ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

BACKGROUND:The stress effect of autophagy on epithelial cells,fibroblasts and myofibroblasts is closely related to the formation process of pulmonary fibrosis.OBJECTIVE:To screen the genes related to autophagy in patients with pulmonary fibrosis,and explore their correlation with the prognosis of patients with pulmonary fibrosis,in order to provide a new target for clinical intervention in pulmonary fibrosis.METHODS:The gene expression profiling dataset downloaded from GSE70866 was used as a training set,differentially expressed genes between pulmonary fibrosis patients and normal healthy individuals was analyzed using the R language and intersected with autophagy-related genes to identify the differentially expressed genes with the most significant changes.Multiple analysis methods were used to identify key prognostic genes and construct genetic prognostic models.Patients with pulmonary fibrosis were divided into high-risk and low-risk groups according to their risk scores,and the validity of the prognostic model was verified using the Siena cohort and Leuven cohort validation sets.A cell model of pulmonary fibrosis was established by inducing HFL-1 cells(human embryonic lung fibroblasts)with transforming growth factor-β1,and an animal model of pulmonary fibrosis was established in mice by tracheal instillation of bleomycin to validate the expressions of prognostic genes.RESULTS AND CONCLUSION:(1)There were 2 650 differentially expressed genes between fibrotic tissue and normal tissue.Among them,34 genes related to autophagy showed significant expression changes.(2)Kaplan-Meier survival analysis curves for the Siena cohort and Leuven cohort validation sets showed significantly lower survival in the high-risk group than in the low-risk group.(3)Three autophagy genes related to prognosis were screened out:myelocytomatosis viral oncogene(MYC),C-C motif chemokine ligand 2(CCL2),and GABA type a receptor associated protein like 1(GABARAPL1).(4)Both in vivo and in vitro studies showed that compared with the control group,the expression levels of myelocytomatosis viral oncogene and C-C motif chemokine ligand 2 mRNA and protein were significantly higher in the lung fibrosis model group(P＜0.01,P＜0.05),while the expression levels of GABA type a receptor associated protein like 1 mRNA and protein were lower(P＜0.001).To conclude,bioinformatics methods are used to analyze the expression of three autophagy-related genes in pulmonary fibrosis and their correlation with the prognosis of patients with pulmonary fibrosis.The constructed prognostic model has good predictive ability for the 1-,2-,and 3-year survival rates of patients with pulmonary fibrosis.Moreover,in vivo and in vitro models have been used to verify that myelocytomatosis viral oncogene and C-C motif chemokine ligand 2 are highly expressed in lung fibroblasts and tissues,and that GABA type a receptor associated protein like 1 is lowly expressed.

BACKGROUND:The stress effect of autophagy on epithelial cells,fibroblasts and myofibroblasts is closely related to the formation process of pulmonary fibrosis.OBJECTIVE:To screen the genes related to autophagy in patients with pulmonary fibrosis,and explore their correlation with the prognosis of patients with pulmonary fibrosis,in order to provide a new target for clinical intervention in pulmonary fibrosis.METHODS:The gene expression profiling dataset downloaded from GSE70866 was used as a training set,differentially expressed genes between pulmonary fibrosis patients and normal healthy individuals was analyzed using the R language and intersected with autophagy-related genes to identify the differentially expressed genes with the most significant changes.Multiple analysis methods were used to identify key prognostic genes and construct genetic prognostic models.Patients with pulmonary fibrosis were divided into high-risk and low-risk groups according to their risk scores,and the validity of the prognostic model was verified using the Siena cohort and Leuven cohort validation sets.A cell model of pulmonary fibrosis was established by inducing HFL-1 cells(human embryonic lung fibroblasts)with transforming growth factor-β1,and an animal model of pulmonary fibrosis was established in mice by tracheal instillation of bleomycin to validate the expressions of prognostic genes.RESULTS AND CONCLUSION:(1)There were 2 650 differentially expressed genes between fibrotic tissue and normal tissue.Among them,34 genes related to autophagy showed significant expression changes.(2)Kaplan-Meier survival analysis curves for the Siena cohort and Leuven cohort validation sets showed significantly lower survival in the high-risk group than in the low-risk group.(3)Three autophagy genes related to prognosis were screened out:myelocytomatosis viral oncogene(MYC),C-C motif chemokine ligand 2(CCL2),and GABA type a receptor associated protein like 1(GABARAPL1).(4)Both in vivo and in vitro studies showed that compared with the control group,the expression levels of myelocytomatosis viral oncogene and C-C motif chemokine ligand 2 mRNA and protein were significantly higher in the lung fibrosis model group(P＜0.01,P＜0.05),while the expression levels of GABA type a receptor associated protein like 1 mRNA and protein were lower(P＜0.001).To conclude,bioinformatics methods are used to analyze the expression of three autophagy-related genes in pulmonary fibrosis and their correlation with the prognosis of patients with pulmonary fibrosis.The constructed prognostic model has good predictive ability for the 1-,2-,and 3-year survival rates of patients with pulmonary fibrosis.Moreover,in vivo and in vitro models have been used to verify that myelocytomatosis viral oncogene and C-C motif chemokine ligand 2 are highly expressed in lung fibroblasts and tissues,and that GABA type a receptor associated protein like 1 is lowly expressed.

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of renal solitary fibrous tumor (SFT).Methods:Five cases of renal SFT with unequivocal diagnoses at the Affiliated Hospital of Qingdao University between January 2011 and July 2025 were subject to analyses of their clinical, morphological, immunophenotypic, and molecular characteristics, accompanied by a literature review.Results:Two males and three females aged between 45 and 62 years were included, all of whom presented with the discovery of a renal mass during routine physical examinations. Gross examination showed that the five tumors were all confined in the kidney. The tumors were nodular with maximum diameters ranging from 2.5 cm to 11.0 cm (mean, 5.8 cm). Upon cross-sectioning, they exhibited gray-white or gray-yellow cut surface. Histologically, the tumor cells exhibited oval or short spindle shapes in four cases, presenting with varying densities and arranged in short bundles, woven patterns, and irregular formation. Various amounts of coarse collagen and scattered staghorn blood-vessels were found in the stroma. In one case (case 5), the tumor cells were long spindle-shaped, densely organized in bundles, and interwoven, exhibiting inconspicuous boundaries, moderate nuclear atypia, and at least 4 mitotic figures per 10 high-power fields. Irregular patchy collagen deposition was particularly prominent at the edges of the tumor tissue. In two cases (cases 3 and 5), scattered and various amounts of renal tubules were observed in the tumor. Two cases (cases 4 and 5) demonstrated focal invasion of the renal parenchyma, although no necrosis was noted. Immunohistochemical staining showed that the tumor cells were diffusely and strongly positive for vimentin and STAT6 in all 5 cases, and positive for CD34. Bcl-2 positivity was present in 4 of the 5 cases. All cases were negative for CKpan, EMA, PAX8, HMB45, Melan A, SMA, and S-100 protein. The p53 status was wild type, and the Ki-67 index ranged from 1% to 8%. Next-generation sequencing was conducted on one case (case 4), revealing the NAB2 (exon 3)::STAT6 (exon 18) gene fusion. The 5 patients were followed up for 1 to 158 months (mean, 56 months), and all were alive with no recurrence or metastasis.Conclusions:SFT of the kidney are rare and morphologically similar to extrarenal SFT. Key morphological features include short spindle-shaped tumor cells arranged in bundles, interwoven patterns or irregularly, accompanied by staghorn blood-vessels and scattered coarse hyaline collagen fibers. SFT with epithelial inclusions may represent a relatively common histological subtype in the kidney. Immunohistochemical staining that demonstrates diffuse and strong positivity for STAT6 and CD34 is instrumental in diagnosing this tumor. The pathogenesis is linked to the centromeric inversion of chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes. Most of these tumors exhibit favorable prognosis.

Objective:To explore the factors influencing researchers' satisfaction with technology commercialization and propose improvement suggestions for enhancing satisfaction.Methods:A questionnaire survey of researchers at Beijing Tiantan Hospital was conducted using simple random sampling. The collected data were analyzed in sequence through descriptive statistics, factor analysis, and structural equation modeling to identify the factors influencing satisfaction with technology commercialization and to construct a structural equation model linking these factors to satisfaction.Results:The path coefficients of service capacity, institutional environment, supporting capacity, and researchers′ participation willingness to satisfaction were 0.35, 0.25, 0.22, and 0.40, respectively, all exerting positive effects, with researchers' participation willingness and service capacity having greater influence; supporting capacity's effect on researchers' participation willingness was not statistically significant. Mediating effect tests indicated that service capacity and institutional environment indirectly enhanced satisfaction through researchers′ participation willingness with significant effects, whereas supporting capacity had a low significance of indirect effect.Conclusions:To improve the satisfaction with technology commercialization in hospitals, targeted work strategies are proposed to enhance the willingness of researchers to participate. Efforts are made to improve the professionalism of hospital technology commercialization management staff. Systemic work systems are established and an innovative transformation ecosystem is created.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

OBJECTIVE: To summarize the clinical characteristics of foot and ankle deformities combined with knee and lower limb deformities and evaluate the advantages, clinical outcomes, and considerations of QIN Sihe's surgical strategy for treating such complex deformities. METHODS: Between January 2022 and December 2024, 32 patients with foot and ankle deformities combined with knee and lower limb deformities were enrolled. The cohort included 23 males and 9 females, aged 10-67 years (mean, 41.1 years). The main etiologies included post-polio sequelae (20 cases) and congenital limb deformities (3 cases). Deformities were categorized as follows: equinovarus foot (12 cases), equinus foot (2 cases), equinovalgus foot (3 cases), equinus foot with swan-neck deformity (2 cases), calcaneus foot (5 cases), foot valgus (2 cases), knee flexion deformity (14 cases), genu recurvatum (4 cases), genu varum (3 cases), genu valgum (3 cases), lower limb shortening (3 cases), and lower limb external rotation (6 cases). QIN Sihe's surgical strategies included osteotomies, tendon releases, and tendon transfers for deformity correction, followed by external fixation for residual deformity adjustment and stabilization. Outcomes were assessed using QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction. RESULTS: All patients were followed up 8-32 months (mean, 16.5 months). Complications included pin tract infection (1 case, 1 site), ankle pain (2 cases), delayed healing at the proximal tibial osteotomy site (1 case), and anterior talar dislocation (1 case). At last follow-up, insufficient correction of foot deformity was observed in 1 case; both knee and lower limb deformities were corrected, with only mild recurrence of knee flexion deformity in 1 case. The foot/ankle and knee joint function improved. Based on QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction, outcomes were rated as excellent in 30 cases and good in 2 cases, with an excellent-good rate of 100%. CONCLUSION Foot and ankle deformities combined with knee and lower limb deformities are complex, QIN Sihe's surgical strategy can achieve satisfactory clinical outcomes for simultaneous correction.
Humans ; Male ; Female ; Adult ; Middle Aged ; Child ; Adolescent ; Aged ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Lower Extremity Deformities, Congenital/surgery* ; Osteotomy/methods* ; Foot Deformities, Congenital/surgery* ; Ankle Joint/surgery* ; Knee Joint/surgery* ; Foot Deformities/surgery*

Objective To elucidate the role of gut microbiota in cognitive impairment induced by adolescent social isolation(ASI)and identify key pathogenic microbial communities.Methods Sixteen male C57BL/6 mice(postnatal days 21～23)were randomly assigned to a control group(group-housed,4/cage,n=8)or an ASI group(single-housed,1/cage,n=8).After 5 weeks of ASI(5-ASI),fecal samples underwent 16S rRNA sequencing for microbiota analysis.Cognitive behavior was assessed using open field,Y-maze,novel object recognition tests.Correlation analysis integrated microbial abundance with behavioral parameters to screen cognition-associated taxa.Results(1)Behavior:5-ASI mice showed unchanged locomotion(open field)but significantly reduced spontaneous alternation(Y-maze,P<0.01)and lower cognitive index(novel object recognition,P<0.001),confirming spatial and recognition memory deficits.(2)Microbiota:5-ASI mice exhibited decreased α-diversity(P<0.05)and altered β-diversity(P<0.001).LEfSe analysis revealed depleted taxa(e.g.,Prevotellaceae_NK3B31_group,Tyzzerella,Allobaculum,Ruminococcus)and enriched taxa(e.g.,Butyricicoccus,Lachnoclostridium).(3)Correlations:Positive associations with cognitive performance were observed for Prevotellaceae_NK3B31_group,Allobaculum,and Ruminococcus(P<0.05),while Butyricicoccus and Lachnoclostridium showed negative correlations(P<0.05).Conclusion Adolescent social isolation induces spatial/recognition memory impairment and gut microbiota dysbio-sis.Specific microbial alterations(Prevotellaceae_NK3B31_group,Butyricicoccus)correlate with cognitive deficits,providing novel insights into microbiota-mediated mechanisms and potential therapeutic targets.