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.

Objective:To establish and assess the quality control and improvement system for metabolic and bariatric surgery in Beijing.Methods:Based on relevant documents from the National Health Commission and the Beijing Municipal Health Commission,and referencing the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) by the American Society for Metabolic and Bariatric Surgery,a quality control system was developed under the Beijing Quality Control and Improvement Center of Metabolic and Bariatric Surgery. The system incorporated on-site evaluations,data registration,and specialized training. From May to December 2023,on-site assessments were conducted at 21 hospitals in Beijing performing bariatric surgery,evaluating personnel qualifications,infrastructure,clinical workflows,and postoperative follow-up. A quality control database was created to collect real-time surgical data,and training was provided for data entry and professional skills. Assessment results were classified as excellent,qualified,or needing improvement,with rectification suggestions offered and follow-up visits conducted to track progress.Results:All 21 hospitals achieved a 100% compliance rate for surgical indications, 16 (76.2%) met standardized surgical operation criteria,and 14 (66.7%) had standardized postoperative management. However,only 5 (23.8%) achieved a 12-month postoperative follow-up rate of ≥60%,and 4 (19.1%) had established specialized databases. Key challenges included insufficient specialized staffing (19.1%), lack of multidisciplinary collaboration (47.6%), inadequate equipment (57.1%), and low follow-up rates (57.1%). The database collected data from over 2 000 patients across 111 fields. After rectification, specialized database coverage rose to 61.9% (13 hospitals). Multi-level training programs developed backbone physicians and specialized nurses,significantly addressing the shortage of specialized personnel.Conclusion:The quality control system established in this study,through the integration of on-site evaluation,data registration,and specialized training,effectively enhances the standardization of surgical practices and data management capabilities.

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:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

AIM To investigate the effects of Jisuishang Formula on neurological function and ferroptosis in a rat model of cervical spondylotic myelopathy(CSM).METHODS The CSM rat models were established and randomly assigned to the model group,the Fer-1 group(2 g/kg Ferrostatin-1 via intraperitoneal injection),the low-dose(9.7 g/kg,intragastrically),medium-dose(19.4 g/kg,intragastrically)and high-dose(38.8 g/kg,intragastrically)Jisuishang Formula groups,and the sham operation group,with 6 rats in each group.Following 4 weeks of treatment administration,BBB locomotor scores and oblique plate test result were recorded to assess their neurological function in rats.Histopathological evaluation utilized HE staining for spinal cord tissue pathology,Nissl staining for Nissl body visualization,and Prussian blue staining for iron ion deposition analysis.Protein expressions of Nrf2,SLC7A11,GPX4,HO-1,TFRC and Cox2 in spinal cord tissues was detected by immunofluorescence and Western blot,while mRNA expressions were quantified using RT-qPCR.RESULTS Compared to the sham group,the CSM model group exhibited significantly reduced BBB locomotor scores and inclined plane test performance at 1,2 and 4 weeks post-operation(P＜0.05);obvious tissue cavitation,cellular edema and Prussian blue positive iron deposition in spinal cord tissues;downregulated protein and mRNA expressions of Nrf2,SLC7A11,GPX4,HO-1(P＜0.05);and upregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).Compared to the model group,the Jisuishang Formula and Fer-1 intervention groups showed significantly improved BBB scores and inclined plane test result at 1,2 and 4 weeks post-operation(P＜0.05);reduced tissue cavitation,attenuated cellular edema and decreased Prussian blue positive iron deposition in spinal cord tissues;upregulated protein and mRNA expression of Nrf2,SLC7A11,GPX4 and HO-1 in spinal cord tissues(P＜0.05);and downregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).CONCLUSION Targeting the Nrf2/SLC7A11/GPX4 signaling pathway,Jisuishang Formula potentially suppresses ferroptosis and alleviates iron accumulation in spinal cord neurons,thereby improving neurological recovery in CSM rats.

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Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

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 explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.