BACKGROUND:Studies have shown that patients with premature ovarian failure have changes in the structure of intestinal flora and that imbalance of intestinal microbiota may be one of the important mechanisms in the development of premature ovarian failure. OBJECTIVE:To investigate the effect of Liuwei Dihuang Wan on oxidative stress and intestinal microbiota in premature ovarian failure mice induced by cyclophosphamide. METHODS:Forty-five female ICR mice were randomized into three groups:blank group(normal mice),model group(premature ovarian failure mice),and Liuwei Dihuang Wan group.A mouse model of premature ovarian failure was prepared by one-time intraperitoneal injection of cyclophosphamide(120 mg/kg)in the latter two groups.After successful modeling,the Liuwei Dihuang Wan group was intragastrically administered for 28 continuous days,and the other two groups were intragastrically administered with the same amount of normal saline for 28 days.Mouse body mass was recorded weekly and ovarian index was calculated.The development of mouse follicles was observed using hematoxylin-eosin staining.ELISA method was used to detect serum levels of anti-Mullerian hormone,estradiol,follicle stimulating hormone,superoxide dismutase,glutathione peroxidase,and malondialdehyde.Meanwhile,the gut microbiome of all mice was detected through 16S rDNA sequencing. RESULTS AND CONCLUSION:The mice in the model group had loose hair,decreased vigor and grip strength,almost no increase in body mass,and decreased ovarian index.Whereas,the mouse body mass and ovarian index were increased after treatment with Liuwei Dihuang Wan(P<0.05).The estrous cycle of mice in the model group was disorganized;Liuwei Dihuang Wan could restore the estrous cycle and reduce the number of atretic follicles in mice with premature ovarian failure.The serum levels of follicle stimulating hormone and malondialdehyde in the model group significantly increased(P<0.01),while the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase significantly decreased(P<0.01).Liuwei Dihuang Wan could significantly decrease the serum levels of follicle stimulating hormone and malondialdehyde(P<0.01),and increase the levels of estradiol,anti-Mullerian hormone,superoxide dismutase,and glutathione peroxidase.According to the 16S rDNA sequencing results,Liuwei Dihuang Wan could regulate the abundance and diversity of intestinal microbiota,and increase the relative abundance of beneficial bacteria.KEGG pathway analysis showed that the intestinal microbiota and metabolic pathways,biosynthesis of secondary metabolites,microbial metabolism in different environments,and biosynthesis of amino acids were regulated by Liuwei Dihuang Wan.To conclude,the changes in the structure of intestinal microbiome may be one of the potential mechanisms of Liuwei Dihuang Wan in treating premature ovarian failure.Liuwei Dihuang Wan can regulate the structure of intestinal microbiome,increase the number of beneficial bacteria,reduce the number of harmful bacteria,and thus improve the balance of intestinal microbiota.This regulatory effect helps to reduce oxidative stress levels and further inhibit ovarian oxidative stress in mice with premature ovarian failure.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective:To define the concept of proactive health behavior.Methods:Literature related to proactive health behavior was retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Embase, and Ovid databases, with a retrieval time frame from database inception to March 1, 2025. Walker and Avant's concept analysis method was used to analyze the concept of proactive health behavior.Results:A total of 46 articles related to proactive health behavior were included. Proactive health behavior encompasses five key attributes: self-initiation, long-term persistence, multidimensional integration, future orientation, and overcoming barriers. Antecedents include individual factors, supportive factors, and environmental factors. Outcomes include promoting individual health and improving quality of life, enhancing personal health literacy, reducing disease burden, and fostering a proactive health atmosphere.Conclusions:The concept attributes of proactive health behavior were clarified through concept analysis. Future researchers may develop proactive health behavior assessment tools and construct intervention strategies based on their connotation.

The KCNQ potassium channels play a crucial role in modulating neural excitability, and their dysfunction is closely associated with epileptic disorders. While variants in KCNQ2 have been extensively studied, KCNQ3-related disorders have rarely been reported. With advances in next-generation sequencing technologies, an increasing number of cases of KCNQ3-related disorders have been identified. However, the correlation between genotype and phenotype remains poorly understood. In this study, we established a variant library consisting of 24 missense mutations in KCNQ3 and introduced these mutations into three different template types: KCNQ3, KCNQ3-A315T (Q3*), and KCNQ3-KCNQ2 tandem (Q3-Q2). We then analyzed the effects of these mutations on the KCNQ3 channel function using patch-clamp recording. The most informative parameter across all three backgrounds was the current density of the mutant channels. The current density patterns in the Q3* and Q3-Q2 backgrounds were similar, with most mutations resulting in an almost complete loss of function (LOF), they were concentrated in the pore-forming domain of KCNQ3. In contrast, mutations in the voltage-sensing domain or C-terminus did not show significant differences from the wild-type channel. Interestingly, these LOF mutations were typically associated with self-limited familial neonatal epilepsy, while neurodevelopmental disorders (NDD) were more closely associated with mutations that did not significantly differ from the wild-type. V_1/2, another important parameter of the electrophysiological properties, could not be accurately determined in the majority of KCNQ3 mutations due to its nearly complete LOF in the Q3* and Q3-Q2 backgrounds. Intriguingly, the V_1/2 of functional mutations were primarily leftward shifted, indicating a gain-of-function (GOF) effect, which was typically associated with NDD. In addition to previously reported mutations, we identified G553R as a novel GOF mutation. In the co-transfection background, parameters such as V_1/2 could be determined, but the dysfunctional effects of these mutations were mitigated by the co-expression of wild-type KCNQ3 and KCNQ2 subunits, resulting in no significant differences between most mutations and the wild-type channel. Furthermore, we applied KCNQ modulators to reverse the electrophysiological abnormalities caused by KCNQ3 variants. The LOF mutations were reversed by the application of Pynegabine (HN37), a KCNQ opener, while the GOF mutation responded well to Amitriptyline (AMI), a KCNQ inhibitor. These findings provide essential insights into the pathogenic mechanisms underlying KCNQ3-related disorders and may inform clinical decision-making.
KCNQ3 Potassium Channel/genetics* ; Humans ; Mutation, Missense/genetics* ; KCNQ2 Potassium Channel/genetics* ; Patch-Clamp Techniques ; HEK293 Cells ; Animals ; Phenylenediamines/pharmacology* ; Carbamates

Objective To explore the value of serum long non-coding RNA KCNQl opioid strand transcript 1(lncRNA KCNQ1OT1)and fibroblast growth factor 2(FGF2)in the evaluation of the condition and control level of pediatric bronchial asthma.Methods 96 children with bronchial asthma(Asthma group)and 76 healthy children(Control group)admitted to Yulin Hospital of Traditional Chinese Medicine from March 2021 to March 2023 were selected.According to the severity of bronchial asthma,the children were divided into a mild group(n=54)and a severe group(n=42).According to the disease control status after treatment,the children were divided into an asthma Control group(n=61)and an uncontrolled Asthma group(n=35).The serum levels of lncRNA KCNQ1OT1 and FGF2 were detected in each group.Multivariate Logistic regression analysis was performed to identify the factors affecting bronchial asthma disease control.The performance of lncRNA KCNQ1OT1 and FGF2 in predicting the control of bronchial asthma disease was evaluated using the receiver operating characteristic curve.Results The serum levels of lncRNA KCNQ1OT1(2.35±0.71)and FGF2(27.35±6.29 pg/ml)in the Asthma group were higher than those in the Control group(1.51±0.33,15.32±4.08 pg/ml),and the differences were statistically significant(t=9.527,14.437,all P<0.001).The serum levels of lncRNA KCNQ1OT1(2.59±0.35)and FGF2(28.65±1.03 pg/ml)in the severe group were higher than those in the mild group(2.16±0.41,26.34±1.24 pg/ml),and the differences were statistically significant(t=5.429,9.737,all P<0.001).The serum levels of lncRNA KCNQ1OT1(2.63±0.27)and FGF2(29.02±1.41 pg/ml)in the uncontrolled asthma group were higher than those in the controlled asthma group(2.19±0.35,26.39±1.52 pg/ml),and the differences were statistically significant(t=5.417,8.374,all P<0.001).High lncRNA KCNQ1OT1 and FGF2 levels were risk factors for uncontrolled disease in children with bronchial asthma(all P<0.05).The AUC of lncRNA KCNQ1OT1 and FGF2 combined to predict uncontrolled disease in children with bronchial asthma,which was higher than of lncRNA KCNQ1OT1 and FGF2 alone,and the differences were statistically significant(Z=3.250,2.096,all P<0.05).Conclusion Serum lncRNA KCNQ1OT1 and FGF2 are both elevated in children with bronchial asthma,which is related to the worsening of bronchial asthma and uncontrolled disease.Combining lncRNA KCNQ1OT1 and FGF2 can predict the level of bronchial asthma disease control.

BACKGROUND:Implant restoration has become an important means to treat anterior tooth loss,and it is particularly important to select appropriate implant restoration materials.However,at present,there are some deficiencies in clinical implant materials,and researchers have been exploring suitable implant materials.OBJECTIVE:To compare the biomechanical characteristics of implants made of different materials in restoring single missing maxillary anterior teeth.METHODS:The cone beam CT data of a patient with single maxillary central incisor loss were imported into 3-matic software to establish a three-dimensional finite element analysis model of single maxillary anterior tooth loss.The model was then imported into Marc Mentat.Eight sets of implant restoration models were designed according to different implant materials(polyetheretherketone,titanium-zirconium alloy,titanium alloy,and zirconia,with the elastic modulus of the four materials increasing in sequence)and cancellous bone density(high density,low density)to simulate the stress conditions of the maxillary anterior teeth in centric occlusion.The total displacements and von Mises stresses of implants,cortical bone stresses and cancellous bone strains were compared and analyzed.RESULTS AND CONCLUSION:(1)The maximum displacement of the implant gradually decreased with the increase of the modulus of elasticity of the material,and the value of the maximum displacement of the implant in the polyetheretherketone group exceeded 10 μm;the implant stress was concentrated in the labial neck in the models.The maximum stress gradually increased with the increase of the modulus of elasticity of the implant material,among which,the zirconia-low density bone model had the highest stress,which was 21.31 MPa;the cortical bone stress was concentrated in the cortical bone at the junction of the implant with the labial side,and the polyetheretherketone-low density bone group had the highest value,which was 29.90 MPa.(2)From the biomechanical point of view,titanium-zirconium alloy,titanium alloy,and zirconia can be used as implant materials for restoration of a single missing anterior tooth,and implant displacement is one of the common problems during implant restorations,but pure polyetheretherketone material may cause excessive implant displacement in implant restorations of anterior areas,causing implant failure.

Objective:To define the concept of proactive health behavior.Methods:Literature related to proactive health behavior was retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Embase, and Ovid databases, with a retrieval time frame from database inception to March 1, 2025. Walker and Avant's concept analysis method was used to analyze the concept of proactive health behavior.Results:A total of 46 articles related to proactive health behavior were included. Proactive health behavior encompasses five key attributes: self-initiation, long-term persistence, multidimensional integration, future orientation, and overcoming barriers. Antecedents include individual factors, supportive factors, and environmental factors. Outcomes include promoting individual health and improving quality of life, enhancing personal health literacy, reducing disease burden, and fostering a proactive health atmosphere.Conclusions:The concept attributes of proactive health behavior were clarified through concept analysis. Future researchers may develop proactive health behavior assessment tools and construct intervention strategies based on their connotation.

Objective To explore the value of serum long non-coding RNA KCNQl opioid strand transcript 1(lncRNA KCNQ1OT1)and fibroblast growth factor 2(FGF2)in the evaluation of the condition and control level of pediatric bronchial asthma.Methods 96 children with bronchial asthma(Asthma group)and 76 healthy children(Control group)admitted to Yulin Hospital of Traditional Chinese Medicine from March 2021 to March 2023 were selected.According to the severity of bronchial asthma,the children were divided into a mild group(n=54)and a severe group(n=42).According to the disease control status after treatment,the children were divided into an asthma Control group(n=61)and an uncontrolled Asthma group(n=35).The serum levels of lncRNA KCNQ1OT1 and FGF2 were detected in each group.Multivariate Logistic regression analysis was performed to identify the factors affecting bronchial asthma disease control.The performance of lncRNA KCNQ1OT1 and FGF2 in predicting the control of bronchial asthma disease was evaluated using the receiver operating characteristic curve.Results The serum levels of lncRNA KCNQ1OT1(2.35±0.71)and FGF2(27.35±6.29 pg/ml)in the Asthma group were higher than those in the Control group(1.51±0.33,15.32±4.08 pg/ml),and the differences were statistically significant(t=9.527,14.437,all P<0.001).The serum levels of lncRNA KCNQ1OT1(2.59±0.35)and FGF2(28.65±1.03 pg/ml)in the severe group were higher than those in the mild group(2.16±0.41,26.34±1.24 pg/ml),and the differences were statistically significant(t=5.429,9.737,all P<0.001).The serum levels of lncRNA KCNQ1OT1(2.63±0.27)and FGF2(29.02±1.41 pg/ml)in the uncontrolled asthma group were higher than those in the controlled asthma group(2.19±0.35,26.39±1.52 pg/ml),and the differences were statistically significant(t=5.417,8.374,all P<0.001).High lncRNA KCNQ1OT1 and FGF2 levels were risk factors for uncontrolled disease in children with bronchial asthma(all P<0.05).The AUC of lncRNA KCNQ1OT1 and FGF2 combined to predict uncontrolled disease in children with bronchial asthma,which was higher than of lncRNA KCNQ1OT1 and FGF2 alone,and the differences were statistically significant(Z=3.250,2.096,all P<0.05).Conclusion Serum lncRNA KCNQ1OT1 and FGF2 are both elevated in children with bronchial asthma,which is related to the worsening of bronchial asthma and uncontrolled disease.Combining lncRNA KCNQ1OT1 and FGF2 can predict the level of bronchial asthma disease control.

BACKGROUND:Implant restoration has become an important means to treat anterior tooth loss,and it is particularly important to select appropriate implant restoration materials.However,at present,there are some deficiencies in clinical implant materials,and researchers have been exploring suitable implant materials.OBJECTIVE:To compare the biomechanical characteristics of implants made of different materials in restoring single missing maxillary anterior teeth.METHODS:The cone beam CT data of a patient with single maxillary central incisor loss were imported into 3-matic software to establish a three-dimensional finite element analysis model of single maxillary anterior tooth loss.The model was then imported into Marc Mentat.Eight sets of implant restoration models were designed according to different implant materials(polyetheretherketone,titanium-zirconium alloy,titanium alloy,and zirconia,with the elastic modulus of the four materials increasing in sequence)and cancellous bone density(high density,low density)to simulate the stress conditions of the maxillary anterior teeth in centric occlusion.The total displacements and von Mises stresses of implants,cortical bone stresses and cancellous bone strains were compared and analyzed.RESULTS AND CONCLUSION:(1)The maximum displacement of the implant gradually decreased with the increase of the modulus of elasticity of the material,and the value of the maximum displacement of the implant in the polyetheretherketone group exceeded 10 μm;the implant stress was concentrated in the labial neck in the models.The maximum stress gradually increased with the increase of the modulus of elasticity of the implant material,among which,the zirconia-low density bone model had the highest stress,which was 21.31 MPa;the cortical bone stress was concentrated in the cortical bone at the junction of the implant with the labial side,and the polyetheretherketone-low density bone group had the highest value,which was 29.90 MPa.(2)From the biomechanical point of view,titanium-zirconium alloy,titanium alloy,and zirconia can be used as implant materials for restoration of a single missing anterior tooth,and implant displacement is one of the common problems during implant restorations,but pure polyetheretherketone material may cause excessive implant displacement in implant restorations of anterior areas,causing implant failure.

Objective:To observe the correlation between blood cell-related inflammatory markers and diabetic retinopathy (DR).Methods:A cross-sectional study. From June 2020 to February 2022, the phase Ⅰ data of Beichen Eye Study in Tianjin Medical University Eye Hospital were included in the study. The research contents included questionnaires, routine systemic and ocular examinations, and laboratory blood cell-related indicators including mean platelet volume (MPV), platelet distribution width (PDW), neutrophils, and lymphocytes were performed. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The diagnosis and classification of DR referred to the international clinical classification standard of DR. Monocular or binocular DR was defined as DR patients. Participants were categorized into different groups based on whether they had diabetes and whether they had DR. The groups included the no-diabetes group, the diabetes without DR group, and the DR group. The Kruskal-Wallis H test was used for the comparison of quantitative data among multiple groups. Wilcoxon test was used for comparison between the two groups. The χ2 test was used to compare the categorical variables between groups. The variables was adjusted step by step, an unadjusted univariate model was built and the different parameters of the model Ⅰ, Ⅱ, Ⅲ were adjusted. The correlation between MPV, PDW, NLR, PLR, and DR in different models was analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different NLR models for DR. Results:A total of 3 328 subjects were recruited. Among them, 1 121 (33.68 %, 1 121/3 328) were males and 2 207 (66.32 %, 2 207/3 328) were females. The median age of the included participants was 61.84 (6.05) years. The no-diabetes group, the diabetes without DR group, and the DR group were 2 679, 476, and 173, respectively. There was no significant difference in MPV and PLR among the three groups ( H=5.98, 1.94; P=0.051, 0.379). However, compared with no-diabetes group and the diabetes without DR group, PDW and NLR in the DR group showed an upward trend. In model Ⅲ with completely adjusted related factors, NLR was an independent risk factor for DR in no-diabetes group and DR group [odds ratio ( OR)=1.440, 95% confidence interval ( CI) 1.087-1.920, P=0.041], diabetes without DR group and DR group [ OR=1.990, 95% CI 1.440-2.749, P<0.001]. The results of ROC curve analysis showed that the diagnostic efficiency of NLR model Ⅲ was the highest, the area under the curve was 0.751 (95% CI 0.706-0.796, P<0.001), the optimal cutoff value was 0.390, and the sensitivity and specificity were 74.3% and 64.8%, respectively. Conclusions:The NLR of the DR group is significantly higher than that of the no-diabetes group and diabetes without DR group. NLR is an independent risk factor for DR.