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.

ObjectiveTo explore the therapeutic effects and mechanisms of modified Danggui Shaoyaosan on acne based on the c-Jun N-terminal kinase （JNK）/p38 mitogen-activated protein kinase （p38 MAPK） pathway. MethodsA rat ear acne model was established in SD rats， and the rats were divided into a blank group， a model group， and low-， medium-， and high-dose groups of modified Danggui Shaoyaosan （7.15， 14.30， 28.60 g·kg·d^-1）， with six rats in each group. After the administration for 14 consecutive days， morphological changes in the rats' auricles were observed， and hematoxylin-eosin （HE） staining was used to examine the pathological changes in the acne-affected ear tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the ear tissue. Quantitative reverse transcription polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression levels of Caspase-3， B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， JNK， and p38 MAPK in the ear tissue. Additionally， Western blot analysis was conducted to assess the protein levels of Caspase-3， Bcl-2， Bax， JNK， and p38 MAPK in the ear tissue. The active components and key targets of modified Danggui Shaoyaosan in the treatment of acne were identified through network pharmacology analysis. Molecular docking was then employed to evaluate the interactions between the main active components and the key targets. ResultsThe results of the animal experiment demonstrated that compared with those in the blank group， rats in the model group exhibited redness， swelling， thickening， hardening， dryness， and roughness of the auricle. The surface showed sebaceous scales and desquamation， accompanied by acne-like lesions such as papule-like elevations or cysts. Histopathological changes included keratinization， epidermal thickening， dermal collagen fiber degeneration and necrosis， subcutaneous muscle degeneration and necrosis， inflammatory cell infiltration， and fibrous tissue proliferation. The mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK were significantly increased （P<0.01）， while those of Bcl-2 were significantly decreased （P<0.01）. In comparison to the model group， the modified Danggui Shaoyaosan groups showed marked improvement in acne-like lesions of the auricle， with varying degrees of histopathological damage reduction. Additionally， the mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK in the tissue were significantly decreased （P<0.05， P<0.01）， while those of Bcl-2 were significantly increased （P<0.05， P<0.01）. Network pharmacology analysis indicated that the key compounds in modified Danggui Shaoyaosan responsible for its effects in treating acne may include acacetin， kaempferol， luteolin， quercetin， wogonin， and baicalein. These compounds exerted their effects by modulating core targets such as TNF， IL-1β， Caspase-3， and Bcl-2， thereby alleviating inflammation and apoptosis and ultimately improving acne symptoms. ConclusionModified Danggui Shaoyaosan may exert its therapeutic effects on acne by inhibiting the activation of the JNK/p38 MAPK pathway， thereby alleviating inflammation and apoptosis.

BACKGROUND:Mesenchymal stem cells can regulate the tumor microenvironment by secreting extracellular vesicles containing cytokines,growth factors and exosomes for the precise regulation of biological behavior of tumor cells. OBJECTIVE:To investigate the effects of human umbilical cord-derived mesenchymal stem cell conditioned medium and their released exosomes on the biological properties of hepatocellular carcinoma cells. METHODS:Human umbilical cord mesenchymal stem cell supernatant was collected,centrifuged and filtered at high speed to obtain human umbilical cord mesenchymal stem cell conditioned medium.Human umbilical cord mesenchymal stem cell supernatant was collected and human umbilical cord mesenchymal stem cell exosomes were extracted by ultra-high speed gradient centrifugation.Human umbilical cord mesenchymal stem cell exosomes were labeled with PKH26 and co-cultured with hepatocellular carcinoma cell MHCC97-H.The uptake of exosomes by MHCC97-H cells was observed by fluorescence microscopy.The effects of human umbilical cord mesenchymal stem cell conditioned medium and human umbilical cord mesenchymal stem cell exosomes on biological functions of hepatocellular carcinoma cells were assessed by the CCK-8 proliferation assay,Transwell migration and invasion assay,and the apoptosis assay. RESULTS AND CONCLUSION:(1)Human umbilical cord mesenchymal stem cell exosomes could be uptaken by MHCC97-H cells and was mainly distributed in the cytoplasm.(2)After treatment with human umbilical cord mesenchymal stem cell conditioned medium,MHCC97-H cells showed a significant increase in proliferation,migration,and invasion(P<0.001,P<0.05,P<0.01),and a significant decrease in apoptosis(P<0.001),while after treatment with human umbilical cord mesenchymal stem cell exosomes,MHCC97-H cells showed a decrease in proliferation(P<0.001)and migration,invasion,and apoptosis were significantly enhanced(P<0.001).(3)The results indicated that human umbilical cord mesenchymal stem cell conditioned medium had the ability to promote the proliferation,migration,invasion,and inhibit apoptosis of MHCC97-H cells,while human umbilical cord mesenchymal stem cell exosomes had the properties of promoting the migration,invasion and apoptosis of MHCC97-H cells,inhibiting the proliferation.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective: To analyze the occupational health literacy (OHL) level and its influencing factors among key populations in the tertiary industry in Lu'an City, Anhui Province, so as to provide a basis for developing targeted health interventions and improving regional occupational health policies. Methods: A stratified cluster random sampling method was employed to select five categories of key populations from the tertiary industry in Lu'an City as study subjects from August to September 2024. Data on gender, age, education level, and OHL were collected through the National OHL Monitoring Questionnaire for Key Populations. The OHL levels were analyzed, and influencing factors of OHL levels among key populations were analyzed using a multivariable logistic regression model. Results: A total of 1 243 individuals were surveyed, comprising 700 (56.32%) males and 543 (43.68%) females. The median age was 42.00 (interquartile range, 17.00) years. There were 609 individuals with OHL, and the OHL level was 48.99%. The OHL levels in fundamental knowledge of occupational health protection, healthy work styles and behaviors, knowledge of occupational health laws, and basic skills for occupational health protection were 84.71%, 60.34%, 43.93%, and 37.09%, respectively. Multivariable logistic regression analysis showed that educational level (primary school and below, OR=0.149, 95%CI: 0.064-0.344; junior high school, OR=0.340, 95%CI: 0.184-0.629; high school, OR=0.408, 95%CI: 0.230-0.723), average monthly personal income (3 000-<5 000 yuan, OR=1.655, 95%CI: 1.092-2.508; 5 000-<7 000 yuan, OR=2.195, 95%CI: 1.302-3.699; ≥7 000 yuan, OR=2.062, 95%CI: 1.016-4.183), employer nature (private enterprises, OR=2.992, 95%CI: 1.569-5.443), and industry category (education, OR=3.423, 95%CI: 1.407-8.327; courier / food delivery services, OR=0.459, 95%CI: 0.268-0.787; healthcare, OR=7.539, 95%CI: 3.255-17.461) were statistically associated with the OHL level among key population. Conclusion The OHL level among key population in the tertiary industry of Lu'an City can be further enhanced, with educational level, average monthly personal income, employer nature, and industry category identified as the primary influencing factors.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.