CCR2 and CCR5 co-inhibition modulates immunosuppressive myeloid milieu in glioma and synergizes with anti-PD-1 therapy.

Immunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade has become a cornerstone of immunotherapy for multiple tumor types, but the treatment of glioblastoma has not yet shown clinical efficacy. A major hurdle to treat GBM with checkpoint blockade is the high degree of myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. A potential strategy to improve anti-tumor efficacy against glioma is to use myeloid-modulating agents to target immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We found that the co-inhibition of the chemokine receptors CCR2 and CCR5 in murine model of glioma improves the survival and synergizes robustly with anti-PD-1 therapy. Moreover, the treatment specifically reduced the infiltration of monocytic-MDSCs (M-MDSCs) into brain tumors and increased lymphocyte abundance and cytokine secretion by tumor-infiltrating CD8 T cells. The depletion of T-cell subsets and myeloid cells abrogated the effects of CCR2 and CCR5 blockade, indicating that while broad depletion of myeloid cells does not improve survival, specific reduction in the infiltration of immunosuppressive myeloid cells, such as M-MDSCs, can boost the anti-tumor immune response of lymphocytes. Our study highlights the potential of CCR2/CCR5 co-inhibition in reducing myeloid-mediated immunosuppression in GBM patients.

Current Situation and Influencing Factors of Delay in Seeking Medical Treatment Among Residents in Rural Areas of Sichuan Province / 中国医学科学院学报

Objective To understand the current situation and explore the influencing factors of delay in seeking medical treatment for common symptoms of residents in the rural areas of Sichuan province. Methods In July 2019,multi-stage random sampling was carried out in Zigong city,Sichuan province,and the data were collected by face-to-face questionnaire interview.The residents who had lived at hometown for more than half a year in the past year and had seen a doctor in the most recent month were surveyed.Logistic regression was adopted to predict the influencing factors of delay in seeking medical treatment. Results A total of 342 subjects were enrolled,and the incidence of delay in seeking medical treatment was 13.45%(46/342).Compared with the young and middle-aged(<65 years)people,the elderly(≥65 years)people were more likely to have delay in seeking medical treatment (OR=2.187,95%CI=1.074-4.457,P=0.031).The rural residents who gave higher score of the overall quality of township health centers were less likely to have delay in seeking medical treatment (OR=0.854,95%CI=0.735-0.992,P=0.039). Conclusions The occurrence of delay in seeking medical treatment for common symptoms of rural residents in Sichuan province is low.Age and the overall quality evaluation of township health centers affect the occurrence of delay in medical treatment among the rural residents in Sichuan province.Efforts should be made to improve the awareness of disease prevention among the elderly in rural areas.The investment in health resources in township health centers should be increased to strengthen the introduction and training of talents.These measures can improve the health services in township health centers,guide residents to make timely use of health resources,and reduce the occurrence of delay in seeking medical treatment.

Relationship Between Maternal Negative Emotions and Feeding Patterns of Infants Aged 0-6 Months in Remote Rural Areas of Sichuan Province / 中国医学科学院学报

Objective To investigate the status of exclusive breastfeeding and bottle feeding in remote rural areas of Sichuan province and explore the relationship between negative emotions of mothers and feeding patterns of infants.Methods Multistage cluster sampling was employed to select the infants aged 0-6 months and their mothers in remote rural areas of Sichuan province.A self-designed questionnaire was used to collect the demographic characteristics of mothers and infants and the basic family information.The Chinese version of Depression Anxiety Stress scale was used to evaluate mothers' negative emotions,and the Breastfeeding Self-efficacy scale to assess the confidence level of mothers' behavior of adhering to exclusive breastfeeding.Results Totally 723 pairs of infants and their mothers were included.The exclusive breastfeeding and bottle feeding rates were 34.16% (247/723) and 57.54% (416/723),respectively.Mothers with depression tendency were less likely to adopt exclusive breastfeeding (OR=0.532,95%CI=0.291-0.974,P=0.041) and more likely to adopt bottle feeding (OR=1.877,95%CI=1.054-3.344,P=0.033).Further subgroup analysis of breastfeeding self-efficacy showed that in the group of low self-efficacy,the mothers with depression tendency were less likely to adopt exclusive breastfeeding (OR=0.461,95%CI=0.236-0.902,P=0.024) and more likely to adopt bottle feeding (OR=1.968,95%CI=1.047-3.701,P=0.036) than the mothers without depression tendency.In the group of high self-efficacy,mothers' depression,anxiety,and stress tendency had no significant correlation with infant feeding patterns (all P>0.05).Conclusions The mothers in the remote rural areas of Sichuan province are more likely to employ bottle feeding than exclusive breastfeeding.The mothers with stronger depression tendency demonstrate lower possibility of exclusive breastfeeding and higher possibility of bottle feeding.Breastfeeding self-efficacy may affect the association between maternal depression and infant feeding patterns.

Factors Associated With Coronary Heart Disease Among Adult Residents in Jinjiang District,Chengdu City / 中国医学科学院学报

Objective To analyze the prevalence of coronary heart disease among community residents over 18 years old in Jinjiang district of Chengdu city,Sichuan province,and explore its associated factors,so as to provide a reference for the prevention and control of coronary heart disease in communities.Methods From October 15 to November 10 in 2021,a total of 5220 adult residents from 33 communities in Jinjiang were selected by multi-stage stratified random sampling for face-to-face questionnaire survey,physical examination,and laboratory blood test.Binary Logistic regression was employed to predict the factors associated with coronary heart disease among adult residents in Jinjiang.Results The crude and standard prevalence rates of coronary heart disease among 5220 adult residents were 3.39% and 2.11%,respectively.Logistic regression analysis showed that age (OR=1.068,95%CI=1.051-1.086,P<0.001),depressive symptoms (OR=1.639,95%CI=1.037-2.591,P=0.034),regular exercise (OR=0.584,95%CI=0.378-0.902,P=0.015),elevated blood pressure (OR=3.529,95%CI=2.344-5.312,P<0.001),dyslipidemia (OR=2.152,95%CI=1.291-3.587,P=0.003),and core knowledge score of chronic diseases (OR=1.144,95%CI=1.066-1.228,P<0.001) were associated with coronary heart disease among adult residents in Jinjiang.Conclusions The prevalence of coronary heart disease is high among adult residents in Jinjiang district of Chengdu.The urban residents who are older,have depressive symptoms,lack of exercise,elevated blood pressure,dyslipidemia,and score higher on core knowledge of chronic diseases are prone to coronary heart disease.

Association of Dietary Diversity with Growth and Development of Children in Multi-ethnic Rural Areas of Sichuan Province / 中国医学科学院学报

Objective To understand the growth and dietary diversity status of children in multi-ethnic areas of Sichuan province,and to explore the associations of dietary diversity with growth and development indicators. Methods Children of 18-36 months old and their primary caregivers were selected with multi-stage cluster random sampling method from rural areas of Han,Tibetan,and Yi ethnic groups in Sichuan province. The sociodemographic information of children and their caregivers was collected using self-designed questionnaire.The dietary diversity score(DDS)was calculated according to the criteria in the Guidelines for Measuring Household and Individual Dietary Diversity released by the Food and Agriculture Organization of the United Nations.The body height(length)and body weight of each child were measured by standard equipment for anthropological measurement,and the height for age Z score(HAZ),weight for age Z score(WAZ),and weight for height Z score(WHZ) were calculated.Multivariate linear regression was performed to analyze the relationship between dietary diversity and growth indicators of children. Results A total of 1092 children were enrolled in this study,and the prevalence of stunting(HAZ<-2),underweight(WAZ<-2),and wasting(WHZ<-2)was 21.1%,4.9%,and 2.5%,respectively.The children had the mean DDS of 4.8±1.7,and 45.3% of children had poor dietary diversity(DDS≤4).The children of Han ethnic group(5.8±1.4)had higher DDS than those of Tibetan ethnic group(4.9±1.6)and Yi ethnic group(3.9±1.6)(P<0.001).The results of multivariate linear regression indicated that DDS was positively correlated with HAZ(β=0.206,95%CI=0.158-0.254,P<0.001)after adjustment of sex,age,birth weight,preterm birth,and parental body height.After further adjustment of family fixed assets,ethnic group,caregiver's type,and caregiver's education background,the correlation between DDS and HAZ remained significant(β=0.077,95%CI=0.026-0.128, P=0.003). Conclusions The children in the multi-ethnic rural areas of Sichuan province showed troublesome growth and development status and low dietary diversity,which were conspicuously different between ethnic groups,especially in the rural areas of Yi ethnic group.The dietary diversity was positively associated with HAZ.It is recommended to carry out nutrition and health education according to the local dietary characteristics and thus improve the growth and development of children in multi-ethnic rural areas in Sichuan.

Evaluation of Accuracy and Influencing Factors for Diagnosis of Two Chronic Diseases by Primary Healthcare Providers in Sichuan Rural Areas Based on Standardized Patients / 中国医学科学院学报

Objective We used standardized patients to evaluate the accuracy and explore the influencing factors of the diagnosis of unstable angina pectoris and type 2 diabetes by primary healthcare providers in Sichuan rural areas,aiming to provide a scientific basis for improving the diagnosis accuracy of primary healthcare providers for the two chronic diseases. Methods A multi-stage stratified random cluster sampling method was adopted to select 100 villages from 50 townships in 5 districts/counties in Zigong city,Sichuan province. General and internal medicine practioners who were on duty on the survey day were enrolled in the survey.Two rounds of data collection were conducted.In the first round,the basic information of providers from township health centers and village clinics was collected.One month after the the first survey,standardized patients were used to collect the information related to the diagnosis of unstable angina pectoris and type 2 diabetes by rural primary providers.Logistic regression was carried out to analyze the factors influencing the diagnosis accuracy. Results A total of 172 rural primary healthcare providers were enrolled in the survey,who completed 186 standardized patient visits and showed the correct diagnosis rate of 48.39%.Specifically,the correct diagnosis rates of unstable angina pectoris and type 2 diabetes were 18.68%(17/91) and 76.84%(73/95),respectively.The providers with medical practitioner qualifications were more likely to make correct diagnosis(OR=4.857,95%CI=1.076-21.933, P=0.040).The providers who involved more necessary consultation and examination items in the diagnosis process had higher probability of correct diagnosis(OR=1.627,95%CI=1.065-2.485, P=0.024).Additionally,the providers were more likely to make a correct diagnosis for type 2 diabetes than for unstable angina pectoris(OR=6.306,95%CI=3.611-11.013, P<0.001). Conclusions The overall diagnosis accuracy of unstable angina pectoris and type 2 diabetes was relatively low among primary healthcare providers in Sichuan rural areas.The training of diagnosis process can be taken as a key for improving providers' practice ability so as to increase the diagnosis accuracy of chronic diseases.

CCL5 of glioma-associated microglia/macrophages regulates glioma migration and invasion via calcium-dependent matrix metalloproteinase 2.

BACKGROUND: Glioma-associated microglia/macrophages (GAMs) comprise macrophages of peripheral origin and brain-intrinsic microglia, which support tumor progression. Chemokine C-C ligand 5 (CCL5) is an inflammatory mediator produced by immune cells and is involved in tumor growth and migration in several cancers, including glioma. However, the mechanisms detailing how CCL5 facilitates glioma invasion remain largely unresolved. METHODS: Glioma migration and invasion were determined by wound healing, transwell assay, and 3D µ-slide chemotaxis assay. The expression levels of CCL5, CD68, matrix metalloproteinase 2 (MMP2), phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), p-Akt, and phosphorylated proline-rich tyrosine kinase 2 were determined by cytokine array, quantitative PCR, western blot, or immunohistochemistry. Zymography and intracellular calcium assays were used to analyze MMP2 activity and intracellular calcium levels, respectively. RESULTS: CCL5 modulated the migratory and invasive activities of human glioma cells in association with MMP2 expression. In response to CCL5, glioma cells underwent a synchronized increase in intracellular calcium levels and p-CaMKII and p-Akt expression levels. CCL5-directed glioma invasion and increases in MMP2 were suppressed after inhibition of p-CaMKII. Glioma cells tended to migrate toward GAM-conditioned media activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) in which CCL5 was abundant. This homing effect was associated with MMP2 upregulation, and could be ameliorated either by controlling intracellular and extracellular calcium levels or by CCL5 antagonism. Clinical results also revealed the associations between CCL5 and GAM activation. CONCLUSION: Our results suggest that modulation of glioma CaMKII may restrict the effect of CCL5 on glioma invasion and could be a potential therapeutic target for alleviating glioma growth.

[Soil-transmitted nematode infections and influencing factors in pupils from rural areas of Yi Ethnicity in Butuo County, Sichuan Province].

OBJECTIVE: To understand the current situation of soil-transmitted nematode infections and influencing factors of pupils in rural areas of Yi Ethnicity in Butuo County, Sichuan Province, so as to provide the evidence for the prevention and control of soil-transmitted nematode infections. METHODS: In 2016, the pupils of 2 villages in Butuo County were selected by the multi-stage random sampling method, and the relevant information was obtained by questionnaires, including social demographic information, diet and hygiene habits and acknowledge of parasitic disease prevention. The soil-transmitted nematode infections were examined by Kato-Katz technique. The results were statistically analyzed by the single factor analysis and multivariate logistic regression methods. RESULTS: A total of 160 pupils were investigated in this survey. The soil-transmitted nematodes included Ascaris lumbricoides, Trichuris trichiura and hookworm. The overall infection rate was 89.38%, and the multi-infection rate was 54.55%. The infection rates of A. lumbricoides and T. trichiura were higher. The infection densities were mild (75.68%) or moderate (22.97%). The logistic regression analysis showed that the protective factor of soil-transmitted nematode infections was the knowledge about correct diet and health habits notified by teachers (OR = 0.67), but the risk factor was drinking unboiled water (OR = 19.26). CONCLUSIONS: The infection rate of nematodes is still high in the pupils in rural areas of Yi Ethnicity in Butuo County, Sichuan Province. Therefore, we should strengthen the prevention and control of soil-transmitted nematode infections, especially A. lumbricoides and T. trichiura infections, and mostly develop the teachers'function in health education.

Soil-transmitted nematode infections and influencing factors in pupils from rural areas of Yi Ethnicity in Butuo County, Sichuan Province / 中国血吸虫病防治杂志

Objective To understand the current situation of soil-transmitted nematode infections and influencing factors of pupils in rural areas of Yi Ethnicity in Butuo County, Sichuan Province, so as to provide the evidence for the prevention and control of soil-transmitted nematode infections. Methods In 2016, the pupils of 2 villages in Butuo County were selected by the multi-stage random sampling method, and the relevant information was obtained by questionnaires, including social demographic information, diet and hygiene habits and acknowledge of parasitic disease prevention. The soil-transmitted nematode infections were examined by Kato-Katz technique. The results were statistically analyzed by the single factor analysis and multivariate logistic regression methods. Results A total of 160 pupils were investigated in this survey. The soil-transmitted nematodes included Ascaris lumbricoides, Trichuris trichiura and hookworm. The overall infection rate was 89.38%, and the multi-infection rate was 54.55%. The infection rates of A. lumbricoides and T. trichiura were higher. The infection densities were mild (75.68%) or moderate (22.97%). The logistic regression analysis showed that the protective factor of soil-transmitted nematode infections was the knowledge about correct diet and health habits notified by teachers (OR = 0.67), but the risk factor was drinking unboiled water (OR = 19.26). Conclusions The infection rate of nematodes is still high in the pupils in rural areas of Yi Ethnicity in Butuo County, Sichuan Province. Therefore, we should strengthen the prevention and control of soil-transmitted nematode infections, especially A. lumbricoides and T. trichiura infections, and mostly develop the teachers’function in health education.

Soil-transmitted nematode infections and influencing factors in pupils from rural areas of Yi Ethnicity in Butuo County, Sichuan Province / 中国血吸虫病防治杂志

Objective To understand the current situation of soil-transmitted nematode infections and influencing factors of pupils in rural areas of Yi Ethnicity in Butuo County, Sichuan Province, so as to provide the evidence for the prevention and control of soil-transmitted nematode infections. Methods In 2016, the pupils of 2 villages in Butuo County were selected by the multi-stage random sampling method, and the relevant information was obtained by questionnaires, including social demographic information, diet and hygiene habits and acknowledge of parasitic disease prevention. The soil-transmitted nematode infections were examined by Kato-Katz technique. The results were statistically analyzed by the single factor analysis and multivariate logistic regression methods. Results A total of 160 pupils were investigated in this survey. The soil-transmitted nematodes included Ascaris lumbricoides, Trichuris trichiura and hookworm. The overall infection rate was 89.38%, and the multi-infection rate was 54.55%. The infection rates of A. lumbricoides and T. trichiura were higher. The infection densities were mild (75.68%) or moderate (22.97%). The logistic regression analysis showed that the protective factor of soil-transmitted nematode infections was the knowledge about correct diet and health habits notified by teachers (OR = 0.67), but the risk factor was drinking unboiled water (OR = 19.26). Conclusions The infection rate of nematodes is still high in the pupils in rural areas of Yi Ethnicity in Butuo County, Sichuan Province. Therefore, we should strengthen the prevention and control of soil-transmitted nematode infections, especially A. lumbricoides and T. trichiura infections, and mostly develop the teachers’function in health education.