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.

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Life Style ; Pneumonia/etiology* ; Prognosis ; Risk Factors ; Smoking

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective To discuss the teaching method of staged target teaching(STT)combined with problem-based learning(PBL)in improving the effectiveness of cerebrovascular intervention training.Methods A total of 44 refresher doctors,who received cerebrovascular interventional training at the Department of Interventional Radiology of the First Affiliated Hospital of Zhengzhou University of China between March 2021 and March 2023,were enrolled in this study.Traditional teaching method was adopted for 20 refresher doctors(control group)and STT+PBL teaching method was adopted for the remaining 24 refresher doctors(study group).Before and after the training,the basic theoretical knowledge,operation skill,comprehensive interventional knowledge and the satisfaction survey were compared between the two groups.Results Before training the differences in the basic theoretical knowledge score and learning motivation between the two groups were not statistically significant(P＞0.05).After 6 months training the completion examination score of the study group was significantly better than that of the control group(P＜0.05).Through independently working in clinical practice for one year after training completion,the operation skill,basic theoretical knowledge and comprehensive ability of the study group were remarkably better than those of the control group(P＜0.05).Moreover,the scores of understanding ability,teacher-student interaction,communication skill,clinical thinking ability,self-learning ability,teamwork skill,knowledge mastery degree in the study group were strikingly higher than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion The combination teaching method of STT and PBL can significantly improve the quality and effectiveness of the training on the interventional treatment of cerebrovascular diseases.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Objective To explore the influencing factors of gastric cancer and construct the clinical prediction model.Methods From December 2020 to October 2023,the clinical data of 1000 patients with stomach neoplasm admitted to Putuo Hospital,Shanghai U-niversity of Traditional Chinese Medicine and Shuguang Hospital,Shanghai University of Traditional Chinese Medicine were collected.Af-ter data cleaning and eliminating abnormal values,the patients were divided into gastric polyps group(n=487)and gastric cancer group(n=479).Non-parametric test was used to screen out meaningful indicators,Lasso regression to screen out the characteristic factors re-lated to gastric cancer with non-zero coefficient,and stepwise Logistic regression analysis to screen out the factors with significant correla-tion,and Lasso-Logistic regression model was constructed.The receiver operator characteristic(ROC)curve was plotted to calculate the area under the curve(AUC)and the confusion matrix to evaluate the model efficiency.Results The results of multivariate Logistic re-gression analysis showed that age,white blood cell(WBC)count,monocyte(M)count,alanine amiontransferase(ALT),cancer anti-gen 724(CA724),cancer antigen 242(CA242),cancer antigen 50(CA50)and carcinoembryonic antigen(CEA)were independent factors affecting gastric cancer.Based on the results of multivariate Logistic regression analysis,the risk prediction nomogram model of gas-tric cancer was constructed.The AUC of test set was 0.91,the accuracy rate was 100％,and the recall rate was 100％;the AUC of valida-tion set was 0.93,the accuracy rate was 93.63％,and the recall rate was 74.1％.The model has good prediction efficiency.Conclusion In this study,8 common predictors of gastric cancer were constructed,and the Lasso-logistic regression prediction model had good differen-tiation,which could be used to complete the early screening of gastric cancer based on the physical examination reports of patients.

Objective:To explore the effects of 10Hz repetitive transcranial magnetic stimulation(rTMS)on verbal and spatial working memory with different loads in patients with stroke. Method:Twenty-nine patients with working memory impairments after the left hemisphere stroke were random-ly assigned into the rTMS group(n=14)and control group(n=15).The patients in the rTMS group were treated with 10Hz rTMS while the patients in the control group received sham stimulation.Before and after the intervention,digital/spatial N-back tasks and digit span forward(DSF)and digit span backward(DSB)tests were used to assess work memory.Montreal Cognitive Assessment(MoCA)and the Functional Indepen-dence Measure(FIM)was used to assess cognitive function. Result:There were statistically significant differences before and after the intervention in the scores of DSF,the accuracy rates of 1-back and 2-back tasks of digit and space,the scores of MoCA,attention,memory,executive function,and FIM for the rTMS and control groups,and the scores of DSB in the rTMS group(P＜0.05).Post-intervention differences in DSB,digit 1 and 2-back,spatial 2-back,FIM,MoCA total score,and subtests of memory and executive function were significant between the groups(P＜0.05).The linear mixed-ef-fect analysis showed that improvements in the accuracy rates of digital N-back tasks in the rTMS group were more affected by load compared to the control group(P＜0.05).Controlling for the confounding factors such as age and effects of different content working memory tasks,improvements in the accuracy rates of digital 1-back and 2-back tasks were positively correlated with the improvements in the score on FIM(P＜0.05),and the improvements of the digital 2-back task was positively correlated with the improvement of MoCA scores and executive function(P＜0.05). Conclusions:rTMS can significantly improve verbal and spatial working memory manipulation in stroke pa-tients,with more significant improvement in high cognitive demand working memory(2-back).In addition,the improvement in higher-load verbal working memory brought by rTMS is associated with the improvement in cognition,self-care,and survival ability of patients with stroke.