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.

OBJECTIVES: To establish a prognostic model for primary liver cancer (PLC) using bioinformatics methods. METHODS: Based on the data from 404 patients in the Cancer Genome Atlas (TCGA) database, we constructed a prognostic model integrating the differentially expressed genes, anoikis, and immune-related genes (DAIs) using univariate Cox regression and the LASSO-Cox approach. The predictive ability of the model was evaluated using Kaplan-Meier method and receiver-operating characteristic curves, and a nomogram was developed to facilitate its clinical applications. Gene set enrichment analysis (GSEA) was performed to explore the associated pathways and relationship between the DAIs and the tumor immune microenvironment, and the half-maximal inhibitory concentration (IC₅₀) of liver cancer drugs was calculated using the "pRRophetic" R package. We also detected the expression of SEMA7A in paired tumor and adjacent tissues from liver cancer patients. RESULTS: We constructed and validated a prognostic model based on 7 DAIs (NR4A3, SEMA7A, IL11, AR, BIRC5, EGF, and SPP1), and obtained consistent results in both the TCGA training cohort and GEO validation cohort (GSE14520), where the patients in the low-risk group were characterized by more favorable clinical outcomes and immune status. By integrating this prognostic signature with clinical information, a composite nomogram was generated. Somatic mutation analysis showed that TTN, TP53, and CTNNB1 mutations accounted for the largest proportion of total mutations, and the patients in the low-risk-low-TMB group had higher survival rate. Drug sensitivity analysis revealed differences in sensitivity to chemotherapeutic agents between high- and low-risk groups and between TP53 mutations and non-mutations. In clinical tissue specimens, SEMA7A expression was significantly higher in liver cancer tissues than in the adjacent tissues. CONCLUSIONS We established a new prognostic model based on DAIs for predicting clinical outcomes and therapeutic response of patients with primary liver cancer.
Humans ; Liver Neoplasms/diagnosis* ; Prognosis ; Anoikis ; Nomograms ; Computational Biology ; Tumor Microenvironment ; Semaphorins/metabolism*

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.

Objective To evaluate the efficacy and safety of polyene phosphatidylcholine injection in the treatment of liver disease.Methods Pubmed,Embase,The Cochrane Library,ClinicalTrial.gov,CNKI,SinoMed,VIP,and WanFang Data were electronically searched to collect randomized controlled trials(RCTs)of polyene phosphatidylcholine injection in the treatment of liver disease from inception to December 31st,2022.Two researchers independently screened literature,extracted data and assessed the risk of bias of the included studies.The Meta-analysis was performed using Stata 17.0 software.Results A total of 10 RCTs were included,including 809 patients.Meta-analysis showed that the effective rate in the polyene phosphatidylcholine injection group was higher than that in the control group(RR=1.12,95％CI 1.04 to 1.20,P=0.003 8).Compared with the control group,polyene phosphatidylcholine injection could decrease ALT level(MD=-18.92 U/L,95％CI-27.75 to-10.09,P＜0.001),AST level(MD=-31.19 U/L,95％CI-46.27 to-16.11,P=0.000 1),TBiL level(MD=-7.31 μmol/L,95％CI-10.75 to-3.88,P＜0.001),and GGT levels(MD=-48.93 U/L,95％CI-54.64 to-43.21,P＜0.001).Only one study reported mild adverse events,and six studies reported no severe adverse events in patients.Conclusion Current evidence shows that polyene phosphatidylcholine injection in the treatment of alcoholic liver disease can increase the effective rate,improve the levels of liver function indicators(ALT,AST,TBiL,and GGT),and has less adverse events.Due to the limited number and quality of included studies,the above conclusions need to be verified by more high-quality studies.

Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery.Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients,and is widely recommended as a first-line clinical treatment.But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices.To address this issue,this consensus,based on a comprehensive literature review and clinical experiences of experts,systematically summarizes the indications,target patients,and contraindications of minimally invasive tooth extraction,the overall workflow of this procedure(preoperative preparation,surgical steps,postoperative management,postoperative instructions,medications,and follow-up),and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery.Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients,and is widely recommended as a first-line clinical treatment.But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices.To address this issue,this consensus,based on a comprehensive literature review and clinical experiences of experts,systematically summarizes the indications,target patients,and contraindications of minimally invasive tooth extraction,the overall workflow of this procedure(preoperative preparation,surgical steps,postoperative management,postoperative instructions,medications,and follow-up),and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

Objective:To evaluate the value of the skeletal muscle index (SMI) and psoas major muscle index(PMI) measured at the third lumbar vertebra(L3) level in the evaluation on nutritional status and prognosis of cirrhosis patients with ascites.Methods:The clinical data of 102 patients with cirrhosis and ascites treated in our department between September 2018 and September 2022 was analyzed retrospectively, the skeletal muscle and psoas muscle area at L3 level were measured, and L3-SMI and L3-PMI were calculated. According to L3-SMI, patients were divided into the sarcopenia group (62 cases) and the normal muscle mass group (40 cases). Differences between the two groups were compared in terms of L3-SMI, L3-PMI, body mass index (BMI), albumin, the rate of re-admissions and mortality during follow-up. The value of each index in nutritional assessment was also explored.Results:L3-SMI, L3-PMI, and albumin in the sarcopenia group were significantly lower than those in the normal muscle mass group, with statistical significance ( P<0.01).The BMI of the sarcopenia group was lower than that of the normal muscle mass group, but the difference was not significant ( P>0.05). L3-PMI showed better performance in nutritional assessment compared with albumin and BMI. The rate of re-admissions and the mortality rate in the sarcopenia group during the follow-up period were significantly higher compared with the normal muscle mass group ( P<0.05). Conclusion:L3-SMI and L3-PMI can effectively reflect the nutritional status of cirrhosis patients with ascites, and are promising indicators for prognosis prediction in cirrhosis patients with ascites.

Objective:To analyze the significance and factors influencing of CT scan under the modified Valsalva maneuver. Methods:Clinical data of 52 patients with hypopharyngeal carcinoma diagnosed from August 2021 to December 2022 were collected, all patients had calm breathing CT scan and modified Valsalva maneuver CT scan. Compare the exposure effect of the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall, and glottis with each CT scanning method. The effects of age, neck circumference, neck length, BMI, tumor site, and T stage on the exposure effect were analyzed. Results:In 52 patients, 50 patients（96.15%） completed CT scan at once time. The exposure effect of the CT scan under modified Valsalva maneuver in the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall was significantly better than CT scan under calm breathing（Z=-4.002, -8.026, -8.349, -7.781, -8.608, all P<0.01）, while CT scan under modified Valsalva maneuver was significantly worse in glottis than CT scan under calm breathing（Z=-3.625, P<0.01）. In the modified Valsalva CT scan, age had no obvious effect on the exposure effect. The exposure effect was better with long neck length, smaller neck circumference, smaller BMI and smaller T stage. The exposure of postcricoid carcinoma was better than pyriform sinus carcinoma and posterior hypopharyngeal wall carcinoma. But differences were not all statistically significant. Conclusion:The anatomical structure of the hypopharynx was clearly under CT scan with modified Valsalva maneuver, which clinical application is simple, but the effect of glottis was worse. The influence of age, neck circumference, neck length, BMI, and tumor T stage on the exposure effect still needs further investigation.
Humans ; Hypopharynx/diagnostic imaging* ; Valsalva Maneuver ; Hypopharyngeal Neoplasms/surgery* ; Tomography, X-Ray Computed ; Carcinoma

Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.