1.Value of Peripheral Blood DLGAP5 and RASSF1A Gene Methylation in the Differential Diagnosis of Benign and Malignant Lung Nodules
Hongmei ZHOU ; Xiaobin ZHAO ; Yaguang WU ; Jing XIAO
Journal of Modern Laboratory Medicine 2025;40(2):53-58
Objective To investigate the value of methylation levels of Discs large-associated protein5(DLGAP5)and Ras association domain family 1A(RASSF1A)in peripheral blood in the differential diagnosis of benign and malignant lung nodules.Methods 110 patients with pulmonary nodules admitted to the Seventh People's Hospital of Hebei Province from December 2022 to June 2024 were selected as study subjects.Based on the diagnosis confirmed by pathological examination,52 patients with malignant lung nodules were included in the malignant group and 58 patients with benign lung nodules were included in the benign group.The methylation levels of DLGAP5 and RASSF1A genes in peripheral blood were determined by quantitative real-time polymerase chain reaction(qRT-PCR).The diagnostic value of methylation of DLGAP5 and RASSF1A genes in peripheral blood on the benign and malignant nature of lung nodules and their relationship with clinicopathological characteristics of patients with malignant lung nodules were analyzed.Spearman's method was used to analyze the correlation between DLGAP5 and RASSF1A gene methylation levels and clinicopathological features.Results Compared with the benign group,the methylation levels of DLGAP5 and RASSF1A genes were higher in the peripheral blood of patients in the malignant group,and the differences were statistically significant(χ2=27.010,24.350,all P<0.001).The sensitivities of DLGAP5 methylation and RASSF1A methylation alone in the detection of malignant lung nodules were 61.54%,67.31%,and the specificity were 86.21%,79.31%,and the accuracies were 74.55%,73.63%,respectively.The sensitivity(84.62%)and accuracy(83.64%)of the combined two-gene methylation test for malignant lung nodules were better than that of single gene methylation(Z=2.816,2.497,all P<0.05).The concordance Kappa values of DLGAP5 methylation and RASSF1A methylation alone and in combination with the pathological results were 0.583,0.569 and 0.712,respectively.The nodules size,histological differentiation degree,lymph nodes and spiculation sign of patients with malignant pulmonary nodules were correlated with DLGAP5 and RASSF1A methylation levels,and the differences were statistically significant(χ2DLGAP5=4.644~14.981,χ2RASSF1A=4.293~12.629,all P<0.05).Correlation analysis showed that the methylation levels of DLGAP5 and RASSF1A genes were positively correlated with nodule size,histologic differentiation,lymph node metastasis and spiculation sign(rDLGAP5=0.512~0.683,rRASSF1A=0.527~0.691,all P<0.05).Conclusion The methylation levels of DLGAP5 and RASSF1A gene in peripheral blood were closely related to histological differentiation,lymph node metastasis and clinical staging.The combined detection of the two has high diagnostic value fro the benign and malignant nature of pulmonary nodules.
2.A case of acute kidney injury due to suspected omadacycline
Huan LIN ; Xiuheng YU ; Xiaobin HUANG ; Yu ZHAO
Chinese Journal of Pharmacoepidemiology 2025;34(3):353-358
An 81-year-old female patient was treated with anti-infective therapy of omadacycline for a soft-tissue skin infection,and developed acute kidney injury(AKI)6 d after the administration of omadacycline.Laboratory tests showed that the urea was 6.11 mmol·L-1,the creatinine was 236.40 μmol·L-1,and the glomerular filtration rate was 18.18 mL·min-1·(1.73m2)-1,which led to the definitive diagnosis of AKI.The association score of the suspected drug using Naranjo's Assessment Scale suggests that the patient's adverse reaction of AKI was suspected to be caused by omadacycline.After stopping omadacycline,the patient's renal function indicators gradually recovered after symptomatic treatment with renal protection and continuous blood purification.This paper discussed the occurrence mechanism and treatment prognosis of AKI caused by omadacycline.It suggestd that clinical use of omadacycline should be alert to the adverse effects of renal injury,and timely medication analysis and symptomatic treatment should be carried out to ensure the safety and effectiveness of treatment.
3.Comparative efficacy of laminoplasty via intermuscular approach or posterior midline approach for cervical spinal cord injury without radiographic abnormality: a multi-center retrospective study
Yunfei HUANG ; Shuai LI ; Jinpeng DU ; Baorong HE ; Yanzheng GAO ; Wei MEI ; Shibao LU ; Zhigan ZHAO ; Liang YAN ; Xiaobin YANG ; Yuan HE ; Zhen CHANG
Chinese Journal of Trauma 2025;41(7):635-644
Objective:To compare the efficacy of laminoplasty via the intermuscular approach or posterior midline approach for treating spinal cord injury without radiographic abnormality (SCIWORA).Methods:A multi-center retrospective cohort study was conducted to analyze the clinical data of 135 patients with SCIWORA admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Xi'an No.5 Hospital, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, Xuanwu Hospital of Capital Medical University from February 2021 to June 2023, including 75 males and 60 females, aged 35-78 years [(55.3±8.1)years]. The injury segments involved C 3-C 6. All the patients underwent posterior cervical open-door laminoplasty, among whom 70 patients were treated via the intermuscular approach (intermuscular group) and 65 via the posterior midline approach (posterior midline group). The operation duration, intraoperative blood loss, postoperative drainage volume, and length of hospital stay were recorded. The visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI), Barthel index, cervical Cobb angle, and cervical range of motion (ROM) were measured preoperatively, at 3, 6, 12 months postoperatively and at the final follow-up. The American Spinal Injury Association (ASIA) scale was evaluated preoperatively, at 3, 12 months postoperatively and at the final follow-up. The postoperative complication rate was recorded as well. Results:All the patients were followed up for 15-19 months [(16.3±1.6)months]. The operation duration, intraoperative blood loss, postoperative drainage and length of hospital stay were (125.0±23.0)minutes, (210.4±34.8)ml, and (165.3±23.7)ml, and (5.3±0.1)days in the intermuscular group, which were significantly shorter or less than (168.0±27.6)minutes, (260.2±45.3)ml, (196.4±31.6)ml, and (6.4±0.2)days in the posterior midline group ( P<0.01). The preoperative VAS score, JOA score, NDI and Barthel index showed no significant differences between the two groups ( P>0.05). The VAS score and JOA score also showed no significant differences between the two groups at 3, 6, 12 months postoperatively or at the final follow-up ( P>0.05). The NDI and Barthel index also showed no significant differences between the two groups at 3 months postoperatively ( P>0.05). At 6, 12 months postoperatively and at the final follow-up, the NDI were (15.4±2.5)points, (11.8±2.1)points and (8.6±1.5)points in the intermuscular group, significantly lower than (19.1±3.4)points, (14.3±2.4)points and (11.9±1.4)points in the posterior midline group ( P<0.01). At 6, 12 months postoperatively and at the final follow-up, the Barthel index were (71.4±6.2)points, (83.4±5.8)points and (89.2±7.1)points in the intermuscular group, significantly higher than (59.6±4.7)points, (74.2±3.9)points and (78.8±6.2)points in the posterior midline group ( P<0.01). Both groups showed significant improvements in VAS score, JOA score, NDI and Barthel index at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05). Among them, the VAS score, NDI and Barthel index were further improved over time ( P<0.05). Simultaneously, the JOA score was significantly improved at 6, 12 months postoperatively and at the last follow-up when compared to that at 3 months postoperatively ( P<0.05), with no significant difference at later time points between the two groups ( P>0.05). The preoperative cervical Cobb angle and ROM showed no significant differences between the two groups ( P>0.05). There was no significant difference in the Cobb angle between the two groups at 3, 6 or 12 months postoperatively ( P>0.05), while it was (13.6±2.4)° in the intermuscular group at the final follow-up, significantly larger than (10.4±2.8)° in the posterior midline group ( P<0.01). At 3, 6, 12 months postoperatively and at the final follow-up, the cervical ROM were (34.1±6.4)°, (32.6±7.3)°, (31.8±9.1)° and (29.6±8.7)° in the intermuscular group, significantly larger than (23.7±8.3)°, (22.3±7.8)°, (22.5±8.1)° and (20.6±9.3)° in the posterior midline group ( P<0.01). In the intermuscular group, the cervical Cobb angle showed no significant changes at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P>0.05). In the posterior midline group, the Cobb angles were significantly reduced at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decrease at 12 months postoperatively and at the final follow-up from those at 3, 6 months postoperatively ( P<0.05), no significant difference at 6 months postoperatively from that at 3 months postoperatively ( P>0.05), and significant decrease at the final follow-up from that at 12 months postoperatively ( P>0.05). In the intermuscular group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively and showed further improvement over time ( P<0.05). In the posterior midline group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decreases at 6, 12 months postoperatively and at the final follow-up from that at 3 months postoperatively ( P<0.05), significant decreases at the final follow-up from those at 6, 12 months postoperatively ( P<0.05), and no significant difference at 12 months postoperatively from that at 6 months postoperatively ( P>0.05). The ASIA grades showed no significant difference between the two groups preoperatively, at 3, 12 months postoperatively and at the final follow-up ( P>0.05) , but were gradually improved over time in both groups ( P<0.05). The postoperative complication rate was 9%(6/70) in the intermuscular group, significantly lower than 48%(31/65) in the posterior midline group ( P<0.01). Conclusion:Compared to the posterior midline approach, the intermuscular approach for laminoplasty in patients with SCIWORA possesses advantages, including shorter operative time and length of hospital stay, reduced intraoperative blood loss and postoperative drainage, less postoperative neck disability, higher daily life quality, better long-term preservation of cervical lordosis and motion, and a lower complication rate.
4.Evaluation of the efficacy of disc radiofrequency ablation combined with radiofrequency of the dorsal medial branch neurotomy in the treatment of chronic low back pain in the elderly
Chi LIU ; Changtai SUN ; Liang ZHANG ; Maoyu ZHAO ; Xiaobin WANG ; Junchuan LIU ; Jingwei LIU ; Qiang WANG
Chinese Journal of Geriatrics 2025;44(7):858-862
Objective:To evaluate the clinical efficacy of intervertebral disc radiofrequency(RF)ablation combined with dorsal medial branch(DMB)neurotomy in elderly patients suffering from chronic low back pain.Methods:A retrospective analysis was conducted on patients aged 60 years and older with chronic low back pain admitted to Beijing Hospital from March 2023 to September 2024.The combined treatment group underwent intervertebral disc radiofrequency ablation combined with radiofrequency treatment of the dorsal medial branch of the spinal nerve.The single treatment group underwent intervertebral disc radiofrequency ablation alone.Pain visual analogue scale(VAS)scores were assessed before treatment and on the first day, 3 months, and 6 months post-treatment.The Oswestry Disability Index(ODI)and Barthel Index were evaluated before treatment and at 3 months and 6 months post-treatment.Clinical efficacy was compared between the two groups.Results:A total of 115 elderly patients with chronic low back pain were enrolled, aged 61 to 72 years(mean 66.5 ± 5.6 years), with 44 males.The combined therapy group consisted of 71 patients, and the monotherapy group consisted of 44 patients.All patients were followed up continuously for 6 months.At all-time points post-treatment, the VAS scores in the combined therapy group were significantly lower than those in the monotherapy group( t=-4.887, -10.095, -7.687, all P<0.05); at 3 and 6 months post-treatment, the combined therapy group showed significantly greater improvements in ODI( t=-3.645, -9.451, both P<0.001)Barthel Index improvement were significantly greater than those in the monotherapy group( t=6.578, 8.530, both P<0.001); the overall good-to-excellent rate in the combined therapy group was 88.7%, higher than the 72.7% in the monotherapy group( χ2=4.85, P<0.05). Conclusions:Combined disc RF ablation and DMB neurotomy provide superior pain relief, functional recovery, and improvement in daily activities compared to single disc ablation in elderly patients with CLBP.This minimally invasive approach represents a safe and effective therapeutic strategy for managing chronic low back pain in the geriatric population.
5.Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique (version 2025)
Sihao HE ; Junchao XING ; Tongwei CHU ; Zhengqi CHANG ; Xigao CHENG ; Fei DAI ; Xiaobing JIANG ; Jie HAO ; Jiang HU ; Jinghui HUANG ; Tianyong HOU ; Fei LUO ; Bo LIAO ; Changqing LI ; Lei LIU ; Guodong LIU ; Peng LIU ; Sheng LU ; Weishi LI ; Yang LIU ; Zhen LIU ; Wei MEI ; Peifu TANG ; Bing WANG ; Bing WANG ; Ce WANG ; Hongli WANG ; Liang WANG ; Shengru WANG ; Xiaobin WANG ; Yang WANG ; Yingfeng WANG ; Zheng WANG ; Jianzhong XU ; Guoyong YIN ; Haiyang YU ; Qiang YANG ; Zhaoming YE ; Bin ZHANG ; Chengmin ZHANG ; Jun ZOU ; Qiang ZHOU ; Min ZHAO ; Rui ZHOU ; Xiaojun ZHANG ; Yongfei ZHAO ; Zhongrong ZHANG ; Zehua ZHANG ; Yingze ZHANG
Chinese Journal of Trauma 2025;41(11):1035-1047
For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.
6.The diagnostic value of endoscopic ultrasound-guided fine needle aspiration in biliary lesions and factors influencing its accuracy
Tan XIANHAO ; Zhou XI ; Zhao MING ; Jiang LIN ; Sun XIAOBIN ; Shan JING
Chinese Journal of Clinical Oncology 2025;52(11):565-570
Objective:To evaluate the diagnostic performance and safety of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)for biliary lesions and to investigate the factors influencing its accuracy.Methods:A retrospective analysis was performed on the clinical data of patients who underwent EUS-FNA at Chengdu Third People's Hospital between January 2021 and December 2023 for suspected malig-nant biliary strictures or masses,including 22 males and 19 females,with a mean age of 65.9(35.0-89.0)years.Diagnostic performance(sensitivity,specificity,positive predictive value,negative predictive value,and accuracy)and factors influencing these outcomes were evalu-ated.Results:The overall sensitivity of EUS-FNA for diagnosing biliary lesions was 85%,with a specificity of 100%,positive predictive value of 100%,negative predictive value of 33%,and accuracy of 86%.The use of a 25G needle and the presence of solid masses were significant factors influencing the diagnostic accuracy of EUS-FNA.In contrast,the puncture site did not impact diagnostic performance.No EUS-FNA-re-lated adverse events were observed during the follow-up period.Conclusions:EUS-FNA is highly accurate and safe for the diagnosis of bili-ary lesions.The diagnostic accuracy of EUS-FNA significantly improves when using a 25G needle and in the presence of solid biliary masses.
7.The relationship between cerebral perfusion status,blood pressure variability and prognosis after combined cerebral revascularization surgery in patients with moyamoya disease
Shao ZHANG ; Liming ZHAO ; Chaoyue LI ; Jiangong MA ; Sen HE ; Dan LI ; Xiaobin WANG
Chinese Journal of Nervous and Mental Diseases 2025;51(6):342-348
Objective To investigate the relationship between cerebral perfusion status,blood pressure variability,and prognosis in patients with moyamoya disease following cerebral revascularization.Methods A retrospective analysis was conducted on 108 patients who underwent their first combined cerebral revascularization between January 2019 and July 2022 at the Department of Neurosurgery,First Affiliated Hospital of Henan University,and Henan Provincial People's Hospital.Based on postoperative cerebral perfusion improvement,patients were categorized into a"good"group and a"general"group.Baseline characteristics,key imaging parameters,blood pressure variability,and symptom scores were compared and analyzed between the two groups.Results In this study,there were 55 cases in the good group and 53 cases in the general group.According to the comparative analysis of the postoperative indicators between the good group and the general group,Statistically significant differences were observed in symptom improvement[42(79.25%)vs.52(94.55%)],TIA[22(41.51%)vs.11(20.00%)],and cerebral infarction[6(11.32%)vs.0(0.00%)],mRS score and the Matsushima classification(P<0.05).However,there was no statistically significant difference in the BPV-related index between the two groups of patients before the operation(all P>0.05).When comparing nine blood pressure variability(BPV)-related indices including the mean of 24-hour,daytime,and nighttime systolic blood pressure,coefficient of variability(CV),and average real variability(ARV)between the two groups,no significant differences were observed in the BPV-related indices before surgery between the two groups(P>0.05).The differences in the BPV-related indices before and after surgery(postoperative index-preoperative index)between the two groups were statistically significant(P<0.05).Postoperative cerebral perfusion status was positively correlated with prognosis and negatively correlated with BPV.Conclusion Patients with good improvement in cerebral perfusion status after combined revascularization for moyamoya disease have less blood pressure variability and better prognosis.
8.The relationship between cerebral perfusion status,blood pressure variability and prognosis after combined cerebral revascularization surgery in patients with moyamoya disease
Shao ZHANG ; Liming ZHAO ; Chaoyue LI ; Jiangong MA ; Sen HE ; Dan LI ; Xiaobin WANG
Chinese Journal of Nervous and Mental Diseases 2025;51(6):342-348
Objective To investigate the relationship between cerebral perfusion status,blood pressure variability,and prognosis in patients with moyamoya disease following cerebral revascularization.Methods A retrospective analysis was conducted on 108 patients who underwent their first combined cerebral revascularization between January 2019 and July 2022 at the Department of Neurosurgery,First Affiliated Hospital of Henan University,and Henan Provincial People's Hospital.Based on postoperative cerebral perfusion improvement,patients were categorized into a"good"group and a"general"group.Baseline characteristics,key imaging parameters,blood pressure variability,and symptom scores were compared and analyzed between the two groups.Results In this study,there were 55 cases in the good group and 53 cases in the general group.According to the comparative analysis of the postoperative indicators between the good group and the general group,Statistically significant differences were observed in symptom improvement[42(79.25%)vs.52(94.55%)],TIA[22(41.51%)vs.11(20.00%)],and cerebral infarction[6(11.32%)vs.0(0.00%)],mRS score and the Matsushima classification(P<0.05).However,there was no statistically significant difference in the BPV-related index between the two groups of patients before the operation(all P>0.05).When comparing nine blood pressure variability(BPV)-related indices including the mean of 24-hour,daytime,and nighttime systolic blood pressure,coefficient of variability(CV),and average real variability(ARV)between the two groups,no significant differences were observed in the BPV-related indices before surgery between the two groups(P>0.05).The differences in the BPV-related indices before and after surgery(postoperative index-preoperative index)between the two groups were statistically significant(P<0.05).Postoperative cerebral perfusion status was positively correlated with prognosis and negatively correlated with BPV.Conclusion Patients with good improvement in cerebral perfusion status after combined revascularization for moyamoya disease have less blood pressure variability and better prognosis.
9.Value of Peripheral Blood DLGAP5 and RASSF1A Gene Methylation in the Differential Diagnosis of Benign and Malignant Lung Nodules
Hongmei ZHOU ; Xiaobin ZHAO ; Yaguang WU ; Jing XIAO
Journal of Modern Laboratory Medicine 2025;40(2):53-58
Objective To investigate the value of methylation levels of Discs large-associated protein5(DLGAP5)and Ras association domain family 1A(RASSF1A)in peripheral blood in the differential diagnosis of benign and malignant lung nodules.Methods 110 patients with pulmonary nodules admitted to the Seventh People's Hospital of Hebei Province from December 2022 to June 2024 were selected as study subjects.Based on the diagnosis confirmed by pathological examination,52 patients with malignant lung nodules were included in the malignant group and 58 patients with benign lung nodules were included in the benign group.The methylation levels of DLGAP5 and RASSF1A genes in peripheral blood were determined by quantitative real-time polymerase chain reaction(qRT-PCR).The diagnostic value of methylation of DLGAP5 and RASSF1A genes in peripheral blood on the benign and malignant nature of lung nodules and their relationship with clinicopathological characteristics of patients with malignant lung nodules were analyzed.Spearman's method was used to analyze the correlation between DLGAP5 and RASSF1A gene methylation levels and clinicopathological features.Results Compared with the benign group,the methylation levels of DLGAP5 and RASSF1A genes were higher in the peripheral blood of patients in the malignant group,and the differences were statistically significant(χ2=27.010,24.350,all P<0.001).The sensitivities of DLGAP5 methylation and RASSF1A methylation alone in the detection of malignant lung nodules were 61.54%,67.31%,and the specificity were 86.21%,79.31%,and the accuracies were 74.55%,73.63%,respectively.The sensitivity(84.62%)and accuracy(83.64%)of the combined two-gene methylation test for malignant lung nodules were better than that of single gene methylation(Z=2.816,2.497,all P<0.05).The concordance Kappa values of DLGAP5 methylation and RASSF1A methylation alone and in combination with the pathological results were 0.583,0.569 and 0.712,respectively.The nodules size,histological differentiation degree,lymph nodes and spiculation sign of patients with malignant pulmonary nodules were correlated with DLGAP5 and RASSF1A methylation levels,and the differences were statistically significant(χ2DLGAP5=4.644~14.981,χ2RASSF1A=4.293~12.629,all P<0.05).Correlation analysis showed that the methylation levels of DLGAP5 and RASSF1A genes were positively correlated with nodule size,histologic differentiation,lymph node metastasis and spiculation sign(rDLGAP5=0.512~0.683,rRASSF1A=0.527~0.691,all P<0.05).Conclusion The methylation levels of DLGAP5 and RASSF1A gene in peripheral blood were closely related to histological differentiation,lymph node metastasis and clinical staging.The combined detection of the two has high diagnostic value fro the benign and malignant nature of pulmonary nodules.
10.A case of acute kidney injury due to suspected omadacycline
Huan LIN ; Xiuheng YU ; Xiaobin HUANG ; Yu ZHAO
Chinese Journal of Pharmacoepidemiology 2025;34(3):353-358
An 81-year-old female patient was treated with anti-infective therapy of omadacycline for a soft-tissue skin infection,and developed acute kidney injury(AKI)6 d after the administration of omadacycline.Laboratory tests showed that the urea was 6.11 mmol·L-1,the creatinine was 236.40 μmol·L-1,and the glomerular filtration rate was 18.18 mL·min-1·(1.73m2)-1,which led to the definitive diagnosis of AKI.The association score of the suspected drug using Naranjo's Assessment Scale suggests that the patient's adverse reaction of AKI was suspected to be caused by omadacycline.After stopping omadacycline,the patient's renal function indicators gradually recovered after symptomatic treatment with renal protection and continuous blood purification.This paper discussed the occurrence mechanism and treatment prognosis of AKI caused by omadacycline.It suggestd that clinical use of omadacycline should be alert to the adverse effects of renal injury,and timely medication analysis and symptomatic treatment should be carried out to ensure the safety and effectiveness of treatment.

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