1.Exploration of mechanism of action of tretinoin polyglucoside in rats with IgA nephropathy based on mitochondrial dynamics
Yan-Min FAN ; Shou-Lin ZHANG ; Hong FANG ; Xu WANG ; Han-Shu JI ; Ji-Chang BU ; Ke SONG ; Chen-Chen CHEN ; Ying DING ; Chun-Dong SONG
Chinese Pharmacological Bulletin 2024;40(11):2069-2074
Aim To investigate the effects of multi-gly-cosides of Tripterygium wilfordii(GTW)on mitochon-drial dynamics-related proteins and the mechanism of nephroprotective effects in IgA nephrophathy(IgAN)rats.Methods SPF grade male SD rats were random-ly divided into the Control group,modelling group,prednisone group(6.25 mg·kg·d-1)and GTW group(6.25 mg·kg·d-1).The IgAN rat model was established by the method of"bovine serum albumin(BSA)+carbon tetrachloride(CCl4)+lipopolysac-charide(LPS)".The total amount of urinary protein(24 h-UTP)and erythrocyte count in urine were meas-ured in 24 h urine.Blood biochemistry of serum albu-min(ALB),alanine aminotransferase(ALT),urea ni-trogen(BUN),and creatinine(Scr)were measured in abdominal aorta of the rats;immunofluorescence and HE staining were used to observe the histopathology of the kidneys;RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of key proteins regulating mitochondrial division and fu-sion:dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),and mitochondrial fusion pro-tein 2(Mfn2),and PTEN-induced putative kinase 1(Pink1),in the kidney tissue of rats.Results GTW significantly reduced urinary erythrocyte count and 24 h-UTP,decreased serum ALT,BUN and Scr levels,in-creased serum ALB levels,improved renal histopatho-logical status in IgAN rats,increased the protein and mRNA expression levels of Mfn1,Mfn2,and Pink1,and decreased the protein and mRNA expression levels of Drp1 in renal tissues.Conclusions GTW may regu-late mitochondrial structure and maintain the dynamic balance of mitochondrial dynamics by promoting the ex-pression of Mfn1,Mfn2,Pink1 and decreasing Drp1.This may result in a reduction in urinary erythrocyte counts and proteinuria,and an improvement in renal function.
2.Effects of Tripterygium glycosides tablets on LIGHT-HVEM/LTβR pathway in rats with IgA nephropathy
Xu WANG ; Hong FANG ; Yan-Min FAN ; Han-Shu JI ; Ke SONG ; Chen-Chen CHEN ; Ji-Chang BU ; Ying DING ; Chun-Dong SONG
Chinese Pharmacological Bulletin 2024;40(12):2277-2282
Aim To explore the mechanism of action of Tripterygium glycosides tablets on kidney of rats with IgA nephropathy based on inflammation-related path-ways.Methods Forty-five male SD rats of SPF grade were randomly divided into control group and modeling group.In addition to the blank group,the modeling group used the combination of bovine serum albumin(BSA)+carbon tetrachloride(CC14)+lipopolysac-charide(LPS)to establish the IgA nephropathy rat model.Successfully modeled rats were randomly divid-ed into the model group,the prednisone group and Tripterygium glycosides tablets group,and the treat-ment group was given the drug by gavage from the 13 th week,and the 24 hours urine,blood and kidney tis-sues of the rats were collected and examined after 4 weeks of the administration of the drug.Urine erythro-cyte count,quantitative 24-h urine protein(24 h-UTP),urea nitrogen(BUN),and blood creatinine(Scr)were detected in each group;serum interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)were detected by enzyme-linked immunosorbent assay(Elisa);the pathological changes in the renal tissues of the rats in each group were observed by horizontal hematoxylin-eosin(HE)staining;and the renal tis-sues in each group were observed by Western blotting.The expressions of LIGHT,HVEM,LTβR proteins and their mRNAs in rat kidney tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction(RT-PCR).Results Tripterygium glycosides tablets significantly reduced the levels of urinary erythrocyte count,24 h-UTP,BUN,and Scr in IgA nephropathy rats(P<0.01),improved renal histopathology,lowered the levels of se-rum inflammatory factors IL-1β and TNF-α(P<0.01),and lowered the levels of LIGHT,HVEM,LTβR proteins and their mRNA expression in renal tis-sues(P<0.01).Conclusions Tripterygium glyco-sides tablets may inhibit the immune response and re-duce the release of inflammatory factors by down-regu-lating the LIGHT-HVEM/LT(3R pathway,thus reduc-ing the inflammatory response,lowering the urinary e-rythrocytes and urinary proteins,improving the renal nephron pathologic injury,and protecting the renal function.
3.Comparison of self-radiopaque markers guiding physician-modified fenestration, chimney technique and hybrid Ⅳb technique on reconstruction of left subclavian artery in thoracic endovascular aortic repair
Xiye ZHAI ; Chang SHU ; Yidan ZHANG ; Bowen FAN ; Hui HAN ; Chuan TIAN ; Kun FANG ; Mingyao LUO
Chinese Journal of General Surgery 2024;39(9):662-666
Objective:To compare the effect of self-radiopaque markers guiding physician-modified fenestration, chimney technique and hybrid Ⅳb technique on reconstruction of left subclavian artery (LSA) in endovascular treatment of aortic dissection (TEVAR).Methods:The clinical and follow-up data of 312 TEVAR patients treated with LSA blood supply reconstruction technology from Jan 2016 to Dec 2019 at Fuwai hospital were retrospectively analyzed.Results:There were 35 patients in the hybrid Ⅳb technique group, 93 in the chimney technique group, and 184 in the in vitro fenestration group. The follow-up period ranged from 12 to 24 months. No artificial blood vessel and stent occlusion occurred in all patients during follow-up, and the LSA blood flow was unobstructed. A total of 19 patients had endoleak by the last follow-up, and there was no statistical difference between the three groups. Eleven patients underwent reintervention surgery, all were from chimney technique group and in vitro fenestration group, with no statistical difference ( P>0.05). Severe complications occurred in 28 patients during hospitalization, and the incidence of complications was the highest in the hybrid Ⅳb technique group ( P<0.01). During follow-up, 4 patients died in the bypass group, 6 died in the external window group, and 8 died in the chimney group, with no significant difference ( P>0.05). Conclusions:The safety and efficacy of the left subclavian artery flow reconstruction by in vitro fenestration and chimney technique were similar. The occurrences of early complications were lower than that of the hybrid Ⅳb technique, but the reintervention rate of endoleak was higher.
4.Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer
Shu-Han CHANG ; Kuan-Gen HUANG ; Lan-Yan YANG ; Yu-Bin PAN ; Chyong-Huey LAI ; Hung-Hsueh CHOU
Journal of Gynecologic Oncology 2024;35(5):e60-
Objective:
This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer.
Methods:
The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables.
Results:
Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH.After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively.The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group.
Conclusion
After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.
5.The role of prostatic urethral angle and intravesical prostatic protrusion on surgical capsule calculi formation in the prostate:A retrospective study
Jonathan YJ CHEN ; Han-Yu TSAI ; Chen-Pang HOU ; Shu-Han TSAO ; Yu-Ting CHEN ; Horng-Heng JUANG ; Yu-Hsiang LIN
Investigative and Clinical Urology 2024;65(5):459-465
Purpose:
To investigate the relationship between prostatic urethral angle (PUA) and the development of surgical capsule calculi (SCC) within the prostate, and to examine the presence and impact of intravesical prostatic protrusion (IPP).
Materials and Methods:
A retrospective analysis was conducted on 90 patients who underwent radical prostatectomy, with preoperative assessments using both transrectal ultrasound of the prostate (TRUS) and magnetic resonance imaging. Patients were divided into groups with and without SCC and further categorized into type 1 and type 2 stones based on the location and severity of the calculi. Statistical analysis included chi-square and independent sample t-tests, with p<0.05 considered significant.
Results:
Of the patients, 82.2% were diagnosed with SCC. No significant difference in PUA was found between patients with and without SCC. However, a notable disparity in IPP presence was observed, suggesting an inverse correlation with SCC development.Additionally, no significant differences were identified when comparing the two types of SCC based on PUA and IPP measurements.
Conclusions
The presence of IPP exhibited an inverse relationship with SCC, suggesting diminished urine flow pressure over the prostatic urethra may reduce the likelihood of SCC formation. However, no direct association between PUA and the presence or severity of SCC was identified. These findings highlight the complexity of factors contributing to prostatic calculi development and the potential role of IPP in this context.
6.Changes of parameters associated with anemia of inflammation in patients with stage Ⅲ periodontitis before and after periodontal initial therapy
Chang SHU ; Ye HAN ; Yuzhe SUN ; Zaimu YANG ; Jianxia HOU
Journal of Peking University(Health Sciences) 2024;56(1):45-50
Objective:To investigate the differences and similarities of parameters associated with ane-mia of inflammation between patients with stage Ⅲ periodontitis and periodontally healthy volunteers,and to explore the influence of periodontal initial therapy on those indicators.Methods:Patients with stageⅢ periodontitis and periodontally healthy volunteers seeking periodontal treatment or prophylaxis at De-partment of Periodontology,Peking University School and Hospital of Stomatology from February 2020 to February 2023 were enrolled.Their demographic characteristics,periodontal parameters(including pro-bing depth,clinical attachment loss,bleeding index),and fasting blood were gathered before periodontal initial therapy.Three months after periodontal initial therapy,the periodontal parameters of the patients with stage Ⅲ periodontitis were re-evaluated and their fasting blood was collected again.Blood routine examinations(including white blood cells,red blood cells,hemoglobin,packed cell volume,mean cor-puscular volume of erythrocytes,and mean corpuscular hemoglobin concentration)were performed.And ferritin,hepcidin,erythropoietin(EPO)were detected with enzyme-linked immunosorbent assay(ELISA).All data analysis was done with SPSS 21.0,independent sample t test,paired t test,and analysis of co-variance were used for comparison between the groups.Results:A total of 25 patients with stage Ⅲperiodontitis and 25 periodontally healthy volunteers were included in this study.The patients with stageⅢ periodontitis were significantly older than those in periodontally healthy status[(36.72±7.64)years vs.(31.44±7.52)years,P=0.017].The patients with stage Ⅲ periodontitis showed lower serum he-moglobin[(134.92±12.71)g/L vs.(146.52±12.51)g/L,P=0.002]and higher serum ferritin[(225.08±103.36)μg/L vs.(155.19±115.38)μg/L,P=0.029],EPO[(41.28±12.58)IU/L vs.(28.38±10.52)IU/L,P<0.001],and hepcidin[(48.03±34.44)μg/L vs.(27.42±15.00)μg/L,P=0.009]compared with periodontally healthy volunteers.After adjusting the age with the co-variance analysis,these parameters(hemoglobin,ferritin,EPO,and hepcidin)showed the same trends as independent-sample t test with statistical significance.Three months after periodontal initial therapy,all the periodontal parameters showed statistically significant improvement.The serum hemoglobin raised[(146.05±15.48)g/L vs.(133.77±13.15)g/L,P<0.001],while the serum ferritin[(128.52± 90.95)μg/Lvs.(221.22±102.15)μg/L,P<0.001],EPO[(27.66±19.67)IU/L vs.(39.63± 12.48)IU/L,P=0.004],and hepcidin[(32.54±18.67)μg/L vs.(48.18±36.74)μg/L,P=0.033]decreased compared with baseline.Conclusion:Tendency of iron metabolism disorder and ane-mia of inflammation was observed in patients with stage Ⅲ periodontitis,which can be attenuated by periodontal initial therapy.
7.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
8.Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer
Shu-Han CHANG ; Kuan-Gen HUANG ; Lan-Yan YANG ; Yu-Bin PAN ; Chyong-Huey LAI ; Hung-Hsueh CHOU
Journal of Gynecologic Oncology 2024;35(5):e60-
Objective:
This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer.
Methods:
The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables.
Results:
Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH.After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively.The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group.
Conclusion
After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.
9.Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer
Shu-Han CHANG ; Kuan-Gen HUANG ; Lan-Yan YANG ; Yu-Bin PAN ; Chyong-Huey LAI ; Hung-Hsueh CHOU
Journal of Gynecologic Oncology 2024;35(5):e60-
Objective:
This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer.
Methods:
The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables.
Results:
Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH.After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively.The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group.
Conclusion
After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.
10.Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity
Chih-Hsin LIN ; Yu-Shao HSIEH ; Ying-Chieh SUN ; Wun-Han HUANG ; Shu-Ling CHEN ; Zheng-Kui WENG ; Te-Hsien LIN ; Yih-Ru WU ; Kuo-Hsuan CHANG ; Hei-Jen HUANG ; Guan-Chiun LEE ; Hsiu Mei HSIEH-LI ; Guey-Jen LEE-CHEN
Biomolecules & Therapeutics 2023;31(1):127-138
Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

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