1.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
;
Dental Cementum/injuries*
;
Consensus
;
Diagnosis, Differential
;
Cone-Beam Computed Tomography
;
Tooth Fractures/therapy*
2.Thermal Ablation of Pulmonary Nodules by Electromagnetic Navigation Bronchoscopy Combined With Real-Time CT-Based 3D Fusion Navigation:Report of One Case.
Yuan XU ; Qun LIU ; Chao GUO ; Yi-Bo WANG ; Xiao-Fang WU ; Chen-Xi MA ; Gui-Ge WANG ; Qian-Shu LIU ; Nai-Xin LIANG ; Shan-Qing LI
Acta Academiae Medicinae Sinicae 2025;47(1):137-141
A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.
Humans
;
Bronchoscopy/methods*
;
Catheter Ablation/methods*
;
Cone-Beam Computed Tomography
;
Electromagnetic Phenomena
;
Imaging, Three-Dimensional
;
Lung Neoplasms/diagnostic imaging*
;
Tomography, X-Ray Computed
3.Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps
Xiangyang ZHANG ; Wei WEI ; Peng XU ; Ning LI ; Wenjing GE ; Xinyi WANG ; Ruifeng LIANG ; Airong XUE
China Pharmacy 2024;35(19):2345-2351
OBJECTIVE To explore the improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis (RA) rats by regulating neutrophil extracellular traps (NETs). METHODS Establishment of rat RA model using bovine type Ⅱ collagen and Freund’s complete adjuvant. The model rats were randomly divided into model group and low-dose, middle-dose and high-dose groups (55, 110, 220 mg/kg) of petroleum ether extract of S. divaricata; the normal group without modeling was also established, with 10 rats in each group. Each group was given corresponding drugs or constant volume of 2% Tween-80 solution intragastrically, once a day, for consecutive 28 days. The toe swelling degree in rats was observed, and the arthritis index (AI) was scored. The serum levels of interleukin-1β (IL-1β), IL-10, IL-17, tumor necrosis factor-α (TNF-α), 25-hydroxyvitamin D3 [25(OH)D3], myeloperoxidase (MPO), neutrophil elastase (NE) and NETs in rats were detected. The histopathological changes in ankle joint were observed. The expression of citrullinated histone H3 (CitH3) in ankle joint as well as the expressions of cytochrome P450 24A1 (CYP24A1), cytochrome P450 27B1 (CYP27B1),vitamin D receptor (VDR) and peptidyl arginine deiminase 4 疾病。E-mail:zhongyao626@126.com (PAD4) in synovium were all determined. RESULTS Compared with the model group, the toe swelling degree and AI score in the middle-dose and high-dose groups of petroleum ether extract of S. divaricata decreased significantly from day 14 to day 28 after administration (P<0.05 or P<0.01). The serum levels of IL-1β, IL-17, TNF-α, MPO, NE and NETs decreased significantly, while the levels of IL-10 and 25(OH)D3 increased significantly (P<0.05 or P<0.01). The widened ankle joint space and the improved structure were found; the expression of CitH3 in ankle joint, and the expressions of CYP24A1 and PAD4 in synovium were down-regulated significantly, while the expressions of CYP27B1 and VDR were up-regulated significantly in synovium (P<0.05 or P<0.01). CONCLUSIONS The petroleum ether extract of S. divaricata may inhibit the production of NETs and improve the symptoms of RA by regulating the vitamin D system.
4.Prognostic nomogram for predicting lower limb venous thrombosis in patients after craniocerebral surgery
Zhiqiang GE ; Gang ZUO ; Qian XU ; Jiyao LIANG ; Yibin CHEN ; Junjie HUO ; Ming JIANG
Journal of Clinical Surgery 2024;32(7):701-705
Objective To explore the risk factors for lower limb venous thrombosis in patients after craniocerebral surgery,and establish a prognostic nomogram for the occurrence of lower limb venous thrombosis.Methods A total of 427 patients who underwent craniotomy for craniocerebral trauma and met the inclusion criteria in the First People's Hospital of Taicang from January 2018 to December 2020 were collected as training group,and the nomogram was drawn and verified internally.And 106 patients who underwent surgery from January 2021 to June 2021 were used as test group,and the model was externally verified set.The nomogram was established and internally validated with the data of the training group,and externally validated with the data of the test group.For the training group,multivariate Logistic regression analysis was performed by including all variables with P<0.05 in univariate analysis,and established the prognostic nomogram by R software.In the training group and the test group,the performance of the nomogram was verified by C-index,calibration chart and decision curve analysis respectively.Results In the training group of 427 people,107 had lower limb venous thrombosis,with an incidence rate of 25.1%.Among the 106 people in the test group,33 developed lower limb venous thrombosis,with an incidence rate of 31.1%.Multivariate logistic regression analysis showed that age,lower preoperative GCS score,postoperative lower limb muscle strength<3,hypertension,and diabetes were independent risk factors for the occurrence of lower limb vein thrombosis after craniocerebral surgery.The C-index of this nomogram in the training group and the test group was 0.837(95%CI:0.796-0.878)and 0.933(95%CI:0.886-0.979),respectively.Conclusion The nomogram including the age,preoperative GCS score,postoperative lower limb muscle strength<3,hypertension,and diabetes can predict the probability of lower limb vein thrombosis after craniocerebral surgery with convenient discrimination and clinical utility.
5.Impact of the Size and Depth of Pulmonary Nodules on the Surgical Approach for Lung Resection in the Treatment of Early-stage Lung Cancer ≤2 cm
TANG ZAIBIN ; GE WENKE ; ZHOU DINGYE ; HE ZHICHENG ; XU JING ; PAN XIANGLONG ; CHEN LIANG ; WU WEIBING
Chinese Journal of Lung Cancer 2024;27(3):170-178
Background and objective Current studies suggest that for early-stage lung cancers with a component of ground-glass opacity measuring ≤2 cm,sublobar resection is suitable if it ensures adequate margins.However,lobectomy may be necessary for some cases to achieve this.The aim of this study was to explore the impact of size and depth on surgical techniques for wedge resection,segmentectomy,and lobectomy in early-stage lung cancer ≤2 cm,and to determine methods for ensuring a safe resection margin during sublobar resections.Methods Clinical data from 385 patients with early-stage lung can-cer ≤2 cm,who underwent lung resection in 2022,were subject to a retrospective analysis,covering three types of procedures:wedge resection,segmentectomy and lobectomy.The depth indicator as the OA value,which is the shortest distance from the inner edge of a pulmonary nodule to the opening of the corresponding bronchus,and the AB value,which is the distance from the inner edge of the nodule to the pleura,were measured.For cases undergoing lobectomy and segmentectomy,three-dimensional computed tomography bronchography and angiography(3D-CTBA)was performed to statistically determine the number of subsegments required for segmentectomy.The cutting margin width for wedge resection and segmentectomy was recorded,as well as the specific subsegments and their quantities removed during lung segmentectomy were documented.Results In wedge resection,segmentectomy,and lobectomy,the sizes of pulmonary nodules were(1.08±0.29)cm,(1.31±0.34)cm and(1.50±0.35)cm,respectively,while the depth of the nodules(OA values)was 6.05(5.26,6.85)cm,4.43(3.27,5.43)cm and 3.04(1.80,4.18)cm for each procedure,showing a progressive increasing trend(P<0.001).The median resec-tion margin width obtained from segmentectomy was 2.50(1.50,3.00)cm,significantly greater than the 1.50(1.15,2.00)cm from wedge resection(P<0.001).In wedge resections,cases where AB value>2 cm demonstrated a higher proportion of cases with resection margins less than 2 cm compared to those with margins greater than 2 cm(29.03%vs 12.90%,P=0.019).When utilizing the size of the nodule as the criterion for resection margin,the instances with AB value>2 cm continued to show a higher proportion in the ratio of margin distance to tumor size less than 1(37.50%vs 17.39%,P=0.009).The median number of subsegments for segmentectomy was three,whereas lobectomy cases requiring segmentectomy involved five subsegments(P<0.001).Conclusion The selection of the surgical approach for lung resection is influenced by both the size and depth of pulmonary nodules.This study first confirms that larger portions of lung tissue must be removed for nodules that are deeper and larger to achieve a safe margin.A distance of ≤2 cm from the inner edge of the pulmonary nodule to the nearest pleura may be the ideal indication for performing wedge resection.
6.Secondary targeted percutaneous vertebroplasty for the treatment of refracture of injured vertebrae after vertebral augmentation for osteoporotic vertebral compression fracture
Chaoyuan GE ; Dingjun HAO ; Zhengwei XU ; Liang YAN ; Baorong HE ; Wenlong YANG ; Lixiong QIAN ; Xiaowei YANG
Chinese Journal of Trauma 2024;40(6):516-521
Objective:To explore the efficacy of secondary targeted percutaneous vertebroplasty (PVP) for the treatment of refracture of injured vertebrae after vertebral augmentation for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective case series study was performed on the clinical data of 25 patients with refracture of injured vertebrae after vertebral augmentation for OVCF admitted to Honghui Hospital, Xi′an Jiaotong University from January 2019 to January 2022, including 10 males and 15 females, aged 62-86 years [(73.8±5.2)years]. The fractured segments involved T 10 in 1 patient, T 11 in 2, T 12 in 10, L 1 in 10 and L 2 in 2. All the patients were treated with secondary targeted PVP. The operation time and the amount of bone cement injected were recorded. The visual analogue scale (VAS) of lower back, Oswestry disability index (ODI), vertebral body index (VBI) and kyphotic angle (KA) were compared before surgery, at 1 day, 6 months after surgery and at the last follow-up. Odom criteria were used to evaluate the efficacy of the surgical procedure at the last follow-up. The intraoperative bone cement leakage and new vertebrae fracture during follow-up were observed. Results:All the patients were followed up for 23-59 months [(36.8±7.6)months]. The operation time was 35-60 minutes [(42.6±5.2)minutes], with the amount of bone cement injected for 3-5 ml [(3.6±0.8)ml]. The VAS scores of lower back at 1 day, 6 months after surgery and at the last follow-up were 3.1(2.0, 4.0)points, 1.7(1.0, 2.0)points and 0.6(0.0, 1.0)points respectively, significantly lower than 7.6(7.0, 9.0)points before surgery ( P<0.01), and a statistically singnificant decrease was found over follow-up time ( P<0.01). The ODI values at 1 day, 6 months after surgery and at the last follow-up were (49.5±5.9)%, (28.5±4.6)% and (19.2±4.8)% respectively, significantly lower than (78.8±6.8)% before surgery ( P<0.01), and a statistically singnificant decrease was found over follow-up time ( P<0.01). The VBI values at 1 day, 6 months after surgery and at the last follow-up were (76.6±4.5)%, (76.3±4.0)% and (76.1±3.8)% respectively, significantly higher than (58.9±5.8)% before surgery ( P<0.01), while there were no significant differences among those at 1 day, 6 months after surgery and at the last follow-up ( P>0.05). The KA values at 1 day, 6 months after surgery and at the last follow-up were (12.4±2.7)°, (12.6±2.5)° and (12.8±2.9)° respectively, significantly lower than (20.8±3.6)° before surgery ( P<0.01), while there were no significant differences among those at 1 day, 6 months after surgery and at the last follow-up ( P>0.05). According to the Odom criteria, 20 patients were rated excellent and 5 good at the last follow-up, with an excellent and good rate of 100%. Intraoperative asymptomatic bone cement leakage occurred in 3 patients (12%), including 2 with intervertebral leakage and 1 with lateral vertebral leakage. No adjacent vertebral body or other vertebral fracture was observed during the follow-up. Conclusions:For patients with refracture of injured vertebrae after vertebral augmentation for OVCF, the secondary targeted PVP has advantages of attenuation of the lower back pain, improvement of the quality of life, restoration of the height of refractured vertebrae, correction of the local kyphosis, and a low incidence of complications.
7.Current status of randomized controlled trials of traditional Chinese medicine in treating coronary heart disease with angina pectoris after percutaneous coronary intervention.
Si-Lin REN ; Zhao GE ; Xu-Dong WU ; Zhou ZHOU ; Zhi-Jun LI ; Meng-Xue ZHOU ; Mo-Han LI ; Xian-Liang WANG
China Journal of Chinese Materia Medica 2024;49(22):6224-6234
This study systematically reviewed the randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of coronary heart disease patients with angina pectoris after percutaneous coronary intervention(PCI). The basic elements of these RCTs, including sample size and estimation method, randomizing scheme, allocation concealment, blind method implementation, data integrity, statistical method, TCM syndrome, intervention measures, treatment course, follow-up time, and outcome indicators, were analyzed to provide reference for the design of future RCT and the clinical application of TCM in treating angina pectoris after PCI. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Chinese Clinical Trial Registry were searched for the RCT about TCM treatment of coronary heart disease patients with angina pectoris after PCI according to pre-defined criteria, with the time interval from inception to January 31, 2024. A total of 188 RCTs were included, of which 184 were clinical research articles and 4 were clinical trial registration schemes. These RCTs involved a total of 15 521 patients, with an average sample size of 83 patients and a maximum sample size of 248 patients. Among them, 126 RCTs reported TCM syndromes, the top three of which were Qi deficiency and blood stasis(38.89%), phlegm combined with stasis(17.46%), and Qi stagnation and blood stasis(9.52%). The control group received guideline-directed medical therapy(GDMT) or GDMT combined with placebo, and the treatment group received GDMT combined with TCM. The treatment mainly lasted for 4-8 weeks, most of the RCTs did not set the follow-up period or the follow-up period was unknown. A total of 160 outcome indicators were used, with the total frequency of 1 348. According to functional attributes, the outcome indicators can be categorized into 6 groups: symptoms/signs(403, 29.90%), TCM syndromes/symptoms(182, 13.50%), physical and chemical examination(468, 34.72%), quality of life(89, 6.60%), long-term prognosis(5, 0.37%), and safety evaluation(201, 14.91%). The clinical trial design of TCM intervention in angina pectoris after PCI of coronary heart disease is becoming more and more rigorous, while it remains to be improved. It is expected that more clinical trial schemes with rigorous design and taking into account the TCM advantages can be adopted in the future to provide a basis for the TCM treatment of angina pectoris after PCI of coronary heart disease.
Humans
;
Randomized Controlled Trials as Topic
;
Angina Pectoris/drug therapy*
;
Coronary Disease/drug therapy*
;
Percutaneous Coronary Intervention
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/administration & dosage*
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Male
;
Treatment Outcome
;
Female
8.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
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Female
;
Humans
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Aged
;
Natriuretic Peptide, Brain
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Simendan/therapeutic use*
;
Non-ST Elevated Myocardial Infarction
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Heart Failure/drug therapy*
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Peptide Fragments
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Arrhythmias, Cardiac
;
Biomarkers
;
Prognosis
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.Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis.
Xia XU ; Haiwen LU ; Jianxiong LI ; Jielin DUAN ; Zhongwei WANG ; Jiawei YANG ; Shuyi GU ; Rongguang LUO ; Shuo LIANG ; Wei TANG ; Fengying ZHANG ; Jingqing HANG ; Juan GE ; Xin LIN ; Jieming QU ; Xinming JIA ; Jinfu XU
Chinese Medical Journal 2023;136(16):1949-1958
BACKGROUND:
Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.
METHODS:
A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.
RESULTS:
The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.
CONCLUSION
Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans
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Aspergillosis, Allergic Bronchopulmonary/complications*
;
Aspergillus fumigatus/genetics*
;
Asthma/genetics*
;
Aspergillus
;
Mutation/genetics*
;
CARD Signaling Adaptor Proteins/genetics*

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