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.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To investigate whether curcumin(CUR)can reduce chondrocyte inflammation and cartilage degradation in osteo-arthritis(OA)and the underlying mechanisms.Methods A rat model of OA was established.Rats were randomly divided into a Sham,OA,CUR+OA,and deferoxamine(DFO)+OA groups with 10 mice in each group.Chondrocytes from 5-day-old SD rats were divided into the control,interleukin-1β(IL-1β),CUR+IL-1β,and DFO+IL-1β groups.A CCK-8 assay was performed to assess the effects of CUR on cell viability alone or combined with IL-1β.Toluidine blue staining and alcian blue staining were used to observe the morphological changes of IL-1β-induced chondrocytes.The expression of inflammatory response-related proteins(COX-2 and iNOS),extracellular matrix degradation-related proteins(COL2A and MMP13),and p53,SLC7A11,and GPX4 proteins during ferroptosis were detected by Western blotting.The mitochondrial membrane potential was detected by JC-1 staining.Mitochondrial morphology was observed using transmission electron microscopy.Safranine O-fast green/HE staining was performed on cartilage tissues.Immunohistochemical staining was performed to detect COL2A and SLC7A11 expression levels.Results CUR and DFO were found to reduce IL-1β-induced inflammation,cartilage degradation,and ferroptosis,and restore mitochondrial function in chondrocytes.CUR also reversed IL-1β-induced changes in collagen Ⅱ,p53,SLC7A11,GPX4,MMP13,iNOS,and COX-2 levels.In vivo,intra-articular injection of CUR significantly improved cartilage injury in the OA rat model,and the percentages of COL2A-and SLC7A11-positive cells significantly increased in the CUR+OA and DFO+OA groups.Conclusion CUR inhibits ferroptosis and ameliorates cartilage degeneration in OA through p53 signaling pathway.

To understand the infection status of main intestinal protozoa in BALB/c mice and pro-vide a basis for further control of intestinal protozoa infection.Five hundred and forty BALB/c mice provided by four domestic suppliers of BALB/c mice were detected for intestinal protozoa,in which 140 from supplier A,130 from supplier B,135 from supplier C,and 135 from supplier D,re-spectively.Fresh faecal samples were collected from each mouse separately to extract the genome and amplified by nested PCR based on primers for the 18S rRNA gene sequences of Pent-atrichomonas hominis(P.hominis)and Cryptosporidium tyzzeri(C.tyzzeri),and the 16S-like rRNA gene sequence of Tritrichomonas muris(T.muris)and sequenced.The results showed that the total intestinal protozoan infection rate was 7.1％(10/140)in 140 mice faecal samples provided by supplier A.Among them,the positivity rate of T.muris was 7.1％(10/140),C.tyzzeri was 2.1％(3/140),and P.hominis was 7.1％(10/140),the co-infection rate of two intestinal protozoa was 7.1％(10 mice:T.muris+P.hominis),and three intestinal protozoa was 2.1％(3 mice:T.muris+P.hominis+C.tyzzeri).The total intestinal protozoan infection rate in 135 mice faecal samples provided by supplier C was 7.4％,in which,7.4％(10/135)was positive for T.muris.There are no intestinal protozoa to be detected in 130 mice faecal samples from supplier B and 135 mice faecal samples from supplier D.The homology analysis showed that the homology of ampli-fied sequence of T.muris,P.hominis and C.tyzzeri was 98.52％,98.27％and 99.87％compared with published sequence of GenBank No:AY886846.1,GenBank No:AF156964.1 and GenBank No:KJ000486.1,which was clustered as an independent branch by phylogenetic analysis respec-tively.In conclusion,there are intestinal protozoan infection in BALB/c mice in some animal sup-pliers.The co-infections of more than 3 parasites such as T.muris,P.hominis and C.tyzzeri has been found.It will provide a basis for control of intestinal protozoa infection in BALB/c mice in the future.

The left maxilla of a patient was resected because of tumor,and the defect was reconstruted with fibular transplantation.The autonomous dental implant robot technology was used to achieve precise implantation of multiple implants and immediate denture restoration within the limited left maxilla.The surgery was minimally invasive and efficient,and significantly reducing patient post-operative discomfort.The final restoration was completed 6 months after surgery.

Early neurological deterioration(END)occurs in patients with acute cerebral infarction after recombinant tissue-plasminogen activator(rt-PA)intravenous thrombolysis,which seriously affects the prognosis of patients and even causes death.However,there is no effective treatment.This report describes two patients with acute ischemic stroke presenting with right-sided limb weakness within 4.5 hours of onset.Brain CT ruled out cerebral hemorrhage and both patients were diagnosed with acute ischemic stroke.END occurred within 24 hours after intravenous thrombolysis with rt-PA.Reexamine Brain CT showed no evidence of cerebral hemorrhage.The patients were treated with continuous tirofiban infusion for 48 hours,overlapping with oral antiplatelet therapy for 4 hours and 6 hours,respectively.After discontinuation of tirofiban,no further neurological deterioration was observed.At the 3-month follow-up,there was no recurrence,and the modified Rankin scale(mRS)scores were 1 and 3,respectively.This study delineates the diagnostic and therapeutic trajectories of two paradigmatic cases to inform clinical decision-making for analogous presentations,thereby contributing to evidence-based management strategies.

Early neurological deterioration(END)occurs in patients with acute cerebral infarction after recombinant tissue-plasminogen activator(rt-PA)intravenous thrombolysis,which seriously affects the prognosis of patients and even causes death.However,there is no effective treatment.This report describes two patients with acute ischemic stroke presenting with right-sided limb weakness within 4.5 hours of onset.Brain CT ruled out cerebral hemorrhage and both patients were diagnosed with acute ischemic stroke.END occurred within 24 hours after intravenous thrombolysis with rt-PA.Reexamine Brain CT showed no evidence of cerebral hemorrhage.The patients were treated with continuous tirofiban infusion for 48 hours,overlapping with oral antiplatelet therapy for 4 hours and 6 hours,respectively.After discontinuation of tirofiban,no further neurological deterioration was observed.At the 3-month follow-up,there was no recurrence,and the modified Rankin scale(mRS)scores were 1 and 3,respectively.This study delineates the diagnostic and therapeutic trajectories of two paradigmatic cases to inform clinical decision-making for analogous presentations,thereby contributing to evidence-based management strategies.

Innovative talents are the main driving force behind the transformation of scientific and technological innovations into new quality productive forces, while the integration of research and teaching represents an advanced form of the deep integration between scientific research and educational teaching. Guangzhou Medical University, focusing on social needs and guided by the IMH (innovation, mission, and humanism) educational philosophy, has established an undergraduate innovative ability cultivation model that integrates research and teaching. By building training platforms, establishing learning communities for teachers and students, constructing courses and projects, and strengthening talent cultivation mechanisms to promote the implementation of the integration of research and teaching, the university has effectively improved the quality of education and teaching, creating a favorable environment for talent growth.

Objective:To investigate the association between short-term blood pressure variability(BPV)and all-cause mortality in elderly patients with early sepsis-associated acute kidney injury(SA-AKI).Methods:A retrospective study was conducted on elderly patients with early SA-AKI from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database between 2008 and 2022.All patients were divided into four groups(Q1-Q4)according to the quartiles of the 24-hour systolic blood pressure coefficient of variation(SBPCV): Q1(SBPCV<8.69%), Q2(8.69%≤SBPCV<10.84%), Q3(10.84%≤SBPCV<13.64%), Q4(SBPCV≥13.64%). Cox regression analysis was used to assess the association between SBPCV and one-year all-cause mortality.Restricted cubic spline regression was used for non-linear testing, and threshold effect analysis was further performed for non-linear relationships.Results:A total of 5 955 elderly patients were included in the study, and 2 746(46.11%)patients died within one year following the diagnosis of early SA-AKI.Patients in groups Q1 to Q4 had one-year all-cause mortality rates of 46.34%(690/1 489), 45.56%(678/1 488), 42.47%(632/1 488), and 50.07%(746/1 490), respectively.After adjusting for relevant confounding variables, Cox regression analysis showed that the Q1 group and Q4 group had a 26%( HR=1.26, 95% CI: 1.13-1.41, P<0.001)and 12%( HR=1.12, 95% CI: 1.01-1.24, P=0.047)higher risk of one-year mortality compared to the Q3 group, respectively.SBPCV and one-year all-cause mortality showed a U-shaped non-linear manner( P for nonlinear<0.001). Threshold effect analysis indicated that when SBPCV<13.07%, each standard deviation increase in SBPCV was associated with a 15% reduction in mortality risk( HR=0.85, 95% CI: 0.78-0.92, P<0.001); conversely, when SBPCV>13.07%, each standard deviation increase in SBPCV was associated with an 11% increase in mortality risk( HR=1.11, 95% CI: 1.03-1.21, P=0.011). Conclusions:Short-term BPV may be associated with long-term all-cause mortality in elderly patients with early SA-AKI in a U-shaped manner.However, these findings require further confirmation through high-quality prospective studies.

Objective To investigate whether curcumin(CUR)can reduce chondrocyte inflammation and cartilage degradation in osteo-arthritis(OA)and the underlying mechanisms.Methods A rat model of OA was established.Rats were randomly divided into a Sham,OA,CUR+OA,and deferoxamine(DFO)+OA groups with 10 mice in each group.Chondrocytes from 5-day-old SD rats were divided into the control,interleukin-1β(IL-1β),CUR+IL-1β,and DFO+IL-1β groups.A CCK-8 assay was performed to assess the effects of CUR on cell viability alone or combined with IL-1β.Toluidine blue staining and alcian blue staining were used to observe the morphological changes of IL-1β-induced chondrocytes.The expression of inflammatory response-related proteins(COX-2 and iNOS),extracellular matrix degradation-related proteins(COL2A and MMP13),and p53,SLC7A11,and GPX4 proteins during ferroptosis were detected by Western blotting.The mitochondrial membrane potential was detected by JC-1 staining.Mitochondrial morphology was observed using transmission electron microscopy.Safranine O-fast green/HE staining was performed on cartilage tissues.Immunohistochemical staining was performed to detect COL2A and SLC7A11 expression levels.Results CUR and DFO were found to reduce IL-1β-induced inflammation,cartilage degradation,and ferroptosis,and restore mitochondrial function in chondrocytes.CUR also reversed IL-1β-induced changes in collagen Ⅱ,p53,SLC7A11,GPX4,MMP13,iNOS,and COX-2 levels.In vivo,intra-articular injection of CUR significantly improved cartilage injury in the OA rat model,and the percentages of COL2A-and SLC7A11-positive cells significantly increased in the CUR+OA and DFO+OA groups.Conclusion CUR inhibits ferroptosis and ameliorates cartilage degeneration in OA through p53 signaling pathway.