1.Association of Rapidly Elevated Plasma Tau Protein With Cognitive Decline in Patients With Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Che-Sheng CHU ; Yu-Kai LIN ; Chia-Lin TSAI ; Yueh-Feng SUNG ; Chia-Kuang TSAI ; Guan-Yu LIN ; Chien-An KO ; Yi LIU ; Chih-Sung LIANG ; Fu-Chi YANG
Psychiatry Investigation 2025;22(2):130-139
Objective:
Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied.
Methods:
We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers.
Results:
After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%.
Conclusion
We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.
2.Association of Rapidly Elevated Plasma Tau Protein With Cognitive Decline in Patients With Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Che-Sheng CHU ; Yu-Kai LIN ; Chia-Lin TSAI ; Yueh-Feng SUNG ; Chia-Kuang TSAI ; Guan-Yu LIN ; Chien-An KO ; Yi LIU ; Chih-Sung LIANG ; Fu-Chi YANG
Psychiatry Investigation 2025;22(2):130-139
Objective:
Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied.
Methods:
We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers.
Results:
After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%.
Conclusion
We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.
3.Association of Rapidly Elevated Plasma Tau Protein With Cognitive Decline in Patients With Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Che-Sheng CHU ; Yu-Kai LIN ; Chia-Lin TSAI ; Yueh-Feng SUNG ; Chia-Kuang TSAI ; Guan-Yu LIN ; Chien-An KO ; Yi LIU ; Chih-Sung LIANG ; Fu-Chi YANG
Psychiatry Investigation 2025;22(2):130-139
Objective:
Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied.
Methods:
We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers.
Results:
After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%.
Conclusion
We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.
4.Association of Rapidly Elevated Plasma Tau Protein With Cognitive Decline in Patients With Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Che-Sheng CHU ; Yu-Kai LIN ; Chia-Lin TSAI ; Yueh-Feng SUNG ; Chia-Kuang TSAI ; Guan-Yu LIN ; Chien-An KO ; Yi LIU ; Chih-Sung LIANG ; Fu-Chi YANG
Psychiatry Investigation 2025;22(2):130-139
Objective:
Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied.
Methods:
We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers.
Results:
After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%.
Conclusion
We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.
5.Association of Rapidly Elevated Plasma Tau Protein With Cognitive Decline in Patients With Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Che-Sheng CHU ; Yu-Kai LIN ; Chia-Lin TSAI ; Yueh-Feng SUNG ; Chia-Kuang TSAI ; Guan-Yu LIN ; Chien-An KO ; Yi LIU ; Chih-Sung LIANG ; Fu-Chi YANG
Psychiatry Investigation 2025;22(2):130-139
Objective:
Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied.
Methods:
We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers.
Results:
After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%.
Conclusion
We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.
6.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
7.Intraoperative slide rail CT assistance in percutaneous sacroiliac joint screws for the treatment of pelvic posterior ring injury
Bin SHENG ; Yi-Wei WANG ; Yu-Si WANG ; De-Long LIU ; Zhan-Yu YANG ; Rui GUAN ; Chao LIU
China Journal of Orthopaedics and Traumatology 2024;37(5):438-444
Objective To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assis-tance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury.Methods A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022.Among them,39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of(44.98±7.33)years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy in-cluding 24 males and 13 females with an average age of(44.37±10.82)years old.Among them,42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation(INFIX)or suprapubic support screws to fix the anterior pelvic ring.Postoperative follow-up time,operation time,complications of the two groups were compared.Results of Matta reduction criteria,Majed efficacy evaluation,the CT grading and the rate of secondary surgical revision were com-pared.Results The nailing time of(32.63±7.33)min in CT group was shorter than that of(52.95±10.64)min in C-arm group(t=-9.739,P<0.05).The follow-up time between CT group(11.97±1.86)months and C-arm group(12.03±1.71)months were not statistically significant(P>0.05).The postoperative complication rates between two groups were not statistically significant(x2=0.159,P>0.05).Results of Matta reduction criteria(Z=2.79,P<0.05),Majeed efficacy evaluation(Z=2.79,P<0.05),CT grading(Z=2.83,P<0.05)in CT group were better than those in C-arm group(P<0.05);the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group(x2=5.641,P<0.05).Conclusion Compared with traditional C-arm fluoroscopy,intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time,high accuracy and safety,and significant decrease in postoperative sec-ondary revision rate,and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.
8.Application of polyetheretherketone rod semi-rigid pedicle screw internal fixation in lumbar non-fusion surgery
Tao LIU ; Xing YU ; Jian-Bin GUAN ; Yong-Dong YANG ; He ZHAO ; Ji-Zhou YANG ; Yi QU ; Feng-Xian WANG ; Ding-Yan ZHAO ; Zi-Yi ZHAO
China Journal of Orthopaedics and Traumatology 2024;37(7):676-683
Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P<0.05).There was no significant differences in postoperative drainage between the two groups(P>0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)%vs(12.1±1.5)%]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)%vs(66.3±8.2)%]were significantly different(P<0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P>0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P>0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)%vs(18.4±2.4)%]and at the last follow-up[(9.8±1.6)%vs(12.1±1.5)%](P<0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P<0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P<0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P<0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P<0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.
9.Research on the equity of Chinese medicine human resource allocation and its driving paths in China:An analysis based on fsQCA method
Yong-Yi GUAN ; Jing ZHAO ; Yun-Han SU ; Ya-Ru LI ; Xin-Ran WANG ; Xin-Yu LIU
Chinese Journal of Health Policy 2024;17(10):46-51
Objective:To analyze the equity of Traditional Chinese medicine(TCM)human resource allocation across 31 provinces in China and explore its influencing pathways,aiming to provide scientific reference for optimizing the allocation of TCM human resources.Methods:The Health Resource Density Index(HRDI)was employed to measure the equity of TCM human resource allocation in China,and the fuzzy-set qualitative comparative analysis(fsQCA)was utilized to explore the configurational pathways influencing this equity.Results:Based on the data from 2021,the HRDI of TCM human resources in China exhibited significant regional disparities,manifesting as a distribution pattern of"high in the east and low in the west."Three pathways promoting high equity were identified:the internal-external balance-driven pathway(H1),the economy-demand co-driven pathway(H2),and the government-led driving pathway(H3).Meanwhile,three pathways leading to low equity were also recognized:the economy-demand constraint pathway(L1)and the internal-external constraint pathways(L2、L3).Conclusion:There are notable regional disparities in the equity of TCM human resource allocation in China,with multiple factors jointly influencing this equity,among which population density serves as a core factor.In subsequent efforts to enhance equity,it is advisable to consider optimizing the synergies among multiple factors and implementing precise policies for different regions to promote efficient allocation and balanced development of TCM human resources.
10.Improving effect of selenium on spermatogenesis in mice with cyclophosphamide-induced spermatogenic impairment and its underlying mechanism
Fan XIAO ; Wen-Jing CHENG ; Guan-Xiang YUAN ; Jin-Quan CHENG ; Pei-Yi LIU
National Journal of Andrology 2024;30(4):291-299
Objective:To investigate the effect of selenium on cyclophosphamide(CTX)-induced spermatogenic impairment(SI)in mice and its underlying mechanism.Methods:We equally randomized 36 male KM mice into 3 SI model and 3 control groups,the first 3 treated by intraperitoneal injection of CTX at 100 mg/kg(the SI model control group),CTX plus SI model control group,selenium deficient model group(-Se SI),selenium supplemented model group(+Se SI),while latter 3 by intraperitoneal injection of normal saline(the normal control),selenium deficiency control group(-Se control),selenium addition control group(+Se control),respectively,all once a week for 6 successive weeks.Then we observed the histopathological changes in the testes of all the mice by HE staining,obtained the sperm count in the epididymides,determined the expressions of glutathione peroxidase 4(GPx4)and SLC7A11 proteins by Western blot and ferroptosis-related genes by RT-qPCR,and examined the changes in the expres-sions of ferroptosis-related proteins and genes in the GC2-spd cells treated with ferroptosis inhibitors and inducers in combination with different concentrations of inorganic sodium selenite(SeS)and organic selenomethionine(SeM).Results:Compared with the nor-mal controls,the SI model mice showed significantly decreased testicular and prostatic organ coefficients,reduced spermatogenic lay-ers,increased voids,decreased serum ferritin concentration(P<0.05),and elevated transferrin concentration(P<0.05).The or-gan coefficients were significantly higher in the+Se SI and+Se control than in the-Se SI and-Se control groups(P<0.05,P<0.01),with evident pathological improvement of the testis tissue in the+Se controls.The expressions of the GPx4 and solute carrier family 7 members 11(SLC7A11)genes in the testis were dramatically down-regulated in the SI model controls(P<0.01),but up-reg-ulated in the+Se SI and+Se control compared with those in the-Se SI and-Se control group(P<0.01 and P<0.05),but there were no statistically significant differences between their protein expressions.The results of in vitro GC2 spd cell experiments indicated that the GPx4 gene and GPx4 protein levels in the-Se group were significantly lower than those in the normal control group(P<0.05),while the SLC7A11 gene level decreased(P<0.01).Different doses of SeS and SeM significantly increased the GPx4 protein expression compared to the average Se group.Low doses of SeM promoted a significant increase in GPx4 gene levels,while high doses of SeS increased the expression levels of SLC7A11 gene and SLC7A11 protein(P<0.05,P<0.01).The Se group showed a signifi-cant decrease in the levels of acsl4 and ptgs2 genes compared to the normal control group.SeM promoted the expression of acsl4,while SeS promoted the expression of ptgs2 and fth1(P<0.01,P<0.05).The intervention results of GC2 spd showed that the Erastin group had a decrease in ptgs2 compared to the normal control group,while the SeS+Erastin and SeM+Erastin groups had an increase in ptgs2 gene expression compared to the Erastin group.However,the ptgs2 expression of Fer-1 was lower than that of the normal con-trol group,and the ptgs2 gene level of SeS+Fer-1 and SeM+Fer-1 groups was lower than that of Fer-1 group(P<0.05);The gene quantity of GPx4 in the SeM+Erastin and SeM+Fer-1 groups increased compared to the Erastin and Fer-1 groups(P<0.01,P<0.05);SeM+Erastin and SeS+Erastin showed a decrease in SLC7A11 compared to the Erastin group,as well as SeM+Fer-1 and SeS+Fer-1 groups compared to the Fer-1 group,accompanied by an increase in acsl4 and fth1(P<0.01).Conclusion:Selenium deficiency causes the reduction of the SLC7A11 and GPx4 gene levels,disorder of ferroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes.Selenium can promote the expression of GPx4,up-regulate the level of SLC7A11,and improve spermatogenesis in the testis of the mouse with SI.There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related genes.

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