Objective To explore the shared potential targets and molecular mechanisms of obesity and type 2 diabetes mellitus(T2DM)using bioinformatics methods,to validate the expression of core targets through animal experiments,and to analyze the intervention potential of active components of traditional Chinese medicine(TCM).Methods The obese population datasets(GSE151839 and GSE162653)were obtained from the Gene Expression Omnibus(GEO)database to screen for differentially expressed genes,which were then intersected with T2DM-related targets from the GeneCards database to identify shared targets.A protein-protein interaction(PPI)network was constructed using the STRING database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed to identify enriched biological processes and signaling pathways.The expression of core targets in adipose tissue from patients with obesity and T2DM was validated using the GEO database.A total of 12 specific-pathogen-free(SPF)male Sprague-Dawley(SD)rats,aged 8 weeks and weighing between 180 and 200 g,were randomly assigned to a control group and a model group(n=6 each).A T2DM rat model was established,and the mRNA and protein expression levels of core targets in adipose tissue were measured.Molecular docking and molecular dynamics simulations were performed to assess the binding ability of TCM active components to core targets.Results A total of 460 and 796 obesity-related differentially expressed genes were identified in the GSE151839 and GSE162653 datasets,respectively,and 109 shared targets were obtained by intersection with T2DM-related targets.According to PPI network analysis,PTPRC,MMP9,ITGB2,CD86,CCR5,and CCR2 were identified as the core targets.GO and KEGG analysis showed that these targets are mainly enriched in biological processes such as inflammatory response,immune regulation,and cell adhesion.Animal experiments confirmed that the mRNA and protein expression of core targets,including PTPRC,ITGAX,MMP9,ITGB2,CCR2,and CXCL1,were significantly upregulated in the adipose tissue of T2DM rats(P<0.05).Molecular docking and molecular dynamics simulations revealed that berberine and puerarin had good binding ability with PTPRC,MMP9,and ITGB2.Conclusion This study reveals the shared molecular mechanisms between obesity and T2DM and shows that core targets,such as PTPRC and MMP9,may promote disease progression by regulating the inflammation-immune network.These findings provide a theoretical basis for the development of targeted therapeutic strategies based on TCM active ingredients.

Mitochondria are the main site of energy metabolism in cardiomyocytes， and at the same time mediate apoptosis and immune response， so mitochondrial dysfunction is closely related to the development of heart failure. Combined with the pathogenesis of mitochondrial dysfunction and heart failure， it is proposed that the mitochondrial function is similar to "sweat pore - collaterals - zang and fu organs"， according to which the treatment of heart failure is based on the theory of "sweat pore - collaterals - zang and fu organs". It is believed that the core mechanism of heart failure is qi deficiency， and qi deficiency leads to the weakness of the sweat pore opening and closing， or even the sweat pore closure， then resulting in qi deficiency and blood stasis， collaterals stagnation fail to flourish， and qi， blood， and body fluids can not infiltrate and nourish zang-fu organs， so that the heart fail to be nourished， and the disease will develop. The treatment should be based on the method of boosting qi and opening sweat pore， using acridity to unblock the collaterals， and invigorating blood and draining water， with medicinal of boosting qi， invigorating blood， and draining water as treatment.

Objective To investigate the correlation between serum homocysteine(Hcy)and severity of acute ischemic stroke(AIS).Methods The clinical data of patients with AIS were collected retrospectively. The National Institutes of Health Stroke Scale (NIHSS) scores were used to evaluate the severity of stroke. The NIHSS score≤8 was defined as mild stroke and >8 was defined as moderate to severe stroke. The baseline clinical data and blood test indices between the 2 groups were compared. Multivariable logistic regression analysis was used to identify the independent factors of severity in patients with AIS. Results A total of 73 patients with AIS were enrolled,including 42 males(57.5％).Their age ranged from 18 to 77 years. There were 39 patients (53.4％) in the mild stroke group and 34 (46.6％) in the moderate to severe stroke group.Univariate analysis showed that Hcy and high-density lipoprotein cholesterol level and the proportions of patients with hypertension and hyperhomocysteinemia in the moderate to severe stroke group were significantly higher than those in the mild stroke group(all P<0.05). Multivariate logistic regression analysis showed that hypertension(odds ratio[OR]5.529, 95％ confidence interval[CI]2.730-11.196; P<0.001) and Hcy (OR 1.682,95％ CI 1.114-2.538;P=0.013)were the independent influencing factors of the severity of stroke in patients with AIS. Conclusion The serum Hcy level in patients with AIS was closely associated with the severity of stroke.

OBJECTIVES: To investigate the otoprotective effects of mouse nerve growth factor (mNGF) in A/J mice. METHODS: The mice at postnatal day 7 (P7) were randomly separated into a mNGF treated group (mNGF group) and a distilled water (for injection) treated group (control group). The mNGF dissolved in distilled water or distilled water alone was given to the mice once every other day from P7 by intramuscular injection in the hips. The otoprotective effects of mNGF in A/J mice were observed in a time course manner. The thresholds of auditory-evoked brainstem response (ABR) were tested from the age of the 3rd to the 8th week. Sections of the inner ears were stained by hematoxylin and eosin, and spiral ganglion neurons (SGNs) were observed at the age of the 3rd, the 6th,and the 8th week. Counts of whole mount outer hair cells (OHCs) in the cochleae were made at the age of 8 weeks. Expression of apoptosis related genes was determined by quantitative real-time polymerase chain reaction and Western blotting. RESULTS: ABR thresholds of the mNGF group were significantly lower than those of the control group at the age of the 6th and the 8th week. Moreover, the mNGF preserved OHC and SGN in the mouse cochleae in this period. Further experiments showed that the expression of caspase genes (including caspase-3) was inhibited in the mouse inner ears in the mNGF group. CONCLUSION: The mNGF improves hearing in A/J mice by preserving SGN and OHC in the cochleae.
Animals ; Apoptosis ; Blotting, Western ; Brain Stem ; Cochlea ; Ear, Inner ; Eosine Yellowish-(YS) ; Hair Cells, Auditory, Outer ; Hearing* ; Hematoxylin ; Hip ; Injections, Intramuscular ; Mice* ; Nerve Growth Factor* ; Neurons ; Real-Time Polymerase Chain Reaction ; Spiral Ganglion ; Water

Objective To study the impact of tumor necrosis factor-α (TNF-α) and its antagonist on the expressions of intestinal mucosa claudin-1,Zonula Occludens-1 (ZO-1) and myosin light chain kinase (MLCK) in rat models of acute liver failure.Methods Fifty four healthy male SpragueDawley (SD) rats were randomly divided into normal control group,model group and intervention group according to a random number table.Rats in normal control (n=6) group were intraperitoneally injected with 0.9％ saline (12 mL/kg).Rats in model group (n=24) and intervention group (n=24) were intraperitoneally injected with a full dose of D-galactosamine (D-GalN) at a dose of 1 200 mg/kg to establish model of acute liver failure,while rats in intervention group were intraperitoneally injected with TNF-α antagonists (rhTNFR∶Fc) at a dose of 12.5 mg/kg before 24 hours given D-GalN.At each time point of hour 8,24,48 and 72,six rats in both model group and the intervention group were sacrificed,respectively,while the normal control group were all anesthetized and sacrificed at 72 h.Models were repeated five times.Serum liver function was detected by biochemical method,and serum TNF-α level was detected by enzyme-linked immunosorbent assay (ELISA).Hematoxylin-eosin (HE) stained sections of liver and terminal ileum were examined under an optical microscope for pathological changes;and protein expression of the terminal ileum Claudin-1,ZO-1 protein and MLCK were determined by immunohistochemistry and Western blot.Means among groups were compared with t test.Results Acute liver failure was successfully induced in the D-GalN injected rats.In the model group,alanine aminotransferase (ALT) began to decline,total bilirubin continued to rise,and enzyme-jaundice separation developed at hour 72.But total bilirubin in intervention group at hour 72 was decreased.Light microscope showed that at hour 72,villus lodged at terminal ileum in the model group with part of villus tip failing off in the model group.Villus mucosa and submucosa interstitial were edema and infiltrated with numerous neutrophils.The terminal ileum kept integrate in the intervention group,and villus mucosa and submucosa were mild edema and only infiltrated with a small amount of neutrophil.Expressions of tumor necrosis necrosis factor (TNF)-α in rats of model group and intervention group were gradually increased and peaked at hour 24 ([239.83 ± 15.81] and [182.71± 17.08] ng/L,respectively),which were significantly higher than that of the control group ([24.19±3.57] ng/L,t=22.68and 15.73,respectively;both P＜0.01).Expression of serumTNF-α in the intervention group was significantly lower than that of model group (t=4.58,P＜0.01).Expressions of Claudin-1 and ZO-1 in model group decreased gradually at an early stage and reached the lowest level at hour 24 (0.355 ± 0.068 and 0.387 ± 0.091,respectively),which were both significantly lower than that of control group (1.640±0.188 and 1.015±0.150,respectively;t=12.87 and 7.14,respectively;both P＜0.01).In the intervention group,expressions of Claudin-1 and ZO-1 also decreased to the lowest level at hour 24 (1.051 ± 0.370 and 0.642 ± 0.082,respectivley),which were both significantly lower than that of control group (t =2.84 and 4.36,respectively;both P＜0.05),but significantly higher than model group with stastically difference (t =3.70 and 4.15,respectively;both P＜0.01).MLCK protein levels in the model and intervention group were gradually increased,which peaked at hour 24 (1.298±0.194 and 1.033 ± 0.073,respectively),significantly higher than the control group (0.460±0.069,t=8.16 and 11.44,both P＜0.01);and MLCK in the intervention group was lower than that in the model group with statistically difference (t=2.56,P＜0.05).Conclusions Expression of serum TNF-α in rat model of acute liver failure increases,which leads to decreased expression of Claudin-1 and ZO-1,and increased expression of MLCK,makes cell shrunk and cell gap increased.TNF-α antagonist could significantly reduce the inflammation and liver cell apoptosis,improve liver function by inhibiting MLCK expression and preventing decrease of Claudin-1 and ZO-1 proteins.

Objective To explore the effect of preoperative neutrophil lymphocyte ratio (NLR) on the prognosis of patients with laryngeal carcinoma.Methods Clinical data of 202 patients with laryngeal carcinoma treated from January 2004 to October 2009 were retrospective analyzed to determine the optimal critical value of NLR.To study whether NLR is an independent factor affecting the recurrence and 5-year survival rate of patients with laryngeal cancer after surgery,single factor and multivariate analyses were performed.The factors included age,gender,T stage,pathological differentiation,lymph node metastasis,primary tumor site and NLR value.The relationship between NLR and cervical lymph node metastasis was analyzed.Results The optimal critical value of NLR was 2.85,by which cases were divided into high NLR group (NLR≥2.85) and low NLR group (NLR ＜ 2.85).Single factor and multivariate analyses indicated that T staging,lymph node metastasis,primary tumor location,and NLR were the independent factors affecting the recurrence of laryngeal carcinoma.T stage and lymph node metastasis were the independent factors affecting 5-year survival rate of laryngeal carcinoma.The increase of NLR value increased the rate of cervical lymph node metastasis.Conclusion Preoperative NLR level influences the recurrence and cervical lymph node metastasis of laryngeal carcinoma and can be considered a prognosis factor of laryngeal cancer.

Objective To explore the prevalence and influencing factors of obstructive sleep apnoea syndrome(OSAS)among hypertensive patients. Methods Two hundred and ninety-eight hypertensive patients who used a portable OSAS monitoring device were selected as our subjects. Of which,197 patients who completed their OSAS monitoring were divided into OSAS group( 165 cases) and non-OSAS group. Stepwise linear regression and Logistic regression analysis were used to analyze the relevant factors correlated to AHI and OSAS with hypertension. Results The average age of the 197 patients(122 were males)were 59. 93 ± 10. 18 years old. The prevalence of OSAS was 83. 8% in hypertension patients. Body mass index( BMI),systolic pressure (SBP),diastolic pressure(DBP),low density lipoprotein cholesterol(LDL-C)and waist circumference in OSAS groups were(26. 37 ± 2. 77)kg/ m2 ,(159. 59 ± 14. 42)mmHg,(98. 71 ± 9. 40)mmHg,(2. 85 ± 0. 82)mmol/L,(90. 56 ± 8. 62)cm,higher than those in non-OSAS group((22. 43 ± 2. 04)kg/ m2 ,(146. 83 ± 4. 60) mmHg,(85. 51 ± 7. 52)mmHg,(2. 22 ± 0. 60)mmol/ l. ,(81. 84 ± 8. 00)cm). There were statistical differences between the two groups(t = - 7. 654,- 4. 945,- 7. 490,- 4. 110 and - 5. 289;P < 0. 001). BMI,SBP and DBP were positively associated with AHI,and they were in depended risk factors of OSAS(OR(95% CI)=2. 554(1. 408 - 4. 632),1. 432(1. 154 - 1. 777),1. 286(1. 058 - 1. 562);P < 0. 05). Conclusion The prevalence of OSAS is high in hypertension patients. Higher BMI,SBP,DBP are associated with OSAS in hypertension pateints.

Objective To investigate the invasive aspergillosis (IA) status in a surgical intensive care unit (SICU).Methods The clinical data including general state,operation,pathogenic microorganisms,infection position,clinical situation,treatment and prognosis of patients with IA admitted to the SICU of Peking University First Hospital from January 2004 to December 2013 were retrospectively analyzed.Results 8 220 patients admitted to the SICU of Peking University First Hospital from January 2004 to December 2013 were enrolled.Of 8 220 patients,there were 29 cases experienced IA,with an incidence of 0.35％,and the incidence of hospital onset of IA infection was 0.27％ (22/8 220).The incidence of hospital onset of IA infection was accounted for 6.98％ (22/315) of the incidence of hospital onset of infection in SICU in the same period.Compared with 2004-2008,in 2009-2013,the incidence of hospital onset of infection was significantly decreased [3.19％ (137/4 293) vs.4.53％ (178/3 927),x2=10.020,P=0.002],while the incidence of IA [0.56％ (24/4 293) vs.0.13％ (5/3 927),x2=10.874,P=0.001],the incidence of hospital onset of IA infection [0.40％ (17/4 293) vs.0.13％ (5/3 927),x2=5.556,P=0.019],and the percentage of incidence of hospital onset of IA infection according to the incidence of hospital onset of infection were increased by 5 years [12.40％ (17/137) vs.2.81％ (5/178),x2=10.982,P=0.001].Of 29 patients with IA,25 cases had occurred after operation,and the majority of them were from the Department of General Surgery (13 cases),and followed by post-renal transplantation (6 cases) and post-thoracic surgery (3 cases).In the total submission of 155 specimens from 29 patients with IA,there were 17 strains isolated aspergillosis,among which included 2 strains of Aspergillus fumigatus,and 15 other un-subgrouped strains.The most common infection site was lower respiratory tract (23 cases,79.31％).Sixteen patients were found with positive galactomannan (GM) test.In all the risk factors contributing to IA,the ratio of the long-term usage of broad-spectrum antibiotics over 4 days was the highest [36.25％ (29/80)],which followed by the long-term use of hormone [18.75％ (15/80)],complicated with acute kidney injury [18.75％ (15/80)],liver injury [13.75％ (11/80)],the long-term use of immunosuppressive orally [7.50％ (6/18)],and complicated with neutropenia [5.00％ (4/80)].In 29 patients with IA,there were 28 patients received anti-fungal treatment except for 1 patient without treatment,and those were single use of itraconazole in 1 case,single use of echinocandins in 3 cases,single use of liposomal amphotericin B in 5 cases,8 cases with voriconazole,single use of liposomal amphotericin B or echinocandins then replaced by voriconazole in 8 cases,and 3 cases of echinocandins therapy combined with voriconazole.Seventeen of 29 patients died,with a mortality rate of 58.62％.Conclusions IA is an uncommon but increasing postoperative complication of patients in SICU in recent 5 years.The most common sites of IA were lower respiratory tract.The mortality of IA is very high.So clinicians should pay more attention to the careful monitor for IA.

OBJECTIVEDiscussion on utility and purposed value of obesity and abdomen obesity when body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) used as indexes predicting hypertension, hyper-blood glucose, and both clusters, to provide scientific basis for the decision on the indexes and their cut-off points of obesity and abdomen obesity in Chinese people.

METHODSUsing the data of diabetes mellitus (DM) from epidemiological studies carried out in 11 provinces/autonomous regions/municipalities of China from July 1995 to June 1997. Partial relative analysis, logistic multi-factors regression analysis, interaction analysis were used. Relative risk (RR), attributable risk proportion (ARP) and population attributable risk proportion (PARP) of hypertension, hyper-blood glucose, and the both cluster as BMI, WC, WHR with the different cut off points were analysed.

RESULTS1) The correlations between BMI, WC and blood pressure, blood glucose were better than the WHR. 2) After adjusted by age, sex, occupation leisure physical activity, education degree and the family history of DM, the results suggested that BMI, WC, WHR were important predictive factors, with relative importance as BMI > WC > WHR. 3) There were augment interactions on BMI, WC and WHR with hypertension, hyper-blood glucose, with the interaction of BMI and WC in particular. Their pure attributable interaction proportion were from 5.95% to 29.34%. 4) The values of RR were about 2.5 when BMI >/= 23, >/= 24 and >/= 25, suggesting the relationship with exposure factors and diseases were with medium and high maleficent extent. Their ARP were from 0.580 to 0.623 with PARP from 0.259 to 0.425. The values of RR were from 2.06 to 3.08 as WC >/= 85 cm in males, WC >/= 80 cm in females while WC >/= 90 cm in males, WC >/= 80 cm in females, which suggested that the relationship with exposure factors and diseases were in medium and high maleficent extent. Their ARP were from 0.515 to 0.676 while PARP from 0.241 to 0.431.

CONCLUSIONSSince the maleficent extent of exposure factors to diseases, the acceptability for overweight and obesity in population, and the prevention and care for overweight and obesity were just in the introduction stage in China. The utility value of predicted hypertension, hyper-blood glucose in BMI and WC seemed to be better then in WHR. We suggested that BMI used as the obesity index, with the diagnostic cut-off point BMI >/= 24. WC as the abdomen obesity index. The diagnostic cut-off points are suggested to be WC >/= 85 cm in males, and WC >/= 80 cm in females.

Adult ; Aged ; Blood Glucose ; metabolism ; Blood Pressure ; physiology ; Body Constitution ; Body Mass Index ; Diastole ; Female ; Humans ; Hyperglycemia ; diagnosis ; physiopathology ; Hypertension ; diagnosis ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Obesity ; physiopathology ; Predictive Value of Tests ; Systole