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.

In response to the clinical needs of cancer treatment and rehabilitation, Professor Lin Hongsheng proposed the Wuzhi Wuyang (five treatments and rehabilitation) concept on the basis of years of clinical experience and the Guben Qingyuan (consolidate the foundation and clear the source) theory. Wuzhi Wuyang emphasizes the importance of treatment and rehabilitation and aims to provide personalized and stage-specific treatment and rehabilitation plans by integrating the advantages of traditional Chinese medicine (TCM) and modern medicine to achieve comprehensive life-cycle management for patients with cancer. The proposal of Wuzhi Wuyang has provided new ideas and methods for the treatment, prevention, and rehabilitation of cancer, along with valuable references for clinical practice and academic research. This article summarizes the connotation of Wuzhi Wuyang and its application in the comprehensive management of cancer prevention and treatment with TCM.

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Objective:To discuss the enhancing effect of cordycepin on ferroptosis inducer RSL3-induced ferroptosis in the hepatocellular carcinoma HepG2 cells,and to clarify its potential mechanism.Methods:The HepG2 cells were divided into control group,RSL3 group,low,medium and high doses of cordycepin groups,RSL3+low,medium and high doses of cordycepin groups,RSL3+medium-dose cordycepin+ferroptosis inhibitor Ferrostatin-1(Fer-1)group,and RSL3+medium-dose cordycepin+ferroptosis inhibitor Liproxstatin-1(Lip-1)group.The HepG2,Huh-7 and HCCLM3 cells were treated with 0,1,5,10,15 and 20 μmol·L-1 RSL3 for 24,48 and 72 h,respectively.Cell counting kit-8(CCK-8)method was used to detect cell viability and determine the optimal concentration and treatment time of RSL3.The HepG2 cells were treated with 0,50,100,200,400,600,800,1 000,and 1 200 μmol·L-1 cordycepin for 24,48 and 72 h,respectively.CCK-8 method was used to detect the survival rate of the cells and the half maximal inhibitory concentration(IC50)was calculated to determine the optimal concentration and treatment time of cordycepin;the apoptosis inhibitor Z-VAD-FMK,autophagy inhibitor Chloroquine(CQ),necroptosis inhibitor Necrostatin-1(Nec-1),Fer-1,Lip-1,Deferasirox and 2,2,6,6-tetramethylpiper idinoxy(TEMPO)were used to treat HepG2 cells,and the survival rate of the cells was calculated;2',7'-Dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect reactive oxygen species(ROS)levels in the HepG2 cells in various groups;C11 BODIPY 581/591 fluorescence probe was used to detect lipid peroxidation(LPO)levels in the HepG2 cells in various groups;FeRhoNox-1 fluorescent probe was used to detect ferrous ion(Fe2+)levels in the HepG2 cells in various groups;kits were used to detect glutathione(GSH)and malondialdehyde(MDA)levels in the HepG2 cells;Western blotting method was used to detect the expression levels of ferroptosis-related proteins,nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in the hepG2 cells in various groups;transmission electron microscope was used to observe the ultrastructural morphology of the HepG2 cells in various groups.Results:The CCK-8 results showed that when the cells were treated with 0.56 μmol·L ?1 RSL3,the viabilities of the three cell types differed significantly.Compared with 0 μmol·L?1 RSL3 group,the survival rates of the cells in 6.4 and 12.8 μmol·L-1 RSL3 groups were significantly decreased(P<0.05).The HepG2 cells had the highest IC50 value and were selected for subsequent experiments.Compared with 0 μmol·L-1 cordycepin group,the survival rates of the HepG2 cells in 200,400,600,800,1 000,and 2 000 μmol·L-1 cordycepin groups were significantly decreased(P<0.05 or P<0.01).0.5×IC50(267.9 μmol·L-1),1×IC50(535.8 μmol·L-1)and 1.5×IC50(803.7 μmol·L-1)were selected as low,medium and high doses of cordycepin groups,respectively,with an intervention time of 24 h.Compared with control group,the survival rates of the HepG2 cells in low,medium,and high doses of cordycepin groups were significantly decreased(P<0.05).Compared with low,medium,and high doses of cordycepin groups,the survival rates of the HepG2 cells in Z-VAD-FMK+low,medium,and high doses of cordycepin groups were significantly increased(P<0.01),and those in Fer-1+medium and high doses of cordycepin groups and Lip-1+low,medium,and high doses of cordycepin groups were significantly increased(P<0.05).Compared with control group,the survival rates of the HepG2 cells in RSL3 group,RSL3+low,medium,and high doses of cordycepin groups,RSL3+cordycepin+Fer-1 group and RSL3+cordycepin+Lip-1 group were significantly decreased(P<0.05 or P<0.01).Compared with RSL3 group,the survival rates of the HepG2 cells in RSL3+low,medium,and high doses of cordycepin groups were significantly decreased(P<0.05).The DCFH-DA results showed that compared with control group,the ROS levels in the cells in medium and high doses of cordycepin groups,RSL3 group and RSL3+low,medium,and high doses of cordycepin groups were significantly increased(P<0.05 or P<0.01).The C11 BODIPY 581/591 results showed that compared with control group,the LPO levels in the HepG2 cells in medium and high doses of cordycepin groups,RSL3 group and RSL3+low,medium and high doses of cordycepin groups were significantly increased(P<0.05 or P<0.01).Compared with RSL3 group,the LPO levels in the HepG2 cells in RSL3+low,medium,and high doses of cordycepin groups were significantly increased(P<0.05 or P<0.01).The FeRhoNox-1 results showed that compared with control group,the Fe2+levels in the HepG2 cells in medium and high doses of cordycepin groups,RSL3 group and RSL3+low,medium,and high doses of cordycepin groups were significantly increased(P<0.05 or P<0.01).Compared with RSL3 group,the Fe2+levels in the HepG2 cells in RSL3+low,medium,and high doses of cordycepin groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the MDA levels in the HepG2 cells in high doses of cordycepin group,RSL3 group and RSL3+low,medium,and high doses of cordycepin groups were significantly increased(P<0.05 or P<0.01).Compared with RSL3 group,the MDA levels in the HepG2 cells in RSL3+low,medium,and high doses of cordycepin groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the GSH levels in the HepG2 cells in medium and high doses of cordycepin groups,RSL3 group and RSL3+low,medium,and high doses of cordycepin groups were significantly decreased(P<0.05 or P<0.01).Compared with RSL3 group,the GSH levels in the HepG2 cells in RSL3+low,medium,and high doses cordycepin groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the ultrastructure of the HepG2 cells in low and medium doses of cordycepin groups showed no significant changes,while the cells in high dose of cordycepin group exhibited reduced mitochondrial cristae,mild swelling and increased membrane density,with slightly distorted inner membrane structure.The cells in RSL3 group and RSL3+low,medium,and high doses of cordycepin groups all showed ultrastructural changes characteristic of ferroptosis.Compared with RSL3 group,the cells in RSL3+low,medium,and high doses of cordycepin groups exhibited ruptured mitochondrial membranes with increased membrane density,abnormally twisted or expanded inner membrane structures,and reduced or even disappeared mitochondrial cristae.The Western blotting results showed that compared with control group,the expression levels of FTH1 and GPX4 proteins in the HepG2 cells in medium and high doses of cordycepin groups were significantly decreased(P<0.05 or P<0.01),while the expression levels of Nrf2 and HO-1 proteins were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression levels of GPX4 protein in the HepG2 cells in low,medium and high doses of cordycepin groups,RSL3 group,and RSL3+cordycepin+Fer-1 group were significantly decreased(P<0.05).Compared with RSL3 group,the expression levels of GPX4 protein in the HepG2 cells in RSL3+low,medium,and high doses of cordycepin groups were significantly decreased(P<0.05).Conclusion:Cordycepin can significantly enhance RSL3-induced ferroptosis in the hepatocellular carcinoma HepG2 cells and down-regulate the expression of Nrf2 and HO-1 proteins in the HepG2 cells.

Objective:The components of Rubus parvifolius L. were analyzed based on UPLC-MS/MS technology and combined with network pharmacology analysis to explore the mechanism of action of Rubi Parvifolii Radix in treating inflammation, cough, fever, influenza and sore throat. Method:The chemical constituents of Rubi Parvifolii Radix were identified according to the information of mass spectrometry. The network pharmacology was used to analyze the corresponding targets and related pathways of its chemical components, and the "component-target-pathway" interaction diagram was drawn. PyMOL 2.5.7 software wasused to perform molecular docking between active components and key targets.Results:Twenty chemical components were identified by UPLC-MS/MS, and 15 components were screened out by network pharmacology, which can be used as quality markers of Rubi Parvifolii Radix, namely Azelaic acid, Procyanidol B3, Caprolactam, Bis (2-ethylhexyl) adipate, Cryptochlorogenic acid, 3-O-Feruloylquinic, Ellagic acid, Aurantiamide acetate, 2 α,3 β,19 α,23-Tetrahydroxyurs-12-en-28-oic acid, L-Epicatechin, (E)-3-Indoleacrylic acid, Euscaphic acid, Suberic acid, Diisononyl phthalate and Prodelphinidin T4. Molecular docking showed that 5 compounds compared with the reference substance could bind to the target proteins of disease well. Conclusions:The 15 active ingredients in Rubi Parvifolii Radix, including Caprolactam and (E)-3-Indoleacrylic acid, may play a therapeutic role in treating colds, high fever, sore throat, and inflammation by acting on targets such as AKT1 and TNF. This provides a certain reference for the clinical application of Rubi Parvifolii Radix.

OBJECTIVE To establish a rapid method for determining of acid yellow 36 in moxibustion. METHODS Based on the principle of acid yellow 36 as an acid-base indicator and discoloration in the pH range of 1.2(red) to 2.3(yellow), 15% sulfuric acid solution was used as the color developing agent to screen the ethanol extract of the sample, and then HPLC method was used to verify the suspicious positive samples in the initial screening, and finally LC-MS method was used to confirm the accuracy of the established rapid physicochemical detection method. RESULTS The established method was applied to 67 batches of samples, and 3 positive samples were detected. The results were consistent with those of HPLC and LC-MS. CONCLUSION The method is accurate and sensitive, which can be used for rapid detection of acid yellow 36 in moxibustion.

Based on the theoretical reflection on the reflective function of medical records,the important findings in the practice of medical records writing in the field of palliative care,and conceptual analysis of narrative medicine tools,combined with empirical investigation materials and analysis,this paper focused on the practice of medical records writing for reflection and research.The main contents include defining the concept of narrative medical records,which are medical records used in clinical practice that incorporate narrative content;clarifying their characteristics and functions at different levels;and exploring practical paths for their application in clinical practice.Based on an in-depth exploration of the uniqueness of narrative medicine practice at Peking Union Medical College,it also emphasized the necessity of writing medical records with narrative thinking.Specifically,it focused on using narrative thinking and forms to enhance the improvement of current medical records writing,and further sought a general framework and multiple possibilities for narrative medicine clinical pathways.

OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.

Objective To explore whether ferulic acid can inhibit the progression of T-cell acute lymphoblastic leukemia in vivo and in vitro by regulating PTEN/PI3K/AKT signaling pathway.Methods The T-cell acute lymphoblastic leukemia Jurkat cells were divided into the control group,the ferulic acid treatment group and the LY294002 treatment group for in vitro experiment.The cells in the control group were given normal culture;cells in the ferulic acid treatment group were given different concentrations(1.25,2.5,5,10,20,40,80,160 μmol/L)of ferulic acid,respectively,and the cell proliferation was detected by CCK-8 method,to screen the experimental concentration;cells in the LY294002 treatment group were given 50 μmol/L PI3K/AKT inhibitor LY294002.The cells proliferation,apoptosis and invasion were detected by clone formation assay,flow cytometry and Transwell assay.The relative expression levels of nuclear protein Ki67,proliferating cell nuclear antigen(PCNA),cleaved caspase-3,cleaved caspase-9,E-cadherin,N-cadherin,Vimentin,PTEN,p-PI3K,PI3K,p-AKT and AKT proteins were detected by Western blot.The nude mice models of transplanted tumors were constructed by 30 male BALB/c nude mice,and they were averagely divided into the normal group and the ferulic acid treatment group for in vivo experiment.The normal group was given normal saline by gavage,while the ferulic acid treatment group was given 75 mg/kg ferulic acid by gavage after inoculating Jurkat cells.The weight and volume changes of transplanted tumors were compared,and the levels of Ki67,cleaved caspase-3/caspase-3,E-cadherin,N-cadherin,PTEN,p-PI3K,PI3K,p-AKT and AKT in tumor tissues were detected.Results In vitro experiment,compared with the control group,the clone formation rate of cells,number of invasion cells,Ki67,PCNA,N-cadherin,Vimentin,p-PI3K/PI3K and p-AKT/AKT in the 5,10,20 μmol/L ferulic acid treatment group and the LY294002 treatment group were significantly decreased(P<0.05),while the apoptosis rate,cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,E-cadherin and PTEN were significantly increased(P<0.05).In vivo experiment,compared with the normal group,the weight and volume of tumors were reduced in the ferulic acid treatment group,Ki67,N-cadherin,p-PI3K/PI3K and p-AKT/AKT in tumor tissues were significantly decreased,cleaved caspase-3/caspase-3,E-cadherin and PTEN were significantly increased,with statistically significant differences(P<0.05).Conclusion Ferulic acid can inhibit the proliferation and invasion of T-cell acute lymphoblastic leukemia Jurkat cells in vivo and in vitro,and induce apoptosis,its mechanism may be related to the regulation of PTEN/PI3K/AKT signaling pathway.

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.