External apical root resorption(EARR)is one of the most common side effects of orthodontic treatment.Contact with sur-rounding anatomical structures during tooth movement is a significant cause for EARR.However,a comprehensive review of factors leading to EARR due to direct contact of surrounding anatomical structures with the root apex during orthodontic treatment is still lac-king.This review summarizes the anatomical structures related to EARR,including alveolar bone,incisive canal,maxillary sinus,ad-jacent teeth,and bone islands.Alveolar bone,incisive canal,and adjacent teeth can directly cause EARR during orthodontic treat-ment,while the impact of the maxillary sinus and bone islands on EARR has not been discovered so far.Analyzing the anatomical structures around the tooth roots can help develop more effective methods to prevent or reduce the occurrence of EARR during orthodon-tic treatment.

Objective To study the consonant articulation performance and speech intelligibility of patients with submucous cleft palate(SMCP)and to provide a reference for clinical speech evaluation and subsequent speech rehabilitation.Methods A total of 333 preoperative SMCP patients aged 4.5 years and older participated in this study.The accuracy,type of error,and error rates were assessed across participant genders and their varying levels of velopharyngeal closure function.Results Among the 333 patients,196 had complete velopharyngeal closure,while 137 had incomplete closure.A total of 145 patients(43.54％)demonstrated normal articulation of all conso-nants,while 188 patients(56.46％)displayed various degrees of articulation disorders.Compensatory articulation behaviors were observed in 66 patients(19.82％).No significant differences in articulation errors were found be-tween male and female patients.The accuracy ranking for consonants was from high to low as follows:nasal sounds,lateral sounds,fricatives,plosives,and affricates.Substitution was the most common error type with an incidence of 35.93％,followed by omission at 34.62％and compensatory errors at 25.51％.The average accuracy rates for plosives,fricatives,affricates,lateral/nasal sounds were 73.27％,78.20％,69.29％,and 93.39％,re-spectively.Substitution was the most common error for plosives and fricatives,while omission was most frequent for affricates.Compensatory errors occurred most often with affricates,and no compensatory errors were found in nasal or lateral sounds.Conclusion Substitution,omission,and compensatory errors are the most common articula-tion errors in SMCP patients,occurring across plosives,fricatives,and affricates.The severity of articulation disor-ders is related to velopharyngeal closure function but is independent of gender.

Pulmonary hypertension(PH)is a serious cardiovascular condition that significantly impacts pa-tients'quality of life.Currently available clinical medications lack selectivity for pulmonary blood vessels,often produce substantial side effects,and are prohibitively expensive.Therefore,it is crucial to explore the mechanisms underlying the onset and progression of PH and to develop new,effective treatments.Ubiquitination is a key form of protein post-transla-tional modification in which specific E3 enzymes recognize substrate proteins and induce ubiquitination,leading to chang-es in their activity or stability.During the onset of PH,the activities of ubiquitin ligases and deubiquitinases undergo vari-ous changes,resulting in altered ubiquitination levels of different proteins.These variations primarily influence the degra-dation rates of substrate proteins within cells,thereby regulating essential physiological processes.Proteasomes play a vi-tal role in the degradation of ubiquitinated proteins,and inhibitors targeting these complexes have been developed,demon-strating therapeutic efficacy in experimental settings of PH.However,their low specificity presents significant challenges for practical applications.In this context,we summarize the relevant mechanisms of ubiquitination regulation in the onset of PH and highlight its practical significance for future therapeutic strategies.

Sarcopenia is a systemic disease characterized by accelerated loss of skeletal muscle mass and function,leading to an increased incidence of adverse outcomes such as falls and fractures.Sarcopenia is classified into primary and secondary types,with primary sarcopenia being closely related to aging and posing a serious threat to a healthy life among the elderly.Sarcopenia has an insidious onset and is often overlooked in terms of its clinical treatment.Its pathogenesis is complex,involving functional changes and pathological alterations in multiple systems,and presenting major research challenges.Cell models can effectively be used to simulate the pathological changes of diseases under controllable conditions,thus facilitating the investigation of the etiology and factors influencing sarcopenia,and providing an important approach for in-depth studies of its mechanism;however,there is currently no standardized cell model in the field of sarcopenia research.Commonly used cell models currently include models involving protein metabolism interventions,oxidative stress,and inflammatory response interventions.This review considers the commonly used skeletal muscle cell types and modeling method of sarcopenia,to provide a solid foundation and important method ological reference for further simulation of the pathological process of sarcopenia in subsequent experimental studies.

Objective To study the consonant articulation performance and speech intelligibility of patients with submucous cleft palate(SMCP)and to provide a reference for clinical speech evaluation and subsequent speech rehabilitation.Methods A total of 333 preoperative SMCP patients aged 4.5 years and older participated in this study.The accuracy,type of error,and error rates were assessed across participant genders and their varying levels of velopharyngeal closure function.Results Among the 333 patients,196 had complete velopharyngeal closure,while 137 had incomplete closure.A total of 145 patients(43.54％)demonstrated normal articulation of all conso-nants,while 188 patients(56.46％)displayed various degrees of articulation disorders.Compensatory articulation behaviors were observed in 66 patients(19.82％).No significant differences in articulation errors were found be-tween male and female patients.The accuracy ranking for consonants was from high to low as follows:nasal sounds,lateral sounds,fricatives,plosives,and affricates.Substitution was the most common error type with an incidence of 35.93％,followed by omission at 34.62％and compensatory errors at 25.51％.The average accuracy rates for plosives,fricatives,affricates,lateral/nasal sounds were 73.27％,78.20％,69.29％,and 93.39％,re-spectively.Substitution was the most common error for plosives and fricatives,while omission was most frequent for affricates.Compensatory errors occurred most often with affricates,and no compensatory errors were found in nasal or lateral sounds.Conclusion Substitution,omission,and compensatory errors are the most common articula-tion errors in SMCP patients,occurring across plosives,fricatives,and affricates.The severity of articulation disor-ders is related to velopharyngeal closure function but is independent of gender.

Pulmonary hypertension(PH)is a serious cardiovascular condition that significantly impacts pa-tients'quality of life.Currently available clinical medications lack selectivity for pulmonary blood vessels,often produce substantial side effects,and are prohibitively expensive.Therefore,it is crucial to explore the mechanisms underlying the onset and progression of PH and to develop new,effective treatments.Ubiquitination is a key form of protein post-transla-tional modification in which specific E3 enzymes recognize substrate proteins and induce ubiquitination,leading to chang-es in their activity or stability.During the onset of PH,the activities of ubiquitin ligases and deubiquitinases undergo vari-ous changes,resulting in altered ubiquitination levels of different proteins.These variations primarily influence the degra-dation rates of substrate proteins within cells,thereby regulating essential physiological processes.Proteasomes play a vi-tal role in the degradation of ubiquitinated proteins,and inhibitors targeting these complexes have been developed,demon-strating therapeutic efficacy in experimental settings of PH.However,their low specificity presents significant challenges for practical applications.In this context,we summarize the relevant mechanisms of ubiquitination regulation in the onset of PH and highlight its practical significance for future therapeutic strategies.

External apical root resorption(EARR)is one of the most common side effects of orthodontic treatment.Contact with sur-rounding anatomical structures during tooth movement is a significant cause for EARR.However,a comprehensive review of factors leading to EARR due to direct contact of surrounding anatomical structures with the root apex during orthodontic treatment is still lac-king.This review summarizes the anatomical structures related to EARR,including alveolar bone,incisive canal,maxillary sinus,ad-jacent teeth,and bone islands.Alveolar bone,incisive canal,and adjacent teeth can directly cause EARR during orthodontic treat-ment,while the impact of the maxillary sinus and bone islands on EARR has not been discovered so far.Analyzing the anatomical structures around the tooth roots can help develop more effective methods to prevent or reduce the occurrence of EARR during orthodon-tic treatment.

Sarcopenia is a systemic disease characterized by accelerated loss of skeletal muscle mass and function,leading to an increased incidence of adverse outcomes such as falls and fractures.Sarcopenia is classified into primary and secondary types,with primary sarcopenia being closely related to aging and posing a serious threat to a healthy life among the elderly.Sarcopenia has an insidious onset and is often overlooked in terms of its clinical treatment.Its pathogenesis is complex,involving functional changes and pathological alterations in multiple systems,and presenting major research challenges.Cell models can effectively be used to simulate the pathological changes of diseases under controllable conditions,thus facilitating the investigation of the etiology and factors influencing sarcopenia,and providing an important approach for in-depth studies of its mechanism;however,there is currently no standardized cell model in the field of sarcopenia research.Commonly used cell models currently include models involving protein metabolism interventions,oxidative stress,and inflammatory response interventions.This review considers the commonly used skeletal muscle cell types and modeling method of sarcopenia,to provide a solid foundation and important method ological reference for further simulation of the pathological process of sarcopenia in subsequent experimental studies.

Objective To explore the expression of serum Hepcidin,long non-coding RNA myocardial infarction-associated transcript(LncRNA MIAT)and creatinine(CRE)in patients with bipolar disorder(BPD)and their relationship with the severity of the disease.Method In this study,150 patients with BPD who were admitted to Baoji Central Hospital from March 2021 to March 2023 were selected as the study subjects and were included in the BPD group.Another 150 healthy subjects were selected as the control group.Hamilton Depression Scale(HAMD)was used to evaluate depression.Young mania ratings scale(YMRS)was used to evaluate the degree of mania.All subjects were tested for serum Hepcidin,LncRNA MIAT and CRE levels.The levels of serum Hepcidin,LncRNA MIAT and CRE were compared between control group and BPD group.The levels of serum Hepcidin,LncRNA MIAT and CRE in BPD groups with different depression/mania degrees were compared.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum Hepcidin,LncRNA MIAT and CRE in BPD.The relationship between serum Hepcidin,LncRNA MIAT and CRE and the severity of BPD was analyzed.Results The levels of serum Hepcidin(46.17±9.17 ng/L),LncRNA MIAT(11.92±2.65)and CRE(74.02±11.89 μ mol/L)in BPD group were higher than those in control group(22.16±5.23 ng/L,4.11±0.95,57.16±8.61 μ mol/L),with significant differences(t=-27.856,-43.079,-14.066,all P＜0.05).The levels of serum Hepcidin,LncRNA MIAT and CRE increased with the increase of depression/mania in BPD patients(F=22.036,25.463,17.499;19.552,15.791,18.335,all P＜0.05).The combined detection of serum Hepcidin,LncRNA MIAT and CRE(95％CI:0.866～0.949)for BPD diagnosis had an area under the ROC curve of 0.914,with high specificity and sensitivity,which was significantly higher than that of serum Hepcidin alone(95％CI:0.693～0.816),LncRNAMIAT(95％CI:0.696～0.819)alone and CRE(95％CI:0.587～0.701)detection alone(AUC=0.759,0.762,0.614,all P＜0.05).Serum Hepcidin,LncRNA MIAT and CRE were positively correlated with depression severity in BPD patients(r=0.784,0.771,0.826,all P＜0.05).Serum Hepcidin,LncRNA MIAT and CRE were positively correlated with mania severity in BPD patients(r=0.806,0.793,0.831,all P＜0.05).Conclusion The levels of serum Hepcidin,LncRNA MIAT and CRE in BPD patients were higher than those in the normal population,and they were positively correlated with the severity of the disease.Combined detection may have a high diagnostic value.

Objective:Hypoxia is a common pathological phenomenon,usually caused by insufficient oxygen supply or inability to use oxygen effectively.Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity.This study aims to explore the synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein(6-OHG)and its methoxylated derivatives. Methods:The 6-OHG and its methoxylated derivatives,including 4',6,7-trimethoxy-5-hydroxyisoflavone(compound 3),4',5,6,7-tetramethoxyisoflavone(compound 4),4',6-imethoxy-5,7-dihydroxyisoflavone(compound 6),and 4'-methoxy-5,6,7-trihydroxyisoflavone(compound 7),were synthesized by methylation,bromination,methoxylation,and demethylation using biochanin A as raw material.The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy(1H-NMR)and mass spectrometry(MS).The purity of these compounds was detected by high pressure chromatography(HPLC).The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical(DPPH)free radical scavenging assay.PC12 cells were divided into a normal group,a hypoxia model group,rutin(1×10-9-1×10-5 mol/L)groups,and target compounds(1×10-9-1×10-5 mol/L)groups under normal and hypoxic conditions.Cell viability was detected by cell counting kit-8(CCK-8)assay,the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened.PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity,and the cell morphology was observed under light microscope.The apoptotic rate was determined by flow cytometry,and the expressions of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Western blotting. Results:The structure of 6-OHG and its 4 methylated derivatives were correct,and the purity was all more than 97%.When the concentration was 4 mmol/L,the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16%and 86.94%,respectively,which were higher than those of rutin,the positive control.The removal rates of chemical compounds 3,4,and 6 were all lower than 20%.Compared with the normal group,the cell viability of the hypoxia model group was significantly decreased(P<0.01).Compared with the hypoxia model group,compounds 3,4,and 6 had no significant effect on cell viability under hypoxic conditions.At all experimental concentrations,the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group(all P<0.05).The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group(both P<0.05).The anti-hypoxia activity of 6-OHG and compound 7 was excellent,and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L.After PC12 cells was treated with 6-OHG(1×10-6 mol/L)and compound 7(1×10-7 mol/L),the cell damage was reduced,the apoptotic rate was significantly decreased(P<0.01),and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group(both P<0.01). Conclusion:The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation.6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities,which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.