Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

Purpose: Exercise is an effective non-pharmacological approach for alleviating treatment-related adverse effects and enhancing physical fitness in breast cancer survivors. A Kinect-based mixed reality device (KMR), with real-time feedback and user data collection, is an innovative exercise intervention for breast cancer survivors. This study aimed to investigate the effect of KMR exercise program on quality of life (QOL) and physical function in breast cancer survivors. Materials and Methods: Seventy-seven participants were randomly assigned to either the KMR exercise group or home stretching group with an 8-week intervention. Physical function (shoulder range of motion, body composition, aerobic capacity, and hand grip strength) was evaluated before and after the intervention period. Participants completed questionnaires such as the Disabilities of the Arm, Shoulder, and Hand (DASH), Functional Assessment of Cancer Therapy-Breast, and International Physical Activity Questionnaire (IPAQ) to assess upper extremity disabilities, QOL, and physical activity levels. Results: Significant group-by-time interaction was found for flexion of the operated arm (154.3±12.5 to 165.8±11.2), and the non-operated arm (158.2±13.8 to 166.5±12.2), abduction of the non-operated arm (154.8±31.6 to 161.1±28.1), and adduction of the operated arm (46.5±9.1 to 52.6±7.2). Significant improvements were also observed in DASH (46.8±9.1 to 40.8±9.3) and IPAQ (1,136.3±612.8 to 1,287±664.1). Conclusion The KMR exercise program effectively improved the physical function, alleviated edema, reduced upper extremity disability, and enhanced the QOL in breast cancer survivors. Coupled with significant group-by-time interactions for various outcomes, the results emphasize the potential benefits of incorporating the KMR exercise program to improve the QOL in breast cancer survivors.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

ObjectiveThe effects of two microbial fertilizers （Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer） on the growth and development， the accumulation of active ingredients， and the microbial community diversity of rhizosphere soil of Atractylodes chinensis were investigated. MethodsA field experiment was carried out with two-year-old Atractylodes chinensis as the test material. Plant samples were collected during the wilt stage （September 26， 2023） to determine the general agronomic traits of Atractylodes chinensis. High-performance liquid chromatography （HPLC） was utilized to evaluate the effects of microbial fertilizers on the synthesis and accumulation of four active ingredients （atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ） in Atractylodes chinensi. PacBio Sequel sequencing technology was used to explore the differences in bacterial community structures and diversity in the rhizosphere soil of Atractylodes chinensis treated with different microbial fertilizers. ResultsThe two microbial fertilizers had significant growth-promoting effects on Atractylodes chinensis. Compared with those of the CK group， the stem diameter， stem and leaf dry and fresh weight， and rhizome dry and fresh weight of Atractylodes chinensis significantly increased by 0.47-1.07 times （P<0.05） after the application of the Bacillus subtilis fertilizer （16 kg/667 m²）， and those significantly increased by 0.62-0.96 times （P<0.05） after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer （1.5 kg/667 m²）. The effect on plant height was not significant. The application of two microbial fertilizers was beneficial to the accumulation of atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ （P<0.01）， and the effect of the Bacillus subtilis fertilizer on the accumulation of active ingredients of Atractylodes chinensis was better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The results of high-throughput sequencing showed that compared with the CK group， the Bacillus subtilis fertilizer （8 kg/667 m²） could significantly increase the diversity of rhizosphere bacterial species by regulating the Simpson index and Shannon index （P<0.05）， and the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer significantly reduced the bacterial diversity （P<0.05）. The relative abundance of dominant bacteria was compared at the phylum and genus levels. The relative abundance of Proteobacteria （45.73%） and Burkholderia_Caballeronia_Paraburkholderia （9.98%） significantly increased after the application of the Bacillus subtilis fertilizer （P<0.01）， and the relative abundance of Acidobacteriota （20.53%） and Sphingomonas （3.63%） increased significantly （P<0.01） after the application of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. The relative abundance of beneficial bacteria in the Bacillus subtilis fertilizer was slightly higher than that in the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer. Pearson correlation analysis showed that Burkholderia_Caballeronia_Paraburkholderia and Sphingomonas were positively correlated with the content of atractylodin， atractylon， β-eudesmol， and atractylenolide Ⅰ （P<0.05）. ConclusionThe application of the Bacillus subtilis fertilizer and Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer can increase the yield of medicinal materials and promote the synthesis and accumulation of active ingredients by regulating the rhizosphere microecological diversity of Atractylodes chinensis， and the application effect of the Bacillus subtilis fertilizer is better than that of the Trichoderma harzianum-Purpureocillium lilacinum compound fertilizer.

Purpose: Exercise is an effective non-pharmacological approach for alleviating treatment-related adverse effects and enhancing physical fitness in breast cancer survivors. A Kinect-based mixed reality device (KMR), with real-time feedback and user data collection, is an innovative exercise intervention for breast cancer survivors. This study aimed to investigate the effect of KMR exercise program on quality of life (QOL) and physical function in breast cancer survivors. Materials and Methods: Seventy-seven participants were randomly assigned to either the KMR exercise group or home stretching group with an 8-week intervention. Physical function (shoulder range of motion, body composition, aerobic capacity, and hand grip strength) was evaluated before and after the intervention period. Participants completed questionnaires such as the Disabilities of the Arm, Shoulder, and Hand (DASH), Functional Assessment of Cancer Therapy-Breast, and International Physical Activity Questionnaire (IPAQ) to assess upper extremity disabilities, QOL, and physical activity levels. Results: Significant group-by-time interaction was found for flexion of the operated arm (154.3±12.5 to 165.8±11.2), and the non-operated arm (158.2±13.8 to 166.5±12.2), abduction of the non-operated arm (154.8±31.6 to 161.1±28.1), and adduction of the operated arm (46.5±9.1 to 52.6±7.2). Significant improvements were also observed in DASH (46.8±9.1 to 40.8±9.3) and IPAQ (1,136.3±612.8 to 1,287±664.1). Conclusion The KMR exercise program effectively improved the physical function, alleviated edema, reduced upper extremity disability, and enhanced the QOL in breast cancer survivors. Coupled with significant group-by-time interactions for various outcomes, the results emphasize the potential benefits of incorporating the KMR exercise program to improve the QOL in breast cancer survivors.

Purpose: Exercise is an effective non-pharmacological approach for alleviating treatment-related adverse effects and enhancing physical fitness in breast cancer survivors. A Kinect-based mixed reality device (KMR), with real-time feedback and user data collection, is an innovative exercise intervention for breast cancer survivors. This study aimed to investigate the effect of KMR exercise program on quality of life (QOL) and physical function in breast cancer survivors. Materials and Methods: Seventy-seven participants were randomly assigned to either the KMR exercise group or home stretching group with an 8-week intervention. Physical function (shoulder range of motion, body composition, aerobic capacity, and hand grip strength) was evaluated before and after the intervention period. Participants completed questionnaires such as the Disabilities of the Arm, Shoulder, and Hand (DASH), Functional Assessment of Cancer Therapy-Breast, and International Physical Activity Questionnaire (IPAQ) to assess upper extremity disabilities, QOL, and physical activity levels. Results: Significant group-by-time interaction was found for flexion of the operated arm (154.3±12.5 to 165.8±11.2), and the non-operated arm (158.2±13.8 to 166.5±12.2), abduction of the non-operated arm (154.8±31.6 to 161.1±28.1), and adduction of the operated arm (46.5±9.1 to 52.6±7.2). Significant improvements were also observed in DASH (46.8±9.1 to 40.8±9.3) and IPAQ (1,136.3±612.8 to 1,287±664.1). Conclusion The KMR exercise program effectively improved the physical function, alleviated edema, reduced upper extremity disability, and enhanced the QOL in breast cancer survivors. Coupled with significant group-by-time interactions for various outcomes, the results emphasize the potential benefits of incorporating the KMR exercise program to improve the QOL in breast cancer survivors.

OBJECTIVE To explore the early detection of large vestibular aqueduct syndrome(LVAS)in children by applying several audiological indicators.METHODS Ninety-two children with hearing loss(aged 1-70 months)were enrolled and divided into an LVAS group(45 cases)and a control group(47 cases).Eleven audiological indicators were statistically analyzed:lateral of hearing loss,the degree of hearing loss,configuration of hearing loss;ABR air-conduction threshold;ABR air-bone gap;ASSR average threshold;ASSR thresholds at 0.5,1,2,and 4 kHz;and tympanogram type.Indicators showing significant two-group differences were used to construct a visualized multifactorial linear prediction model using the R language.RESULTS Nine indicators demonstrated statistically significant differences between groups(P<0.05):laterality,configuration of hearing loss,ABR air-conduction threshold,ASSR average threshold,ASSR thresholds at all frequencies(0.5,1,2,4 kHz),and tympanogram type.A prediction model was established.When the total model score ranged between 200 and 240 points,the predicted LVAS risk probability was 0.1 to 0.99.The consistency index(C-index)was 0.85,indicating good predictive ability of the model.CONCLUSION The identified nine audiological indicators are valuable for the early detection of LVAS in children.The developed model can estimate LVAS risk.After refinement,this model holds potential to support early clinical diagnosis and intervention.

Objective:To investigate the efficacy and safety of high-frequency irreversible electroporation (H-FIRE) in treating benign prostatic hyperplasia (BPH).Methods:This randomized controlled open-label multicenter clinical trial enrolled patients from nine medical centers in China between August 2020 and July 2022. Inclusion criteria: age 50–80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Q max) >5 ml/min and ≤15 ml/min. Exclusion criteria: prostate malignancy, contraindications to surgery or anesthesia. Patients were randomized 1∶1 into the H-FIRE group (experimental) or the control group (daily oral 0.2 mg tamsulosin hydrochloride sustained-release capsules). Primary outcomes included Q max, IPSS, prostate volume, and International Index of Erectile Function-5 (IIEF-5) scores, measured at baseline, 1 and 3 months post-treatment. Results:A total of 160 cases were included in this study, including 80 cases in the experimental group and 80 cases in the control group, 30 cases in Renji Hospital, 7 cases in Qilu Hospital of Shandong University, 8 cases in Tongji Hospital, 3 cases in Hunan Provincial Hospital, 13 cases in Shanghai Pudong Hospital, 29 cases in Hwa Mei Hospital, 18 cases in Yiyuan County People's Hospital, and 38 cases in Shanghai East Hospital, and 14 cases in Sun Yat-sen Memorial Hospital. At 3 months of post-treatment, Q max in the experimental group increased by a median of 7.50 (3.55, 14.50) ml/s from the baseline value, whereas in the control group it increased by a median of 1.70 (-1.40, 6.00) ml/s, and the difference between the two groups was statistically significant ( P < 0.01, U = 1 083); and at 3 months of post-treatment, IPSS in the experimental group decreased by a median of 12.00 (7.00, 17.00) points in the test group and 6.00 (2.00, 11.00) points in the control group, and the magnitude of improvement in IPSS scores in the test group was significantly higher than that in the control group ( P < 0.01, U = 1 248); at 3 months of post-treatment, the prostate volume decreased by a median of 12.16 (5.69, 18.27) ml in the experimental group and 0 (-3.94, 6.89) ml in the control group, suggesting that H-FIRE significantly reduced prostate gland volume ( P<0.01, U=1 111). The difference in elevated IIEF-5 scores from baseline at 3 months of treatment between the experimental and control groups was not statistically significant[0(-2.00, 1.00) points vs. 0(-2.00, 1.50) points; P=0.54, U=2 338]. There were no serious adverse events in the two groups. Conclusions:H-FIRE could significantly improve both subjective and objective symptoms of BPH with a low risk of severe complications.

BACKGROUND:Asperosaponin Ⅵ has good osteogenic effects,but its ability to promote cellular osteogenesis under hypoxia environment is not yet clear.OBJECTIVE:To investigate the effect and potential mechanism of Asperosaponin Ⅵ on osteogenic differentiation of MC3T3-E1 cells under hypoxia environment.METHODS:MC3T3-E1 cells were divided into three groups.Cells in the control group were cultured in a complete medium under normoxic conditions(volume fraction of 21％O2);cells in the hypoxia group were cultured in the complete medium under hypoxia conditions(volume fraction of 0.5％O2);and cells in the Asperosaponin Ⅵ group were cultured in the complete medium containing Asperosaponin Ⅵ under hypoxia conditions(volume fraction of 0.5％oxygen).After 24 hours of culture,cell counting kit-8 method and EdU staining were used to detect cell proliferation activity,TUNEL staining and western blot assay were performed to detect cell apoptosis,and flow cytometry was used to detect intracellular reactive oxygen species levels and cell cycle distribution.Each group of cells was cultured in an osteogenic induction medium containing 1×10-5,1×10-6,and 1×10-7 mol/L Asperosaponin Ⅵ under hypoxia conditions for 7 days.The optimal concentration of Asperosaponin Ⅵ for intervention was identified using alkaline phosphatase staining under optical microscopy.Western blot was used to detect the expression of bone morphogenetic protein 2,osteopontin,and PI3K/AKT signaling axis-related proteins.RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation ability of MC3T3-E1 cells decreased under hypoxia conditions.1×10-6 mol/L Asperosaponin Ⅵ could significantly improve the cell proliferation ability under hypoxia conditions and reduce cell apoptosis.(2)Compared with the hypoxia group,the Asperosaponin Ⅵ group showed a decrease in intracellular reactive oxygen species and a significant increase in the proportion of cells in the S phase.(3)Compared with the hypoxia group,the cell morphology in the 1×10-6 mol/L Asperosaponin Ⅵ group was elongated,with more protrusions and darker alkaline phosphatase staining.(4)Compared with the hypoxia group,the expression of bone morphogenetic protein 2 and osteopontin increased in the Asperosaponin Ⅵ group,while the expression of p-PI3K and p-AKT proteins decreased.These findings indicate that under hypoxia conditions,Asperosaponin Ⅵcan promote osteogenic differentiation of MC3T3-E1 cells,possibly by regulating the PI3K/AKT pathway.