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.

Objective:To study the influence of image panel of different source image distances(SID)of beam central axis of Portal Dosimetry(PD)dose verification system on the verification of volumetric modulated arc therapy(VMAT)plan,so as to provide reference for dose verification in selecting the appropriate SID position and evaluation criteria.Methods:From July 2022 to May 2024,10 patients,who received radiotherapy on tumor at different-site in Specialized Medical Center of the Chinese People's Armed Police Force,were selected.All patients underwent VMAT.Ten simulated dose verification plans were established according to the data of patients,with a total of 10 arcs.The non-crystalline silicon image panel was calibrated at 0,-30,-40,-50 and-60 cm from the isocenter on the beam central axis,and the verification plans of PD system were established.Dose verification was carried out using electronic portal imaging device(EPID)(a-Si EPID)of non-crystalline silicon image panel that was onboard by accelerator.The γ pass rates under the standards of 3%/3 mm and 3%/2 mm were compared and analyzed.Results:Under the evaluation standard of 3%/3 mm,the γ pass rates of the collected doses were(98.93±0.81)%,(94.77±9.00)%,(92.18±11.34)%,(89.72±12.54)%and(87.05±13.06)%when the SID values were respectively 100,130,140,150 and 160 cm,which were all higher than these under the evaluation standard of 3%/2 mm,and the differences were statistically significant(t=2.75,3.44,3.59,4.16,6.47,P<0.05).There were significant differences between the average γ pass rate of the collected dose under evaluation standards of 3%/3 mm and 3%/2 mm when SID was 100cm,and the 100%of γ pass rate(t=-3.21,-3.62,P<0.05),while the differences of the obtained γ pass rates among other SID positions were not statistically significant(P>0.05).Conclusion:Under the evaluation standards of 3%/3 mm and 3%/2 mm,the γ pass rate of the collected dose at SID 100 cm is the highest.The γ pass rate of the collected dose at SID 130 cm can meet the basically clinical requirements.In EPID dose verification,the collection for dose should be prioritized for selection when SID was 100 cm,and the γ pass rate of dose verification is higher,the influence of interference is less at this time,which verification results have higher credibility.

Objective:To establish and evaluated a logistic regression model for predicting the acute biliary pancreatitis (ABP) based on liver-injury related indexes.Methods:Clinical data of 210 patients diagnosed with acute pancreatitis (AP) at the Affiliated Hospital of Jiangnan University from October 2020 to December 2022 were retrospectively analyzed, including 113 males and 97 females, with a median age of 52 years (range, 43 to 58). Among these, 88 were diagnosed with ABP and 122 with acute non-biliary pancreatitis (ANBP). Additionally, a test cohort was created using data from 101 AP patients diagnosed between January and December 2023, including 60 males and 41 females, with a median age of 53 years (range, 43 to 63). Based on the original dataset, univariate and multivariate logistic regression analyses were conducted to identify the factors influencing ABP. A prediction probability formula (Pre) was then established based on the multivariate results. The effectiveness of each indicator in predicting ABP was evaluated using the receiver operating characteristic (ROC) curve. The ROC curve analysis determined the optimal cutoff value of Pre, which was subsequently used to diagnose ABP and ANBP in the test cohort.Results:Multivariate logistic regression analysis showed the factors influencing ABP include direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), and fibrinogen (FIB). Based on the multivariate analysis results, the prediction probability formula (Pre) for ABP was established as follows: P=1/{1+ exp[-(4.807+ 0.134×DBIL-1.859×AST/ALT-0.0003×CHE-0.387×FIB)]}. ROC curve analysis revealed that the area under the curve (AUC) for Pre in predicting ABP was 0.858, with an optimal cutoff value of 0.56, at which the sensitivity was 69.3% and the specificity was 91.0%. Using the cutoff value of 0.56 for Pre, ABP was diagnosed when Pre≥0.56 and ANBP was diagnosed when Pre<0.56. This criterion was applied to diagnose patients in the test cohort, where the sensitivity and specificity of Pre for diagnosing ABP were 86.1% and 92.3%, respectively.Conclusion:The logistic regression model based on liver injury-related indicators is a valuable tool for clinically assessing the incidence of ABP.

A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) represent a diverse family of secreted metalloproteinases, comprising 19 distinct members categorized into five groups based on their substrate specificity: proteoglycanases, procollagen N-peptidases, von Willebrand factor-cleaving protease, cartilage oligomeric matrix proteases and other proteases. Among these, ADAMTS proteoglycanases predominantly target hyalectans, pivotal components in extracellular matrix (ECM) remodeling and inflammation. Dysfunction of ADAMTS proteoglycanases disrupts the structure and function of hyalectans, thereby perturbing ECM homeostasis, resulting in reproduction disorders, including abnormal follicular development, ovulation dysfunction, impaired implantation, placentation and preterm labor. Hence, investigation of the role of ADAMTS proteoglycanases offers valuable insights into the molecular mechanisms underlying the physiological or pathological processes within the female reproductive system, thereby paving the way for innovative strategies in predicting, preventing and treating reproductive system diseases. This review summarizes the recent research advances in the structure and regulation of ADAMTS proteoglycanases and their role in female reproductive system.
Humans ; Female ; ADAMTS Proteins/physiology* ; ADAM Proteins/physiology* ; Pregnancy ; Animals ; Genitalia, Female/enzymology* ; Extracellular Matrix/metabolism*

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

Objective:To study the influence of image panel of different source image distances(SID)of beam central axis of Portal Dosimetry(PD)dose verification system on the verification of volumetric modulated arc therapy(VMAT)plan,so as to provide reference for dose verification in selecting the appropriate SID position and evaluation criteria.Methods:From July 2022 to May 2024,10 patients,who received radiotherapy on tumor at different-site in Specialized Medical Center of the Chinese People's Armed Police Force,were selected.All patients underwent VMAT.Ten simulated dose verification plans were established according to the data of patients,with a total of 10 arcs.The non-crystalline silicon image panel was calibrated at 0,-30,-40,-50 and-60 cm from the isocenter on the beam central axis,and the verification plans of PD system were established.Dose verification was carried out using electronic portal imaging device(EPID)(a-Si EPID)of non-crystalline silicon image panel that was onboard by accelerator.The γ pass rates under the standards of 3%/3 mm and 3%/2 mm were compared and analyzed.Results:Under the evaluation standard of 3%/3 mm,the γ pass rates of the collected doses were(98.93±0.81)%,(94.77±9.00)%,(92.18±11.34)%,(89.72±12.54)%and(87.05±13.06)%when the SID values were respectively 100,130,140,150 and 160 cm,which were all higher than these under the evaluation standard of 3%/2 mm,and the differences were statistically significant(t=2.75,3.44,3.59,4.16,6.47,P<0.05).There were significant differences between the average γ pass rate of the collected dose under evaluation standards of 3%/3 mm and 3%/2 mm when SID was 100cm,and the 100%of γ pass rate(t=-3.21,-3.62,P<0.05),while the differences of the obtained γ pass rates among other SID positions were not statistically significant(P>0.05).Conclusion:Under the evaluation standards of 3%/3 mm and 3%/2 mm,the γ pass rate of the collected dose at SID 100 cm is the highest.The γ pass rate of the collected dose at SID 130 cm can meet the basically clinical requirements.In EPID dose verification,the collection for dose should be prioritized for selection when SID was 100 cm,and the γ pass rate of dose verification is higher,the influence of interference is less at this time,which verification results have higher credibility.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.