Research advances in the role of Rab GTPases in Alzheimer's disease / 生理学报

Extracellular deposition of β-amyloid (Aβ) and intracellular hyperphosphorylated tau are the predominant pathological changes in Alzheimer's disease (AD). Increasing evidence demonstrates a critical role of a variety of small GTPases, namely Ras-related proteins (Rabs), in the pathogenesis of AD. As crucial regulators of intracellular membrane trafficking, alteration in Rab protein expression and function represents one of the primary factors contributing to the abnormal membrane trafficking in AD. Additionally, the Rab GTPases are also involved in the development of Aβ, tau and other pathological changes associated with AD. In this article, we conduct a comprehensive review on the primary functions of multiple Rab proteins and their involvement in the pathogenesis of AD.

Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity / 中西医结合学报

OBJECTIVE@#Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.@*METHODS@#Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence.@*RESULTS@#Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.@*CONCLUSION@#SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6. Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; 21(5): 464-473.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse / 中华医学杂志(英文版)

BACKGROUND@#It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011.@*METHODS@#A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided).@*RESULTS@#The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107).@*CONCLUSIONS@#The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly.@*TRIAL REGISTRATION NUMBER@#NCT03620565, https://register.clinicaltrials.gov.

Short-term efficacy of pectopexy in the treatment of middle pelvic defects / 中国实用妇科与产科杂志

OBJECTIVE: To explore the short-term clinical effect and safety of pectopexy in the treatment of female middle pelvic defects.METHODS: Collect the clinical data and follow-up information of 32 patients,who underwent pectopexy due to pelvic prolapse with POP-Q score aboveⅡ in the Third Affiliated Hospital of Zhengzhou University and Shengjing Hospital of China Medical University from August 2018 to January 2019.The objective clinical efficacy and the results of PFDI-20 and PFIQ-7 questionnaires for pelvic floor dysfunction were evaluated by comparing the locations of Aa,Ba,Ap,Bp,C and TVL indicators of quantitative pelvic organ prolapse(POP-Q)scale before operation,1 month and 3 months after operation.RESULTS: The 32 patients completed pectopexy in 52-75 minutes,the average time being(59.22 ± 29.21)minutes;intraoperative bleeding was 10-400 mL,the average being(83.75 ± 78.89)mL;indwelling catheter days were 1-5 days,the average being(2.24±0.83)days;residual urine was 0-100 mL,the average being(32.79±29.81)mL;postoperative hospitalization days were 5-12 days,the average being(7.41±1.59)days.There was 1 case(3.13%)of asymptomatic venous thrombosis in the lower extremity during the perioperative period and 1 case(3.13%)of hypostatic pneumonia,and they were cured after active treatment.No complications occurred in the otherpatients during the perioperative period.During the follow-up period,pelvic discomfort occurred in 1 case(3.13%),which was relieved after active treatment,andno complications occurred in the rest of the patients.There was no significant difference(P>0.05)between TVL preoperatively and postoperatively at 1 and 3 months[(7.94±0.84)cm vs.(7.73±0.60)cm vs.(7.61±0.58)cm].There were significant differences in Aa[(0.94±1.92)cm vs.-(2.81±0.40)cm vs.-(2.81±0.40)cm],Ba[(2.28±2.62)cm vs.-(2.78±0.42)cm vs.-(2.78±0.42)cm],Ap[-(2.00±1.41)cm vs.-(2.92±0.26)cm vs.-(2.91±0.30)cm],Bp[-(0.91±2.78)cm vs.-(2.25±0.44)cm vs.-(2.25±0.44)cm]and C[(3.58±2.47)cm vs.-(7.72±0.58)cm vs.-(7.56±0.58)cm]among the other indicators(P<0.05).There were significant differences in PFIQ-7[(77.56±40.87)vs.(7.87±10.92)]and PFDI-20[(68.55 ± 35.05)vs.(7.66 ± 6.50)]scores before and 3 months after operation(P<0.05).CONCLUSION: Pectopexy provides new ideas and options for the treatment of pelvic defects.At present,large sample data and longterm follow-up are still needed to further observe the long-term efficacy.

Expression and subcellular localization of APOBEC3G in peripheral blood mononuclear cells and liver tissues of chronic HBV patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the expression level and intracellular localization of APOBEC3G in peripheral blood mononuclear cells (PBMCs) and liver tissues of chronic HBV patients.</p><p><b>METHODS</b>The expression level and intracellular localization of APOBEC3G in PBMCs and liver tissues were detected using the western blot and confocal laser scanning microscope (CLSM).</p><p><b>RESULTS</b>Western-blot showed that the expression level of APOBEC3G in PBMCs of healthy controls was very low. The relative expression levels of APOBEC3G in PBMC of patients with chronic hepatitis B, chronic severe hepatitis, liver cirrhosis, or liver cancer were 4.12+/-0.21, 4.07+/-0.28, 4.16+/-0.36 or 4.21+/-0.39 respectively, which were higher than that in the healthy controls. However, there was no significant difference in APOBEC3G expression among different chronic HBV patients (q = 0.931, 0.744, 1.675, 1.675, 2.606 or 0.931, respectively, all P values more than 0.05). In addition, there was no significant difference on APOBEC3G in liver tissues between chronic hepatitis B patients and hepatocellular carcinoma patients (4.40+/-0.34 vs 4.34+/-0.43, q = 0.588, P more than 0.05). CLSM indicated that the localization of APOBEC3G protein was in cytoplasm of PBMCs and hepatocytes.</p><p><b>CONCLUSION</b>APOBEC3G is upregulated in the PBMCs of chronic hepatitis B patients.</p>