ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Objective To evaluate the ability of longitudinal changes in urinary extracellular domain of neurotrophin receptor p75(p75ECD)to serve as a prognostic biomarker of severity,progression and survival time in patients with amyotrophic lateral sclerosis(ALS).Methods Forty patients with ALS attended follow-up appointments at 3-to 6-month interval,and 51 healthy control(HC)volunteers were recruited.The concentrations of urinary p75ECD were tested by a sandwich ELISA.The ALSFRS-r was used to quantify the severity of ALS.The change rate of urinary p75ECD(Δp75ECD)was calculated as the average monthly change during the period between the first and the last sampling.Results The concentration of urinary p75ECD was higher at the last follow-up than at baseline(P=0.002 3).Spearman analysis showed that there was a negative correlation between urinary p75ECD and ALSFRS-r score(r=-0.35,P=0.001 3);the course of ALS in the fast-changing Δp75ECD group was shorter than that in the slow-changing group(P=0.015 8);the Δp75ECD and course of ALS showed a negative correlation(r=-0.39,P=0.014),and the Δp75ECD in the fast-progression ALS group was significantly higher than in the slow-progression group(P=0.001 6).There was a positive correlation between Δp75ECD and progression in ALS patients(r=0.34,P=0.005).Kaplan-Meier survival analysis showed a longer median survival time in those with slow-changing Δp75ECD(P=0.03).Conclusion The change rate of urinary p75ECD has shown great potential as a biomarker for the prognosis of the severity,progression and survival time of ALS.

BACKGROUND:In recent years,methods for incorporating biominerals into bone tissue engineering scaffolds have been extensively studied,including solvent casting,freeze-drying,and 3D printing.However,the diverse types and complex compositions of biominerals lead to varying impacts on scaffold performance and differing requirements for fabrication processes,necessitating systematic research on their applicability.OBJECTIVE:To explore biomineral grinding and screening processes,and evaluate their solution rheological properties,hydrophilicity,mechanical properties,and biocompatibility when prepared as composite materials with polymer materials.METHODS:Five representative biominerals were selected,including turtle shell,eggshell,cuttlebone,deer antler,and pearl.These were ground into powders and screened,then mixed with polycaprolactone in specific proportions to prepare composite materials.The feasibility of applying biominerals in bone tissue engineering was explored by testing the elemental composition and particle size distribution of the powder,as well as the solution rheological properties,hydrophilicity,mechanical properties,and biocompatibility of the composite material.RESULTS AND CONCLUSION:(1)Most biomineral powders followed the rule that the longer the grinding time,the smaller the particle size.The desired particle size range could be obtained through methods such as sieving.Elemental mapping and Fourier Transform Infrared spectroscopy analyses indicated that the main inorganic mineral components of these five biominerals were calcium carbonate and calcium phosphate,containing the elements C,O,P,and Ca.(2)The method of dissolving polycaprolactone in 1,4-dioxane and adding biomineral powders to prepare scaffolds did not significantly alter the composite material composition and did not reduce biocompatibility.The addition of biomineral powders improved the hydrophilicity and 3D printability of polycaprolactone materials but decreased their mechanical properties.(3)These findings suggest that when applying biomineral powders to bone tissue engineering scaffolds,the proportion of powder added should be carefully chosen to balance hydrophilicity,printability,and mechanical properties.

BACKGROUND:In recent years,methods for incorporating biominerals into bone tissue engineering scaffolds have been extensively studied,including solvent casting,freeze-drying,and 3D printing.However,the diverse types and complex compositions of biominerals lead to varying impacts on scaffold performance and differing requirements for fabrication processes,necessitating systematic research on their applicability.OBJECTIVE:To explore biomineral grinding and screening processes,and evaluate their solution rheological properties,hydrophilicity,mechanical properties,and biocompatibility when prepared as composite materials with polymer materials.METHODS:Five representative biominerals were selected,including turtle shell,eggshell,cuttlebone,deer antler,and pearl.These were ground into powders and screened,then mixed with polycaprolactone in specific proportions to prepare composite materials.The feasibility of applying biominerals in bone tissue engineering was explored by testing the elemental composition and particle size distribution of the powder,as well as the solution rheological properties,hydrophilicity,mechanical properties,and biocompatibility of the composite material.RESULTS AND CONCLUSION:(1)Most biomineral powders followed the rule that the longer the grinding time,the smaller the particle size.The desired particle size range could be obtained through methods such as sieving.Elemental mapping and Fourier Transform Infrared spectroscopy analyses indicated that the main inorganic mineral components of these five biominerals were calcium carbonate and calcium phosphate,containing the elements C,O,P,and Ca.(2)The method of dissolving polycaprolactone in 1,4-dioxane and adding biomineral powders to prepare scaffolds did not significantly alter the composite material composition and did not reduce biocompatibility.The addition of biomineral powders improved the hydrophilicity and 3D printability of polycaprolactone materials but decreased their mechanical properties.(3)These findings suggest that when applying biomineral powders to bone tissue engineering scaffolds,the proportion of powder added should be carefully chosen to balance hydrophilicity,printability,and mechanical properties.

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective:To investigate the risk factors of skin adverse events associated with immune checkpoint inhibitor (ICI) therapy in patients with urologic neoplasms, and establish a predictive model.Methods:A single-center retrospective case-control study enrolled 91 advanced urologic neoplasms patients who received ICI therapy at the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2025. Patients were divided into the skin lesion group ( n=44) and the control group ( n=47). Patients in the skin lesion group experienced related skin adverse events during ICI treatment, while patients in the control group did not experience such events during ICI treatment. The general data and laboratory indicators were compared between the two groups. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; the non-normally distributed measurement data were expressed as the median (interquartile range) [ M ( Q1, Q3)], and the Kruskal-Wallis test was used for comparison between groups. The count data were expressed as the number of cases and percentages, and the Chi-test was used for comparison between groups. First, a univariate analysis was conducted on the influencing factors of skin adverse events in patients with urologic neoplasms after ICI treatment. Then, the indicators with statistically significant differences in the univariate analysis were further included in the multivariate Logistic regression model to screen the independent risk factors for predicting skin adverse events. The R software was used to incorporate the factors with significant differences from multivariate analysis into the prediction model and construct a Nomogram. The calibration curve was utilized to evaluate the consistency between predicted values and actual observed results. Meanwhile, the discrimination of the model was verified by the receiver operating characteristic (ROC) curve and the area under the curve (AUC), so as to comprehensively verify the reliability and clinical application value of the prediction model. Results:The results of univariate analysis showed that there were statistically significant differences between the skin lesion group and the control group in terms of the proportion of other immune responses, serum albumin level, absolute eosinophil count, and C-reactive protein (CRP) levels ( P<0.05). These factors were included in multivariate Logistic regression, which identified elevated absolute eosinophil count and elevated CRP as the independent risk factors for related skin adverse events in patients with urologic neoplasms after ICI treatment. A predictive nomogram was built based on these factors. The calibration curve showed high consistency between predicted and actual probabilities, and ROC analysis confirmed the combined model had high predictive value (AUC=0.883, P<0.001). Conclusions:Elevated absolute eosinophil count and elevated CRP level are independent predictors of immune-related skin adverse events in urologic neoplasms patients after ICI treatment. The prediction model constructed based on these two factors facilitates early clinical screening and identification of high-risk patients.

Kidney stones are a disease with high incidence, high recurrence rate and heavy economic burden. Current clinical treatments clear formed stones but fail to target the pathophysiological core of recurrence. Beyond systemic risk factors like obesity and diabetes, diet-driven gut dysbiosis is a key potential mediator of stone recurrence. Moreover, the gut-kidney syndrome and gut-kidney axis theories reveal the bidirectional regulation between intestine and kidney, among these, the gut microbiota-metabolite axis as the core functional carrier of the gut-kidney axis has a regulatory mechanism key to resolving recurrence. Currently, 16S rRNA sequencing and metagenomic sequencing have identified gut microbiota differences between stone and non-stone groups: kidney stone patients show reduced alpha diversity, imbalanced Firmicutes/ Bacteroidetes ratio, significantly higher abundance of harmful bacteria (e.g., Escherichia- Shigella), and lower abundance of oxalate-degrading bacteria ( Oxalobacter formigenes, Lactobacillus) and short-chain fatty acid (SCFA)-producing bacteria ( Faecalibacterium). Notably, gut dysbiosis persists even after surgery.Meanwhile, targeted and non-targeted metabolomics show significant abnormalities in intestinal and urinary metabolites (e.g., SCFA tryptophan derivatives) in stone patients, along with downregulated pathways including purine metabolism, caffeine metabolism and aromatic amino acid metabolism. These abnormalities promote stone formation by disrupting the intestinal barrier, worsening renal inflammation and triggering renal oxidative stress. This article reviews the aforementioned gut microbiota, metabolites and related regulatory pathways with significant inter-group differences. Combined with advances in genomics and metabolomics, it aims to provide theoretical references for further clarifying the mechanism of gut microbiota-metabolite axis regulates kidney stone formation and recurrence, and for developing microecological interventions.

Objective To explore the predictive value of automated breast ultrasound(ABUS)features combined with Ki-67 in predicting pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)in triple-negative breast cancer(TNBC).Methods A retrospective analysis was conducted on 127 female TNBC patients treated at Xijing Hospital,Air Force Medical University from March 2019 to December 2023.All patients underwent NAC and surgical treatment after ABUS examination.Based on postoperative pathological results,patients were divided into pCR group(n=60)and non-pathological complete response(npCR)group(n=67).Differences in various parameters before NAC were compared between the two groups.LASSO regression was used to identify independent factors influencing pCR after NAC in TNBC patients,and a predictive model was constructed using multivariate logistic regression.The prediction model was internally validated using the Bootstrap method(1000 resamples).The discriminative ability of the model was evaluated using receiver operating characteristic(ROC)curves,and the area under the curves(AUCs)of different prediction models were compared using De-long's test.The accuracy of the model was assessed using calibration curves,and the clinical benefit of the model was evaluated using clinical decision curve analysis(DCA).Results Significant differences were observed between two groups in terms of age,Ki-67,menopausal status,tumor type,posterior echo,coronal plane convergence sign,coronal plane skip sign,and coronal plane white wall sign before NAC(P<0.05).LASSO regression analysis showed that Ki-67,coronal plane convergence sign,and coronal plane white wall sign were independent influencing factors of pCR after NAC in TNBC patients(P<0.05).The AUC of the multivariate logistic regression model based on Ki-67 was 0.733(95%CI 0.646-0.819),the AUC of ABUS model was 0.777(95%CI 0.695-0.858),and the AUC of ABUS combined with Ki-67 model was 0.816(95%CI 0.741-0.890).De-long's test showed that the AUC of the combined model was higher than those of ABUS feature model and Ki-67 model,with statistically significant differences(P<0.05).There was no significant difference in the AUC between ABUS feature model and Ki-67 model(P=0.40).Hosmer-Lemeshow test indicated that the combined model had a good fit(P=0.304).Internal validation results showed that the combined model had a good stability with a consistency index(C-index)of 0.820(95%CI 0.726-0.879).The calibration curve demonstrated good consistency between the predicted and actual probabilities of the combined prediction model,and the DCA curve indicated that the model had favorable clinical benefit.Conclusion The combined ABUS feature and Ki-67 model can be used to predict the probability of pCR after NAC in TNBC patients,providing a reference for the formulation of clinical treatment plans in TNBC patients.