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 explore the application value of extracellular volume fraction (ECVF) based on multi-phase CT images in the prognosis evaluation after radical resection of pancreatic cancer.Methods:Retrospective analysis of the clinical data of 119 patients with pancreatic ductal adenocarcinoma admitted to the First Affiliated Hospital of Wannan Medical College from January 2015 to December 2023, including 73 males and 46 females, aged 69 (62, 73) years. The clinical data including the patient's gender, age, imaging data, tumor major axis length, carbohydrate antigen (CA) 199, CA125 were collected. Based on multi-phase CT images, the ECVF of patients was calculated and subsequently 119 patients were divided into two groups according to the optimal cut-off value of ECVF: ECVF<0.31 group ( n=63) and ECVF≥0.31 group ( n=56). Postoperative survival information of patients was collected through telephone follow-up. The Kaplan-Meier method was used for survival analysis, and the log-rank test was applied for survival rate comparison. The Cox proportional hazards regression model was employed to analyze the impact of variables on overall survival time. Results:The differences in tumor location, tumor poor differentiation, and tumor major axis between the ECVF<0.31 group and the ECVF≥0.31 group were statistically significant (all P<0.05). The cumulative survival rates at 1, 3, and 5 years post-operation for patients in the ECVF<0.31 group were 34.7%, 10.3%, and 2.6%, respectively, while for patients in the ECVF≥0.31 group, they were 75.0%, 37.0%, and 25.6%, respectively. The cumulative survival rate after radical pancreatic cancer surgery for patients in the ECVF<0.31 group was lower than that for the ECVF≥0.31 group, and the difference is statistically significant ( χ2=24.50, P<0.001). Multivariate Cox analysis revealed that ECVF≥0.31 ( HR=0.25, 95% CI: 0.11-0.57), vascular invasion ( HR=2.43, 95% CI: 1.09-5.44), lymph node metastasis ( HR=3.01, 95% CI: 1.09-8.33), low tumor differentiation ( HR=2.32, 95% CI: 1.10-4.91), and lymphocyte count ≥1.25×10 9/L ( HR=0.31, 95% CI: 0.13-0.73) were risk factors affecting the overall survival of patients with pancreatic ductal adenocarcinoma after radical resection of pancreatic cancer (all P<0.05). Conclusion:ECVF based on multi-phase CT images has a predictive effect on the overall survival of patients with pancreatic ductal adenocarcinoma after radical resection of pancreatic cancer, and ECVF<0.31 is an independent risk factor for a short overall survival.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To investigate the correlation between peri-coronary fat attenuation index (FAI) and plaque formation in patients with myocardial bridge (MB) of the left anterior descending artery (LAD) using coronary computed tomography angiography (CCTA) and to develop an optimal predictive model to explore the potential application of FAI in the primary prevention of MB related atherosclerosis.Methods:In this retrospective study, prediction models associated with perivascular fat inflammation were developed and validated using both logistic regression and machine learning (ML) algorithm. A training dataset was collected from 253 patients who underwent ≥2 coronary computed tomography angiography (CCTA) with ≥3 months intervals from one tertiary hospital from January 2007 to April 2021 and had baseline CCTA showing no plaques in LAD MB. The median follow-up time was 3.2 years. According to the same criteria, a total of 75 LAD MB patients from four other hospitals were included to form an independent external validation dataset, with a median follow-up time of 1.8 years. Receiver operating characteristic (ROC) curve analysis with integrated discrimination improvement (IDI) and category net reclassification index (NRI) were used to compare the performance of the predictive models.Results:62 patients (24.5%) in the training dataset had proximal plaque formation in LAD MB, while 22 patients (29.3%) in the external validation dataset had plaque formation during the follow-up period. Baseline FAI within the longitudinal distance equal to 30 mm proximal to the MB entrance was an independent predictor ( OR=1.068, P=0.046). According to the model results, ROC curves were plotted. The AUC of Model 1 was 0.822, and the AUCs of Model 2 and 1 were 0.821 and 0.591 in the training dataset. After the DeLong test, the AUC of Model 1 was superior to that of Model 2 ( Z=2.839, P=0.005) and Model 1 ( Z=6.124, P<0.001). These findings were further validated in the external validation dataset, where ML-model 3 yielded the best predictive performance, outperforming the logistic regression-based Model 2 (categorical NRI=0.359, P=0.048; IDI=0.108, P=0.046). Conclusion:FAI measured within the 30 mm proximal to the entrance of MBs due to its prone to plaque development is an independent predictor for atherosclerotic plaque formation. The ML-prediction model based on a decision tree algorithm combines FAI, MB anatomical features, and patient risk factors, which is beneficial for patients undergoing routine CCTA examination to identify inflamed coronary arteries in advance and guide the clinical adoption of more targeted preventive treatment, including anti-inflammatory treatment.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

Objective:To explore the distribution of TCM syndromes in ulcerative colitis (UC) and their relationship with the characteristics colonoscopy mucosal and histological grading.Methods:A retrospective analysis was conducted on the TCM syndrome classification, colonoscopy mucosal images, and histological grading of 303 UC patients at Henan Provincial Traditional Chinese Medicine Hospital from January 2023 to January 2024. The characteristics and correlation of colonoscopy mucosal images and histological grading in UC patients with different TCM syndrome types was explored.Results:The top three TCM syndrome types of UC patients were large intestine damp-heat syndrome (24.75%), spleen-qi deficiency syndrome (21.12%) and liver-stagnation and spleen-deficiency syndrome (19.80%). Compared with the syndrome of spleen deficiency and dampness accumulation, heat and toxin exuberance, cold and heat mixed syndrome, liver stagnation and spleen deficiency syndrome, spleen and kidney yang deficiency syndrome, spleen qi deficiency syndrome, yin and blood deficiency syndrome, blood stasis and intestinal collateral syndrome, patients with colonic damp-heat syndrome type Ⅰ accounted for the highest proportion ( χ2=12.79, 16.24, 4.26, 16.54, 11.53, 14.16, 7.75, 10.91, P<0.05). The proportion of type Ⅲ patients was the lowest ( χ2=30.57, 33.59, 12.71, 23.63, 7.90, 19.88, 18.31, 17.31, P<0.05). Among the patients with different TCM syndrome types, the proportion of large intestine damp-heat syndrome in histological grade Ⅳ was the highest (66.67%), the proportion of blood stasis and intestinal meridian syndrome in histological grade Ⅲ was the highest (53.33%), the proportion of liver stagnation and spleen deficiency syndrome in histological grade Ⅱ was the highest (50.00%), and the proportion of spleen and kidney yang deficiency syndrome in histological grade Ⅰ was the highest (40.00%). Spearman correlation analysis showed that the large intestine damp-heat syndrome was significantly correlated with the characteristics of colonoscopy mucosal image and histological grade ( r=-0.563, 0.612, respectively, all P<0.001). The syndrome of spleen deficiency and dampness accumulation, heat and toxin exuberance, yin and blood deficiency, blood stasis and intestinal collateral were significantly positively correlated with the characteristics of colonoscopy mucosa ( r=0.373, 0.342, 0.263, 0.331, all P<0.05). The syndrome of liver stagnation and spleen deficiency and spleen and kidney yang deficiency were significantly negatively correlated with histological grade ( r=-0.417, -0.425, all P<0.01). Conclusions:The main TCM syndromes are large intestine damp-heat syndrome, spleen-qi deficiency syndrome and liver-qi deficiency syndrome, which are significantly correlated with the mucosal features and histological grade of colonoscopy. Colonoscopy and histophiologic examination can be used as objective indicators for TCM syndrome differentiation.

Objective:To investigate the correlation between peri-coronary fat attenuation index (FAI) and plaque formation in patients with myocardial bridge (MB) of the left anterior descending artery (LAD) using coronary computed tomography angiography (CCTA) and to develop an optimal predictive model to explore the potential application of FAI in the primary prevention of MB related atherosclerosis.Methods:In this retrospective study, prediction models associated with perivascular fat inflammation were developed and validated using both logistic regression and machine learning (ML) algorithm. A training dataset was collected from 253 patients who underwent ≥2 coronary computed tomography angiography (CCTA) with ≥3 months intervals from one tertiary hospital from January 2007 to April 2021 and had baseline CCTA showing no plaques in LAD MB. The median follow-up time was 3.2 years. According to the same criteria, a total of 75 LAD MB patients from four other hospitals were included to form an independent external validation dataset, with a median follow-up time of 1.8 years. Receiver operating characteristic (ROC) curve analysis with integrated discrimination improvement (IDI) and category net reclassification index (NRI) were used to compare the performance of the predictive models.Results:62 patients (24.5%) in the training dataset had proximal plaque formation in LAD MB, while 22 patients (29.3%) in the external validation dataset had plaque formation during the follow-up period. Baseline FAI within the longitudinal distance equal to 30 mm proximal to the MB entrance was an independent predictor ( OR=1.068, P=0.046). According to the model results, ROC curves were plotted. The AUC of Model 1 was 0.822, and the AUCs of Model 2 and 1 were 0.821 and 0.591 in the training dataset. After the DeLong test, the AUC of Model 1 was superior to that of Model 2 ( Z=2.839, P=0.005) and Model 1 ( Z=6.124, P<0.001). These findings were further validated in the external validation dataset, where ML-model 3 yielded the best predictive performance, outperforming the logistic regression-based Model 2 (categorical NRI=0.359, P=0.048; IDI=0.108, P=0.046). Conclusion:FAI measured within the 30 mm proximal to the entrance of MBs due to its prone to plaque development is an independent predictor for atherosclerotic plaque formation. The ML-prediction model based on a decision tree algorithm combines FAI, MB anatomical features, and patient risk factors, which is beneficial for patients undergoing routine CCTA examination to identify inflamed coronary arteries in advance and guide the clinical adoption of more targeted preventive treatment, including anti-inflammatory treatment.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To explore the application value of extracellular volume fraction (ECVF) based on multi-phase CT images in the prognosis evaluation after radical resection of pancreatic cancer.Methods:Retrospective analysis of the clinical data of 119 patients with pancreatic ductal adenocarcinoma admitted to the First Affiliated Hospital of Wannan Medical College from January 2015 to December 2023, including 73 males and 46 females, aged 69 (62, 73) years. The clinical data including the patient's gender, age, imaging data, tumor major axis length, carbohydrate antigen (CA) 199, CA125 were collected. Based on multi-phase CT images, the ECVF of patients was calculated and subsequently 119 patients were divided into two groups according to the optimal cut-off value of ECVF: ECVF<0.31 group ( n=63) and ECVF≥0.31 group ( n=56). Postoperative survival information of patients was collected through telephone follow-up. The Kaplan-Meier method was used for survival analysis, and the log-rank test was applied for survival rate comparison. The Cox proportional hazards regression model was employed to analyze the impact of variables on overall survival time. Results:The differences in tumor location, tumor poor differentiation, and tumor major axis between the ECVF<0.31 group and the ECVF≥0.31 group were statistically significant (all P<0.05). The cumulative survival rates at 1, 3, and 5 years post-operation for patients in the ECVF<0.31 group were 34.7%, 10.3%, and 2.6%, respectively, while for patients in the ECVF≥0.31 group, they were 75.0%, 37.0%, and 25.6%, respectively. The cumulative survival rate after radical pancreatic cancer surgery for patients in the ECVF<0.31 group was lower than that for the ECVF≥0.31 group, and the difference is statistically significant ( χ2=24.50, P<0.001). Multivariate Cox analysis revealed that ECVF≥0.31 ( HR=0.25, 95% CI: 0.11-0.57), vascular invasion ( HR=2.43, 95% CI: 1.09-5.44), lymph node metastasis ( HR=3.01, 95% CI: 1.09-8.33), low tumor differentiation ( HR=2.32, 95% CI: 1.10-4.91), and lymphocyte count ≥1.25×10 9/L ( HR=0.31, 95% CI: 0.13-0.73) were risk factors affecting the overall survival of patients with pancreatic ductal adenocarcinoma after radical resection of pancreatic cancer (all P<0.05). Conclusion:ECVF based on multi-phase CT images has a predictive effect on the overall survival of patients with pancreatic ductal adenocarcinoma after radical resection of pancreatic cancer, and ECVF<0.31 is an independent risk factor for a short overall survival.

Objective To investigate the prevalence of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among local residents in Yantai City, Shandong Province in 2021, so as to provide insights into formulation of anisakiasis control interventions. Methods Marine fishes were purchased from Shunxin Port, Yantai City, Shandong Province in November 2021, and the presence of Anisakis was detected in different species of fishes and different fish sites. The correlations between body length and weight of marine fish and intensity of Anisakis infections were examined using Spearman’s rank correlation analysis, and the dietary habits and anisakiasis control knowledge were investigated using questionnaire surveys among local residents. Results A total of 201 marine fishes belonging to 20 species were dissected, and Anisakis was detected in 77 marine fishes (38.31%) belonging to 11 species (55.00%), with a mean infection intensity of 45.04 parasites per fish (3 468/77). Spearman’s rank correlation analysis revealed that the body length (r_s = 0.74, P < 0.05) and weight (r_s = 0.79, P < 0.01) of the monkfish correlated positively with the intensity of Anisakis infections, and the body length (r_s = 0.68, P < 0.05) of the flatfish correlated positively with the intensity of Anisakis infections, while no correlations were examined between the body length or weight of other marine fishes and the intensity of Anisakis infections. Of all respondents, 53.38% men and 56.67% women did not know anisakiasis control knowledge at all, and there was a significant difference in the proportion of respondents using separate chopping boards for raw and cooked food from different villages (χ² = 17.89, P < 0.01), while there was an age-specific proportion of respondents with habitats of eating raw or semi-raw seafood (χ² = 28.27, P < 0.01). Conclusions The prevalence and intensity of Anisakis infections were high in coastal marine fishes in Yantai City in 2021, and the awareness of anisakiasis control knowledge was low among local residents. Intensified health education pertaining to anisakiasis control knowledge is recommended to reduce the risk of Anisakis infections.