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 To explore the valve regurgitation status of left heart after the implantation of left ventricular assist device (LVAD) and its effect on prognosis of patients with LVAD implantation. Methods A total of 35 patients with cardiomyopathy who underwent magnetic levitation LVAD implantation at Zhongshan Hospital, Fudan University from February 2021 to July 2024 were retrospectively selected. Clinical data during hospitalization were collected, including preoperative basic data and postoperative valve regurgitation status. Telephone follow-ups were conducted to monitor patients’ survival status and transthoracic echocardiography was used to assess left valve function. Kaplan-Meier survival curves and log-rank test were employed to compare the survival rate of patients with different levels of valve regurgitation. Results The 35 patients had a mean age of (53.9±11.1) years, with 85.7% male, and 3 patients (8.6%) died during hospitalization. Preoperatively, 17 patients (48.6%) had moderate or greater mitral regurgitation, while all 35 patients had less than moderate aortic regurgitation. One month postoperatively, thirty patients were followed up, among which 24 patients (80%) had less than moderate mitral regurgitation, including 11 cases with alleviated regurgitation compared to pre-surgery; 6 patients (20%) had moderate or greater mitral regurgitation, including 4 cases with stable regurgitation and 2 cases with progression of regurgitation compared to pre-surgery; 2 patients (6.7%) had progression of aortic regurgitation to moderate or greater. The follow-up time was 1.2 (1.0, 2.1) years, with 1-year survival rate of 91.4% and 3-year survival rate of 71.1%. Survival analysis showed that the 3-year survival rate of patients with moderate or greater mitral regurgitation one month postoperatively was significantly lower than that of patients with less than moderate regurgitation (66.7% vs 83.3%, P＝0.046). Conclusions After the implantation of magnetic levitation LVAD, most patients showed improvement in mitral regurgitation, while aortic regurgitation remained unchanged. The degree of mitral regurgitation one month postoperatively is associated with prognosis.

In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

To explore the effects of different exercise prescriptions on glycemic metabolism in East Asian patients with type 2 diabetes mellitus (T2DM) and to compare the differences in the impact of population characteristics and exercise components on glycemic metabolism.

BACKGROUND:A network-based pharmacological approach has identified multifunctional effects of the main bioactive compounds in the Trichosanthis Fructus-Allii Macrostemonis Bulbus on coronary heart disease;however,the mechanism of its therapeutic effect on coronary heart disease has not been fully elucidated. OBJECTIVE:To investigate the role and mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus in improving coronary heart disease by regulating the composition of gut microbiota. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups:blank control group(n=10),model group(n=10),positive drug group(n=10),and medicine pair group(n=10).A rat model of coronary heart disease was established by continuous gastric perfusion of fat emulsion and injection of pituitrin.After modeling,rats in the model group were gavaged with distilled water(10 mL/kg)for control,rats in the positive drug group were gavaged with simvastatin 4 mg/kg per day,and rats in the medicine pair group were gavaged with Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs 7.56 g/kg per day.All interventions lasted for 14 days.Electrocardiograms and myocardial pathology were observed,and blood lipid levels were measured.The structure of gut microbiota was analyzed using 16S rDNA sequencing technology. RESULTS AND CONCLUSION:Electrocardiogram results showed ST segment elevation in the model group.There were no significant abnormalities in the electrocardiograms of the positive drug group and medicine pair group.Compared with the blank control group,the levels of total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol were significantly higher in the model group(P<0.05).Compared with the model group,the levels of total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol were significantly lower in the positive drug group and medicine pair group(P<0.05).Compared with the blank control group,focal myocardial cell necrosis was observed in the model group,while partial myocardial cell disarray was observed in the positive drug group and medicine pair group.Compared with the blank control group,the Ace,Shannon,and Chao indices were increased(P<0.05)and the Simpson index was decreased(P<0.05)in the model group,positive drug group and medicine pair group.Compared with the model group,the Ace and Chao indices were decreased(P<0.05),while the Shannon index showed no significant difference(P>0.05)and the Simpson index was also decreased(P<0.05)in the positive drug group and medicine pair group.Compared with the blank control group,the relative abundances of Desulfovibrionia,Muribaculaceae_norank,etc.were increased in the model group,while those of Clostridia,[Eubacterium]_coprostanoligenes_group_norank,etc.were decreased.Compared with the model group,the relative abundances of WPS-2_norank,Muribaculaceae_norank,etc.were increased in the medicine pair group,while those of Clostridia,[Eubacterium]_coprostanoligenes_group_norank,etc.were decreased;the relative abundances of Desulfobacterota,[Eubacterium]_coprostanoligenes_group_norank,etc.were increased in the positive drug group,while those of Firmicutes,Muribaculaceae_norank,etc.were decreased.Compared with the positive drug group,the relative abundances of Desulfobacterota,Bacteroides,etc.were increased in the medicine pair group,while those of Firmicutes,[Eubacterium]_coprostanoligenes_group_norank,etc.were decreased.The LEfSe results showed that the medicine pair group had the highest microbial enrichment,followed by the blank control group and positive drug group,with the model group having the lowest microbial enrichment.To conclude,Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs can improve the development of coronary heart disease by regulating gut microbiota composition,providing new insights for further research and development of Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders （TD） based on microglial polarization and the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor （NF）-κB pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly assigned into six groups： control， model， tiapride （0.025 g·kg^-1）， and low-， medium-， and high-dose （12， 24， 48 g·kg^-1， respectively） modified Xiehuangsan， with 12 rats in each group. Except the control group， the other groups received intraperitoneal injection of 3，3'-iminodipropionitrile （IDPN） for 7 consecutive days for the modeling of TD. After successful modeling， the control and model groups were given normal saline via gavage， and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention， rat behaviors were observed， and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4， TLR4， MyD88， and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 （Iba1）， Fc receptor family for immunoglobulin （Ig）G type Ⅲ （CD16）， mannose receptor （CD206）， TLR4， MyD88， and NF-κB p65 in the striatum. ResultsCompared with the control group， the model group showed increased stereotyped behaviors， locomotor activity， total movement distance， and movement speed， shortened resting time （P<0.01）， and noticeable pathological changes in the striatum. Compared with the model group， the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior， locomotor activity， total movement distance， and movement speed， prolonged resting time （P<0.05， P<0.01）， and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups， the high-dose group had the best intervention effect and the mildest pathological changes. Therefore， the high-dose group was selected for further research. Compared with the control group， the modeling of TD increased Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the mRNA levels of IL-1β and TNF-α （P<0.05， P<0.01）， down-regulated the mRNA level of IL-4 （P<0.05）， up-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.05， P<0.01）， and up-regulated the protein level of NF-κB p65 （P<0.01）. Compared with the model group， modified Xiehuangsan reduced Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the protein level of CD206 （P<0.05， P<0.01）， down-regulated the mRNA levels of IL-1β and TNF-α （P<0.05）， up-regulated the mRNA level of IL-4 （P<0.01）， and down-regulated the mRNA and protein levels of TLR4， MyD88， and NF-κB p65 （P<0.05， P<0.01）. ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

[Objective] To investigate and summarize the clinicopathological features, diagnosis, treatment and prognosis of adrenocortical carcinoma with rhabdoid features. [Methods] The clinical diagnosis and treatment of a case of adrenocortical carcinoma with rhabdoid features admitled to Department of Urology, Weifang People's Hospital were reported.The clinical manifestations, pathological features, diagnosis and prognosis of the disease were analyzed in combination with relevant literature. [Results] A 34-year-old male patient was admitted due to scrotal distension and pain that had persisted for 6 months.Imaging examination showed a huge soft tissue tumor in the left adrenal region of the retroperitoneum with compression displacement of the left kidney, leading to obstruction of venous return in the left spermatic vein, which in turn caused varicose veins.The levels of serum renin, angiotensin, aldosterone, cortisol, and catecholamine were within normal ranges.Surgical resection of the tumor was performed, and postoperative pathological examination revealed that the tumor tissue was predominantly composed of rhabdoid cells, exhibiting positive immunohistochemical staining for INI 1, Syn, Calretinin and Vimentin.Genetic testing did not identify any deletion of SMARCB1 and SMARCA4 mutations.Therefore, the diagnosis was adrenocortical carcinoma with rhabdoid features.At the current 20-month follow-up, no recurrence or metastasis was observed.A review of the literature found that only 7 cases of this disease had been reported. [Conclusion] Adrenocortical carcinoma with rhabdoid features is a rare disease, and a definitive diagnosis is dependent upon pathological examination.Surgical resection remains the primary treatment.Long-term follow-up is essential, and further research is needed to evaluate the impact of adjuvant therapy.