1.Intensive phototherapy don't affect cellular immune function and short-term reactions after discharge in neonatal hyperbilirubinemia
Zhen LIU ; Dalian WANG ; Jie ZHANG ; Qixing ZHANG ; Fei WANG
Basic & Clinical Medicine 2024;44(3):379-383
Objective To investigate the effect of intensive phototherapy for neonatal hyperbilirubinemia on cellular immune function and short-term immune-related adverse effects.Methods Totally 180 infants with hyperbilirubi-nemia were treated with different light intensity,the efficacy,cellular immune function and immune adverse effects were followed up for six months after discharge.Results After phototherapy,serum interleukin-6(IL-6)in both groups were decreased and CD4+(%)and CD4+/CD8+were increased than that before phototherapy.The decrease rate of total bilirubin in the intensive phototherapy group was significantly faster than that in the conventional photo-therapy group,at the same time,the total duration of phototherapy and hospital stay were significantly shorter than that in the conventional phototherapy group(P<0.05).No statistical significance in the incidence of diarrhea,rash,fever and hypo-calcemia during hospitalization and no immune-related adverse effects in 6 months after discharge were recorded.Conclusions Compared with conventional phototherapy,intensive phototherapy reduces serum bilirubin level more quickly and shorten the duration of phototherapy and hospital stay.No common adverse effects nor immune-related adverse effects are recorded during hospitalization and the period of six months after discharge.
2.Construction and Validation of A Deep Learning-based Bone Age Prediction Model for Children Living in Both Plain and Highland Regions
Qixing LIU ; Huogen WANG ; Wangjiu CIDAN ; Awang TUDAN ; Meijie YANG ; Qiongda PUQIONG ; Xiao YANG ; Hui PAN ; Fengdan WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1439-1446
To construct and validate a deep learning-based bone age prediction model for children living in both plain and highland regions. A model named "ethnicity vision gender-bone age net (EVG-BANet)" was trained using three datasets, including the Radiology Society of North America (RSNA) dataset [training set( EVG-BANet exhibited MAD of 0.34 and 0.52 years in RSNA and RHPE test sets, respectively. In the self-established test set, the model achieved MAD of 0.47 years (95% CI: 0.43-0.50) with accuracy within 1 year of 97.72% (95% CI: 95.56-99.01%). For the external test set, MAD was 0.53 years(95% CI: 0.48-0.58), with accuracy within 1 year of 89.45% (95% CI: 85.03-92.93). EVG-BANet demonstrated high accuracy in bone age prediction, and therefore can be applied in children living in both plain and highland.
3.Construction and Validation of A Deep Learning-based Bone Age Prediction Model for Children Living in Both Plain and Highland Regions
Qixing LIU ; Huogen WANG ; Wangjiu CIDAN ; Awang TUDAN ; Meijie YANG ; Qiongda PUQIONG ; Xiao YANG ; Hui PAN ; Fengdan WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1439-1446
To construct and validate a deep learning-based bone age prediction model for children living in both plain and highland regions. A model named "ethnicity vision gender-bone age net (EVG-BANet)" was trained using three datasets, including the Radiology Society of North America (RSNA) dataset [training set( EVG-BANet exhibited MAD of 0.34 and 0.52 years in RSNA and RHPE test sets, respectively. In the self-established test set, the model achieved MAD of 0.47 years (95% CI: 0.43-0.50) with accuracy within 1 year of 97.72% (95% CI: 95.56-99.01%). For the external test set, MAD was 0.53 years(95% CI: 0.48-0.58), with accuracy within 1 year of 89.45% (95% CI: 85.03-92.93). EVG-BANet demonstrated high accuracy in bone age prediction, and therefore can be applied in children living in both plain and highland.
4.Changes of complement fragment C3a and its receptor in lung injury induced by silica nanoparticles
Sifan ZHOU ; Zhoujian WANG ; Lei GAO ; Yuansheng DUAN ; Muyue CHEN ; Jiaxiang ZHANG ; Qixing ZHU
Journal of Environmental and Occupational Medicine 2023;40(8):877-883
Background Silica nanoparticles (SiNPs) enter the human body through respiratory tract, digestive tract, and skin, causing body damage. Lung is one of the main damaged organs. Objective To observe the expressions of complement activated fragment C3a and its receptor C3aR in the lungs of mice exposed to SiNPs through respiratory tract, and to explore the involvement of C3a/C3aR in lung injury induced by SiNPs exposure. Methods The ultrastructure of SiNPs (particle size 5-20 nm) was determined under a transmission electron microscope, and the hydrodynamic diameter and surface Zeta potential of SiNPs were determined using a nanoparticle size analyzer. A total of 88 SPF C57BL/6J mice were randomly divided into five groups: a blank control group without any treatment (14 mice), a vehicle control group treated with 50 μL stroke-physiological saline solution by intratracheal instillation (14 mice), and three SiNPs exposure groups (low-dose group, medium-dose group, and high-dose group with 20 mice in each group, who were given 50 μL SiNPs suspension of 7, 21, and 35 mg·kg−1 respectively and exposed once every 3 days for 5 times). The mice were anesthetized on day 1 (1-day model group) and day 15 (15-day model group) after exposure, then sacrificed after extraction of bronchoalveolar lavage fluid (BALF), and lung tissues were retained. The morphological changes of lung tissues were observed by HE staining, the expression level of C3a in BALF was detected by enzyme-linked immunosorbent assay, the deposition of C3a and C3aR in lung tissues were observed by immunohistochemistry, the protein expression level of C3aR was determined by Western blotting, and the localization and semi-quantitative detection of C3a and C3aR in lung tissues was observed by immunofluorescence. Results SiNPs agglomerated in stroke-physiological saline solution. The average hydrodynamic diameter was (185.60±7.39) nm and the absolute value of Zeta potential was (43.33±0.76) mV. The condition of mice in the 1-day model group and the 15-day model group was good, while 2 mice died in the medium-dose group of the 1-day model group due to misoperation. The autopsy results of the two mice showed congestion of the lung tissue, emphysema, and no imperfection of trachea integrity. No death was observed in other dose groups. The HE staining results showed pathological damage to the mouse lung, including alveolar wall thickening and inflammatory cell infiltration after SiNPs exposure. The pathological damage became more serious with the increase of dose. Regarding pathological changes, the 15-day model group was slightly relieved compared with the 1-day model group, but there were still pathological changes. The enzyme-linked immunosorbent assay results showed that there was no difference in the expression level of C3a between the blank control group and the vehicle control group (P>0.05), the expression levels of C3a in the medium-dose group and the high-dose group were significantly higher than that in the vehicle control group (P<0.05). The immunohistochemistry results showed that C3a deposition was consistent with the enzyme-linked immunosorbent assay results. The Western blotting and the immunohistochemistry results showed that C3aR expression was low in the blank control group and the vehicle control group, while the expression in each dose group tended to increase with the increase of dose. The immunofluorescence results showed that the fluorescence signals of C3a and C3aR were weak in the blank control group and the vehicle control group in the 1-day model group and the 15-day model group, while the fluorescence signals in the lung tissues of mice in the SiNPs exposure groups tended to increase with the increase of dose. Conclusion The increased expressions of C3a and C3aR in complement activation may be related to lung injury induced by intratracheal instillation of SiNPs, suggesting that C3a/C3aR may be involved in lung injury induced by SiNPs exposure.
5.Effects of lung rehabilitation based on Spiro-tiger training apparatus on respiratory mechanics and airway remodeling in stable COPD patients
Jie DING ; Wenhai XIANG ; Qixing WANG ; Xiuling GONG ; Yang YANG ; Guili WANG ; Wei XIAO
Chinese Journal of Medical Physics 2023;40(12):1558-1563
Objective To explore the effects of lung rehabilitation using Spiro-tiger training apparatus on the respiratory mechanics and airway remodeling in patients with chronic obstructive pulmonary disease(COPD)in stable stage.Methods Ninety-three stable COPD patients admitted to Nanxiang Branch of Shanghai Ruijin Hospital were randomly divided into control group(46 cases)and observation group(47 cases).Control group was treated with the training for pursed lips breathing and abdominal breathing,and observation group was trained with Spiro-tiger training apparatus in addition to the treatment given to control group.Both groups were intervened continuously for 9 weeks.The two groups were compared in terms of respiratory mechanics(respiratory frequency,tidal volume,minute ventilation,and peak respiratory pressure),airway remodeling[matrix metalloproteinase-9(MMP-9),vascular endothelial growth factor(VEGF),and transforming growth factor-β1(TGF-β1)],and lung function[forced vital capacity(FVC),forced expiratory volume in the first second(FEV1),and FEV1/FVC],blood gas analysis indexes[arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2)],6-minute walking distance(6MWD)and health status[Borg scale and St.George's respiratory questionnaire(SGRQ)].The patients were followed up for 6 months,and the incidence of acute exacerbation of COPD was recorded.Results After 9 weeks of intervention,compared with control group,observation group had lower peak respiratory frequency and respiratory pressure,and higher tidal volume(P<0.05).There was no significant difference in minute ventilation between two groups(P>0.05).The levels of MMP-9,VEGF,TGF-β1 and PaCO2 were lower,and FVC,FEV1,FEV1/FVC and PaO2 were higher in observation group than in control group(P<0.05).Observation group had longer 6MWD,and lower Borg score and SGRQ score as compared with control group(P<0.05).After 6-month follow-up,the incidence of COPD acute exacerbation in observation group was lower than that in control group(4.26%vs19.57%,P<0.05).Conclusion Lung rehabilitation using Spiro-tiger training apparatus can effectively improve respiratory mechanics,lung function,blood gas analysis indexes and health status in stable COPD patients,alleviate airway remodeling,and avoid acute exacerbation of COPD.
6.Role of serum exosomal miR⁃30d⁃5p targeting RHOB in occupational medicamentosa⁃like dermatitis due to trichloroethylene
Shuyang Cai ; Hui Wang ; Xuesong Zhang ; Xulei Zuo ; Jinru Ma ; Yiting Hong ; Qifeng Wu ; Qixing Zhu
Acta Universitatis Medicinalis Anhui 2023;58(5):718-723,730
Objective:
To detect the expression of serum exosomal miR⁃30d⁃5p in occupational dermatitis medicamentosa⁃like of trichloroethylene(OMDT) patients and its correlation with liver function , then perform bioinformatics analysis and verify the target gene.
Methods :
Serum exosomes were extracted from 6 OMDT patients and 6 healthy controls , and miRNA was extracted from exosomes which were identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. The expression of serum exosomal miR⁃30d⁃5p was detected by real⁃time fluorescence quantitative PCR , then the correlation with liver function was analyzed. The target genes of miR⁃30d⁃5p were predicted by the miRWalk and miRBD databases. Gene ontology analysis and KEGG pathways analysis were performed. Finally , RHOB was verified by Dual⁃luciferase reporter assay.
Results:
The expression of serum exosomal miR⁃30d⁃5p significantly decreased in 6 OMDT patients at the peak of the disease(P < 0. 05) , and it was negatively correlated with the level of AST , ALT and GGT (correlation coefficient : rs = - 0. 943 ,P = 0. 005 ;rs = - 0. 886 , P = 0. 019 ; rs = - 0. 886 , P = 0. 019 ) . Bioinformatics analysis and dual⁃luciferase reporter assay showed that RHOB was the target gene of miR⁃30d⁃5p.
Conclusion
The expression of serum exosomal miR⁃30d-5p decreases in OMDT patients , which is negatively correlated with the level of liver function , and the target gene RHOB may be involved in the process of liver injury induced by trichloroethylene.
7.A randomized controlled study on the long-term efficacy of intra-cervical lymphatic immunotherapy for adult allergic rhinitis
Kai WANG ; Yang QIN ; Qixing WANG ; Weijun HUANG ; Qingqing YU ; Yin LI ; Yu XIONG ; Yingwei GUO ; Jun TANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(9):871-877
Objective:To determine the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT) for adult allergic rhinitis (AR) by comparing it with subcutaneous immunotherapy (SCIT).Methods:A total of 100 adult AR patients with dust mite allergy in Department of Otorhinolaryngology, First People′s Hospital of Foshan from Feb 2018 to Dec 2019 were randomly divided into two groups, 50 in SCIT group [including 42 males and 8 females, aging (32.55±9.72) years] and 50 in ICLIT group [including 45 males and 5 females, aging (31.33±9.84) years]. The changes in total symptom score (total system score, TSS), nasal symptom score (total nasal symptom score, TNSS), eye symptom score (total ocular scoring system, TOSS), drug score (total medication score, TMS), and quality of life score of the two groups of patients were evaluated before and after treatment, and the adverse reactions of all patients during the treatment period were recorded. The changes in the level of dust mite specific IgE (sIgE) in the serum were evaluated. GraphPad Prism 9.0 software was used for statistical analysis.Results:In the SCIT group, 38 patients completed treatment and follow-up, with a dropout rate of 24%. In the ICLIT group, 48 patients completed treatment and follow-up, with a dropout rate of only 4%. The scores of TSS, TNSS, TOSS, TMS, and quality of life in the ICLIT group before treatment were 32.1±3.0, 27.3±3.1, 4.8±2.8, 2.3±0.9, and 68.1±28.7, respectively; After 36 months of treatment, the scores were 21.8±11.4, 18.1±9.4, 3.7±2.9, 1.3±1.1, and 36.0±26.7, respectively, which were significantly lower than those before treatment (all P<0.001). After 36 months of treatment, the TSS of the ICLIT group improved by 10.3±11.2 compared to before, while the TSS of the SCIT group improved significantly by 21.9±11.0 compared to before, with statistically significant differences between the groups ( P<0.001). No serious systemic adverse reactions occurred in both groups of patients. Conclusions:ICLIT treatment for adult AR has long-term efficacy, high safety, and high compliance, but its long-term efficacy is not as good as SCIT. ICLIT can be considered as a new complementary option for AR immunotherapy.
8.Effect of oral exposure to trichloroethylene on JMJD3 expression and polarization of M1 Kupffer cells
Hua HUANG ; Baiwang DING ; Xulei ZUO ; Yi YANG ; Jiale PENG ; Yican WANG ; Jiaxiang ZHANG ; Qixing ZHU
Journal of Environmental and Occupational Medicine 2022;39(1):65-70
Background Trichloroethylene (TCE) can enter human body through biological accumulation of polluted water or air, resulting in health hazards. The most commonly involved organs are the liver. Objective To observe potential polarization of M1 Kupffer cells (KCs) in mice liver exposed to TCE orally, and to investigate the relationship between histones lysin demethylase JMJD3 and M1 KCs polarization. Methods A total of 72 SPF BALB/c mice aged 6 to 8 weeks were randomly divided into a blank control group (n=18), a vehicle control group (n=18), a 2.5 mg·mL−1 TCE group (n=18), and a 5.0 mg·mL−1 TCE group (n=18) after adaptive feed for one week. A TCE transoral exposure model was established after eight weeks of administration according to previous research of the research group. In the 2nd, 4th, and 8th weeks, the mice were sacrificed and liver tissue samples were collected. Western blotting was used to detect the expression level of JMJD3 in the liver tissue samples. Immunofluorescence was used to co-locate the macrophage marker F4/80 and the surface marker CD11c of M1 macrophages. Immunohistochemistry was used to detect the expressions of CD16/32, a marker of M1 macrophages, and TNF-α, an inflammatory factor of M1 macrophages in mouse liver. Results In the 2nd, 4th, and 8th weeks, the mice in each group were generally in good condition, and no individual died due to TCE. There was no statistically significant difference in the amount of water consumed by each group, nor in the body weight gain and the liver coefficient of mice at each time point (P>0.05). The results of Western blotting analysis showed that there was no statistically significant difference in JMJD3 protein expression level between the blank control group and the vehicle control group at each time point, the expression levels of JMJD3 protein in the 2.5 mg·mL−1 TCE group and the 5.0 mg·mL−1 TCE group were higher than that in the control group , and the expression level of JMJD3 protein in the 5.0 mg·mL−1 TCE group was higher than that in the 2.5 mg·mL−1 TCE group (P<0.05). The results of immunofluorescence co-localization showed that the expressions of F4/80 and CD11c were low in the blank control group and the vehicle control group, while the expressions of F4/80 and CD11c were increased in the 2.5 mg·mL−1 and the 5.0 mg·mL−1 TCE groups. The results of immunohistochemistry showed that the expressions of CD16/32 and TNF-α in the blank control group and the vehicle control group were low, and there were large deposits in the 2.5 mg·mL−1 TCE group and the 5.0 mg·mL−1 TCE group. Conclusion The polarization of M1 KCs and the expression of proinflammatory factors may be related to an increased expression level of JMJD3 induced by oral TCE exposure.
9.Cathepsin L aggravated kidney injury by activating PKC signal in TCE-sensitized mice
Yican Wang ; Yiting Hong ; Meng Huang ; Jiaxiang Zhang ; Feng Wang ; Jiale Peng ; Qixing Zhu
Acta Universitatis Medicinalis Anhui 2022;57(7):1116-1121
Objective:
To investigate the mechanism of cathepsin L(CTSL)-mediated kidney injury in trichloroethene(TCE)-sensitized mice.
Methods:
41 BALB/C mice were randomly divided into blank group(n=5), solvent group(n=5), TCE treatment group(n=15) and TCE+CTSLi treatment group(n=16). TCE percutaneous sensitization mouse model was established, and the mice were evaluated as positive group and negative group according to skin sensitization score. The renal pathology of mice was observed by electron microscopy and HE staining, the renal function level of mice was assessed by serum urea nitrogen(BUN). The expression of CTSL was detected by immunofluorescence, the apoptosis of renal cells was assessed by TUNEL staining, and the activation of renal protein kinase C(PKC) signal molecule was detected by Western blot.
Results:
The sensitization rates of TCE treatment group and TCE+CTSLi treatment group were 53.3%(8/15) and 50.0%(8/16), respectively, and there was no statistical difference in sensitization rates(P>0.05). Pathological results showed that TCE sensitized-mice showed edema and vacuolar degeneration of renal tubular cells, thickening of glomerular basement membrane, fusion of podocytes and mitochondria vacuolar degeneration. The results of renal function showed that the serum BUN level of TCE sensitized mice was higher than that of other groups. Immunofluorescence results showed that the expression level of CTSL in the kidney of TCE-sensitized positive mice increased(P<0.05,F=82.438), and the apoptosis level of renal structure cells was also higher than that of other groups(P<0.05). Western blot showed that the phosphorylation of PKC protein in the kidney of TCE-sensitized mice increased, while the expression of PKC protein in TCE+CTSLi sensitized mice was down-regulated after CTSLi pretreatment(P<0.05,F=35.686), the level of renal cell apoptosis decreased, and renal damage was improved.
Conclusion
CTSL might aggravate renal damage via activation of PKC signaling in TCE-sensitized mouse.
10.Cathepsin L mediates glomerular endothelial cell injury by cleavaging complement C3 in trichloroethylene-sensitized mice
Meng HUANG ; Shuangping CHEN ; Yuying DAI ; Yi YANG ; Wei JIANG ; Feng WANG ; Jiaxiang ZHANG ; Qixing ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(1):5-11
Objective:To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice.Methods:In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group ( n=5) , vehicle control group ( n=5) , TCE group ( n=15) and TCE+CTSLi group ( n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results:The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups ( P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group ( P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group ( P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group ( P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group ( P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant ( P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group ( P<0.05) . Conclusion:CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.


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