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.

BackgroundPatients with chronic schizophrenia often suffer from cognitive impairment. Traditional cognitive rehabilitation training has problems such as a single form and poor compliance， making it urgent to develop new cognitive intervention methods. ObjectiveTo explore the intervention effect of smartphone games on the cognitive function of patients with chronic schizophrenia， and to analyze the differences in cognitive function improvement between patients of different genders， in order to provide references for the cognitive function intervention of these patients. MethodsThis study was a prospective cohort study. A total of 30 patients who were hospitalized in the Psychiatry Department of Chaohu Hospital Affiliated to Anhui Medical University from March to October 2021， met the diagnostic criteria for schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）， and had a disease duration of above 5 years， were selected as the research subjects. All patients received smartphone game intervention for 12 weeks， 5 times a week， each session lasting 1 hour， in addition to conventional antipsychotic drug treatment. At the baseline and at 3， 6， 9， and 12 weeks of the intervention， the cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）， the Positive and Negative Syndrome Scale （PANSS） was used to assess mental symptoms， and the Problematic Mobile Gaming Questionnaire （PMGQ） was used to assess addiction symptoms. ResultsA total of 26 patients （86.67%） completed the study， including 13 females and 13 males. The time effects， group effects， and interaction effect between time and group for the immediate memory factor score of RBANS in the female group and the male group were all statistically significant （F=36.682， 5.712， 3.090， P<0.05 or 0.01）， and the time effects and group effects for the verbal and delayed memory factors as well as the total score in both groups were also statistically significant （F=3.841， 6.149， 15.372， P<0.05 or 0.01）. The time effects and group effects of the total score of PANSS in both groups had no statistical significance （F=2.041， 0.623， P>0.05 for both）， and the interaction effect between time and group was statistically significant （F=5.728， P<0.01）. The time effects， group effects， and interaction effect of the total score of PMGQ in both groups were all without statistical significance （F=2.672， 0.166， 0.642， P>0.05 for both）. ConclusionSmartphone game intervention may help improve the cognitive function of patients with chronic schizophrenia （especially immediate memory， verbal function， and delayed memory）， and the benefits are greater for female patients. The smartphone game intervention did not induce game addiction， but no significant improvement in psychotic symptoms was observed. ［Funded by Excellent Young Talents Support Program of Anhui Provincial Department of Education （number， gxyqZD2022022）； www.chictr.org.cn number， ChiCTR2100044113］

Objective To analyze the influencing factors for postoperative anastomotic leak (AL) in carcinoma of the esophagus and gastroesophageal junction and construct a nomogram predictive model. Methods The patients who underwent radical esophagectomy at Jinling Hospital Affiliated to Nanjing University School of Medicine from January 2018 to June 2020 were included in this study. Relevant variables were screened using univariate and multivariate logistic regression analyses. A nomogram was then developed to predict the risk factors associated with postoperative AL. The predictive performance of the nomogram was validated using the receiver operating characteristic (ROC) curve. Results A total of 468 patients with carcinoma of the esophagus and gastroesophageal junction were included in the study, comprising 354 males and 114 females, with a mean age of (62.8±7.2) years. The tumors were predominantly located in the middle or lower esophagus, and 51 (10.90%) patients experienced postoperative AL. Univariate logistic regression analysis indicated that age, body mass index (BMI), tumor location, preoperative albumin levels, diabetes mellitus, anastomosis technique, anastomosis site, and C-reactive protein (CRP) levels were potentially associated with AL (P<0.05). Multivariate logistic regression analysis identified age, BMI, tumor location, diabetes mellitus, anastomosis technique, and CRP levels as independent risk factors for AL (P<0.05). A nomogram was developed based on the findings from the multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was 0.803, indicating a strong concordance between the actual observations and the predicted outcomes. Furthermore, decision curve analysis demonstrated that the newly established nomogram holds significant value for clinical decision-making. Conclusion The predictive model for postoperative AL in patients with carcinoma of the esophagus and gastroesophageal junction demonstrates strong predictive validity and is essential for guiding clinical monitoring, early detection, and preventive strategies.

Background As one of the key populations in the prevention and treatment of iodine deficiency disorders, it is important to continuously monitor the iodine nutritional level of school-age children. The current reference interval for thyroid volume in China is based on age only, without taking into account differences in individual developmental levels, and the distribution of thyroid volume may vary regionally due to economic, demographic, and environmental factors. The current reference cut-off points for thyroid volume proposed by the World Health Organization are not based on the Chinese population. Objective To understand the iodine nutritional status and distribution of thyroid volume (Tvol) among children aged 8-10 years in Huangpu District, Shanghai, China, to identify impact factors of Tvol, and to propose a reference range upper limit for local thyroid health surveillance, so as to provide a basis for goiter control and prevention. Methods Six hundred children aged 8-10 years in Huangpu District were recruited in 2017, 2020, and 2023, and body height, weight, thyroid volume, urinary iodine, and iodine content of household edible salt were determined. A multilevel model was constructed using population density and area as regional variables, and age, body surface area (BSA), and body mass index (BMI) as potential impact factors for at the individual level, to assess their effects on thyroid volume. Quantile regression of thyroid volume was performed, and the 98th percentile (P₉₈) of thyroid volume was predicted based on age and BSA. Results The iodized salt coverage in the households of surveyed children in 2017, 2020, and 2023 was 72.0%, 57.0%, and 48.0%, respectively, and the iodized salt coverage decreased by year (χ²=24.31, P<0.001). The urinary iodine level of children in 2017 was higher than that in 2020 and 2023 (χ²=18.77, P<0.001). The Tvol medians of children in 2017, 2020, and 2023 were 2.29, 2.49, and 2.97 mL, respectively, and the Tvol increased by year (χ²=60.04, P<0.001). The proportion of goiter was higher in children in 2023 than in 2017 and 2020 (χ²=6.57, P<0.05). Sex differences were not statistically significant for urinary iodine levels, thyroid volume, and goiter. The median Tvol was 2.26, 2.58, and 2.76 mL in children of 8, 9, and 10 years old respectively, and the Tvol increased with age (χ²=49.02, P <0.001). Tvol was positively correlated with age, BSA, and BMI with correlation coefficients of 0.2846, 0.3723, and 0.2950, respectively. The final quantile regression model showed that the strongest effect of BSA was associated with the 98th percentile of Tvol. Multilevel models considering population density or area as regional variables failed to achieve convergence. Conclusion To establish the upper limit of the reference interval for thyroid volume of healthy children in Huangpu District, the effects of age and BSA should be considered at the individual level, and the upper limit of the normal interval for goiter screening is suggested to be the 98th percentile value of BSA at the same age. In addition, the adaptability of population density and regional area as indicators of regional aggregation of thyroid volume distribution still needs to be further explored.

Background: This study established sex-specific reference intervals (RIs) for hematological parameters, including the monocyte distribution width (MDW), in Korean adults and assessed the need for separate RIs according to sex in older adults. Methods: Hematological parameters were measured using a DxH 900 hematology analyzer (Beckman Coulter, USA) on 328 peripheral blood samples from 124 men and 204 women aged 19–93 years. Results: The RIs for white blood cells, red blood cells (RBCs), Hb, Hct, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, monocyte percentage, and neutrophil, eosinophil, lympho­cyte, and monocyte counts differed significantly by sex (P<0.05). Mean corpuscular volume was significantly positively associated with age, whereas RBC and platelet counts were significantly negatively correlated with age in both men and women. Age-based analysis revealed significant shifts in the RBC parameters beginning at 60 years of age in men and 70 years of age in women. The MDW did not show significant differences according to sex or age. Conclusions This study supports the use of sex-specific RIs and highlights the importance of considering age when interpreting results regarding hematological parameters in clinical practice.

BACKGROUND/OBJECTIVES: This study aimed to use plasma metabolites to identify clusters of breast cancer survivors and to compare their dietary characteristics and health-related factors across the clusters using unsupervised machine learning. SUBJECTS/METHODS: A total of 419 breast cancer survivors were included in this crosssectional study. We considered 30 plasma metabolites, quantified by high-throughput nuclear magnetic resonance metabolomics. Clusters were obtained based on metabolites using 4 different unsupervised clustering methods: k-means (KM), partitioning around medoids (PAM), self-organizing maps (SOM), and hierarchical agglomerative clustering (HAC). The t-test, χ2 test, and Fisher’s exact test were used to compare sociodemographic, lifestyle, clinical, and dietary characteristics across the clusters. P-values were adjusted through a false discovery rate (FDR). RESULTS: Two clusters were identified using the 4 methods. Participants in cluster 2 had lower concentrations of apolipoprotein A1 and large high-density lipoprotein (HDL) particles and smaller HDL particle sizes, but higher concentrations of chylomicrons and extremely large very-low-density-lipoprotein (VLDL) particles and glycoprotein acetyls, a higher ratio of monounsaturated fatty acids to total fatty acids, and larger VLDL particle sizes compared with cluster 1. Body mass index was significantly higher in cluster 2 compared with cluster 1 (FDR adjusted-PKM < 0.001; PPAM = 0.001; PSOM < 0.001; and PHAC = 0.043). CONCLUSION The breast cancer survivors clustered on the basis of plasma metabolites had distinct characteristics. Further prospective studies are needed to investigate the associations between metabolites, obesity, dietary factors, and breast cancer prognosis.

BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

BACKGROUND/OBJECTIVES: Rosa hybrida has been demonstrated to exert biological effects on several cell types. This study investigated the efficacy of the edible ethanol extract of R.hybrida (EERH) against human colorectal carcinoma cell line (HCT116) cells.MATERIALS/METHODS: HCT116 cells were cultured with different concentrations of EERH (0, 400, 600, 800, and 1,000 µg/mL) in Dulbecco’s modified Eagle medium. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide and viable cell counting assays. Cell cycle pattern was observed by flow cytometry analysis. The wound-healing migration assay, invasion assay, and zymography were used to determine the migratory and invasive level of HCT116 cells treated with EERH. The protein expression and binding ability level of HCT116 cells following EERH treatment were analyzed via immunoblotting and the electrophoretic mobility shift assay. RESULTS: EERH suppressed HCT116 cell proliferation, thus arresting the G1-phase cell cycle.It also reduced cyclin-dependent kinases and cyclins, which are associated with p27KIP1 expression. Additionally, EERH differentially regulated the phosphorylation of extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase, p38, and protein kinase B. Moreover, EERH treatment inhibited the enzymatic activity of matrix metalloproteinase-9 (MMP-9) and MMP-2, resulting in HCT116 cell migration and invasion. The EERH-induced inhibition of MMP-9 and MMP-2 was attributed to the reduced transcriptional binding of activator protein-1, specificity protein-1, and nuclear factor-κB motifs in HCT116 cells. Kaempferol was identified as the main compound contributing to EERH's antitumor activity. CONCLUSION EERH inhibits HCT116 cell proliferation and metastatic potential. Therefore, it is potentially useful as a preventive and curative nutraceutical agent against colorectal cancer.

Objective: Objective of this study is to evaluate the association between high risk of depression and metabolic diseases such as hypertension, diabetes, and dyslipidemia in Korean cervical cancer patients. Methods: A total of 330 women with cervical cancer were included in this study, using data from the Korea National Health and Nutrition Examination Survey from 2010 to 2021. Participants were categorized into two groups—high risk of depression and non-depression—based on their answers to survey items related to depression. A multivariate logistic regression analysis was used to evaluate the influence of metabolic diseases on high risk of depression in patients with cervical cancer. Results: A total of 78 (23.64%) and 252 (76.36%) women were classified into the high risk of depression and non-depression groups, respectively. In multivariate logistic regression analysis adjusting for age, menopausal status, and smoking status, diabetes was associated with an odds ratio of 2.47 (95% confidence interval: 1.205, 5.071) for high risk of depression in cervical cancer patients. However, among the metabolic diseases, hypertension, and dyslipidemia were not associated with high risk of depression in patients with cervical cancer. Conclusion This study suggests that diabetes may be associated with a increased risk of high risk of depression in cervical cancer patients. Therefore, appropriate treatment of diabetes in cervical cancer patients may contribute to lowering the risk of depression in the future.

Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.