1.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.
Shuran FAN ; Ming QI ; Qi QI ; Qun MIAO ; Lijuan DENG ; Jinghua PAN ; Shenghui QIU ; Jiashuai HE ; Maohua HUANG ; Xiaobo LI ; Jie HUANG ; Jiapeng LIN ; Wenyu LYU ; Weiqing DENG ; Yingyin HE ; Xuesong LIU ; Lvfen GAO ; Dongmei ZHANG ; Wencai YE ; Minfeng CHEN
Acta Pharmaceutica Sinica B 2024;14(2):682-697
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
2.Impact of early and timely treatment and initial antiviral treatment regimen on antiviral treatment mortality and attrition among HIV-infected patients in Liuzhou, Guangxi
QIN Litai ; HUANG Jinghua ; CHEN Huanhuan ; LAN Guanghua ; FENG Yi ; XING Hui ; ZHU Jinhui ; CAI Wenlong ; RUAN Yuhua ; ZHU Qiuying ; XIE Yihong
China Tropical Medicine 2024;24(2):126-
Objective To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.
3.Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021
Ni CHEN ; He JIANG ; Huanhuan CHEN ; Qiuying ZHU ; Xiuling WU ; Jianjun LI ; Nengxiu LIANG ; Qin MENG ; Xuanhua LIU ; Jinghua HUANG ; Wenxuan HOU ; Zhaoquan WANG ; Guanghua LAN
Chinese Journal of Epidemiology 2024;45(4):529-535
Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.
4.Construction of postoperative prognostic model for primary liver cancer based on SMOTE and machine learning
Bi PAN ; Jinghua YU ; Yixian HUANG ; Yazhou WU ; Fang LI
Journal of Army Medical University 2024;46(19):2236-2240
Objective To construct a prognosis prediction model of primary liver cancer after surgical treatment based on synthetic minority over-sampling technique(SMOTE)algorithm and machine learning model.Methods A retrospective cohort study was conducted on 4 297 patients with primary liver cancer from the surveillance,epidemiology,and end results(SEER)database.One-Hot Encoding and Multiple Imputation were used to preprocess the collect data,and SMOTE algorithm was employed to solve the imbalance of data categories.The obtained clinical variables were included in the machine learning model.Based on decision tree(DT),random forest(RF),gradient boosting decision tree(GBDT)and eXtreme Gradient Boosting(XGBoost),a prognostic prediction model(SMOTE+DT/RF/GBDT/XGBoost)was build,and then the best prediction model was determined by comparing the performance of various models.Finally,a prognostic analysis system for primary liver cancer was developed based on the optimal model,which was then visualized.Results The combination model SMOTE+RF showed the best predictive performance,with higher area under the curve(0.895),accuracy(0.811)and precision(0.806)than those of other models in receiver operating characteristic curve(ROC)analysis.Conclusion The SMOTE+RF prognostic prediction model can effectively predict the survival outcome of patients with primary liver cancer.
5.Application of resting-state brain mirror homotopic connectivity in patients with concomitant exotropia
Juan CHEN ; Jinghua CHENG ; Han JIN ; Xin HUANG
Recent Advances in Ophthalmology 2024;44(11):878-882
Objective To investigate the cerebellar hemisphere homotopic functional connectivity in patients with concomitant exotropia(CE)based on voxel-mirrored homotopic connectivity(VMHC),aiming to provide a reference basis for the neuropathogenesis of CE.Methods A total of 36 CE patients who visited the Ophthalmology Department of Jian-gxi Provincial People's Hospital from October 2021 to October 2022 were included as the study group(CE group),while healthy volunteers who were recruited from society and matched in age and gender with the CE group were included as the control group(HC group).Subjects in both groups underwent 3.0T functional magnetic resonance imaging scans,and the magnetic resonance data were processed using DPABI_V4.0 software and SPM8 to compare the differences in VMHC values of various brain regions of subjects in the two groups.Results Compared with the HC group,the VMHC values in the cerebellar regions 6,8 and 9 on both sides and vermis cerebelli region 2 of subjects in the CE group were significantly re-duced(all P<0.05).The difference pattern of VMHC values in cerebellar regions showed that compared with the HC group,the VMHC values in cerebellar regions 6,8,9 and vermis cerebelli region 2 of subjects in the CE group were signifi-cantly different,especially the VMHC value in cerebellar region 9.Conclusion Functional changes in the cerebellar hemisphere,especially in cerebellar hemisphere region 9,play an important role in the pathogenesis of CE,which may be closely related to eye position voxel control and fusion.
6.Construction of an interactive health care participation program for patients undergoing lower limb bone transport
Xue GONG ; Jinghua YANG ; Wenyan HUANG ; Chen YANG ; Huijuan SONG
Chinese Journal of Modern Nursing 2024;30(32):4378-4385
Objective:To construct an interactive health care participation program for patients undergoing lower limb bone transport based on the interactive patient participation safety theory framework and the Patient Health Engagement model.Methods:From August to November 2022, through literature review and interviews with patients undergoing lower limb bone transport, a preliminary draft of the interactive health care participation program was developed based on the interactive patient participation safety theory framework and the Patient Health Engagement model. The Delphi method was used to conduct two rounds of consultations with 25 experts to screen and revise the program items.Results:The expert positive coefficients for the two rounds of expert consultations were 92.00% (23/25) and 100.00% (23/23). The authority coefficient was 0.913, and the Kendall's W coefficients for consistency were 0.127 and 0.140 ( P<0.01). The final program included three primary items, 22 secondary items, and 65 tertiary items. Conclusions:The interactive health care participation program for patients undergoing lower limb bone transport constructed in this study is both scientific and practical, can provide a theoretical basis and practical guidance for patient engagement in health care.
7.Influencing factors of metabolic syndrome in community patients with schizophrenia
Yu FAN ; Shaoling ZHONG ; Liang ZHOU ; Jinghua SU ; Xiyuan CHEN ; Xiaomin HUANG
Sichuan Mental Health 2023;36(6):515-520
BackgroundPatients with schizophrenia are at high risk of suffering from metabolic syndrome. Most previous studies on the influencing factors of metabolic syndrome focused on the inpatients and limited ones on patients dwelling in community. ObjectiveTo explore the influencing factors at different risk levels of metabolic syndrome in community-dwelling patients with schizophrenia in Guangzhou, so as to provide references for future interventions on metabolic syndrome in this patient population. MethodsIn November 2021, 3 339 patients with schizophrenia who were registered in and administered by Guangzhou Mental Health Information System were included. All these patients had finished the physical examination in 2020, and whether they had metabolic syndrome was assessed basing on Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition). Patients were divided into high-risk group (n=423), critical group (n=1 524) and metabolic syndrome group (n=1 392) according to the Chinese expert consensus on the management of metabolic syndrome in patients with schizophrenia. Multiple logistic regression analysis were performed on the risk factors of metabolic syndrome in community-dwelling patients with schizophrenia. ResultsThe prevalence rate of metabolic syndrome in community-dwelling patients with schizophrenia was 41.69%. Univariate analysis showed that the results in gender (χ2=44.610), age (χ2=55.992), marriage status (χ2=30.755), illness course (χ2=25.913) and body mass index (χ2=829.265) were significantly different among the three groups (P<0.01). Kruskal-Wallis H test showed that the levels of waist circumference (H=920.331), systolic blood pressure (H=436.673), diastolic blood pressure (H=393.337), fasting blood glucose (H=807.304), triglyceride (H=1 134.125) and high-density lipoprotein cholesterol (H=593.615) among the three groups were significantly different (P<0.01). Logistic regression analysis showed that age ≥50 (OR=1.761, 95% CI: 1.087~2.853), overweight (OR=2.418, 95% CI: 1.862~3.140) and obesity (OR=57.903, 95% CI: 14.340~233.802) were risk factors contributing to high-risk patients becoming critical population (P<0.05 or 0.01). Female gender (OR=1.295, 95% CI: 1.034~1.622), aged 40~49 (OR=2.597, 95% CI: 1.582~4.263), age ≥50 (OR=4.392, 95% CI: 2.609~7.395), overweight (OR=7.844, 95% CI: 6.018~10.223) and obesity (OR=426.785, 95% CI: 105.724~1 722.839) were risk factors for high-risk patients developing into metabolic syndrome population (P<0.05 or 0.01). ConclusionThe prevalence rate of metabolic syndrome is higher in community-dwelling patients with schizophrenia. Female gender, older age, overweight and obesity would increase the risk of metabolic syndrome in schizophrenic patients. [Funded by Health Science and Technology Project in Guangzhou (number, 20221A010028)]
8.The change trend analysis of incidence of intracerebral hemorrhage in Tengzhou City,Shandong Province from 2013 to 2021
Xin WANG ; Jinghua FAN ; Yuluan XU ; Nana YAN ; Xianli SONG ; Wen HUANG ; Li CHENG ; Liyu ZHOU ; Hongyu ZHU ; Shujun YE ; Zongyi WU ; Fengping ZHAO ; Fuzhong SI
Chinese Journal of Neurology 2023;56(7):770-779
Objective:To analyze the changing trend of intracerebral hemorrhage (ICH) incidence among residents with different characteristics during 9 years of comprehensive hypertension prevention and control (hypertension prevention and control) in Tengzhou from 2013 to 2021.Methods:From January 1, 2013 to December 31, 2021, the new ICH cases collected by the Center for Disease Control and Prevention in Tengzhou City were analyzed to calculate the incidence of ICH, and the trend of its distribution was analyzed among residents with different ages, sexes, and between urban and rural areas. The registered population information came from Tengzhou Public Security Bureau. Age and sex standardized incidence was calculated based on the 7th National Population Census in 2020. The Cochran-Armitage test was used to analyze the time and age trends of the incidence.Results:The overall ICH crude and standardized incidence in Tengzhou City decreased from 97.30/100 000 to 52.13/100 000 ( Z=-9.93, P<0.001) and 119.30/100 000 to 50.69/100 000 ( Z=-15.40, P<0.001) from 2013 to 2021, and both elevated to form a single peak in 2020, with 22.58% ( χ 2=24.02, P<0.001) and 18.09% ( χ 2=17.08, P<0.001) higher than in 2019, respectively. The trends in male and female incidence over the same period were similar to the overall trends, and the incidence was higher in males than in females in all years. The incidence of ICH increased with age in all years. The difference of increase in male incidence rate in 2020 was statistically significant in three age groups ≥45 years compared with 2019 (36.29%, 23.57% and 16.18%, respectively, χ 2=6.73, 4.65, 4.00, P<0.001). The incidence of ICH decreased by 70.07% and 36.23% ( Z=18.44, 5.22, P<0.001) in urban and rural areas respectively from 2013 to 2021, whereas increased by 34.15% ( χ 2=10.88, P<0.01) and 22.08% ( χ 2=18.63, P<0.001) in 2020 compared with 2019 separately. Conclusions:The incidence of ICH in Tengzhou from 2013 to 2021 showed a significant downward trend, with the decrease in the incidence of ICH in women exceeding that in men. The decrease in the incidence of ICH in urban areas exceeded that in rural areas, and male morbidity seemingly had a younger trend.
9.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.
10.Effect of salidroside on the proliferation and invasion of prostate cancer cells through LINC01207-miRNA-1182 signaling pathway
Geng HUANG ; Chen YUAN ; Zuwei XU ; Shuai LUO ; Jinghua WAN ; Xiaoling ZHANG
Cancer Research and Clinic 2023;35(12):894-898
Objective:To investigate the effect of salidroside on the proliferation and invasion of prostate cancer PC-3M cells and the possible molecular mechanism.Methods:PC-3M cells were treated with different concentrations (0, 50, 100, 150, 200 nmol/L) of salidroside for 48 h, and MTS assay was used to detect the effect of salidroside on the proliferation of PC-3M cells. The PC-3M cells treated with the most obvious inhibitory effect concentration of salidroside were selected as the salidroside group, and the PC-3M cells treated with 0.9% NaCl were selected as the control group. Transwell assay was used to detect the effect of salidroside on PC-3M cell invasion. The expression difference of LINC01207 between prostate cancer tissues and adjacent tissues was analyzed by using GEPIA database. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC01207 and miR-1182 in PC-3M cells after salidroside treatment. Western blot was used to detect the expressions of proliferation and invasion related proteins in PC-3M cells after salidroside treatment.Results:After treated with 0, 50, 100, 150, and 200 nmol/L salidroside, the absorbance values of prostate cancer PC-3M cells were 0.98±0.17, 0.72±0.08, 0.47±0.10, 0.12±0.03, and 0.42±0.05, respectively, and the difference was statistically significant ( F = 42.02, P < 0.05); and 150 nmol/L salidroside had the most significant inhibitory effect. The salidroside group (150 nmol/L salidroside) was performed to do the subsequent experiment. The invasion number of PC-3M cells in the control group and the salidroside group were (80±11) and (36±13), respectively ( t = 5.15, P < 0.05). GEPIA database online analysis showed that the expression of LINC01207 in prostate cancer tissues was higher than that in paracancerous tissues ( P < 0.01). qRT-PCR results showed that the relative expression level of LINC01207 in PC-3M cells of the control group and the salidroside group was (6.2±1.1) and (1.2±0.7), respectively; and the expression of LINC01207 in PC-3M cells of the salidroside group was lower than that of the control group ( t = 7.88, P < 0.01). The relative expression level of miRNA-1182 was (1.00±0.20) and (7.02±0.35), respectively; the expression of miRNA-1182 in PC-3M cells of the salidroside group was higher than that of the control group ( t = 30.07, P < 0.01). Western blot results showed that after PC-3M cells were treated with salidroside, the expressions of cell proliferation proteins CDK2 and cyclin E decreased; the expressions of cell invasion proteins CD147, matrix metalloproteinases (MMP)-2, MMP-9 decreased. Conclusions:Salidroside inhibits prostate cancer PC-3M cell proliferation and invasion by downregulating LINC01207 expression and activating miRNA-1182 expression.