ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective To investigate the anti-inflammatory properties of bergaptenand its inhibition of bone resorption in the treatment of periodontitis,as well as its potential underlying mechanisms.Methods A total of 35 male Wistar rats were randomly di-vided into five groups(control group,model group,and low-,medium-,and high-dose bergapten groups,with 7 rats in each group).Except for the control group,periodontitis was induced in all other groups by orthodontic ligation of the bilateral maxillary first molars(M1)and feeding a high-sugar diet.After successful modeling,the control and model groups received gavage of isotonic saline,while the bergapten groups received gavage of 50,100,and 200 mg/kg bergapten,respectively,once daily for 4 consecutive weeks.Perio-dontal symptoms were observed,and GI,SBI grades,and PLI scores were recorded.Rats were sacrificed within 24 hours after the last administration,and their maxillae were immediately subjected to Micro-CT scanning to assess alveolar bone resorption.Histopathological changes in the periodontal tissues were observed using HE staining,and serum levels of pro-inflammatory cytokines(IL-6 and IL-1β)were measured by ELISA.Results Compared with the control group,the model group exhibited significantly higher levels of IL-6,IL-1β,GI,SBI grades,PLI scores,and CEJ-ABC distance,while bone volume to total volume ratio(BV/TV),trabec-ular number(Tb.N),and trabecular thickness(Tb.Th)were significantly reduced(P＜0.001).In comparison to the model group,the bergapten groups(with the exception of the low-dose group for IL-6)demonstrated reductions in IL-6,IL-1β levels,GI,SBI grades,PLI scores,and CEJ-ABC distance,with the medium-dose group showing the most pronounced effect(except for IL-6).Conclusion Bergapten can effectively prevent and treat periodontitis by inhibiting the secretion of IL-6 and IL-1β cytokines,achieving anti-inflam-matory effects and inhibiting bone resorption.

AIM To explore the clinical effects of Qutan Jiangni Pingchuan Formula combined with Compound Ipratropium Bromide on patients with acute exacerbation of chronic obstructive pulmonary disease.METHODS One hundred and ten patients were randomly assigned into control group(55 cases)for 2-week intervention of both Compound Ipratropium Bromide and conventional treatment,and observation group(55 cases)for 2-week intervention of Qutan Jiangni Pingchuan Formula,Compound Ipratropium Bromide and conventional treatment.The changes in clinical effects,relevant scores(TCM syndrome score,mMRC grade,CAT score),disappearance time for clinical symptoms(cough,wheezing,pulmonary wheeze),airway inflammatory indices(sICAM-1,IL-8,MCP-1),pulmonary function indices(FEV1,PEF25,TLC),sputum indices(24 h sputum volume,sputum viscosity)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05),along with shorter disappearance time for clinical symptoms(P＜0.05).After the treatment,the two groups displayed decreased relevant scores,airway inflammatory indices,24 h sputum volume(P＜0.05),and increased pulmonary function indices(P＜0.05),especially for the observation group(P＜0.05);the observation group demonstrated elevated number of people with grade Ⅰ sputum viscosity(P＜0.05),which was more obvious than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with acute exacerbation of chronic obstructive pulmonary disease,Qutan Jiangni Pingchuan Formula combined with Compound Ipratropium Bromide can safely and effectively improve clinical symptoms,reduce inflammatory levels,enhance lung functions,and promote sputum secretion in airways.

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the anti-inflammatory properties of bergaptenand its inhibition of bone resorption in the treatment of periodontitis,as well as its potential underlying mechanisms.Methods A total of 35 male Wistar rats were randomly di-vided into five groups(control group,model group,and low-,medium-,and high-dose bergapten groups,with 7 rats in each group).Except for the control group,periodontitis was induced in all other groups by orthodontic ligation of the bilateral maxillary first molars(M1)and feeding a high-sugar diet.After successful modeling,the control and model groups received gavage of isotonic saline,while the bergapten groups received gavage of 50,100,and 200 mg/kg bergapten,respectively,once daily for 4 consecutive weeks.Perio-dontal symptoms were observed,and GI,SBI grades,and PLI scores were recorded.Rats were sacrificed within 24 hours after the last administration,and their maxillae were immediately subjected to Micro-CT scanning to assess alveolar bone resorption.Histopathological changes in the periodontal tissues were observed using HE staining,and serum levels of pro-inflammatory cytokines(IL-6 and IL-1β)were measured by ELISA.Results Compared with the control group,the model group exhibited significantly higher levels of IL-6,IL-1β,GI,SBI grades,PLI scores,and CEJ-ABC distance,while bone volume to total volume ratio(BV/TV),trabec-ular number(Tb.N),and trabecular thickness(Tb.Th)were significantly reduced(P＜0.001).In comparison to the model group,the bergapten groups(with the exception of the low-dose group for IL-6)demonstrated reductions in IL-6,IL-1β levels,GI,SBI grades,PLI scores,and CEJ-ABC distance,with the medium-dose group showing the most pronounced effect(except for IL-6).Conclusion Bergapten can effectively prevent and treat periodontitis by inhibiting the secretion of IL-6 and IL-1β cytokines,achieving anti-inflam-matory effects and inhibiting bone resorption.

Objective This study aimed to investigate natural infection of rodents with Ehrlichia and Neoehrlichia at major Chinese land-border ports along the"Belt and Road".Methods In 2022,rodents were monitored in 10 ports in northern and southern China and identified based on diagnostic morphological characteristics.The 16S rRNA genes of Ehrlichia and Neoehrlichia were detected by PCR using universal primers from rodent samples and phylogenetic analysis was performed based on the sequences of the detected positive pathogens.Results A total of 356 rodents were sampled,including 2 orders,5 families,15 genera,and 20 species.Predominantly,73,61,56,and 58 were Meriones unguiculatus(20.51%),Rattus norvegicus(17.13%),Apodemus agrarius(15.73%),and Microtus gregalis(16.29%).Only one Microtus fortis from Suifenghe Port was infected with Ehrlichia sp.Moreover,12 rodents were infected with Neoehrlichia spp.(overall positivity rate:3.37%).Conclusions Natural infections with Ehrlichia spp.and Neoehrlichia spp.were demonstrated in rodents at important Chinese land-border ports.The positivity rate of Neoehrlichia spp.was high in some ports,indicating that surveillance for ticks and their prevention and control measures should be intensified in these regions.

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*