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.

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-HsAlg1_23-464 were constructed and expressed in Escherichia coli, and the activity of recombinant HsAlg1 and HsAlg1_23-464 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, HsAlg1_23-464 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 ; Escherichia coli/metabolism* ; Mannosyltransferases/biosynthesis* ; Glycosylation ; Recombinant Proteins/metabolism* ; Protein Domains

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.

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.

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.

[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.

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.

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.

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.

Objective:To analyze the immunology-related risk factors for short-term prognosis in patients with demyelinating diseases of central nervous system, and to evaluate their predictive value.Methods:From January 2012 to October 2022 in Beijing Tiantan Hospital of Capital Medical University and General Hospital of Tianjin Medical University, the clinical data of 362 patients with demyelinating diseases of central nervous system were analyzed, including neuromyelitis optic spectrum disease (NMOSD) 181 cases, multiple sclerosis (MS) 129 cases, anti-myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) 38 cases, acute disseminated encephalomyelopathy (ADEM) 14 cases. According to the expanded disability status scale (EDSS) score at discharge, the patients were divided into good prognosis group (EDSS≤3 scores, 267 cases) and poor prognosis group (EDSS>3 scores, 95 cases). The clinical data, admission severity (admission EDSS score), treatment, autoantibodies and immunoglobulin level and serum inflammatory factor level were compared between two groups. Multivariate Logistic regression was used to analyze the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system; and the predictive efficacy was evaluated by receiver operating characteristic (ROC) curve.Results:Compared with the good prognosis group, the admission EDSS score in the poor prognosis group was significantly higher: 2.5 (1.5) scores vs. 6.5 (3.5) scores. The positive rates of autoimmune disease-related antibody, systemic autoantibody, anti-nuclear antibody, anti-extractable nuclear antigen antibody, thyroid peroxidase antibody and thyroid globulin antibody were significantly higher: 89.5% (85/95) vs. 59.6% (159/267), 75.8% (72/95) vs. 52.1% (139/267), 65.3% (62/95) vs. 38.6% (103/267), 42.1% (40/95) vs. 23.2% (62/267), 40.0% (38/95) vs. 19.1% (51/267) and 42.1% (40/95) vs. 19.9% (53/267). The serum IgM was significantly lower: 0.84 (0.78) g/L vs. 1.00 (0.75) g/L. The serum tumor necrosis factor-α, interleukin-2 receptor and cerebrospinal fluid IgG were significantly higher: 8 055 (3 118) pg/L vs. 6 830 (3 515) pg/L, 348 (175) kU/L vs. 314 (146) kU/L and 47.50 (46.50) g/L vs. 33.00 (24.00) g/L. And there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that the admission EDSS score and anti-nuclear antibody positive were the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system ( OR = 5.034 and 6.942, 95% CI 3.289 to 7.705 and 2.250 to 21.422, P<0.01). ROC curve analysis result showed that the area under the curve of anti-nuclear antibody positive combined with admission EDSS score predicted the short-term prognosis in patients with demyelinating diseases of central nervous system was 0.972, with a sensitivity of 90.5%, and a specificity of 92.5%. Conclusions:The admission EDSS score and anti-nuclear antibody positive are the independent risk factors for poor prognosis in patients with demyelinating diseases of central nervous system. And the combination of two indexes can better predict the short-term prognosis.