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.

ObjectiveTo construct and validate a clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure （CHF），aiming to assist clinical diagnosis and provide tools and methods for individualized treatment of CHF. MethodsThe clinical data of patients with chronic heart failure treated at Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2022 to January 2024 were retrospectively collected. The patients were randomly divided into a training group and a validation group with a ratio of 7∶3. First， the least absolute shrinkage and selection operator （LASSO） regression analysis was used to preliminarily screen the predictive factors affecting the diagnosis of Qi deficiency and blood stasis syndrome in CHF. Subsequently， the Logistic regression method was applied to conduct a more in-depth and detailed analysis of these factors. Variables with P<0.05 in the results of the multi-factor Logistic regression were carefully selected and included. Based on the regression coefficients obtained from this analysis， a model was constructed， and a nomogram was accurately drawn. Using R software，the receiver operating characteristic （ROC） curve，calibration curve，and decision curve analysis （DCA） were precisely drawn. These analyses were used to comprehensively evaluate the model from three crucial aspects： discrimination，calibration，and clinical applicability. Additionally， the accuracy，specificity，sensitivity，positive predictive value，and negative predictive value of the model were meticulously calculated to conduct a more all-round and comprehensive assessment. ResultsIn total， 168 cases were successfully obtained in the training group， and 71 cases were included in the validation group. After a thorough comparison， it was found that there were no statistically significant differences in the baseline data between the two groups. After being rigorously screened by the LASSO-multivariate logistic regression method， dark red tongue，smoking history，cardiac troponin I，and N-terminal pro-B-type natriuretic peptide （NT-ProBNP） were identified as the influencing factors for diagnosing patients with the Qi deficiency and blood stasis syndrome in CHF. The constructed model demonstrated an area under the curve （AUC） of 0.812 in the training group and 0.719 in the validation group. The calibration curve showed that the predicted curve of the model was close to the actual observed curve. DCA indicated that the model could provide substantial clinical benefits for patients at the decision thresholds ranging from 0.2 to 0.9. ConclusionThe clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure constructed in this study shows good performance. It has certain application value in clinical practice， which may contribute to the improvement of the diagnosis and treatment of CHF patients with this syndrome.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

ObjectiveTo analyze the incidence rate and mortality of acute myocardial infarction (AMI) and their changing trends among the registered residents in Xiaoshan District, Hangzhou City from 2017 to 2023, so as to provide references for formulating policies related to AMI prevention. MethodsThe morbidity and mortality data of AMI among the registered residents in Xiaoshan District from 2017 to 2023 were collected through the Hangzhou Chronic Disease and Death Cause Monitoring System. Software such as Excel 2019, SPSS 25.0 and Joinpoint 4.9.1.0 were used to calculate the incidence rate, mortality, and average annual percentage change (AAPC) of AMI. ResultsFrom 2017 to 2023, the average annual crude incidence rate, age-standardized incidence rate using China standard population (ASIRC), and the age-standardized incidence rate using World standard population (ASIRW) of AMI in Xiaoshan District were 48.25/100 000, 29.14/100 000, and 21.64/100 000, respectively, and, from which the AAPCs were 5.495%, 6.010%, and 6.533%, respectively, all showing an upward trend. The average annual crude mortality rate, the age-standardized mortality rate using China standard population (ASMRC), and the age-standardized mortality rate using World standard population (ASMRW) were 11.76/100 000, 6.52/100 000, and 4.71/100 000, respectively, from which the AAPCs were -9.669%, -10.433% and -9.615%, respectively, all showing a downward trend. The average annual crude incidence rate of AMI was higher in males (65.87/100 000) than that in females (31.31/100 000). Moreover, the average annual crude mortality rate of AMI was higher in males (14.08/100 000) than that in females (9.52/100 000), and the difference was statistically significant (all P<0.001) .After age grouping, the crude incidence rate of AMI among the residents aged 35-, 45-, 55-, and 65- years in Xiaoshan District from 2017 to 2023 showed an upward trend over time, with AAPCs of 16.993%, 17.149%, 8.523%, and 5.002%, respectively. While the crude mortality rate in residents aged 35-, 75-, and 85-102 years showed an decreasing trend over time, with AAPCs of -23.977%, -15.467%, and -17.415%, respectively, but there was no statistically significant difference in the trends in incidence rate and mortality of other age groups (all P>0.05). ConclusionThe situation of AMI prevention and control among the registered residents in Xiaoshan District is not optimistic, and targeted measures should be strengthened for the male residents aged ≥35 years old.

Xenotransplantation is an important approach to addressing the shortage of donor organs. However, it still faces numerous challenges, such as acute rejection and zoonotic diseases. Organoid-on-a-chip technology refers to a microcell culture device that simulates the physiological functions of human organs in vitro. In recent years, it has achieved a series of important results in the field of allotransplantation and has great application prospects in the field of xenotransplantation, bringing new opportunities for xenotransplantation research. Therefore, this article discusses the current research status and progress of organoid-on-a-chip technology, combined with the various problems faced by xenotransplantation, to explore the application of organoid-on-a-chip technology in solving the selection of immunosuppressive regimens, matching and viral reactivation in xenotransplantation. This aims to open up new avenues for solving the current problems in the field of xenotransplantation and promote its further development.

AIM:To observe the defocus state and myopia control in myopic children wearing single-vision, defocus, and orthokeratology lenses using multispectral refraction topography(MRT).METHODS: A total of 279 myopic patients aged 8-14 years old, with a spherical equivalent(SE)from -7.00 to -0.50 D, treated at the Chengdu Aier Eye Hospital from June 2022 to December 2023. Patients who volunteered for the study were assigned to three groups. A total of 94 cases were provided with single-vision spectacle lenses(SVL group), 90 cases received individualized ocular refraction customization(IORC group), and 95 cases received orthokeratology lenses(OK group). Simultaneously, the three groups were further categorized into low(-3.00 to -0.50 D), moderate(-6.00 to -3.25 D), and high myopia(-7.00 to -6.25 D)groups according to different SE. MRT was used to measure and compare the defocus changes of the retina in supperior, inferior, nasal, and temporal quadrants(RDV-S, RDV-I, RDV-N, RDV-T), and three angles of field of view, including 0-15°, 15°-30°, and 30°-45°(RDV-15, RDV-30, RDV-45)in the three groups(the data divide for the connected regions is grouped to the latter group). A one-way analysis of variance was used for intergroup comparisons. Univariate and multivariate linear regression analyses were used to analyze the factors related to changes in the axial length(AL)at 1 a after intervention.RESULTS:There were significant differences in 1-year SE and AL growth among patients in the SVL, IORC, and OK groups before and after intervention(P<0.001). The 1-year SE and the difference of AL growth in patients with low myopia was significantly different among SVL, IORC, and OK groups(P<0.001); however, there was no significant difference between the IORC and OK groups(P>0.05); there were significant differences in the SE and AL growth changes between the OK group and the IORC and SVL groups in moderate myopia(P<0.001); and there were significant differences between the OK group and the IORC and SVL groups in SE and AL growth of high myopia group after wearing lenses for 1 a(P<0.001), while there were no significant differences between the IORC and SVL groups(P>0.05). In addition, there were significant differences in the relative peripheral refractive errors(RPRE)of 4 quadrants and 3 eccentric regions among the three groups of patients in different degrees of myopia groups(P<0.001). Pair-wise comparison of the growth difference of eccentric D-RDV-15 in low myopia group after wearing lenses for 1 a showed significant differences between the SVL, IORC, and OK groups(P<0.001), but no significant differences between the IORC and OK groups(P>0.05). The angle of field of view D-RDV-30 in moderate myopia subgroups was statistically different between the SVL group and the IORC and OK groups after wearing lenses for 1 a(P<0.001), while the IORC and OK groups showed no significant differences(P>0.05); the angle of field of view D-RDV-15 in high myopia subgroups was statistically different between the OK group and the IORC and SVL groups after wearing lenses for 1 a(P<0.001), but there was no significant difference between the IORC and SVL groups(P>0.05). Univariate and multivariate linear regression model analysis showed that the changes in D-TRVD, D-RDV-45, D-RDV-N, and D-RDV-I correlated with the increase in the difference in 1 a AL.CONCLUSION: MRT can be used to guide the clinical control of myopia. Myopia development is related to the peripheral retinal defocus state, and the difference of defocus quantity in the inferior nasal side at 30°-45° eccentricity may be a factor regulating the rapid progression of myopia.

Objective: To explore the interactive mechanisms of middle school students lifestyle with depressive and anxiety symptoms, so as to provide a basis for constructing a precise prevention system of middle school students mental health. Methods: From October to December in 2024, a stratified cluster random sampling method was used to select 6 251 middle school students from Guangxi. The Lifestyle Questionnaire, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 ( GAD- 7) were used to investigate middle school students lifestyle, depressive symptoms and anxiety symptoms. The relationship of adolescent lifestyle with depressive and anxiety symptoms was analyzed through binary Logistic regression. The network analysis method was used to construct the network of middle school students lifestyle with depressive and anxiety symptoms. Results: A total of 1 690 individuals (27.0%) exhibited depressive symptoms, and 1 071 individuals (17.1%) exhibited anxiety symptoms. Binary Logistic regression analysis revealed that smoking, alcohol consumption, excessive intake of sugary drinks, insufficient vegetable intake, not eating breakfast daily, frequent consumption of fast food, prolonged sedentary time on both weekdays and weekends, insufficient sleep duration on weekdays and weekends, and excessive screen time on weekdays were all associated with depressive symptom ( OR =1.19-2.07) and anxiety symptom ( OR =1.20-1.91) in middle school students(all P ＜0.05). Additionally, excessive screen time on weekends was associated only with depressive symptoms ( OR =1.35, P <0.05). The connection between the lifestyle-depressive symptom cluster was mainly through "breakfast" and "suicidal ideation" (weight=0.31); the connection between the lifestyle-anxiety symptom cluster was mainly through "sedentary time on weekdays" and "uncontrollable worry" (weight=0.34). In the depressive symptom network, "depressed mood" had the highest node strength; in the anxiety symptom network, "uncontrollable worry" had the highest node strength. "Suicidal ideation" was a key bridge node between lifestyle and depressive and anxiety symptoms. Conclusions Unhealthy lifestyles are significant modifiable risk factors for depressive and anxiety symptoms among middle school students. Regular breakfast intake and management of sedentary behavior should be prioritized as important intervention entry points.

ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.

ObjectiveTo establish background data for a 90-day feeding trial of SD rats to ensure the reliability of research data. MethodsBackground data from six independent 90-day feeding trials of SD rats conducted by the National Center for Safety Evaluation of Drugs from 2020 to 2023 were summarized. These studies involved a blank control group of 120 SPF-grade 4-week-old SD rats, with an equal number of males and females, which were only given standard full-nutrient pelleted rat feed. After the quarantine period, the animals were observed for an additional 90 days, followed by intraperitoneal injection of Zoletil (50 mg/mL) for anesthesia, blood sampling, euthanasia, and necropsy. By analyzing the data from the blank control group, a relevant background database for SD rats was established. ResultsBoth male and female rats exhibited steady weight gain, with a more pronounced increase in male rats. Within 90 days, the average body weight of male and female rats increased to over 500 g and 300 g, respectively. Three weeks later, the average daily food intake of male rats stabilized at approximately 25~28 g per rat, while that of female rats remained stable at approximately 16~19 g per rat. The food utilization rate of all animals gradually decreased from the first week of the experiment. In the white blood cell (WBC) differential count results, significant differences were observed in the counts of WBCs, neutrophils (Neut), lymphocytes (Lymph), and monocytes (Mono) between males and females (P<0.001). However, there were no significant differences in the percentages of neutrophil (%Neut), lymphocyte (%Lymph), and monocyte (%Mono) between the sexes (P>0.05). The average red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were higher in male animals than in female animals (P<0.05). The average values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CK), lactate dehydrogenase (LDH), glucose (GLU), and triglyceride (TG) in male rats were higher than those in female rats (P<0.05). The urinary pH range for male animals was 5.0 to 8.5, while for female animals it was 6.5 to 9.0. The majority of male animals had a urinary specific gravity lower than 1.020, and the majority of female animals had a urinary specific gravity lower than 1.015. The weights of various organs (excluding the adrenal glands and reproductive organs) in male animals were heavier than those in female animals (P<0.001), while the organ/body weight ratios (excluding the kidneys and reproductive organs) of female animals were higher than those of male animals (P<0.001). ConclusionThis study summarizes the background reference ranges for body weight, food intake, hematology, and serum biochemistry indicators in SPF-grade SD rats in the untreated control group from six 90-day feeding trials conducted by the National Center for Safety Evaluation of Drugs. It provides important reference data for related research. By summarizing the background and spontaneous histopathological changes in rats, this study aids in the standardization and normalization of subsequent research, as well as in the evaluation and analysis of abnormal results.