ObjectiveTo investigate the relationship between periodontitis severity and brain functional indices-amplitude of low-frequency fluctuations （ALFF） and fractional ALFF （fALFF） in cognitively normal middle-aged and older adults， and to examine their associations with cognitive performance. Methods42 cognitively normal middle-aged and older participants were enrolled. Periodontal data—including the number of remaining teeth （NTP）， bleeding on probing positivity rate （BOP%）， probing depth （PD）， and clinical attachment loss （CAL） as well as resting-state functional magnetic resonance imaging data were collected. Participants were divided into a mild periodontitis group and a moderate-to-severe periodontitis group according to periodontitis severity. Group differences in ALFF and fALFF were compared， and correlation analyses were performed. ResultsCompared with the mild periodontitis group， the moderate-to-severe group showed decreased ALFF values in the right lingual gyrus， superior occipital gyrus， paracentral lobule， and in the left calcarine cortex as well as the precentral and postcentral gyri. Decreased fALFF values were observed in the right lingual gyrus， cuneus， and left calcarine cortex. Indicators related to periodontitis progression ［BOP%， PD=4-5 mm （%）， PD≥6 mm （%）， CAL=3-4 mm （%） and CAL≥5 mm （%）］ were negatively correlated with ALFF， fALFF and cognitive performance， whereas indicators reflecting better periodontal function ［PD=1-3 mm （%） and CAL=0-2 mm （%）］ were positively correlated with these measures. ConclusionIn cognitively normal middle-aged and older adults， periodontitis severity is associated with alterations in brain functional activity and cognitive performance.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

Objective: To explore sex differences in 3D T1texture features in the progression of Alzheimer's disease (AD) and to predict the diagnosis of AD patients of different sex． Methods: Seventy-seven AD patients (34 males and 42 females) ，74 amnestic mild cognitive impairment ( aMCI) patients ( 35 males and 39 females) and 75 healthy controls (HC) (35 males and 40 females) were recruited and high-resolution 3-dimensional T1 structural images were collected． Brain regions closely related to AD brain damage were selected as regions of interest ( ROIs) ，texture feature extraction and feature screening were performed．Analyses were performed by sex，and the support vector machine (SVM) was used for classification and prediction. Results : In the AD vs HC，AD vs aMCI and aMCI VS HC groups by different sex，we obtained some brain regions with relatively high recognition index in different subgroups，and found that there were significant differences between female patients and male patients with high recognition index，and the recognition index of female patients ( area under the curve，accuracy，sensitivity and specificity were generally higher than that of male． Conclusion There are significant sex differences in texture features in AD process，and the classification and prediction ability of texture features in female patients is better， suggesting the importance of sex differences in AD research．This study provides some reliable biomarkers for early sex-specific identification of AD，which may be helpful for the early diagnosis and treatment of AD in the future.

The secondary structure is a fundamental feature of both non-coding RNAs (ncRNAs) and messenger RNAs (mRNAs). However, our understanding of the secondary structures of mRNAs, especially those of the coding regions, remains elusive, likely due to translation and the lack of RNA-binding proteins that sustain the consensus structure like those binding to ncRNAs. Indeed, mRNAs have recently been found to adopt diverse alternative structures, but the overall functional significance remains untested. We hereby approach this problem by estimating the folding specificity, i.e., the probability that a fragment of an mRNA folds back to the same partner once refolded. We show that the folding specificity of mRNAs is lower than that of ncRNAs and exhibits moderate evolutionary conservation. Notably, we find that specific rather than alternative folding is likely evolutionarily adaptive since specific folding is frequently associated with func-tionally important genes or sites within a gene. Additional analysis in combination with ribosome density suggests the ability to modulate ribosome movement as one potential functional advantage provided by specific folding. Our findings reveal a novel facet of the RNA structurome with important functional and evolutionary implications and indicate a potential method for distinguishing the mRNA secondary structures maintained by natural selection from molecular noise.

Objective: To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF. Methods: We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis. Results: (1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation. Conclusions The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.

Objective: To construct Bayes discriminant function for clinical classification of common and severe Japanese encephalitis (JE) cases, and to identify cases accurately with quantitative indicators. Methods: Samples of confirmed common and severe JE cases reported by the epidemic surveillance system of Gansu Provincial Center for Disease Control and Prevention from 2005 to 2017 were collected. Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis were used to screen meaningful clinical indicators, so as to construct and evaluate Bayes discriminant function. Results: There were 256 common JE cases and 257 severe JE cases. There were no significant differences in sex, age and occupation distributions between the two groups (P>0.05) and there was significant difference in case fatality rate (P<0.05). Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis, combined with using related literature, to screen 11 clinical indicators for the construction of Bayes discriminant function. Interactive validation showed that the sensitivity of discriminant function was 71.48% (95%CI: 65.53%-76.93%) and the specificity was 73.93% (95%CI: 68.11%-79.19%). The area under ROC curve was 0.761 (95%CI: 0.720-0.803) and the total accuracy rate was 72.71%. Conclusion Bayes discriminant function can be used to identify common and severe JE cases more accurately, which is helpful for the reasonable treatment and good prognosis of JE patients.

Objective To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF. Methods We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non?conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis. Results (1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non?cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation ( OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter ( OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation. Conclusions The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.

This article was aimed to explore the effect ofSan-Huang (SH) decoction on improving chemosensitivity of MCF-7 cells to epirubicin and inhibition of Aurora kinase A, in order to discuss its underlying mechanism. The inhibition of MCF-7 cells proliferation on breast cancer by SH decoction was determined by CCK-8 assay. RT-PCR and western blot were used to detect the Aurora A, p53 mRNA and protein expression level of MCF-7 cells by SH decoction. The siRNA silenced Aurora A of MCF-7 cells. CCK-8 assay was used to detect the inhibition of MCF-7 cells proliferation. CCK-8 assay and AnnexinV-FITC/PI staining were used to detect the inhibition rate and apoptosis rate of MCF-7 cells treated by the combination of SH decoction and epirubicin. Western blot analysis was used to detect the expression of apoptosis-related proteins. The results showed that SH decoction inhibited the proliferation of MCF-7 cells in a dose-dependent manner (P< 0.05). The effect of 48 h medication was better than 24 h (P < 0.05). There was no statistical difference with medication for 72 h (P > 0.05). SH decoction can regulate the Aurora A, p53 protein and mRNA expression of MCF-7 cells. siRNA silenced Aurora A, which downregulated the inhibition rate of MCF-7 cells by SH decoction for 50.0% (from 49.2% to 24.8%). The combination of SH decoction and epirubicin enhanced the effect of epirubicin on inhibiting the proliferation rate and apoptosis rate of MCF-7 cell, regulated the expression levels of apoptosis-related protein such as c-PARP, c-Caspase 3, Bcl-2, Bax, as well as the protein level of Aurora A. It was concluded that SH decoction can increase the chemosensitivity of MCF-7 cells to epirubicin, which may be related to the inhibition of Aurora Kinase A by SH decoction.

ABSTRACTOBJECTIVE To explore the effect of San Huang decoction on the apoptosis of breast cancer cells and the effect on the mRNA and protein expression and function of Aurora kinase A and discuss the underlying mechanism of San Huang in-duced apoptosis.METHODS The inhibition of breast cancer cells proliferation was determined by CCK?8 assay.The apoptosis of breast cancer cells was detected by AnnexinV?FITC/PI Staining.The expression of mRNA of Aurora A was examined by q ?PCR analysis.The expression of apoptosis?related proteins and Aurora A were determined by Western Blot analysis.RE-SULTS San Huang decoction inhibited the proliferation of breast cancer cells in a does?dependent mannerP <0.05.The effect of inhibition caused by San Huang decoction 48 hours after delivering to breast cancer cells was better than 24 hoursP <0.05 although similar as 72 hoursP >0.05.San Huang decoction was also found to induce apoptosis in both MCF?7 and MDA?MB?231 cell lines in a dose?dependent manner.Consistent with cellular resultsSan Huang decoction treatment signifi-cantly increased the apoptosis?related protein level of cleaved?PARPc?PARPcleaved?Caspase 3c?Caspase 3and Baxdown ?regulated Bcl?2 in a does?dependent manner.MeanwhileSan Huang decoction decreased the mRNA and protein level of Auro-ra A and increased those of p53 in a does?dependent manner.CONCLUSION San Huang decoction at the first time was able to promote the apoptosis of breast cancer cells via inducing the suppression of Aurora A.