Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Objective: To investigate the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Haishu District, Ningbo City, Zhejiang Province from 2011 to 2022, so as to provide the basis for the formulation of HFMD prevention and control strategies. Methods: Data of HFMD in Haishu District from 2011 to 2022 were collected from Chinese Disease Prevention and Control Information System, and the epidemiological and etiological characteristics were analyzed using a descriptive epidemiological method. The trends in incidence of HFMD and prevalence of positive etiological tests were analyzed using annual percent change (APC). Results: A total of 33 334 cases of HFMD were reported in Haishu District from 2011 to 2022, with an average annual reported incidence of 279.16/105, showing no significant trend (APC=-5.492%, P>0.05). The average annual reported incidence of HFMD was lower after the enterovirus 71 vaccine was launched (from 2017 to 2022) than before (from 2011 to 2016; 219.69/105 vs. 343.70/105, P<0.05). The incidence of HFMD showed seasonal characteristics, with a peak from May to July. There were 19 720 male and 13 614 female cases, with a male-to-female ratio of 1.45∶1. The age of the HFMD cases ranged from 27 days to 63 years old, and the children aged 5 years and below were predominant (30 657 cases, 91.97%). A total of 1 976 specimens of HFMD cases were collected from 2011 to 2022, and 1 509 enterovirus positive specimens were detected, with a positive rate of 76.37%. The positive rates of enterovirus 71 decreased (APC=-32.599%, P<0.05), the positive rates of coxsackievirus A16 increased (APC=9.226%, P<0.05), while the positive rates of other enteroviruses showed no significant change (APC=0.808%, P>0.05). Conclusions The average annual reported incidence of HFMD in Haishu District from 2011 to 2022 decreased after the enterovirus 71 vaccine was launched, with a peak in spring and summer. Children aged 5 years and below were the high-incidence population, and coxsackievirus A16 was the main serotype.

G-protein coupled receptors (GPCRs) are an essential family of proteins on the cell membrane, widely distributed in various types of tissues and cells. Typical GPCRs are composed of characteristic 7 transmembraneα-helix domains, extracellular domain and intracellular domain. They play a key role in transmitting information inside and outside cells. These receptors can sense and respond to a variety of external signals, including odor molecules, hormones, neurotransmitters, chemokines, and so on, thereby regulating the physiological functions and metabolic activities of cells. When external signal molecules bind, these receptors undergo conformational changes, thereby activating signal transduction pathways inside cells. The most common downstream signal pathway is the activation of G proteins, but it may also activate the β-arrestin signaling pathway. This series of signal transduction processes ultimately regulates physiological processes such as cell metabolism, proliferation, and differentiation, and also plays an important role in the occurrence and development of diseases. Due to its importance in regulating cell functions and participating in the development of diseases, GPCRs have become important targets in the field of drug research and development. The mechanism of action of many drugs is achieved by intervening in the GPCR signaling pathway. As important form of function regulating, dimerization has attracted widespread attention in the research of GPCR field. In the early days, the formation of GPCR dimerization and its effect on receptor function were mainly studied by immunoprecipitation, immunofluorescence and radioligand binding experiments in overexpression systems. Nowadays, with the continuous development of biochemical and biophysical methods, more and more GPCR dimers have been identified. GPCR dimer refers to the process in which two GPCR subunits bind to each other to form a complex. The same GPCR subunits form homodimers, and different GPCR subunits form heterodimers through direct interaction. Dimerization changes the activity, affinity, internalization, localization and transport, and signal transduction characteristics of GPCR, thereby producing more complex and delicate regulation of cellular physiological processes. In recent years, the research on GPCR dimers has been continuously deepened, revealing its important role in a variety of physiological and pathological processes. In general, the structure of GPCR dimers is complex and diverse, and its formation and stability are affected by many factors, including the specificity of receptor interaction interface, the conformational changes of receptor, and the regulation of intracellular and extracellular environment. By understanding the mechanism of GPCR dimerization, we can better understand the behavior of these receptors in signal transduction and provide new ideas and opportunities for the development of novel drug targets. More and more studies have reported the dimerization of GPCR and its structure and function regulation mechanism. This article reviews the research progress on the structure and function of GPCR dimers, and summarizes some research methods and technologies, which provide a basis for understanding the discovery of GPCR dimers, dimerization methods, structure and function regulation mechanisms, and further targeting GPCR dimers. It provides a research basis for the development of polymer drugs.

BACKGROUND:At present,bone marrow mesenchymal stem cells are the main seed cells used in cell therapy for the treatment of intervertebral disc degeneration.However,the use of bone marrow mesenchymal stem cells as seed cells for the regeneration of fibrous rings is at risk of heterotopic ossification and teratoma at the repair site.Therefore,it is of great economic and social significance to find a new kind of seed cells for tissue engineering of annulus fibrosus for the treatment of intervertebral disc degeneration. OBJECTIVE:To isolate and purify rat annulus fibrosus-derived stem cells by adherent method combined with fibronectin differential adhesion screening method,and to observe its purification effect and biological characteristics. METHODS:Annulus fibrosus tissue was obtained from a SD rat intervertebral disc.Primary annulus fibrosus-derived stem cells were obtained by the mechanical-enzymatic digestion method.Annulus fibronectin differential adhesion method was used to purify annulus fibrosus-derived stem cells.Morphological changes and proliferation of cells were observed through a microscope.The expression levels of stem cell markers were detected by immunofluorescence technique and qPCR.The screened cells were subjected to multi-lineage cell differentiation and characteristic gene detection. RESULTS AND CONCLUSION:(1)The purified cells grew well,and most of them were angular and star-shaped multi-process cells,which had good proliferation ability.(2)Cells were positive for cell membrane surface antigens CD73,CD90 and CD105,while negative for CD45 and CD34.(3)After specific induction,cells could successfully differentiate into osteoblasts,chondroblasts and lipoblasts.(4)Collagen-I,Runx-2 after osteogenic induction,Collagen Ⅱ,Sox-9 after chondrogenic induction,and PPAR-γ and LPL after lipogenic induction were highly expressed in cells,and the difference was significant compared with that before induction(P<0.05).(5)These findings confirm that the adherent method combined with fibronectin differential adhesion method is effective enough to screen,isolate and purify rat annulus fibrosus-derived stem cells,and has good cell biological properties,good proliferation ability and multiple differentiation potential.

The importance of evaluating the oxygen supply system of the medical aircraft was introduced.With considerations on the characteristics of the oxygen supply system of the medical aircraft during its development and application,an oxygen supply system effectiveness evaluation method was proposed based on the analytic hierarchy process and the experience of experts in the field of medical aircraft,which involved in seven evaluation indexes of total oxygen supply,pipeline airtight-ness,single-nozzle flow adjustment characteristics,single-nozzle outlet pressure adjustment characteristics,disassembly and assembly,mechanical operation and fixation ability.The effectiveness evaluation method proposed was of significance for accurately grasping the changes in the performance of the oxygen supply system.References were provided for the ground maintenance of the oxygen supply system of the medical aircraft.[Chinese Medical Equipment Journal,2024,45(1):89-92]