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BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

ObjectiveTo investigate how Xiaoyao Shukun decoction （XYSKD） regulates the formation and release of neutrophil extracellular traps （NETs） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， thereby reducing inflammation， inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue， decreasing adhesion and fibrosis， and repairing the tissue damage in sequelae of pelvic inflammatory disease （SPID）. MethodsA total of 84 Wistar rats were randomly allocated into seven groups： blank， model， XYSKD （8 mg·kg^-1）， mTOR agonist （10 mg·kg^-1）， mTOR agonist + XYSKD （10 mg·kg^-1+8 mg·kg^-1）， mTOR inhibitor （2 mg·kg^-1）， and mTOR inhibitor + XYSKD （2 mg·kg^-1+8 mg·kg^-1）. The rat model of SPID was constructed by starvation， fatigue， and ascending Escherichia coli infection. After 14 days of drug intervention， the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus， fallopian tube， and ovary was observed by laparotomy. The levels of interleukin-1β （IL-1β）， interleukin-17 （IL-17）， and tumor necrosis factor-α （TNF-α） in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of myeloperoxidase （MPO） and citrullinated histone 3 （H3） in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the relative protein and mRNA levels， respectively， of neutrophil elastase （NE）， intercellular adhesion molecule-1 （CD54）， α-smooth muscle actin （α-SMA）， H3， PI3K， and Akt. ResultsCompared with the blank group， the model group presented a large number of collagen fibers in bundles， numerous cytoplasmic folds of fibroblasts， reduced or absent mitochondrial cristae， and disordered and expanded endoplasmic reticulum. By laparotomy， extensive pelvic congestion， connective tissue hyperplasia， thickening and hardening of the tubal end near the uterus， and tubal and ovarian adhesion or cyst were observed in the model group. In addition， the model group showed raised levels of IL-1β， IL-17， and TNF-α in the peritoneal flushing fluid （P<0.01）， increased average fluorescence intensities of MPO and H3 （P<0.01）， and up-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.01）. Compared with the model group， the mTOR agonist group showed increased fibroblasts and cytoplasmic folds， absence of mitochondrial cristae， endoplasmic reticulum dilation， and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine， fallopian tube， and ovarian tissues. The levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid elevated （P<0.01） and the average fluorescence intensities of MPO and H3 enhanced （P<0.01） in the mTOR agonist group. In contrast， the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers， alleviated mitochondrial crista loss and endoplasmic reticulum dilation， improved morphology and appearance of the uterine， fallopian tube， and ovarian tissues， lowered levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.05）. Compared with the mTOR agonist group， the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue， declined levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein levels of NE， H3， CD54， α-SMA， p-PI3K/PI3K， and p-Akt/Akt （P<0.01） and mRNA levels of NE， H3， CD54， α-SMA， PI3K， and Akt （P<0.01）. Compared with the mTOR inhibitor group， the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue， reduced levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE and CD54 （P<0.05）. ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue， thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β， IL-17， and TNF-α and down-regulating the expression of NE， H3， CD54， α-SMA， PI3K， and Akt in the pelvic adhesion tissue.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Objective To investigate the role of scar epithelial cells and its potential molecular mechanisms in the efficacy of low-energy CO2 fractional laser treating post-burn scars.Methods The model of post-major burn scars on the back of rat was established.Three rats with post-major burn scars received 30 mJ low-energy CO2 fractional laser treatment to detect the activation of scar epidermal cells.Epidermal tissue of scars was isolated for RNA sequencing to screen activated pathways.Subsequently,18 rats with post-major burn scars were randomly divided into 3 groups(n=6):the control group without laser treatment,the laser group receiving 30 mJ CO2 fractional laser treatment,and the laser+inhibitor group receiving laser treatment and intra-scar injection of IWR-1(a Wnt/β-catenin pathway inhibitor),to verify the activation status and effects of the selected pathways.Hematoxylin-eosin staining,Masson staining,and Western blotting were used to detect the proliferation of epithelial cells and fibroblasts,the activation of Wnt/β-catenin pathway,as well as the improvement of scar profiles.Results After low-energy laser treatment,there was a significant increase in the number of Ki67-positive,proliferating cell nuclear antigen(PCNA)-positive,cytokeratin 19(CK19)-positive,and p63-positive cells in the scar epithelial tissue.RNA sequencing coupled with literature analysis identified Wnt/β-catenin pathway as a potential candidate pathway.In the confirmatory experiment,compared to the control group,the Wnt/β-catenin pathway was activated in scar epithelial cells in the laser group 5 d post-laser intervention.After 30 d laser intervention,dermal collagen exhibited a more loosened arrangement,with reduced dermal thickness and significantly less α-smooth muscle actin(α-SMA)-positive fibroblasts compared to the control group.CollagenⅠ,collagen Ⅲ,and the relative ratio of collagen Ⅰ to Ⅲ in the laser group were at a lower level than those in the control group.Administration of the Wnt/β-catenin pathway inhibitor blocked the activation of the Wnt/β-catenin pathway induced by low-energy laser,the proliferation of scar epithelial cells and the improvement of scar profiles.Conclusion Low-energy CO2 fractional laser treatment can activate the Wnt/β-catenin pathway of scar epithelial cells,thereby activating epithelial cells and yielding significant scar improvements.

Objective We aimed to explore the mechanism by which Bushen Yangjing Soup improves elderly infertility based on oocyte mitochondrion.Methods C57BL/6J mice were used,including 15 young females(6-8 weeks old),45 elderly females(10 months old),and ten young males(6-8 weeks old).The female 6-8-week-old young mice were assigned to the young group,and the female 10-month-old elderly mice were randomly divided into the model group,the dehydroepiandrosterone(DHEA)group,and the Bushen Yangjing Soup group.Mice in the DHEA and Bushen Yangjing Soup groups were given DHEA[11.26 mg/(kg·d)]and Bushen Yangjing Soup[11.41 g/(kg·d)].Mice in the other groups were given normal saline.After 45 days,oocytes were collected,the number of oocytes and the proportion of mature oocytes were recorded,and in vitro fertilization(IVF)was carried out,followed by calculation of the successful fertilization rate.Real-time PCR was used to determine the copy number of mitochondrial DNA in oocytes,mito-tracker green was used to observe the distribution of mitochondria,and the mitochondrial membrane potential(MMP)of oocytes was determined using the JC-1 kit.The mRNA and protein levels of mitofusin 2(Mfn2)in oocytes were determined by real-time PCR and Western blotting,respectively.Results Compared with the young group,the number of oocytes,the proportion of mature oocytes,and the IVF rate were significantly reduced(P＜0.01),the copy number of mitochondrial DNA in oocytes was decreased,the rate of abnormal mitochondrial distribution was increased,the MMP was decreased(P＜0.01),and the mRNA and protein levels of Mfn2 were decreased(P＜0.01)in the elderly model mice.Compared with the elderly model group,the number of oocytes,the proportion of mature oocytes,and the IVF rate were significantly increased(P＜0.05),the copy number of mitochondrial DNA in oocytes was increased(P＜0.05),the rate of abnormal mitochondrial distribution was decreased,the MMP was increased(P＜0.05),and the mRNA and protein levels of Mfn2 were increased(P＜0.01)in the Bushen Yangjing Soup group.Compared with the DHEA group,the number of oocytes,the proportion of mature oocytes,and the IVF rate were increased,the copy number of mitochondrial DNA in oocytes was increased,the rate of abnormal mitochondrial distribution was decreased,the MMP was increased,the mRNA and protein levels of Mfn2 were increased in the Bushen Yangjing Soup group,and there was a significant difference in the number of oocytes and the expression of Mfn2 protein(P＜0.05).Conclusion Bushen Yangjing Soup may improve the quantity,distribution,and function of oocyte mitochondria by increasing the mRNA and protein levels of Mfn2,thereby improving oocyte quality.This is one of the possible mechanisms for clinical application of Bushen Yangjing Soup to improve ovarian function and treat elderly infertility.

End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-Ⅱ(MAL-Ⅱ)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.