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.

Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

General anesthesia, pivotal for surgical procedures, requires precise depth monitoring to mitigate risks ranging from intraoperative awareness to postoperative cognitive impairments. Traditional assessment methods, relying on physiological indicators or behavioral responses, fall short of accurately capturing the nuanced states of unconsciousness. This study introduces a machine learning-based approach to decode anesthesia depth, leveraging EEG data across different anesthesia states induced by propofol and esketamine in rats. Our findings demonstrate the model's robust predictive accuracy, underscored by a novel intra-subject dataset partitioning and a 5-fold cross-validation method. The research diverges from conventional monitoring by utilizing anesthetic infusion rates as objective indicators of anesthesia states, highlighting distinct EEG patterns and enhancing prediction accuracy. Moreover, the model's ability to generalize across individuals suggests its potential for broad clinical application, distinguishing between anesthetic agents and their depths. Despite relying on rat EEG data, which poses questions about real-world applicability, our approach marks a significant advance in anesthesia monitoring.
Animals ; Machine Learning ; Electroencephalography/methods* ; Ketamine/administration & dosage* ; Rats ; Male ; Propofol/administration & dosage* ; Rats, Sprague-Dawley ; Anesthesia, General/methods* ; Brain/physiology* ; Intraoperative Neurophysiological Monitoring/methods*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

The construction of a new cultural system for high-quality development in public hospitals serves as a crucial pillar for achieving their high-quality advancement.During this developmental processe stablishing a cultural framework that aligns with the new development model holds particular significance.Through content analysis methodology,it identifies 18 core elements of the new cultural system for high-quality development in public hospitals.Furthermore it synthesizes seven implementation pathways across three dimensions-organizational patientand employee perspectives:digital leadership organizational reform capability talent innovation capability resource integration capability normative constraint force value co-creation capability and employee support capability.These findings provide both theoretical and practical references for cultivating new cultural constructs that facilitate high-quality development in public hospitals.

Objective To analyze the trends of suicide mortality and disease burden among the elderly aged 60 and above in Chongqing from 2012 to 2023,providing evidence for targeted interventions.Methods Death cases of elderly aged 60 and above were extracted from death registration between 2012 and 2023 according to death records(International Statistical Classification of Diseases and Related Health Problems,10th version:X60-X84,Y87).The data were analyzed to calculate indicators such as the mortality rate,standardized mortality rate,years of life lost(YLL)rate,and average years of life lost(AYLL),and the composition ratio of different causes of death with using Excel 2010 and SPSS 26.0.The comparison of mortality rates between male and female,urban and rural area was conducted using the x2 test.The trend changes of the rates were expressed by the annual percentage change(APC)and the average annual percentage change(AAPC).Results From 2012 to 2023,the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above generally showed a downward trend,decreasing by 3.54%and 4.02%,respectively(P<0.05).From 2012 to 2016,the suicide mortality rate increased by an average of 4.53%per year,and from 2016 to 2021,it decreased by an average of 8.91%per year,and both trends were significant(P<0.05).Only in 2020 and 2022,the male suicide mortality rate was significantly higher than that of females(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate of males and females decreased by an average of 2.86%,3.44%,4.21%,and 4.69%per year respectively,and the trends were significant(P<0.05).The suicide mortality rate of the elderly aged 60 and above in rural areas was significantly higher than that in urban areas over the years(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate in urban areas remained relatively stable(P>0.05),while the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above in rural areas decreased by an average of 3.44%and 4.02%per year respectively,and the trends were significant(P<0.05).The YLL rate and AYLL caused by suicide among the elderly aged 60 and above decreased from 3.03‰ and 18.54 years in 2012 to 2.26‰ and 17.50 years in 2023 respectively,and the AAPC were-4.02%and-0.60%respectively,and the trends were significant(P<0.05).By comparing the composition of deaths by different suicide methods over the years,it was found that the proportion of deaths due to pesticide poisoning showed a downward trend,while the proportions of deaths by hanging,jumping from a height,and drowning showed an upward trend.Conclusion The suicide mortality rate of the elderly aged 60 and above in Chongqing is relatively high.Although demonstrating an overall downward trend,enhanced efforts toward early identification and intervention for elderly suicide should be enhanced.

Objective To analyze the trends of suicide mortality and disease burden among the elderly aged 60 and above in Chongqing from 2012 to 2023,providing evidence for targeted interventions.Methods Death cases of elderly aged 60 and above were extracted from death registration between 2012 and 2023 according to death records(International Statistical Classification of Diseases and Related Health Problems,10th version:X60-X84,Y87).The data were analyzed to calculate indicators such as the mortality rate,standardized mortality rate,years of life lost(YLL)rate,and average years of life lost(AYLL),and the composition ratio of different causes of death with using Excel 2010 and SPSS 26.0.The comparison of mortality rates between male and female,urban and rural area was conducted using the x2 test.The trend changes of the rates were expressed by the annual percentage change(APC)and the average annual percentage change(AAPC).Results From 2012 to 2023,the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above generally showed a downward trend,decreasing by 3.54%and 4.02%,respectively(P<0.05).From 2012 to 2016,the suicide mortality rate increased by an average of 4.53%per year,and from 2016 to 2021,it decreased by an average of 8.91%per year,and both trends were significant(P<0.05).Only in 2020 and 2022,the male suicide mortality rate was significantly higher than that of females(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate of males and females decreased by an average of 2.86%,3.44%,4.21%,and 4.69%per year respectively,and the trends were significant(P<0.05).The suicide mortality rate of the elderly aged 60 and above in rural areas was significantly higher than that in urban areas over the years(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate in urban areas remained relatively stable(P>0.05),while the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above in rural areas decreased by an average of 3.44%and 4.02%per year respectively,and the trends were significant(P<0.05).The YLL rate and AYLL caused by suicide among the elderly aged 60 and above decreased from 3.03‰ and 18.54 years in 2012 to 2.26‰ and 17.50 years in 2023 respectively,and the AAPC were-4.02%and-0.60%respectively,and the trends were significant(P<0.05).By comparing the composition of deaths by different suicide methods over the years,it was found that the proportion of deaths due to pesticide poisoning showed a downward trend,while the proportions of deaths by hanging,jumping from a height,and drowning showed an upward trend.Conclusion The suicide mortality rate of the elderly aged 60 and above in Chongqing is relatively high.Although demonstrating an overall downward trend,enhanced efforts toward early identification and intervention for elderly suicide should be enhanced.