Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

AIM:To evaluate the clinical efficacy of three types of spectacle lenses with different peripheral microstructure designs in controlling myopia progression among children.METHODS: Retrospective case analysis was conducted. Children diagnosed with myopia aged 6 to 12 y who were received initial spectacle fitting and completed 1-year follow-up at the Optometry Clinic of Suining Central Hospital between January 2023 and August 2024 were enrolled. Only right eye data of all subjects were included for analysis. Based on the type of spectacle lenses independently selected by the children and their parents/guardians, they were divided into four groups: diffusion optics technology(DOT), cylindrical annular refractive element(CARE), highly aspherical lenslets(HAL), and single-vision lenses(SVL). Changes in axial length(AL)and spherical equivalent(SE)from baseline were observed after 1-year lens wear in four groups. Variations between three peripheral microstructure-designed spectacles and single-vision spectacles were compared. The effects of different lens designs on spherical power, astigmatism, corneal curvature, corneal astigmatism, anterior chamber depth, lens thickness, and vitreous cavity depth were analyzed.RESULTS:In this retrospective study, a total of 118 eyes from 118 myopic children were included. There were 28 eyes in 28 children in DOT group [16 males and 12 females, age 10(9, 12)y]. CARE group contained 26 eyes in 26 children, [12 males and 14 females, age 11(9, 12)y]. HAL group had 26 eyes in 26 children [16 males and 10 females, age 10(9, 11)y]. SVL group included 38 eyes in 38 children [20 males and 18 females, age 11(9, 12)y]. There were no significant differences in age, gender, baseline AL, or SE among the four groups(all P>0.05). After 1-year wearing, no increase and slight regression were observed in AL and SE in the DOT group, with no significant differences compared with baseline(all P>0.05). AL and SE increased to varying degrees in the CARE, HAL and SVL groups(all P<0.01). Significant inter-group differences were found in the changes of AL and SE(F=22.820, 30.949, both P<0.001). The mean changes in AL and SE for the DOT group(-0.034±0.180 mm, 0.040±0.243 D)were significantly smaller than those in the CARE group(0.225±0.174 mm, -0.375±0.308 D)and the HAL group(0.147±0.130 mm, -0.255±0.256 D). The changes of AL and SE in the three groups were significantly lower than those in the SVL group(0.355±0.240 mm, -0.891±0.592 D)(all P<0.05).CONCLUSION: In children, short-term wear of spectacles with peripheral microstructural design demonstrates better myopia control efficacy compared to single-vision spectacles. DOT lenses show superior short-term efficacy compared with CARE and HAL lenses.

Objective: We aimed to explore the mechanism of Pizhan Powder in regulating the Wnt4/β-catenin signaling pathway to promote wound healing in mice with chronic skin ulcer. Methods: Male BALB/c mice were divided into blank, model, Pizhan Powder, Pizhan powder removed bark medications, bark medications, inhibitor, and Pizhan Powder + inhibitor groups using the random number table method, with six mice per group. Except for the blank group, chronic skin ulcer wound models were prepared in the other groups by implanting foreign bodies. The blank control group received no treatment, whereas the wounds of the model group were cleaned with furacilin solution. The Pizhan Powder, Pizhan Powder removed bark medications, and bark medications groups were each administered 0.1 g of the corresponding medication on the skin wounds. The inhibitor group received an intraperitoneal injection of 3-(4-methylphenylsulfonamido) benzoic acid methyl ester (MSAB) at a dosage of 10 mg/kg. The Pizhan Powder + inhibitor group was administered 0.1 g of Pizhan Powder on the skin wound, and an intraperitoneal injection of MSAB was also administered (10 mg/kg). These treatments were administered once a day for 14 consecutive days. Wound healing was observed on the first, third, seventh, and 14th day of treatment; hematoxylin and eosin staining was used to observe the pathological changes of ulcerated skin; keratin 10 (CK10), keratin 14 (CK14), cell proliferation nuclear antigen (Ki-67), α-smooth muscle actin (α-SMA), and β-catenin expression in wounds was observed through immunofluorescence; Western blotting was used to detect the expression of signaling pathway-related proteins (Wnt4 and β-catenin). Results: Compared to the model group, the Pizhan Powder group showed a reduced wound area and an increased wound healing rate (P<0.05) and elevated CK10, CK14, Ki-67, α-SMA, β-catenin, and Wnt4 protein expressions (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the bark medications and Pizhan Powder removed bark medications groups was reduced (P<0.05). The wound healing rate and the fluorescence expression of CK10, CK14, Ki-67, and α-SMA in the Pizhan Powder removed bark medications group were lower than that in the bark medications group (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the Pizhan Powder + inhibitor group was reduced, and CK10, CK14, Ki-67, α-SMA, β-catenin and Wnt4 protein expression were lower (P<0.05). Conclusion Pizhan Powder promotes wound healing in chronic skin ulcers of mice by regulating the Wnt4/β-catenin signaling pathway. The bark medications (buffalo hide, white mulberry root-bark, and Chinese wolfberry root-bark) play a crucial role, representing a concrete application of the traditional Chinese medicine theory of " treating skin with skin.

Objective: Based on spinopelvic parameters and biomechanical principles, the pedicle-facet joint (PFJ) morphological characteristics of isthmic and degenerative spondylolisthesis were analyzed, and the mechanism of their onset and progression was discussed. Methods: This retrospective cross-sectional study included 194 patients with L5 spondylolysis or L5–S1 low-grade isthmic spondylolisthesis (IS group), 172 patients with L4–5 degenerative spondylolisthesis (DS group), and 366 patients with nonlumbar spondylolysis (NL group). The spinopelvic parameters and PFJ morphological parameters of the patients were measured, the differences in these parameters among and within the 3 groups were compared, and the correlations were analyzed. Results: Sacral slope (SS) and lumbar lordosis (LL) were the highest in the IS group, the second highest in the DS group, and the lowest in the NL group. Among the 3 groups, the L4 facet joint angle (FJA) was the largest in the IS group, the second largest in the NL group, and the smallest in the DS group. The L4 pedicle-facet joint angle (PFA) was the largest in the DS group, the second largest in the IS group, and the smallest in the NL group. Pearson correlation analysis showed that within each group, SS and LL were negatively correlated with FJA and positively correlated with PFA. Conclusion This study found a correlation between the PFJ morphological characteristics of patients with lumbar spondylolisthesis and spinopelvic parameters, suggesting that the morphological characteristics of PFJs may be caused by varying stresses under different spinopelvic morphologies.

Objective: Based on spinopelvic parameters and biomechanical principles, the pedicle-facet joint (PFJ) morphological characteristics of isthmic and degenerative spondylolisthesis were analyzed, and the mechanism of their onset and progression was discussed. Methods: This retrospective cross-sectional study included 194 patients with L5 spondylolysis or L5–S1 low-grade isthmic spondylolisthesis (IS group), 172 patients with L4–5 degenerative spondylolisthesis (DS group), and 366 patients with nonlumbar spondylolysis (NL group). The spinopelvic parameters and PFJ morphological parameters of the patients were measured, the differences in these parameters among and within the 3 groups were compared, and the correlations were analyzed. Results: Sacral slope (SS) and lumbar lordosis (LL) were the highest in the IS group, the second highest in the DS group, and the lowest in the NL group. Among the 3 groups, the L4 facet joint angle (FJA) was the largest in the IS group, the second largest in the NL group, and the smallest in the DS group. The L4 pedicle-facet joint angle (PFA) was the largest in the DS group, the second largest in the IS group, and the smallest in the NL group. Pearson correlation analysis showed that within each group, SS and LL were negatively correlated with FJA and positively correlated with PFA. Conclusion This study found a correlation between the PFJ morphological characteristics of patients with lumbar spondylolisthesis and spinopelvic parameters, suggesting that the morphological characteristics of PFJs may be caused by varying stresses under different spinopelvic morphologies.

Objective To analyze the application effects of artificial intelligence (AI) software and Mimics software in preoperative three-dimensional (3D) reconstruction for thoracoscopic anatomical pulmonary segmentectomy. Methods A retrospective analysis was conducted on patients who underwent thoracoscopic pulmonary segmentectomy at the Second People's Hospital of Huai'an from October 2019 to March 2024. Patients who underwent AI 3D reconstruction were included in the AI group, those who underwent Mimics 3D reconstruction were included in the Mimics group, and those who did not undergo 3D reconstruction were included in the control group. Perioperative related indicators of each group were compared. Results A total of 168 patients were included, including 73 males and 95 females, aged 25-81 (61.61±10.55) years. There were 79 patients in the AI group, 53 patients in the Mimics group, and 36 patients in the control group. There were no statistical differences in gender, age, smoking history, nodule size, number of lymph node dissection groups, postoperative pathological results, or postoperative complications among the three groups (P>0.05). There were statistical differences in operation time (P<0.001), extubation time (P<0.001), drainage volume (P<0.001), bleeding volume (P<0.001), and postoperative hospital stay (P=0.001) among the three groups. There were no statistical differences in operation time, extubation time, bleeding volume, or postoperative hospital stay between the AI group and the Mimics group (P>0.05). There was no statistical difference in drainage volume between the AI group and the control group (P=0.494), while there were statistical differences in operation time, drainage tube retention time, bleeding volume, and postoperative hospital stay (P<0.05). Conclusion For patients requiring thoracoscopic anatomical pulmonary segmentectomy, preoperative 3D reconstruction and preoperative planning based on 3D images can shorten the operation time, postoperative extubation time and hospital stay, and reduce intraoperative bleeding and postoperative drainage volume compared with reading CT images only. The use of AI software for 3D reconstruction is not inferior to Mimics manual 3D reconstruction in terms of surgical guidance and postoperative recovery, which can reduce the workload of clinicians and is worth promoting.

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

Objective To evaluate the inhibitory effects of prophylactic administration of α-zearalanol(α-ZAL)on bone microarchitecture and bone resorption activity in ovariectomized osteoporotic rats,and to investigate its regulatory effects on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods A total of 606-month-old unmated female Sprague-Dawley(SD)rats weighing(300±20)g were randomly divided into the sham surgery group(Sham group),ovariectomy group(OVX group),solvent group(Oil group),estradiol benzoate treatment group(Post-E2 group),α-ZAL prevention group(Pre-ZAL group),and α-ZAL treatment group(Post-ZAL group),with 10 rats in each group.An osteoporosis rat model was established using the ovariectomy method.Rats in the Sham group underwent the same surgical procedures except for ovarian removal.Seventy-two hours after ovarian removal,the Oil group received intramuscular injections of 0.5 mL of oil solvent,and the Pre-ZAL group received intramuscular injections of α-ZAL(1.5 mg·kg-1),administered every 3 days for 120 consecutive days.The Post-E2 group and Post-ZAL group began intramuscular injections of estradiol benzoate(1.5 mg·kg-1)and α-ZAL(1.5 mg·kg-1),respectively,90 days after ovariectomy,administered every 3 days for 120 consecutive days.After drug administration,bone density and bone tissue microstructure morphology were analyzed using a micro-CT small animal in vivo imaging system and staining methods.Osteoclasts were isolated and their activity was detected.Femoral BMSCs were obtained to assess their osteoblast and adipocyte differentiation capabilities,and uterine tissue morphological changes were observed via histological sections.Results Compared with the OVX group,BMD in the Sham group,Post-E2 group,Pre-ZAL group,and Post-ZAL group increased by 133.12%,75.97%,69.64%,and 24.69%,respectively(all P<0.01).BMD in the Pre-ZAL group was 36.09%higher than in the Post-ZAL group(P<0.01),and there was no significant difference in BMD between the Post-E2 and Pre-ZAL groups(P>0.05).Tb.N in the Sham group,Post-E2 group,Pre-ZAL group,and Post-ZAL group increased by 160.08%,118.14%,94.76%,and 46.76%,respectively,compared with the OVX group(all P<0.01).Tb.Ar increased by 324.21%,203.83%,177.99%,and 82.71%,respectively(all P<0.01).Tb.N in the Pre-ZAL group increased by 32.71%compared to the Post-ZAL group(P<0.05),while Tb.Ar increased by 52.15%(P<0.01).Tb.Sp in the Sham,Post-E2,and Pre-ZAL groups decreased by 58.53%,42.18%,and 35.61%,respectively,compared with the OVX group(all P<0.01).The MAR of the upper tibial cancellous bone in the Sham,Post-E2,and Pre-ZAL groups increased by 257.81%,156.72%,and 142.63%,respectively,compared with the OVX group(all P<0.01),BFR increased by 192.19%,137.23%,and 88.13%,respectively(all P<0.01).MAR and BFR in the Pre-ZAL group increased by 58.10%and 43.63%,respectively,compared with the Post-ZAL group(both P<0.01).There were no significant differences in MAR and BFR between the Post-E2 group and the Pre-ZAL group(P>0.05).MMP-9,TRAP,and CK mRNA expression was significantly downregulated in both the Post-E2 group and the Pre-ZAL group(P<0.01).The osteoblast differentiation capacity of BMSCs in the Post-E2 group and all Post-ZAL groups was enhanced,with a significant increase in the number of mineralized nodules,and the expression levels of OCN,COL1,and OPN mRNA were significantly increased(P<0.01),while the ability to differentiate into adipocytes was weakened.The number of intracellular lipid droplets in BMSCs was significantly reduced,the lipid droplet volume was smaller,and the expression levels of PPAR-γ2 and aP2 mRNA were decreased(P<0.05).There were no significant differences between the Post-E2 group and the Pre-ZAL group(P>0.05).There was no significant increase in body weight in the Post-E2,Pre-ZAL,and Post-ZAL groups,but uterine weight significantly increased in the Post-E2 group(P<0.05),with marked uterine epithelial hyperplasia.Uterine weight in the Pre-ZAL and Post-ZAL groups showed no significant difference compared to the OVX group(P>0.05),and no significant changes were observed in uterine epithelium.Conclusion α-ZAL can effectively protect bone mass,improve bone microstructure,and reduce estrogen-related uterine adverse reactions by regulating the osteogenic/adipogenic differentiation balance of BMSCs,providing a potential new therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis.