ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

As the important source of bone cells, osteoblasts are involved in bone formation and repair, and play a key role in maintaining bone balance. If the osteogenic differentiation process in vivo is disrupted, a variety of bone-related diseases may occur. Natural products, which have a wide range of sources, a wide variety of physiological activities, and few toxic side-effects, have been found in recent years to be able to regulate osteoblast differentiation. Based on the sources of natural products, this paper reviews the intervention of natural products from plant, animal and microbial sources on osteogenic differentiation, aiming to provide a theoretical basis for natural products in the treatment of bone diseases.

Objective:To investigate the influencing factors of adverse reactions of reconstructive flaps after postoperative precision radiation therapy for head and neck tumors.Methods:Medical records of 46 patients who underwent radiotherapy after flap reconstruction for head and neck tumors in the Affiliated Hospital of Inner Mongolia Medical University between January 2016 and October 2022 were retrospectively analyzed. The overall survival (OS), local regional control (LRC) and dosimetric parameters after radiotherapy were analyzed. The adverse reactions mainly including radiation dermatitis and flap necrosis at 3 and 6 months after radiotherapy, flap atrophy, flap fibrosis, dysphagia and chewing dysfunction at 12 and 24 months after radiotherapy were recorded. Adverse reactions were graded using the common terminology criteria for adverse events (CTCAE) version 5.0. Quantitative data were analyzed by one-way analysis of variance or rank-sum test. Qualitative data were analyzed by chi-square test or Fisher's exact test. Multivariate analysis of influencing factors of adverse reactions was performed using binary logistic stepwise regression.Results:All 46 patients were aged 57.6 years on average. The median follow-up time was 65 months (12-100 months). After the follow-up, 22 patients died, 6 recurred, and 7 had distant metastases. The 5-year OS rate was 48% and 5-year LRC rate was 69%. The incidence of radiation dermatitis was decreased over time after the end of radiotherapy: 80% (37/46) and 65% (30/46) at 3 months and 6 months after radiotherapy, respectively. The incidence of grade 3 radiation dermatitis was 11% (5/46) and 0 at 3 and 6 months after radiotherapy, respectively. The incidence of grade 2 flap necrosis was 4% (2/46) at 3 months after radiotherapy. At 12 months after radiotherapy, the incidence of flap atrophy and fibrosis was 83% (38/46) and 67% (31/46) , and the incidence of grade 3 flap atrophy and fibrosis was equally 4% (2/46) , respectively. All patients had dysphagia and chewing dysfunction at 12 months after radiotherapy. At 24 months after radiotherapy, 83% (38/46) and 61% (28/46) of patients still had dysphagia and chewing dysfunction. Multivariate regression analysis showed that irradiated flap volume, total radiotherapy dose, pharyngeal constrictor D mean and pharyngeal constrictor V 60 Gy, the interval between surgery and radiotherapy, gender and age were the independent influencing factors of adverse reactions of reconstructive flaps after precision radiation therapy for head and neck tumors. Conclusions:For patients undergoing flap reconstruction for head and neck tumors, under the premise of ensuring tumor control, the dose to normal tissue and flap blood supply area should be strictly limited, the irradiated volume should be reduced, and the interval between surgery and radiotherapy should be shortened (≤6 weeks) to reduce the risk of adverse reactions. Hypo-fractionated radiotherapy plan should be formulated or the total radiotherapy dose should be appropriately adjusted for elderly patients to reduce long-term complications.

Objective To investigate the diagnostic value of cytokeratin 19 fragment(CYFRA21-1),squa-mous cell carcinoma antigen(SCC),neuron-specific enolase(NSE)combined with fibrinogen(FIB)in patho-logical type and lymph node metastasis of lung cancer.Methods A total of lung cancer patients admitted to Deyu Medical Maanshan General Hospital from September 2022 to March 2024 were selected as the lung canc-er group,including 14 cases of lung squamous cell carcinoma,36 cases of lung adenocarcinoma,8 cases of small cell lung cancer,39 cases of lymph node metastasis and 19 cases of no lymph node metastasis.In addition,45 patients with benign pulmonary lesions in Deyu Medical Ma'anshan General Hospital during the same period were selected as the control group.The levels of CYFRA21-1,SCC,NSE and FIB were compared between the two groups.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of CY-FRA21-1,SCC,NSE combined with FIB for pathological type and lymph node metastasis of lung cancer.Re-sults The levels of CYFRA21-1,NSE,SCC and FIB in lung cancer group were higher than those in control group(P<0.05).There were statistically significant differences in CYFRA21-1,NSE,SCC and FIB levels in patients with different pathological types of lung cancer(P<0.05).The levels of FIB and NSE levels in pa-tients with small cell lung cancer were higher than those in patients with lung squamous cell carcinoma and lung adenocarcinoma.The levels of CYFRA21-1 and SCC in patients with lung squamous cell carcinoma were higher than those in patients with lung adenocarcinoma and small cell lung cancer(P<0.05).The levels of CYFRA21-1,NSE,SCC and FIB in patients with lymph node metastasis were higher than those in patients without lymph node metastasis(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of CYFRA21-1,NSE,SCC and FIB alone and in combination were 0.795,0.620,0.672,0.757 and 0.812,re-spectively.The AUC of combined detection in the diagnosis of lung cancer,lung adenocarcinoma,lung squa-mous cell carcinoma,small cell lung cancer and lymph node metastasis were 0.812,0.837,0.786,0.922 and 0.875,respectively.Conclusion CYFRA21-1,SCC,NSE combined with FIB can improve the diagnostic value of pathological type and lymph node metastasis of lung cancer.

Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

Objective:To investigate the influencing factors of adverse reactions of reconstructive flaps after postoperative precision radiation therapy for head and neck tumors.Methods:Medical records of 46 patients who underwent radiotherapy after flap reconstruction for head and neck tumors in the Affiliated Hospital of Inner Mongolia Medical University between January 2016 and October 2022 were retrospectively analyzed. The overall survival (OS), local regional control (LRC) and dosimetric parameters after radiotherapy were analyzed. The adverse reactions mainly including radiation dermatitis and flap necrosis at 3 and 6 months after radiotherapy, flap atrophy, flap fibrosis, dysphagia and chewing dysfunction at 12 and 24 months after radiotherapy were recorded. Adverse reactions were graded using the common terminology criteria for adverse events (CTCAE) version 5.0. Quantitative data were analyzed by one-way analysis of variance or rank-sum test. Qualitative data were analyzed by chi-square test or Fisher's exact test. Multivariate analysis of influencing factors of adverse reactions was performed using binary logistic stepwise regression.Results:All 46 patients were aged 57.6 years on average. The median follow-up time was 65 months (12-100 months). After the follow-up, 22 patients died, 6 recurred, and 7 had distant metastases. The 5-year OS rate was 48% and 5-year LRC rate was 69%. The incidence of radiation dermatitis was decreased over time after the end of radiotherapy: 80% (37/46) and 65% (30/46) at 3 months and 6 months after radiotherapy, respectively. The incidence of grade 3 radiation dermatitis was 11% (5/46) and 0 at 3 and 6 months after radiotherapy, respectively. The incidence of grade 2 flap necrosis was 4% (2/46) at 3 months after radiotherapy. At 12 months after radiotherapy, the incidence of flap atrophy and fibrosis was 83% (38/46) and 67% (31/46) , and the incidence of grade 3 flap atrophy and fibrosis was equally 4% (2/46) , respectively. All patients had dysphagia and chewing dysfunction at 12 months after radiotherapy. At 24 months after radiotherapy, 83% (38/46) and 61% (28/46) of patients still had dysphagia and chewing dysfunction. Multivariate regression analysis showed that irradiated flap volume, total radiotherapy dose, pharyngeal constrictor D mean and pharyngeal constrictor V 60 Gy, the interval between surgery and radiotherapy, gender and age were the independent influencing factors of adverse reactions of reconstructive flaps after precision radiation therapy for head and neck tumors. Conclusions:For patients undergoing flap reconstruction for head and neck tumors, under the premise of ensuring tumor control, the dose to normal tissue and flap blood supply area should be strictly limited, the irradiated volume should be reduced, and the interval between surgery and radiotherapy should be shortened (≤6 weeks) to reduce the risk of adverse reactions. Hypo-fractionated radiotherapy plan should be formulated or the total radiotherapy dose should be appropriately adjusted for elderly patients to reduce long-term complications.

Objective:To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands.Methods:Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People′s Hospital and two cases from Department of Pathology, Henan Provincial People′s Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed.Results:There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption.Conclusions:IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.

Objective:To investigate the effects of Wenpi Tongluo Kaiqiao Prescription combined with scalp acupuncture on the expression levels of hippocampal autophagy markers Beclin1, P62 and MAP1-LC3 in Alzheimer's disease (AD) model rats.Methods:The AD rat model was established by stereotactic drug injection, and randomly divided into model group, acupuncture-medicine group, and Western medicine group. Sham-operation group and control group were set, with 10 rats in each group. The acupuncture-medicine group was treated with scalp acupuncture plus Wenpi Tongluo Kaiqiao Prescription (16.8 g/kg); the Western medicine group was treated with donepezil hydrochloride tablets (0.08 mg/kg in week 1, 0.16 mg/kg in week 2, 0.24 mg/kg in week 3, 0.32 mg/kg in week 4) for gavage. The sham-operation group, the control group and the model group were treated with equal volume of normal saline for gavage. The drug was administered 2 weeks after modeling. Morris water maze was used to test the learning and memory abilities of rats in each group after continuous administration for 4 weeks, and the hippocampus of the animal was taken after Morris water maze. HE staining and TUNEL staining were used to observe the pathological changes of the hippocampal CA1 region in each group. Western blot was used to detect the expression levels of Beclin1, P62 and MAP1-LC3 protein genes.Results:Compared with the model group, the escape latency of rats in the acupuncture-medicine group and Western medicine groups was significantly shortened ( P<0.05), and the number of times they crossed the platform increased ( P<0.05). The HE and TUNEL results indicated that the model group rats had abnormal tissue structure and cell morphology in the CA1 area of the hippocampus, with significant cell degeneration. There were more autophagic vesicles in the cytoplasm of hippocampal neurons, and the structure of autophagic lysosomes was clear and complete; the tissue structure, cell morphology, and cellular degeneration of the CA1 area in the hippocampus of rats treated with acupuncture and medicine were significantly improved. The percentage of cell apoptosis in the acupuncture-medicine group and Western medicine group decreased ( P<0.05), the expression of Beclin1 protein in hippocampal tissue increased, and the expressions of MAP1-LC3 and P62 proteins decreased ( P<0.05). Conclusion:Wenpi Tongluo Kaiqiao Prescription combined with scalp acupuncture can suppress the apoptosis of hippocampal CA1 neurons, promote cognitive and memory recovery in AD rats by promoting the expression of Beclin1 in the hippocampus, inhibiting the expression of P62 and LC3, enhancing autophagy levels, and increasing autophagic activity.