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 explore the microbiological characteristics of Staphylococcus epidermidis with hemolytic phenotype （SEHP）. MethodsHemolytic phenotype was detected using the three-point inoculation method， involving a total of 5 strains of SEHP and 5 strains of Staphylococcus epidermidis with non-hemolytic phenotype （SENHP） . Bacterial species were identified using the Microflex LT MALDI-TOF mass spectrometer， and a phylogenetic tree was constructed through 16S rRNA sequence alignment. Growth curves were monitored through the microcultivation assay. Biofilm formation ability was assessed by microplate crystal violet staining. Red blood cell toxicity was detected using the microplate method. Antimicrobial susceptibility testing of SEHP and SENHP against commonly used antibiotics was performed using a VITEK 2 GP639 test kit. Antagonistic effects of SEHP and SENHP against Staphylococcus aureus and Corynebacterium striatum were evaluated by the Oxford cup inhibition assay. ResultsCompared with SENHP， SEHP exhibited a marked decrease in growth rate during the late logarithmic phase， accompanied by significant hemolytic toxicity. Additionally， it showed lower resistance rates to levofloxacin and moxifloxacin， and could antagonize Staphylococcus aureus and Corynebacterium striatum. ConclusionThe microbiological characteristics of SEHP differ from those of SENHP in that SEHP demonstrates antagonistic effects against S. aureus and C. striatum.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

BackgroundAlcohol dependence patients are prone to relapse after their attempts to quit drinking， which poses a considerable threat to their physical and mental health and creates a heavy burden on their families. Currently， empowerment education is increasingly being utilized in the rehabilitation management of chronic diseases， but there remains a striking lack of empirical research on the application of "Internet +" empowerment education based on timing it right in alcohol dependence patients. ObjectiveTo explore the impact of "Internet +" empowerment education based on timing it right on patients with alcohol dependence， in order to maximize the reduction in relapse rates， craving for alcohol and severity of anxiety symptoms. MethodsA total of 120 patients who were hospitalized in the Department of Addiction Medicine， Hebei Provincial Mental Health Center from May 2022 to April 2023 and met the diagnostic criteria for alcohol dependence in the International Classification of Diseases， tenth edition （ICD-10） were enrolled， and they were classified into study group （n=62） and control group （n=58） using random number table methods. Both groups received standard medication and routine care. Additionally， study group underwent a 6-month "Internet +" empowerment education based on timing it right. At baseline， all subjects were assessed using Penn Alcohol Craving Scale （PACS） and Self-rating Anxiety Scale （SAS）. Three months and six months after intervention， assessments were conducted using PACS， SAS and Michigan Alcoholism Screening Test （MAST）. ResultsThe relapse rates after three and six months of intervention were both lower in study group than those in control group， with statistically significant differences （χ²=8.575， 8.828， P<0.01）. ANOVA with repeated measures on PACS total score and scores of each item revealed a significant time effect， group effect and time×group interaction effect （F=159.714~837.751， 84.645~393.606， 24.302~137.896， P<0.01）. And significant time effect， group effect and time×group interaction effect were also reported on SAS scores （F=166.237， 65.325， 24.724， P<0.01）. Conclusion"Internet +" empowerment education based on timing it right may help reduce relapse rates， alcohol cravings and severity of anxiety symptoms among patients with alcohol dependence. ［Funded by 2023 Annual Hebei Provincial Medical Scientific Research Project Plan （number， 20231537）］

ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， the chemical constituents of Qili Qiangxin capsules was identified， and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules， as well as the serum， brain， heart， lung， spleen， liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software， the compound information database was constructed， and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time， accurate relative molecular mass and fragments， the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds， including 70 terpenoids， 60 flavonoids， 23 organic acids， 17 alkaloids， 20 steroids， 7 coumarins and 36 others， were identified or predicted from Qili Qiangxin capsules， 73 of which were identified matching with standard substances. Tissue distribution results showed that 71， 17， 38， 33， 32， 58 and 43 migrating components were detected in blood， brain， heart， lung， spleen， liver and kidney， respectively. Thirty-seven components were absorbed into the blood and heart， including quinic acid， benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues， including calycosin， methylnissolin， formononetin， alisol B， alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them， astragaloside Ⅳ， salvianolic acid B， ginsenoside Rb₁， ginsenoside Rb₃， ginsenoside Rd， ginsenoside Rg₃， calycosin-7-glucoside， and sinapine may be the important components for the treatment of heart failure， which can provide useful reference for its quality control and research on pharmacodynamic material basis.

OBJECTIVE To evaluate the cost-utility of ciclesonide （CIC） versus budesonide （BUD） for the maintenance treatment of mild to moderate bronchial asthma. METHODS From the perspective of Chinese health service system， a Markov model was established based on the data from a clinical trial in China and some literature. The cycle length was 1 week， the time horizon was 60 years. A discount rate of 5% per year was applied. Cost-utility analysis was performed on therapeutic scheme of CIC and BUD using three times of China’s per capita gross domestic product （GDP） in 2023 as the threshold of willing-to-pay （WTP）. One-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were applied to test the uncertainty of basic analysis. RESULTS Compared with BUD scheme， the incremental cost of the CIC scheme was 9 401.67 yuan， and the incremental quality-adjusted life years（QALYs） were 0.001 3； incremental cost-effectiveness ratio （ICER） was 6 928 868.26 yuan/QALY， far beyond the threshold of WTP 268 074 yuan/QALY. One-way sensitivity analysis showed that the usage， dosage and unit price of CIC and BUD were parameters that had a significant impact on ICER； probabilistic sensitivity analysis showed that the basic analysis results were relatively robust； scenario analysis showed that， when the price of CIC reduced to 159.95 yuan/branch， the probability of CIC scheme having economics was similar to that of BUD scheme. CONCLUSIONS At the current price， CIC is not economical compared with BUD for the maintenance treatment of mild to moderate asthma， using three times of China’s GDP in 2023 as the threshold of WTP.

OBJECTIVE To evaluate the cost-utility of ciclesonide （CIC） versus budesonide （BUD） for the maintenance treatment of mild to moderate bronchial asthma. METHODS From the perspective of Chinese health service system， a Markov model was established based on the data from a clinical trial in China and some literature. The cycle length was 1 week， the time horizon was 60 years. A discount rate of 5% per year was applied. Cost-utility analysis was performed on therapeutic scheme of CIC and BUD using three times of China’s per capita gross domestic product （GDP） in 2023 as the threshold of willing-to-pay （WTP）. One-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were applied to test the uncertainty of basic analysis. RESULTS Compared with BUD scheme， the incremental cost of the CIC scheme was 9 401.67 yuan， and the incremental quality-adjusted life years（QALYs） were 0.001 3； incremental cost-effectiveness ratio （ICER） was 6 928 868.26 yuan/QALY， far beyond the threshold of WTP 268 074 yuan/QALY. One-way sensitivity analysis showed that the usage， dosage and unit price of CIC and BUD were parameters that had a significant impact on ICER； probabilistic sensitivity analysis showed that the basic analysis results were relatively robust； scenario analysis showed that， when the price of CIC reduced to 159.95 yuan/branch， the probability of CIC scheme having economics was similar to that of BUD scheme. CONCLUSIONS At the current price， CIC is not economical compared with BUD for the maintenance treatment of mild to moderate asthma， using three times of China’s GDP in 2023 as the threshold of WTP.

Methods: Seventy-five patients with atlas fracture were included from January 2015 to December 2020. Based on the anatomy of the fracture line, atlas fractures were divided into three types. Each type was divided into two subtypes according to the fracture displacement. Unweighted Cohen kappa coefficients were applied to evaluate the reliability and reproducibility. Results: According to the new classification, 17 cases of type A1, 12 of type A2, seven of type B1, 13 of type B2, 12 of type C1, and 14 of type C2 were identified. The K-values of the interobserver and intraobserver reliability were 0.846 and 0.912, respectively, for the new classification. The K-values of interobserver reliability for types A, B, and C were 0.843, 0.799, and 0.898, respectively. The K-values of intraobserver reliability for types A, B, and C were 0.888, 0.910, and 0.935, respectively. The mean K-values of the interobserver and intraobserver reliability for subtypes were 0.687 and 0.829, respectively. Conclusions The new classification of atlas fractures can cover nearly all atlas fractures. This system is the first to evaluate the severity of fractures based on the C1 articular facet and fracture displacement and strengthen the anatomy ring of the atlas. It is concise, easy to remember, reliable, and reproducible.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.