ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules （QDYF） alleviate nasal mucosal remodeling in allergic rhinitis （AR） via the interleukin-33 （IL-33）/growth stimulation expressed gene 2 （ST2）/interleukin-1 receptor accessory protein （IL-1RAP） signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst， according to the previous network pharmacology results， this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways， components， and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently， a rat model of ovalbumin （OVA）-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups： Control， model， low-dose QDYF （QDYF-L， 4.04 g·kg^-1）， medium-dose QDYF （QDYF-M， 8.08 g·kg^-1）， high-dose QDYF （QDYF-H， 16.16 g·kg^-1）， and loratadine （0.9 mg·kg^-1）. After 14 days of intervention， behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin （HE） staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction （CVF）. The expression of E-cadherin （E-cad） in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 （Th2） cytokines interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） as well as helper T cell 1 （Th1） cytokines interleukin-2 （IL-2） and interferon-γ （INF-γ） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of transforming growth factor-beta 1 （TGF-β₁）， IL-33， ST2， and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33， ST2， and IL-1RAP had strong binding ability with the main active ingredients—wogonin， 7-methoxy-2-methylisoflavone， formononetin， naringenin， stigmasterol， and beta-sitosterol of QDYF， with the binding energy < -4.25 kcal⋅mol^-1（1 cal≈4.184 J）. The results of in vivo experiments showed that compared with the control group， the model group exhibited increased behavioral scores （P<0.05）， aggravated pathological damage of nasal mucosa， increased collagen fiber deposition and CVF （P<0.05）， elevated serum levels of IL-4， IL-5， and IL-13， up-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）， down-regulated expression of E-cad， and declined serum levels of IL-2， IFN-γ， and IFN-γ/IL-4 ratio （P<0.05）. Compared with the model group， the QDYF groups and loratadine group showed reduced behavioral scores （P<0.05）， alleviated pathological damage of nasal mucosa， reduced collagen fiber deposition and CVF （P<0.05）， and up-regulated E-cad expression （P<0.05）. Compared with the model group， the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio （P<0.05）， declined serum levels of IL-4， IL-5， and IL-13， and down-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）. In addition， the QDYF-H group exhibited an elevated serum IL-2 level （P<0.05）. The QDYF-M group showed down-regulated protein levels of TGF-β₁， IL-33 and IL-1RAP in the nasal mucosa （P<0.05）. The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa （P<0.05）. ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway， thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

Objective:To investigate the application value of intraoperative electrocochleography（ECochG） monitoring technique and insertion techniques in cochlear implant（CI） and analyze its relationship with postoperative residual hearing（RH） preservation. Methods:Thirty-one patients（35 ears） who received CI in our hospital from June 2022 to July 2024 were enrolled. The Advanced Bionics Active Insertion Monitoring（AIM） system was used for real-time ECochG monitoring during surgery. Intraoperative cochlear microphonics （CM） waveform changes were recorded and analyzed in relation to postoperative RH preservation. Results:①ECochG recordings were successfully obtained in 34 of 35 ears （97.1%）. ②According to Harris classification, there were 7 ears（20.6%） of Type A（rising）, 7 ears（20.6%） of Type C（declining）, 8 ears（23.5%） of Type CC（fluctuating）, and 12 ears（35.3%） of Type D（no response）. ③The total CM amplitude decrease was significantly moderately correlated with postoperative low-mid frequency hearing loss（r=0.67, P=0.017）. The total CM amplitude decrease was significantly moderately correlated with postoperative low frequency hearing loss（r=0.65, P=0.023）. ④For the mean amplitude variation, the Amax was 30.70 μV, the Amin was 8.64 μV, and the Aend was 18.27 μV. ⑤Sixteen cases completed postoperative follow-up, with an average low-mid frequency（125-1 000 Hz） residual hearing loss of 15.25 dB HL and a RH preservation rate of 87.5%. Conclusion:Intraoperative ECochG monitoring can effectively predict postoperative residual hearing changes, effectively guide surgical manipulation, and improve residual hearing preservation rate.
Humans ; Cochlear Implantation/methods* ; Audiometry, Evoked Response ; Cochlear Implants ; Male ; Female ; Adult ; Middle Aged ; Monitoring, Intraoperative ; Adolescent ; Young Adult ; Minimally Invasive Surgical Procedures ; Child ; Aged ; Postoperative Period

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Structural optimization of lead compounds is a crucial step in drug discovery. One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules, thereby accelerating the molecular optimization process. Deep molecular diffusion generative models simulate a gradual process that creates novel, chemically feasible molecules from noise. However, the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules, leading to challenges in modifying the scaffold-based molecular structures, and creates limitations in the stability and diversity of the generated molecules. To address these challenges, we propose a deep molecular diffusion generative model, the three-dimensional (3D) equivariant diffusion-driven molecular generation (3D-EDiffMG) model. The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder (dual-SWLEE) is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions. Additionally, a gate multilayer perceptron (gMLP) block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies. The experimental results show that 3D-EDiffMG effectively generates unique, novel, stable, and diverse drug-like molecules, highlighting its potential for lead optimization and accelerating drug discovery.