 1095 were 2.0% (9/456) and 0.7% (3/456) respectively. Furthermore, the 1027A > G, 1109T > C and 1431G > A variants conferred increased sensitivity to ototoxic drugs or non-syndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this 12S rRNA gene. Moreover, clinical data showed a wide range of age-of-onset, variety of severity and various audiometric configurations in subjects carrying the 1555A > G mutation.</p><p><b>CONCLUSIONS</b>Our data demonstrated that the mitochondrial 12S rRNA gene is the hot spot for mutations associated with aminoglycoside ototoxicity and non-syndromic hearing loss. Nuclear modifier genes, mitochondrial haplotypes and environmental factors might play a role in the phenotypic manifestation of these mutations.</p>

Cosmetic efficacy of topical 5-aminolaevulinic acid-photodynamic therapy on cephalic and facial skin tumors / 中华医学美学美容杂志

Objective To investigate and summarize the clinieal effects and cosmetic results of 5-aminolaevulinic acid-photodynamic therapy (ALA-PDT) on cephalic and facial skin tumors.Methods Patientswith skin basal eell carcinoma(BCC),squamous cell carcinoma (SCC),keratosis seborrheica (KS),and solar keratosis (SK) were included in this study.Inoperable cases were given topical ALAPDT,and received clinical response evaluation and satisfying questionnaire after 3 months follow-up.Resalts28 patients including 16 BCCs,8 SCCs,2 KSs and 2 SKs received ALA-PDT.100% BCC had responseto PDT,including 15 cases with complete response (CR);only one recurred.Overall response rate was 67% for SCC,2 of 8 cases failed to continue the treatment,3 eases CR,1 case partial response (PR) and 1 patient with no response.Response rate was 0% in KS.100% of SK had response to PDT,and 2 cases showed CR and PR,respectively.64.2% patients (18/28) showed extreme satisfaction for cosmetic outcome,11% (3 cases) satisfaction,7.1% (2 cases) little satisfaction,and 10.7% (3 cases) no satisfaction.Conclusion Topical ALA-PDT is an effective and satisfied treatment with lower recurrent rates, especially for cephalic and facial skin tumors including BCC,SCC and SK,but no response for KS.

Effect of diabetes control after small intestine exclusion surgery in Goto-Kakizaki rat with non-obese type 2 diabetes mellitus / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect and possible mechanisms of diabetes control after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with non-obese type 2 diabetes mellitus.</p><p><b>METHODS</b>Forty GK rats with non-obese type 2 diabetes mellitus underwent duodenal bypass (Group A, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum alone; duodenal-jejunal bypass (Group B, n = 8), a stomach-preserving RYGB that excludes the duodenum and proximal jejunum; duodenum and total jejunum exclusion (Group C, n = 8); sub-total small intestine exclusion (Group D, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum, jejunum and sub-total ileum; controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO, n = 8). The rats were observed for 24 weeks after surgery. Body weight, food intake and fasting blood glucose level were tested at 0, 1, 3, 6, 12, 24 weeks after the operation in those groups. The concentrations of insulin and glucagon-like peptide-1 (GLP-1) concentrations were measured before (baseline) and then 30, 60, 120, and 180 minutes after OGTT at 0, 12, 24 weeks after the operation.</p><p><b>RESULTS</b>Mean operating time of all groups was similar. The mean body weight and food intake decreased significantly at 1 week after surgery (P < 0.01) and with no differences among the groups. Fasting blood glucose level decreased significantly after surgery in all the operation groups through the entire follow-up period (P < 0.05). No significant changes in fasting blood glucose level in SO group was found in 12 weeks after the operation, and it increased at 12 and 24 weeks after. Fasting blood glucose levels in group B decreased significantly compared with group A (P < 0.05), but no difference was found among group B, C and D (P > 0.05). Oral glucose-stimulated peak (30 min) levels of blood insulin and GLP-1 increased markedly in operation groups (A, B, C and D) after surgery (P < 0.01). Compared with group A, peak levels of blood insulin and GLP-1 in group B were strikingly higher (P < 0.05), but no difference was found when compared with group C or D (P > 0.05).</p><p><b>CONCLUSIONS</b>In spontaneously non-obese type 2 diabetes mellitus rats, small intestinal exclusion including proximal gut is effective in terms of glucose control and has no direct relation with body weight and food intake loss. Restoration of the first-phase insulin secretion and high secretion of GLP-1 in type 2 diabetic subjects after gastrointestinal bypass surgery seem to be helpful to diabetes control. Taking intestinal nutrient absorption into consideration, duodenal-jejunal bypass may be a better surgery for diabetes control.</p>

Effects of Ginkgo biloba extract on expressions of IL-1beta, TNF-alpha, and IL-10 in U937 foam cells / 药学学报

This study is to investigate the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in U937 foam cells and effects of Ginkgo biloba extract (GbE) on the cytokines. U937 cells were cultured with different concentrations of GbE (0.1, 1, and 10 microg x L(-1)), and stimulated by 100 mg x L(-1) oxidized low density lipoprotein (ox-LDL) for 24 h. The expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in culture solution were detected by enzyme-linked immunosorbant assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that incubated with 100 mg x L(-1) ox-LDL for 24 h, the U937 cells became foam cells, the protein or mRNA expressions of IL-1beta, TNF-alpha, IL-10, and its receptor IL-10R in U937 foam cells were higher markedly than those in normal U937 cells. When the cells were pretreated with GbE (0.1, 1, and 10 microg x L(-1)), the increases of IL-1beta and TNF-alpha in U937 foam cells were remarkably inhibited, but IL-10 expression increased greatly. Especially when cells were pretreated with 10 microg x L(-1) GbE, the protein and mRNA expressions of IL-1beta and TNF-alpha were markedly lower than those in U937 foam cells. The protein expression of IL-10 and mRNA expressions of IL-10 and its receptor IL-10R were markedly higher than those in U937 foam cells. GbE inhibited production of pro-inflammatory cytokines IL-1beta and TNF-alpha, but up-regulated the production of anti-inflammatory cytokine IL-10 and its receptor IL-10R in U937 foam cells, which might be related with its anti-atherosclerotic actions.