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.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To assess the effectiveness of the evaluation of military physical function(EMPF)system in predicting the occurrence of military training injuries among new recruits to provide scientific guidance and methodological choice for military training.Methods A total of 527 new recruits from 5 grassroots units from July 2016 to February 2018 were selected for the study.The recruits underwent EMPF testing,and their military training injuries were monitored over a 2-year follow-up period.Those who sustained injuries during training were divided into injury group(n=163),while the remaining recruits were placed in healthy group(n=364).The predictive ability of the total EMPF score for training injuries was assessed using the receiver operating characteristic curve(ROC),and the correlation between the total EMPF score,individual test scores,and military training injuries were analyzed using binary logistic regression.Results The total EMPF score of new recruits in injury group(19.52±1.97)was significantly lower than that of healthy group(24.31±1.54)(P<0.001),which also demonstrated a high diagnostic value in predicting the risk of military training injuries,with an area under the curve(AUC)of ROC of 0.971(P<0.001).A cut-off value of 22 scores was found to have the highest accuracy in predicting future training injuries,with an odds ratio(OR)of 25.63,sensitivity of 0.939,specificity of 0.879,positive likelihood ratio of 7.76,and a post-test probability of 0.67.Binary logistic regression analysis revealed that 6 EMPF tests,including holding the ball over and leaning back,bending forward and touching the ground with the ball,lunge squat and twist,swallow balance with holding the ball afterward,vertical jump,and respiratory pattern assessment,were negatively associated with the risk of military training injuries(P<0.0001).Conclusion The EMPF system can effectively predict the risk of military training injuries,with military personnel whose total EMPF score is less than 22 being at higher risk of sustaining such injuries.

Objective:To investigate the safety of early whole body computed tomography (WBCT) combined with coronary angiography (CAG) in patients with extracorporeal cardiopulmonary resuscitation (ECPR) and its application value in the diagnosis of cardiac arrest and complications of cardiopulmonary resuscitation (CPR).Methods:This was a retrospective study. Patients who underwent ECPR in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2021 were enrolled in this research. Patients younger than 18 years or with incomplete clinical data were excluded. The results of WBCT and CAG examinations after ECPR were collected.Results:A total of 89 patients with ECPR, aged (47±17) years, were enrolled in the study, all underwent WBCT examination, and no adverse events such as ECMO and tracheal tube shedding occurred. WBCT found 7 cases of pulmonary embolism, 3 cases of aortic dissection and 2 cases of cerebral hemorrhage. WBCT identified CPR-related complications in 42 cases, including rib fractures ( n=20), pneumothorax ( n=5), mediastinal emphysema ( n=5), subcutaneous emphysema ( n=6), and hematoma or swelling at puncture site ( n=6). Fifty-five patients underwent CAG examination, the most common culprit vessels were the left anterior descending branch disease (58.2%) followed by the left circumflex branch disease (27.3%), the right coronary artery disease (21.8%) and left main artery disease (12.7%). Conclusions:Early WBCT and CAG examinations are of great significance and safety for the guidance of treatment in ECPR patients.

Objective:To analyze whether lower anticoagulation intensity can reduce the incidence of complications in patients with extracorporeal membrane oxygenation (ECMO).Methods:Clinical data of 88 non-cardiac surgery patients who received ECMO support for more than 72 h were collected in the Extracorpical Life support Center of Jiangsu Province Hospital from March 2015 to March 2021. According to the average activated partial thromboplastin time (APTT) level on the third day of ECMO, the patients were divided into the APTT < 50 s group ( n=53) and APTT ≥50 s group ( n=35). The venovenous ECMO (VV-ECMO) subgroup was divided into the APTT <50 s group ( n=23) and APTT ≥50 s group ( n=10). The venoarterial ECMO (VA-ECMO) subgroup was divided into the APTT <50 s group ( n=30) and APTT≥50 s group ( n=25). The average daily transfusion volume of red blood cells during ECMO, the incidence of bleeding, the incidence of thrombosis and all-cause mortality were compared between the two groups. Results:There were no significant differences in the incidence of thrombosis and all-cause mortality in the APTT <50 s group compared with the APTT ≥50 s group ( P>0.05), but the incidence of bleeding and the daily transfusion volume of red blood cells were significantly decreased (7.5% vs. 35.7%; 0.50 U vs. 0.88 U) ( P < 0.05). In 33 VV-ECMO patients, the all-cause mortality, incidence of bleeding, average daily transfusion volume of red blood cells in the APTT <50 s group were lower than those in the APTT ≥50 s group, and the incidence of thrombosis was higher, but there was no statistical difference between the two groups ( P>0.05). In the 55 VA-ECMO patients, there were no significant differences in all-cause mortality, incidence of bleeding, thrombosis and average daily transfusion volume of red blood cells between the two groups ( P > 0.05). Conclusions:The lower anticoagulation intensity in patients without anticoagulation can reduce the occurrence of bleeding in ECMO patients. It is reasonable for such patients to have a lower anticoagulation intensity and studies with larger sample size need to be carried out.

Objective:To study the application of blood products in patients with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and evaluate its effect on the prognosis.Methods:A total of 83 adult patients treated with VA-ECMO in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from January 2017 to January 2020 were grouped by survival to explore the risk factors of 28-day mortality using binary logistic regression, and the threshold was calculated by ROC curve.Results:Platelet transfusion ( OR=2.506, 95% CI: 1.142-5.499) and non-myocarditis disease ( OR=6.881, 95% CI: 1.615-29.316) were the risk factors of 28-day mortality in adult VA-ECMO patients. The threshold of platelet transfusion was 0.427 mL/(kg·d) (sensitivity 78.4%, specificity 69.6% , AUC 0.735). Conclusions:The increased platelet transfusion is related to the poor prognosis of adult patients with VA-ECMO. Refractory myocarditis patients are better treated with VA-ECMO.

OBJECTIVE: To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation. METHODS: Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot. RESULTS: The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2. CONCLUSION The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.
Codon, Nonsense ; Factor IX/metabolism* ; HeLa Cells ; Humans ; Mutation ; RNA Splicing ; RNA, Messenger/metabolism*

Pituitary adenomas (PAs) are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. ErbB receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor (EGFR) can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1 ( LRIG1), a negative mediated gene of ErbB receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.
Animals ; Apoptosis ; genetics ; Brain Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MAP Kinase Signaling System ; genetics ; Membrane Glycoproteins ; biosynthesis ; genetics ; Mice ; Oncogene Protein v-akt ; biosynthesis ; Phosphatidylinositol 3-Kinases ; genetics ; Pituitary Neoplasms ; genetics ; pathology ; Xenograft Model Antitumor Assays ; raf Kinases ; biosynthesis ; genetics

Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group (P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin (r=-0.161, P=0.003) and OPG (r=-0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin (β=-0.165, P=0.009) and BMD (β=-0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX (β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.
Female ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Middle Aged ; Osteoporosis, Postmenopausal ; blood ; beta Catenin ; blood

Objective:This study aimed to clarify the correlation of SPRY4-IT1 expression with the clinicopathological character-istics and prognosis of patients with esophageal squamous cell carcinoma (ESCC), as well as the role of SPRY4-IT1 in promoting ES-CC cell growth. Methods:Quantitative real-time polymerase chain reaction for SPRY4-IT1 expression was performed on 50 paired can-cerous and adjacent non-cancerous esophageal specimens. Small interfering RNA was used to suppress SPRY4-IT1 expression to fur-ther explore its role in tumor progression. Cell viability was tested in vitro by MTT assay (OD=490 nm), and cell apoptosis and cell cy-cle were investigated by flow cytometry. Results:We found markedly elevated SPRY4-IT1 expression in cancerous tissues compared with adjacent non-cancerous tissues (90%, P<0.01). Relative SPRY4-IT1 expression levels were correlated with some clinicopathologi-cal characteristics, such as tumor size (χ2=5.333, P=0.021), elevated TNM (2009) stage classi fi cation (χ2=5.556, P=0.018), and de-creased overall survival rates (χ2=5.296, P=0.021). SPRY4-IT1 expression level was not correlated with patient age, gender, smoking status, or alcohol consumption (all P>0.05). Further experiments showed that SPRY4-IT1 expression levels were significantly higher in three ESCC cell lines than in the normal human esophageal epithelial cell line Het-1A. In vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of SPRY4-IT1 expression by small interfering RNA reduced cell growth, mediated cell cycle arrest at the G0-G1 phase, and promoted cell apoptosis (all P<0.01). Conclusion:SPRY4-IT1 was overexpressed in ESCC tissues and ESCC cell lines and promoted the growth of ESCC cells. The dysregulated expression of long non-coding RNA SPRY4-IT1 may play an important role in the process of ESCC development and may be developed as a useful biomarker for the diagnosis and prognosis of ESCC.