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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE: To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism. METHODS: MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot. RESULTS: RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G₁ phase was increased, and that in G₂/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV. CONCLUSION RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.
Humans ; Resveratrol/pharmacology* ; Multiple Myeloma/metabolism* ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; MicroRNAs/genetics*

This study was aimed at identifying the bioactive components of the crude and stir-baked hawthorn for invigorating spleen and promoting digestion, respectively, to clarify the processing mechanism of hawthorn by applying the partial least squares(PLS) algorithm to build the spectrum-effect relationship model. Firstly, different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions were prepared, respectively. Then, the contents of 24 chemical components were determined by ultra-high performance liquid chromatography-mass spectrometry. The effects of different polar fractions of crude hawthorn and stir-baked hawthorn aqueous extracts and combinations of different fractions were evaluated by measuring the gastric emptying rate and small intestinal propulsion rate. Finally, the PLS algorithm was used to establish the spectrum-effect relationship model. The results showed that there were significant differences in the contents of 24 chemical components for different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions, and the gastric emptying rate and small intestinal propulsion rate of model rats were improved by administration of different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions. The bioactive components of crude hawthorn identified by PLS models were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, neochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, malic acid, quinic acid and fumaric acid, while neochlorogenic acid, cryptochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, quinic acid and fumaric acid were the bioactive components of stir-baked hawthorn. This study provided data support and scientific basis for identifying the bioactive components of crude and stir-baked hawthorn, and clarifying the processing mechanism of hawthorn.
Animals ; Rats ; Spleen ; Crataegus ; Quinic Acid ; Least-Squares Analysis ; Vanillic Acid ; Algorithms ; Digestion

Objective:To compare the cost-effectiveness of hospitalized Chinese patients undergoing nucleic acid screening strategies for hepatitis B and hepatitis C, immunological screening strategy, and no screening strategy under different willingness to pay (WTP). The results might aid to decision-making for the optimal strategy.Methods:In this study, nucleic acid screening, immunological screening and no screening were used as screening strategies, and China′s GDP in 2021 (80 976 yuan) was used as the threshold of WTP to construct a Markov model. After introducing parameters related to the diagnosis and treatment of hepatitis B and C in inpatients, a cohort population of 100 000 inpatients was simulated by TreeAge Pro 2021 software, the total cost, total health effects, incremental cost-effectiveness ratio and average cost-effectiveness ratio of different screening strategies were calculated, and cost-effectiveness analysis was conducted. Univariate and probabilistic sensitivity analysis were used to assess the impact of parameter uncertainty on the final results.Results:Compared with the non-screening strategy, the incremental total cost of the hepatitis B immunological screening strategy for cohort patients was 11 049 536 yuan, and the incremental cost-effectiveness ratio was 24 762 yuan/quality-adjusted life years (QALY), while the total incremental cost of nucleic acid screening was 19 208 059 yuan, and the incremental cost-effectiveness ratio was 29 873 yuan/QALY; the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 834 yuan/QALY. Compared with the non-screening strategy, the incremental cost-effectiveness ratio of hepatitis C immunological screening strategy was 5 731 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening strategy was 8 722 yuan/QALY, the incremental cost-effectiveness ratio of nucleic acid screening and immunological screening was 45 591 yuan/QALY. The results of probabilistic sensitivity analysis showed that when the cost of nucleic acid testing exceeded 214.53 yuan, it was not cost-effective to perform hepatitis B nucleic acid screening under the WTP as 1 fold GDP. When the cost of nucleic acid testing exceeded 132.18 yuan, it was not cost-effective to conduct hepatitis C screening under the WTP as 1 fold GDP.Conclusions:Nucleic acid screening strategy can achieve more cost-effectiveness and is worthy of vigorous promotion. Compared with no screening, both the nucleic acid and immunological screening strategies are cost-effective, and hepatitis nucleic acid screening is the optimal strategy for hospitalized patients.

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.
Animals ; Rats ; Interleukin-6 ; Network Pharmacology ; Animal Experimentation ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Liver Cirrhosis/genetics* ; Medicine, Chinese Traditional ; Capsules ; Class I Phosphatidylinositol 3-Kinases ; Collagen ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To study the expression of miR-21 in multiple myeloma (MM) cell lines and plasma cells of patients, and explore the mechanism of miR-21 in MM. METHODS: Bone marrow samples from 30 patients with MM and 18 healthy controls were collected. The plasma cells were separated by magnetic beads. MM cell lines (MM1.S cells, RPMI-8226 cells and U266 cells) were cultured. The expression level of miR-21 was detected by real-time fluorescent quantitative PCR (qRT-PCR). After transfection with hsa-miR-21 mimics and hsa-miR-21 inhibitor, the proliferation of MM cells was detected by CCK-8 and cell cloning assay. The target genes regulated by miR-21 were predicted by bioinformatics website. The binding sites of miR-21 and KLF5 were detected by luciferase reporter gene assay. The expression of KLF5 were detected by Western blot and qRT-PCR after hsa-miR-21 mimics and hsa-miR-21 inhibitor were transfected into RPMI-8226 cells. KLF5 plasmid with 3'UTR knockout was synthesized and cotransfected into RPMI-8226 cells with hsa-miR-21 mimics, and the proliferation of MM cells was detected by CCK-8 and cell cloning assay. RESULTS: Compared with healthy donors, the expression level of miR-21 in plasma cells of patients with MM was significantly increased (P<0.001); the expression of miR-21 in MM cell lines MM1.S, RPMI-8226 and U266 was significantly higher than that in control group (P<0.05). After hsa-miR-21 mimics transfection, the proliferation and the number of colony formation of MM cells was significantly increased, while the proliferation and the number of colony formation of MM cells was decreased after hsa-miR-21 inhibitor transfection (P<0.01). The results of luciferase reporter gene assay showed that miR-21 could bind to 3'UTR of KLF5, and the expression level of KLF5 protein was significantly decreased after hsa-miR-21 mimics transfection. After 3'UTR-knockout KLF5 plasmid and hsa-miR-21 mimics were cotransfected into RPMI-8226 cells, the proliferation of the cells was significantly decreased. CONCLUSION MiR-21 may be involved in regulating the proliferation of MM cells by inhibiting the expression of KLF5.
3' Untranslated Regions ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Kruppel-Like Transcription Factors ; Luciferases/genetics* ; MicroRNAs/metabolism* ; Multiple Myeloma/genetics* ; Sincalide/genetics*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases