Objective To investigate the effect of co-stimulatory molecular CD137 and CD28 on the cell proliferation, IL-2 secretion and cell apoptotic rate of activated T cells in naturally senile mice and subacute senile mice induced by D-galactose. Methods Seven-week-old BALB/c male mice were divided into D-galactose induced subacute senile group (D-gal group) , control group and young group randomly. Subacute senile mice model was established by back hypodermic injection of D-galactose (120 mg/kg, dissolved in 0. 1 ml distilled water) everyday for five month. Control group was established by injection of 0. 1 ml distilled water everyday for five month. Young group was injected with nothing. And 16-month-old BALB/c male mice was taken as aged group. The spleen T cells of each group were isolated and activated in vitro stimulation with ConA + IgG, ConA + CD137mAb or ConA + CD28mAb. The cell proliferation, apoptotic rate and IL-2 concentration in cell culture supernate of T cells were detected. Results (1) The cell proliferation (0.422?0.057, A), IL-2 secretion(0.632?0.066, A)and apoptotic rate(68.0%?2. 4%) of T cells in D-gal group stimulated in vitro with ConA+IgG showed no significant difference when compared with those of aged group. Compared with young and control group, activation of T cell in D-gal and aged groups were significantly decreased; (2) Cell proliferation, IL-2 secretion and cell survival of T cells in D-gal group and aged group were significantly promoted by both ConA + CD137mAb [(0. 639?0. 053, A) , (1.119?0.035,A), (53.3%?2.4)%, respectively] and ConA +CD28mAb. CD137 mAb had less effect on both groups than did CD28 mAb. Conclusions (1) Similar age-associated alterations happen in T cells of both D-gal group and aged group. (2) CD137 and CD28 can promote the activation and survival of T cells in aged and D-gal group. But CD28 has stronger effect on regulation of T cells than CD137.

Objective To evaluate the long-term efficacy and safety of donepezil in treating patients with Alzheimer's disease(AD).Methods Totally 86 patients with AD were randomly divided into control group(n =43)and treatment group(n =43).The control grou,p received conventional therapy with aniracetam,nimoldipine and ginkgo tablet,while the study group was administrated with donepezil(10 mg/d)on the basis of conventional therapy.The improvements of recognitive ability,mental state,activities of daily life were graded by mini-mental state examination (MMSE),Alzheimer's disease assessment scale-cog(ADAS-cog),activity of daily living(ADL)and global deterioration scale(GDS).The scores were compared between the groups before the treatment and 3,6,12,18,24,30,36,42,48,54,60,66 and 72 months after the treatment,respectively.Results The scores of MMSE,ADAS-cog and GDS after 3 months and ADL score after 6 months (t=2.361,-2.198,-1.790,-2.420,P＜0.05 or P＜0.01)were improved in treatment group than in control group with the best effects at 12 months(all P＜0.01)and the scores continued to decrease after 36 months.At 72 months,the score improvements in treatment group were 7.5 for MMSE,20.3 for ADAS-cog,19.5 for ADL,and 1.4 for GDS as compared with control group(all P ＜0.01).In contrast to pretreatment,there were statistically significant differences in the scores of MMSE,ADAS-cog and GDS at 3,6,12,18 and 24 months,and in the score of ADL at 6,12,18,24 and 30 months after treatment(P＜0.05 or P＜0.01).The differences in the scores of ADAS-cog and GDS after 24 months as well as MMSE and ADL after 30 months were not found(P＞0.05)between pre-treatment and post-treatment.Conclusions Donepezil might be long term effective and safe in slowing down the recognitive and overall function deterioration of AD.

Aim To study the relationship between the expressions of Fas,Fas-L and the spontaneous apoptosis of thymocytes in vitro. Methods The expressions of Fas,Fas-L and the apoptotic rate of thymocytes were assayed by flow cytometry. Results The apoptosis and the Fas expression of thymocytes of different culture times in vitro were increased time-dependently in vitro. The Fas-L expression of thymocytes cultured for 24 h was also significant increase. There was significant corelation between the increase of Fas expression and the increase of apoptosis of thymocytes in vitro. Conclusion Fas is an important molecule which mediates spontaneous apoptosis of thymocytes cultured in vitro.

Objective To evaluate the potential influencing factors associated with pathologic complete response ( pCR) after neoadjuvant chemoradiotherapy for locally advanced rectal cancer ( LARC) . Methods A retrospective analysis was performed on the clinical data 265 patients with stageⅡandⅢ( the 7th version of AJCC) rectal cancer admitted to our hospital from 2011 to 2013. All patients underwent neoadjuvant concurrent chemoradiotherapy ( CCRT ) followed by surgery with/or without induction chemotherapy during the interval between the complete of CCRT and surgery. The predictors associated with pCR were analyzed by univariate and multivariate logistic regression analyses. With the use of the independent predictive variables for pCR from multivariate analysis, a clinical risk score model was established according to the following criteria:no?risk group (0 factor);low?risk group (1 factor);high?risk group ( 2 factors) . Results Among these 265 patients, 50( 18. 9%) achieved pCR. The univariate analysis showed that carcinoembryonic antigen ( CEA) level before CCRT ( P=0. 017) , T stage before CCRT ( P=0. 001), interval between complete of CCRT and surgery (P=0. 000), and the maximum tumor thickness before CCRT ( P=0. 040) were significantly associated with pCR. The multivariate analysis showed that pre?CCRT CEA level ( P=0. 021 or 0. 446) and interval between the complete of CCRT and surgery ( P=0. 000 or 3. 774) were significant predictors of pCR. When stratifying for smoking status, only low pre?CCRT CEA level was significantly associated with pCR in the non?smoking patients ( P=0. 044) . For the prediction of pCR by the clinical risk score model, the sensitivity was 0. 805, the specificity was 0. 460, the area under the receiver operating curve was 0. 690 ( 95% CI= 0. 613?0. 767 ) , the positive predictive value was 35 . 4 9%, the negative predictive value was 8 6 . 5%, and the predictive accuracy was 7 3 . 9%. Conclusions For locally advanced rectal cancer, pCR can be achieved in some patients after neoadjuvant therapy. Low pre?CCRT CEA level and long interval time between CCRT and surgery are independent factors associated with pCR, and only low pre?CCRT CEA level is an associated factor in the group of nonsmokers. The clinical risk score model based on pre?CCRT CEA level>5 ng/ml and time interval from CCRT completion to surgery≤8 weeks can be used to predict pCR after neoadjuvant chemoradiotherapy for LARC.

Objective To evaluate the clinical efficacy and safety of different full spectrum light times in treating patients with Alzheimer's disease (AD).Methods A total of 127 AD patients with sleep disorder were randomly divided into a blank group (n=34),a 30 min group (n=31),a 60 min group (n=33) and a 120 min group (n=29).After one month treatment by 10 000 lux full spectrum fluorescent light,the improvements of sleep quality,excessive daytime sleepiness,cognitive ability,mental state,dementia degree were graded by Pittsburgh sleep quality index (PQSI),Epworth sleepiness scale (ESS),Neuropsychiatric inventory (NPI),mini-mental state examination (MMSE),global deterioration scale (GDS).The scores were compared among the groups before the treatment and after the treatment respectively.Results (1) Compared with before treatment,the scores of PQSI,ESS,NPI of the 30 min group,60min group and 120min group were statistically significant (in 30 min group 14.4 ±5.2vs 11.7±4.9,14.4±4.1 vs 11.8±3.7,14.2±1.3 vs 10.9±1.7,t=2.071,2.609,8.446.P=0.043,0.011,0.000; in 60 min group13.4±4.0 vs 8.1±3.7,14.5±3.0 vs 9.4±2.0,13.7±5.8 vs 8.7±4.3,t=5.650,8.209,3.902,all P＜0.01 ;in 120 min group 14.0±3.2 vs 7.0±2.3,14.7-±2.3 vs 7.0± 1.9,14.9±3.6 vs 8.1±3.7,t=9.474,13.926,7.062,all P＜0.01),but the scores of MMSE,GDS were not statistical significances(all P＞0.05).(2)Compared with the blank group,the scores of PQSI,ESS,NPI of 30 min group,60 min group and 120 min group were statistically significant (30 min group t=1.936,4.524,2.482,P=0.031,0.000,0.016.60 min group t=5.945,5.153,7.319,all P=0.000.120 min group t=7.896,6.767,10.776,all P=0.000), but the scores of MMSE,GDS were not statistical significances(all P＞0.05).(3)Compared with the 30 min group,the scores of PQSI,ESS,NPI of 60 min group and 120 min group were statistically significances (60 min group t =3.288,2.694,3.354,P=0.002,0.009,0.001.120 min group t=4.615,3.930,6.303,all P =0.000),the scores of MMSE,GDS were not statistical significances (all P＞0.05).Compared with the 60 min group,the scores of ESS of 120 min group was statistically significant(t=4.854,P=0.000),but the scores of PQSI,NPI,MMSE,GDS were not statistical significances (all P ＞ 0.05).Conclusion It is demonstrated good curative effects that light therapy treat patients on AD patients in the matter of sleep quality,excessive daytime sleepiness,mental state,but have not apparent effect for their cognitive ability and dementia degree.And the effect of light therapy with 60 or 120 minutes is better than that of 30 minute,illumination time of 120 minutes is superior to that of 60 minutes in improving excessive daytime sleepiness.Light therapy has no obvious impacts in the cognitive ability and the degree of dementia in the patients with AD and has not appear obvious adverse reaction in the process of treatment.

Objective:To investigate the correlation of sleep disorders(SD)with serum levels of amyloid β-proteins(Aβ 1-42)and tau phosphorylated at threonine(P-Tau 181)in patients with Alzheimer's disease(AD). Methods:A total of 126 patients with mild and moderate AD who met the inclusion criteria in the memory clinic, sleep clinic and geriatrics department of Jianghan Oilfield General Hospital affiliated to Yangtze University from February 2017 to January 2020 were included.The Pittsburgh Sleep Quality Index(PSQI)was used to evaluate sleep quality.Patients with PSQI scores ≥7 were included in the AD group with sleep disorders(AD-SD group), and patients with PSQI scores <7 were included in the AD group without sleep disorders(AD-NSD group). The Montreal Cognitive Assessment(MoCA), Global Deterioration Scale(GDS), Clinical Dementia Rating(CDR), Hamilton Rating Scale for Depression(HRSD)and Hamilton Anxiety Rating Scale(HAM-A)were used to evaluate cognitive and psychosocial symptoms.During the same time, biological markers such as serum Aβ 1-42, Aβ 1-40 and P-Tau 181 were detected by using enzyme-linked immunosorbent assays.Patients in the two groups received donepezil as an anti-dementia therapy, while the AD-SD group was treated additionally with a targeted sleep intervention.All patients underwent neuropsychological assessment and biochemical tests at enrollment and at the end of the 6th month, and results from all parameters at baseline and at the end of the 6th month were compared.At the end of the six-month treatment, patients in the AD-SD group were further divided into the recovery AD-SD sub-group and the no-recovery AD-SD sub-group based on the extent of sleep improvement. Results:Of the 126 AD patients, 93(73.8%)had sleep disorders.There was no statistically significant difference between the two groups in gender, age, onset age, educational level, course of disease, CDR, GDS, MoCA, Aβ 1-40 or Aβ 1-42/Aβ 1-40(all P>0.05). The scores of PSQI, HRSD and HAM-A and serum levels of Aβ 1-42 and p-Tau 181 showed statistically significant differences between the AD-ND and AD-NSD groups( P<0.05 or P<0.01). At the end of the 6th month, the scores of PSQI, GDS, HRSD and HAM-A and levels of Aβ 1-42, Aβ 1-40, and P-Tau 181 also showed statistically significant differences between the AD-ND and AD-NSD groups( P<0.05 or P<0.01). There was no statistically significant difference in results from other parameters( P>0.05). Spearman correlation analysis showed that PSQI was correlated with HRSD( r=0.271, P=0.009), HAM-A( r=0.479, P=0.000), Aβ 1-42( r=0.470, P=0.000), Aβ 1-42/ Aβ 1-40( r=0.479, P=0.000)and P-Tau 181( r=0.371, P=0.000)in the AD-SD group at baseline.Multivariate Logistic regression model showed that serum Aβ 1-42 and P-Tau 181 levels and HRSD had predictive effects on changes in sleep quality in AD patients( OR=1.897, 1.269 and 1.889, P=0.000, 0.003 and 0.000). The areas under the receiver operating characteristic(ROC)curves for Aβ 1-42, P-Tau 181 and HRSD were 0.926(95% CI: 0.860-0.991), 0.837(95% CI: 0.746-0.927)and 0.854(95% CI: 0.776-0.932), respectively. Conclusions:Sleep quality is correlated with serum Aβ 1-42and P-Tau 181 levels in AD patients.Elevated serum levels of Aβ 1-42 and P-Tau 181 and high HRSD scores are important predictors of SD in AD patients and may be used as indexes for clinical treatment efficacy.

OBJECTIVETo investigate the dynamic expression and its relation of gelatinase A (MMP-2), its natural inhibitor (TIMP-2) and DNA index (DI) changes during carcinogenesis, invasion and metastasis in Wistar rats.

METHODSSquamous cell carcinoma of lung was induced with 3-methylcholanthrene (MCA) and diethyinitrosamine (DEN) in iodized oil by left intra-bronchial instillation in 80 Wistar rats. Immrno histochemistay (IHC) and in situ hybridigation were used in the monitor of MMP-2, TIMP-2 proteins and mRNA expression during invasion and metastasis of lung cancer in these rats, DNA index (DI) value was measured by guantitatove image analysis on feulgen stained sections.

RESULTSAlong with the carcinogenis, the average poritive MNP-2 and TIMP-2 expressions increased, with positive rates of 8.5% - 85.7% and 6.4% - 35.7%. DI value also underwent the same changes (1.47 +/- 0.54) - (2.87 +/- 0.55). The difference of MMP-2 expression in carcinoma in situ versus early carcinoma and early carcinoma versus metastatic carcinoma are statistically significant (P < 0.05). Companing lung carcinome, the contrel group and non-cancerous lesions, the elevation of MNP-2 and TIMP-2 expressions were also sigmificant (P < 0.01). The DI elevation in carcinoma in situ and dysplasia were obviously significant (P < 0.05). Meanwhile a negative relation was noted in TINP-2 and MMP-2 expressions during carcinogenesis. There was a positive relation between MMP-2 expression and DNA poikiloidy (P < 0.01), which was related to the close relationship between MMP-2 and metastasis in advanced rat lung carcinoma (P < 0.05).

CONCLUSIONThe excess degradation and disruption of basement membranes by activated MMP-2 may be a key step in inducing lung cancer invasion and metastasis. The imbalance between MMP and TIMP may be a critical factor which affects biologic behavior of lung carcinogenesis, invasion and metastasis.

Alkylating Agents ; toxicity ; Animals ; Carcinoma, Squamous Cell ; chemically induced ; genetics ; pathology ; Diethylnitrosamine ; toxicity ; Female ; Gene Expression Regulation, Neoplastic ; Lung ; drug effects ; metabolism ; pathology ; Lung Neoplasms ; chemically induced ; genetics ; pathology ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Methylcholanthrene ; toxicity ; Neoplasm Invasiveness ; Neoplasm Metastasis ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism

BACKGROUNDTo study the specific expression of tumor-related genes (p53, bcl-2 and c-myc) in non small cell lung cancer with neuroendocrine differentiation (NSCLC-NE).

METHODSThe expression of neuron-specific enolase (NSE), chromogranin A (CgA), synaptophysin(Syn), c-myc, bcl-2 and p53 was detected in 60 surgically resected and paraffin-embedded non-small cell lung cancer (NSCLC) specimens by immunohistochemistry (S-P method).

RESULTSThe positive rates of NSE, CgA, Syn expressed in 60 cases of NSCLC were 45.00%(27/60), 13.33%(8/60), 31.67% (19/60) respectively. According to the results of these three markers, 41.67%(25/60) of 60 specimens was proved to be as NE differentiation cancer. The NE differentiation in NSCLC was remarkably related to differentiation of tumor cells (P < 0.05). NSCLC-NE had a higher metastatic rate (P < 0.05) and a higher clinical staging (P < 0.05) than NSCLC without NE differentiation. The positive rates of bcl-2, p53 and c-myc expression in NSCLC-NE were 68.00% (17/25), 80.00% (20/25), 68.00% (17/25) respectively, and the expression of bcl-2 and p53 was closely related to NE differentiation (P < 0.05).

CONCLUSIONSA certain part of NSCLC have NE differentiation, which has different biological features from NSCLC without NE differentiation. High expression of bcl-2 and mutant p53 can be observed in NSCLC-NE, and bcl-2/Bax unbalance associated with p53 mutation may play an important role in oncogenesis and development of NSCLC-NE.

OBJECTIVETo study the absorption kinetic characteristics of mollugin and purpurin in each intestinal segment of rats.

METHODThe in situ single-way perfusion rat model was established to study absorption characteristics of mollugin and purpurin in each intestinal segment of rats. The volume of recirculation fluid was regulated by phenol red.

RESULTDifferent quality concentrations (12.33, 24.66, 49.32 mg x L(-1)) of mollugin and (8.455, 16.91, 33.82 mg x L(-1)) purpurin showed a concentration gradient of absorption dose in each intestinal segment, with the osmotic coefficient increasing to more than 0.2 x 10(-4) cm x s(-1). In the same concentration, mollugin and purpurin showed an identical trend of P(eff) in each intestinal segment in the order of colon > duodenum > ileum > jejunum, with a significant difference (P < 0.05).

CONCLUSIONMollugin and purpurin are highly permeable in rat intestinal segments, with absorption in each segment, while the specific absorption existed in the colon segment.

Animals ; Anthraquinones ; metabolism ; Female ; Intestinal Absorption ; Male ; Pyrans ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results

BACKGROUNDTo investigate the expression of cyclooxygenase-2 (COX-2) protein and inducible nitric oxide synthase (iNOS) protein during the experimental lung carcinogenesis in rats, as well as their association with microvessel density (MVD).

METHODSDiethylinitrosamine and 3-methylcholanthrene were instilled into the left lobar bronchus to induce lung squamous cell carcinoma in 88 Wistar rats, and 10 nomal rats as controls. COX-2, iNOS expression and MVD count of the specimens obtained from the rats were examined by immunohistochemistry.

RESULTSA total of 155 specimens of various pathological phase during the carcinogenesis were obtained: 14 hyperplasia, 25 squamous metaplasia, 33 dysplasia, 12 carcinoma in situ, 54 infiltration carcinoma, and 17 metastasis. The immunohistochemical score (IHS) of COX-2 significantly increased in dysplasia, carcinoma in situ and metastasis (P < 0.01,P < 0.05,P < 0.01). IHS of iNOS significantly increased in hyperplasia and metastasis (P < 0.05,P < 0.01 ). Remarkably increased MVD was found in carcinoma in situ, infiltration carcinoma and metastasis (P < 0.01, P < 0.01, P < 0.01). There was a positive correlation between COX-2 and iNOS (r=0.601 6,P < 0.001) expression. Expression of COX-2 or iNOS were remarkably related to MVD count (P < 0.01,P < 0.01)

CONCLUSIONSCOX-2 and iNOS may play important roles in the carcinogenesis of experimental rat lung squamous cell carcinoma as well as its progress, and it may be associated with stimulating angiogenesis.