Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

OBJECTIVE To prepare Neuritic acid oral emulsion ，to optimize its formulation and preparation technology ，and to investigate its stability. METHODS Neuritic acid oral emulsion was prepared by mechanical method. On the basis of single factor experiment ，the appearance ，centrifugal stability ，centrifugal stability constant （Ke）and particle size of the emulsion as indexes，the formulation was optimized by orthogonal design ，taking the dosage of oleic acid ，octylphenol polyoxyethylene ether-10 and propylene glycol as factors ，the preparation technology was optimized by taking emulsification temperature ，shear time，pressure of high-pressure homogenization and cycle times of high-pressure homogenization as factors. The content of neuritic acid was determined by high performance liquid chromatography. The stability of Neuritic acid oral emulsion was investigated by high temperature test ，accelerated test and long-term test. RESULTS The optimal formulation and preparation technology were as follows：neuritic acid of 1 g，oleic acid of 5％ ，octylphenol polyoxyethylene ether- 10 of 4％ ，propylene glycol of 2％ ， emulsification temperature of 60 ℃ ，shear time of 2 min，homogenization pressure of 40 MPa and cycle times of twice. After three experiments ，the average particle size of Neuritic acid oral emulsion was 158.05 nm（RSD＝1.58％，n＝3），the average Ke was 0.39（RSD＝1.49％，n＝3），and the appearance was uniform milky white ，there was no stratification. The results of high temperature test showed that Neuritic acid oral emulsion was prone to stratification in high temperature environment ，and the content of neuritic acid increased. The results of accelerated test and long-term test showed that there was no significant change in the appearance or the content of neuritic acid when Neuritic acid oral emulsion was placed at room temperature for 6 months. CONCLUSIONS The formulation and preparation technology are stable and feasible ，and can be used for the preparation of Neuritic acid oral emulsion. Neuritic acid oral emulsion should not be placed in high temperature environment. It has good stability at room temperature for 6 months.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

This study is to report the establishment of an UPLC-MS/MS method for the determination of plasma concentration of UA carried in self-microemulsifying drug delivery system (SMEDDS) and its pharmacokinetics in rats. It was used for determination and analysis when serum with internal standard was extracted from C18 solid-phase column. Acquity UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 microm) was used for separation. The mobile phase was acetonitrile -0.1% ammonia with gradient elution at the flow rate of 0.2 mL x min(-1). The column temperature was 40 degrees C and the detection wave length was 210 nm. It was detected by negative ion using electrospray ionization source (ESI) and scanned by multiple reaction ion monitoring (MRM) mode. The liner relationship of UA was very good in the range of 1.19-3 815.00 ng x mL(-1) (r = 0.999 0). Recovery rate of different concentrations were 87.42%-89.95%. The precision of inter-day and intra-day were less than 11%. The method developed in our study was proved to be sensitive, rapid and simple. It is suitable for the pharmacokinetic study of UA-SMEDDS in rats.

OBJECTIVETo observe the injury in rat primary cultured neurons induced by Abeta(1-40) and the protective effects of combination of ginseng and ginko extracts.

METHODPrimary neurons were induced by Abeta(1-40) to establish the cell model of toxic injury. Using flow cytometry with Annexin V-FITC/PI double staining, MTP assay, transmission electron microscopy and Western blot, the appropriate concentration and duration of AP for cell model establishment were determined. The effects of extracts of ginseng and ginko (EGGB)on cellular proliferative activity, apoptotic rate, ultrastructure and caspase-3 expression were detected.

RESULTThe apoptotic rate was increased significantly after neurons were induced by 1 micromol x L(-1) Abeta(-40) for 24 h (P < 0.01). EGGB (5, 50 mg L(-1)) significantly enhanced the proliferative activity (P < 0.05). Meanwhile, EGGB (50 mg L(-1)) inhibited neuronal apoptosis and caspase-3 overexpression and improved cellular ultrastructure remarkably (P < 0.05, P < 0.01).

CONCLUSIONAbeta(1-40) could significantly induce primary cultured neurons to apoptosis in vitro. EGGB showed beneficial neuroprotective effects against neuronal apoptosis, which might be due to improving the structures of neuron and its subcellular organelles, enhancing cellular proliferative activity and inhibiting caspase-3 overexpression in neurons.

Alzheimer Disease ; drug therapy ; Amyloid beta-Peptides ; pharmacology ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation, Enzymologic ; drug effects ; Ginkgo biloba ; chemistry ; Male ; Neurons ; cytology ; drug effects ; metabolism ; ultrastructure ; Panax ; chemistry ; Peptide Fragments ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Time Factors