1.GPCRs identified on mitochondrial membranes: New therapeutic targets for diseases.
Yanxin PAN ; Ning JI ; Lu JIANG ; Yu ZHOU ; Xiaodong FENG ; Jing LI ; Xin ZENG ; Jiongke WANG ; Ying-Qiang SHEN ; Qianming CHEN
Journal of Pharmaceutical Analysis 2025;15(7):101178-101178
G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.
2.Prokaryotic expression of human Alg1 protein and analysis of the transmembrane domain properties.
Dongzhi WEI ; Zhenghui CHEN ; Chundi WANG ; Xiaodong GAO ; Ning WANG
Chinese Journal of Biotechnology 2025;41(4):1535-1546
As the most common type of protein glycosylation, N-glycosylation begins with the synthesis of the dolichol-linked oligosaccharide (DLO) precursor in the endoplasmic reticulum. The mannosyltransferase Alg1 catalyzes the addition of the first mannose molecule to DLO, serving as a key enzyme in this biochemical pathway. The defect of human ALG1 gene can lead to the congenital disorders of glycosylation (CDG), i.e., ALG1-CDG. Therefore, it is of great significance to establish the expression and activity assay system of Homo sapiens Alg1 (HsAlg1) in vitro. In this study, full-length plasmid pET28a-His6-HsAlg1 and transmembrane domain-lacking plasmid pET28a-His6-HsAlg123-464 were constructed and expressed in Escherichia coli, and the activity of recombinant HsAlg1 and HsAlg123-464 was measured by liquid chromatography tandem mass spectrometry (LC-MS) with dolichyl-pyrophosphate GlcNAc2 (DPGn2) as the substrate. The results showed that HsAlg1 had transglycosylation activity, while the activity decreased after protein purification, which was partially restored upon re-addition of membrane components. However, HsAlg123-464 was unable to catalyze glycosylation. The results indicate that the N-terminal transmembrane domain (TMD) of HsAlg1 plays an important role in the catalytic reaction. This study lays a foundation for further expression and activity analysis of ALG1-CDG-related mutants.
Humans
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Escherichia coli/metabolism*
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Mannosyltransferases/biosynthesis*
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Glycosylation
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Recombinant Proteins/metabolism*
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Protein Domains
3.Incidence and risk factors of acute renal injury after Stanford type A aortic dissections
Xiao XU ; Xiaodong LI ; Jing WEN ; Jiaolin NING
Journal of Army Medical University 2025;47(14):1642-1651
Objective To explore the occurrence of acute kidney injury(AKI)in patients with Stanford type A aortic dissection(TAAD)after surgical treatment,analyze the risk factors,and construct a prediction model.Methods A retrospective case-control study was conducted on 138 TAAD patients undergoing surgical treatment in our hospital from January 2016 to June 2024.After Kidney Disease Improving Global Outcomes(KDIGO)criteria was performed within 1 week after surgery,they were divided into AKI(n=95)and non-AKI(n=43)groups.Univariate and multivariate logistic regression analyses were performed to identify the perioperative risk factors.Then a nomogram model were constructed,and receiver operating characteristic(ROC)curve was plotted to analyze its predictive efficacy.Results The incidence of postoperative AKI was 68.84%(95 cases)in the TAAD patients,including 51.58%(49 cases)of stage 3 AKI and 38.95%(37 cases)requiring continuous renal replacement therapy.The length of ICU stay,time to extubation,and abandonment of treatment were significantly higher in the AKI group than the non-AKI group(P<0.001).Multifactorial analysis showed that the monocyte count on postoperative day 1(OR=3.521)and preoperative creatinine level(OR=1.019)were independent risk factors for AKI,postoperative uric acid level(OR=1.005)was correlated with AKI,and intraoperative urine volume(OR=0.739)and globulin level at 1 d postoperatively(OR=0.781)were protective factors.The area under the ROC curve of the constructed model was 0.866,with a sensitivity of 0.811 and a specificity of 0.791.Conclusion Postoperative AKI occurrence can be reduced in TAAD patients by optimizing the intraoperative urine output,modulating the postoperative inflammatory response,and strengthening nutritional support.Our prediction model for AKI risk is of significance for early clinical identification of high-risk patients in TAAD patients after surgical treatment.
4.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
5.Effects of biorhythm factors on development of acute kidney injury after cardiac surgery using cardiopulmonary bypass: a retrospective cohort study
Xiaodong LI ; Jing WEN ; Xiao XU ; Xianjian LIAO ; Yuxi SONG ; Jiaxiang DUAN ; Kaizhi LU ; Bin YI ; Jiaolin NING
Chinese Journal of Anesthesiology 2024;44(9):1093-1096
Objective:To evaluate the effects of biorhythm factors on the occurrence of acute kidney injury (AKI) after cardiac surgery using cardiopulmonary bypass.Methods:This was a retrospective cohort study. Data from patients undergoing heart surgery involving cardiopulmonary bypass from June 2018 to December 2019 were collected and divided into 2 groups ( n=125 each) based on the time of anesthesia operation: morning rhythm group (group Ⅰ) and afternoon rhythm group (group Ⅱ). Anesthesia operation was performed from 8: 00 to 12: 00 in group Ⅰ. Anesthesia was performed from 14: 00 to 18: 00 in group Ⅱ. The occurrence of postoperative AKI and other postoperative complications (pulmonary infection, sepsis, cerebral infarction) was recorded. Results:Compared with group Ⅱ, the incidence of postoperative AKI was significantly increased, the relative risk was 3.2 (95% confidence interval 1.31-7.70), and no significant change was found in the incidence of pulmonary infection, sepsis and cerebral infarction in group Ⅰ ( P>0.05). Conclusions:Biorhythm factors affect the development of AKI after cardiac surgery using cardiopulmonary bypass, and performing surgeries in the afternoon rather than the morning helps reduce the risk of postoperative AKI.
6.Application of pelvic floor muscle training based on timing theory in patients undergoing radical prostatectomy
Xiaoli YAN ; Ning LIN ; Xiaodong LI ; Xiaodan LIN ; Ping JIANG
China Modern Doctor 2024;62(24):59-63
Objective To investigate the effect of pelvic floor muscle training based on timing theory in patients undergoing robot-assisted laparoscopic radical prostatectomy.Methods A total of 112 patients undergoing robot-assisted laparoscopic radical resection of prostate cancer in the First Affiliated Hospital of Fujian Medical University were selected as the study subjects from August 2021 to August 2022.57 patients in control group were given routine intervention measures,and 55 patients in experimental group were given pelvic floor muscle intervention based on timing theory on the basis of routine intervention measures.The intervention lasted for 1 year.The intervention effects of urinary control ability,urinary incontinence recovery rate and pelvic floor function rehabilitation were compared between two groups in each period after surgery.Results 24h after catheter removal,3 months and 6 months after the intervention,the experimental group had more advantages in urinary control score,urinary incontinence recovery rate and pelvic floor function recovery score(P<0.05),but there was no statistical significance in the above aspects between the two groups at 12 months after the operation(P>0.05).Conclusion The pelvic floor muscle training method based on the timing theory is scientific and feasible to a certain extent,and the intervention starts before surgery and lasts until 1 year after surgery,which significantly improves the postoperative urinary incontinence symptoms of patients with robot-assisted laparoscopic radical prostatectomy within the baseline level,improves the recovery rate of urinary incontinence,and helps the early rehabilitation of patients with postoperative urinary control ability.
7.Study on dosimetric analysis and efficacy of VMAT hypofractionated radiotherapy after breast cancer radical operation
Yajing ZHUANG ; Ning WANG ; Yantao GUO ; Pingyan LIAO ; Xiaodong LIU ; Haitao SUN ; Yuanyuan LU ; Xiangchen LIU ; Guosen HUANG
Chongqing Medicine 2024;53(16):2448-2452,2457
Objective To investigate the effectiveness and safety of volumetric modulated arc therapy (VMAT) hypofractionated radiotherapy and intensity modulated conformal radiotherapy technique (IMRT) conventional fractionated radiotherapy after breast cancer radical operation.Methods Eighty-five patients with breast cancer modified radical operation admitted and treated in this hospital from March 1,2021 to De-cember 30,2021 were selected as the research subjects and divided into the VMAT group (n=41) and the IM-RT group (n=42) according to the random number table method.The VMAT group adopted the hypofrac-tionated radiotherapy,with the single fractionated dose of 2.9 Gy/frequency and radiotherapeutic total dose of 43.5 Gy/15 frequencies;the IMRT group adopted the IMRT conventional fractionated radiotherapy,with the single fractionated dose of 2.0 Gy/frequency and radiotherapeutic total dose of 50.0 Gy/25 frequencies.The planning target region V95,V110,conformity index,homogeneity index,treatment time,V5,V20,V30,average dose (Dmean) in the affected side lung,humeral head Dmean and heart V30,Dmean were compared between the two groups.Meanwhile,local recurrence,distant metastasis,disease-free survival and acute and chronic radiation injury were compared between the two groups.Results Compared with the IMRT group,V95 in the VMAT was higher,V110 and homogeneity index were lower,the treatment time was shorter,V5 in the affected lung,Dmean and Dmean in the affected humeral head were lower,V30 in the affected lung was higher,heart V30 in the left side breast cancer was lower,heart Dmean in the right side breast cancer was lower,and the differences were statistically significant (P<0.05).All patients survived without local relapse.The distant metastasis rate and disease free survival rate had no statistical difference between the two groups (P>0.05).Follow up lasted for 12 months,the incidence rates of grade Ⅰ-Ⅱ acute radiodermatitis,radiation esophagitis,chronic radioder-matitis and radiation pneumonia had no statistical differences between the two groups (P>0.05).The inci-dence rate of grade Ⅰ-Ⅱ shoulder dysfunction in the VMAT group was lower than that in the IMRT group with statistical difference (P<0.05).No grade Ⅱ and above acute and chronic radiation injury in the two groups occurred.Conclusion VMAT hypofractionated radiotherapy after breast cancer radical operation is safe and effective.
8.Influencing factors of poor anal function after laparoscopic intersphincteric resection for extremely low rectal cancer and to construct a predictive model
Ning HAN ; Xiaodong WANG ; Yingchun LI ; Haihua ZHOU ; Linlin PAN ; Chen YU
Journal of Clinical Surgery 2024;32(8):887-891
Objective To analyze the influencing factors of poor anal function after laparoscopic intersphincteric resection(Lap-ISR)for extremely low rectal cancer,and to construct and verify a prediction model based on this model,in order to provide guidance for improving the anal function of patients with extremely low rectal cancer after Lap-ISR.Method A total of 127 patients with extremely low rectal cancer who underwent Lap-ISR in Taizhou People's Hospital from June 2020 to June 2022 were retrospectively selected.Patients were followed up for 12 months after surgery,and postoperative anal function was evaluated by the anal incontinence score(Wexner).According to Wexner score,the patients were divided into good anal function group(106 cases)and poor anal function group(21 cases).The clinical data of patients were collected and the risk factors affecting postoperative poor anal dysfunction were analyzed,and a Nomogram model was constructed to predict the risk of postoperative anal dysfunction in patients after Lap-ISR,and the receiver operating characteristic curve(ROC)was drawn.The area under the curve(AUC)was used to analyze the predictive efficacy of the prediction model for poor anal dysfunction after Lap-ISR.Result The incidence of anal dysfunction after Lap-ISR in patients with extremely low rectal cancer was 16.54%(21/127).Univariate analysis showed that there was no significant difference in gender,age,body mass index,clinical stage,combined underlying diseases,operation time,intraoperative blood loss,anastomosis method,and the distance from the lower edge of the tumor to the dentate line between the two groups(P>0.05).The proportion of tumor diameter≥5 cm,the proportion of neoadjuvant chemotherapy,the distance between anastomosis and anal verge<2 cm,and the proportion of anastomotic leakage in the anal dysfunction group were higher than those in the good anal function group(P<0.05).Cox multivariate regression analysis showed that tumor diameter≥5 cm(OR=5.124),neoadjuvant chemotherapy(OR=5.761)and anastomotic leakage(OR=6.881)were risk factors for postoperative anal function(P<0.05).Wexner score of patients with tumor diameter ≥5 cm was higher than that of patients with tumor diameter<5 cm,Wexner score of patients with neoadjuvant chemotherapy was higher than that of patients without neoadjuvant chemotherapy,and Wexner score of patients with anastomotic leakage was higher than that of patients without anastomotic leakage(P<0.05).Internal validation of Bootstrap method showed that the C-index was 0.785(95%CI:0.692-0.851).The results of ROC curve showed that the sensitivity and specificity of the nomogram model in predicting postoperative poor anal function of patients were 85.70%and 88.70%,respectively,and the AUC was 0.895(95%CI:0.795-0.984).Conclusion Tumor diameter,neoadjuvant chemotherapy and anastomotic leakage are risk factors for poor anal function after Lap-ISR in patients with extremely low rectal cancer.The nomogram risk prediction model based on the above risk factors has a good risk efficiency in evaluating the risk of postoperative anal dysfunction in patients.
9.Efficacy of transurethral blue laser prostatomy in the treatment of small volume benign prostatic hyperplasia
Miao YAO ; Ning TAO ; Xiaodong LI ; Maimaitiming ABULAITI ; Apizi AIRETI ; Niyazi SIDIKEJIANG ; Hengqing AN
Journal of Modern Urology 2024;29(11):984-987
[Objective] To explore the clinical efficacy and feasibility of blue laser transurethral incision of prostate (BLTUIP) in the treatment of small volume (≤30 mL) benign prostatic hyperplasia (BPH). [Methods] The clinical data of 34 BPH patients treated with BLTUIP in the First Affiliated Hospital of Xinjiang Medical University during Mar.and Oct.2023 were retrospectively analyzed.The operation time, 450 nm blue laser light emission time, 980 nm red laser light emission time, postoperative bladder irrigation time, international prostate symptom score (IPSS), quality of life score (QoL), maximum flow rate (Qmax), post-void residual (PVR), international index of erectile function-5 (IIEF-5), ejaculation and incidence of postoperative complications were analyzed. [Results] All operations were successful, without conversion to open or transurethral resection of the prostate (TURP). The operation time was 12.7 (10.8, 14.3) min, the 450 nm blue laser light emission time was 11.7 (9.6, 13.3) min, the 980 nm red laser light emission time was 1.0 (1.0, 2.0) min, the postoperative bladder irrigation time was 5.0 (2.8, 8.0) h, the total hospital stay was 6.0 (4.0, 7.0) d, the postoperative hospital stay was 2.0 (2.0, 3.0) d, and the postoperative catheter retention time was 2.0 (0, 2.0) d. After 3 or 6 months of follow-up, the IPSS, QoL and PVR were significantly lower than those before operation, while the Qmax was significantly higher, with significant differences (P<0.001); but there was no significant difference in the IIEF-5 score (P>0.05). During the 3-month follow-up, 4 patients (11.8%) had fever; during the 3-6 month follow-up, 1 patient (2.9%) had external urethral stricture; of the 8 patients with sexual life before operation, 1 (12.5%) had retrograde ejaculation after operation.No hematuria occurred. [Conclusion] BLTUIP is a new, safe and efficient surgical treatment for BPH with a volume ≤30 mL, which can shorten the operation time, reduce postoperative complications, and improve the quality of life.
10.The Chinese guideline for management of snakebites
Lai RONGDE ; Yan SHIJIAO ; Wang SHIJUN ; Yang SHUQING ; Yan ZHANGREN ; Lan PIN ; Wang YONGGAO ; Li QI ; Wang JINLONG ; Wang WEI ; Ma YUEFENG ; Liang ZIJING ; Zhang JIANFENG ; Zhou NING ; Han XIAOTONG ; Zhang XINCHAO ; Zhang MAO ; Zhao XIAODONG ; Zhang GUOQIANG ; Zhu HUADONG ; Yu XUEZHONG ; Lyu CHUANZHU
World Journal of Emergency Medicine 2024;15(5):333-355
In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

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