ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.

ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

OBJECTIVE: To investigate the relationship between angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) and semen parameters. Methods： The semen samples of 820 male patients who were treated in the Reproductive Medicine Center of Taiyuan Central Hospital from August 2022 to August 2023 were retrospectively analyzed. The levels of AT1-AA and Ang Ⅱ of semen were detected by ELISA, and the function of AT1-AA was detected by cardiomyocyte beating assay in suckling rats. The patients were divided into low group, median group and high group according to the OD values of AT1-AA. The differences in general data and semen parameters between different groups were analyzed. And the correlation between AT1-AA level and semen parameters in semen of all study subjects was analyzed by the method of Spearman analysis. And the relationships between AT1-AA OD value, Ang Ⅱ level and semen parameters in the AT1-AA high value group were analyzed as well. RESULTS: AT1-AA was present in semen with good function. There was no significant difference in the general data of patients in different AT1-AA levels (P>0.05). In the comparison of semen parameters among the groups with different levels of AT1-AA, there were differences in sperm concentration, PR concentration, NP％, and ALH among the three groups (P<0.05). And AT1-AA OD value was positively correlated with total sperm count, sperm concentration, PR concentration, and NP％, and negatively correlated with semen volume (P<0.05). In the AT1-AA high value group, the OD value of AT1-AA in semen was negatively correlated with inactive sperm, and positively correlated with total motility (［PR+NP］％), curve rate, mean path rate, and ALH. However, there was no correlation between the level of Ang Ⅱ in semen and semen parameters (P>0.05). CONCLUSION The presence of AT1-AA in semen may be associated with the promotion of sperm motility.
Male ; Humans ; Autoantibodies ; Sperm Motility ; Semen ; Retrospective Studies ; Receptor, Angiotensin, Type 1/immunology* ; Animals ; Rats ; Angiotensin II ; Adult ; Sperm Count ; Semen Analysis ; Receptor, Angiotensin, Type 2/immunology*

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome