Objective:To study the effects of obesity on alveolar bone loss and gut microbiota in mice with periodontitis.Methods:Twenty-four seven-week-old female C57BL/6J mice were randomly divided into four groups based on table of random numbers ( n=6 in each group): normal-fat diet group (NFD group), high-fat diet group (HFD group), normal-fat diet and periodontitis group (NFD_PD group) and high-fat diet and periodontitis group (HFD_PD group). NFD and HFD groups were fed with normal or high-fat diet for twelve weeks respectively; NFD_PD and HFD_PD groups were induced to periodontitis by ligating the bilateral maxillary second molars with 5-0 silk thread at the fourth week after feeding with normal or high-fat diet respectively. The body weight was measured weekly. The mice were euthanized for collecting the samples at the end of the 12th week. Liver, kidneys, perirenal and retroperitoneal fat were weighed. Serum was collected to detect the level of serum lipids and inflammatory factors. The right maxilla bones were scanned by micro-CT. HE staining was performed to observe the periodontal tissue. The cecum contents were collected for gut microbiota 16S rRNA gene sequencing. Spearman correlation analysis was performed to analyze the correlation between the abundance of gut microbiota and serum inflammatory level and CT value. Results:After 12 weeks of high-fat diet fed, the body weight of HFD group [(26.52±1.96) g] was significantly higher than that of NFD group [(20.95±0.63) g] ( t=6.63, P<0.001). The body weight of HFD_PD group [(23.82±1.12) g] was significantly higher than that of NFD_PD group [(20.73±0.47) g] ( t=6.23, P=0.001). The serum levels of total cholesterol, triglyceride and low density lipoprotein in HFD group and HFD_PD group were significantly higher than those in NFD group and NFD_PD group ( P<0.01). The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC) on the mesial site of maxillary second molar in HFD_PD group [(647.46±47.46) μm] was significantly higher than that in NFD_PD group [(440.48±68.08) μm] ( t=5.58, P<0.001). HE staining showed that the maxillary second molar attachment loss, collagen fiber destruction and inflammatory cell infiltration were more significant serious in HFD_PD group compared with NFD_PD group. The levels of interleukin (IL)-1β, IL-6 and monocyte chemotactic protein-1 (MCP-1) of serum in HFD_PD group [(17.11±1.92), (31.61±3.20) and (204.42±35.96) ng/L, respectively] were significantly higher than those in NFD_PD group [(10.44±1.65), (19.96±2.09) and (147.36±10.76) ng/L, respectively] ( P<0.001, P<0.001, P=0.004). The 16S rRNA gene analysis revealed that the Bacteroides/Firmicutes ratio in HFD_PD group (4.00±3.30) was significantly higher than that in NFD_PD group (0.62±0.19) ( t=2.50, P=0.030). The abundance of Oscillospira in HFD_PD group [(12.25±0.05) %] was significantly higher than that in NFD_PD group [(2.80±0.01) %] ( t=4.64, P<0.001). The abundance of Parabacteroides in HFD_PD group [(0.25±0.27)% ] was significantly lower than that in NFD_PD group [(2.04±0.02)%] ( t=2.32, P=0.043). The β-diversity analysis of gut microbiota based on Bray-Curtis distance showed that samples of HFD_PD group and NFD_PD group were obviously grouped. Correlation analysis showed that the abundance of Oscillospira was positively correlated with IL-1β, IL-6, MCP-1 concentration and CEJ-ABC value in serum significantly ( r values were 0.80, 0.79, 0.80, 0.89, P<0.05). The abundance of Parabacteroides was negatively correlated with IL-1β, IL-6 concentration and CEJ-ABC value in serum significantly ( r values were -0.71, -0.71, -0.86, -0.95, P<0.05). Conclusions:Obesity promotes alveolar bone resorption in periodontitis mice and changes the gut microbiota. Oscillospira and Parabacteroides may play a key role.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVES: A stable, reliable, and easily implementable clinical diagnostic method for marginal velopharyngeal insufficiency (MVPI) was established on the basis of the subjective hearing judgement of hypernasality and objective examination of velopharyngeal closure to address the lack of unified diagnostic criteria for MVPI. METHODS: Nasopharyngeal fiberscopy and speech assessment results were collected from postoperative patients with cleft palate. These results were used to analyze the differences in the distribution of nasal resonance in patients with different velopharyngeal closure ratios and the correlation between velopharyngeal closure ratios and nasal resonance status. Mild-to-moderate hypernasality with its corresponding elopharyngeal closure ratio was employed to establish the diagnostic criteria of MVPI. The reproducibility of the criteria and whether the patients with MVPI diagnosed by using the criteria exhibited significantly different speech characteristics compared with other patients were verified. RESULTS: A strong correlation was found between velopharyngeal closure ratios and nasal resonance (P<0.001). Mild-to-moderate hypernasality mainly corresponded to velopharyngeal closure ratios ranging from 90% to 99%, and the combination of the two characteristics as the diagnostic criteria for MVPI demonstrated good consistency (Kappa value=0.789, P<0.001). Moreover, under the diagnostic criteria, significant differences in nasal resonance (P<0.001), nasal emission (P=0.007), and misarticulation (P<0.001) were found between patients with velopharyngeal insufficiency and those with MVPI. CONCLUSIONS Combining the subjective hearing judgement of mild-to-moderate hypernasality with velopharyngeal closure ratios over 90% under nasopharyngeal fiberscopy provides a reliable and effective clinical method for diagnosing MVPI.
Humans ; Velopharyngeal Insufficiency/physiopathology* ; Reproducibility of Results ; Cleft Palate/surgery* ; Male ; Female ; Child

Intelligence encompasses various abilities, including logical reasoning, comprehension, self-awareness, learning, planning, creativity, and problem-solving. Extensive research and practical experience suggest that there are sex differences in intellectual development, with females typically maturing earlier than males. However, the key genes and molecular network mechanisms underlying these sex differences in intellectual development remain unclear. To date, Genome-Wide Association Studies (GWAS) have identified 507 genes that are significantly associated with intelligence. This study first analyzed RNA sequencing data from different stages of brain development (from BrainSpan), revealing that during the late embryonic stage, the average expression levels of intelligence-related genes are higher in males than in females, while the opposite is observed during puberty. This study further constructed interaction networks of intelligence-related genes with sex-differential expression in the brain, including the prenatal male network (HELP-M: intelligence genes with higher expression levels in prenatal males) and the pubertal female network (HELP-F: intelligence genes with higher expression levels in pubertal females). The findings indicate that the key genes in both networks are Ep300 and Ctnnb1. Specifically, Ep300 regulates the transcription of 53 genes in both HELP-M and HELP-F, while Ctnnb1 regulates the transcription of 45 genes. Ctnnb1 plays a more prominent role in HELP-M, while Ep300 is more crucial in HELP-F. Finally, this study conducted sequencing validation on rats at different developmental stages, and the results indicated that in the prefrontal cortex of female rats during adolescence, the expression levels of the intelligence genes in HELP-F, as well as key genes Ep300 and Ctnnb1, were higher than those in male rats. These genes were also involved in neurodevelopment-related biological processes. The findings reveal a sex-differentiated intelligence gene network and its key genes, which exhibit varying expression levels during the neurodevelopmental process.
Female ; Intelligence/physiology* ; Male ; Sex Characteristics ; Animals ; Brain/growth & development* ; E1A-Associated p300 Protein/physiology* ; beta Catenin/physiology* ; Transcriptome ; Rats ; Gene Expression Profiling ; Genome-Wide Association Study

Objective:To develop a culturally adapted Advance Care Planning (ACP) Decision Balance Scale for Family Members of Patients with Advanced Cancer in China, and to test its reliability and validity.Methods:Based on the transtheoretical model-decisional balance framework, the item pool was established through literature analysis, qualitative interviews, and research team discussions. After expert panel meetings and semantic debugging pre-surveys among family members of patients with advanced cancer, item screening was conducted to form the pilot scale. From October to December 2024, the scale was administered to 310 family members of inpatients with advanced cancer in five Class Ⅲ Grade A hospitals in Chongqing. SPSS and AMOS software were used for item analysis and reliability and validity testing, and the final formal scale was developed.Results:The ACP Decision Balance Scale for Family Members of Patients with Advanced Cancer consisted of 2 dimensions, perceived cost of choice and perceived benefit of choice, with a total of 12 items. The Cronbach's α coefficient of the scale was 0.875, the split-half reliability was 0.905, and the test-retest reliability was 0.856. The item-level content validity index ranged from 0.880 to 1.000, and the scale-level content validity index was 0.980. Exploratory factor analysis extracted 2 common factors, with a cumulative variance contribution rate of 65.365%. Confirmatory factor analysis showed χ 2/ df=1.743, and the model fit indices met the requirements. The scale also demonstrated good convergent validity and discriminant validity. Conclusions:The ACP Decision Balance Scale for Family Members of Patients with Advanced Cancer developed in this study demonstrated good reliability and validity. It can be used as a tool to assess the level of ACP decision-making participation of family members of patients with advanced cancer, and to systematically, comprehensively, and effectively evaluate, collect, and analyze their behavioral intentions and barriers regarding ACP decision-making.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

Objective:To develop a culturally adapted Advance Care Planning (ACP) Decision Balance Scale for Family Members of Patients with Advanced Cancer in China, and to test its reliability and validity.Methods:Based on the transtheoretical model-decisional balance framework, the item pool was established through literature analysis, qualitative interviews, and research team discussions. After expert panel meetings and semantic debugging pre-surveys among family members of patients with advanced cancer, item screening was conducted to form the pilot scale. From October to December 2024, the scale was administered to 310 family members of inpatients with advanced cancer in five Class Ⅲ Grade A hospitals in Chongqing. SPSS and AMOS software were used for item analysis and reliability and validity testing, and the final formal scale was developed.Results:The ACP Decision Balance Scale for Family Members of Patients with Advanced Cancer consisted of 2 dimensions, perceived cost of choice and perceived benefit of choice, with a total of 12 items. The Cronbach's α coefficient of the scale was 0.875, the split-half reliability was 0.905, and the test-retest reliability was 0.856. The item-level content validity index ranged from 0.880 to 1.000, and the scale-level content validity index was 0.980. Exploratory factor analysis extracted 2 common factors, with a cumulative variance contribution rate of 65.365%. Confirmatory factor analysis showed χ 2/ df=1.743, and the model fit indices met the requirements. The scale also demonstrated good convergent validity and discriminant validity. Conclusions:The ACP Decision Balance Scale for Family Members of Patients with Advanced Cancer developed in this study demonstrated good reliability and validity. It can be used as a tool to assess the level of ACP decision-making participation of family members of patients with advanced cancer, and to systematically, comprehensively, and effectively evaluate, collect, and analyze their behavioral intentions and barriers regarding ACP decision-making.

Objective:To study the effects of obesity on alveolar bone loss and gut microbiota in mice with periodontitis.Methods:Twenty-four seven-week-old female C57BL/6J mice were randomly divided into four groups based on table of random numbers ( n=6 in each group): normal-fat diet group (NFD group), high-fat diet group (HFD group), normal-fat diet and periodontitis group (NFD_PD group) and high-fat diet and periodontitis group (HFD_PD group). NFD and HFD groups were fed with normal or high-fat diet for twelve weeks respectively; NFD_PD and HFD_PD groups were induced to periodontitis by ligating the bilateral maxillary second molars with 5-0 silk thread at the fourth week after feeding with normal or high-fat diet respectively. The body weight was measured weekly. The mice were euthanized for collecting the samples at the end of the 12th week. Liver, kidneys, perirenal and retroperitoneal fat were weighed. Serum was collected to detect the level of serum lipids and inflammatory factors. The right maxilla bones were scanned by micro-CT. HE staining was performed to observe the periodontal tissue. The cecum contents were collected for gut microbiota 16S rRNA gene sequencing. Spearman correlation analysis was performed to analyze the correlation between the abundance of gut microbiota and serum inflammatory level and CT value. Results:After 12 weeks of high-fat diet fed, the body weight of HFD group [(26.52±1.96) g] was significantly higher than that of NFD group [(20.95±0.63) g] ( t=6.63, P<0.001). The body weight of HFD_PD group [(23.82±1.12) g] was significantly higher than that of NFD_PD group [(20.73±0.47) g] ( t=6.23, P=0.001). The serum levels of total cholesterol, triglyceride and low density lipoprotein in HFD group and HFD_PD group were significantly higher than those in NFD group and NFD_PD group ( P<0.01). The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC) on the mesial site of maxillary second molar in HFD_PD group [(647.46±47.46) μm] was significantly higher than that in NFD_PD group [(440.48±68.08) μm] ( t=5.58, P<0.001). HE staining showed that the maxillary second molar attachment loss, collagen fiber destruction and inflammatory cell infiltration were more significant serious in HFD_PD group compared with NFD_PD group. The levels of interleukin (IL)-1β, IL-6 and monocyte chemotactic protein-1 (MCP-1) of serum in HFD_PD group [(17.11±1.92), (31.61±3.20) and (204.42±35.96) ng/L, respectively] were significantly higher than those in NFD_PD group [(10.44±1.65), (19.96±2.09) and (147.36±10.76) ng/L, respectively] ( P<0.001, P<0.001, P=0.004). The 16S rRNA gene analysis revealed that the Bacteroides/Firmicutes ratio in HFD_PD group (4.00±3.30) was significantly higher than that in NFD_PD group (0.62±0.19) ( t=2.50, P=0.030). The abundance of Oscillospira in HFD_PD group [(12.25±0.05) %] was significantly higher than that in NFD_PD group [(2.80±0.01) %] ( t=4.64, P<0.001). The abundance of Parabacteroides in HFD_PD group [(0.25±0.27)% ] was significantly lower than that in NFD_PD group [(2.04±0.02)%] ( t=2.32, P=0.043). The β-diversity analysis of gut microbiota based on Bray-Curtis distance showed that samples of HFD_PD group and NFD_PD group were obviously grouped. Correlation analysis showed that the abundance of Oscillospira was positively correlated with IL-1β, IL-6, MCP-1 concentration and CEJ-ABC value in serum significantly ( r values were 0.80, 0.79, 0.80, 0.89, P<0.05). The abundance of Parabacteroides was negatively correlated with IL-1β, IL-6 concentration and CEJ-ABC value in serum significantly ( r values were -0.71, -0.71, -0.86, -0.95, P<0.05). Conclusions:Obesity promotes alveolar bone resorption in periodontitis mice and changes the gut microbiota. Oscillospira and Parabacteroides may play a key role.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.