BACKGROUND:In recent years,numerous studies have found that long non-coding RNA is involved in the occurrence and development of osteoporosis.p38MAPK signaling pathway is involved in the differentiation of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts,and participates in the development of osteoporosis.LncRNA can directly or indirectly participate in the occurrence and development of osteoporosis by affecting the p38MAPK signaling pathway. OBJECTIVE:To review the effect of long non-coding RNA directly or indirectly on the progression of osteoporosis through the p38MAPK signaling pathway,and to provide a new idea for long non-coding RNA in the prevention and treatment of osteoporosis. METHODS:PubMed,CNKI,and Wanfang databases were searched with"long non-coding RNA,osteoporosis,mesenchymal stem cells,osteoblasts,osteoclasts,p38 signaling pathway"as the Chinese and English search terms.Old,repeated and low-credibility views were excluded.The retrieved literature was summarized,summed up,and analyzed.Seventy-six representative articles were selected. RESULTS AND CONCLUSION:(1)Long non-coding RNA participates in the prevention and treatment of osteoporosis through a variety of ways,including promoting the osteogenic differentiation of bone marrow mesenchymal stem cells,promoting the differentiation and secretion activity of osteoblasts,inhibiting the proliferation and bone resorption of osteoclasts,and regulating the activation or inhibition of osteoblast-related cellular pathways.Activation of p38MAPK signaling pathway can delay the progression of osteoporosis,and inhibition of p38MAPK signaling pathway can inhibit the absorption of osteoclasts,thereby affecting the occurrence and development of osteoporosis.(2)The overexpression or low expression of the corresponding long non-coding RNA can affect the proliferation or differentiation of osteoblasts and osteoclasts through the p38MAPK signaling pathway,regulate the process of bone remodeling,and then affect the occurrence and development of osteoporosis.A large number of basic research results show that long non-coding RNA and p38MAPK signaling pathway may be potential application and clinical translation value in the treatment of osteoporosis.Moreover,the corresponding long non-coding RNA overexpression or low expression lentivirus,transfection plasmid,and the corresponding p38MAPK signaling pathway inhibitor have been confirmed to have targeted regulatory effects in vitro cell experiments and animal models.(3)Therefore,targeting long non-coding RNA and p38MAPK signaling pathways to regulate the differentiation and function of bone marrow mesenchymal stem cells or inhibiting the proliferation and differentiation of osteoclasts may provide an innovative therapeutic strategy to delay the progression of osteoporosis.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

OBJECTIVE To investigate the differential expression of CXC chemokine receptor 1(CXCR1)in chronic rhinosinusitis(CRS)and its correlation with neutrophil infiltration.METHODS A total of 60 CRS patients with nasal polyps(CRSwNP group),30 CRS patients without nasal polyps(CRSsNP group),and 30 patients with deviated nasal septum(control group)were enrolled in this study.ELISA,immunohistochemistry,and reverse transcription polymerase chain reaction were employed to measure CXCR1 expression levels.Correlation analysis was conducted to evaluate the relationship between CXCR1 expression,neutrophil infiltration,and clinical symptom scores.RESULTS CXCR1 was highly expressed in both tissues and serum of CRSwNP patients.Serum CXCR1 levels showed positive correlations with peripheral blood neutrophil counts(r=0.363,P=0.004 4),neutrophil percentage(r=0.323,P=0.011 7),visual analog scale(VAS)score(r=0.328,P=0.010 5),Lund-Kennedy endoscopic score(r=0.331,P=0.009 9),and Lund-Mackay CT score(r=0.262,P=0.045 0).Tissue CXCR1 levels were positively correlated with tissue neutrophil counts(r=0.506,P=0.011 6)and percentage(r=0.564,P=0.004 1).CONCLUSION CXCR1 is highly expressed in CRSwNP patients,and its expression level is positively correlated with the degree of neutrophil infiltration and clinical symptom scores.Higher CXCR1 levels are associated with increased neutrophil migration in both serum and tissues,as well as more severe clinical symptoms.

ObjectiveTo investigate the changes in the pathogen spectrum of viral diarrhea in local pediatric inpatients as well as any variations in genotypes of major pathogens during the COVID-19 control period. MethodsFecal samples were collected from the children <5 years who were hospitalized due to acute gastroenteritis in a pediatric hospital in Shanghai. PCR test was carried out to detect rotavirus， norovirus， sapovirus， astrovirus and enteric adenovirus， and then genotyping was performed for major pathogens. ResultsOut of 546 samples， 37.55% tested positive for virus with the following positive rate ranking： norovirus GⅡ （22.16%）， group A rotavirus （16.12%）， astrovirus （2.93%）， enteric adenovirus （2.38%）， sapovirus （0.92%） and norovirus GⅠ （0.18%）. The predominant genotype within norovirus GⅡ were GⅡ.4［P31］ and GⅡ.4［P16］ with a proportion of 24.79% and 14.05% respectively. The detection rate of GⅡ.4［P31］ dropped significantly over the 2-year period （χ²＝16.140，P<0.001）. In addition， an emerging rotavirus genotype G8P ［8］， which was rarely found nationally， was discovered for the first time locally with an increasing proportion， accounting for 7.95% of all rotavirus positive cases. Phylogenic analysis demonstrated that the representative strains of this genotype were genetically closer to the DS-1-like G8P ［8］ strain found in Southeast Asia. ConclusionThe changes in the prevalence of various norovirus genotypes together with the emergence of rare rotavirus genotype in the local area illustrate the importance of continuous monitoring of viral diarrhea and genotyping of key pathogens. Increased local activity of the rare genotype also adds new parameters in the efficacy evaluation of marketed vaccines and development of potential new vaccines in near future.

Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.

BACKGROUND:Indolepropionic acid has been shown to reduce diabetes-induced central nervous system inflammation.However,there is a lack of research on whether to inhibit microglia M1 polarization for the treatment of spinal cord injury. OBJECTIVE:To investigate the mechanism of indolepropionic acid inhibition of microglial cell M1 polarization for the treatment of spinal cord injury through cell and animal experiments. METHODS:(1)In vitro experiments:BV2 cell viability was assessed using the CCK-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,BV2 cells were categorized into control group,administration group(50 μmol/L indolepropionic acid),lipopolysaccharide group(100 ng/mL lipopolysaccharide),and treatment group(100 ng/mL lipopolysaccharide + 50 μmol/L indolepropionic acid).Nitric oxide content was quantified using the Griess method.Real-time quantitative PCR and western blot assay were employed to measure mRNA and protein levels of pro-inflammatory factors.Cell immunofluorescence staining was conducted to assess inducible nitric oxide synthase expression.The Seahorse assay was employed to assess glycolytic stress levels in BV2 cells.(2)In vivo experiments:30 SD rats were randomly divided into three groups:sham surgery group,spinal cord injury group,and indolepropionic acid group.Motor function recovery in rats after spinal cord injury was assessed using BBB scoring and the inclined plane test.Immunofluorescence staining of spinal cord tissue was conducted to evaluate the expression of inducible nitric oxide synthase in microglial cells.ELISA was employed to measure protein expression levels of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in spinal cord tissue. RESULTS AND CONCLUSION:(1)In vitro experiments:Indolepropionic acid exhibited significant suppression of BV2 cell viability when its concentration exceeded 50 μmol/L.Indolepropionic acid achieved this by inhibiting the activation of the nuclear factor κB signaling pathway,thereby suppressing the mRNA and protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α),as well as the M1 polarization marker,inducible nitric oxide synthase,in BV2 cells.Additionally,indolepropionic acid notably reduced the glycolytic level in BV2 cells induced by lipopolysaccharides.(2)In vivo experiments:Following indolepropionic acid intervention in spinal cord injury rats,there was a noticeable increase in BBB scores and the inclined plane test angle.There was also a significant decrease in the number of M1-polarized microglial cells in spinal cord tissue,accompanied by a marked reduction in the protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α).(3)These results conclude that indolepropionic acid promotes functional recovery after spinal cord injury by improving the inflammatory microenvironment through inhibition of microglia M1 polarization.