1.Lipopolysaccharide-induced Autophagy Increases SOX2-positive Astrocytes While Decreasing Neuronal Differentiation in the Adult Hippocampus
Wen-Chung LIU ; Chih-Wei WU ; Mu-Hui FU ; You-Lin TAIN ; Chih-Kuang LIANG ; I-Chun CHEN ; Chun-Ying HUNG ; Yu-Chi LEE ; Kay L.H. WU
Experimental Neurobiology 2022;31(5):307-323
Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g -1 •hour -1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2 + -Beclin 1 + and SOX2 + -S100β + cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.
2.Nucleophosmin modulates the alleviation of atopic dermatitis caused by the marine-derived compound dihydroaustrasulfone alcohol
Han Chun HUNG ; Chien Wei FENG ; Yen You LIN ; Chun Hong CHEN ; Kuan Hao TSUI ; Wu Fu CHEN ; Chieh Yu PAN ; Jyh Horng SHEU ; Chun Sung SUNG ; Zhi Hong WEN
Experimental & Molecular Medicine 2018;50(2):e446-
Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.
3.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
4.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
5.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
6.Treatment outcomes of patients with stage II pure endometrioid-type endometrial cancer: a Taiwanese Gynecologic Oncology Group (TGOG-2006) retrospective cohort study.
Hung Chun FU ; Jen Ruei CHEN ; Min Yu CHEN ; Keng Fu HSU ; Wen Fang CHENG ; An Jen CHIANG ; Yu Min KE ; Yu Chieh CHEN ; Yin Yi CHANG ; Chia Yen HUANG ; Chieh Yi KANG ; Yuan Yee KAN ; Sheng Mou HSIAO ; Ming Shyen YEN
Journal of Gynecologic Oncology 2018;29(5):e76-
OBJECTIVE: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. METHODS: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. RESULTS: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p < 0.001), recurrent urinary tract infections (p = 0.013), and leg lymphedema (p = 0.038). Age over 50-year (HR = 9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR = 7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR = 5.13; 95% CI, 1.38–19.1) and DSS (HR = 5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p = 0.046), but no impact on survival. CONCLUSION: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.
Cohort Studies*
;
Endometrial Neoplasms*
;
European Union
;
Female
;
Gynecology
;
Humans
;
Hysterectomy
;
Leg
;
Lymphedema
;
Neoplasm Grading
;
Obstetrics
;
Radiotherapy
;
Radiotherapy, Adjuvant
;
Recurrence
;
Retrospective Studies*
;
Urinary Tract Infections
;
Uterine Neoplasms
7.Innovative Nerve Root Protection in Full-Endoscopic Facet-Resecting Lumbar Interbody Fusion: Controlled Cage Glider Rotation Using the GUARD (Glider Used As a Rotary Device) Technique
Yu-Chia HSU ; Hao-Chun CHUANG ; Wei-Lun CHANG ; Yuan-Fu LIU ; Chao-Jui CHANG ; Yu-Meng HSIAO ; Yi-Hung HUANG ; Keng-Chang LIU ; Chien-Min CHEN ; Hyeun-Sung KIM ; Cheng-Li LIN
Neurospine 2024;21(4):1141-1148
This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.
8.Reducing Postoperative Neurological Complications in Uniportal Full-Endoscopic Lumbar Interbody Fusion: Efficacy of the GUARD Technique Combined With Delayed Ligamentum Flavectomy
Hao-Chun CHUANG ; Yu-Chia HSU ; Yuan-Fu LIU ; Chao-Jui CHANG ; Yu-Meng HSIAO ; Yi-Hung HUANG ; Keng-Chang LIU ; Chien-Min CHEN ; Hyeun Sung KIM ; Cheng-Li LIN
Neurospine 2024;21(4):1199-1209
Objective:
Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF.
Methods:
A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented.
Results:
Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates.
Conclusion
The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.
9.Innovative Nerve Root Protection in Full-Endoscopic Facet-Resecting Lumbar Interbody Fusion: Controlled Cage Glider Rotation Using the GUARD (Glider Used As a Rotary Device) Technique
Yu-Chia HSU ; Hao-Chun CHUANG ; Wei-Lun CHANG ; Yuan-Fu LIU ; Chao-Jui CHANG ; Yu-Meng HSIAO ; Yi-Hung HUANG ; Keng-Chang LIU ; Chien-Min CHEN ; Hyeun-Sung KIM ; Cheng-Li LIN
Neurospine 2024;21(4):1141-1148
This video presents a case of L4–5 unstable spondylolisthesis treated with full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF), emphasizing the GUARD (Glider Used as a Rotary Device) technique for nerve root protection. This innovative approach involves controlled rotation of the cage glider before cage insertion to minimize the risk of nerve root injury, a significant complication in Endo-TLIF procedures. The GUARD technique, validated in previous cadaveric studies, provides enhanced safety during cage insertion by protecting the nerve root. A 48-year-old woman with a 3-year history of progressive low back pain and bilateral lower extremity radiculopathy (right-sided predominance) was diagnosed with L4–5 unstable spondylolisthesis and spinal stenosis. After failure of conservative management, she underwent uniportal full-endoscopic facet-resecting transforaminal lumbar interbody fusion using the GUARD technique. Postoperatively, the patient experienced significant symptomatic improvement and resolution of radiculopathy, without any intraoperative nerve root injury or postoperative neurological deficits. This case demonstrates the effectiveness of the GUARD technique in reducing neurological complications and improving patient outcomes.
10.Reducing Postoperative Neurological Complications in Uniportal Full-Endoscopic Lumbar Interbody Fusion: Efficacy of the GUARD Technique Combined With Delayed Ligamentum Flavectomy
Hao-Chun CHUANG ; Yu-Chia HSU ; Yuan-Fu LIU ; Chao-Jui CHANG ; Yu-Meng HSIAO ; Yi-Hung HUANG ; Keng-Chang LIU ; Chien-Min CHEN ; Hyeun Sung KIM ; Cheng-Li LIN
Neurospine 2024;21(4):1199-1209
Objective:
Uniportal full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) carries a unique risk of nerve traction and abrasion injury during cage insertion. This study aims to evaluate the clinical efficacy of the GUARD technique and delayed ligamentum flavectomy in reducing postoperative radicular pain and neurapraxia in patients undergoing uniportal FE-TLIF.
Methods:
A retrospective analysis was conducted on 45 patients with an average age of 53.9±12.4 years who underwent either FE facet-sparing TLIF (FE fs-TLIF) or FE facet-resecting TLIF (FE fr-TLIF). Patients were divided into 2 groups: the sentinel group (21 patients) using traditional sentinel pin techniques, and the GUARD group (24 patients) using the GUARD technique with delayed ligamentum flavectomy. Patient-reported outcomes included the visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index. Complication rates, including incidental durotomy, postoperative neurapraxia, and hematoma, were also documented.
Results:
Postoperative radicular pain in the legs was significantly reduced at 6 weeks in the GUARD group compared to the sentinel group (VAS: 2.201 vs. 3.267, p=0.021). The incidence of postoperative neurapraxia was markedly lower in the GUARD group (0% vs. 19%, p=0.047). Both groups showed similar improvements in disc height, segmental lordosis, and lumbar lordosis at the 1-year follow-up, with no significant differences in endplate injury or fusion rates.
Conclusion
The GUARD technique and delayed ligamentum flavectomy significantly enhance patient safety by reducing postoperative radicular pain and neurapraxia without incurring additional costs. These techniques are easy to learn and integrate into existing surgical workflows, offering a valuable improvement for surgeons performing FE-TLIF procedures.