OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

ObjectiveTo observe the effect of functional pelvic floor muscle training on pelvic floor muscle function, incontinence symptoms and quality of life in female patients with stress urinary incontinence (SUI). MethodsFrom February, 2024 to July, 2025, 40 female patients with SUI were recruited from Beijing Bo'ai Hospital and advertisements. They were randomly divided into control group (n = 20) and experimental group (n = 20). The control group received conventional pelvic floor muscle contraction and relaxation training, and the experimental group received functional pelvic floor muscle contraction and relaxation training, for eight weeks. The data of pelvic floor muscle strength, pelvic floor muscle surface electromyography (sEMG), 1-hour urine pad test and Incontinence Quality of Life questionnaire (I-QOL) were collected before and after training. The compliance rate was counted after training. ResultsOne case dropped down in the control group and three cases dropped down in the experimental group. After treatment, the pelvic floor muscle strength increased in both groups (|Z| > 3.317, P < 0.01), the pre-resting average value, sustained contraction average value and durable contraction average value of sEMG improved in the control group (|t| > 2.731, P < 0.05), the mass of 1-hour urine pad significantly reduced (t > 9.215, P < 0.001) and the I-QOL score significantly increased (|t| > 13.229, P < 0.001) in both groups; compared with the control group, the pelvic floor muscle strength significantly increased (Z = -2.281, P = 0.023), the mass of 1-hour urine pad significantly reduced (t = 4.215, P < 0.001), the I-QOL score significantly increased (t = -4.501, P < 0.001), and the compliance rate significantly increased (Z = -2.798, P < 0.01) in the experimental group . ConclusionFunctional pelvic floor muscle training can significantly improve pelvic floor muscle strength, incontinence symptoms and quality of life in female patients with SUI.

Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

OBJECTIVE To explore the effects of dihydroartemisinin(DHA)on the functions of cancer-associated fibroblasts(CAFs)in the tumor microenvironment in hypopharyngeal squamous cell carcinoma(HPSCC).METHODS The influence of conditioned media from CAFs and normal fibroblasts(NFs)on tube formation was assessed using a tube formation assay.Secreted protein levels of IL-6,VEGFA,and VEGFC were measured by immunofluorescence and ELISA.Western blotting was used to evaluate the expression of α-SMA,p-STAT3,STAT3,VEGF-A,and VEGF-C within the STAT3 signaling pathway.After treatment with DHA,the optimal concentration for DHA's effect was determined using CCK8 assays and morphological observations of cells.The impact of DHA on angiogenesis was analyzed through tube formation assays,changes in IL-6 expression were detected using ELISA and immunofluorescence,and alterations in α-SMA,p-STAT3,and STAT3 expression were examined by Western blot.RESULTS Both CAFs and NFs exhibited pro-angiogenic and pro-lymphangiogenic effects,with CAFs showing a more pronounced impact.Activated CAFs overexpressed and secreted high levels of IL-6,VEGF-A,and VEGF-C.The concentration of IL-6 in the conditioned medium supernatants of CAF1 and CAF2 was significantly higher than that of NF1 and NF2(P1<0.001,P2<0.05).Similarly,the concentration of VEGF-A was significantly increased(P1<0.05,P2<0.01),and the concentration of VEGF-C was also significantly increased(P1<0.05,P2<0.01).Treatment with DHA inhibited the activated state of CAFs,reducing the expression and secretion of IL-6 and p-STAT3,thereby suppressing tube formation.CONCLUSION Our findings indicate that CAFs promote angiogenesis and lymphangiogenesis in HPSCC via activation of the STAT3 pathway.DHA effectively inhibits this process,suggesting a potential new therapeutic strategy for the treatment of HPSCC.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Objective To evaluate retinal vascular and neural changes in patients with coronary artery disease with depression(CADD)and to investigate their association with depression severity.Methods A total of 40 patients with CADD,56 patients with CAD without depressive disorder(CADND),and 31 healthy controls were included in this study.The vessel density of superficial capillary plexus(SCP)and deep capillary plexus(DCP),and the thickness of the retinal nerve fiber layer(RNFL)and ganglion cell complex(GCC),were quanti-fied using optical coherence tomography angiography(OCTA)to analyze the differences between the groups and their correlation with PHQ-9 scores.Results Compared with the healthy control group,SCP and DCP were signifi-cantly decreased in both CADD and CADND groups(P<0.05).Both superior hemi in RNFL thickness and GCC thickness(including mean,superior hemi,and inferior hemi)were significantly increased in patients with CADD compared with patients with CADND(P<0.05).PHQ-9 scores were negatively correlated with the mean and infe-rior RNFL thickness(P<0.05).Conclusion Both retinal vascular neural structures were altered in patients with CADD,and the neural alterations were strongly correlated with the severity of the patient's depression symptom.