1.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.
2.Separation and Enrichment of β-Agonists from Animal Livers Based on Magnetic Solid-Phase Extraction with Automated-treatment Device
Shu-Lin WEI ; Zi-Hao WANG ; Tong LI ; Huai-En ZHU ; Ji-Hao SHAN ; Zhi-Chao SONG ; Rui-Guo WANG
Chinese Journal of Analytical Chemistry 2024;52(2):277-285
A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.
3.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.
4.Pathological mechanism of hypoxia-inducible factor-1α in tumours and the current status of research on Chinese medicine intervention
Yu LIU ; Li-Ying ZHANG ; Guo-Xiong HAO ; Ya-Feng QI ; Qian XU ; Ye-Yuan LIU ; Chao YUAN ; Peng ZHU ; Yong-Qi LIU ; Zhi-Ming ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1670-1674
Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.
5.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
6.Visualized Analysis of Application Research of Wuling San in Recent 10 Years
Qi GUO ; Wei-Chi LU ; Zhang-Zhi ZHU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2195-2202
Objective A visualized analysis of the relevant literature on the application of Wuling San(Five-Ingredient Powder Containing Poria)in China in the recent 10 years was conducted to explore the application of Wuling San.Methods The applied research of Wuling San issued in the academic journals of CNKI from January 1,2013 to December 31,2022 were retrieved.The corresponding knowledge graphs were drawn with CiteSpace software,and the keywords of the literature were visualized and analyzed.Results A total of 1 121 articles related to the applied research of Wuling San were obtained after preliminary retrieval,and 1 104 articles were included for visual analysis after screening.The results of keyword co-occurrence analysis showed that Wuling San was usually used for treating cirrhosis ascites,chronic heart failure,diabetic nephropathy and other multi-system diseases,and it was mostly used by the compatibility of Taohong Siwu Decoction,Zhenwu Decoction,Xiaochaihu Decoction,Shenqi Pills and Linggui Zhugan Decoction.Wuling San was indicated for the symptoms of edema,dysuria and urinary retention.The commonly-used research methods for Wuling San included network pharmacology,molecular docking,etc.The results of keyword burst analysis showed that the hotspots of Wuling San applied research were as follows:cirrhosis in 2013,Yinchenhao Decoction in 2015,cerebral edema in 2018,and network pharmacology,novel coronavirus-infected pneumonia and cardiac function since 2020.Conclusion Wuling San is widely used in the clinic,and is indicated for water metabolism disorders.Wuling San in the treatment of cirrhotic ascites,chronic heart failure and diabetic nephropathy becomes the research hotspots in recent years.The applied researches of Wuling San on novel coronavirus-infected pneumonia and on improving cardiac function have become the trend and focus of current research.
7.Application Value of Xuanbai Chengqi Decoction Combined with Enteral Nutrition Support in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease Guided by the Theory of Simultaneous Treatment of Lung and Intestine
Guo-Qing ZHU ; Yan ZHOU ; Xian-Zhen LI ; Li-Li TANG ; He CHEN ; Zhi-Liang LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2312-2318
Objective To explore the application value of Xuanbai Chengqi Decoction combined with enteral nutrition support in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)guided by the theory of simultaneous treatment of lung and intestine.Methods A total of 92 patients with AECOPD were randomly divided into an observation group and a control group,46 cases in each group.Both groups were given routine symptomatic treatment.In addition,the control group was given enteral nutrition support intervention,and the observation group was given Xuanbai Chengqi Decoction combined with enteral nutrition support intervention.The course of treatment lasted for two weeks.The changes in the nutritional parameters such as serum albumin(ALB),prealbumin(PA),and transferrin(TF),and in the distribution of intestinal flora of the two groups were observed before and after treatment.After treatment,the clinical efficacy and the incidence of adverse reactions were compared between the two groups.Results(1)After two weeks of treatment,the total effective rate of the observation group was 97.83%(45/46),and that of the control group was 82.61%(38/46).The comparison between the two groups(tested by chi-square test)showed that the therapeutic efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the serum levels of nutritional parameters of ALB,PA and TF in the two groups were significantly higher than those before treatment(P<0.05),and the increase of serum ALB,PA and TF levels in the observation group was significantly superior to that in the control group,the differences being statistically significant(P<0.05 or P<0.01).(3)After treatment,the number of Lactobacillus and Bifidobacterium strains of intestinal flora in the two groups was significantly higher than that before treatment(P<0.05),and the number of Enterococcus strain was significantly lower than that before treatment(P<0.05).The increase in the number of Lactobacillus and Bifidobacterium strains and the decrease in the number of Enterococcus strains in the observation group were significantly superior to those in the control group,and the differences were statistically significant(P<0.05 or P<0.01).(4)The incidence of adverse reactions in the observation group was 4.35%(2/46),which was significantly lower than that in the control group(19.57%,9/46).The difference between the two groups was statistically significant(P<0.05).Conclusion Significant clinical efficacy has been achieved after the application of Xuanbai Chengqi Decoction combined with enteral nutrition support in treating AECOPD patients with lung heat and bowel excess syndrome guided by the theory of simultaneous treatment of lung and intestine.The combined therapy is effective on improving the nutritional status and intestinal flora imbalance of patients,and reducing the incidence of adverse reactions.
8.Localization and anatomical measurement of lateral compression Ⅱscrew guide needle insertion point for pelvic fracture
Yong-Zheng CHEN ; Zhen-Hua HU ; Shao-Juan LI ; Xia-Cun LIANG ; Li-Kang HOU ; Shu-Liang ZHU ; Xin-Ying BAI ; Jin-Jian HE ; De-Meng YANG ; Zhi-Guo CHEN
Acta Anatomica Sinica 2024;55(6):728-733
Objective To measure the distance between the lateral compression Ⅱ(LC-Ⅱ)screw guide needle and the surrounding important structures around the anterior inferior iliac spine in pelvic fractures and to locate the needle point,so as to provide anatomical reference for clinical nail placement.Methods Totally 40 adult gross specimens of embalming were implanted with LC-Ⅱ screw guide needle under the surveillance of C-arm machine,and the specimens were dissected.The shortest distance between the insertion point and the lateral femoral cutaneous nerve,femoral nerve,femoral artery,femoral vein,anterior superior iliac spine and inguinal ligament was measured.The triangle was constructed between the insertion point,anterior superior iliac spine and inguinal ligament,and the exact location of the entry point was calculated.Results The average distance between the insertion point of the male needle and the femoral vein was(50.67±7.29)mm>the anterior superior iliac spine(43.83±7.58)mm>the femoral artery(38.35±6.63)mm>the femoral nerve(31.17±1.67)mm=the inguinal ligament(28.69±6.59)mm>the lateral femoral cutaneous nerve(7.98±3.81)mm.The mean distance between the insertion point of the female needle and the anterior superior iliac spine was(45.28±7.07)mm=femoral vein(43.72±6.89)mm>femoral artery(33.76±6.33)mm>femoral nerve(25.66±6.46)mm=inguinal ligament(23.22±5.00)mm>lateral femoral cutaneous nerve(8.97±4.76)mm.The projection distance of the entry point was 31.77 mm for men and 38.41 mm for women.The Angle b was 42.81°for men and 31.71° for women.Conclusion The lateral femoral cutaneous nerve is most vulnerable to injury when LC-Ⅱ screw is inserted,and the risk of injury has nothing to do with sex.The insertion point positioning method a and b made LC-Ⅱ screw placement quickly,safely and accurately,and reduced fluoroscopy time and frequency.
9.Analysis of influencing factors of textbook outcome after pancreaticoduodenectomy and construction of nomogram model
Changqian TANG ; Yuqi GUO ; Yongnian REN ; Hengli ZHU ; Zhuangzhuang YAN ; Xingbo WEI ; Yifan ZHI ; Jizhen LI ; Deyu LI ; Liancai WANG
Chinese Journal of Hepatobiliary Surgery 2024;30(6):439-444
Objective:To analyze the influencing factors of achieving textbook outcome (TO) after pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma, and to construct a nomograph model to explore its predictive value in TO.Methods:The clinical data of 205 patients with pancreatic ductal adenocarcinoma treated by PD in Henan University People's Hospital from January 2019 to December 2022 were analyzed retrospectively, including 88 males and 117 females with the age of (61.3±9.8) years old. Patients were divided into two groups based on whether they achieved TO after surgery: TO group ( n=113) and non-TO group ( n=92). Clinical data such as age, gender, intraoperative blood loss, operation time, blood transfusion volume, pancreatic CT value, and tumor differentiation degree were collected. Logistic regression analysis screened the influencing factors of PD postoperative TO and built a nomogram model. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. Results:Multivariate logistic regression analysis showed that the higher the degree of tumor differentiation was in patients with pancreatic ductal adenocarcinoma (high differentiation to medium differentiation: OR=7.20, 95% CI: 1.20-43.28; high differentiation to low differentiation: OR=16.55, 95% CI: 2.01-136.11), CT value>38.45 Hu ( OR=0.29, 95% CI: 0.13-0.65), blood transfusion volume ≤350 ml ( OR=8.05, 95% CI: 2.94-22.01) and operative time ≤407.5 min ( OR=10.88, 95% CI: 3.90-30.41), the easier it was to achieve TO after PD (all P<0.05). Based on the above influencing factors, a nomogram model of the postoperative effect of PD on TO was established, and the consistency index of this column graph model was 0.863 (95% CI: 0.816-0.911). The sensitivity and specificity of ROC curve were 0.804 and 0.752, respectively. The calibration diagram showed that the calibration curve fits well with the ideal curve, and the decision curve showed that the model had obvious positive net benefit. Conclusion:The degree of tumor differentiation, CT value, blood transfusion volume, and operation time are independent influencing factors for the achievement of TO after PD in patients with pancreatic ductal adenocarcinoma, and the nomogram model constructed based on which has good predictive performance for TO.
10.Effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma after laparoscopic radical surgery
Xingbo WEI ; Yifan ZHI ; Changqian TANG ; Jizhen LI ; Hengli ZHU ; Yuqi GUO ; Yongnian REN ; Zuochao QI ; Dongxiao LI ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2024;30(9):641-645
Objective:To analyze the effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) after laparoscopic radical resection.Methods:Clinical data of 165 patients with HCC undergoing laparoscopic radical resection in Henan University People's Hospital from January 2018 to December 2021 were retrospectively analyzed, including 122 males and 43 females, aged (55.5±11.4) years. Patients were divided into sarcopenia group ( n=79) and control group (non-sarcopenia, n=86) according to the skeletal muscle index. The survivals were analyzed using the Kaplan-Meier method, and were compared by the log-rank test. Univariate and multivariate Cox regression were utilized to analyze the effect of sarcopenia on the prognosis of HCC after laparoscopic radical surgery. Results:The 1- and 3-year cumulative survival rates of control group were 96.4% and 81.2%, which were higher than those of the sarcopenia group (83.2% and 48.9%, respectively, χ2=19.67, P<0.001). The 1- and 3-year recurrence-free survival (RFS) rates of control group were 88.4% and 66.1%, which were higher than those of sarcopenia group (70.9% and 37.7%, respectively, χ2=18.80, P<0.001). Multivariate Cox regression analysis showed that the risk of recurrence ( HR=1.35, 95% CI: 1.20-1.59, P<0.001) and the risk of death ( HR=2.21, 95% CI: 1.23-3.41, P=0.001) after laparoscopic radical resection for HCC in patients with sarcopenia rises compared to non-sarcopenic patients. Conclusion:Sarcopenia is a risk factor for the survival and recurrence of HCC after laparoscopic radical surgery.

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