1.Lactate Transferase Function of Alanyl-transfer t-RNA Synthetase and Its Relationship With Exercise
Ying-Ying SUN ; Zheng XING ; Feng-Yi LI ; Jing ZHANG
Progress in Biochemistry and Biophysics 2025;52(6):1337-1348
Lactylation (Kla), a protein post-translational modification characterized by the covalent conjugation of lactyl groups to lysine residues in proteins, is widely present in living organisms. Since its discovery in 2019, it has attracted much attention for its role in regulating major pathological processes such as tumorigenesis, neurodegenerative diseases, and cardiovascular diseases. By mediating core biological processes such as signal transduction, epigenetic regulation, and metabolic homeostasis, lactylation contributes to disease progression. However, the lactylation donor lactyl-CoA has a low intracellular concentration, and the specific enzyme catalyzing lactylation is not yet clear, which has become an urgent issue in lactate research. A groundbreaking study in 2024 found that alanyl-transfer t-RNA synthetase 1/2 (AARS1/2), members of the aminoacyl-tRNA synthetase (aaRS) family, can act as protein lysine lactate transferases, modifying histones and metabolic enzymes directly with lactate as a substrate, without relying on the classical substrate lactyl-CoA, promoting a new stage in lactate research. Although exercise significantly increases lactate levels in the body and can induce changes in lactylation in multiple tissues and cells, the regulation of lactylation by exercise is not entirely consistent with lactate levels. Research has found that high-intensity exercise can induce upregulation of lactate at 37 lysine sites in 25 proteins of adipose tissue, while leading to downregulation of lactate at 27 lysine sites in 22 proteins. The level of lactate is not the only factor regulating lactylation through exercise. We speculate that the lactate transferase AARS1/2 play an important role in the process of lactylation regulated by exercise, and AARS1/2 should also be regulated by exercise. This review introduces the molecular biology characteristics, subcellular localization, and multifaceted biological functions of AARS, including its canonical roles in alanylation and editing, as well as its newly identified lactate transferase activity. We detail the discovery of AARS1/2 as lactylation catalysts and the specific process of them as lactate transferases catalyzing protein lactylation. Furthermore, we discuss the pathophysiological significance of AARS in tumorigenesis, immune dysregulation, and neuropathy, with a focus on exploring the expression regulation and possible mechanisms of AARS through exercise. The expression of AARS in skeletal muscle regulated by exercise is related to exercise time and muscle fiber type; the skeletal muscle AARS2 upregulated by long-term and high-intensity exercise catalyzes the lactylation of key metabolic enzymes such as pyruvate dehydrogenase E1 alpha subunit (PDHA1) and carnitine palmitoyltransferase 2 (CPT2), reducing exercise capacity and providing exercise protection; physiological hypoxia caused by exercise significantly reduces the ubiquitination degradation of AARS2 by inhibiting its hydroxylation, thereby maintaining high levels of AARS2 protein and exerting lactate transferase function; exercise induced lactate production can promote the translocation of AARS1 cytoplasm to the nucleus, exert lactate transferase function upon nuclear entry, regulate histone lactylation, and participate in gene expression regulation; exercise induced lactate production promotes direct interactions between AARS and star molecules such as p53 and cGAS, and is widely involved in the occurrence and development of tumors and immune diseases. Elucidating the regulatory mechanism of exercise on AARS can provide new ideas for improving metabolic diseases and promote health through exercise.
2.Genetic diversity of Ixodes persulcatus in parts of Inner Mongolia
Meng-Yu CUI ; Si SU ; Li-Li XING ; Lan MU ; Rui-Juan GAO ; Qi-Qi GUO ; Hong REN ; Dong-Dong QI ; Jing-Feng YU
Chinese Journal of Zoonoses 2024;40(4):295-301
The aim of this study was to clarify the genetic diversity and population history of Ixodes persulcatus in some ar-eas of Inner Mongolia in order to provide accurate data for effective vector control programs and reveal the transmission mecha-nism.Samples were collected in 10 areas of Inner Mongolia during the active tick season(April 2021-July 2023)using the flag-dragging and manual sampling methods.The 16S rRNA and COI gene were sequenced to clarify genetic diversity of I.per-sulcatus.The positivity rates for the COI gene and 16S rRNA were 90.00%and 98.33%respectively.Overall,18 and 15 haplotypes were identified for the COI gene and 16S rRNA,respectively,with a total haplotype diversity>0.762 and total nucleotide diversity<0.005.The Tajima's values and Fu's Fs were negative for significance.A nucleotide mismatch map was shown as a single peak.The genetic differentiation index FST of the population indicates a small degree of genetic differ-entiation of the population,while analysis of molecular vari-ance indicates that the variation within populations was greater than between populations.Phylogenetic tree and haplotype network plots showed confounding distributions between hap-lotypes.I.persulcatus from the Hinggan League and Hulun-buir regions can adapt to environmental changes and possess abundant genetic diversity.Genetic differentiation is mainly concentrated within the population and no geographical isolation was observed.
3.Spouse smoking cessation benefits the pregnancy outcomes of the women with polycystic ovary syndrome
Meng-Yi ZHU ; Jia-Xing FENG ; Yang LIU ; Jing-Shu GAO ; Yu WANG ; Xiao-Ke WU
National Journal of Andrology 2024;30(11):994-1001
Objective:To investigate the effect of spouse smoking cessation(SSC)on the pregnancy outcome of the patients with polycystic ovary syndrome(PCOS)based on a secondary analysis of the results of a large randomized clinical trial.Methods:Basedon the inclusion and exclusion criteria,this secondary analysis included 861 female participants in the Trial of Acu-puncture Combined with Clomiphene for PCOS from 2011 to 2015.According to the smoking status of their husbands,we divided the subjects into a smoking group(n=345),a non-smoking group(n=387),and a smoking cessation group(n=129),collected their general demographics,anthropometric indexes,laboratory results and pregnancy outcomes,compared them among the three groups,and analyzed the relationship of SSC with the pregnancy outcomes of the PCOS patients.Results:The levels of total testos-terone(T)and low-density lipoprotein cholesterol(LDL-C)in the smoking cessation group were similar to those in the non-smoking group,but significantly lower than those in the smoking group(P=0.014 and P=0.011).The contents of fasting insulin,total cho-lesterol,and apolipoprotein B exhibited statistically significant differences among the three groups(P=0.029,P=0.018 and P=0.024),dramatically lower in the smoking cessation and non-smoking groups than in the smoking group,but similar between the for-mer two.The ovulation rate of the smoking cessation group was similar to that of the non-smoking group,remarkably higher than that of the smoking group(P=0.038).No statistically significant differences were observed in other indicators among the three groups(P>0.05).Multivariate logistic regression analysis showed that SSC during pregnancy preparation was a protective factor for ovulation in the PCOS patients(OR=1.74,95%CI:1.04-2.92,P=0.035).Conclusion:SSC can improve androgen and glucolipid me-tabolisms of infertile patients with PCOS,and thereby significantly increase the ovulation rate.It is of positive significance to encourage SSC clinically for improving the pregnancy outcomes of infertile women with PCOS.
4.Efficacy and safety of tenofovir amibufenamide in the treatment of patients over 65 years of age with chronic hepatitis B
Sasa CHU ; Xing LIU ; Cheng XU ; Guozheng QIU ; Yao XU ; Jing DENG ; Meili FU ; Yulong PENG ; Feng GAO
Chinese Journal of Hepatology 2024;32(10):904-909
Objective:To investigate the efficacy and safety of tenofovir amibufenamide in patients over 65 years old with chronic hepatitis B and liver cirrhosis.Methods:We recruited 45 patients in Linyi People's Hospital with chronic hepatitis B and liver cirrhosis who were treated with TMF antiviral therapy for 48 weeks, compared the virologic response rate and HBV DNA decrease level at 12, 24 and 48 weeks, and the changes in hepatitis B surface antigen, alanine aminotransferase, glomerular filtration rate, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum phosphorus and blood lipids, and the changes in ALT normalization rate at 48 weeks. P<0.05 was statistically significant. Results:The age of the enrolled patients was 69.0 (67.0, 72.5) years. At 12, 24, and 48 weeks of treatment, the complete virological response rates were 32.4% (12/37), 70.0% (28/40), and 84.6% (33/39) respectively, and the level of HBV DNA decreased from baseline ( P<0.05). After 48 weeks of treatment, the level of HBsAg decreased ( P<0.05), and there was no negative HBsAg conversion and seroconversion. After 48 weeks of treatment, the level of ALT decreased ( P<0.05). At 48 weeks of treatment, the rates of ALT reverted to normality were 88.9% (16/18) and 70.4% (19/27), respectively. There was no significant difference in the levels of glomerular filtration rate, creatinine, phosphorus, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol estimated at baseline before and after treatment ( P>0.05), and no serious adverse events were observed. Conclusions:For patients over 65 years old with chronic hepatitis B and liver cirrhosis, TMF can significantly inhibit HBV DNA replication, and the ALT normalization rate is high and well tolerated.
5.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Exploration on the Application of Partially Nested Design in Effectiveness Assessment of Different Treatment for the Same Disease in TCM and Its Methodology
Shuo FENG ; Jizheng MA ; Yufeng GUO ; Jian CAO ; Jing HU ; Xing LIAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):26-30
Objective To introduce a partially nested design based on the characteristics of TCM in treating the same disease with different treatments and syndrome differentiation and treatment.Methods Partially nested design was used for standardized treatment of complex interventions.The TCM group was divided into multiple subsets according to"syndrome type-treatment method-prescription"(with nested structure),while the control group was treated with standardized Western medicine(without nested structure);taking a case study of"different treatments for the same disease"data for ulcerative colitis,this design type was applied and analyzed using a multi-level model.Results The partially nested design was consistent with the feature of TCM of"different treatments for the same disease"and met the methodological requirements for evidence-based evaluation.Multilevel models allowed analyses with this type of data.Conclusion The use of partially nested design enables the evaluation of the comprehensive effectiveness of"different treatments for the same disease",which can provide a methodological reference for the assessment of clinical effectiveness of TCM.
8.Clinical trial of pegylated losenatide in the treatment of obese patients with type 2 diabetes mellitus undergoing axial gastrectomy
Jing-Feng GU ; Hai-Xia LIU ; Feng FENG ; Jian ZHANG ; Dong-Yang XING ; Hao-Wen GAO ; Gui-Qi WANG
The Chinese Journal of Clinical Pharmacology 2024;40(3):330-334
Objective To observe the effects of pegylated losenatide injection combined with metformin tablets on serum metabolism,lipid levels and intestinal flora in obese type 2 diabetes mellitus(T2DM)patients after axial gastrectomy.Methods Obese T2DM patients who underwent axial gastrectomy were divided into treatment group and control group by cohort methods.The control group was treated with metformin hydrochloride tablet 0.5 g orally,tid.The treatment group was treated by subcutaneous injection of pegylated losenatide injection 0.2 mg once a week on the basis of control group.Both groups were treated continuously for 3 months.Body mass index(BMI),serum metabolic indexes,blood lipid levels,blood glucose levels,intestinal flora and adverse drug reactions were compared between the two groups.Results In this study,a total of 70 subjects were included in the treatment group,and 50 subjects were included in the control group.After three months of treatment,the BMI indices of the treatment and control groups were(26.35±2.36)and(29.34±3.59)kg·m-2,respectively;the glutathione peroxidase levels were(192.42±13.18)and(134.27±12.86)U;interleukin-6 levels were(6.14±1.78)and(7.65±2.09)μg·L-1;fasting blood glucose levels were(5.36±0.41)and(7.43±0.78)mmol·L-1;total cholesterol levels were(2.55±0.67)and(3.47±0.79)mmol·L-1 for the treatment and control groups,respectively.The levels of Bifidobacteria,Bacteroides,Lactobacilli,Enterobacteria,and Enterococci in the treatment group were(8.79±1.36),(9.62±1.37),(6.74±2.15),(7.98±0.61),and(7.23±1.29)logN·g-1,respectively;in the control group,these levels were(7.98±1.79),(8.13±1.45),(5.71±2.41),(9.21±0.88),and(8.15±1.54)logN·g-1.The differences in the above indicators between the treatment and control groups were statistically significant(all P<0.05).The main adverse drug reactions in the treatment group included nausea,headache,dizziness,elevated blood pressure,and indigestion.In the control group,the main adverse drug reactions were nausea,headache,and indigestion.The total incidence of adverse drug reactions in the treatment and control groups was 8.57%and 6.00%,respectively,with no statistically significant difference(P>0.05).Conclusion Pegylated losenatide injection combined with metformin tablets has a significant effect on axial gastrectomy in obese type 2 diabetes patients.
9.Clinical study on efficacy of different androgen deprivation regimens in the treatment of advanced prostate cancer
Huai-Jing LUO ; Ting-Ting ZHANG ; Xing-Mo DONG ; Chao-Lu LIN ; Feng YU
The Chinese Journal of Clinical Pharmacology 2024;40(4):519-523
Objective To compare the application effect of intermittent androgen deprivation(IAD)and continued androgen deprivation(CAD)on advanced prostate cancer and influence on prognosis.Methods The patients with advanced prostate cancer were divided into treatment group(86 cases)and control group(62 cases)according to the cohort method.The treatment group was given IAD regimen(subcutaneous injection of 3.6 mg goserelin once every 28 days)combined with oral administration of flutamide(250 mg every 3 times a day)or combined with oral administration of bicalutamide(50 mg once a day),and the control group was treated with CAD regimen(bilateral orchiectomy combined with continuous flutamide or bicalutamide orally,with the same dosage as the treatment group).The observation follow-up time of both groups was ≥9 months.Efficacy,serum total testosterone(TT),prostate specific antigen(PSA)and vascular endothelial growth factor(VEGF)were compared between the two groups after treatment,and the side effects of treatment,quality of life[Functional Assessment of Cancer Therapy-Prostate(FACT-P)]and disease progression were evaluated.Results At 9 months after treatment,the objective response rates(ORR)in treatment group and control group were 30.99%(22 cases/71 cases)and 29.09%(16 cases/55 cases),and the disease control rates(DCR)were 71.83%(51 cases/71 cases)and 69.09%(38 cases/55 cases)respectively(P>0.05).Serum TT levels in treatment group and control group were(25.53±9.44)and(22.51±8.28)ng·dL-1,PSA levels were(4.48±1.02)and(4.32±0.95)ng·mL-1,and VEGF levels were(121.03±35.26)and(118.65±33.42)pg·mL-1 respectively(all P>0.05).The incidence rates of hot flash in treatment group and control group were 21.13%and 56.36%,the incidence rates of breast swelling pain were 16.90%and 34.55%,and the incidence rates of osteoporosis were 8.45%and 25.45%respectively(all P<0.05).The scores of physical condition of FACT-P in treatment group and control group were(24.15±4.22)and(20.28±3.71)points,the scores of life condition were(20.28±2.94)and(17.81±2.84)points,scores of prostate cancer specific(PCS)module were(33.21±6.32)and(28.42±5.43)points,respectively,the difference were all statistically significant(all P<0.05).The cumulative progression-free survival rates in treatment group and control group were 61.97%and 58.18%(P>0.05).Conclusion IAD is as effective as CAD in the treatment of advanced prostate cancer and has a similar effect on the prognosis of patients,but the former one has fewer side effects of treatment and helps to improve the quality of life of patients.
10.Polycystin-2 Ion Channel Function and Pathogenesis in Autosomal Dominant Polycystic Kidney
Kai WANG ; Yuan HUANG ; Ce-Fan ZHOU ; Jing-Feng TANG ; Xing-Zhen CHEN
Progress in Biochemistry and Biophysics 2024;51(1):47-58
Polycystin-2 (also known as PC2, TRPP2, PKD2) is a major contributor to the underlying etiology of autosomal dominant polycystic kidney disease (ADPKD), which is the most prevalent monogenic kidney disease in the world. As a transient receptor potential (TRP) channel protein, PC2 exhibits cation-permeable, Ca2+-dependent channel properties, and plays a crucial role in maintaining normal Ca2+ signaling in systemic physiology, particularly in ADPKD chronic kidney disease. Structurally, PC2 protein consists of six transmembrane structural domains (S1-S6), a polycystin-specific “tetragonal opening for polycystins” (TOP) domain located between the S1 and S2 transmembrane structures, and cytoplasmic N- and C-termini. Although the cytoplasmic N-terminus and C-terminus of PC2 may not be significant in the gating of PC2 channels, there is still much protein structural information that needs to be thoroughly investigated, including the regulation of channel function and the assembly of homotetrameric ion channels. This is further supported by the presence of human disease-associated mutation sites on the PC2 structure. Moreover, PC2 synthesized in the endoplasmic reticulum is enriched in specific subcellular localization via membrane transport and can assemble itself into homotetrameric ion channels, as well as form heterotrimeric receptor-ion channel complexes with other proteins. These complexes are involved in a wide range of physiological functions, including the regulation of mechanosensation, cell polarity, cell proliferation, and apoptosis. In particular, PC2 assembles with chaperone proteins to form polycystic protein complexes that affect Ca2+ transport in cell membranes, cilia, endoplasmic reticulum, and mitochondria, and are involved in activating cell fate-related signaling pathways, particularly cell differentiation, proliferation, survival, and apoptosis, and more recently, autophagy. This leads to a shift of cystic cells from a normal uptake, quiescent state to a pathologically secreted, proliferative state. In conclusion, the complex structural and functional roles of PC2 highlight its critical importance in the pathogenesis of ADPKD, making it a promising target for therapeutic intervention.

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