1.Trends in global burden due to visceral leishmaniasis from 1990 to 2021 and projections up to 2035
Guobing YANG ; Aiwei HE ; Yongjun LI ; Shan LÜ ; Muxin CHEN ; Liguang TIAN ; Qin LIU ; Lei DUAN ; Yan LU ; Jian YANG ; Shizhu LI ; Xiaonong ZHOU ; Jichun WANG ; Shunxian ZHANG
Chinese Journal of Schistosomiasis Control 2025;37(1):35-43
Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/105, 95% UI: (1.49/105, 4.07/105)], prevalence [0.64/105, 95% UI: (0.37/105, 1.02/105)], mortality [0.51/105, 95% UI: (0, 1.80/105)] and DALYs rates of VL [33.81/105, 95% UI: (0.06/105, 124.09/105)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/105, 95% UI: (0.45/105, 0.72/105); 0.14/105, 95% UI: (0.11/105, 0.18/105)] than among women [0.27/105, 95% UI: (0.21/105, 0.33/105); 0.06/105, 95% UI: (0.05/105, 0.08/105)], and the highest mortality of VL was found among children under 5 years of age [0.24/105, 95% UI: (0.08/105, 0.66/105)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/105, 0.03/105, 0.02/105 and 1.44/105 in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.
2.Evaluation of surgical efficacy in patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023
Xixi CHENG ; Yu FENG ; Xu WANG ; Zhiyi WANG ; Jiaxi LEI ; Mingzhe JIANG ; Guobing YANG ; Xiaojuan ZHANG ; Shijie YANG ; Liying WANG
Chinese Journal of Schistosomiasis Control 2025;37(3):247-254
Objective To evaluate the therapeutic efficacy for surgical treatments among patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023, so as to provide insights into optimization of the diagnosis and treatment strategies against hepatic cystic echinococcosis. Methods The demographic and clinical data of all echinococcosis cases included in central government fiscal transfer payment program for echinococcosis control and undergoing surgical treatments in Gansu Province from 2006 to 2023 were captured. Hepatic cystic echinococcosis patients with complete medical records and follow-up data were included in the study, and patients’ characteristics, including hospital where patients received diagnosis and treatment, methods of case identification, year of surgery, classification of lesions, number of lesions, size of lesions, course of disease, surgical methods, and post-surgical follow-up data. The cure and recurrence of hepatic cystic echinococcosis were evaluated according to the Guidelines for Management of Echinococcosis Patients in the Central Government Fiscal Transfer Payment Program, and the cure and recurrent rates were calculated. Results Data were collected from 1 686 surgical patients with hepatic cystic echinococcosis. According to the inclusion and exclusion criteria, 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments were included during the period from 2006 to 2022, including 1 166 cured patients (95.42%) and 88 patients with postsurgical recurrence (7.20%), and the cure rate of surgical treatments appeared a tendency towards a rise among patients with hepatic cystic echinococcosis from 2008 to 2022 (χ2trend = 19.39, P < 0.05). The cure rates of hepatic cystic echinococcosis were 100% (177/177), 94.81% (128/135) and 94.62% (861/910) among patients detected through regular physical examinations, screened by the central government fiscal transfer payment program for echinococcosis control, and those who passively sought healthcare services, respectively (χ2 = 9.95, P < 0.05). The cure rates of hepatic cystic echinococcosis were 95.96% (1 046/1 090) among patients with a disease course of 2 years and less and 90.90% (120/132) among patients with a disease course of over 2 years (χ2 = 6.87, P < 0.05), and there were significant differences in the cure rates among patients with hepatic cystic echinococcosis in terms of number of lesions (χ2 = 24.44, P < 0.05) and surgical methods (P < 0.05). The cure rate of hepatic cystic echinococcosis patients was significantly higher following initiation of the central government fiscal transfer payment program for echinococcosis control (96.06%, 1 096/1 141) than before the program (86.42%, 70/81) (χ2 = 16.06, P < 0.05), and the cure rate of hepatic cystic echinococcosis patients was significantly higher in designated hospitals (96.48%, 741/768) than in non-designated hospitals (93.37%, 366/392) (χ2 = 5.78, P < 0.05). The median follow-up period was 4 (interquartile range, 7) years among 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments. The recurrent rate of hepatic cystic echinococcosis appeared a tendency towards a decline from 2008 to 2022 (χ2trend = 36.86, P < 0.05), with a reduction from 23.08% (9/39) in 2008 to 1.85% (1/54) in 2021, and the post-surgical recurrence rate of hepatic cystic echinococcosis was lower following initiation of the central government fiscal transfer payment program for echinococcosis control (5.87%, 67 / 1 141) than before the program (25.93%, 21/81) (χ2 = 45.51, P < 0.05). In addition, the post-surgical recurrence rate of hepatic cystic echinococcosis was higher in non-designated hospitals (10.46%, 41/392) than in designated hospitals (5.60%, 43/768) (χ2 = 9.12, P < 0.05), and there was a significant difference in the post-surgical recurrence rate among patients with hepatic cystic echinococcosis in terms of surgical methods (P < 0.05), with the highest recurrence rate (11.54%) seen among patients undergoing percutaneous fine-needle aspiration of cyst fluids-based surgical procedures (P < 0.05). Conclusion Since the initiation of the central government fiscal transfer payment program for echinococcosis control in Gansu Province in 2006, an increase in the surgical cure rate and a reduction in the recurrence of hepatic cystic echinococcosis had been found among patients with hepatic cystic echinococcosis, indicating a high overall therapeutic efficacy.
3.Prediction of suitable habitats of Phlebotomus chinensis in Gansu Province based on the Biomod2 ensemble model
Dawei YU ; Yandong HOU ; Aiwei HE ; Yu FENG ; Guobing YANG ; Chengming YANG ; Hong LIANG ; Hailiang ZHANG ; Fan LI
Chinese Journal of Schistosomiasis Control 2025;37(3):276-283
Objective To investigate the suitable habitats of Phlebotomus chinensis in Gansu Province, so as provide insights into effective management of mountain-type zoonotic visceral leishmaniasis (MT-ZVL). Methods The geographical coordinates of locations where MT-ZVL cases were reported were retrieved in Gansu Province from 2015 to 2023, and data pertaining to 26 environmental variables were captured, including 19 climatic variables (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter), five geographical variables (elevation, annual normalized difference vegetation index, vegetation type, landform type and land use type), and two population and economic variables (population distribution and gross domestic product). Twelve species distribution models were built using the biomod2 package in R project, including surface range envelope (SRE) model, generalized linear model (GLM), generalized additive model (GAM), multivariate adaptive regression splines (MARS) model, generalized boosted model (GBM), classification tree analysis (CTA) model, flexible discriminant analysis (FDA) model, maximum entropy (MaxEnt) model, optimized maximum entropy (MAXNET) model, artificial neural network (ANN) model, random forest (RF) model, and extreme gradient boosting (XGBOOST) model. The performance of 12 models was evaluated using the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS), and Kappa coefficient, and single models with high performance was selected to build the optimal ensemble models. Factors affecting the survival of Ph. chinensis were identified based on climatic, geographical, population and economic variables. In addition, the suitable distribution areas of Ph. chinensis were predicted in Gansu Province under shared socioeconomic pathway 126 (SSP126), SSP370 and SSP585 scenarios based on climatic data during the period from 1991 to 2020, from 2041 to 2060 (2050s), and from 2081 to 2100 (2090s) . Results A total of 11 species distribution models were successfully built for prediction of potential distribution areas of Ph. chinensis in Gansu Province, and the RF model had the highest predictive accuracy (AUC = 0.998). The ensemble model built based on the RF model, XGBOOST model, GLM, and MARS model had an increased predictive accuracy (AUC = 0.999) relative to single models. Among the 26 environmental factors, precipitation of the wettest quarter (12.00%), maximum temperature of the warmest month (11.58%), and annual normalized difference vegetation index (11.29%) had the greatest contributions to suitable habitats distribution of Ph. sinensis. Under the climatic conditions from 1991 to 2020, the potential suitable habitat area for Ph. chinensis in Gansu Province was approximately 5.80 × 104 km2, of which the highly suitable area was 1.42 × 104 km2, and primarily concentrated in the southernmost region of Gansu Province. By the 2050s, the unsuitable and lowly suitable areas for Ph. chinensis in Gansu Province had decreased by varying degrees compared to that of 1991 to 2020 period, while the moderately and highly suitable areas exhibited expansion and migration. By the 2090s, under the SSP126 scenario, the suitable habitat area for Ph. chinensis increased significantly, and under the SSP585 scenario, the highly suitable areas transformed into extremely suitable areas, also showing substantial growth. Future global warming is conducive to the survival and reproduction of Ph. chinensis. From the 2050s to the 2090s, the highly suitable areas for Ph. chinensis in Gansu Province will be projected to expand northward. Under the SSP126 scenario, the suitable habitat area for Ph. chinensis in Gansu Province is expected to increase by 194.75% and 204.79% in the 2050s and 2090s, respectively, compared to that of the 1991 to 2020 period. Under the SSP370 scenario, the moderately and highly suitable areas will be projected to increase by 164.40% and 209.03% in the 2050s and 2090s, respectively, while under the SSP585 scenario, they are expected to increase by 195.98% and 211.66%, respectively. Conclusions The distribution of potential suitable habitats of Ph. sinensis gradually shifts with climatic changes. Intensified surveillance and management of Ph. sinensis is recommended in central and eastern parts of Gansu Province to support early warning of MT-ZVL.
4.Spatiotemporal clustering and hot spot analysis of visceral leishmaniasis in Gansu Province from 1993 to 2023
Dawei YU ; Aiwei HE ; Yu FENG ; Guobing YANG ; Chengming YANG ; Fan LI
Chinese Journal of Schistosomiasis Control 2024;36(4):334-338
Objective To investigate the spatiotemporal clustering characteristics of the reported incidence of visceral leishmaniasis (VL) in Gansu Province from 1993 to 2023, so as to provide insights into the containment of VL and prevention of VL recurrence. Methods County (district)-level epidemical data of VL in Gansu Province from 1993 to 2023 were collected, and the geographical information database of reported VL incidence in Gansu Province was created according to the county-level administrative code and electronic maps in Gansu Province. In addition, the spatial autocorrelation analysis and hot spot analysis of the reported VL incidence were performed in Gansu Province using the software ArcGIS 10.8. Results A total of 2 597 VL cases were reported in Gansu Province from 1993 to 2023, with an annual average incidence rate of 3.036/105. Spatial autocorrelation analysis showed spatial clustering of the reported VL incidence in Gansu Province (Moran’s I = 0.605, Z = 5.240, P < 0.001), appearing high-high clustering features (Getis-Ord G = 0.080, Z = 4.137, P < 0.001), and high-high clustering of the reported incidence of VL was identified in Diebu County, Tanchang County, Zhouqu County and Wenxian County. Hot spot analysis showed hot-spot areas of the reported VL incidence in Tanchang County, Zhouqu County, Wudu District and Wenxian County along the Bailong River basins and cold-spot areas in Qin’an County and Gangu County. Conclusions There was spatial clustering and hot spots of the reported VL incidence in Gansu Province from 1993 to 2023. Intensified surveillance and control is required to prevent the spread of VL.
5.Epidemiological characteristics of visceral leishmaniasis in Gansu Province from 2017 to 2023
Fan LI ; Dawei YU ; Hong LIANG ; Chengming YANG ; Guobing YANG ; Junke YANG
Chinese Journal of Schistosomiasis Control 2024;36(4):339-345
Objective To analyze the epidemiological characteristics of visceral leishmaniasis in Gansu Province from 2017 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy in the province. Methods All epidemiological features of confirmed and clinically diagnosed cases of visceral leishmaniasis reported in Gansu Province from January 1, 2017 to December 31, 2023 were retrieved from the Chinese Disease Prevention and Control Information System, and the epidemiological characteristics of visceral leishmaniasis cases were analyzed descriptively. Results A total of 280 visceral leishmaniasis cases were reported in 39 counties (cities and districts) of Gansu Province from 2017 to 2023, including 258 local cases reported in 21 endemic counties (districts) and 22 imported cases reported in 18 non-endemic areas. Of the 280 cases, there were 262 cases with mountain type zoonotic visceral leishmaniasis (MT-ZVL), 12 cases with desert-type zoonotic visceral leishmaniasis (DT-ZVL), and 6 cases with unknown type. Re-emerging MT-ZVL occurred in Maiji District, Qinzhou District, Lixian County, Kangxian County, Zhenyuan County, Qin’an County and Yongjing County, and re-emerging DT-ZVL occurred in Dunhuang City, while emerging DT-ZVL occurred in Yumen City. The five counties (districts) reporting the highest number of visceral leishmaniasis cases included Wudu District, Wenxian County, Tanchang County, Zhouqu County and Diebu County, and a total of 220 cases were reported in these five counties, accounting for 78.57% of all visceral leishmaniasis cases in the province. Visceral leishmaniasis cases were reported each month throughout the year, with the peak in July. All reported visceral leishmaniasis cases had ages of 6 months to 81 years, including 50.71% (142/280) under 15 years of age, 49.29% (138/280) at ages of 15 years and older, and of all cases under 15 years of age, children at ages of 0 to 3 years were the most commonly affected (27.14%, 76/280). Among 280 visceral leishmaniasis cases, there were 173 males and 107 females with a male to female ratio of 1.62∶1, and farmer was the most common occupation (40.36%), followed by diaspora children (37.86%). Conclusions The prevalence of visceral leishmaniasis appeared an overall tendency towards a decline in Gansu Province from 2017 to 2023; however, there are still multiple challenges for visceral leishmaniasis control in the province. Reinforced dog monitoring and management, intensified human health education and improved capability building among professionals are recommended to manage the rebounding and spread of visceral leishmaniasis.
6.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
7.Influence of individual factors and labor organization on musculoskeletal disorders of automobile manufacturing workers
Hong YIN ; Yong MEI ; Kangkang ZHANG ; Guobing ZHAO ; Qin LI ; Shaohua YANG ; Jiabing WU
Journal of Public Health and Preventive Medicine 2024;35(4):99-102
Objective To investigate the influence of individual factors and labor organization factors on work-related musculoskeletal disorders (WMSDs) in automobile manufacturing workers, and to provide a scientific basis for the prevention and treatment of WMSDs in automobile manufacturing workers. Methods In April 2020, 5564 workers in an automobile factory were selected by cluster sampling method. The prevalence of WMSDs was investigated by using the Musculoskeletal Disorders Questionnaire, and the influence of individual factors and labor organization factors on WMSDs was investigated by using generalized estimation equation. Results The prevalence rate of WMSDs was 79.00% (4396/5564), and the prevalence rate of multisite WMSDs was 67.95% (3781/5564). The analysis of generalized estimation equation showed that doing the same job every day (OR= 1.478, P < 0.05), age ≥40 years (OR=1.416, P< 0.05), personnel shortage (OR= 1.356, P < 0.05), and work length of 6~10 years and 11~15 years (OR= 1.349, P< 0.05) were the main risk factors for WMSDs in automobile manufacturing workers. Shift work and working time > 40 hours per week increased the risk of WMSDs (P< 0.05). Male and adequate rest time were protective factors for WMSDs. The job correlation matrix showed that WMSDs in most parts had a positive correlation. Conclusions The prevalence of multisite WMSDs of workers in automobile manufacturing industry is high, and unreasonable labor organization is the main risk factor of WMSDs. Appropriate work breaks can effectively reduce the risk of WMSDs, and effective intervention measures should be carried out to prevent the occurrence of WMSDs in workers in automobile manufacturing industry. The generalized estimation equation can better analyze the influencing factors of WMSDs.
8.Effects of Notch1 signaling on regulatory T cells and coronary artery lesions in childhood Kawasaki disease
Yuxin GUO ; Li YANG ; Guobing WANG ; Pengqiang WEN ; Zhongxiang QI ; Mingguo XU ; Cong LIU ; Chengrong LI
Chinese Journal of Rheumatology 2022;26(10):649-656,C10-1
Objective:To explore the effect of Notch1 signaling on regulatory T cells and its roles in vascular damage in patients with Kawasaki disease (KD).Methods:A total of 42 children with KD were enrolled in the present study from March 2019 to June 2020, as 32 age-matched healthy children were recruited as control. The proportions of CD4 +CD25 hiFoxp 3+ regulatory T cells (Treg) and expressions of transcription factor forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte associated antigen-4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and Notch1 protein were evaluated by flow cytometry. Chromatin immunoprecipitation was conducted to detect acetylation level of histone H4 (H4Ac) associated with the promoter of Foxp3 gene and its binding abilities of Notch1 intracellular domain 1 (NICD1), recombination signal binding protein for immunoglobulin kappa J region (RBP-J) and p300 in CD4 + T cells. Transcription levels of Foxp3, presenilin 1 (PSEN1), mastermind like transcriptional coactivator 1 (MAML1), and RBP-J in CD4 + T cells were determined by real-time polymerase chain reaction (PCR). Concentrations of interleukin (IL)-10 and transforming growth factor-β (TGF-β) in plasma and culture supernatant stimulated with Jagged1 were measured by enzyme linked immunosorbent assay. Independent-sample t-test, Pearson correlation analysis was used as the statistical method in this study. Results:① The frequencies of Treg in acute KD patients decreased significantly [(4.3±1.5)% vs (7.9±2.9)%; t=6.41, P<0.001], as protein levels of Foxp3, CTLA4 and GITR and concentrations of IL-10 and TGF-β in plasma reduced remarkably in acute KD patients ( t=6.87, P<0.001; t=4.26, P<0.001; t=7.88, P<0.001; t=8.42, P<0.001; t=13.01, P<0.001). All parameters afore-mentioned in patients combined with coronary artery lesions (CAL) were lower than those of patients without coronary artery lesions (NCAL) ( t=5.83, P<0.001; t=3.83, P<0.001; t=3.28, P=0.002; t=5.05, P<0.001; t=5.96, P<0.001; t=5.17, P<0.001), and increased after therapy ( t=7.13, P<0.001; t=6.10, P<0.001; t=4.31, P<0.001; t=6.55, P<0.001; t=7.40, P<0.001; t=7.84, P<0.001). ② H4Ac associated with promoter of Foxp3 gene and the binding abilities of NICD1 and p300 in acute KD patients were lower than those of the controls ( t=10.25, P<0.001; t=6.93, P<0.001; t=6.75, P<0.001), and increased remarkably after therapy ( t=7.72, P<0.001; t=4.16, P<0.001; t=5.76, P<0.001). Meanwhile, the three items in CAL group were found to be less than those of NCAL group ( t=6.08, P<0.001; t=2.66, P=0.011; t=6.02, P<0.001). Pearson correlation analysis showed a positive correlation between H4Ac associated with Foxp3 promoter and its mRNA level in acute KD patients ( r=0.47, P<0.001). No statistical significant difference about the binding ability of RBP-J with Foxp3 promoter were found among the groups ( t=0.57, P>0.05; t=0.61, P>0.05; t=1.20, P>0.05). ③ Protein level of Notch1 and the expressions of PSEN1, MAML1 and RBP-J mRNA in CD4 + T cells from acute KD patients were down-regulated remarkably ( t=5.28, P<0.001; t=6.31, P<0.001; t=11.78, P<0.001; t=8.06, P<0.001), and restored after therapy ( t=4.77, P<0.001; t=6.43, P<0.001; t=11.95, P<0.001; t=7.79, P<0.001). In parallel, the four indexes aforementioned of CAL group were lower than those of NCAL group ( t=3.16, P=0.003; t=4.13, P<0.001; t=5.42, P<0.001; t=4.05, P<0.001). Upon rhJagged1 stimulation for 48 hours, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in CD4 + T cells in KD patients and control group was significantly higher than those of untreated group [(KD: t=15.36, P<0.001; t=7.25, P<0.001; t=14.29, P<0.001), (Ctrl: t=7.87, P<0.001; t=5.71, P<0.001; t=8.74, P<0.001)], as the binding ability of RBP-J with Foxp3 promoter increased slightly without statistically significant difference (KD: t=1.11, P>0.05; Ctrl: t=1.37, P>0.05). Simultaneously, H4Ac level of Foxp3 promoter and its binding abilities with NICD1 and p300 in KD group were still lower than those of the control group after stimulation ( t=3.86, P<0.001; t=3.42, P=0.001; t=2.85, P=0.006). ④ After incubation of PBMC from heathy children with KD serum, the proportion of Treg cells, protein level of Foxp3 and expressions of Notch1 and RBP-J in CD4 + T cells in the group treated with IVIG increased significantly compared with the untreated group ( t=7.10, P<0.001; t=10.16, P<0.001; t=8.06, P<0.001; t=9.77, P<0.001), as well as H4Ac level of Foxp3 promoter and its binding abilities with NICD1 in the group treat with IVIG were also higher than the latter ( t=7.24, P<0.001; t=8.24, P<0.001). Conclusion:Insufficiency and impaired function of Treg caused by aberrant Notch1 signaling may be the important factor contributing to immune dysfunction and vascular damage in KD.
9.Changes and significance of granulocyte-like myeloid-derived suppressor cells during acute phase of Kawasaki disease
Pengqiang WEN ; Guobing WANG ; Jiehua MEI ; Zhongxiang QI ; Li YANG ; Mingguo XU ; Cong LIU ; Chengrong LI
Chinese Journal of Microbiology and Immunology 2022;42(7):540-548
Objective:To investigate the changes and significance of granulocyte-like myeloid-derived suppressor cells (G-MDSC) in the acute phage of Kawasaki disease (KD).Methods:Forty-two children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC, the concentration of reactive oxygen species (ROS) and the expression of arginase-1 (Arg-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte associated protein 4 (CTLA4), glycoprotein 130 (gp130) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) at protein level were detected by flow cytometry. Quantitative real-time PCR was used to measure the expression of inducible nitric oxide synthase (iNOS), interferon regulatory factor 8 (IRF-8), IL-6 receptor α subunit (IL-6Rα), granulocyte colony-stimulating factor receptor (G-CSFR), CCAAT/enhancer binding protein β (C/EBPβ), suppressor of cytokine signaling 1 (SOCS1) and SOCS3 at mRNA level in G-MDSC. Chromatin immunoprecipitation was performed to detect the acetylation of histone H3 at the promoters of SOCS1 and SOCS3 genes. Plasma concentrations of IL-6 and granulocyte colony-stimulating factor (G-CSF) and protein levels of IL-10, transforming growth factor-β (TGF-β) and nitric oxide (NO) in the culture supernatant of G-MDSC stimulated with LPS were measured by ELISA. Results:(1) Compared with the control group, the proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC as well as the concentration of ROS and the expression of inhibitory molecules (Arg-1, PD-L1 and CTLA4) in G-MDSC increased significantly in patients with acute KD ( P<0.05). Moreover, the concentrations of IL-10 and TGF-β in culture supernatant of G-MDSC were also higher than those of the control group after stimulation with lipopolysaccharide for 48 h ( P<0.05). All of the seven afore-mentioned indexes in KD patients with coronary artery lesion (CAL group ) were lower than those in patients without coronary artery lesion (NCAL group) ( P<0.05), and restored to some extent after IVIG therapy ( P<0.05). There were no statistical differences in iNOS expression or NO concentration in culture supernatant of G-MDSC among different groups ( P<0.05). (2) Plasma concentrations of IL-6 and G-CSF, and the expression of IL-6Rα, gp130, G-CSFR, pSTAT3 and C/EBPβ increased remarkably during acute phase of KD ( P<0.05). The expression of IRF-8 at transcription level in patients with acute KD was found to be lower than that of healthy controls ( P<0.05), and restored significantly after IVIG therapy ( P<0.05). Moreover, the plasma concentrations of IL-6 and G-CSF and the expression of IL-6Rα, gp130, G-CSFR and IRF-8 in the CAL group were higher than those in the NCAL group ( P<0.05), while the expression of pSTAT3 and C/EBPβ was lower in the CAL group ( P<0.05), which were restored by IVIG therapy ( P<0.05). (3) In patients with acute KD, the expression of SOCS1 and SOCS3 at mRNA level and histone acetylation at the promoters of SOCS1 and SOCS3 genes were reduced significantly in comparison with those in healthy controls ( P<0.05) , but were increased remarkably after IVIG treatment( P<0.05). The four indexes were higher in the CAL group than in the NCAL group ( P<0.05). Pearson correlation analysis showed the expression of SOCS1 and SOCS3 was negatively correlated with the protein level of pSTAT3 in G-MDSC of patients with acute KD ( r=-0.46 and -0.32, P<0.05). Conclusions:Changes in the number and function of G-MDSC caused by aberrant histone acetylation at SOCS1 and SOCS3 genes might contribute to the immune dysfunction and vascular damage in patients with KD.
10.Analysis and follow-up of home mechanical ventilation in 11 children with chronic respiratory failure
Bizhen ZHU ; Lihua LIN ; Jinzhun WU ; Guobing CHEN ; Yungang YANG
Chinese Journal of General Practitioners 2021;20(1):84-88
Objective:To explore the feasibility and safety of long-term home mechanical ventilation(HMV) in children with chronic respiratory failure.Methods:Clinical data of 11 children with chronic respiratory failure, who underwent HMV with the care of the First Affiliated Hospital of Xiamen University from January 2013 to December 2019, were retrospectively reviewed. The clinical manifestation, growth and development, quality of life, adverse events and prognosis of HMV children were analyzed.Results:There were 8 boys and 3 girls with the onset age of 26 days to 13 years old; and the age at starting HMV was 3 months to 13 years old. Eight children were diagnosed as neuromuscular diseases, and 3 children were diagnosed as respiratory diseases. The duration of institutional mechanical ventilation was 2 weeks to 8 months. Six patients underwent invasive HMV via a tracheostomy, and 5 received non-invasive ventilation via nasal and face masks. Bi-level positive airway pressure ventilation mode was applied in all the patients. The duration of HMV was 3 months to 27 months. During follow-up, no HMV related adverse events were observed. Both the quality of life and nutritional status were improved in all cases. One patient lost follow-up 9 months later and 1 patient died of severe adenovirus pneumonia during hospitalization for examination, the remaining 9 cases survived. Liberation from HMV was obtained in 4 patients. The frequency of readmission was 1 to 2 times.Conclusion:It is suggested that long-term HMV is safe and feasible for children with chronic respiratory failure.


Result Analysis
Print
Save
E-mail