Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.

Objective To establish an efficient and stable model of pelvic inflammatory disease in rats via a non-surgical method,and to evaluate its application in pharmacodynamic testing.Methods Female Sprague-Dawley rats were divided randomly into the following groups:control group;model group with phenol for 7 d;model group with phenol for 10 d;treatment group modeled with phenol;model group with low concentration of bacteria;model group with high concentration of bacteria;and treatment group modeled with bacteria.Rats in the model and treatment groups were injected with 25%phenol gel and 2×107 or 2×108 Escherichia coli and Staphylococcus aureus mixture via a non-surgical method,to construct a rat model of pelvic inflammatory disease.Rats in the treatment groups received the Chinese patent medicine Jingangteng capsules by gavage,and rats in the control group received the same volume of solvent solution.The health status,weight changes,and uterine appearance were monitored and the uterine coefficient was calculated.Pathological changes in the uterus and fallopian tubes,endometrial thickness,and number of glands were detected by hematoxylin and eosin staining.Serum levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay.Protein expression of the macrophage marker CD68 was detected by immunofluorescence.Expression of Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB pathway-related proteins in the uterus was detected by Western blot.Results The mortality rate in the model group was only 5%.Compared with the control group,model rats showed decreased body weight,increased uterine coefficient,pathological changes in the uterus and Fallopian tubes,thinner endometrium,fewer glands,significantly higher serum levels of IL-1β,IL-6,and TNF-α and more macrophages in the uterine tissue,and activation of the TLR4/NF-κB signaling pathway.The 7 d phenol and low-concentration bacterial solution models were judged to be mild pelvic inflammatory disease models,and the 10 d phenol and high-concentration bacterial solution models were considered severe pelvic inflammatory disease models.Treatment with Jingangteng capsules relieved the pathological symptoms in the uterus and fallopian tubes,in line with the efficacy evaluation of clinical pelvic inflammatory disease.Conclusions We established rat models of pelvic inflammatory disease using phenol and a mixed bacterial solution via a non-surgical method,to simulate the different pathological states of pelvic inflammatory disease caused by different factors.These models will be suitable for evaluating drug efficacy and elucidating the pathological mechanism of pelvic inflammatory disease.

Objective To explore the clinical value of high frequency ultrasound combined with dermoscopy in preoperative evaluation of cutaneous malignant tumors.Methods A total of 323 patients with suspected cutaneous malignant tumors were selected from Jinhua Municipal Central Hospital from January 2022 to December 2023.The clinical value of high frequency ultrasound,dermoscopy and their combined examination in preoperative diagnosis of cutaneous malignant tumors were analyzed and compared.Results A total of 323 patients with suspected cutaneous malignant tumors,223 patients with confirmed cutaneous malignant tumors by skin pathology,234 skin lesions,and 100 patients with benign skin tumors were included.141 skin lesions were detected by dermoscopy,195 skin lesions by high frequency ultrasound,and 213 skin lesions by the combination of dermoscopy and high frequency ultrasound.The sensitivity,specificity and accuracy of high frequency ultrasound combined with dermoscopy in diagnosis of cutaneous malignant tumors were 87.6％,92.0％and 88.9％,respectively,which was higher than that of single high frequency ultrasound and single dermoscopy.The diagnosis results of dermoscopy combined with high frequency ultrasound were in good agreement with the pathological results(kappa=0.75).Conclusion Dermoscopy and high frequency ultrasound are convenient,non-invasive and sensitive imaging methods for skin detection.They can balance resolution and depth of detection,reveal morphological information of tumors,and predict the risk of tumor recurrence.

Objective To explore the clinical value of high frequency ultrasound combined with dermoscopy in preoperative evaluation of cutaneous malignant tumors.Methods A total of 323 patients with suspected cutaneous malignant tumors were selected from Jinhua Municipal Central Hospital from January 2022 to December 2023.The clinical value of high frequency ultrasound,dermoscopy and their combined examination in preoperative diagnosis of cutaneous malignant tumors were analyzed and compared.Results A total of 323 patients with suspected cutaneous malignant tumors,223 patients with confirmed cutaneous malignant tumors by skin pathology,234 skin lesions,and 100 patients with benign skin tumors were included.141 skin lesions were detected by dermoscopy,195 skin lesions by high frequency ultrasound,and 213 skin lesions by the combination of dermoscopy and high frequency ultrasound.The sensitivity,specificity and accuracy of high frequency ultrasound combined with dermoscopy in diagnosis of cutaneous malignant tumors were 87.6％,92.0％and 88.9％,respectively,which was higher than that of single high frequency ultrasound and single dermoscopy.The diagnosis results of dermoscopy combined with high frequency ultrasound were in good agreement with the pathological results(kappa=0.75).Conclusion Dermoscopy and high frequency ultrasound are convenient,non-invasive and sensitive imaging methods for skin detection.They can balance resolution and depth of detection,reveal morphological information of tumors,and predict the risk of tumor recurrence.

OBJECTIVE To detect the common pathogens for the patients with eczematous dermatitis and analyze associations between the pathogens and the clinical stages.METHODS A total of 206 patients with eczematous der-matitis who were treated in Jinhua Central Hospital from Jan.2014 to Jan.2024 were enrolled in the study and were divided into the secondary skin lesion group with 92 cases and the non-secondary skin lesion group with 114 cases according to the characteristics of the lesions.Meanwhile,the people who received physical examination and had no history of eczematous dermatitis were chosen as the control group with 91 cases.The distribution and den-sity of the common pathogens were compared among the three groups and among the patients with different clini-cal stages(the acute stage,the subacute stage and the chronic stage)of eczematous dermatitis.The scores of skin lesion were compared among the patients.RESULTS Staphylococcus aureus,Staphylococcus epidermidis and Malassezia were dominant among the isolated pathogens;both the positive rates of pathogens and the densities of pathogens,from the high to the low,were as follows:the secondary skin lesion group＞the non-secondary skin lesion group＞the control group(P＜0.05).The isolation rate of S.aureus of the secondary skin lesion group and the non-secondary skin lesion group were higher than that of the control group(P＜0.05);the isolation rate of Malassezia of the secondary skin lesion group was higher than that of the non-secondary skin lesion group(P＜0.05).The score of skin lesion of the patients detected positive for pathogens was higher than that of the patients detected negative(P＜0.05).Among the patients detected positive for pathogens,the score of skin lesion of the a-cute stage patients was higher than that of the subacute stage patients and the chronic stage patients(P＜0.05);the isolation rates of S.aureus and Malassezia and the density of pathogens of the acute stage patients were higher than those of the chronic stage patients(P＜0.05),and the density of pathogens of the subacute stage patients was higher than that of the chronic stage patients(P＜0.05).CONCLUSIONS S.aureus,S.epidermidis and Malassezia are the common pathogens isolated from the patients with eczematous dermatitis.The positive rates and densities of pathogens are higher among the patients with secondary skin lesions,and the infections with the pathogens are associated with the severity of skin lesion and the clinical stage.

OBJECTIVE To detect the common pathogens for the patients with eczematous dermatitis and analyze associations between the pathogens and the clinical stages.METHODS A total of 206 patients with eczematous der-matitis who were treated in Jinhua Central Hospital from Jan.2014 to Jan.2024 were enrolled in the study and were divided into the secondary skin lesion group with 92 cases and the non-secondary skin lesion group with 114 cases according to the characteristics of the lesions.Meanwhile,the people who received physical examination and had no history of eczematous dermatitis were chosen as the control group with 91 cases.The distribution and den-sity of the common pathogens were compared among the three groups and among the patients with different clini-cal stages(the acute stage,the subacute stage and the chronic stage)of eczematous dermatitis.The scores of skin lesion were compared among the patients.RESULTS Staphylococcus aureus,Staphylococcus epidermidis and Malassezia were dominant among the isolated pathogens;both the positive rates of pathogens and the densities of pathogens,from the high to the low,were as follows:the secondary skin lesion group＞the non-secondary skin lesion group＞the control group(P＜0.05).The isolation rate of S.aureus of the secondary skin lesion group and the non-secondary skin lesion group were higher than that of the control group(P＜0.05);the isolation rate of Malassezia of the secondary skin lesion group was higher than that of the non-secondary skin lesion group(P＜0.05).The score of skin lesion of the patients detected positive for pathogens was higher than that of the patients detected negative(P＜0.05).Among the patients detected positive for pathogens,the score of skin lesion of the a-cute stage patients was higher than that of the subacute stage patients and the chronic stage patients(P＜0.05);the isolation rates of S.aureus and Malassezia and the density of pathogens of the acute stage patients were higher than those of the chronic stage patients(P＜0.05),and the density of pathogens of the subacute stage patients was higher than that of the chronic stage patients(P＜0.05).CONCLUSIONS S.aureus,S.epidermidis and Malassezia are the common pathogens isolated from the patients with eczematous dermatitis.The positive rates and densities of pathogens are higher among the patients with secondary skin lesions,and the infections with the pathogens are associated with the severity of skin lesion and the clinical stage.

Objective To investigate how vismodegib(Vis)influences the pathogenesis of basal cell carcinoma(BCC)via a chromatin remodeling factor,bromodomain containing protein 9(BRD9),and to analyze the expression profile of BRD9 in BCC and its relationship with the immune checkpoint,programmed cell death-1 ligand 1(PD-L1)and the Hedgehog(Hh)signaling pathway.Methods ① A UVB-induced BCC model was established in SKH-1 hairless background Ptch1+/-;LacZ reporter mice.Then the mice were treated with Vis,and those without treatment served as control.X-gal staining,immunohistochemistry(IHC)staining,immunofluorescence(IF)assay,and Western blotting were used to assess the expression and localization of BRD9 and PD-L1 in tumor tissues and to evaluate immune-cell infiltration.② In vitro,mouse BCC cell line ASZ001(ASZ cells)were treated with Vis or a BRD9 degrader(dBRD9),and BRD9-overexpressing cells were generated.Cell viability and the protein and mRNA levels of BRD9,PD-L1,Gli1,and cyclin D1(Ccnd1)were measured.ChIP-qPCR was performed to examine BRD9 and H3K27ac enrichment at the PD-L1 promoter,including the promoter-proximal site(P1)and an upstream active segment(P2).Results ① At the tissue level,BRD9 was highly expressed in BCC,and co-localization of BRD9 and PD-L1 was observed within tumor regions,with evident immune-cell infiltration.Vis markedly suppressed UVB-induced BCC formation,reduced the probability of large-volume tumors(by probability-density analysis),decreased the X-gal-positive lesion area(P<0.000 1),down-regulated BRD9(P=0.024 9),and attenuated immune-cell infiltration.② At the cellular level,Vis treatment reduced cell viability and down-regulated BRD9,Gli1,and Ccnd1 in ASZ cells(P<0.000 1).dBRD9 inhibited ASZ cell viability in a dose-dependent manner and decreased PD-L1,Gli1,and Ccnd1(P<0.000 1),whereas its overexpression increased the expression of these molecules(P<0.000 1).In ASZ cells,BRD9 and H3K27ac were enriched at the PD-L1 promoter P1/P2 regions.Treatment with dBRD9 or Vis reduced BRD9 and H3K27ac enrichment at P1/P2 regions(P<0.000 1).Conclusion In BCC,BRD9 maintains chromatin activation at the proximal PD-L1 promoter and modulates Hh/Gli1 signaling,thereby promoting immune evasion.Vis remodels the tumor immune microenvironment by inhibiting the Hh-BRD9-PD-L1 axis.

Objective:To evaluate the clinical efficacy of Huaiqi Huang Granules combined with conventional Western medicine therapy for the treatment of Kawasaki disease in children.Methods:A randomized controlled trial study was conducted. A total of 96 children with Kawasaki disease admitted to Hebei Children's Hospital from August 2022 to July 2024 were selected as the research objects and divided into the observation group and the control group by the random number table method, with 48 cases in each group. The control group received conventional Western medicine treatment on the basis of symptomatic treatment, while the observation group took Huaiqi Huang Granules on the basis of the control group. The treatment for both groups lasted 7 d. TCM symptoms scores of both groups were evaluated. ELISA was used to detect the levels of TNF-α, MCP-4, and IL-8, while fluorescence immunoassay was used to detect the levels of von Willebrand factor (vWF), endothelin-1 (ET-1), and nitric oxide (NO); flow cytometry was used to detect CD4 +, CD3 +, CD8 + levels and calculate CD4 +/CD8 +ratio; adverse reactions were recorded during treatment and clinical efficacy was evaluated. Results:The total effective rate was 93.75% (45/48) in the observation group and 77.08% (37/48) in the control group, with statistical significance ( χ2=5.35, P=0.021). After treatment, the scores of persistent high fever, skin macules, red throat and eyes, and fatigue in the observation group were lower than those in the control group ( t values were 5.66, 5.45, 5.03, and 5.42 respectively, P<0.01). After treatment, the levels of serum TNF-α, MCP-4 and IL-8 in the observation group were lower than those in the control group ( t values were 4.10, 5.97 and 3.82 respectively, P<0.01). After treatment, the levels of serum vWF [(19.43±3.85) μg/L vs. (23.02±4.13) μg/L, t=4.41] and ET-1 [(38.54±5.12) μg/L vs. (43.90±5.26) μg/L, t=5.06] in the observation group were lower than those in the control group ( P<0.01); the level of NO [(81.23±8.44) μg/L vs. (74.42±8.13) μg/L, t=4.03] was higher than that of the control group ( P<0.01); after treatment, the levels of serum CD4 + and CD3 + and the ratio of CD4 +/CD8 + in the observation group were higher than those in the control group ( t values were 4.91, 4.23, and 3.81 respectively, P<0.01); the CD8 + level was lower than that of the control group ( t=4.19, P<0.01). During the treatment period, the incidence of adverse reactions was 10.42% (5/48) in the observation group and 8.33% (4/48) in the control group, without statistical significance ( χ2=0.12, P=0.726). Conclusion:Huaiqi Huang Granules combined with conventional Western medicine therapy can effectively reduce the TCM syndrome score of children with Kawasaki disease, inhibit the levels of inflammatory factors, improve vascular endothelial function, enhance the body's immunity, and have good medication safety.

Grounded in organizational change-complex systems theory,it investigates the pathways and mechanisms for deep integration of Artificial Intelligence(AI)into clinical management.Addressing structural challenges in current clinical management systems,it propose a dynamic three-phase model"unfreezing-changing-refreezing"driven by AI technologies.By deconstructing systemic contradictions arising from technological penetration e.g.,multi-agent coordination,ethical risks,and responsibility ambiguity,a layered governance framework and dynamic regulatory mechanisms are established.Through synergistic evolution of technology,organization,and institution,an adaptive transition in clinical management paradigms can be achieved,ultimately fostering an AI-augmented healthcare ecosystem that balances efficiency with safety.

Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.