High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective: To explore the therapeutic mechanism of puerarin in treating rheumatoid arthritis (RA) rats based on the serine/tyrosine protein kinase B (AKT)-phosphorylated forkhead box protein O1 (FOXO1)-interleukin-9 (AKT-FOXO1-IL-9) signaling pathway. Methods : 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . Results: Compared with the blank group , the model group had the lowest toe thickness , and X-ray images showed more obvious segmental stenosis and more severe marginal bone invasion ; scaly like changes appeared at the edges of joints stained with safranin green , accompanied by the exudation of inflammatory cells and increased proliferation and secretion of chondrocytes ; the expression levels of inflammatory factors IL-9 and rheumatoid factors were the highest , and the expression levels of AKT and FOXO1 proteins were the highest (P < 0. 05) . Compared with the model group , the toe thickness of rats treated with different doses of puerarin decreased ; X-ray images showed that the puerarin treatment group of rats showed improvement in plantar joint stenosis and marginal bone invasion ; the results of safranin green staining showed that after treatment with different doses of puerarin , the infiltration of inflammatory cells decreased , and the expression levels of inflammatory factor IL-9 , rheumatoid factors , AKT , and FOXO1 proteins decreased significantly ( P < 0. 05 ) , with the high-dose puerarin group showing the most significant difference. Compared with the high-dose puerarin group , the positive control group showed a significant decrease in the above results and statistical differences (P < 0. 05) . Conclusion Puerarin has a good therapeutic effect on rats with RA by inhibiting the AKT-FOXO1-IL-9 pathway. The high-dose puerarin group (60 mg/kg) has the best therapeutic effect and the results show a dose-response relationship.

Objective:To investigate the factors influencing horizontal sound localization ability in patients with unilateral sensorineural hearing loss (USHL), with the aim of providing evidence-based guidance for clinical rehabilitation.Methods:This cross-sectional study included 43 patients diagnosed with USHL (22 males, 21 females; age range: 30-60 years, mean age: 46.5 years), recruited from Beijing Chaoyang Hospital, Capital Medical University, between October 2023 and April 2024. A control group of 20 age-matched normal-hearing participants (8 males, 12 females; mean age: 45.5 years) was also enrolled. Data collected included demographic variables, four-frequency pure-tone averages (4fPTA at 500, 1 000, 2 000, and 4 000 Hz) for both ears, and duration of hearing loss. Based on the residual hearing in the affected ear, USHL patients were divided into a group with residual hearing (defined as having at least one frequency threshold ≤65 dBHL) and a group with no detectable hearing (all frequencies >65 dBHL). Furthermore, patients in the residual hearing group were categorized by hearing loss severity into those with moderate hearing loss (35 dBHL ≤4fPTA <50 dBHL) and those with moderate-to-severe hearing loss (4fPTA≥50 dBHL). All participants underwent horizontal sound localization testing using speech stimuli under four listening conditions: quiet, and noise at signal-to-noise ratios (SNRs) of +5 dB, 0 dB, and -5 dB. Localization performance was quantified using root-mean-square error (RMSE), and data were analyzed using two-way ANOVA and Pearson correlation in SPSS 26.0.Results:Both the degree of hearing loss and background SNR significantly influenced localization accuracy (hearing level: F=47.59, P<0.01; SNR: F=69.79, P<0.01), with a significant interaction between the two factors ( F=2.81, P<0.01). In quiet environments, even patients with moderate hearing loss demonstrated significantly poorer localization performance compared to normal-hearing controls ( P<0.01). Among those with residual hearing, localization ability at SNR=+5 dB was not significantly different from that in quiet ( P>0.05), but performance deteriorated significantly at SNR=0 dB ( P<0.001). In contrast, patients without residual hearing exhibited significant deficits even at SNR=+5 dB ( P<0.001). Pearson correlation analysis revealed no significant association between RMSE and sex, age, or duration of hearing loss (all P>0.05). However, a strong positive correlation was observed between hearing loss severity and RMSE across all noise conditions ( r=0.760-0.800, all P<0.001), indicating that worse hearing thresholds were associated with poorer localization performance. Conclusions:Even moderate unilateral sensorineural hearing loss can impair horizontal sound localization, and this deficit is exacerbated by increasing hearing loss severity and background noise. Both hearing threshold and SNR are key determinants of localization ability and should be prioritized when designing individualized rehabilitation and intervention strategies for USHL patients.

Objective To develop a postoperative self-management question prompt list for adult liver transplant recipients and conduct preliminary application,aiming to provide an effective tool for facilitating their engagement in postoperative self-management.Methods From August to September 2024,the first draft of the postoperative self-management question prompt list for adult liver transplant recipients was developed through literature search and qualitative interviews,including 9 primary items and 50 secondary items.From October to November 2024,16 experts from Qingdao,Jinan,Beijing,and Fuzhou were interviewed on the Delphi method for 2 rounds to revise the question prompt list.From February to March 2025,19 patients after liver transplantation were selected for the preliminary application of the question prompt list.Results The response rates in the 2 rounds of consultations were both 100％and the authority coefficients of experts were both 0.88.The Kendall's W in the 2 rounds was 0.336 and 0.344(P＜0.001),respectively.The final question prompt list includes 9 primary items and 49 secondary items.The study showed that QPL demonstrated high clinical practicability in helping patients systematically understand the self-management framework after liver transplantation,promoting doctor-patient communication,and enhancing the initiative of self-management.Conclusion The question prompt list of postoperative self-management for adult liver transplant recipients established in this study is scientific,reliable,and practical,which is helpful for patients to obtain information about self-management from medical staff.

Objective:To investigate the efficacy of preoperative ultrasound-guided injection of carbon nanoparticle suspension in cervical lymph node dissection for thyroid cancer reoperation.Methods:Ninety-four patients undergoing reoperation for thyroid cancer admitted by the same physician team of the Department of Thyroid and Breast Surgery of the Ninety-sixty Hospital of the People’s Liberation Army (PLA) from Jan. 2019 to Sep. 2024 were retrospectively analyzed. According to the different scope of the initial surgery, they were divided into the re-specification clearance group, the regional lymph node clearance group, and the metastatic lymph node dissection group, and the groups were subdivided into the carbon nanoparticle group and the control group according to whether they were injected with carbon nanoparticle before the surgery or not. The t-test, χ2-test, and non-parametric test were used to compare the age, gender, surgical method, duration of surgery, total number of lymph nodes detected, and positive lymph node detection rate between the nano-charcoal group and the control group in the three groups. Results:There was no statistically significant difference between the three groups in terms of age, gender, surgical methods, or the total number of lymph nodes detected (all P>0.05) , and the difference between the surgical time of the carbon nanoparticle group in the re-regulation clearance group and the control group was not statistically significant ( P>0.05) ; the surgical time of the carbon nanoparticle group was shorter than that of the control group in both the regional lymph node clearance and the metastatic lymph node dissection groups, and the difference was statistically significant (all P<0.05) ; the positive detection rate of lymph nodes in the carbon nanoparticle group was higher than that in the control group among the three groups, and the difference was statistically significant (all P<0.05) . Conclusion:In the operation of cervical lymph node dissection for papillary thyroid cancer, preoperative ultrasound-guided injection of carbon nanoparticle can accurately localize the lymph nodes, increase the positive detection rate of lymph nodes, reduce the difficulty of surgical operation, and shorten the operation time.

Objective:To investigate the efficacy of preoperative ultrasound-guided injection of carbon nanoparticle suspension in cervical lymph node dissection for thyroid cancer reoperation.Methods:Ninety-four patients undergoing reoperation for thyroid cancer admitted by the same physician team of the Department of Thyroid and Breast Surgery of the Ninety-sixty Hospital of the People’s Liberation Army (PLA) from Jan. 2019 to Sep. 2024 were retrospectively analyzed. According to the different scope of the initial surgery, they were divided into the re-specification clearance group, the regional lymph node clearance group, and the metastatic lymph node dissection group, and the groups were subdivided into the carbon nanoparticle group and the control group according to whether they were injected with carbon nanoparticle before the surgery or not. The t-test, χ2-test, and non-parametric test were used to compare the age, gender, surgical method, duration of surgery, total number of lymph nodes detected, and positive lymph node detection rate between the nano-charcoal group and the control group in the three groups. Results:There was no statistically significant difference between the three groups in terms of age, gender, surgical methods, or the total number of lymph nodes detected (all P>0.05) , and the difference between the surgical time of the carbon nanoparticle group in the re-regulation clearance group and the control group was not statistically significant ( P>0.05) ; the surgical time of the carbon nanoparticle group was shorter than that of the control group in both the regional lymph node clearance and the metastatic lymph node dissection groups, and the difference was statistically significant (all P<0.05) ; the positive detection rate of lymph nodes in the carbon nanoparticle group was higher than that in the control group among the three groups, and the difference was statistically significant (all P<0.05) . Conclusion:In the operation of cervical lymph node dissection for papillary thyroid cancer, preoperative ultrasound-guided injection of carbon nanoparticle can accurately localize the lymph nodes, increase the positive detection rate of lymph nodes, reduce the difficulty of surgical operation, and shorten the operation time.

Objective To develop a postoperative self-management question prompt list for adult liver transplant recipients and conduct preliminary application,aiming to provide an effective tool for facilitating their engagement in postoperative self-management.Methods From August to September 2024,the first draft of the postoperative self-management question prompt list for adult liver transplant recipients was developed through literature search and qualitative interviews,including 9 primary items and 50 secondary items.From October to November 2024,16 experts from Qingdao,Jinan,Beijing,and Fuzhou were interviewed on the Delphi method for 2 rounds to revise the question prompt list.From February to March 2025,19 patients after liver transplantation were selected for the preliminary application of the question prompt list.Results The response rates in the 2 rounds of consultations were both 100％and the authority coefficients of experts were both 0.88.The Kendall's W in the 2 rounds was 0.336 and 0.344(P＜0.001),respectively.The final question prompt list includes 9 primary items and 49 secondary items.The study showed that QPL demonstrated high clinical practicability in helping patients systematically understand the self-management framework after liver transplantation,promoting doctor-patient communication,and enhancing the initiative of self-management.Conclusion The question prompt list of postoperative self-management for adult liver transplant recipients established in this study is scientific,reliable,and practical,which is helpful for patients to obtain information about self-management from medical staff.

Objective:To investigate the factors influencing horizontal sound localization ability in patients with unilateral sensorineural hearing loss (USHL), with the aim of providing evidence-based guidance for clinical rehabilitation.Methods:This cross-sectional study included 43 patients diagnosed with USHL (22 males, 21 females; age range: 30-60 years, mean age: 46.5 years), recruited from Beijing Chaoyang Hospital, Capital Medical University, between October 2023 and April 2024. A control group of 20 age-matched normal-hearing participants (8 males, 12 females; mean age: 45.5 years) was also enrolled. Data collected included demographic variables, four-frequency pure-tone averages (4fPTA at 500, 1 000, 2 000, and 4 000 Hz) for both ears, and duration of hearing loss. Based on the residual hearing in the affected ear, USHL patients were divided into a group with residual hearing (defined as having at least one frequency threshold ≤65 dBHL) and a group with no detectable hearing (all frequencies >65 dBHL). Furthermore, patients in the residual hearing group were categorized by hearing loss severity into those with moderate hearing loss (35 dBHL ≤4fPTA <50 dBHL) and those with moderate-to-severe hearing loss (4fPTA≥50 dBHL). All participants underwent horizontal sound localization testing using speech stimuli under four listening conditions: quiet, and noise at signal-to-noise ratios (SNRs) of +5 dB, 0 dB, and -5 dB. Localization performance was quantified using root-mean-square error (RMSE), and data were analyzed using two-way ANOVA and Pearson correlation in SPSS 26.0.Results:Both the degree of hearing loss and background SNR significantly influenced localization accuracy (hearing level: F=47.59, P<0.01; SNR: F=69.79, P<0.01), with a significant interaction between the two factors ( F=2.81, P<0.01). In quiet environments, even patients with moderate hearing loss demonstrated significantly poorer localization performance compared to normal-hearing controls ( P<0.01). Among those with residual hearing, localization ability at SNR=+5 dB was not significantly different from that in quiet ( P>0.05), but performance deteriorated significantly at SNR=0 dB ( P<0.001). In contrast, patients without residual hearing exhibited significant deficits even at SNR=+5 dB ( P<0.001). Pearson correlation analysis revealed no significant association between RMSE and sex, age, or duration of hearing loss (all P>0.05). However, a strong positive correlation was observed between hearing loss severity and RMSE across all noise conditions ( r=0.760-0.800, all P<0.001), indicating that worse hearing thresholds were associated with poorer localization performance. Conclusions:Even moderate unilateral sensorineural hearing loss can impair horizontal sound localization, and this deficit is exacerbated by increasing hearing loss severity and background noise. Both hearing threshold and SNR are key determinants of localization ability and should be prioritized when designing individualized rehabilitation and intervention strategies for USHL patients.

Objective:To perform two-step clustering analysis based on urodynamics in patients with neurogenic bladder (NB) and exploring characteristics affecting success rate of sacral neuromodulation (SNM).Methods:The data of 174 NB patients who received SNM therapy in our hospital from September 2018 to August 2023, were retrospectively analysed. There were 94 males and 80 females, with average age of (50.4±17.9)years, median duration of 2 (1, 3)years, and body mass index of 21.5 (20, 25) kg/m 2. Among them, 50 patients had chronic diseases (hypertension or diabetes). Additionally, 77 patients (44.3%) presented with voiding symptoms, 47 patients (27.0%) with storage symptoms, and 50 patients (28.7%) with mixed symptoms. The etiologies included spinal cord lesions in 110 patients (63.2%), brain lesions in 21 patients (12.1%), peripheral nerve lesions in 36 patients (20.7%), and other causes in 7 patients (4.0%). All patients underwent urodynamics and SNM phase 1 test. If patient's subjective symptoms or objective indicators improved > 50%, it is defined as treatment success and feasible to received second stage of SNM. The success rate was analyzed. Clinical indicators and urodynamic parameter were collected for exploring the difference of the above indicators between two groups (with or without conversion). The 174 patients were grouped using two-step clustering analysis, dividing them into two groups. The differences in clinical data, urodynamic parameters, and the conversion rate of SNM phase II between the two groups were compared. Results:Among these patients, 126 (72%) underwent the second stage of SNM. Compared with the non-conversion group, patients in the conversion group exhibited the following characteristics: high proportion of female[51.6% (65/126) vs. 31.2% (15/48)], younger[(48.1± 18.3)year vs. (56.4±15.4) year], lower proportion of history of chronic disease[23.9% (30/126) vs. 41.7% (20/48)], storage predominant symptoms predominant[33.3% (42/126) vs. 10.4% (5/48)], sensitive bladder sensation[50.0% (63/126) vs. 11.1% (14/48)], normal detrusor contractility [26.2% (33/126) vs. 10.4% (5/48)] and detrusor-sphincter dyssynergia [21.4% (27/126) vs. 4.2% (2/48)]and lower post-void residual [105.5(49.3, 231.3) ml vs. 197.9(114.8, 284.8) ml], ( P<0.05). After excluding multicollinearity, patients were divided into two group mainly based on coordination, detrusor stability, and detrusor contractility through two-step clustering analysis: 98 patients in Group 1 and 76 patients in Group 2. The success rate was higher in Group 2 [82.9% (63/76) vs. 64.3% (63/98), P=0.006]. Compared with Group 1, Group 2 exhibited the following characteristics: higher proportion of storage symptoms [43.4% (33/76) vs. 14.3% (14/98)], sensitive bladder sensation [67.1% (51/76) vs. 26.5% (26/98)], detrusor overactivity [46.1% (35/76) vs. 3.1% (3/98)], normal detrusor contractility [43.4% (33/76) vs. 5.1% (5/98)], and detrusor-sphincter dyssynergia [38.2% (29/76) vs. 0] ( P all<0.05). Additionally, group 2 had lower post-void residual [69.0 (23.8, 136.6) ml and 197.9 (123.2, 287.4) ml] and smaller bladder capacity [(281.9±144.9) ml vs. (430.4±176.7) ml] ( P all<0.01). Conclusions:Patients with storage symptoms, low post-void residual, sensitive bladder sensation, detrusor overactivity, normal contractility, or detrusor-sphincter dyssynergia indicate a higher conversion rate to second stage, making them more suitable for SNM testing.

Objective:To evaluate the role of microRNA-149-5p (miR-149-5p) in resveratrol-induced reduction of lipopolysaccharide (LPS)-induced cardiomyocyte injury in rats.Methods:Rat cardiomyocyte cell line H9C2 was cultured and then divided into 5 groups ( n=27 each) using a random number method: control group (C group), LPS group, resveratrol group (RSV group), miR149-5p inhibitor negative control group (LRN group), and miR149-5p inhibitor group (LRI group). A cardiomyocyte injury model was prepared by incubating cells with culture medium containing 10 μg/ml LPS for 24 h. RSV group was incubated with resveratrol (final concentration of 10 μmol/L) for 24 h, followed by incubation with culture medium containing 10 μg/ml LPS for another 24 h. LRN group and LRI group were transfected with miR149-5p inhibitor negative control and miR149-5p inhibitor, respectively, and then the other treatments were similar to those previously described in RSV group. The cell viability was measured by CCK-8 assay, the apoptosis rate by flow cytometry, the concentration of lactate dehydrogenase (LDH) and content of glutathione (GSH) in the supernatant by microplate method, the content of malondialdehyde (MDA) by TBA reaction method, the activity of superoxide dismutase (SOD) by WST-1 method, the level of reactive oxygen species (ROS) by DCFH-DA fluorescent probe, the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the supernatant by enzyme-linked immunosorbent assay, and the expression of miR-149-5p by quantitative real-time polymerase chain reaction. Results:Compared with C group, the expression of miR-149-5p was significantly down-regulated, the cell viability was decreased, the concentrations of LDH, TNF-α and IL-6 in supernatant, apoptosis rate, ROS level and MDA content were increased, and the GSH content and SOD activity were decreased in LPS group ( P<0.05). Compared with LPS group, the expression of miR-149-5p was significantly up-regulated, the cell viability was increased, the concentrations of LDH, TNF-α and IL-6 in supernatant, apoptosis rate, ROS level and MDA content were decreased, and the GSH content and SOD activity were increased in RSV group ( P<0.05). Compared with RSV group or LRN group, the expression of miR-149-5p was significantly down-regulated, the cell viability was decreased, the concentrations of LDH, TNF-α and IL-6 in supernatant, apoptosis rate, ROS level and MDA content were increased, and the GSH content and SOD activity were decreased in LRI group ( P<0.05). Conclusions:The mechanism by which resveratrol alleviates LPS-induced cardiomyocyte injury is associated with the up-regulation of miR-149-5p expression and inhibition of cell apoptosis, oxidative stress and inflammatory responses in rats.