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 assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals ; Male ; Apoptosis/drug effects* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; bcl-2-Associated X Protein/genetics* ; Rehmannia/chemistry* ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Signal Transduction/drug effects* ; Neurons/cytology* ; Rats, Inbred SHR ; Rats, Inbred WKY ; Humans ; Corpus Striatum/cytology* ; Plant Extracts

The orientation of the acetabular cup in hip joint anteroposterior radiograph is a key factor in evaluating the postoperative outcomes of total hip arthroplasty (THA). Currently, measurement of the acetabular cup anteversion angle primarily relies on manual drawing of auxiliary lines by orthopedic surgeons and calculations using scientific calculators. This study proposes an automated computer-aided measurement method for the acetabular cup anteversion angle based on hip joint anteroposterior radiograph. The proposed method segments hip prosthesis images using an improved Otsu algorithm, identifies feature points at the acetabular cup opening by combining circle-fitting theory and the cup's geometric characteristics, and fits an ellipse to the cup opening to calculate the anteversion angle. A total of 104 hip joint anteroposterior radiographs, including 71 right-sided and 81 left-sided prostheses, were analyzed. Two orthopedic surgeons independently measured the postoperative anteversion angles, and the results were compared with computer-generated measurements for correlation analysis. Spearman and Pearson correlation analyses demonstrated significant correlations between the proposed method and manual measurements for both the right group ( r = 0.795, P < 0.01) and the left group ( r = 0.859, P < 0.01). This method provides a reliable reference for orthopedic surgeons to assess postoperative prognosis.
Humans ; Acetabulum/anatomy & histology* ; Arthroplasty, Replacement, Hip/methods* ; Algorithms ; Hip Prosthesis ; Hip Joint/diagnostic imaging* ; Radiography ; Image Processing, Computer-Assisted/methods*

OBJECTIVE: To assess the mid-term clinical efficacy of the direct anterior approach for window decompression and bone grafting surgery in the treatment of early to mid-stage osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was performed on 40 patients (40 hips) diagnosed with osteonecrosis of the femoral head (ONFH), classified as types L1 and L2 according to the China-Japan Friendship Hospital (CJFH) classification system, and at stagesⅡ, ⅢA, and ⅢB based on the Association Research Circulation Osseous (ARCO) staging system. All patients underwent head-neck junction fenestration decompression and bone grafting via the direct anterior approach between January 2015 and May 2022, with complete follow-up data available for a minimum of three years. The ages of the patients ranged from 35 to 69 years old, with a mean of (49.13±6.14 ) years old;their body mass index (BMI) ranged from 20.02 to 27.94 kg·m^-2, with a mean of (23.65±1.69) kg·m^-1;the duration of the disease ranged from 13 to 36 months, with a mean of (24.55±4.14) months. Preoperative and 3-year postoperative X-ray parameters were collected, including the anterior preserved angle(APA), lateral preserved angle (LPA), and combined preserved angle (CPA). Additionally, hip joint disability and osteoarthritis outcome scores (HOOS) and Harris hip scores (HHS) were recorded. RESULTS: Forty patients were followed up for a period ranging from 36 to 59 months, with a mean duration of (47.18±6.18) months. At 3 years postoperative, none of the patients underwent hip replacement surgery. The APA (73.15±19.35)°, LPA (75.35 ±21.48)°, and CPA (136.25±26.78)° at the 3-year postoperative significantly improved compared to preoperative measurements (61.93±20.54)°, (59.46±22.67)°, and (116.58±32.47)°, with statistical significance (P<0.05). The HOOS (20.37±1.39) and HHS (89.74±3.28) scores at the 3-year postoperative were significantly improved from preoperative scores (12.36±1.58) and (50.27±6.15), respectively, with statistical significance (P<0.05). CONCLUSION The direct anterior approach for window decompression and bone grafting surgery can relieve joint pain, improve joint function, and enhance X-ray preserved angles, effectively preventing femoral head collapse, making it an effective surgical method for treating ONFH classified as L1, L2 according to CJFH and stagesⅡ, ⅢA, ⅢB according to ARCO.
Humans ; Middle Aged ; Male ; Female ; Adult ; Decompression, Surgical/methods* ; Bone Transplantation ; Femur Head Necrosis/surgery* ; Follow-Up Studies ; Aged ; Retrospective Studies

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies