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 investigate the clinical effect of shoulder arthroscopic rotator cuff repair combined with shoulder three needles in treatment of rotator cuff injury.Methods 86 patients with rotator cuff injury from June 2021 to May 2023 were divided into two groups using a random number table method.The research group received 43 cases of rotator cuff repair under arthroscopy combined with shoulder three needles rotator cuff repair,while the control group received 43 cases of rotator cuff repair under arthroscopy combined with placebo needling.Then compare the pain level,shoulder joint function,and shoulder joint range of motion between the two groups before and 6 months after surgery,and calculate the excellent and good shoulder joint function rates between the two groups at 6 months after surgery,and compare the changes in inflammatory factors between the two groups at before and 4 weeks after surgery.Results 6 months after surgery,the visual analogue scale(VAS)score of both groups was lower than that before surgery,and the VAS score in research group(including the moderate tearing subgroup and the major tearing subgroup)was lower than that of the control group(including the moderate tearing subgroup and the major tearing subgroup),while the American Shoulder and Elbow Surgeons(ASES)score and shoulder joint range of motion were higher than those before surgery,and the ASES score and shoulder joint range of motion in research group(including the moderate tearing subgroup and the major tearing subgroup)were higher than those of the control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).6 months after surgery,the excellent and good rate of shoulder joint function in the research group was higher than that in the control group,the difference was statistically significant(P＜0.05).At 4 weeks after surgery,the levels of tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),and interleukin-8(IL-8)in both groups were lower than those before surgery,and the research group(including the moderate tearing subgroup and the major tearing subgroup)were lower than those of control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).Conclusion Arthroscopic rotator cuff repair combined with shoulder three needles can alleviate the pain level of patients with rotator cuff injury,improve shoulder joint function and range of motion,increase the excellent and good rate of shoulder joint function,and reduce inflammatory reaction.It is worthy of clinical application.

Diabetic encephalopathy(DE)is a complication of the central nervous system induced by diabetes,characterized by insidious onset and complex pathological mechanisms.Recent research has revealed that the pathological mechanisms of DE are closely associated with the imbalance of intercellular communica-tion across multiple organs.Exosomes,serving as vital media-tors of intercellular communication,are involved in the patholog-ical progression of DE and hold promise as diagnostic biomarkers and therapeutic targets for DE.Traditional Chinese medicine(TCM)can improve communication between brain cells and be-tween peripheral and brain tissues by regulating exosomes and their contents,thereby preventing and treating DE.Meanwhile,exosomes,as targeted delivery carriers of active molecules,can carry TCM monomers more easily across the blood-brain barrier to prevent and treat DE.In light of this,this review summarizes the regulatory role of exosomes in the pathological progression of DE and explores the enormous potential of TCM in the preven-tion and treatment of DE by regulating exosomes and using exo-somes as traditional Chinese medicine carriers,aiming to pro-vide new evidence for the prevention and treatment of DE with TCM.

Objective:To evaluate the feasibility and safety of open ventilation masks in patients with proliferative diabetic retinopathy (PDR) undergoing vitrectomy under local anesthesia.Methods:A randomized clinical trial was conducted.Eighty PDR patients (80 eyes) undergoing vitrectomy with local anesthesia were enrolled at Xuzhou Municipal Hospital from May to July 2024.Patients were randomly divided into an experimental group and a control group using a random number table method, with 40 cases (40 eyes) in each group.The experimental group received oxygen through an ophthalmic surgical open ventilation mask during the operation, while the control group used a traditional nasal cannula.The respiratory rate, heart rate, systolic blood pressure, diastolic blood pressure, and oxygen saturation before and after oxygen inhalation during the operation were compared between the two groups.Patient comfort level, airway patency, anxiety status, satisfaction level, operation time, surgical success rate, and incidence of intraoperative complications were also compared.This study adhered to the Declaration of Helsinki and the study protocol was appreed by the Ethics Committee of Xuzhou Municipal Hospital (No.2024-KY-065).Results:After oxygen inhalation during the operation, improvements in respiratory rate, heart rate, and oxygen saturation were greater in the experimental group than in the control group, with statistically significant differences ( t=4.671, 7.894, 1.588; all P<0.05).The Borg, and Hamilton Anxiety Scale scores were lower in the experimental group than in the control group, with statistically significant differences ( t=2.828, 4.880; both P<0.05), while the Bruggrmann Comfort Scale score was higher than that in the control group ( t=2.774, P<0.05).There were no statistically significant differences in operation time, surgical success rate or incidence of complications between the two groups ( t=0.595, P=0.554; χ2=0.346, 0.263; both P>0.05).Satisfaction rate of patients in the experimental group was 97.5%(39/40), which was higher than 85.0%(34/40) in the control group, with a statistically significant difference ( χ2=3.914, P=0.048). Conclusions:For PDR patients undergoing vitreous surgery under local anesthesia, using an ophthalmic surgical open ventilation mask for oxygen inhalation can effectively enhance respiratory comfort level, alleviate anxiety, maintain stable vital signs, improve overall comfort level, and ensure smooth surgery, without observed adverse reactions related to mask use, which makes it worthy of clinical promotion and application.

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). As a key brain region involved in emotional regulation and stress responses, the amygdala has been implicated in the pathogenesis of PMS/PMDD. The amygdala is composed of multiple subregions, each playing distinct roles in emotion, memory, and stress responses, and forms complex brain areas. Summarizing the interconnections among amygdala, subregions and their connectivity with external areas, and exploringt the neuroimaging characteristics of the amygdala, as well as changes in its neural circuits and brain networks in these patients, will help provide a theoretical foundation for targeted modulation of amygdala function in the treatment of PMS/PMDD.
Humans ; Amygdala/diagnostic imaging* ; Female ; Premenstrual Dysphoric Disorder/pathology* ; Premenstrual Syndrome/pathology* ; Emotions/physiology* ; Magnetic Resonance Imaging

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Objective:Analyze the risk factors for acute lung injury of postoperative acute lung injury(ALI)in patients with Stanford type A aortic dissection(STAAD),and construct a nomogram predictive model.Methods:A retrospective cohort study design was adopted.A total of 112 patients with STAAD who underwent surgical treatment in our hopital from January 2021 to August 2024 were included.They were divided into two groups according to the occurrence of ALI after the surgical:non-ALI group(73 cases)and ALI group(39 cases).Clinical data were collected from both groups of patients.The influencing factors of postoperative ALI in patients with STAAD were analyzed by multivariate logistic regression.Established nomogram prediction model based on influencing factors and validated.Results:Among 112 patients with STAAD who underwent surgical treatment,39 case postoperative ALI occurred,with an incidence rate of 34.82％.Age,preoperative creatinine,body mass index(BMI),preoperative white blood cell count,preoperative lactate and other aspects compared,The difference were statistically significant(P＜0.05).The length of stay in the intensive care unit(ICU)of the ALI group was longer than that of the non ALI group(P＜0.05).The intraoperative red blood cell transfusion volume and extracorporeal circulation time in the ALI group were higher than those in the non ALI group(P＜0.05).Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count were risk factors for postoperative ALI(P＜0.05).The receiver operating characteristic(ROC)curve analysis results show that,the Area under the curve(AUC)of the nomogram prediction model was 0.871.When the optimal critical value was 0.472,its sensitivity and specificity wew 0.887 and 0.776,respectively.The internal validation results of Bootstrap show that,the C-index of the column chart prediction model was 0.862,with an absolute error of 0.032.The calibration curve is close to the ideal curve and the original curve,with a slope close to 1.Conclusions:Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count are independent risk factors for postoperative ALI in patients with STAAD.The nomogram model constructed based on the above risk factors can effectively evaluate the risk of postoperative ALI in patients with STAAD.