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.Full-length transcriptome sequencing and bioinformatics analysis of Polygonatum kingianum
Qi MI ; Yan-li ZHAO ; Ping XU ; Meng-wen YU ; Xuan ZHANG ; Zhen-hua TU ; Chun-hua LI ; Guo-wei ZHENG ; Jia CHEN
Acta Pharmaceutica Sinica 2024;59(6):1864-1872
The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of
3.RNA SNP Detection Method With Improved Specificity Based on Dual-competitive-padlock-probe
Qin-Qin ZHANG ; Jin-Ze LI ; Wei ZHANG ; Chuan-Yu LI ; Zhi-Qi ZHANG ; Jia YAO ; Hong DU ; Lian-Qun ZHOU ; Zhen GUO
Progress in Biochemistry and Biophysics 2024;51(11):3021-3033
ObjectiveThe detection of RNA single nucleotide polymorphism (SNP) is of great importance due to their association with protein expression related to various diseases and drug responses. At present, splintR ligase-assisted methods are important approaches for RNA direct detection, but its specificity will be limited when the fidelity of ligases is not ideal. The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection. MethodsIn this study, a dual-competitive-padlock-probe (DCPLP) assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation. To verify the method, we employed dual competitive padlock probe-mediated rolling circle amplification (DCPLP-RCA) to genotype the CYP2C9 gene. ResultsThe specificity was well improved through the competition and strand displacement of dual padlock probe, with an 83.26% reduction in nonspecific signal. By detecting synthetic RNA samples, the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L. Furthermore, clinical samples were applied to the method to evaluate its performance, and the genotyping results were consistent with those obtained using the qPCR method. ConclusionThis study has successfully established a highly specific direct RNA SNP detection method, and provided a novel avenue for accurate identification of various types of RNAs.
4.Analysis of the efficacy of arthroscopic transverse release of iliotibial band through peritrochanteric space for the treatment of external snapping hip
Yidong WU ; Kangkang YU ; Zhongyao LI ; Lu GAN ; Qi JIA ; Zhongyuan ZHAO ; Yang HE ; Zhikai GUO ; Chunbao LI
Chinese Journal of Orthopaedics 2024;44(1):18-24
Objective:To analyze the clinical efficacy of arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip.Methods:A total of 30 patients (12 males and 18 females) with bilateral external snapping hip underwent arthroscopic transverse release of the iliotibial band through peritrochanteric space in Department of Sports Medicine, Senior Department of Orthopaedics, the Fourth Medical Center, Chinese PLA General Hospital were retrospectively analyzed from May 2021 and June 2022. The average age was 32.5±8.2 years (range, 17-51 years). At the same time, 30 patients who underwent arthroscopic external release of the iliotibial band through the external surface of the iliotibial band (external iliotibial band group) were selected as control group, including 13 males and 17 females, aged 29.5±6.8 years (range, 11-45 years). The visual analogue scale (VAS), modified Harris hip score (mHHS), and gluteal muscle contracture disability scale (GDS) were compared between the two groups at preoperative, 6 months postoperative, and final follow-up.Results:All patients successfully completed the operation and were followed up for 17.5±3.3 months (range, 12-25 months). The VAS scores of the two groups at the last follow-up were lower than those before operation ( P<0.05). The mHHS scores before operation, 6 months after operation and at the last follow-up in the peritrochanteric space group were 76.5 (67.0, 85.5), 98.5 (94.8, 100.0) and 100.0 (97.0, 100.0), respectively, and those in the external iliotibial band group were 80.5 (70.0, 86.0), 100.0 (96.0, 100.0) and 100.0 (99.5, 100.0). The differences in mHHS scores between the two groups were statistically significant for intragroup comparisons ( P<0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in mHHS scores between groups at different time points ( P>0.05). The GDS before operation, at 6 months after operation and at the last follow-up were 47.0 (35.8, 64.5), 90.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the peritrochanteric space group, and 51.0 (38.0, 64.5), 50.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the external iliotibial band group, respectively. The differences in GDS between the two groups were statistically significant for intragroup comparisons ( P< 0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in GDS between groups at different time points ( P>0.05). Conclusion:Arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip can effectively reduce hip pain and improve hip function, with satisfactory clinical results, and can be used as an alternative treatment to transverse release through the external surface of the iliotibial band.
5.Predicting the death trend of stroke in Minhang District,Shanghai from 2023 to 2027 based on grey GM(1,1)model
Lin-Li CHEN ; Shui-Li XUAN ; Jing-Yi NI ; Jia-Qi GUO ; Wei LIU ; Hui-Lin XU ; Yi-Bin ZHOU
Fudan University Journal of Medical Sciences 2024;51(6):915-920,930
Objective To study the trend of stroke mortality in Minhang District,Shanghai from 2012 to 2022 and to predict stroke mortality from 2023 to 2027.Methods Annual percentage change(APC)of stroke deaths in Minhang District,Shanghai from 2012 to 2022 was calculated,and then Joinpoint linear regression model was used to analyze the time trend of stroke deaths.A grey GM(1,1)model was constructed based on the stroke mortality rate in Minhang District,Shanghai from 2012 to 2022.The model was used to predict and analyze the stroke mortality rate in Minhang District,Shanghai from 2023 to 2027.The fitting effect of the model was evaluated using relative error and grade deviation.Results From 2012 to 2022,the overall mortality rate of stroke in Minhang District,Shanghai was on the rise for both males and females(total population:APC=2.50%,P<0.001;male:APC=3.41%,P<0.001;female:APC=1.46%,P=0.008).The grey GM(1,1)model was used to predict the increasing trend of stroke mortality rate in Minhang District from 2023 to 2027.The crude mortality rate of stroke in the entire population in 2027 would be 97.55/100000,with 112.31/100000 for males and 83.33/100000 for females.The fitting effect of the model was tested and evaluated to meet high requirements.Conclusion In the past decade,the mortality rate of stroke in Minhang District,Shanghai has shown a significant upward trend.The 5-year prediction results showed that the mortality rate will still on the rise year by year.
6.Improved unilateral puncture PVP based on 3D printing technology for the treatment of osteoporotic vertebral com-pression fracture
Wei-Li JIANG ; Tao LIU ; Qing-Bo ZHANG ; Hui CHEN ; Jian-Zhong BAI ; Shuai WANG ; Jia-Wei CHENG ; Ya-Long GUO ; Gong ZHOU ; Guo-Qi NIU
China Journal of Orthopaedics and Traumatology 2024;37(1):7-14
Objective To investigate the clinical effect of unilateral percutaneous vertebroplasty(PVP)combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture.Methods A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study,all of which were vertebral body compression fractures caused by trauma.According to different treatment methods,they were di-vided into experimental group and control group.Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group,there were 5 males and 27 females,aged from 63 to 91 years old with an average of(77.59±8.75)years old.Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty,including 7 males and 38 females,aged from 60 to 88 years old with an average of(74.89±7.37)years old.Operation time,intraoperative C-arm X-ray times,anesthetic dosage,bone cement injection amount,bone cement diffusion good and good rate,complications,vertebral height,kyphotic angle(Cobb angle),visual analogue scale(VAS),Oswestry disability index(ODI)and other indicators were recorded before and after surgery,and statistically analyzed.Results All patients were followed up for 6 to 23 months,with preoperative imaging studies,confirmed for thoracolumbar osteoporosis com-pression fractures,two groups of patients with postoperative complications,no special two groups of patients'age,gender,body mass index(BMI),time were injured,the injured vertebral distribution had no statistical difference(P>0.05),comparable data.Two groups of patients with bone cement injection,bone cement dispersion rate,preoperative and postoperative vertebral body height,protruding after spine angle(Cobb angle),VAS,ODI had no statistical difference(P>0.05).The operative time,intra-operative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P<0.05).Compared with the traditional bilateral puncture group,the modified unilateral puncture group combined with 3D printing technology had shorter operation time,fewer intraoperative fluoroscopy times and less anesthetic dosage.The height of anterior vertebral edge,kyphosis angle(Cobb angle),VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P<0.05).Conclusion In the treatment of thoracolumbar osteoporotic compression fractures,3D printing technology is used to improve unilateral puncture PVP,which is convenient and simple,less trauma,short operation time,fewer fluoroscopy times,satisfactory distribution of bone cement,vertebral height recovery and kyphotic Angle correction,and good functional improvement.
7.Hypericin inhibits the expression of NLRP3 in microglia of Parkinson's disease mice and alleviates the damage of DA-ergic neurons
Li-Shan FAN ; Jia ZHANG ; Si-Xiang NIU ; Qi XIAO ; Hui-Jie FAN ; Lei XU ; Li-Xia YANG ; Lu JIA ; Shao-Chen QIN ; Bao-Guo XIAO ; Cun-Gen MA ; Zhi CHAI
The Chinese Journal of Clinical Pharmacology 2024;40(17):2523-2527
Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9%NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P<0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.
8.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
9.Effects of Needle Retention Time for Scalp Acupuncture on Motor Dysfunction and Serum C-Reactive Protein,Blood Glucose and Blood Lipid of Post-Stroke Patients
Qi ZHONG ; Hai-Yan CAI ; Bing-Xu JIN ; Zhan-Xin HUO ; Hui-Yi LUO ; Qiu-Xia ZHONG ; Hao-Xun GUO ; Jia-Wen CHEN ; Shu-Hui ZOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1510-1516
Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P<0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P<0.05 or P<0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P<0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P<0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P<0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P>0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P<0.05 or P<0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P<0.05 or P<0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P<0.05 or P<0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P>0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.
10.Automatic nuclei segmentation of gastrointestinal cancer pathological images based on deformable attention transformer
Zhi-Xian TANG ; Zhen LI ; Qiao GUO ; Jia-Qi HU ; Xue WANG ; Xu-Feng YAO
Fudan University Journal of Medical Sciences 2024;51(3):396-403
Objective To achieve automatic segmentation of cell nuclei in gastrointestinal cancer pathological images by using a deep learning algorithm,so as to assist in the quantitative analysis of subsequent pathological images.Methods A total of 59 patients with gastrointestinal cancer treated in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from Jan 2022 to Feb 2022,were selected as the research objects.Python and LabelMe were used for data anonymization,image segmentation,and region of interest annotation of patients'pathological images.A total of 944 pathological images were included,and 9 703 nuclei were annotated.Then,a new semantic segmentation model based on deep learning was constructed.The model introduced deformable attention transformer(DAT)to realize automatic,accurate and efficient segmentation of pathological image nuclei.Finally,multiple segmentation evaluation criteria are used to evaluate the model's performance.Results The mean absolute error of the segmentation results of the model proposed in this paper was 0.112 6,and the dice coefficient(Dice)was 0.721 5.Its effect was significantly better than the U-net baseline model,and it was ahead of models such as ResU-net++,R2Unet and R2AttUnet.Moreover,the segmentation results were relatively stable with good generalization.Conclusion The segmentation model established in this study can accurately identify and segment the nuclei in the pathological images,with good robustness and generalization,which is helpful to play an auxiliary diagnostic role in practical applications.

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