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.

Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Objective To summarize the clinicopathological characteristics and prognostic factors of salivary duct carcinoma(SDC)patients.Methods This study was reviewed and approved by the Ethics Committee,and informed consent was obtained from the patients.The clinical data of 30 SDC patients who were admitted to the Fourth Hospital of Hebei Medical University from 2014 to 2022,including case records,pathological diagnoses,immunohistochemical indicators,treatment methods,follow-up data,and other data,were retrospectively analyzed.SPSS 26.0 software was used to process the data and construct relevant curves.The chi-square test was used to analyze the correlation between different immunohistochemical indices and the recurrence and metastasis of SDC,and a single factor was used to ana-lyze clinical prognostic factors.Results Among the 30 SDC patients,the male-to-female ratio was 5∶1,with a median age of 61.5 years.Approximately 60％of cases occurred in the parotid gland,whereas the remainder occurred in the submaxillary gland,sublingual gland,or minor salivary gland.Among them,19 patients were androgen receptor-positive,23 patients were human epidermal growth factor receptor-2 positive,and 26 patients were Ki-67 positive.Postoperative follow-up was 18-94 months,with a median follow-up of 37 months.There were 13 cases of recurrence and 14 cases of distant metastasis.The 5-year overall survival rate was only 31.2％.The long-term survival of patients who underwent postoperative radiotherapy and chemoradiotherapy was better than that of patients who underwent surgery alone(P=0.027).T stage and lymph node invasion were associated with prognosis and survival(P＜0.05).There was a correlation between a Ki-67-positive cell count ≥ 40％and postoperative recurrence or metastasis(P=0.025).Conclusion Radi-cal surgery combined with postoperative radiotherapy and chemoradiotherapy is helpful for improving long-term overall survival,and tumor T stage and lymph node metastasis may be the main factors affecting the prognosis of patients with SDC.Patients with Ki-67-positive cell counts ≥ 40％are prone to postoperative recurrence or metastasis.

Objective:To investigate the clinical effect of magnetic stimulation combined with moxibustion on mild to moderate overactive bladder(OAB)and sexual function in women.Methods:We enrolled 80 female patients with mild to moderate OAB in this study and equally randomized them into a control and an experimental group,the former treated by magnetic stimulation and the latter by magnetic stimulation combined with moxibustion,both for 8 weeks.We obtained from the patients their OAB syndrome scores(OABSS),72-hour urination diary(72-h UD)scores,International Consultation on Incontinence Questionnaire-Overactive Bladder(ICIQ-OAB)scores and female sexual function indexes(FSFI),and compared them between the two groups before and after interven-tion.Results:A total of 77 patients completed the study,37 in the control and 40 in the experimental group.There were no statisti-cally significant differences in the baseline data between the two groups(P＞0.05).Compared with the baseline,the experimental group showed significant improvement after treatment in the OABSS(7.54±1.12 vs 4.46±0.96),72-h urine volume([126.40±46.04]vs[216.63±38.26]ml),urination frequency(15.55±3.21 vs 8.03±1.40),ICIQ-OAB score(10.25±1.15 vs 6.32±1.07)and FSFI(20.00±12.40 vs 33.30±21.00)(all P＜0.05),even more significantly than in the control group(OABSS:4.46±0.96 vs 5.59±0.90;72-h urine volume:[216.63±38.26]vs[173.41±15.55]ml;urination frequency:8.03±1.40 vs 9.90±1.49;ICIQ-OAB score:6.32±1.07 vs 7.89±0.77;FSFI:33.30±21.00 vs 30.40±10.40)(all P＜0.01).Conclu-sion:Magnetic stimulation combined with moxibustion can improve the symptoms of mild to moderate overactive bladder and improve sexual function in females.

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.
Animals ; Zebrafish/genetics* ; Apoptosis ; Larva ; Chemical and Drug Induced Liver Injury

OBJECTIVE: To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs). METHODS: A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery. RESULTS: In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred. CONCLUSION For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.
Humans ; Tarlov Cysts/epidemiology* ; Retrospective Studies ; Neoplasm Recurrence, Local/complications* ; Cysts/surgery* ; Pain

Objective To understand the distribution and antimicrobial resistance changes of bacteria isolated from pleural and peritoneal effusion in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Provincial Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacteria antimicrobial resistance surveillance method was imple-mented according to technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),and WHO-NET 5.6 software was used to analyze the data of bacteria isolated from pleural and peritoneal effusion as well as antimicrobial susceptibility testing results.Results From 2012 to 2021,a total of 28 934 bacterial strains were iso-lated from specimens of pleural and peritoneal effusions from member units of Hunan Provincial Antimicrobial Re-sistance Surveillance System,with 5 752 strains from pleural effusion and 23 182 from peritoneal effusion.The top five bacteria isolated from pleural effusion were Escherichia coli(n=907,15.8％),Staphylococcus aureus(n=535,9.3％),Klebsiella pneumoniae(n=369,6.4％),Staphylococcus epidermidis(n=452,7.9％),and Staphy-lococcus haemolyticus(n=285,5.0％).The detection rate of methicillin-resistant Staphylococcus aureus(MR-SA)from pleural effusion was 24.3％-39.2％,and that of methicillin-resistant coagulase negative Staphylococcus(MRCNS)was 58.8％-77.1％.The top five bacteria isolated from peritoneal effusion were Escherichia coli(n=8 264,35.6％),Klebsiella pneumoniae(n=2 074,9.0％),Enterococcus faecium(n=1 458,6.3％),Staphylo-coccus epidermidis(n=1 383,6.0％),and Pseudomonas aeruginosa(n=1 152,5.0％).The detection rate of MRSA from peritoneal effusion was 22.1％-52.4％,which presented a decreasing trend(P=0.004).The detec-tion rate of MRCNS was 60.4％-79.4％.The resistance rates of Enterobacterales from peritoneal effusion to ce-fazolin,cefuroxime,ceftriaxone and cefepime all showed decreasing trends(all P＜0.05).Vancomycin-,linezo-lid-,and teicoplanin-resistant Staphylococcus strains were not found in pleural and peritoneal effusions.The resis-tance rates of Enterococcus faecium to most tested antimicrobial agents were higher than those of Enterococcus fae-calis.The resistance rates of Enterobacterales to imipenem and meropenem were ≤8.5％.The resistance rates of non-fermentative Gram-negative bacilli to imipenem and meropenem were ≤43.3％.Conclusion The data structure of Hunan Antimicrobial Resistance Surveillance System for pleural and peritoneal effusions from 2012 to 2021 is relatively complete.The constituent and antimicrobial susceptibility of isolated pathogenic bacteria vary in different years.

Objective To understand the epidemiology of clinically isolated Acinetobacter baumannii(A.bauma-nnii)in Hunan Province.Methods Bacterial antimicrobial resistance surveillance was carried out according to the requirements of the technical program of National Antimicrobial Resistance Surveillance System.Clinical data of Acinetobacter spp.reported to Hunan Provincial Antimicrobial Resistance Surveillance System by multiple centers in Hunan Province from 2012 to 2021 were summarized and analyzed with reference to the standards of the American Clinical and Laboratory Standards Institute.Results A total of 169 438 strains of Acinetobacter spp.were detected during the 10-year period,with the detection rate of A.baumannii being the highest(82.74％).70 923 strains(53.63％)of carbapenem-resistant A.baumannii(CRAB)and 58 149 strains(43.97％)of carbapenem-sensitive A.baumannii(CSAB)were detected respectively.Both CRAB and CSAB were detected most frequently in the age group＞70 years,which were 34.44％and 32.02％,respectively.The percentage of CRAB and CSAB detected in the intensive care unit were 34.80％and 11.31％,respectively.CRAB and CSAB were mainly isolated from spu-tum/bronchoalveolar lavage fluid,followed by pus/secretion,urine,and blood.The resistance rates of CRAB to commonly used antimicrobial agents didn't change much during the 10-year period.Resistance rates of CRAB to ceftazidime and cefepime were both＞84％,to ampicillin/sulbactam and piperacillin/tazobactam were both＞82％,to aminoglycosides and quinolones were both＞59％,to minocycline and polymyxin B were 15.9％-25.0％and 1.3％-6.9％,respectively.CSAB were sensitive to commonly used antimicrobial agents.Conclusion The isolation rate of CRAB is high and there is no significant change in resistance to commonly used antimicrobial agents.

OBJECTIVE: To investigate the surgical strategy for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. METHODS: The clinical data of 16 patients with large and giant recurrent meningioma in the middle and posterior third part of the superior sagittal sinus with extracranial invasion who underwent surgery in the Department of Neurosurgery of Peking University Third Hospital from May 2019 to May 2022 were retrospectively analyzed. All the patients underwent brain-enhanced magnetic resonance imaging (MRI), magnetic resonance venography (MRV), computed tomography angiography (CTA) and three-dimensional skull computed tomography (CT) before, to evaluate the extent of tumor invasion, the edema of brain tissue, the degree of skull damage, the blood supply of the tumor, and the degree of compression of the superior sagittal sinus, etc, and to formulate an individualized surgical plan. The neurological function of the patients was evaluated 1 week, 1 month, and 3 months after the operation, and the tumor condition was evaluated by brain-enhanced MRI 3 months, 6 months, and 1 year after the operation. RESULTS: The tumors in the 16 patients were all located in the middle and posterior 1/3 part of the superior sagittal sinus and invaded extracranially. Among them, 8 cases were operated for the second time, 6 cases for the third time, and 2 cases for the fourth time; In the last operation, the bone flap was used to repair the skull in 4 cases, and the titanium mesh was used in 12 cases; Tumor arterials of 3 cases were embolized under digital subtraction angiography (DSA). Tumors of 10 cases were resected at Simpson grade Ⅰ, and 6 cases at Simpson grade Ⅱ; 2 cases underwent decompressive craniectomy during operation, and 14 cases underwent cranioplasty at the same time; scalp incisions of 14 cases were directly sutured, and flap transposition was used in 14 cases. When evaluating nerve function after operation, the limb muscle strength was improved compared with that before operation, and the Karnofsky performance scale (KPS) score reached 100 points 3 months after operation. During the follow-up, 1 patient's tumor recurred after 1 year and received Gamma Knife treatment, and the rest of the patients had no recurrence during the follow-up period. CONCLUSION Surgical treatment is the first choice for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. It is a safe and effective surgical method to take individualized surgical plan after detailed preoperative assessment of cerebral edema, tumor blood supply, venous sinus compression, and scalp invasion.
Humans ; Meningeal Neoplasms/surgery* ; Meningioma/surgery* ; Neoplasm Recurrence, Local/surgery* ; Retrospective Studies ; Superior Sagittal Sinus/surgery* ; Titanium

OBJECTIVE: To explore the feasibility and key technology of microscopic resection of lumbar intraspinal tumor through microchannel keyhole approach. METHODS: The clinical features, imaging characteristics and surgical methods of 54 cases of lumbar intraspinal tumor which were microscopically operated by microchannel from February 2017 to September 2019 were reviewed and analyzed. There were 8 cases of extradural tumor, 3 cases of extra-and intradural tumor and 43 cases of subdural extramedullary tumor (including 3 cases of ventral spinal tumor). The tumors were 0.5-3.0 cm in diameter. The clinical symptoms included 49 cases of pain in the corresponding innervation area, 5 cases of sensory disturbance (numbness) at or below the tumor segment, 7 cases of limb weakness and 2 cases of urination and defecation dysfunction. RESULTS: In the study, 37 tumors were resected through hemilaminectomy, 14 tumors were resected through interlaminar fenestration, 3 tumors were resected through hemilaminectomy or interlaminar fenestration combined with facetectomy of medial 1/4 facet. All of the 54 tumors were totally resected. The operation time was 75-135 min, with an average of 93.3 min. The postoperative hospital stay was 4-7 days, with an average of 5.7 days. Postoperative pathology included 34 cases of schwannoma, 4 cases of meningioma, 9 cases of ependymoma, 1 case of enterogenous cyst, 5 cases of teratoma/epidermoid/dermoid cyst, and 1 case of paraganglioma. No infection or cerebrospinal fluid leakage was found after operation. No neurological dysfunction occurred except 1 case of urination dysfunction and 4 cases of limb numbness. The follow-up period ranged from 3 to 33 months with an average of 14.4 months. Five patients with new onset symptoms returned to normal. The pain symptoms of 49 patients were completely relieved; 4 of 5 patients with hypoesthesia recovered completely, the other 1 patient had residual mild hypoesthesia; 7 patients with limb weakness, and 2 patients with urination and defecation dysfunction recovered to normal. No spinal instability or deformity was found, and no recurrence or residual tumors were found. According to McCormick classification, they were of all grade Ⅰ. CONCLUSION The lumbar intraspinal extramedullary tumors within two segments (including the ventral spinal tumors) can be totally resected at stage Ⅰ through microchannel keyhole approach with appropriate selection of the cases. Microchannel technique is beneficial to preserve the normal structure and muscle attachment of lumbar spine, and to maintain the integrity and stability of lumbar spine.
Humans ; Hypesthesia ; Lumbar Vertebrae/surgery* ; Meningeal Neoplasms ; Pain ; Retrospective Studies ; Spinal Cord Neoplasms/surgery* ; Spinal Neoplasms/surgery* ; Treatment Outcome