1.Relationship between physical development and onset and progression of myopia among children and adolescents
MA Xiaohui, GONG Yizhuo, QIU Tingting, LIU Zheng, HUO Huanhuan, HU Yuanyuan, BI Hongsheng
Chinese Journal of School Health 2026;47(5):723-727
Objective:
To investigate the relationship between physical development indicators and the onset and progression of myopia among children and adolescents, so as to provide theoretical support for coordinated vision and physical health management.
Methods:
A prospective cohort study was conducted. In September 2022, 3 102 students from grade one in primary school to grade three in junior high school (five year primary school and four year junior high school) from six schools in Huantai County, Shandong Province, were selected using multistage cluster random sampling method to participate in an epidemiological survey on myopia, with follow up completed in September 2023. Follow up value minus baseline value( d ) was used to assess changes in physical development and vision indicators. Multivariate Logistic regression analysis was used to examine the relationship between physical development indicators and the incidence of myopia. Generalized linear models were established to analyze the relationship between physical development indicators and changes in d spherical equivalent (SE) and d axial length (AL) .
Results:
Multivariate Logistic regression analysis showed that, after adjusting for factors such as gender, age, and baseline body mass index, the third ( Q 3)and fourth ( Q 4)quartiles of d height showed increased risks of myopia onset within one year compared to the first quartile( Q 1) ( OR =1.85,95% CI =1.18-2.88; OR =1.74,95% CI =1.09-2.78,both P <0.05). Results from the generalized linear model indicated that, after adjusting for confounding factors such as gender, age, and baseline SE, d SE was negatively correlated with d height and d weight in children and adolescents ( β =-0.024, 95% CI =-0.031 to -0.018; β =-0.006, 95% CI =-0.011 to -0.001), d AL was positively correlated with d height and d weight in children and adolescents ( β =0.011, 95% CI =0.008-0.013; β =0.005, 95% CI =0.003-0.007) (all P <0.05).
Conclusions
Physical development indicators in children and adolescents were associated with the onset and progression of myopia. Dynamic monitoring and early intervention of myopia should be strengthened for children and adolescents with rapid height and weight gain to achieve coordinated management of myopia and physical development.
2.Analysis of risk factors for neurological complications in patients with Stanford type A aortic dissection
Chuanwen LI ; Qingyan SUN ; Yanqing GAN ; Xianqing LI ; Teng CAI ; Hongsheng LIU ; Liangchun NI ; Zhonghua FEI
Chinese Journal of Postgraduates of Medicine 2025;48(7):635-642
Objective:To explore how one-sided/two-sided brain blood flow affects the occurrence of neurological complications in patients with Stanford type A aortic dissection, as well as to assess the factors that contribute to the development of neurological complications.Methods:A total of 162 patients diagnosed with Stanford type A aortic dissection who had undergone ascending aorta and total aortic arch replacement at Affiliated Hospital of Jining Medical College from August 2020 to December 2023 were retrospectively reviewed. These patients were categorized into two groups based on the presence of postoperative neurological complications: a group with neurological complications comprising 77 cases and a group without neurological complications comprising 85 cases. A comparative analysis was carried out on general clinical data, surgical and brain perfusion characteristics, as well as preoperative test indicators between these two groups in order to investigate the factors influencing the occurrence of postoperative neurological complications in patients with Stanford type A aortic dissection. The data was analyzed using Logistic regression to identify the risk factors associated with postoperative neurological complications and to develop a predictive nomogram model. Calibration curves, receiver operating characteristic (ROC) curves and decision curve (DCA) were generated to assess the accuracy and predictive capability of the nomogram model.Results:In the group of patients who experienced neurological complications, there was a higher prevalence of a history of hypertension, longer operation time, extended periods of cardiopulmonary bypass, cross-clamping, brain perfusion, cooling, and rewarming, as well as increased postoperative drainage volume. Additionally, the levels of preoperative blood urea nitrogen (BUN), creatinine (Cr) and lactic acid (Lac) were elevated compared to those in the non-neurological complications group: 77.9% (60/77) vs. 52.9% (45/85), (409.99 ± 104.26) min vs. (348.29 ± 63.12) min, (223.36 ± 66.86) min vs. (179.25 ± 38.59) min, 112 (94, 133) min vs. 96 (84, 113) min, (35.23 ± 9.89) min vs. (32.14 ± 6.81) min, (82.19 ± 28.69) min vs. (68.76 ± 29.06) min, (79.30 ± 22.60) min vs. (69.54 ± 16.42) min, 806 (529, 1 127) ml vs. 663 (449, 925) ml, 6.78 (5.38, 8.84) mmol/L vs. 6.08 (4.66, 7.76) mmol/L, 86.3 (64.0, 131.9) μmol/L vs. 71.0 (55.6, 84.9) μmol/L, 2.1(1.2, 4.0) mmol/L vs. 1.5 (0.9, 2.3) mmol/L. On the other hand, the percentage of patients who underwent bilateral brain perfusion was lower, and they experienced lower lowest temperature, preoperative platelet count, and ejection fraction levels than those in the non-neurological complications group: 57.1% (44/77) vs. 75.3% (64/85), (25.69 ± 1.04) ℃ vs. (26.04 ± 0.82) ℃, (175.79 ± 58.14) ×10 9/L vs. (213.87 ± 77.29) ×10 9/L, (54.18 ± 3.84)% vs. (55.34 ± 3.56)% ( P<0.05). Multivariate Logistic regression analysis revealed that a prior history of high blood pressure, prolonged cardiopulmonary bypass duration were identified as autonomous risk factors for the development of postoperative neurological issues in individuals with Stanford type A aortic dissection, while simultaneous brain perfusion emerged as an independent protective element ( P<0.05). Subsequently, a predictive nomogram was constructed incorporating these three pivotal factors to assess the likelihood of postoperative neurological complications in patients with Stanford type A aortic dissection. The calibration curve exhibited a noteworthy level of accuracy for the nomogram predictive model ( χ2 = 9.01, P = 0.342). Additionally, the ROC curve analysis displayed an area under the curve of 0.84 (95% CI 0.78 to 0.90) for the nomogram model in predicting postoperative neurological complications in patients with Stanford type A aortic dissection, indicating a high predictive accuracy. Moreover, DCA analysis indicated that the nomogram model provided a net benefit above 0 across the spectrum of 0 to 90%. Conclusions:Postoperative neurological complications in patients with Stanford type A aortic dissection is linked to factors such as a previous history of hypertension, unilateral brain perfusion, an extended cardiopulmonary bypass duration. By developing a nomogram model that incorporates these factors, it becomes feasible to accurately forecast the likelihood of postoperative neurological complications in this patient population. This predictive tool holds significant value in facilitating proactive clinical risk evaluation and preventive measures.
3.CT and MRI findings of giant cell reparative granuloma in lateral skull base
Pengfeng SUN ; Jiping DONG ; Xiaoping WU ; Xiangchun YANG ; Caixia PEI ; Hongsheng LIU ; Run LIU
Journal of Practical Radiology 2025;41(4):560-563
Objective To investigate the CT and MRI features of giant cell reparative granuloma(GCRG)in lateral skull base.Methods The CT,MRI and clinicopathological data of 8 patients with GCRG in lateral skull base were collected and analyzed.Results All of the eight lesions were unilateral and solitary(three on the left side and five on the right side),with widespread involvement affecting two or more bony structures of the lateral skull base.All lesions showed expansile and lytic bone destruction on CT scans,the margins were clear(7/8),and the sclerotic changes could be seen at the margin of all eight lesions.On MRI,the lesions revealed heterogeneous isointense and hypointense on T1WI,and heterogeneous hypointense with focal cystic changes on T2WI,without fluid-fluid levels.The enhanced scan showed heterogeneous enhancement.Seven cases extended to the middle cranial fossa,caused com-pression of the temporal lobe brain tissue,with thickened and strengthened adjacent meninges.Conclusion The GCRG in lateral skull base has certain characteristic appearances on CT and MRI;understanding these characteristic manifestations can provide a basis for accurate diagnosis.
4.Association between near work, screen time, outdoor time and myopia in children
Huanhuan HUO ; Suyun LI ; Tingting QIU ; Yizhuo GONG ; Xianwei YAO ; Qian XU ; Guoyong LIU ; Yuanyuan HU ; Hongsheng BI
Chinese Journal of Experimental Ophthalmology 2025;43(6):548-555
Objective:To analyze the correlation between near work, screen time, outdoor time and myopia in children based on objective monitoring technology and to explore the influencing factors related to myopia in children.Methods:A cross-sectional study was conducted.From October 2022 to March 2023, the purposive sampling method was used to select 596 children in Grade 2 and Grade 3 from two primary schools in Shandong Province as study subjects.Eye-Monitor technology of eye-use behavior based on artificial intelligence was used to quantify parameters of near work, screen time and outdoor time.The eye-use behavior parameters were compared within each subject and between non-myopic and myopic children on weekdays and weekends.A multivariate binary logistic regression model was constructed to analyze the influencing factors related to myopia.The study protocol was approved by the Medical Ethics Committee of the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.HEC-HY-2022023KY).Written informed consent was obtained from the legal guardian of each subject.Results:For each subject, the proportion of near work time on weekdays was greater than on weekends, the proportion of time spent looking at cell phones, computer screens, and outdoor activities was smaller, the duration of single continuous near eye use was longer, the tilt angle of the head in sitting position was greater, and the light intensity was stronger, showing statistically significant differences ( t=19.427, -9.964, -5.916, -10.470, 2.211, 2.898, 15.061; all P<0.05).During weekdays, compared with the non-myopia group, the myopia group had longer total near work duration, longer single continuous near eye use duration, shorter outdoor activity duration, closer eye use distance, larger proportion of near work time, and smaller proportion of outdoor activity time, showing statistically significant differences (all P<0.05).During weekends, compared with the non-myopia group, the myopia group had longer time spent looking at cell phones and computer screens, shorter outdoor activity time, greater proportion of time spent looking at cell phones and computer screens, and smaller proportion of outdoor activity time, with statistically significant differences (all P<0.05).During weekdays, after adjusting for confounding factors, longer single continuous near eye use duration ( OR=1.138, 95% CI: 1.086-1.192, P<0.001) was the risk factor for myopia, and longer working distance ( OR=0.906, 95% CI: 0.847-0.970, P=0.004) and longer outdoor activity time ( OR=0.127, 95% CI: 0.023-0.703, P=0.018) were protective factors for myopia.During weekends, after adjusting for confounding factors, longer time spent on looking at cell phone screens ( OR=2.437, 95% CI: 1.460-4.068, P<0.001) and longer time spent on looking at computer screens ( OR=2.260, 95% CI: 1.283-3.979, P=0.005) were risk factors for myopia, and longer outdoor activity time ( OR=0.624, 95% CI: 0.416-0.934, P=0.022) was the protective factor for myopia. Conclusions:The eyes with continuous near work, prolonged use of smartphone and computer screens, closer eye use distance, and less time spent outdoors have been confirmed to be significantly correlated with myopia based on objective monitoring data.When formulating intervention measures for myopia prevention and control in children, it is advocated to further pay attention to control the distance and duration of near work on weekdays and strengthen screen time management on weekends.
5.Effects of maytansine on proliferation,migration,invasion,apoptosis and autophagy of human thyroid cancer cells
Na GU ; Cheng TAN ; Luyao WANG ; Hongsheng SHEN ; Xijing LI ; Xinyan LI ; Cuicui LIU ; Xiumei ZHAO
Practical Oncology Journal 2025;39(1):21-29
Objective The objective of this study was to investigate the effects of maytansine on proliferation,migration,in-vasion,apoptosis and autophagy of human thyroid cancer C643 cells.Methods C643 cells were treated with different concentrations(0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L)of maytansine,the effect of maytansine on the proliferation of C643 cells was detected by the sulforhodamine B(SRB)method,and the concentration of subsequent experiments was determined.C643 cells in the logarithmic growth stage period were divided into the control group,low-dose group,mid-dose group and high-dose group.The effects of maytansine on migration and invasion abilities of C643 cells were detected by cell scratch and Transwell chamber assay;The levels of reactive oxygen species(ROS)were detected by 2′,7′-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe experi-ment;The apoptosis rate of C643 cells was detected by flow cytometry;The expression of proteins related to apoptosis or autophagy was detected by Western blot.Results Maytansine at concentrations of 0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L could in-hibit the proliferation of C643 cells(P<0.05),and exhibited a significant concentration time dependence.The half maximal inhibitory concentrations(IC50)at 24,48 and 72 h were 54.255,5.193 and 0.647 μmol/L,respectively;The cell scratch and Transwell chamber results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could reduce the migration and invasion abilities of C643 cells(P<0.05 and P<0.01).The fluorescence probe results showed that maytansine at concentrations of 0.1,1 and 10μmol/L could increase the intracellular ROS levels of C643 cells(P<0.01).The flow cytometry results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could concentration dependently increase the apoptosis rate of C643 cells(P<0.01).The Western blot results showed that with the increase of maytansine concentrations,the expression of Bax protein related to apoptosis in C643 cells increased(P<0.05),the expression of Bcl-2 decreased(P<0.05),the expression of LC3Ⅱ/Ⅰ(P<0.05)and Beclin-1(P<0.01)increased,while the expression of p62 decreased(P<0.001).Conclusion Maytansine can inhibit the proliferation,migration and invasion of human thyroid cancer C643 cells,and induce the synergistic effect on apoptosis and autophagy by increasing intracellular ROS levels.
6.Influence of aortic root repair and replacement on the surgical effect and postoperative complications of Stanford type A aortic dissection patients
Chuanwen LI ; Qingyan SUN ; Yanqing GAN ; Xianqing LI ; Teng CAI ; Hongsheng LIU ; Liangchun NI
International Journal of Surgery 2025;52(3):176-181
Objective:To investigate the effect of aortic root repair and replacement on the surgical effect and postoperative complications of Stanford type A aortic dissection.Methods:By retrospective case-control study, 190 patients with Stanford type A aortic dissection admitted to the Affiliated Hospital of Jining Medical College from August 2020 to December 2023.According to the different surgical treatment methods, they were divided into repair group ( n=65) and replacement group ( n=125). Patients in the repair group received aortic root repair, while patients in the replacement group received aortic root replacement, that was, Bentall operation. The surgical related indexes, surgical effect, postoperative outcome and mid-term survival rate of the two groups were compared. The measurement data conforming to the normal distribution were expressed by the mean standard deviation ( ± s), and the comparison between groups adopted t-test; The measurement data of skewed distribution were expressed by M( Q1, Q3), and the comparison between groups was conducted using the rank sum test. Counting data were expressed by the number of cases and percentage (%), and the comparison between groups was conducted by chi-square test or Fisher exact probability method. Results:There was no significant difference in distal aortic operation, cardiopulmonary bypass time, hypothermic circulatory arrest time and occlusion time between repair group and replacement group ( P>0.05).There was no significant difference in ventilator-assisted time, intensive care unit stay time, visual analogue score(VAS) after waking up and hospitalization time between repair group and replacement group ( P>0.05).There was no significant difference between the two groups in 30-days mortality rate after discharge (9.2% vs 11.2%) and postoperative complications (18.5% vs 22.4%) ( P>0.05). Kaplan-Meier survival curve analysis showed that there was no significant relationship between the medium-term survival rate of patients in repair group and replacement group ( χ2=0.46, P=0.500). During the follow-up period, one patient in the replacement group underwent reoperation, including Bentall operation, with an interval of 14 months. Conclusions:the choice of aortic root repair or replacement has no effect on the surgical effect and postoperative complications of Stanford A aortic dissection patients. The short-term and medium-term survival rate of aortic root repair is similar to that of replacement, and no patient received proximal surgery again during the follow-up period, which is feasible and safe.
7.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
8.Analysis of risk factors for neurological complications in patients with Stanford type A aortic dissection
Chuanwen LI ; Qingyan SUN ; Yanqing GAN ; Xianqing LI ; Teng CAI ; Hongsheng LIU ; Liangchun NI ; Zhonghua FEI
Chinese Journal of Postgraduates of Medicine 2025;48(7):635-642
Objective:To explore how one-sided/two-sided brain blood flow affects the occurrence of neurological complications in patients with Stanford type A aortic dissection, as well as to assess the factors that contribute to the development of neurological complications.Methods:A total of 162 patients diagnosed with Stanford type A aortic dissection who had undergone ascending aorta and total aortic arch replacement at Affiliated Hospital of Jining Medical College from August 2020 to December 2023 were retrospectively reviewed. These patients were categorized into two groups based on the presence of postoperative neurological complications: a group with neurological complications comprising 77 cases and a group without neurological complications comprising 85 cases. A comparative analysis was carried out on general clinical data, surgical and brain perfusion characteristics, as well as preoperative test indicators between these two groups in order to investigate the factors influencing the occurrence of postoperative neurological complications in patients with Stanford type A aortic dissection. The data was analyzed using Logistic regression to identify the risk factors associated with postoperative neurological complications and to develop a predictive nomogram model. Calibration curves, receiver operating characteristic (ROC) curves and decision curve (DCA) were generated to assess the accuracy and predictive capability of the nomogram model.Results:In the group of patients who experienced neurological complications, there was a higher prevalence of a history of hypertension, longer operation time, extended periods of cardiopulmonary bypass, cross-clamping, brain perfusion, cooling, and rewarming, as well as increased postoperative drainage volume. Additionally, the levels of preoperative blood urea nitrogen (BUN), creatinine (Cr) and lactic acid (Lac) were elevated compared to those in the non-neurological complications group: 77.9% (60/77) vs. 52.9% (45/85), (409.99 ± 104.26) min vs. (348.29 ± 63.12) min, (223.36 ± 66.86) min vs. (179.25 ± 38.59) min, 112 (94, 133) min vs. 96 (84, 113) min, (35.23 ± 9.89) min vs. (32.14 ± 6.81) min, (82.19 ± 28.69) min vs. (68.76 ± 29.06) min, (79.30 ± 22.60) min vs. (69.54 ± 16.42) min, 806 (529, 1 127) ml vs. 663 (449, 925) ml, 6.78 (5.38, 8.84) mmol/L vs. 6.08 (4.66, 7.76) mmol/L, 86.3 (64.0, 131.9) μmol/L vs. 71.0 (55.6, 84.9) μmol/L, 2.1(1.2, 4.0) mmol/L vs. 1.5 (0.9, 2.3) mmol/L. On the other hand, the percentage of patients who underwent bilateral brain perfusion was lower, and they experienced lower lowest temperature, preoperative platelet count, and ejection fraction levels than those in the non-neurological complications group: 57.1% (44/77) vs. 75.3% (64/85), (25.69 ± 1.04) ℃ vs. (26.04 ± 0.82) ℃, (175.79 ± 58.14) ×10 9/L vs. (213.87 ± 77.29) ×10 9/L, (54.18 ± 3.84)% vs. (55.34 ± 3.56)% ( P<0.05). Multivariate Logistic regression analysis revealed that a prior history of high blood pressure, prolonged cardiopulmonary bypass duration were identified as autonomous risk factors for the development of postoperative neurological issues in individuals with Stanford type A aortic dissection, while simultaneous brain perfusion emerged as an independent protective element ( P<0.05). Subsequently, a predictive nomogram was constructed incorporating these three pivotal factors to assess the likelihood of postoperative neurological complications in patients with Stanford type A aortic dissection. The calibration curve exhibited a noteworthy level of accuracy for the nomogram predictive model ( χ2 = 9.01, P = 0.342). Additionally, the ROC curve analysis displayed an area under the curve of 0.84 (95% CI 0.78 to 0.90) for the nomogram model in predicting postoperative neurological complications in patients with Stanford type A aortic dissection, indicating a high predictive accuracy. Moreover, DCA analysis indicated that the nomogram model provided a net benefit above 0 across the spectrum of 0 to 90%. Conclusions:Postoperative neurological complications in patients with Stanford type A aortic dissection is linked to factors such as a previous history of hypertension, unilateral brain perfusion, an extended cardiopulmonary bypass duration. By developing a nomogram model that incorporates these factors, it becomes feasible to accurately forecast the likelihood of postoperative neurological complications in this patient population. This predictive tool holds significant value in facilitating proactive clinical risk evaluation and preventive measures.
9.Fibroblast Growth Factor 8 Suppresses Neurotoxic Astrocytes and Alleviates Neuropathic Pain via Spinal FGFR3 Signaling.
Huizhu LIU ; Lanxing YI ; Guiling LI ; Kangli WANG ; Hongsheng WANG ; Yuqiu ZHANG ; Benlong LIU
Neuroscience Bulletin 2025;41(12):2218-2232
Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3⁺ astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia-astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
Animals
;
Astrocytes/drug effects*
;
Neuralgia/pathology*
;
Receptor, Fibroblast Growth Factor, Type 3/metabolism*
;
Signal Transduction/physiology*
;
Male
;
Mice
;
Microglia/drug effects*
;
Fibroblast Growth Factor 8/pharmacology*
;
Mice, Inbred C57BL
;
Hyperalgesia/drug therapy*
;
Spinal Cord/drug effects*
;
Complement C3/metabolism*
;
Spinal Cord Dorsal Horn/metabolism*
10.Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: a long-term follow-up pilot study.
Zhao ZHANG ; Hua JIANG ; Li HUANG ; Sixi LIU ; Xiaoya ZHOU ; Yun CAI ; Ming LI ; Fei GAO ; Xiaoting LIANG ; Kam-Sze TSANG ; Guangfu CHEN ; Chui-Yan MA ; Yuet-Hung CHAI ; Hongsheng LIU ; Chen YANG ; Mo YANG ; Xiaoling ZHANG ; Shuo HAN ; Xin DU ; Ling CHEN ; Wuh-Liang HWU ; Jiacai ZHUO ; Qizhou LIAN
Protein & Cell 2025;16(1):16-27
Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans
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Leukodystrophy, Metachromatic/genetics*
;
Pilot Projects
;
Genetic Therapy/methods*
;
Hematopoietic Stem Cell Transplantation
;
Male
;
Follow-Up Studies
;
Female
;
Lentivirus/genetics*
;
Child
;
Child, Preschool
;
Hematopoietic Stem Cells/metabolism*
;
Cerebroside-Sulfatase/metabolism*
;
Adolescent


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