ObjectiveTo explore the molecular mechanism by which gypenoside L （Gyp-L） promotes apoptosis and inhibits ovarian cancer （OC） through the FK506-binding protein （FKBP） prolyl isomerase 8 （FKBP8）/B-cell lymphoma-2 （Bcl-2） axis， with the piR-hsa-2804461 pathway as a breakthrough point. MethodsThe effects of different concentrations of Gyp-L and cis-platinum on the proliferation of OVCAR3 cells were determined by the cell count kit-8 method to identify the appropriate intervention concentration for subsequent experiments. OVCAR3 cells were allocated into blank， low-dose Gyp-L （Gyp-L-L， 50 µmol·L^-1）， high-dose Gyp-L （Gyp-L-H， 100 µmol·L^-1）， and cis-platinum （15 µmol·L^-1） groups. The migration， colony formation， and apoptosis of OVCAR3 cells were detected by the cell scratch assay， colony formation assay， and flow cytometry， respectively. The mRNA levels of piR-hsa-2804461 and FKBP8/Bcl-2 axis-related genes in OVCAR3 cells were determined by Real-time PCR， and the expression levels of FKBP8/Bcl-2 axis-related proteins were determined by simple Western blot. Further， an OVCAR3 cell model with piR-hsa-2804461 knocked out was constructed. The cells were allocated into blank， NC-inhibitor， inhibitor， NC-inhibitor+Gyp-L， and inhibitor+Gyp-L groups. The colony formation of OVCAR3 cells was detected by the colony formation assay. The mRNA levels of piR-hsa-2804461 and FKBP8/Bcl-2 axis-related genes and the expression levels of FKBP8/Bcl-2 axis-related proteins were determined by Real-time PCR and simple Western blotting， respectively. ResultsGyp-L inhibited the migration and proliferation （P<0.01）， promoted the apoptosis （P<0.05）， up-regulated the mRNA level of piR-hsa-2804461 （P<0.05）， and down-regulated the mRNA and protein levels of FKBP8 and Bcl-2 （P<0.05） in OVCAR3 cells. Furthermore， Gyp-L increased the mRNA and protein levels of Bcl-2-associated X protein （Bax）， cysteinyl aspartate-specific proteinase （Caspase）-3， and Caspase-9， which are related to the FKBP8/Bcl-2 axis （P<0.05）. ConclusionGyp-L may promote apoptosis by regulating the piR-hsa-2804461/FKBP8/Bcl-2 axis， thus affecting the occurrence of ovarian cancer.

ObjectiveTo explore the molecular mechanism of gypenoside L （Gyp-L） in the treatment of ovarian cancer （OC） by taking the glycolytic pathway of OC as the key point. MethodsThe proliferation activity of OVCAR3 cells was measured by the cell counting kit-8 （CCK-8） assay to determine the appropriate intervention concentration for subsequent experiments. The cell clone formation assay and the scratch healing assay were employed to assess the proliferation and migration capabilities of OVCAR3 cells. OVCAR3 cells were divided into a blank group， a Gyp-L-L group （low concentration of Gyp-L， 50 µmol·L^-1）， a Gyp-L-H group （high concentration of Gyp-L， 100 µmol·L^-1）， and a cisplatin （15 µmol·L^-1） group. The glucose consumption in OC cells was determined using a kit， and the expression levels of related mRNAs in OVCAR3 cells were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of related proteins were detected by Wes automatic Western blot quantitative analysis. ResultsValidated by the cell scratch assay， the scratch healing rate of OVCAR3 cells was decreased after Gyp-L intervention， reflecting that Gyp-L could significantly inhibit the migration of OVCAR3 cells （P<0.05）. According to the clone formation assay， the cell colony formation ability of the Gyp-L-L group， Gyp-L-H group， and cisplatin group was significantly lower than that of the control group （P<0.05）. In OVCAR3 cells， compared with those in the control group， the levels of glucose consumption and lactate generation in the Gyp-L-L group and Gyp-L-H group were significantly reduced （P<0.05）， indicating that Gyp-L could effectively inhibit the glycolysis level of OC cells. Meanwhile， Gyp-L could suppress the expression levels of glucokinase （GCK）， phosphofructokinase liver （PFKL）， signal transducer and activator of transcription 3 （STAT3）， lactate dehydrogenase D （LDHD）， phosphoglycerate mutase 1 （PGAM1）， mRNAs， and proteins related to the glycolytic pathway in OC cells. ConclusionGyp-L may inhibit the occurrence and development of OC by influencing the GCK-mediated glycolytic pathway.

ObjectiveTo explore the molecular mechanism by which gypenoside L （Gyp-L） promotes apoptosis and inhibits ovarian cancer （OC） through the FK506-binding protein （FKBP） prolyl isomerase 8 （FKBP8）/B-cell lymphoma-2 （Bcl-2） axis， with the piR-hsa-2804461 pathway as a breakthrough point. MethodsThe effects of different concentrations of Gyp-L and cis-platinum on the proliferation of OVCAR3 cells were determined by the cell count kit-8 method to identify the appropriate intervention concentration for subsequent experiments. OVCAR3 cells were allocated into blank， low-dose Gyp-L （Gyp-L-L， 50 µmol·L^-1）， high-dose Gyp-L （Gyp-L-H， 100 µmol·L^-1）， and cis-platinum （15 µmol·L^-1） groups. The migration， colony formation， and apoptosis of OVCAR3 cells were detected by the cell scratch assay， colony formation assay， and flow cytometry， respectively. The mRNA levels of piR-hsa-2804461 and FKBP8/Bcl-2 axis-related genes in OVCAR3 cells were determined by Real-time PCR， and the expression levels of FKBP8/Bcl-2 axis-related proteins were determined by simple Western blot. Further， an OVCAR3 cell model with piR-hsa-2804461 knocked out was constructed. The cells were allocated into blank， NC-inhibitor， inhibitor， NC-inhibitor+Gyp-L， and inhibitor+Gyp-L groups. The colony formation of OVCAR3 cells was detected by the colony formation assay. The mRNA levels of piR-hsa-2804461 and FKBP8/Bcl-2 axis-related genes and the expression levels of FKBP8/Bcl-2 axis-related proteins were determined by Real-time PCR and simple Western blotting， respectively. ResultsGyp-L inhibited the migration and proliferation （P<0.01）， promoted the apoptosis （P<0.05）， up-regulated the mRNA level of piR-hsa-2804461 （P<0.05）， and down-regulated the mRNA and protein levels of FKBP8 and Bcl-2 （P<0.05） in OVCAR3 cells. Furthermore， Gyp-L increased the mRNA and protein levels of Bcl-2-associated X protein （Bax）， cysteinyl aspartate-specific proteinase （Caspase）-3， and Caspase-9， which are related to the FKBP8/Bcl-2 axis （P<0.05）. ConclusionGyp-L may promote apoptosis by regulating the piR-hsa-2804461/FKBP8/Bcl-2 axis， thus affecting the occurrence of ovarian cancer.

ObjectiveTo explore the molecular mechanism of gypenoside L （Gyp-L） in the treatment of ovarian cancer （OC） by taking the glycolytic pathway of OC as the key point. MethodsThe proliferation activity of OVCAR3 cells was measured by the cell counting kit-8 （CCK-8） assay to determine the appropriate intervention concentration for subsequent experiments. The cell clone formation assay and the scratch healing assay were employed to assess the proliferation and migration capabilities of OVCAR3 cells. OVCAR3 cells were divided into a blank group， a Gyp-L-L group （low concentration of Gyp-L， 50 µmol·L^-1）， a Gyp-L-H group （high concentration of Gyp-L， 100 µmol·L^-1）， and a cisplatin （15 µmol·L^-1） group. The glucose consumption in OC cells was determined using a kit， and the expression levels of related mRNAs in OVCAR3 cells were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of related proteins were detected by Wes automatic Western blot quantitative analysis. ResultsValidated by the cell scratch assay， the scratch healing rate of OVCAR3 cells was decreased after Gyp-L intervention， reflecting that Gyp-L could significantly inhibit the migration of OVCAR3 cells （P<0.05）. According to the clone formation assay， the cell colony formation ability of the Gyp-L-L group， Gyp-L-H group， and cisplatin group was significantly lower than that of the control group （P<0.05）. In OVCAR3 cells， compared with those in the control group， the levels of glucose consumption and lactate generation in the Gyp-L-L group and Gyp-L-H group were significantly reduced （P<0.05）， indicating that Gyp-L could effectively inhibit the glycolysis level of OC cells. Meanwhile， Gyp-L could suppress the expression levels of glucokinase （GCK）， phosphofructokinase liver （PFKL）， signal transducer and activator of transcription 3 （STAT3）， lactate dehydrogenase D （LDHD）， phosphoglycerate mutase 1 （PGAM1）， mRNAs， and proteins related to the glycolytic pathway in OC cells. ConclusionGyp-L may inhibit the occurrence and development of OC by influencing the GCK-mediated glycolytic pathway.

Objective:To investigate the clinical diagnosis and treatment of IgG4-related disease（IgG4-RD） primarily involving the nasal cavity and skull base. Methods:A retrospective analysis was conducted on the clinical data of 8 patients with IgG4-RD primarily involving the nasal cavity and skull base who visited the Nasal and Skull Base Surgery Department at Xiangya Hospital from October 2017 to January 2024. The cohort comprised 4 males and 4 females, aged 8 to 69 years. Clinical data, laboratory examination results, imaging findings, histopathological results, and treatment plans were collected. The clinical manifestations, diagnosis, treatment and follow-up results of IgG4-RD primarily involving nasal cavity and skull base were summarized and previous literature were also reviewed. Results:The initial symptoms in the 8 patients included nasal congestion, headache, sensory function decline, and facial deformities. Three patients also had parotid and pulmonary involvement. Among the 8 patients, 4 underwent partial surgical resection combined with glucocorticoid therapy; 1 underwent partial surgical resection combined with glucocorticoid and immunosuppressant therapy; 1 received glucocorticoid therapy alone; and 2 received glucocorticoid combined with immunosuppressant therapy. Follow-up was conducted one month after treatment, lasting from 5 to 79 months. During the follow-up period, recurrence was observed in 1 patient treated with glucocorticoid combined with immunosuppressants and in 1 patient treated with glucocorticoid alone, while the other 6 patients achieved significant remission. Conclusion:The diagnosis of nasal cavity and skull base IgG4-RD requires the combination of histopathology, laboratory tests, and imaging results. Treatment primarily includes glucocorticoids or combined immunosuppressants. For patients with significant compression symptoms, sensory function impairment, or facial deformities, surgical resection is an important treatment option. Given the high risk of recurrence, early intervention, active treatment, and long-term follow-up are crucial.
Humans ; Male ; Skull Base/pathology* ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Nasal Cavity/pathology* ; Adult ; Immunoglobulin G4-Related Disease/therapy* ; Immunoglobulin G ; Child ; Young Adult ; Adolescent

Objective:To investigate the clinical effect of free anterolateral thigh myocutaneous flap combined with oral repair membrane in the reconstruction of nasal mucosa defect after maxillary malignant tumor surgery. Methods:A total of 12 patients with maxillary gingival squamous cell carcinoma and maxillary sinus cancer who had been treated in Department of Oral and Maxillofacial Surgery, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, were selected from November 2020 to November 2023. Free anterolateral thigh musculocutaneous flap transplantation combined with oral repair membrane were used in all patients. Meanwhile, maxillary soft and hard tissue defects and nasal mucosa defects left after tumor operation were repaired and reconstructed. The clinical effect was evaluated after 6-12 months follow-up. Results:Subtotal maxillary resection was performed in 1 case, total maxillary resection in 9 cases and extended maxillary resection in 2 cases. The musculocutaneous flaps of all patients survived, the facial appearance was basically symmetrical, no obvious depression deformity, the swallowing and speech function recovered well, the mouth and nasal cavity were closed completely, the food could be eaten through the mouth, and the lower nasal passage was not blocked. Conclusion:The free anterolateral thigh musculoflap combined with oral repair membrane can be used to repair and reconstruct maxillary malignant tumor complicated with extensive maxillary tissue and nasal mucosa defect after operation, and the appearance and function can be recovered well after operation, which is a choice for maxillary malignant tumor complicated with nasal mucosa defect.
Humans ; Myocutaneous Flap ; Plastic Surgery Procedures/methods* ; Maxillary Neoplasms/surgery* ; Carcinoma, Squamous Cell/surgery* ; Male ; Middle Aged ; Female ; Nasal Mucosa/surgery* ; Maxilla/surgery* ; Thigh/surgery* ; Maxillary Sinus Neoplasms/surgery*

ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 （TRPV1） and bitter taste receptor 14 （TAS2R14） in the lung tissue of the rat model of cold asthma. MethodSeventy SD rats were randomized into 7 groups： normal， model， Shegan Mahuangtang， pungent Chinese herbs， bitter Chinese herbs （6.43 g·kg^-1）， dexamethasone （0.5 g·kg^-1）， and Guilong Kechuanning （10 g·kg^-1）. The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin （OVA） and aluminium hydroxide in the limbs， combined with 2% OVA atomization and cold （2-4 ℃） stimulation. The rats were treated with corresponding drugs by gavage and atomization， and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation， airway inflammation and cell proliferation were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and Masson staining of the lung tissue. The levels of interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， thymic stromal lymphopoietin （TSLP）， and transforming growth factor-β₁ （TGF-β₁） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1， TAS2R14， phospholipase Cβ₂ （PLCβ₂）， B-cell lymphoma-2 （Bcl-2）， and α-smooth muscle actin （α-SMA） in the lung tissue was determined by Western blot. ResultCompared with the normal group， the model group showed decreased water intake， food intake， and body weight， increased airway inflammatory cell infiltration， goblet cell proliferation， tissue fibrosis and collagen deposition， elevated levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， upregulated expression of TRPV1， PLCβ₂， and α-SMA， and downregulated expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. Compared with model group， Shecgan Mahuangtang， pungent Chinese herbs， and bitter Chinese herbs increased the water intake， food intake， and body weight， reduced the inflammatory cell infiltration and goblet cell proliferation， alleviated tissue fibrosis and collagen deposition， lowered the levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， downregulated the expression of TRPV1， PLCβ₂， and α-SMA， and upregulated the expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation， downregulate the expression of TRPV1， PLCβ₂， and α-SMA， and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover， bitter Chinese herbs outperformed pungent Chinese herbs， and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14.

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains unclear. Methods We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAP-periodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM specimens.Glioma stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional culture.For the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were studied. Results VM and high pATM expression occurred in 38.5%and 41.8%of tumors,respectively,and were significantly associated with reduced progression-free and overall survival.Patients with VM-positive GBMs exhibited higher pATM levels(rs=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in vitro.ATM inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin B2. Conclusion VM may predict a poor GBM prognosis and is associated with pATM expression.We propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

Objective:To investigate the characteristics of extracellular matrix vesicle mimetics prepared by mechanical extrusion and their effects on the cell viability and osteogenic differentiation potential of human periodontal ligament stem cells (PDLSC).Methods:PDLSC derived extracellular matrix vesicles were prepared by collagenase digestion, while the cell derived vesicle mimetics were simulated by mechanical extrusion. The obtained extracellular matrix vesicles and parental cell derived vesicle mimetics were divided into 4 groups: matrix vesicles derived from PDLSC cultured in basic medium for 7 days (PDLSC matrix vesicles, MVs), vesicle mimetics derived from PDLSC cultured in basic medium for 7 days (PDLSC vesicle mimetics, CVMs), matrix vesicles derived from PDLSC cultured in osteogenic inducing medium for 7 days (osteogenic-induced PDLSC matrix vesicles, O-MVs) and vesicle mimetics derived from PDLSC cultured in osteogenic inducing medium for 7 days (osteogenic-induced PDLSC vesicle mimetics, O-CVMs). Vesicles morphologies and sizes were observed by transmission electron microscopy and nanoparticle tracking analysis. Vesicles uptake was detected by immunofluorescence. With PDLSC as the control group, the effects of vesicles on the viability of PDLSC were detected by cell activity assay (cell counting kit-8), and the effects of vesicles on the osteogenic differentiation potential of PDLSC were detected by alizarin red staining and Western blotting.Results:Vesicles in MVs, O-MVs, CVMs and O-CVMs were all observed with a round structure (size 50-250 nm), and could be taken up by PDLSC without affecting the cell viability. Under osteogenic inducing conditions, PDLSC incubated with O-MVs or O-CVMs could produce more mineralized nodules than those in the control group (PDLSC). MVs, O-MVs, CVMs and O-CVMs could promote the expression of osteogenic-related proteins in PDLSC. PDLSC in group O-CVMs showed significant higher expressions of osteogenic-related proteins, including alkaline phosphatase (ALP) (1.571±0.348), osteopontin (OPN) (1.827±0.627) and osteocalcin (OCN) (1.798±0.537) compared to MVs (ALP: 1.156±0.170, OPN: 1.260±0.293, OCN: 1.286±0.302) ( P<0.05). Compared to CMVs-incubated PDLSC, O-CVMs-incubated PDLSC expressed more Runt-related transcription factor 2 (1.632±0.455 vs 1.176±0.128) and OPN (1.827±0.627 vs 1.428±0.427) ( P<0.05). Moreover, there was no significant difference in the expression levels of osteoblast-related proteins in PDLSC cultured with MVs, O-MVs and CVMs ( P>0.05). Conclusions:The vesicle mimetics prepared by mechanical extrusion method are similar in shape and size to the extracellular matrix vesicles. MVs, O-MVs, CVMs and O-CVMs do not affect the cell viability of PDLSC, and can promote the osteogenic differentiation potential of PDLSC to a certain extent.

The implementation of ideological and political education in medical colleges and universities should be combined with the talent cultivation goals of medical education,in line with the internal needs of medical career development and scientific research ethics construction,and enhance the pertinence and effectiveness of education.Medical students in the new era should be rich in"benevolence"and have firm political beliefs in their ideology,be full of"benevolent skills"and abide by professional ethics and morality.Therefore,it's an important measure for medical colleges and universities to carry out the innovations of ideological and political education in the integration of political beliefs and professional ethics that are guided by political beliefs and based on professional ethics.To enhance the effect of"integration",comprehensive policies need to be implemented from the aspects of educational content,educational field,educational form,and educational team,to achieve the"organic integration"and"mutual penetration"of political belief education and professional ethics education,as well as create a new model of ideological and political education in medical colleges and universities.