1.Expression and functional study of FKBP10 in oral squamous cell carcinoma
FANG Zhikai ; JIN Hui ; YANG Shan ; JIANG Nan ; ZHANG Mingyu ; ZHOU Shuang ; LI Chang ; LI Lili
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):529-541
Objective:
To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC.
Methods:
A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot.
Results:
According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05).
Conclusion
FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.
2.Application study of platelet-rich plasma combined with arterial supercharging technique to enhance survival of ischemic cross-body region skin flaps in rabbits.
Huajian ZHOU ; Mingyu JIA ; Zhihong CHEN ; Yangyang LIU ; Kuankuan ZHANG ; Zhonglian ZHU ; Min WU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(7):873-880
OBJECTIVE:
To investigate the effects of combined platelet-rich plasma (PRP) and arterial supercharging technique on the survival rate and functional restoration of cross-body region skin flaps in rabbits.
METHODS:
Twelve healthy 6-month-old New Zealand White rabbits were randomly assigned to 4 groups ( n=3): sham group, PRP group, anastomosis group, and combined treatment group. An axial skin flap with an area of 12 cm×6 cm on the inner side of the hind limbs of all animals were prepared, with the saphenous artery as the main blood supply. Following the ligation of both the proximal and distal ends of the saphenous artery across all groups, the sham group received no further intervention, the PRP group was subjected to PRP injection, the anastomosis group underwent in situ end-to-end anastomosis of the distal saphenous artery, and the combined treatment group received both in situ distal saphenous artery anastomosis and PRP administration. Flap survival was evaluated and recorded on postoperative days 1, 3, and 7, with survival rates calculated accordingly. On day 7, flap tissue samples were harvested for HE staining to assess basal tissue morphology. Additionally, immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and CD31 in the flap tissues.
RESULTS:
At postoperative day 1, no significant difference in flap survival rates were observed among the 4 groups ( P>0.05). At day 3, the PRP group showed no significant difference compared to the sham group ( P>0.05); however, both the anastomosis and combined treatment groups exhibited significantly higher survival rates than the sham group ( P<0.05), the combined treatment group further demonstrated superior survival rates compared to both the PRP and anastomosis groups ( P<0.05). At day 7, the combined treatment group maintained significantly higher survival rates than all other groups ( P<0.05), while both the PRP and anastomosis groups exceeded the sham group ( P<0.05). HE staining at day 7 revealed persistent inflammatory cell infiltration, sheet-like erythrocyte deposition, and disordered collagen fibers in the sham group. The PRP group showed nascent microvessel formation and early collagen reorganization, whereas the anastomosis group displayed mature microvasculature with resolved interstitial edema. The combined treatment group exhibited differentiated microvessels with densely packed collagen bundles. Immunohistochemical analysis at day 7 demonstrated significantly larger relative area percentages of α-SMA, VEGF, and CD31 positive cells in the combined treatment group compared to all other groups ( P<0.05). Both the PRP and anastomosis groups also showed significantly higher values than the sham group ( P<0.05).
CONCLUSION
The combination of PRP and arterial supercharging techniques significantly enhances flap healing, potentially through mechanisms involving augmented angiogenesis and improved blood supply.
Animals
;
Rabbits
;
Platelet-Rich Plasma
;
Surgical Flaps/blood supply*
;
Graft Survival
;
Anastomosis, Surgical/methods*
;
Ischemia/surgery*
;
Arteries/surgery*
;
Skin/blood supply*
;
Vascular Endothelial Growth Factor A/metabolism*
;
Male
;
Skin Transplantation/methods*
3.Preparation of calcium phosphate nanoflowers and evaluation of their antioxidant and osteogenic induction capabilities in vitro.
Mingyu JIA ; Zhihong CHEN ; Huajian ZHOU ; Yukang ZHANG ; Min WU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(9):1203-1211
OBJECTIVE:
To investigate the antioxidant and osteogenic induction capabilities of calcium phosphate nanoflowers (hereinafter referred to as nanoflowers) in vitro at different concentrations.
METHODS:
Nanoflowers were prepared using gelatin, tripolyphosphate, and calcium chloride. Their morphology, microstructure, elemental composition and distribution, diameter, and molecular constitution were characterized using scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive spectroscopy. Femurs and tibias were harvested from twelve 4-week-old Sprague Dawley rats, and bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured using the whole bone marrow adherent method, followed by passaging. The third passage cells were identified as stem cells by flow cytometry and then co-cultured with nanoflowers at concentrations of 0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 2.8, 3.2, and 3.6 mg/mL. Cell counting kit 8 (CCK-8) assay was performed to screen for the optimal concentration that demonstrated the best cell viability, which was subsequently used as the experimental concentration for further studies. After co-culturing BMSCs with the screened concentration of nanoflowers, the biocompatibility of the nanoflowers was verified through live/dead cell staining, scratch assay, and cytoskeleton staining. The antioxidant capacity was assessed by using reactive oxygen species (ROS) fluorescence staining. The in vitro osteoinductive ability was evaluated via alkaline phosphatase (ALP) staining, alizarin red staining, and immunofluorescence staining of osteocalcin (OCN) and Runt-related transcription factor 2 (RUNX2). All the above indicators were compared with the control group of normally cultured BMSCs without the addition of nanoflowers.
RESULTS:
Scanning electron microscopy revealed that the prepared nanoflowers exhibited a flower-like structure; transmission electron microscopy scans discovered that the nanoflowers possessed a multi-layered structure, and high-magnification images displayed continuous atomic arrangements, with the nanoflower diameter measuring (2.00±0.25) μm; energy-dispersive spectroscopy indicated that the nanoflowers contained elements such as C, N, O, P, and Ca, which were uniformly distributed across the flower region; Fourier transform infrared spectroscopy analyzed the absorption peaks of each component, demonstrating the successful preparation of the nanoflowers. Through CCK-8 screening, the concentrations of 0.8, 1.2, and 1.6 mg/mL were selected for subsequent experiments. The live/dead cell staining showed that nanoflowers at different concentrations exhibited good cell compatibility, with the 1.2 mg/mL concentration being the best (P<0.05). The scratch assay results indicated that the cell migration ability in the 1.2 mg/mL group was superior to the other groups (P<0.05). The cytoskeleton staining revealed that the cell morphology was well-extended in all concentration groups, with no significant difference compared to the control group. The ROS fluorescence staining demonstrated that the ROS fluorescence in all concentration groups decreased compared to the control group after lipopolysaccharide induction (P<0.05), with the 1.2 mg/mL group showing the weakest fluorescence. The ALP staining showed blue-purple nodular deposits around the cells in all groups, with the 1.2 mg/mL group being significantly more prominent. The alizarin red staining displayed orange-red mineralized nodules around the cells in all groups, with the 1.2 mg/mL group having more and denser nodules. The immunofluorescence staining revealed that the expressions of RUNX2 and OCN proteins in all concentration groups increased compared to the control group, with the 1.2 mg/mL group showing the strongest protein expression (P<0.05).
CONCLUSION
The study successfully prepares nanoflowers, among which the 1.2 mg/mL nanoflowers exhibits excellent cell compatibility, antioxidant properties, and osteogenic induction capability, demonstrating their potential as an artificial bone substitute material.
Animals
;
Osteogenesis/drug effects*
;
Mesenchymal Stem Cells/drug effects*
;
Calcium Phosphates/pharmacology*
;
Rats, Sprague-Dawley
;
Rats
;
Antioxidants/chemistry*
;
Cells, Cultured
;
Cell Differentiation/drug effects*
;
Nanostructures/chemistry*
;
Tissue Engineering/methods*
;
Bone Marrow Cells/cytology*
;
Coculture Techniques
;
Tissue Scaffolds/chemistry*
;
Male
;
Biocompatible Materials/chemistry*
;
Cell Survival
;
Core Binding Factor Alpha 1 Subunit/metabolism*
;
Cell Proliferation
4.Mortality from cerebrovascular diseases in China: Exploration of recent and future trends
Bin LV ; Ge SONG ; Feng JING ; Mingyu LI ; Hua ZHOU ; Wanjun LI ; Jiacai LIN ; Shengyuan YU ; Jun WANG ; Xiangyu CAO ; Chenglin TIAN
Chinese Medical Journal 2024;137(5):588-595
Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.
5.Measurement of pelvic parameters by magnetic resonance imaging to predict surgical difficulty of robot-assisted total mesorectal excision for mid and low rectal cancer
Mingyu HAN ; Xiaofei DUAN ; Quanbo ZHOU ; Weitang YUAN ; Yugui LIAN
Chinese Journal of Gastrointestinal Surgery 2024;27(8):824-832
Objective:To evaluate the relationship between pelvimetric parameters and surgical difficulty in robot-assisted total mesorectal excision (TME) performed by experienced colorectal surgeons, and to build a nomogram model.Methods:This was a retrospective observational study. The inclusion criteria were as follows: (1) tumor within 10 cm of the anal verge; (2) cancer confirmed by pathological examination of the postoperative specimen; (3) preoperative complete magnetic resonance imaging (MRI) data available; (4) depth of tumor invasion T1-3; (5) circumferential resection margin assessed as negative by MRI; and (6) R0 resection achieved. The exclusion criteria comprised (1) history of pelvic fractures; (2) history of pelvic surgery; and (3) emergency required because of tumor-related intestinal obstruction and/or perforation. Application of above criteria yielded 82 patients who had undergone robot-assisted total mesorectal excision of mid and low rectal cancer in the Department of Colorectal Surgery of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022 (modeling group). Additionally, data of 35 patients with mid and low rectal cancer who had undergone robotic-assisted TME at the same center in 2023 January–August were collected for validation of the model (validation group). The following 13 pelvic parameters were studied: pelvic inlet diameter, pelvic outlet diameter, pubic tubercle height, sacral height, sacral depth, interspinous distance, inter-tuberosity distance, lateral mesorectal span, anterior-posterior mesorectal span, anterior mesorectal thickness, posterior mesorectal thickness, rectal area, and mesorectal area. Operating time was used as an indicator of the degree of surgical difficulty, this being defined as the time from the start of skin incision to the end of abdominal closure. Variables related to the duration of surgery were subjected to univariate and multivariate logistic regression analyses to identify factors associated with the difficulty of TME, after which a nomogram for predicting the difficulty of the procedure was established. We constructed receiver operating characteristic and calibration curves to validate the predictive power of nomogram. Furthermore, data from the validation group were used for external validation of the model.Results:The model group comprised 82 patients, including 54 men and 28 women of median age 61.0 years. The median body mass index (BMI) was 23.7 kg/m 2, median distance between the tumor and anal verge 6.1 cm, and median tumor diameter 4.5 cm. Fourteen of these patients had received preoperative adjuvant therapy and 12 had a history of abdominal surgery. There were 35 patients (24 men and 11 women) of median age 64.0 years in the validation group. Their median BMI was 23.7 kg/m 2 and median distance between the tumor and anal verge 6.3 cm. Multivariable analyses of the model group showed that BMI (OR=1.227, 95%CI: 1.240–1.469, P=0.026), distance between the tumor and anal verge (OR=0.733, 95%CI: 0.562–0.955, P=0.022), and interspinous distance (OR=0.468, 95%CI: 0.270–0.812, P=0.007) were independent predictors of surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC=0.804, 95%CI: 0.707–0.900). Calibration curves showed that the S:P in this model was 0.987 and the C-index 0.804. Area under the receiver operating characteristic curve of the predictive model in the validation dataset was 0.767 (95%CI: 0.606–0.928). Conclusion:MRI-based measurements of pelvic parameters are associated with difficulty of performing robot-assisted TME for mid and low rectal cancer. Our nomogram model constructed based on measurements of pelvic parameters has a good predictive ability.
6.Measurement of pelvic parameters by magnetic resonance imaging to predict surgical difficulty of robot-assisted total mesorectal excision for mid and low rectal cancer
Mingyu HAN ; Xiaofei DUAN ; Quanbo ZHOU ; Weitang YUAN ; Yugui LIAN
Chinese Journal of Gastrointestinal Surgery 2024;27(8):824-832
Objective:To evaluate the relationship between pelvimetric parameters and surgical difficulty in robot-assisted total mesorectal excision (TME) performed by experienced colorectal surgeons, and to build a nomogram model.Methods:This was a retrospective observational study. The inclusion criteria were as follows: (1) tumor within 10 cm of the anal verge; (2) cancer confirmed by pathological examination of the postoperative specimen; (3) preoperative complete magnetic resonance imaging (MRI) data available; (4) depth of tumor invasion T1-3; (5) circumferential resection margin assessed as negative by MRI; and (6) R0 resection achieved. The exclusion criteria comprised (1) history of pelvic fractures; (2) history of pelvic surgery; and (3) emergency required because of tumor-related intestinal obstruction and/or perforation. Application of above criteria yielded 82 patients who had undergone robot-assisted total mesorectal excision of mid and low rectal cancer in the Department of Colorectal Surgery of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022 (modeling group). Additionally, data of 35 patients with mid and low rectal cancer who had undergone robotic-assisted TME at the same center in 2023 January–August were collected for validation of the model (validation group). The following 13 pelvic parameters were studied: pelvic inlet diameter, pelvic outlet diameter, pubic tubercle height, sacral height, sacral depth, interspinous distance, inter-tuberosity distance, lateral mesorectal span, anterior-posterior mesorectal span, anterior mesorectal thickness, posterior mesorectal thickness, rectal area, and mesorectal area. Operating time was used as an indicator of the degree of surgical difficulty, this being defined as the time from the start of skin incision to the end of abdominal closure. Variables related to the duration of surgery were subjected to univariate and multivariate logistic regression analyses to identify factors associated with the difficulty of TME, after which a nomogram for predicting the difficulty of the procedure was established. We constructed receiver operating characteristic and calibration curves to validate the predictive power of nomogram. Furthermore, data from the validation group were used for external validation of the model.Results:The model group comprised 82 patients, including 54 men and 28 women of median age 61.0 years. The median body mass index (BMI) was 23.7 kg/m 2, median distance between the tumor and anal verge 6.1 cm, and median tumor diameter 4.5 cm. Fourteen of these patients had received preoperative adjuvant therapy and 12 had a history of abdominal surgery. There were 35 patients (24 men and 11 women) of median age 64.0 years in the validation group. Their median BMI was 23.7 kg/m 2 and median distance between the tumor and anal verge 6.3 cm. Multivariable analyses of the model group showed that BMI (OR=1.227, 95%CI: 1.240–1.469, P=0.026), distance between the tumor and anal verge (OR=0.733, 95%CI: 0.562–0.955, P=0.022), and interspinous distance (OR=0.468, 95%CI: 0.270–0.812, P=0.007) were independent predictors of surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC=0.804, 95%CI: 0.707–0.900). Calibration curves showed that the S:P in this model was 0.987 and the C-index 0.804. Area under the receiver operating characteristic curve of the predictive model in the validation dataset was 0.767 (95%CI: 0.606–0.928). Conclusion:MRI-based measurements of pelvic parameters are associated with difficulty of performing robot-assisted TME for mid and low rectal cancer. Our nomogram model constructed based on measurements of pelvic parameters has a good predictive ability.
7.Tanshinone ⅡA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 13C metabolic flux analysis
Shan BAIXI ; Zhou HAOYAN ; Guo CONGYING ; Liu XIAOLU ; Wu MINGYU ; Zhai RAO ; Chen JUN
Journal of Pharmaceutical Analysis 2024;14(2):244-258
Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.
8.Does the homologous booster with the inactivated coronavirus disease 2019 vaccine work for the omicron variant? Real-world evidence from Jilin, China.
Jun GUO ; Lei ZHA ; Kai ZENG ; Mingyu SHAO ; Dan CHEN ; Bing WANG ; Yun ZHOU ; Gang YANG ; Xue ZHANG ; Xia ZOU ; Yan ZHANG ; Yan KANG
Chinese Medical Journal 2023;136(23):2892-2894
9.Efficacy and safety of Omalizumab for the treatment of pediatric allergic asthma: a retrospective multicenter real-world study in China
Li XIANG ; Baoping XU ; Huijie HUANG ; Mian WEI ; Dehui CHEN ; Yingying ZHAI ; Yingju ZHANG ; Dan LIANG ; Chunhui HE ; Wei HOU ; Yang ZHANG ; Zhimin CHEN ; Jingling LIU ; Changshan LIU ; Xueyan WANG ; Shan HUA ; Ning ZHANG ; Ming LI ; Quan ZHANG ; Leping YE ; Wei DING ; Wei ZHOU ; Ling LIU ; Ling WANG ; Yingyu QUAN ; Yanping CHEN ; Yanni MENG ; Qiusheng GE ; Qi ZHANG ; Jie CHEN ; Guilan WANG ; Dongming HUANG ; Yong YIN ; Mingyu TANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(1):64-71
Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.
10.Correlation between CITP/MMP-1 ratio and myocardial fibrosis in patients with chronic heart failure
Yuting LIU ; Weili GUO ; Guiying DU ; Tian ZHOU ; Xuejing HAN ; Mingyu JIA ; Lijuan FAN ; Kegang JIA
Chinese Journal of Laboratory Medicine 2023;46(12):1259-1267
Objective:To investigate the association between CITP/MMP-1 ratio and the severity of Myocardial fibrosis (MF) in patients with Chronic Heart failure (CHF) and its diagnostic and prognostic value in patients with MF.Methods:A retrospective study was conducted to select 110 cases [86 males, (56.60±11.15) years old;24 females, (60.06±12.02) years old] who were hospitalized in the Department of Cardiology, Teda International Cardiovascular Hospital from May 18, 2021 to February 30, 2022 and underwent magnetic magnetic examination. Serum CITP and MMP-1 were detected by enzyme-linked immunoassay and CITP/MMP-1 ratio was calculated. Plasma brain natriuretic peptide (BNP) was detected by automatic chemiluminescence analyzer. Anova and non-parametric test were used to compare the difference of indexes among all groups. Spearman analysis was used to analyze the correlation between serum collagen metabolites and the severity of myocardial fibrosis. Logistic regression analysis was performed for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of related indexes. Major adverse cardiac events within 1 year after discharge were recorded, including cardiogenic death, HF rehospitalization, malignant arrhythmia, and myocardial infarction. The risk factors of poor prognosis were analyzed by Cox regression. Patients were divided by the median value of CITP/MMP-1 ratio or the median value of CITP/MMP-1 ratio and BNP. Survival analysis was performed by Kaplan-Meier and Log Rank test was performed.Results:Serum MMP-1 and BNP in LGE (+) group were higher than those in LGE (-) group (1.79 ng/ml > 0.91 ng/ml, Z=-2.924; 503 pg/ml > 367 pg/ml, Z=-1.932; P<0.05); The CITP/MMP-1 ratio in the LGE (+) group was lower than that in the LGE (-) group (3.84 < 10.85, Z=-3.601, P<0.001). MMP-1 in CHF with arrhythmia group was higher than that in CHF group (1.98 ng/ml > 1.25 ng/ml, Z=-2.016), while CITP/MMP-1 ratio was lower than that in CHF group (3.25 < 5.73, Z=-2.751), all P<0.05. CITP/MMP-1 ratio in CHF patients was negatively correlated with the severity of MF ( r=-0.363, P<0.001), and BNP and MMP-1 were positively correlated with the severity of MF ( r=0.267, r=0.264, P<0.05). Serum BNP was positively correlated with collagen metabolite MMP-1 and negatively correlated with CITP/MMP-1 ratio (all P<0.05). Logistic multivariate regression analysis showed that only CITP/MMP-1 was a predictor of myocardial fibrosis, with an OR value of 0.624 ( P=0.005). ROC curve was used to evaluate serum BNP, MMP-1 and CITP/MMP-1 ratio in the diagnosis of myocardial fibrosis in HF patients, with AUC of 0.653, 0.696 and 0.754, respectively. The accuracy of CITP/MMP-1 ratio in diagnosing fibrosis was better than that of BNP by comparing their AUC, and the difference was statistically significant ( Z=-3.808, P<0.001). Cox regression analysis showed that CITP/MMP-1 ≤3.84 was a risk factor for poor prognosis, OR=2.647 ( P=0.009). Kaplan-Meier survival analysis at 1-year follow-up showed that the survival rate of the group with lower CITP/MMP-1 ratio was significantly lower than that of the group with higher CITP/MMP-1 ratio ( P=0.014). The survival rate of CITP/MMP-1 increased and BNP decreased group was higher than that of CITP/MMP-1 decreased and BNP increased group ( P=0.011). Conclusions:The ratio of CITP/MMP-1 can be used as a negative correlation indicator of the degree of cross-linking, which is better than BNP in the evaluation of MF, and has a good auxiliary diagnostic value for myocardial fibrosis in patients with chronic heart failure, and is expected to become a protective indicator for patients with chronic heart failure and be used in clinical evaluation of myocardial fibrosis. CITP/MMP-1 ratio is associated with the incidence of major adverse cardiac events, and CITP/MMP-1 ≤3.84 can be used as a predictor of prognostic adverse cardiovascular events in CHF patients.


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