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: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Dopamine(DA)is an essential neurotransmitter.Research on its dynamic concentration fluctuations,particularly within the extracellular microenvironment,is crucial for elucidating neural signaling mechanisms and pathogenesis of related disorders.Among DA detection methods,fluorescence probe-based imaging offers advantages such as high sensitivity,high specificity,and non-invasiveness.However,the application of these probes for in situ DA monitoring has been limited by the challenges including probe internalization and difficulties in labeling across cells.Here,leveraging the programmability and high stability of DNA nanostructures,a DNA prism-based probe for imaging DA release at the single-cell level was designed and constructed.This probe utilized surface-modified cholesterol for efficient membrane anchoring and a DA aptamer-based"turn-on"sensing module to detect DA directly on the cell membrane.Using this probe,rapid DA release triggered by high K+stimulation was observed,with the released DA concentration increasing over time and peaking at 8 min post-stimulation.More notably,exploiting the probe's ability to simultaneously anchor to two cells,thereby forming cell clusters,revealed that the distribution of DA within the intercellular space was significantly higher than that in the cell body regions.This probe not only provided a method for DA imaging on the cell membrane but also laid a theoretical foundation for developing broader neurotransmitter detection platforms,holding significant scientific merit and application potential.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

ObjectiveThis paper proposes a novel real-time bedside pulmonary ventilation monitoring method for the diagnosis of chronic obstructive pulmonary disease (COPD), based on electrical impedance tomography (EIT). Four indicators—center of ventilation (CoV), global inhomogeneity index (GI), regional ventilation delay inhomogeneity (RVDI), and the ratio of forced expiratory volume in one second to forced vital capacity (FEV₁/FVC)—are calculated to enable the spatiotemporal assessment of COPD. MethodsA simulation of the respiratory cycles of COPD patients was first conducted, revealing significant differences in certain indicators compared to healthy individuals. The effectiveness of these indicators was then validated through experiments. A total of 93 subjects underwent multiple pulmonary function tests (PFTs) alongside simultaneous EIT measurements. Ventilation heterogeneity under different breathing patterns—including forced exhalation, forced inhalation, and quiet tidal breathing—was compared. EIT images and related indicators were analyzed to distinguish healthy individuals across different age groups from COPD patients. ResultsSimulation results demonstrated significant differences in CoV, GI, FEV₁/FVC, and RVDI between COPD patients and healthy individuals. Experimental findings indicated that, in terms of spatial heterogeneity, the GI values of COPD patients were significantly higher than those of the other two groups, while no significant differences were observed among healthy individuals. Regarding temporal heterogeneity, COPD patients exhibited significantly higher RVDI values than the other groups during both quiet breathing and forced inhalation. Moreover, during forced exhalation, the distribution of FEV₁/FVC values further highlighted the temporal delay heterogeneity of regional lung function in COPD patients, distinguishing them from healthy individuals of various ages. ConclusionEIT technology effectively reveals the spatiotemporal heterogeneity of regional lung function, which holds great promise for the diagnosis and management of COPD.

[Objective] To analyse and predict the tendencies of using erythrocyte blood in Changsha based on the autoregressive integrated moving average (ARIMA) model, long short-term memory (LSTM) and ARIMA-LSTM combination model, so as to provide reliable basis for designing a feasible and effective blood inventory management strategy. [Methods] The data of erythrocyte usage from hospitals in Changsha between January 2012 and December 2023 were collected, and ARIMA model, LSTM model and ARIMA-LSTM combination model were established. The actual erythrocyte consumption from January to May 2024 were used to assess and verify the prediction effect of the models. The extrapolation prediction accuracy of the models were tested using two evaluation indicators: mean absolute percentage error (MAPE) and root mean square error (RMSE), and then the prediction performance of the model was compared. [Results] The RMSE of LSTM model, optimal model ARIMA(1,1,1)(1,1,1)12 and ARIMA-LSTM combination model were respectively 5 206.66, 3 096.43 and 2 745.75, and the MAPE were 18.78%,11.54% and 9.76% respectively, which indicated that the ARIMA-LSTM combination model was more accurate than the ARIMA model and LSTM model, and the prediction results was basically consistent with the actual situation. [Conclusion] The ARIMA-LSTM model can better predict the clinical erythrocyte consumption in Changsha in the short term.

Objective:To compare the efficacy of Ilizarov ring external fixation and unilateral rail external fixation in the treatment of infected bone defects following surgery for tibial fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 50 patients with infected bone defects after surgery for tibial fractures, who were admitted to the 940th Hospital of the Joint Logistics Support Force of the PLA from August 2019 to November 2021, including 37 males and 13 females, aged 19-59 years [(42.2±8.8)years]. After debridement and osteotomy, 28 patients were treated with Ilizarov ring external fixation (Ilizarov group) and 22 with unilateral rail external fixation (unilateral fixation group). All the patients in the two groups had previously undergone internal fixation with plates or Kirschner wires for tibial fracture before bone transport. Bone transport started at one week for three stages after successful infection control and osteotomy and was conducted. The following parameters were compared between the two groups: frame-wearing time and healing index after bone transport, self-rating anxiety scale (SAS) grade at 6 months after bone transport, Paley score and Association for the Study and Application of the Method of Ilizarov (ASAMI) score at the last follow-up, Hospital for Special Surgery (HSS) knee score and Baird-Jackson ankle score on admission, after external fixator removal and at the last follow-up, and incidence of postoperative complications.Results:All the patients were followed up for 28-36 months [(32.5±1.6)months]. There were no significant differences in frame-wearing time or healing index between the two groups after bone transport ( P>0.05). At 6 months after bone transport, the SAS grade in the unilateral fixation group (13 patients with mild anxiety, 8 with moderate anxiety, and 1 with severe anxiety) was better than that in the Ilizarov group (6 patients with mild anxiety, 19 with moderate anxiety, 3 with severe anxiety) ( P<0.01). No significant differences were found in the Paley score or ASAMI score between the two groups at the last follow-up ( P>0.05). There were no significant differences in HSS knee score or Baird-Jackson ankle score between the two groups on admission, after external fixator removal or at the last follow-up ( P>0.05). No significant differences were observed in the incidence of pin tract infection, poor healing, infection in the bone elongation area, or re-fracture between the two groups ( P>0.05). The incidence of postoperative axial deviation was 0 in the Ilizarov group, lower than 18% in the unilateral fixation group (4/22) ( P<0.05). Conclusion:Although Ilizarov ring external fixation and unilateral rail external fixation demonstrate comparable efficacy in the treatment of infected bone defects after surgery for tibial fractures, the former provides superior mechanical stability and postoperative axial deviation correction, while the latter offers advantages in reducing psychological burden and enhancing treatment tolerance.

Objective To explore the optimal warning threshold of motor evoked potentials(MEP)in decompression surgery for ossification of the posterior longitudinal ligament(OPLL)at cervical and thoracic segments,and the predictive role of different MEP parameters on postoperative lower extremity motor function.Methods A retrospective analysis was conducted on the clinical data of 227 patients diagnosed with cervical or thoracic OPLL and underwent decompression surgery from January 2022 to January 2024 in the hospital.There were 131 males and 96 females,with an average age of(60±10)years.All patients underwent continuous neuro-physiological monitoring during the operation,and the minimum ratio of MEP amplitude change to the baseline at the beginning of the operation(Dmax)and the ratio of MEP terminal amplitude change to the baseline at the end of the operation(Dend)were recorded.The correlations between these two ratios and the lower extremity motor func-tion immediately after the operation and at 1 year were compared.According to the Medical Research Council muscle strength score(MRC)standard,a postoperative score increase of≥1 point compared to preoperative was defined as postoperative motor dysfunction.Pearson correlation coefficients were used to evaluate the correlations between Dmax and Dend and the lower extremity motor function immediately after the operation and at 1 year.Receiver operating characteristic(ROC)curves were drawn to predict postoperative lower extremity motor dysfunc-tion using Dmax and Dend.Results Among the 227 patients,186 had cervical OPLL and 41 had thoracic OPLL.The incidence of lower extremity motor dysfunction immediately after the operation and at 1 year was 7 cases(3.76%)and 2 cases(1.08%)in the cervical group,and 9 cases(21.95%)and 3 cases(7.32%)in the thoracic group,respectively.The incidence of lower extremity motor dysfunction in the thoracic group was higher than that in the cervical group(P<0.001).The baseline induction rate of bilateral lower extremity MEPs was 98.92%(368/372)in the cervical group and 96.34%(79/82)in the thoracic group.The Pearson correlation coefficients of Dend with the bilateral lower extremity motor function immediately after the operation in the cervical and thoracic groups were both greater than those of Dmax,and the differences were statistically significant(cervical group:r=0.669,0.517,P=0.001 2;thoracic group:r=0.882,0.727,P=0.003 6),while the differences in the Pearson corre-lation coefficients of Dend and Dmax with the bilateral lower extremity motor function at 1 year were not statistically significant(cervical group:r=0.457,0.352,P=0.088;thoracic group:r=0.760,0.625,P=0.098).The cut-off values of Dend for the cervical group were 0.853 immediately after the operation and at 1 year,and the cut-off values of Dmax were 0.881 and 0.978,respectively.For the thoracic group,the cut-off values of Dend were 0.532 immediately after the operation and 0.639 at 1 year,and the cut-off values of Dmax were 0.532 and 0.640,respec-tively.Conclusions In OPLL surgery,the MEP monitoring strategy should be adjusted according to the surgical segment.For the cervical segment,Dmax should be emphasized to balance high sensitivity and specificity,while for the thoracic segment,Dmax or Dend can be flexibly selected.Higher MEP warning thresholds are required for cervical OPLL surgery(Dmax:0.881 immediately after the operation and 0.978 at 1 year;Dend:0.853),while significantly lower thresholds are needed for thoracic OPLL(Dmax/Dend:0.532 immediately after the operation and 0.640 at 1 year).

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.