P-glycoprotein(P-gp)is an ATP-dependent efflux transporter that is distributed in many tissues and organs.P-gp can selectively pump endogenous substrates and exogenous chemicals from the cell to the outside of the cell to maintain a stable endo-environment.However,it meanwhile restricts the entry of therapeutic drug into tissues and organs,and in particular,mediates the multidrug resistance of tumor cells to chemotherapeutic drugs.Therefore,understanding the localization of P-gp in different tissues and organs may be an important breakthrough point for disease treatment.In this paper,we mainly review the molecular structure,transport mechanism,localization,and regulation of P-gp in different tissues and organs,providing reference for the subsequent treatment of diseases.
Humans ; ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry* ; Animals ; Drug Resistance, Multiple

Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies.Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group,and cyclophosphamide+fungal infection low,medium,and high dose groups,with 12 animals in each group.General clinical observations were performed daily,and the serum levels of immunoglobulin(Ig)G and IgM and galactomannan(GM)were detected by ELISA on the 3rd and 7th days of modeling.Simultaneously,the ratio of CD4+and CD8+cells,content of white blood cells(WBCs)and neutrophils(Neu)in peripheral blood,the Aspergillus niger load in alveolar lavage,and morphological changes to rat lung tissue were observed.Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling,and rats in the cyclophosphamide+fungal infection group also had shortness of breath and audible wet rhonchi in the lungs.Compared with the normal control group,rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+,WBC,Neu,IgG,and IgM in the blood,and their proportion of CD8+cells was significantly higher(P＜0.05,P＜0.01).Compared with the cyclophosphamide control group,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly reduced blood levels of IgG,IgM,and CD4+cells(P＜0.05,P＜0.01);while the cyclophosphamide+fungal infection low-,medium-,and high-dose groups had significantly reduced blood levels of WBC and Neu(P＜0.05,P＜0.01).Additionally,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly increased blood CD8+cells(P＜0.05,P＜0.01),Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide+fungal infection low-,medium-,and high-dose groups compared with the cyclophosphamide control group(P＜0.05,P＜0.01).The lung tissues of the cyclophosphamide+fungal infection low-,medium-,and high-dose groups showed mycelial distribution and destruction of alveolar epithelium,increase of bronchial epithelial cup cells in the alveoli,and infiltration of inflammatory cells,and the degree of lesions was positively correlated with the modeling dose.Conclusions In this study,we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease.The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time,confirming that cellular immunity plays an important role in the pathogenesis of the disease.At the same time,Ig can also affect the development of invasive pulmonary aspergillosis,and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.

Objective:To investigate the effect of Xidi Liangxue recipe on the proliferation and apoptosis of HaCaT cells through the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) /microRNA (miR) -485-5p/signal transducer and activator of transcription 3 (STAT3) regulatory network. Methods:HaCaT cells were induced by interleukin-17 (IL-17), and the mRNA and protein expression of lncRNA NEAT1, miR-485-5p and STAT3 was detected in IL-17-induced HaCaT cells and normal human epidermal keratinocytes (NHEK) by quantitative PCR (qPCR) and Western blot analysis, respectively. The location of lncRNA NEAT1 and miR-485-5p in IL-17-induced HaCaT cells was observed by fluorescence in situ hybridization (FISH), and the targeted regulatory relationship among lncRNA NEAT1, miR-485-5p and STAT3 was verified by double-luciferase reporter gene assay. Chinese herbs were decocted according to the Xidi Liangxue recipe, SD rats were divided into two groups to be gavaged with the above decoctions (medicated group) or physiological saline (control group) for 5 days, and then serum samples were collected from the above two groups of rats separately. The IL-17-induced HaCaT cells were divided into 4 groups: control group treated with the control sera, lncRNA-NEAT1 overexpression group transfected with lncRNA-NEAT1 overexpression vectors and treated with the control sera, Xidi Liangxue recipe group treated with the medicated sera, and Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group transfected with lncRNA-NEAT1 overexpression vectors and treated with the medicated sera. qPCR, Western blot analysis, flow cytometry, and cell counting kit (CCK8) assay were performed to determine the mRNA and protein expression of lncRNA NEAT1, miR-485-5p and STAT3, and to evaluate cell proliferation and apoptosis. The two independent samples t-test was used for comparisons between two groups, one-way analysis of variance for comparisons among multiple groups, and least significant difference (LSD) t-test for multiple comparisons. Results:The IL-17-induced HaCaT cell group showed significantly increased relative expression levels of lncRNA NEAT1 and STAT3 mRNA (1.84 ± 0.21, 2.20 ± 0.24, respectively) and significantly increased protein expression of STAT3 and p-STAT3 (1.27 ± 0.13, 2.43 ± 0.16, respectively), but significantly decreased expression level of miR-485-5p (0.32 ± 0.04) compared with the NHEK group (lncRNA NEAT1 and STAT3 mRNA: 1.00 ± 0.11, 1.00 ± 0.11, respectively, both P < 0.05; STAT3 and p-STAT3 protein: 1.00 ± 0.11, 1.00 ± 0.10, t = 2.54, 3.02, respectively, both P < 0.05; miR-485-5p: 1.00 ± 0.12, t = 2.94, P = 0.015). FISH demonstrated that miR-485-5p and lncRNA NEAT1 were co-located in the cytoplasm of HaCaT cells. The double-luciferase reporter gene assay showed that the relative activity of luciferase was significantly lower in the miR-485-5p group than in the negative control group (both P < 0.05) after the transfection with wild-type lncRNA NEAT1 or STAT3 recombinant plasmids, while there were no significant differences between the miR-485-5p group and negative control group after the transfection with mutant lncRNA NEAT1 or STAT3 recombinant plasmids (both P > 0.05). Compared with the control group, the lncRNA-NEAT1 overexpression group showed significantly increased expression of lncRNA NEAT1 and STAT3 (including STAT3 mRNA, STAT3 protein, and p-STAT3 protein) in HaCaT cells (all P < 0.05), but significantly decreased miR-485-5p expression ( P < 0.05) ; the Xidi Liangxue recipe group showed significantly decreased expression of lncRNA NEAT1 and STAT3 (all P < 0.05), but significantly increased miR-485-5p expression compared with the control group ( P < 0.05) ; significantly decreased expression of lncRNA NEAT1 and STAT3, but significantly increased miR-485-5p expression was observed in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group compared with the lncRNA-NEAT1 overexpression group (all P < 0.05). After 24-, 48-, and 72-hour intervention, CCK8 assay showed that the proliferative activity of HaCaT cells was significantly higher in the lncRNA-NEAT1 overexpression group than in the control group (all P < 0.05), as well as in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group than in the Xidi Liangxue recipe group (all P < 0.05), and the cellular proliferative activity was significantly lower in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group and Xidi Liangxue recipe group than in the control group (all P < 0.05). The apoptosis rate was significantly lower in the lncRNA-NEAT1 overexpression group (5.84% ± 0.28%) than in the control group (14.75% ± 0.83%, LSD- t = 3.48, P = 0.002), but significantly higher in the Xidi Liangxue recipe group (35.72% ± 3.62%) than in the control group (LSD- t = 5.34, P = 0.001) ; the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group showed significantly increased apoptosis rate (27.64% ± 2.82%) compared with the lncRNA-NEAT1 overexpression group (LSD- t = 9.06, P < 0.001) . Conclusion:The Xidi Liangxue recipe could inhibit the proliferation of IL-17-induced HaCaT cells and promote their apoptosis, which may be related to the intervention in the lncRNA NEAT1/miR-485-5p/STAT3 regulatory network.

Objective:To establish an animal model of pneumonia for research on clinical prevention and treatment of bacterial pneumonia by infecting immunocompromised rats with drug-resistant Acinetobacter baumannii ( Ab) strains. Methods:Drug-resistant Ab strains were selected. Forty-eight SD rats were randomly divided into four groups: normal group, cyclophosphamide control group (intraperitoneal injection of 45 mg/kg cyclophosphamide), bacterial infection group (intratracheal instillation of 1.5×10 8 CFU Ab suspension), and bacterial infection+ immunosuppression group (intraperitoneal injection of 45 mg/kg cyclophosphamide+ intratracheal instillation of 1.5×10 8 CFU Ab suspension). Flow cytometry analysis was used to detect the proportion of CD4 + , CD8 + and NK cells in rat peripheral blood before as well as 3 d and 7 d after infection. A lung function meter was used to detect peak inspiratory flow (PIF), peak expiratory flow (PEF), tidal volume (Vt ) and forced expiratory volume in the second second/forced vital capacity (FEV 200/FVC) at 3 d and 7 d after modeling. ELISA was used to detect the levels of IL-6, TNF-α and IL-10 in the alveolar lavage fluid. HE staining was used to observe the morphology of rat lung tissues in each group. Bacterial loads in rat lung tissues were counted by bacterial culturing. Results:A decrease in voluntary activity was observed in rats in the cyclophosphamide control group, bacterial infection group and bacterial infection+ immunosuppression group after modeling. Lung rales could be heard in the bacterial infection group and bacterial infection+ immunosuppression group. Compared with the normal group, the cyclophosphamide control group showed decreased proportion of CD4 + and CD11b + NK cells and increased CD8 + cells in peripheral blood; the bacterial infection group showed decreased PIF, PEF, Vt and FEV 200/FVC, increased IL-6 and TNF-α levels and decreased IL-10 level in the alveolar lavage fluid, and higher bacterial load in lung tissues with mild widening of alveolar walls and inflammatory cell infiltration ( P<0.05, P<0.01). Compared with the cyclophosphamide control group and the bacterial infection group, the bacterial infection+ immunosuppression group showed a lower proportion of CD4 + cells and a higher proportion of CD8 + cells in rat peripheral blood, decreased PIF, PEF, Vt and FEV 200/FVC, increased IL-6 and TNF-α levels and decreased IL-10 level in alveolar lavage fluid, higher bacterial load in lung tissues, and aggravated widening of alveolar walls and inflammatory cell infiltration ( P<0.05, P<0.01). The proportion of CD11b + NK cells in peripheral blood of rats in the bacterial infection+ immunosuppression group was significantly lower than that in the bacterial infection group ( P<0.05, P<0.01). Conclusions:A bacterial pneumonia model was successfully constructed by infecting rats with Ab alone or in combination with cyclophosphamide immunosuppression. In the model constructed with Ab and cyclophosphamide immunosuppression, the rats had more severe pneumonia, which might be related to the reduced cellular immune function and the aggravated bacterial infection in rat lung tissues by cyclophosphamide.

Objective To explore the risk factors of recurrent low hemoglobin(RLH) level among students from 6 to 13 years old, and to formulate strategies and policies in this regard. Methods Surveillance on hemoglobin concentration was conducted among 71 742 students aged from 6 to 13y between 2013-2014 based on the annual physical examination for primary and middle school in Minhang District.Of those students, 670 were diagnosed with low hemoglobin level according to WHO criteria.A 1 ︰ 1 matched case-control study was conducted based on gender, age and school type.Questionnaire surveys for data collection were analyzed using Cox′s proportional hazards regression. Results Factors as pregnancy anemia(OR=2.32, 95%CI:1.49-3.63), non-pregnancy anemia(OR=4.65, 95%CI:1.22-17.69), maternal anemia(OR=2.51, 95%CI:1.50-4.21), drinking strong tea(OR=2.56, 95%CI:1.27-5.13) and dietary bias(OR=1.94, 95%CI:1.45-2.59) were risk factors of recurrent low hemoglobin level.Chewing pencils(OR=1.80, 95%CI:1.25-2.59) or toys(OR=1.79, 95%CI:1.10-2.86) and wasting(OR=3.37, 95%CI:1.11-10.21)might be the risk factors. Conclusion The risk factors of recurrent low hemoglobin level among students aged from 6 to 13 years are related to maternal anemia status and their dietary habits.We should strengthen education for women of child-bearing age, and help to develop healthy eating practices for their babies.Emaciated students should be focused on in this regard.

Objective To analyze malnutrition epidemiologic trend among students aged 6-18 years from 2010 to 2016 in Minhang district of Shanghai,and to provide reference for malnutrition prevention and treatment.Methods Physical examination data from healthy monitoring schools in Minhang District from 2010 to 2016 were used to screened out the malnutrition of students aged 6-18 years via National standard 2014 and analyzed the different type of malnutrition in different population.Results During the period of 2010 to 2016,malnutrition rate of students demonstrated a fluctuated trend.Malnutrition rate in 2010 was 4.0％ and 4.4％ in 2016.The major type of malnutrition is wasting with a proportion more than 88％ during these years.Rate of wasting increased from 3.5％ to 7.8％ in boys aged 13-18 years old and from 1.3％ to 3.9％ in girls aged 13-18 years old.Conclusions The malnutrition of students in Minhang District is under control,while the screening rate of wasting increased in students aged 13-18 years old.Intensified intervention of prevention and treatment should be administrated and integrated with obesity control in Minhang District of Shanghai.

Objective To analyze the epidemic features of anemia among students aged 6-11 years old in Minghang District,to provide basis for the control and prevention strategies of anemia among school students.Methods Surveillance on hemoglobin concentration was conducted among 42 872 students aged from 6 to 11 years old between 2012 and 2015.All data analyses were completed by SPSS 18.0 statistical software.Results The prevalence rate of anemia among school students 6-11 years old was 5.05％ (95％CI:4.84-5.26).The prevalence rate of anemia among girls was 5.28％,which was significantly higher than that 4.84％ among boys (x2 =4.24,P =0.037).Six-year-old boys and girls were most susceptible to anemia.Compared to students in Hope Schools,public school students are more vulnerable to anemia (boys:OR =2.37,95 ％ CI:2.03-2.76;girls:OR =2.08,95 ％ CI:1.74 -2.49).Overweight and obese students had a lower risk of anemia than average students (boys:OR =0.65,95 ％ CI:0.55-0.76;girls:OR =0.75,95 ％ CI:0.61-0.92).The three-year cumulative incidence of anemia was 12.80％ (95 ％CI:12.49-13.12).The cumulative incidence among girls was 14.52％,which was significantly higher than that of 11.28％ among boys (x2 =100.26,P＜0.001).Six-year-old boys have the highest three-year cumulative risk among all students,while 10-11-year-old girls have the highest three-year cumulative incidence.The risk of anemia in Hope School was found highest in all schools (boys:RR =1.93,95％CI:1.72-2.16;girls:RR =1.20,95 ％CI:1.04-1.39).Overweight and obesity were considered protective factors to anemia (boys:RR =0.75,95％CI:0.67-0.84;girls:RR =0.77,95％CI:0.68-0.88).The primary and recurrent detection rates of anemia were 14.58％ and 2.54％.The anemia among students was mainly detected during the first examination despite the differences in ages,schools and nutrition conditions (P ＜ 0.05).Conclusions The prevalence of anemia among primary school students in Minhang District is at a mild level.Control measures should be adopted,including monitoring of hemoglobin in all school children and adolescents,taking individual intervention measures based on results,promoting the health education for adolescent girls and parents of school children,and paying special attention to Hope School and students with recurrent and continuous anemia.

Objective To investigate the relationship between eating habits and childhood obesity by the method of cross-sectional survey in order to provide scientific basis for the prevention and intervention of childhood obesity.Methods We enrolled first-year students in Minhang District of Shanghai who participated in physical examination in 2014.Information was obtained from standardized face to face interviews of their parents or guardians with detailed questions on demographic characteristics,dietary habit,food preference,physical activity,sleep time and so on.Odds ratio (OR) and 95％ CI were calculated by unconditional Logistic regression models.Results Finally,5 752 students were enrolled in the study.The rate of obesity was 15.16％ (boys:18.35％;girls:11.83％) and the rate of over weight was 14.31％ (boys.:15.15％;girls:13.43％).Meat-based diet (OR=1.58,95％ CI:1.32-1.91),skipping breakfast (OR =1.87,95％ CI:1.01-3.46),eating too much caffeine-containing food (OR =1.66,95％ CI:1.09-2.51) and eating fast (OR:3.32-14.95) were associated with an increased risk of childhood obesity.Plant-based diet (OR =0.51,95％ CI:0.35-0.74) and choosy in food (OR:0.38-0.64) were associated with a decreased risk of childhood obesity.Besides,we found that children who preferred meat (OR =2.11,95％CI:1.42-3.14) and cured food (OR =1.42,95％ CI:1.05-1.92) had a higher risk of obesity.Conclusions Our results support the association between eating habits and childhood obesity.

Objective To analyze the spatial and temporal clustering characteristics of typhoid and paratyphoid fever and its change pattern in Yunnan, Guizhou and Guangxi provinces in southwestern China in recent years. Methods The incidence data of typhoid and paratyphoid fever cases at county level in 3 provinces during 2001-2012 were collected from China Information System for Diseases Control and Prevention and analyzed by the methods of descriptive epidemiology and geographic informatics. And the map showing the spatial and temporal clustering characters of typhoid and paratyphoid fever cases in three provinces was drawn. SaTScan statistics was used to identify the typhoid and paratyphoid fever clustering areas of three provinces in each year from 2001 to 2012. Results During the study period, the reported cases of typhoid and paratyphoid fever declined with year. The reported incidence decreased from 30.15 per 100000 in 2001 to 10.83 per 100000 in 2006 (annual incidence 21.12 per 100000);while during 2007-2012, the incidence became stable, ranging from 4.75 per 100000 to 6.83 per 100000 (annual incidence 5.73 per 100000). The seasonal variation of the incidence was consistent in three provinces, with majority of cases occurred in summer and autumn. The spatial and temporal clustering of typhoid and paratyphoid fever was demonstrated by the incidence map. Most high-incidence counties were located in a zonal area extending from Yuxi ofYunnan to Guiyang of Guizhou, but were concentrated in Guilin in Guangxi. Temporal and spatial scan statistics identified the positional shifting of class Ⅰ clustering area from Guizhou to Yunnan. Class Ⅰ clustering area was located around the central and western areas (Zunyi and Anshun) of Guizhou during 2001-2003, and moved to the central area of Yunnan during 2004-2012. Conclusion Spatial and temporal clustering of typhoid and paratyphoid fever existed in the endemic areas of southwestern China, and the clustering area covered a zone connecting the central areas of Guizhou and Yunnan. From 2004 to 2012, the most important clustering area shifted from Guizhou to Yunnan. Findings from this study provided evidence for the identifying key areas for typhoid and paratyphoid fever control and prevention and allocate health resources.

Objective To explore the clinical characteristics and related factors of mental disorder caused by brain injury in the judicial identiifcation of mental illness. Methods Forensic case data of brain injury ware collected and analized. Brain injury sverity was classied into 3 groups, namely severe group(group A); moderate group (group B) and mild group(group C) according to neurosurgery GCS scores; clinical characteristics were analyzed, diagnosis were made against the Chinese Classiifcation of Mental Disorders (the 3rd ed.) (CCMD-3). Relationship between the clinical characteristics and brain damage severity was analyzed. Results Organic neurosis-like syndromes are the main manifestation of mental disorders caused by mild and moderate brain injuries. Organic intellectual deifciency is the main manifestation of mental disorders due to severe brain injury. The difference between the three groups was significant (P ≤ 0.01). Conclusion Different clinical features are related to different brain injury severities in the forensic evaluation of mental disability.