Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

The objective of this experiment was to investigate the inhibitory effect and mechanism of mammary-derived extracellular vesicles(MmEVs)from mastitis dairy cows on the biofilm for-mation of Staphylococcus aureus SA1.The biofilm-forming ability of Staphylococcus aureus SA1 was confirmed using Congo red staining,and the biofilm growth curve of S.aureus SA1 was plot-ted using the crystal violet staining method.The minimum inhibitory concentration(MIC)and minimum biofilm inhibitory concentration(MBIC)of MmEVs against S.aureus SA1 were deter-mined.After treating S.aureus SA1 with different concentrations of MmEVs,the cell morphology of S.aureus SA1 was observed using transmission electron microscopy.The effects of MmEVs on S.aureus SA1 under low pH(pH value=5)or heat stress(58℃)were investigated.The hydro-phobicity index was explored using the microbial adhesion to hydrocarbons(MATH)assay.Bacte-rial conductivity was measured.The expression levels of biofilm-related genes(SarA,icaB,FnbA,ClfB,CidA,and gyrB)were detected using quantitative real-time PCR(qPCR).The results showed that MIC of MmEVs against the biofilm of S.aureus SA1 was 1 000 mg/L,and the MBIC was 500 mg/L.Under the influence of MmEVs,the internal substances of S.aureus SA1 leaked,the biofilm boundary became blurred,and the cell wall separated.At the MBIC concentration,MmEVs significantly reduced the tolerance of S.aureus SA1 to low pH(P＜0.001)and high tem-perature(P＜0.001),decreased hydrophobicity(P＜0.001),and increased bacterial conductivity(P＜0.001).At the MBIC concentration,MmEVs significantly downregulated the gene expression of Sa rA(P＜0.001),icaB(P＜0.001),FnbA(P＜0.001),ClfB(P＜0.001),and CidA(P＜0.001)in S.aureus SA1,while no significant effect was observed on the expression of the gyrB gene.In summary,MmEVs inhibit the formation of Staphylococcus aureus SA1 biofilms by sup-pressing the gene expression of SarA,icaB,FnbA,ClfB,and CidA within the biofilm.This dis-ruption damages the biofilm's morphological structure,reduces its tolerance to low pH and high temperature,decreases hydrophobicity,and increases bacterial conductivity,thereby ultimately in-hibiting the formation of S.aureus SA1 biofilms.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

The objective of this experiment was to investigate the inhibitory effect and mechanism of mammary-derived extracellular vesicles(MmEVs)from mastitis dairy cows on the biofilm for-mation of Staphylococcus aureus SA1.The biofilm-forming ability of Staphylococcus aureus SA1 was confirmed using Congo red staining,and the biofilm growth curve of S.aureus SA1 was plot-ted using the crystal violet staining method.The minimum inhibitory concentration(MIC)and minimum biofilm inhibitory concentration(MBIC)of MmEVs against S.aureus SA1 were deter-mined.After treating S.aureus SA1 with different concentrations of MmEVs,the cell morphology of S.aureus SA1 was observed using transmission electron microscopy.The effects of MmEVs on S.aureus SA1 under low pH(pH value=5)or heat stress(58℃)were investigated.The hydro-phobicity index was explored using the microbial adhesion to hydrocarbons(MATH)assay.Bacte-rial conductivity was measured.The expression levels of biofilm-related genes(SarA,icaB,FnbA,ClfB,CidA,and gyrB)were detected using quantitative real-time PCR(qPCR).The results showed that MIC of MmEVs against the biofilm of S.aureus SA1 was 1 000 mg/L,and the MBIC was 500 mg/L.Under the influence of MmEVs,the internal substances of S.aureus SA1 leaked,the biofilm boundary became blurred,and the cell wall separated.At the MBIC concentration,MmEVs significantly reduced the tolerance of S.aureus SA1 to low pH(P＜0.001)and high tem-perature(P＜0.001),decreased hydrophobicity(P＜0.001),and increased bacterial conductivity(P＜0.001).At the MBIC concentration,MmEVs significantly downregulated the gene expression of Sa rA(P＜0.001),icaB(P＜0.001),FnbA(P＜0.001),ClfB(P＜0.001),and CidA(P＜0.001)in S.aureus SA1,while no significant effect was observed on the expression of the gyrB gene.In summary,MmEVs inhibit the formation of Staphylococcus aureus SA1 biofilms by sup-pressing the gene expression of SarA,icaB,FnbA,ClfB,and CidA within the biofilm.This dis-ruption damages the biofilm's morphological structure,reduces its tolerance to low pH and high temperature,decreases hydrophobicity,and increases bacterial conductivity,thereby ultimately in-hibiting the formation of S.aureus SA1 biofilms.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Autism spectrum disorder (ASD) is a range of neurodevelopmental diseases characterized by social dysfunction and stereotypic behaviors. The etiology of ASD remains largely unexplored, resulting in a diverse array of described clinical manifestations and varying degrees of severity. Currently, there are no drugs approved by a supervisory organization that can effectively treat the core symptoms of ASD. Childhood and adolescence are crucial stages for making significant achievements in ASD treatment, necessitating the development of drugs specifically for these periods. Based on the drug targets and mechanisms of action, it can be found that atypical psychotropic medications, anti-inflammatory and antioxidant medications, hormonal medications, ion channel medications, and gastrointestinal medications have shown significant improvement in treating the core symptoms of ASD in both children and adolescents. In addition, comparisons of drugs within the same category regarding efficacy and safety have been made to identify better alternatives and promote drug development. While further evaluation of the effectiveness and safety of these medications is needed, they hold great potential for widespread application in the clinical treatment of the principal symptoms of ASD.
Humans ; Autism Spectrum Disorder/drug therapy* ; Child ; Adolescent ; Psychotropic Drugs/therapeutic use* ; Antioxidants/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Gastrointestinal Agents/therapeutic use*

Objective To systematically evaluate the risk prediction model for central venous catheter-related bloodstream infections and provide references for clinical practice.Methods Databases such as CNKI,Wanfang,CBM,VIP,PubMed,Web of Science,Cochrane Library,etc.were retrieved.The search period is from database establishment to June 2,2023.There are 2 researchers who independently screened and extracted the literature,and evaluated the quality of the literature using bias assessment tools of predictive model risk.Results A total of 9 articles were included,including 9 risk prediction models for catheter-related bloodstream infections.The total sample size was 80～11 901 cases;the number of outcome events was 19～403 cases;the C index of the included model was 0.81～0.93.The area under the curve of the subjects ranged from 0.73～0.90.The predictors that appear more frequently in the model mainly included the history of diabetes,albumin value,the number of days of catheterization,the location of catheterization.The evaluation results of the bias assessment tool of predictive model risk for research show that the overall applicability of the included risk prediction models is good,but the bias risk is high.The reasons are related to the improper source of research sample data,inappropriate processing of continuous variable methods,failure to process missing data,insufficient model performance evaluation,and non-standard evaluation indicators.Conclusion There are still some shortcomings in the risk prediction model for central venous catheter-related bloodstream infections.In the future,the quality of related model research should be further improved,especially in terms of predictive factor analysis,model evaluation indicators,etc.,which should be further standardized.

Objective:To observe any effects of contralateral repeated transcranial magnetic stimulation (rTMS) of the swallowing motor cortex on the swallowing and brainstem auditory evoked potentials (BAEPs) of stroke survivors with dysphagia.Methods:A total of 83 stroke survivors with dysphagia were randomly divided into an ipsilesional stimulation group ( n=22), a contralesional stimulation group ( n=21), a bilateral stimulation group ( n=20), and a control group ( n=20). In addition to their conventional dysphagia training, those in the three stimulation groups received 3Hz rTMS while the control group was given fake stimulation. The treatment was administered daily for 20 minutes, 6 days a week, for 5 consecutive weeks. Before and after the treatment, swallowing function was assessed videofluoroscopically and using the Dysphagia Outcome and Severity Scale (DOSS). The oral and pharyngeal stages of swallowing were evaluated using the videofluoroscopic dysphagia scale (VDS). Brain stem conduction was assessed using BAEPs. Results:After treatment the average DOSS scores of all 4 groups were significantly better than before the treatment. The average DOSS scores of the contralesional and bilateral sti-mulation groups were then significantly better than those of the other two groups. The sub-item and total VDS scores of all 4 groups had decreased significantly, but the average score of the bilateral stimulation group was significantly lower than the control group′s average. Ipsilesional stimulation significantly improved the VDS sub-item scores for the triggering of pharyngeal swallowing, laryngeal elevation, and pharyngeal transit time compared with the control group. In the contralesional stimulation group the average total score and the VDS sub-item scores for apraxia, premature bolus loss, oral transit times, the triggering of pharyngeal swallowing, vallecular residue, laryngeal elevation, coating on the pharyngeal wall, and pharyngeal transit time were significantly lower than those of the control group, on average. After the treatment the latencies of BAEP waves I, III and V and the I-III, III-V and I-V interpeak intervals had decreased significantly in all four groups, but the average latencies and intervals of the bilateral and contralesional groups were significantly shorter than those of the control group. The latencies and intervals of the bilateral stimulation group were then significantly shorter than those in the ipsilesional stimulation group on average. The average latency of wave V in the bilateral stimulation group (6.53±0.73ms) was significantly shorter than that in the contralesional stimulation group after the treatment.Conclusion:Bilateral rTMS over the swallowing motor cortex combined with conventional dysphagia training can significantly improve the swallowing of dysphagic stroke survivors.