Objective To apply an artificial intelligence (AI) -based pelvic floor optimization training system using human motion analysis technique in patients undergoing pelvic floor rehabilitation, so as to assist clinicians in providing guidance, improving clinical efficiency, and enhancing the efficacy of patients' independent training. Methods A total of 60 patients with overactive bladder (OAB) complicated with urgent urinary incontinence (UUI) treated in our hospital during Sep. 2024 and Dec. 2025 were enrolled and randomly divided into the routine guidance group (n=30) and AI guidance group (n=30). The routine guidance group received conventional pelvic floor optimization training under clinicians' instruction, while the AI guidance group underwent training with the AI-based pelvic floor optimization system using human motion analysis. After 6 weeks of intervention, outcomes were compared between the two groups, including the international consultation on incontinence questionnaire-short form (ICI-Q-SF), incontinence quality of life scale (I-QoL), overactive bladder symptom score (OABSS), patient's perception of bladder condition (PPBC) score, pelvic floor muscle function (myoelectric values in the preresting, post-resting, type Ⅰ muscle, type Ⅱ muscle, and endurance test phases), urine output, average flow rate (Qavg), and maximum flow rate (Qmax). Results After 6 weeks of treatment, the ICI-Q-SF, I-QoL, OABSS, PPBC score, type I muscle myoelectric value, Qavg and Qmax were significantly improved in both groups compared with baseline (P＜0.05). After 6 weeks of intervention, the I-QoL score was significantly higher in the AI guidance group than in the routine guidance group[81.82 (79.55, 84.38) vs.77.84 (75.00, 79.55) ], with significant difference (P＜0.05). Compared with the routine guidance group, the AI guidance group showed significant improvements in myoelectric values in the pre-resting, post-resting, type I muscle and endurance testing phases (P＜0.05). Conclusion The AI-based pelvic floor optimization training system can effectively assist clinicians in guiding patients to complete pelvic floor optimization training, improve rehabilitation efficiency and efficacy of independent exercise, and reduce dependence on specialized clinicians, which exhibits favorable safety.

ObjectiveTo investigate the molecular mechanisms by which Acan-Gal-1 regulates macrophage immune phenotypes and Annexin A2/S100A10 membrane translocation in Angiostrongylus cantonensis. MethodsImmunofluorescence assay （IFA） was performed to determine the subcellular localization of Annexin A2 and S100A10 in macrophages. Flow cytometry and ELISA were used to assess functional changes in macrophage. siRNA interference of Annexin A2 was used to detect the effect of Acan-Gal-1 on various indicators. The expression levels of related genes and proteins were analyzed by Western blot， qRT-PCR， and ELISA methods. Bioinformatics analyses were conducted to characterize the structural features of Acan-Gal-1， and sequence alignment and molecular interaction prediction were performed to explore its potential interaction with Annexin A2. ResultsThis study found that Acan-Gal-1 can reverse LPS-induced promotion of macrophage migration and phagocytic function； it significantly upregulated M2-type markers in macrophages （Arg-1， IL-10， TGF-β） while inhibiting the expression of M1-type markers （iNOS， IL-6， IL-1β） induced by LPS. Acan-Gal-1 reduced the protein levels of Annexin A2 in macrophages under an immunologically activated state； after interfering with Annexin A2 expression， Acan-Gal-1 not only fails to induce macrophages to transition to an immunologically inhibitory phenotype but also fails to inhibit LPS-induced transition of macrophages to an immunologically activated phenotype. Although Acan-Gal-1 did not affect the expression of Annexin A2 or its chaperone protein S100A10 in macrophages， it markedly promoted their translocation to the plasma membrane. ConclusionsAcan-Gal-1 facilitates the enrichment of the Annexin A2/S100A10 complex at the macrophage membrane， thereby exerting immunomodulatory effects on macrophage polarization.

Objective:To explore molecular mechanism of high-altitude hypoxia regulates PPAR signaling pathway induced ferroptosis in spleen.Methods:Hypoxia animal model was constructed,target genes were screened and predicted by combination of transcriptomics and protein omics.Key genes in PPAR and ferroptosis pathways under hypoxia exposure were explored by GO and KEGG enrichment analysis and verified by RT-qPCR and Western blot.Results:Combination of transcriptomics and protein omics showed that 95 predicted target genes(protein)showed significantly differential expression under hypoxic exposure.GO annotation analysis and KEGG enrichment analysis showed that differential genes were mainly significantly enriched in PPAR and ferroptosis signaling pathways.A negative correlation was found between PPAR and ferroptosis signaling pathways,and GSEA showed that differential gene sets of PPAR and ferroptosis signaling pathways exhibited opposite expression trend in high-altitude hypoxia group.Validation of key genes PPARA,RXRB,APOA1 and SCD-1 in PPAR signaling pathway revealed that both mRNA and protein expres-sions were down-regulated under hypoxic exposure.Subsequently,differential expression was observed in mRNA and protein expres-sions of GPX4 in endogenous pathway and SLC7A11,TRP53 and TFRC in exogenous pathway in ferroptosis signaling pathway.Corre-lations between four key genes for ferroptosis and differential inflammation-associated genes(DE-IRGs)were positively or negatively.IL-1β,IL-6,IL-12,IL-18,IFN-γ and TNF-α expressions in spleen tissue were up-regulated under hypoxic exposure.Conclusion:High-altitude hypoxia exposure further induces ferroptosis through PPAR signaling pathway-mediated lipid metabolism disorders,and accompanied by occurrence of inflammatory response,which causes damage of spleen tissue.

Objective:To analyze the protective effect of a respiratory syncytial virus (RSV) vaccine based on bacterial outer membrane vesicle (OMV) in mice.Methods:The pre-fusion protein (preF) of RSV was linked to the surface of OMV through the transmembrane protein cytolysin A (ClyA) to form the nanovaccine OMV-preF. The morphological characteristics of OMV and OMV-preF were observed under a transmission electron microscope. OMV-preF was intramuscularly injected into BALB/c mice and the elicited humoral and cellular immune responses were evaluated. The protective effect of OMV-preF was assessed by challenging the immunized mice with RSV Long strain. One-way analysis of variance and Tukey test were used for statistical analysis.Results:The results showed that preF was stably expressed in OMV, and both OMV-preF and OMV exhibited a double-layer vesicle structures under the microscope. OMV-preF could significantly activate the cellular and humoral immune responses in mice, causing a significant increase in CD8 + T cells and CD19 + B cells as well as a significant increase in the serum level of specific IgG. The neutralizing antibodies produced in the immunized mice could significantly inhibit the replication of RSV Long strain in vivo. Conclusions:The nanovaccine OMV-preF can induce high-level humoral and cellular immune responses, and the antibodies produced following immunization can effectively inhibit viral replication. This study provides a new strategy for RSV subunit vaccines.

Objective:To investigate risk factors for adverse pregnancy outcomes(APO) in women with hypertriglyceridemia(HTG) during late pregnancy despite normal thyroid function, focusing on thyroid-stimulating hormone receptor(TSHR) levels.Methods:A total of 242 pregnant women with normal thyroid function who delivered in General Hospital of Central Theater Command from October 2023 to June 2024 were divided into HTG( n=111) and non-HTG groups( n=131). Clinical data, lipid profiles, thyroid function, TSHR levels, and APO were compared, and the influencing factors of APO were analyzed. Results:Compared with non-HTG group, APO, adverse maternal outcomes, and gestational diabetes mellitus(GDM) were significantly more frequent in the HTG group( P<0.05). The HTG group also had higher triglyceride(TG), fasting plasma glucose(FPG), triglyceride glucose index(TyG), triglyceride/high density lipoprotein cholesterol(TG/HDL-C), thyroid stimulating hormone(TSH) and TSHR, with lower free triiodothyronine (FT 3)( P<0.05). TSHR was an independent risk factor for APO, maternal adverse outcomes, and GDM in all pregnant women( OR=1.112, 95% CI 1.007-1.229; OR=1.126, 95% CI 1.020-1.243; OR=1.133, 95% CI 1.025-1.253) and was also an independent risk factor for APO in the HTG group( OR=1.165, 95% CI 1.005-1.351). Conclusion:Pregnant women with normal thyroid function and HTG in late pregnancy are more likely to have APO, manifested as maternal adverse outcomes and GDM. TSHR is an independent risk factor for APO.

Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.

Objective:To explore the clinical characteristics of bilateral nodular adrenal cortical disease（BmacAD）and primary pigmentary nodular adrenal cortical disease（PPNAD）.Methods:A retrospective analysis was conducted on the clinical records of 58 patients with BmacAD and 26 patients with PPNAD who were treated at Peking Union Medical College Hospital from January 2005 to December 2024. The clinical manifestations，endocrine examination，and surgical results between BmacAD patients and PPNAD patients were compared. Endocrine related examinations were reexamined 1 to 7 days and 15 to 30 days after the operation，and the recovery of cortisol within 30 days after the operation was recorded.Results:The male to female ratios of BmacAD patients and PPNAD patients were 31/27 and 11/15，with no statistically significant difference（ P > 0.05）. The age of BmacAD patients and PPNAD patients were 53.5（45.0，61.0）years and 19.0（15.8，24.0）years，respectively，with a statistically significant difference（ P < 0.001）. In terms of clinical manifestations，the proportion of BmacAD patients and PPNAD patients with Cushing syndrome appearance were 50.00%（29/58）and 96.15%（25/26），respectively，with a statistically significant difference（ P < 0.001）. There were no statistically significant differences between BmacAD and PPNAD patients in hypertension［87.93%（51/58）and 80.77%（21/26）］，abnormal glucose tolerance/diabetes［39.66%（23/58）and 34.62%（9/26）］and hypokalemia［18.97%（11/58）and 15.38%（4/26）］（ P > 0.05）. The difference in the proportion of osteopenia/osteoporosis /fracture between the two group was statistically significant［13.79%（8/58）and 53.85%（14/26）， P < 0.001］. In terms of hormone secretion，the median levels of 24-hour urinary free cortisol in BmacAD and PPNAD patients before surgery were 174.00（85.35，531.43）μg/24 h and 408.35（334.28，800.78）μg/24h（ P < 0.001），respectively. The proportion of preoperative plasma adrenocorticotropic hormone（ACTH）levels less than 5 pg/ml were 60.34%（35/58）and 84.62%（22/26）（ P < 0.05），respectively. Among the BmacAD patients 32 underwent unilateral total adrenalectomy，23 underwent unilateral partial adrenalectomy，and 3 underwent unilateral total adrenalectomy+contralateral partial adrenalectomy；the proportion of patients with increased preoperative cortisol secretion who recovered to normal within 30 days after surgery was 79.17%（38/48）. All 26 PPNAD patients underwent unilateral adrenalectomy. Within 30 days after surgery，68.00%（17/25）of the PPNAD patients had normal 24-hour urinary free cortisol levels. Conclusions:The cortisol secretion level in PPNAD patients is significantly higher than that in BmacAD patients，and the proportion of abnormal bone metabolism is higher. The short-term therapeutic efficacy of unilateral adrenalectomy or unilateral partial adrenalectomy is significant for both BmacAD and PPNAD.

Objective This study preliminarily investigated the potential mechanisms of the Huoxue Tongluo prescription(HXTLP)in treating spinal cord injury(SCI)through a combination of network pharmacology,molecular docking technology,and in vivo experimental verification.Methods The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)were utilized to select the active ingredients,targets of action were obtained from Swiss target prediction database,and an"active ingredients-targets"network was constructed.SCI-related targets were obtained by accessing online mendelian inheritance in man(OMIM)and human gene database(GeneCards),and a protein interaction network of the common targets of HXTLP and SCI was established based on the search tool for the retrieval of interacting genes/protein(STRING)database.The Metascape database was used in KEGG pathway enrichment and GO analyses of the common targets.Molecular docking of active ingredients and key targets was performed through Autodock 1.5.7 software,and the results were visualized with Pymol 2.4.0 software.Finally,the effect of HXTLP on SCI was verified by animal experiments.Results A total of 184 intersection targets were obtained,and the key targets were serine/threonine kinase(AKT1),signal transducer and activator of transcription 3(STAT3),heat shock protein 90 kDa alpha,class A member 1(HSP90AA1),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),phosphoinositide-3-kinase regulatory subunit 1(PIK3R1),harvey ras(HRAS),estrogen receptor 1(ESR1),mitogen-activated protein kinase 1(MAPK1),and epidermal growth factor receptor(EGFR).Molecular docking result showed strong binding abilities between the core active components and key targets.In the animal experiments,the behavioral scores of mice in the HXTLP group increased(P＜0.05),the motor function of hind limbs was improved,and the histological morphology of the injured area was more complete compared with those of the model group.Western Blot result revealed that HXTLP effectively inhibited the key target protein(HSP90AA1)and the expression of phospho-STAT3(P-STAT3)and promoted the expression of phospho-phosphatidylinositol-3-kinase(P-PI3K)and phospho-AKT1(P-AKT1).Conclusions This study verified that HXTLP has multi-component,multi-target,and multi-pathway synergistic effects in the treatment of SCI and has provided experimental and theoretical bases for further clinical medication research for SCI.

Objective:The aim of this study was to explore the risk factors that affect implementation of the innovative technique of single-incision laparoscopic appendectomy (solo-SLA) without assistance in patients with complicated appendicitis, the goal being improving surgical success rates and reducing the incidence of complications.Methods:This was an observational study. Indications for solo-SLA surgery were as follows: (1) computed tomography or ultrasound findings suggestive of acute appendicitis, accompanied by a high white blood cell count and C-reactive protein concentration; (2) disease course exceeding 72 hours, standard anti-infection treatment ineffective, inflammatory reaction not localized, surgery mainly aimed at abscess drainage, and the appendix removed if indicated intraoperatively; (3) acute onset stabilized for more than 3 months after conservative treatment; and (4) recurrent chronic appendicitis. Relative contraindications comprised: (1) cardiopulmonary insufficiency, extremely high risk for general anesthesia for laparoscopic surgery; (2) severe coagulation dysfunction; and (3) imaging findings suggestive of formation of a peri-appendiceal abscess, stable after anti-infection treatment, and a tendency for the inflammatory reaction to localize. We retrospectively collected clinical data of 106 patients with complicated appendicitis who had undergone solo-SLA in the Department of Emergency Surgery, Peking University People's Hospital from February to October 2023. Preoperative computed tomography showed appendiceal fecaliths, blurring of the tissue surrounding fat, intra- and extra-luminal gas and exudate, peri-appendiceal abscess, ascites, and intestinal obstruction by appendicitis. The study cohort comprised 53 male and 53 female patients aged (41.4±17.4) years. The median body mass index was (24.2±3.6) kg/m 2 and median preoperative body temperature (37.3±0.9)℃ Appendicitis had been present for >3 days in 21 of the patients (19.8%) and the maximum diameter of the appendix was (12.4±3.8) mm. The efficacy of the surgery was assessed and logistic regression analysis used to explore the factors affecting the duration of the procedure. The relationship between the maximum diameter of the appendix and duration of surgery was non-linear and was explored using a logistic regression model with restricted cubic spline (RCS). Results:Only one patient required conversion to open surgery; all the other patients successfully completed solo-SLA with a median intraoperative blood loss of 10 (1-100) ml and a surgical time of (65.4±31.7) minutes. Pain scores on postoperative Day 1 and 7 were (3.4±3.2) points and (1.5±1.7) points, respectively. There were no significant postoperative complications .The postoperative hospital stay was (3.5±1.5) days and the interval to resuming normal activities 14 (2-40) days. According to univariate and multivariate analyses, disease course >3 days (OR=5.19, 95%CI: 1.59-16.98, P=0.006) and C-reactive protein >10 mg/L (OR=1.01,95%CI: 1.00-1.02, P=0.003) were independent risk factors for surgical duration >60 minutes, whereas the maximum diameter of the appendix was not independently associated with duration of surgery (OR=1.10, 95%CI: 0.97-1.25, P=0.119). RCS analysis results showed a "U-shaped" association between the maximum diameter of the appendix and duration of surgery, the inflection point of the RCS curve being at a diameter of 10 mm. When the maximum diameter of the appendix was <10 mm, increases in diameter were not associated with longer duration of surgery (OR=1.15,95%CI: 0.55-2.58, P=0.710); whereas when the diameter was ≥10 mm, the maximum diameter of the appendix was associated with increased duration of surgery (OR=1.20, 95% CI: 1.04-1.42, P=0.022). Conclusion:The solo-SLA procedure can be performed to treat complicated appendicitis. A disease course >3 days, C-reactive protein concentration >10 mg/L, and maximum diameter of the appendix ≥10 mm are all associated with greater difficulty of solo-SLA surgery.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with intellectual development disorder and seizures due to a variant of AP2M1 gene. METHODS: Clinical data of a child with intellectual development disorder and epilepsy who was admitted to the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in January 2021 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected for whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The three-dimensional structure of the AP2M1 protein was visualized using Chimera v1.10.1 software. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants from the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). With "AP2M1 gene" "epilepsy" "intellectual disability" as the keywords, relevant cases were searched from CNKI, Wanfang Data knowledge service platform and PubMed databases with the search time spanning from the establishment of the database to September 2024. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2020-57). RESULTS: The child was a 8-years-and-6-months-old boy, who could raise his head at 3 months and sit alone at 8 months old. He could not walk alone at 1 year old and underwent 2 months' rehabilitation treatment, and could walk alone and call his parents at 1-and-a-half-years-old. At 4-years-and-10-months-old, he started to have frequent seizures, manifesting as low level of consciousness, body shaking, accompanied by blinking, lasting about a few seconds several times a day and could be relieved. With the treatment of sodium valproate combined with lamotrigine, the convulsions were controlled, but his movement and cognition were lagged behind. DNA sequencing revealed that he has harbored a novel variant of the AP2M1 gene (NM_004068.3) c.508C>T (p.Arg170Trp). Sanger sequencing confirmed that both of his parents were of the wild-type. According to the guidelines from the American College for Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PS2+PS4+PM1+PM2+PP2+PP3). The difference between the wild-type and mutant AP2M1 proteins can be clearly viewed through its three-dimensional structure. Two previous reports have included 5 cases due to the same variant. Common manifestations have included seizures (100%, 5/5), motor retardation (100%, 5/5), intellectual impairment (100%, 5/5), autism spectrum disorder (60%, 3/5), ataxia (100%, 5/5), and special facial features (20%, 1/5). CONCLUSION The c.508C>T (p.Arg170Trp) variant of the AP2M1 gene may underlie the intellectual retardation and seizure in this child.
Humans ; Male ; Child ; Intellectual Disability/genetics* ; Seizures/genetics* ; Exome Sequencing ; Mutation