BACKGROUND AND OBJECTIVEAs chemotherapy is generally used in the clinical treatment of cancer, the problem of multidrug resistance (MDR) of tumors against the chemotherapeutic agents becomes more and more serious. It has been the major cause for the failure of the chemotherapy. We detected the expressions of beta-catenin and tumor drug resistance related proteins, MRP2, P-gp, and Bcl-2, in esophageal squamous cell carcinoma (ESCC) to explore their function and correlation in the occurrence and development of MDR in ESCC.

METHODSWe used the tissue microarray technique, immunohistochemistry, and image analysis methods to detect the expressions of MRP2, P-gp, beta-catenin, and Bcl-2 proteins and analyze their relationships with clinical data in a ESCC tissue microarray consisting of 582 specimens of ESCC, 294 specimens of normal mucosa, 92 specimens of basal cell hyperplasia, and 87 specimens of dysplasia adjacent to cancer tissue.

RESULTSThe integral optical density (IOD) of MRP2 and Bcl-2, which was 195.7 +/- 175.9 x 10(3)) and 90.5 +/- 112.5 x 10(3)), respectively, was significantly higher in ESCC than in normal mucosa, which was 104.8 +/- 86.1 x103) and 25.2 +/- 46.6 x 10(3)), respectively (P < 0.01). The IOD of P-gp and beta-catenin, which was 57.7 +/- 75.5 x 10(3)) and 32.0 +/- 47.0 x 10(3)) respectively, was significantly lower in ESCC than in normal mucosa, which was 114.8 +/- 106.6 x 10(3)) and 46.1 +/- 35.7 x 10(3)), respectively (P < 0.01). According to the following order, well differentiated moderately differentiated poorly differentiated, the IOD of MRP2 increased in ESCC (P < 0.01). The IOD of beta-catenin was higher in poorly differentiated ESCC than in well or moderately differentiated ESCC (P < 0.01). The IOD of Bcl-2 was lower in well differentiated ESCC than in poorly and moderately differentiated ESCC (P < 0.01). The IOD of beta-catenin and Bcl-2 was higher in the ESCC of specimens with infiltration depths that were in membrane mucosa than those in the muscular layer or serous coat (P < 0.01). The IOD of Bcl-2 was significantly higher in cases with lymph node metastasis than in cases without (P < 0.01). Positive correlations which were respectively between the expressions of P-gp and MRP2, the expressions of P-gp and Bcl-2 were found (r = 0.288 and r = 0.253, respectively, P < 0.01).

CONCLUSIONSMRP2, P-gp, and Bcl-2 may be taken as prognostic factors for MDR of ESCC. beta-catenin may play an important role in carcinogenesis and progression of ESCC.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Differentiation ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Young Adult ; beta Catenin ; metabolism

Background and Objective:As chemotherapy is generally used in the clinical treatment of cancer,the problem of multidrug resistance(MDR)of tumors against the chemotherapeutic agents becomes more and more serious.It has been the major cause for the failure of the chemotherapy.We detected the expressions of β-catenin and tumor drug resistance related proteins,MRP2,P-gp,and Bcl-2,in esophageal squamous cell carcinoma (ESCC)to explore their function and correlation in the occurrence and development of MDR in ESCC.Methods:We used the tissue microarray technique,immunohistochemistry,and image analysis methods to detect the expressions of MRP2,P-gp,β-catenin,and Bcl-2 proteins and analyze their relationships with clinical data in a ESCC tissue microarray consisting of 582 specimens of ESCC,294 specimens of normal mucosa,92 specimens of basal cell hyperplasia,and 87 specimens of dysplasia adjacent to cancer tissue.Results:The integral optical density(IOD)of MRP2 and Bcl-2,which was 195.7±175.9(×10~3)and 90.5±112.5(×10~3),respectively,was significantly higher in ESCC than in normal mucosa.which was 1 04.8±86.1(×10~3)and 25.2±46.6(×10~3),respectively(P＜0.01).The IOD of P-gp and β-catenin,which was 57.7±75.5(×10~3)and 32.0±47.0(×10~3)respectively,was significantly lower in ESCC than in normal mucosa,which was 114.8±106.6(×10~3)and 46.1±35.7(×10~3),respectively(P＜0.01).According to the following order.well differentiated-moderately differentiated-poorly differentiated.the 1OD of M RP2 increased in ESCC(P＜0.01).The IOD of β-catenin was higher in poorly differentiated ESCC than in well or moderately differentiated ESCC(P＜0.01).The IOD of Bcl-2 was lower in well differentiated ESCC than in poorly and moderately differentiated ESCC(P＜0.01).The IOD of β-catenin and Bcl-2 was higher in the ESCC of specimens with infiltration depths that were in membrane mucosa than those in the muscular layer or serous coat(P＜0.01).The IOD of Bcl-2 was significantly higher in cases with Iymph node metastasis than in cases without (P＜0.01).Positive correlations which were respectively between the expressions of P-gp and MRP2,the expressions of P-gp and Bcl-2 were found(r=0.288 and r=0.253.respectively,P＜0.01).Conclusions:MRP2,P-gp,and Bcl-2 may be taken as prognostic factors for MDR of ESCC.β-catenin may play an important role in carcinogenesis and progression of ESCC.

AIM To observe the oxidant stress and opoptotic effects of anisodine hydromide (AH) on chronic cerebral hypoperfusion (CCH) rats.METHODS In vivo CCH models were established in adult male SpragueDawley rats by permanent ligation of bilateral common carotid arteries [two-vessel occlusion (2-VO)] surgery.Rats were randomly divided into six groups,sham group,model group,positive group of n-butylphthalide and sodium chloride injection,and AH groups (1.2 mg/kg high-dose group,0.6 mg/kg medium-dose group,and 0.3 mg/kg low-dose group).Antioxidant indices including the activity of SOD,CAT,LDH and iNOS and the content of GSH and NO were measured.In the in vitro trial,PC12 cells were divided into control group,model group,positive group of n-butylphthalide,and AH groups (100 μmol/L high-dose group,50 μmol/L mediumdose group,and 25 μmol/L low-dose group),and the hypoxic models were established by treating PC12 cells with CoCl2.The cells had their release of NO and LDH detected,their cellular apoptosis determined by Hochest 33342 fluorescence staining,and the expression of P53 protein identified by IF (immunofluorescence) and Western blotting method.RESULTS The in vivo trial revealed AH's enhancement in serum SOD activity and inhibition in serum iNOS activityof the CCH rats,and its power in the cerebral GSH and LDH release reduction.The in vitro trial showed the resultant lower LDH and NO release,decreased number of neuro-apoptosis,and inhibited P53 pro tein expression after AH intervention.CONCLUSION The antioxidant and antiapoptotic effects of AH on CCH rats may be associated with down regulation of P53 protein.

BACKGROUNDThe ADRA2B gene insertion/deletion (I/D) polymorphism is associated with various cardiovascular and metabolic phenotypes. Large (C1) and small (C2) artery compliance, assessed by pulse wave analysis, is considered as sensitive markers or risk factors for cardiovascular disease. Therefore whether the ADRA2B I/D polymorphism is associated with C1 and C2 need to be investigated.

METHODSA total of 227 men and 243 women were enrolled in a Chinese family-based study. C1 and C2 were measured by pulse wave analysis. ADRA2B genotypes were determined by polymerase chain reaction. Statistical methods included generalized estimation equations and quantitative transmission disequilibrium test.

RESULTSThe II (31.9%), ID (46.8%) and DD (21.3%) genotype frequencies were in Hardy-Weinberg equilibrium (P = 0.73). The covariates selected by stepwise regression for C1 and C2 were age, systolic pressure and gender. The population based association analysis showed that C1 and C2 were not associated with ADRA2B genotype both before (C1: P = 0.28; C2: P = 0.27) and after (C1: P = 0.58; C2: P = 0.18) the adjustment. The family-based analyses of 128 informative offspring showed that transmission of the D-allele was not associated with C1 or C2, both before (C1: P = 0.42; C2: P = 0.85) and after (C1: P = 0.31; C2: P = 0.82) the adjustment.

CONCLUSIONThe study do not support that the ADRA2B gene I/D polymorphism has a major gene effect on C1 or C2 in the Chinese population of current sample size.

Adult ; Aged ; Arteries ; physiology ; Blood Pressure ; Compliance ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Adrenergic, alpha-2 ; genetics

This study was aimed to clarify whether valproic acid (VPA) induces apoptosis of leukemia HL-60 cell line and its possible mechanism. The effect of different concentrations and treatment time of VPA on HL-60 cell proliferation was assayed by cytotoxicity test (CCK-8 method) and fluorescence microscopy, and flow cytometry was used to detect cell apoptosis. The expressions of telomerase subunit h-tert mRNA and apoptosis-related protein as well as caspase-3 activity were detected by real time-quantitative PCR, Western blot and ELISA respectively. The results indicated that VPA inhibited proliferation of HL-60 cells and induced cell apoptosis in a dose dependent manner (r = -0.87). The expressions of anti-apoptotic protein BCL-2 and h-tert mRNA were significantly decreased while the pro-apoptotic protein BAX and caspase-3 activity increased after treatment with VPA. The apoptosis rate of HL-60 cell was negatively correlated with expression of h-tert mRNA. It is concluded that VPA can inhibit leukemia HL-60 cell proliferation and induce apoptosis. The VPA displays anti-leukemia activity possibly through reducing h-tert mRNA and BCL-2 protein expression, increasing BAX expression and activity of caspase-3.
Apoptosis ; drug effects ; Caspase 3 ; metabolism ; HL-60 Cells ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Telomerase ; metabolism ; Valproic Acid ; pharmacology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo study the influence of cow's milk protein allergy (CMPA) on the diagnosis of functional gastrointestinal diseases (FGID) based on the Rome IV standard in infants and young children.

METHODSA total of 84 children aged 1 month to 3 years who were diagnosed with CMPA were enrolled as the case group, and 84 infants and young children who underwent physical examination and had no CMPA were enrolled as the control group. The pediatricians specializing in gastroenterology asked parents using a questionnaire for the diagnosis of FGID based on the Rome IV standard to assess clinical symptoms and to diagnose FGID.

RESULTSThe case group had a significantly higher incidence rate of a family history of allergies than the control group (P<0.05). In the case group, 38 (45%) met the Rome IV standard for the diagnosis of FGID, while in the control group, 13 (15%) met this standard (P<0.05). According to the Rome IV standard for FGID, the case group had significantly higher diagnostic rates of reflex, functional diarrhea, difficult defecation, and functional constipation than the control group (P<0.05). The children who were diagnosed with FIGD in the control group were given conventional treatment, and those in the case group were asked to avoid the intake of cow's milk protein in addition to the conventional treatment. After 3 months of treatment, the case group had a significantly higher response rate to the treatment than the control group (P<0.05).

CONCLUSIONSIn infants and young children, CMPA has great influence on the diagnosis of FGID based on the Rome IV standard. The possibility of CMPA should be considered during the diagnosis of FGID.

Objective:The present study aim to explore the difference and characteristics of disgust in obsessive-compulsive disorder(OCD) with/without contamination washing symptoms,adding to the growing literature on the heterogeneity and clinical treatment of OCD.Methods:Totally 66 patients with OCD meeting the criteria of International Statistical Classification of Diseases and Related Health Problems,Tenth Revision (ICD-10) and 51 healthy controls matched with gender,age and level of education were recruited.All patients were divided into two subgroups namely washing symptoms group(n =26) and other symptoms group(n =40) based on the contamination washing symptoms.Participants respectively completed the lexical decision task.The results of the tasks were indicators reflecting the disgust feelings,including the accuracy,reaction time to core disgust words,moral disgust words,neutral words,and the rating intensity of disgust provoked by all of the words.Results:The reaction time for core disgust words[(723 ± 89)ms,(746 ± 95) ms vs.(676 ± 96) ms] and moral disgust words[(772 ± 98)ms,(796± 92)ms vs.(723 ± 94)ms] were longer in both group of patients with OCD than in healthy controls.The patients also rated higher degree of disgust for core disgust words[(6.7 ± 1.5),(6.9 ± 1.6)vs.(5.8 ± 1.7)]and moral disgust words [(6.8 ± 1.7),(7.2 ± 1.3)vs.(6.3 ± 1.5)] than healthy controls (Ps ＜0.05).But there were no difference existed between patients with and without contamination washing symptoms on the results of lexical decision task(Ps ＜0.05).Conclusion:It shows that patients with OCD tend to experience intense disgust feelings,and there is no difference between contamination washing symptoms and other symptoms on disgust.These findings suggest that intense disgust feelings may play a role on the etiology and maintenance of OCD,and reducing disgust could be a potential approach for OCD treatment.

Objective To propose a method for high-energy photon 3D decoding of PET detector to decode reactive crystal position and calculate γ ray depth in the scintillating crystal. Methods Light transmitting windows were set between the crystal arrays, visible photon groups were guided to distribute in the photoelectric sensor array during a single event, and sensor signal intensity was regulated to realize position and depth decoding of the high-energy photon.Monte Carlo method was used to compare the designs of different light transmitting windows to determine the effects of the crystal surface treatment mode on the results. Experiments were executed for further verification. Results The experimental results had consistency with simulation ones;the signal received through the reaction crystal was always stronger than that through the adjacent, which could decode the reaction crystals; the relations between the depth of interaction (DOI) and energy differences of the photo sensors were monotonic with the changes of DOI,and thus could be used to calculate the DOI;when using single window,the DOI vs.Diff.Energy curves had two segments which were not desired for DOI measurement;crystals with rough surfaces were more desired since the qualities of their DOI vs.Diff.Energy curves were better;the dual window method had the best DOI vs.Diff.Energy curves in term of linearity.Conclusion The method can realize 3D decoding of the discrete crystal array,which improves the energy resolution of the PET system. [Chinese Medical Equipment Journal, 2018,39(5):22-28,63]

Objective To explore the role of protein kinase C (PKC) in the mechanism of central sensitization of migraine.Methods Sixty healthy adult male SD rats,weighting from 200 to 250 g,were randomly divided into five groups:normal group,sham-operated group,migraine model group,chloroform treatment group and H-7 (the inhibitor of PKC) treatment group (n=12).Dural blood flow monitor was performed by laser Doppler blood flow imager and extracellular discharge frequency in the spinal trigeminal nucleus was observed by multi-conductive polygraph; the dural blood flow and discharge frequency changes were analyzed and compared.Results Two hours after the success of model making,the dural blood flow in the migraine model group increased obviously as compared with that in the sham-operated group (P＜0.05); as compared with that in the migraine model group,the dural blood flow in the H-7 treatment group decreased obviously (P＜0.05); as compared with sham operation group,blood flow decreased obviously in H-7 group (P＜0.05).Extracellular discharge frequency in the spinal trigeminal nucleus increased 2 h after the success of model making; 2 hours after model making,the extracellular discharge frequency was (323.82±11.00) ％ of baseline level; as compared with that in the migraine model group,discharge frequency in the H-7 treatment group decreased obviously (P＜0.05); as compared with that in the sham-operated group,discharge frequency in the H-7 treatment group had no obvious changes (P＞0.05).Conclusion PKC may play an important role in the mechanism of central sensitization of migraine.

Objective:To explore the effect of ultraviolet-C (UV-C) combined with Kangfuxin liquid wet compress and oxygen blowing method on the post chemotherapy oral mucositis (OM) in patients with hematological malignancies.Methods:From January 2022 to February 2023, convenience sampling was used to select 120 patients with post chemotherapy OM in the Department of Hematology of the Affiliated Huai'an First People's Hospital of Nanjing Medical University. The patients were randomly divided into a control group and an observation group, with 60 cases in each group. The control group received Kangfuxin liquid wet compress, while the observation group carried out a combination of UV-C irradiation and oxygen oral blowing method on the basis of the control group. This study compared the Visual Analogue Scale (VAS) score before and two days after treatment, the healing status of OM after treatment on the 5th day, and the healing time of OM between the two groups of patients.Results:A total of 108 patients completed the study, with 52 in the control group and 56 in the observation group. After two days of treatment, the VAS scores of both groups of patients were lower than those before treatment, and those of the observation group were lower than those of the control group, with statistically significant differences ( P<0.05). On the 5th day of treatment, the healing rate of OM in the observation group was higher than that in the control group, and the difference was statistically significant (χ 2=5.425, P<0.05). The healing time of OM in the observation group was shorter than that in the control group, and the difference was statistically significant ( t=2.458, P<0.05) . Conclusions:The combination of UV-C, Kangfuxin liquid and oxygen blowing method can alleviate pain, improve the healing rate of OM, and shorten the healing time of post chemotherapy OM in patients with hematological malignancies, which is worthy of clinical promotion.