1.Characterization of Metabolic Reprogramming in Head and Neck Squamous Cell Carcinoma and Application Prospects for Targeted Therapy
Ruilin WANG ; Yuxiu MA ; Xuelin LIU ; Qi ZHANG ; Guoyin WANG ; Hongling LI
Cancer Research on Prevention and Treatment 2024;51(12):1046-1050
Head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignant tumor in the world, with a 5-year survival rate of only about 50%. Thus, discovering more effective diagnostic and therapeutic approaches is an urgent need. The metabolic reprogramming of tumor cells is a key feature in the development of HNSCC, which widely exhibits alterations in glycolytic metabolism, lipid metabolism, and amino acid metabolism compared with normal cells. Metabolic reprogramming affects the energy supply and biosynthesis of tumor cells. It also participates in the regulation of the tumor microenvironment and promotes key biological processes such as proliferation, invasion, and metastasis of HNSCC. With the progressive understanding of the complexity of tumor biology, targeted-therapy strategies against metabolic reprogramming in HNSCC are emerging as a promising therapeutic approach. These metabolically targeted therapies have performed well in preclinical studies, but their clinical application requires further validation. In the future, we need to deeply explore the more complex features of metabolic reprogramming and its biological significance in HNSCC, with the aim of discovering more effective diagnostic and therapeutic targets, as well as providing new strategies to improve the prognosis of HNSCC patients.
2.The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial
Leilei DUAN ; Yubin ZHAO ; Yuliang ER ; Pengpeng YE ; Wei WANG ; Xin GAO ; Xiao DENG ; Ye JIN ; Yuan WANG ; Cuirong JI ; Xinyan MA ; Cong GAO ; Yuhong ZHAO ; Suqiu ZHU ; Shuzhen SU ; Xin'e GUO ; Juanjuan PENG ; Yan YU ; Chen YANG ; Yaya SU ; Ming ZHAO ; Lihua GUO ; Yiping WU ; Yangnu LUO ; Ruilin MENG ; Haofeng XU ; Huazhang LIU ; Huihong RUAN ; Bo XIE ; Huimin ZHANG ; Yuhua LIAO ; Yan CHEN ; Linhong WANG
Chinese Journal of Epidemiology 2024;45(2):250-256
Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.
3.Relationship between Doppler ultrasound parameters of uterine artery,umbilical artery,middle cerebral artery and placental vasculopathology and pregnancy outcome in preeclampsia rat model
Ruilin MA ; Yu LIU ; Guixiang XU ; Haoran SHI ; Jianjian CUI ; Zejun YANG ; Yan MAO ; Yin ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(5):543-551
Objective·To measure the parameters of the uterine artery,umbilical artery and middle cerebral artery in a rat model of preeclampsia(PE)by Doppler ultrasound,and compare the pathological changes in placental blood vessels and pregnancy outcomes,in order to provide an effective method and reference for evaluating placental function in PE animal models.Methods·PE(n=8)and normal pregnancy(NP,n=8)groups in Sprague-Dawley(SD)rat models were established by intraperitoneal injections of N'-nitro-L-arginine methylesterhydrochloride(L-NAME)and 0.9%sodium chloride solution.Blood pressure and proteinuria indexes were detected to evaluate whether the model was successfully established.On gestational day 19(GD19),Doppler ultrasound was utilized to measure the parameters of the uterine artery,umbilical artery and the fetal middle cerebral artery in both the PE and NP groups.After termination of the pregnancies,placental function was evaluated through the pathology of placental blood vessels and the quality of the fetuses and placentas.Results·In the PE group,both blood pressure(GD15:P=0.001;GD19:P=0.001)and proteinuria(GD15:P=0.001;GD19:P=0.001)were significantly higher than those in the NP group.The pulsatility index(PI)of the umbilical artery and uterine artery was notably elevated in the PE group compared to the NP group(both P=0.000).Furthermore,the resistance index(RI)of the fetal middle cerebral artery was significantly lower than that in the PE group(P=0.000).While the number of fetal rats did not differ significantly,the quality of placental and fetal rats was notably lower in the PE group(P=0.006 and P=0.000,respectively).Immunohistochemical staining of placental tissue revealed that the number of placental micro vessel densities in the PE group was less than that in the NP group(P=0.001).Correlation analysis revealed that placental micro vessel density,fetal quality and placental quality were inversely related with the RI of the umbilical artery and the PI and RI of the uterine artery,and positively correlated with the S/D,PI and RI of the fetal middle cerebral artery(all P<0.05).Conculsion·Doppler ultrasound assessment of the uterine artery,umbilical artery and middle cerebral artery indices in L-NAME-induced PE rat models effectively reflects pregnancy outcomes and placental vascular pathology.This method is valuable for evaluating placental vascular perfusion in PE rat models,offering practicality and convenience for research involving animal models.
4.Construction of AQHI based on joint effects of multi-pollutants in 5 provinces of China
Jinghua GAO ; Chunliang ZHOU ; Jianxiong HU ; Ruilin MENG ; Maigeng ZHOU ; Zhulin HOU ; Yize XIAO ; Min YU ; Biao HUANG ; Xiaojun XU ; Tao LIU ; Weiwei GONG ; Donghui JIN ; Mingfang QIN ; Peng YIN ; Yiqing XU ; Guanhao HE ; Xianbo WU ; Weilin ZENG ; Wenjun MA
Journal of Environmental and Occupational Medicine 2023;40(3):281-288
Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.
5.Determination of gross α and gross β radioactivity in IAEA-2020-intercomparison samples
Xiufeng MA ; Qingyun LIU ; Ruilin GAN ; Zhe WANG
Chinese Journal of Radiological Medicine and Protection 2022;42(1):50-54
Objective:To summarize the practices in measuring the gross α and gross β radioactivity in IAEA-2020-intercomparison samples, which could be expected to be beneficial to the similar analysis and research.Methods:With 241Am, Th, 90Sr/ 90Y, 40K and 137Cs solution as standard materials, the gross α and gross β radioactivity in water and aerosol samples were determined using thin source method. With 241Am, 40K powder as standard materials, the gross α and gross β radioactivity in water and fish samples were measured using thick source method combined with evaporation. Results:The result showed that the relative deviation and Z-score by using thin source method were 4.12%-31.6% and 0.14-1.71, respectively, and those from thick source combined with evaporation were 2.63%-32.5% and 0.11-0.93, respectively, with the acceptance rate being 100%. Conclusions:Generally, standard material shall be selected in the same types of radionuclides and energies as in samples. The thin source method is appropriate for emergency monitoring in the event of an accident. The thick source combined with evaporation should be perfered to the environmental monitoring or the analysis of unknown samples in laboratory. And then an intercomparison should be done with thin source method based on the radioactivity in samples. This work can provide a technical reference for similar measurements.
6.Association of compound hot extreme with blood pressure in Guangdong province
Zhixing LI ; Shunwei LIN ; Xiaojun XU ; Ruilin MENG ; Guanhao HE ; Jianxiong HU ; He ZHOU ; Weilin ZENG ; Xing LI ; Jianpeng XIAO ; Tao LIU ; Wenjun MA
Journal of Environmental and Occupational Medicine 2022;39(3):247-252
Background It is projected that the frequency, density, and duration of compound hot extreme may increase in the 21st century in the context of global warming. Objective To explore the association between compound hot extreme and blood pressure, and identify sensitive populations. Methods This was a cross-sectional study. The study subjects were from six Guangdong Province Chronic Disease and Nutrition Surveys during 2002 through 2015. A questionnaire was administered to the participants with questions about demographic information, drinking and smoking status, and measurements on their height, weight, and blood pressure were also collected. We chose the data of May, September, and October to explore the association between compound hot extreme and blood pressure. Compound hot extreme means a hot day with a proceeding hot night. Daily meteorological data were obtained from China Meteorological Data Service Centre. We employed inverse distance weighting to interpolate the temperature and relative humidity values for each participant. A distributed lag non-linear model was used to estimate the association between compound hot extreme and blood pressure. Stratified analyses by sex, age, area, body mass index (BMI), smoking status, and drinking status were also performed to identify sensitive populations. A sensitivity analysis was conducted by adjusting the degrees of freedom for lag spline and removing relative humidity. Result A total of 10967 participants without history of hypertension were included in this study. The average systolic blood pressure (SBP) was 120.8 mmHg and the average diastolic blood pressure (DBP) was 74.5 mmHg. The proportion of participants who experienced hot day, hot night, or compound hot extreme were 9.34%, 17.95% and 2.90%, respectively. Compared to hot day, hot night and compound hot extreme were related with decreased blood pressure, and the effect of compound hot extreme was stronger: the changes and 95%CI for SBP was −6.2 (−10.3-−2.1) mmHg, and for DBP was −2.7 (−5.2-−0.2) mmHg. Compound hot extreme induced decreased SBP among male, population ≥ 65 years, and those whose BMI < 24 kg·m-2, and their ORs (95%CIs) were −6.2 (−10.7-−1.6). −19.1 (−33.0-−5.1), and −6.7 (−11.8~−1.6) mmHg, respectively, and also decreased DBP among population ≥ 65 years, and its OR (95%CI) was −8.4 (−15.6-−1.1) mmHg. During compound hot extremes, participants living in rural areas showed decreased SBP and DBP, and the ORs (95%CIs) were −10.5 (−16.6-−4.5) and −4.4 (−7.7-−1.1) mmHg respectively, while those living in urban areas showed increased SBP, and the OR (95%CI) was 9.7 (2.9-16.5) mmHg. A significant decrease in blood pressure [OR (95%CI)] was also found in non-smokers [DBP, −3.7 (−6.6-−0.8) mmHg] and non-drinkers [SBP, −4.8 (−9.4-−0.2) mmHg; DBP, −3.4 (−6.0-−0.9) mmHg]. Conclusion Compound hot extreme is negatively associated with SBP, and being male, aged 65 years and over, and having BMI < 24 kg·m−2 may be more sensitive to compound hot extreme.
7.Effects of ambient temperature on metabolic syndrome and pathway analysis
Jie HU ; Jiali LUO ; Zihui CHEN ; Siqi CHEN ; Guiyuan JI ; Xiaojun XU ; Ruilin MENG ; Jianpeng XIAO ; Guanhao HE ; Haorong MENG ; Jianxiong HU ; Weilin ZENG ; Xing LI ; Lingchuan GUO ; Wenjun MA
Journal of Environmental and Occupational Medicine 2022;39(3):253-260
Background In recent years, the incidence of metabolic syndrome (MS) is increasing significantly in China. Some studies have found that temperature is related to single metabolic index, but there is a lack of research on associated mechanism and identifying path of the influence of temperature on MS. Objective Based on the data of Guangdong Province, to investigate the effect of temperature on MS and its pathway. Methods A total of 8524 residents were enrolled by multi-stage random sampling from October 2015 to January 2016 in Guangdong. Basic characteristics, behavioral characteristics, health status, and physical activity level were obtained through questionnaires and physical examinations, and meteorological data were obtained from meteorological monitoring sites. We matched individual data both with the temperature data of the physical examination day and of a lag of 14 d. A generalized additive model was used to explore the exposure-effect relationship between temperature and MS and its indexes, calculate effect values, and explore the effects of single-day lag temperature. Based on the literature and the results of generalized additive model analysis, a path analysis was conducted to explore the pathways of temperature influencing MS. Results The association between daily average temperature on the current day or lag 14 day and MS risk was not statistically significant. When daily average temperature increased by 1 ℃, the change values of fasting blood-glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high density lipoprotein cholesterol (HDL-C) were −0.033 (95%CI: −0.040-−0.026) mmol·L−1, −0.662 (95%CI: −0.741-−0.583) mmHg, −0.277 (95%CI: −0.323-−0.230) mmHg, and −0.005 (95%CI: −0.007-−0.004) mmol·L−1 respectively. The effects of average daily temperature on FBG, blood pressure, HDL-C, and waist circumference lasted until lag 14 day. The effects of daily average temperature on SBP and DBP were the largest on the current day. Daily average temperature of current day had direct and indirect effects on FBG and SBP. Temperature had an indirect effect on TG, and the intermediate variables were waist circumference and FBG, with an indirect effect value of −0.011 (95%CI: −0.020-−0.002). The indirect effects of daily average temperature on SBP, FBG, and TG were weak. Conclusion There is no significant correlation between temperature and risk of MS, and daily average temperature of current day could significantly affected blood pressure and FBG with a lag effect. Daily average temperature of current day has indirect effects on FBG and TG.
8.Relationship between heatwave and years of life lost associated with stroke in Guangdong Province: Based on Bayesian spatio-temporal model
Lixia YUAN ; Ruilin MENG ; Jiali LI ; Lifeng LIN ; Xiaojun XU ; Jianpeng XIAO ; Guanhao HE ; Jianxiong HU ; Zuhua RONG ; Wenjun MA ; Tao LIU
Journal of Environmental and Occupational Medicine 2022;39(3):268-274
Background Stroke has become a main cause of death in China. With global warming, the studies on temperature and stroke have attracted much attention. Objective To analyze he relationships between heatwave and the years of life lost (YLL) by different subtypes of stroke by controlling temporal and spatial effects with Bayesian spatio-temporal model, and to study the modifiers of the health effect of heatwave. Methods The daily information of stroke deaths, meteorological data, and air pollutant data in 40 districts and counties of Guangdong Province were collected during the warm seasons (from May to October) in the years from 2014 to 2017. The individual YLL was first calculated by matching age and gender according to the life table, and then the daily YLL rate (person-years/100 000 people) was obtained by summarizing the daily YLL and correcting it with the population of each district or county. Bayesian spatio-temporal model was used to fit a proposed exposure-response relationship between heatwave and the YLL rates of different subtypes of stroke. Finally, stratified analyses were conducted by age (<65 years, ≥65 years), gender (male, female), and region (Pearl River Delta and non-Pearl River Delta regions) to identify the major modifiers for the association between heatwave and stroke mortality. Results During the warm seasons from 2014 to 2017, a total of 23 heatwave events occurred in the 40 districts or counties of Guangdong Province, cumulatively lasting for 145 d. A total of 30 852 stroke deaths were recorded in the same time periods. The average daily YLL rate of total stroke was (2.39±3.63) person-years/100 000 people, and those for hemorrhagic stroke and ischemic stroke were (1.54±2.99) person-years/100 000 people and (0.84±1.85) person-years/100 000 people, respectively. Heatwave was associated with increased YLL rate of stroke in residents, and it had a greater impact on ischemic stroke with a lag effect. The largest cumulative effect of heatwave was at lag 0-1 day, which was associated with an increased YLL rate of total stroke and ischemic stroke by 0.17 (95%CI: 0.03-0.29) person-years/100 000 people and 0.13 (95%CI: 0.06-0.20) person-years/100 000 people, respectively. The results of stratified analyses showed that heatwave had a larger effect on ischemic stroke in residents of aged 65 years or older, male, and non-Pearl River Delta regions, and the rates of YLL increased by 1.11 (95%CI: 0.58-1.55), 0.13 (95%CI: 0.03-0.23), and 0.20 (95%CI: 0.07-0.32) person-years/100 000 people, respectively; Heatwave only had an effect on hemorrhagic stroke in residents aged 65 years or older with an increased YLL rate of 0.79 (95%CI: 0.26-1.31) person-years/100 000 people. Conclusion Heatwave could elevate the level of years of life lost associated with stroke in Guangdong residents, with greater impacts on ischemic stroke of the aged, men, and residents in non-Pearl River Delta regions, and on hemorrhagic stroke in the elderly.
9.Serum metabolomic profiling reveals potential biomarkers in assessing the management of women with polycystic ovary syndrome: a randomized controlled trial.
Xuesong DING ; Yan DENG ; Yanfang WANG ; Wei XUE ; Shiyang ZHU ; Xiao MA ; Ruilin MA ; Aijun SUN
Chinese Medical Journal 2021;135(1):79-85
BACKGROUND:
As one of the most common endocrinal disorders for women at childbearing age, the diagnostic criteria of polycystic ovary syndrome (PCOS) have been defined differently among different international health organizations. Phenotypic heterogeneity of PCOS also brings about difficulties for its diagnosis and management assessment. Therefore, more efficient biomarkers representing the progression of PCOS are expected to be integrated into the monitoring of management process using metabolomic approaches.
METHODS:
In this prospective randomized controlled trial, 117 PCOS patients were enrolled from December 2016 to September 2017. Classical diagnostic parameters, blood glucose, and metabolome were measured in these patients before and at 2 months and 3 months of different medical interventions. The receiver operating characteristic (ROC) curves were built based on multivariate statistical analysis using data at baseline and 3 months' management, and combinational biomarkers with appreciable sensitivity and specificity were selected, which then validated with data collected at 2 months.
RESULTS:
A set of metabolites including glutamic acid, aspartic acid, 1-methylnicotinamide, acetylcarnitine, glycerophosphocholine, and oleamide were filtered out with high performance in representing the improvement through 3-month management of PCOS with high sensitivity and specificity in ROC analysis and validation with other two groups showed an appreciable area under the curve over 0.96.
CONCLUSIONS:
The six metabolites were representative of the remission of PCOS through medical intervention, making them a set of potential biomarkers for assessing the outcome of PCOS management.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03264638.
Biomarkers
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Female
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Humans
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Metabolomics
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Polycystic Ovary Syndrome/diagnosis*
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Prospective Studies
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ROC Curve
10.Monitoring and analysis of gross radioactivity of centralized drinking-water of township in Beijing
Xiufeng MA ; Yue FENG ; Zhe WANG ; Lu LIU ; Qingyun LIU ; Ruilin GAN ; Zengyan GONG ; Wei HUANG
Chinese Journal of Radiological Health 2021;30(5):568-572
Objective To investigate the distribution of gross α and gross β levels of centralized drinking-water of township in Beijing from 2018 to 2019, so as to carry out better monitoring and evaluating the radioactivity in water. Methods A total of 215 underground drinking water samples were collected from 12 districts of Beijing, then monitored and evaluated according to the Determination of gross alpha activity in water-thick source method EJ/T 1075—1998 and Determination of gross beta activity in water-evaporation method EJ/T 900—1994. Results The gross α level of centralized drinking water of township in Beijing was 0.050 (0.052) Bq/L, ranging from 0.001 to 0.210 Bq/L, and the gross β level was 0.048 (0.038) Bq/L, ranging from 0.002 to 0.261 Bq/L from 2018 to 2019. Gross α and gross β levels of all samples did not exceed the guidance value recommended by standards for drinking water quality. There was no significant difference in the distribution of gross α and gross β levels of samples of all districts from 2018 to 2019(P > 0.05), there were significant differences in the distribution of gross α and gross β levels of samples from different district in the same period (P < 0.05). And the levels of Miyun, Huairou and Shunyi in Chaobai River system were higher than other districts. Conclusion The distribution of radioactive background of centralized drinking-water of township in Beijing was mastered, which was in the normal range.

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