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.

ObjectiveToll-like receptor 4 （TLR4）， a receptor for pathogen-associated molecular patterns of innate immunity， is associated with neurodegenerative diseases. Interleukin （IL）-6， IL-1β， and tumor necrosis factor-α （TNF-α） as common pro-inflammatory cytokines and high-sensitivity C-reactive protein （hs-CRP） are related to inflammatory responses. This study evaluated the clinical efficacy and possible mechanisms of therapeutic effects of Fengyintang on early and mid-stage PD with excessive heat generating wind by observing the effects of Fengyintang on the serum levels of TLR4， IL-6， IL-1β， TNF-α， and hs-CRP in the patients with PD. MethodsSixty-eight PD patients who met the inclusion criteria were randomly assigned into the control group and the observation group （n=34）. Both groups were treated with anti-PD Western medicine and the observation group was additionally treated with Fengyintang. Both groups were treated for 8 weeks. Before and after 8 weeks of treatment， the patients in the two groups were measured for their TCM symptom scores， International Movement Disorder Society Unified Parkinson's Disease Rating Scale （MDS-UPDRS） score， Parkinson's Disease Non-Motor Symptom Scale （NMSS） score， Patient Assessment of Constipation Symptom （PAC-SYM） score， Pittsburgh Sleep Quality Index （PSQI）， Hamilton Anxiety Scale （HAMA） score， Hamilton Depression Scale （HAMD） score， and changes in serum TLR4， IL-6， IL-1β， TNF-α， and hs-CRP levels. ResultsOne case in the control group was removed due to loss of visit， and a total of 67 PD patients （33 in the control group and 34 in the observation group） who met the criteria were included for analysis. After treatment， patients in the observation group showed decreases in scores of TCM symptoms， MDS-UPDRS， NMSS， PAC-SYM， PSQI， HAMA， and HAMD （P<0.05， P<0.01）. Moreover， the observation group had lower scores of TCM symptoms， MDS-UPDRS， NMSS， PAC-SYM， PSQI， HAMA， and HAMD than the control group （P<0.05， P<0.01）. The observation group showed higher efficacy in terms of TCM symptoms and MDS-UPDRS score than the control group （Z=-0.57， P<0.05）. The overall response rate was higher in the observation group than in the control group （Z=-0.62， P<0.05， P<0.01）. The serum TLR4， TNF-α， IL-1β， IL-6， and hs-CRP levels of the observation group were lower than those of the control group （P<0.05， P<0.01）. ConclusionFengyintang combined with Western medicine can safely and effectively alleviate the clinical symptoms， reduce the levels of inflammatory factors， improve the quality of life， and delay the disease progression of PD patients by inhibiting peripheral TLR4 expression and thus suppressing the downstream inflammatory response.

As a common type of primary liver cancer， hepatocellular carcinoma （HCC） is a major health threat in China. Ultrasound is a crucial imaging modality in the clinical diagnosis and treatment of HCC， and the development and application of new ultrasound technologies have high clinical value. Currently， ultrasound and contrast-enhanced ultrasound combined with artificial intelligence have shown promising potential in the detection of focal liver lesions， image-based HCC diagnosis， outcome assessment， and prognostic prediction； furthermore， ultrasound fusion imaging technology has shown certain clinical value in guidance and efficacy evaluation of percutaneous thermal ablation； three-dimensional ultrasound has certain advantages in assisting ablation and assessing ablation margins； endoscopic ultrasonography can be used as a supplementary method for HCC cases that are difficult to scan or guide via percutaneous ultrasound.

OBJECTIVES: We propose a segmented backprojection tensor degradation feature encoding (SBP-MAC) model for motion artifact correction in dental cone beam computed tomography (CBCT) to improve the quality of the reconstructed images. METHODS: The proposed motion artifact correction model consists of a generator and a degradation encoder. The segmented limited-angle reconstructed sub-images are stacked into the tensors and used as the model input. A degradation encoder is used to extract spatially varying motion information in the tensor, and the generator's skip connection features are adaptively modulated to guide the model for correcting artifacts caused by different motion waveforms. The artifact consistency loss function was designed to simplify the learning task of the generator. RESULTS: The proposed model could effectively remove motion artifacts and improve the quality of the reconstructed images. For simulated data, the proposed model increased the peak signal-to-noise ratio by 8.28%, increased the structural similarity index measurement by 2.29%, and decreased the root mean square error by 23.84%. For real clinical data, the proposed model achieved the highest expert score of 4.4221 (against a 5-point scale), which was significantly higher than those of all the other comparison methods. CONCLUSIONS The SBP-MAC model can effectively extract spatially varying motion information in the tensors and achieve adaptive artifact correction from the tensor domain to the image domain to improve the quality of reconstructed dental CBCT images.
Cone-Beam Computed Tomography/methods* ; Artifacts ; Humans ; Motion ; Image Processing, Computer-Assisted/methods* ; Signal-To-Noise Ratio ; Algorithms

OBJECTIVE: To compare the effectiveness of clavicular hook plate fixation in the treatment of acromioclavicular joint dislocation and distal clavicle fractures. METHODS: A clinical data of 90 patients, who underwent clavicular hook plate fixation between January 2014 and June 2023, was retrospectively analyzed. There were 40 patients with distal clavicle fractures (fracture group) and 50 with acromioclavicular joint dislocations (dislocation group). There was no significant difference in the baseline data of gender, age, cause of injury, side of injury, time from injury to operation, and constituent ratio of osteoporosis patients between the two groups ( P>0.05). The time to remove the internal fixators and the occurrence of complications were recorded. Before removing the internal fixator and at 3 months after removing, the visual analogue scale (VAS) score was used to evaluate the degree of pain, and the mobility of the shoulder joint in forward flexion, elevation, and abduction was measured. Before removing the internal fixators, the Constant-Murley score and the University of California, Los Angeles (UCLA) score were used to evaluate the function of the shoulder joint. X-ray films of the shoulder joint were taken during follow-up to observe the occurrence of subacromial osteolysis, acromioclavicular joint osteoarthritis, and distal clavicle bone atrophy. Subgroup comparison was conducted between patients with and without subacromial osteolysis in the two groups. RESULTS: All incisions healed by first intention in both groups. All patients were followed up 1-9 years, with a median of 5 years; the difference in follow-up time between the two groups was not significant ( P>0.05). During follow-up, subacromial osteolysis occurred in 74 cases, including 41 cases of typeⅠand 33 cases of type Ⅱ, distal clavicle bone atrophy in 15 cases, and acromioclavicular joint osteoarthritis in 8 cases. There were significant differences in the removal time of internal fixators, the incidence of bone atrophy, and the incidence of osteoarthritis between the two groups ( P<0.05). There was no significant difference in the incidence of subacromial osteolysis ( P>0.05). Before removing the internal fixators, there was no significant difference in VAS score, UCLA score, and Constant-Murley score between the two groups ( P>0.05), while there were significant differences in shoulder joint range of motion in all directions ( P<0.05). After removing the internal fixators, only the difference in elevation was significant ( P<0.05). Within the group comparison, the VAS score and mobility of shoulder joint in abduction and elevation after removing the internal fixators were significantly superior to those before removing ( P<0.05). In the fracture and dislocation groups, there was only a significant difference in plate length between the subgroup with and without subacromial osteolysis ( P<0.05), while there was no significant difference in the above other indicators ( P>0.05). CONCLUSION Clavicular hook plate is a good choice for treating acromioclavicular dislocation or distal clavicle fractures, but the incidence of subacromial osteolysis is higher, and the degree of bone resorption is more severe in fracture patients. After removal of the internal fixator, the shoulder functions significantly improve. It is recommended to remove the internal fixator as soon as possible within the allowable range of the condition.
Humans ; Clavicle/surgery* ; Acromioclavicular Joint/surgery* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/surgery* ; Male ; Retrospective Studies ; Female ; Adult ; Middle Aged ; Treatment Outcome ; Joint Dislocations/surgery* ; Aged ; Range of Motion, Articular ; Young Adult ; Postoperative Complications

Objective:To explore the effectiveness of immersive virtual reality (VR)-guided core stability-assisted training in improving the balance of ischemic stroke survivors.Methods:Sixty-six hemiplegic ischemic stroke survivors were randomly divided into a conventional rehabilitation training group (CON) of 32 and an immersive VR-guided core stability-assisted training group (VR-TOT) of 34. In addition to basic internal medical treatment, the CON group underwent conventional rehabilitation therapy, while the VR-TOT group received VR-guided core stability-assisted training. Before and after 4 weeks of the treatments, the subjects′ balance was evaluated using the Fugl-Meyer balance scale. A three-dimensional force platform was used to collect the sway amplitude, sway speed, peripheral area and total trajectory length of the center of pressure COP of the bilateral plantar in the left-right and anterior-posterior directions while the subjects stood with the eyes open and closed.Results:After the treatments, the average Fugl-Meyer balance scores of both groups had improved significantly. In the eyes-open condition, after the treatment, there was a significant decrease in the average COP sway amplitude in the anteroposterior direction on the hemiplegic side among the CON group, as well as in both the mediolateral and anteroposterior directions on both sides in the VR-TOT group. The sway velocity in the anteroposterior direction on the hemiplegic side had decreased significantly in both groups, and the sway velocity in both the mediolateral and anteroposterior directions on the non-hemiplegic side had also decreased significantly. In the CON group the peripheral area on the non-hemiplegic side had decreased and the total trajectory length had shortened significantly. In the VR-TOT group there were significant decreases in the peripheral area on both sides and in the total trajectory length on both sides. Comparing the two groups after treatment, the peripheral area on the hemiplegic side in the VR-TOT group was significantly smaller. In the eyes-closed condition, the sway amplitude of the COP on the hemiplegic side in the anteroposterior direction and on the non-hemiplegic side in both the mediolateral and anteroposterior directions had decreased significantly in the VR-TOT group after the treatment. The average sway velocity had decreased significantly in the anteroposterior direction on the non-hemiplegic side in the CON group. In the VR-TOT group this was observed in the anteroposterior direction on the hemiplegic side and in both the mediolateral and anteroposterior directions on the healthy side. In the CON group the average peripheral area of the COP on the hemiplegic side had decreased, and the total trajectory length had shortened, both significantly. In the VR-TOT group, the peripheral area on the non-hemiplegic side had decreased significantly as well.Conclusions:Core stability-assisted training based on immersive virtual reality can effectively improve the balance of ischemic stroke survivors. It shows promise for clinical application.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

OBJECTIVE To provide standardized whole-process guidance on drug traceability codes for medical institutions in Sichuan province， ensuring medication safety and compliance with medical insurance supervision requirements. METHODS Based on evidence-based principles and expert consensus， Expert Consensus on Whole-process Management of Drug Traceability Codes in Medical Institutions of Sichuan Province （hereinafter referred to as the Consensus） was formulated through systematic literature review， field investigations， establishment of a multidisciplinary expert committee and multiple rounds of questionnare consultation via the modified Delphi method， and finalized through consensus meetings. RESULTS & CONCLUSIONS The Consensus clarifies key operating procedures for code verification， code assignment and code return， whole-process operational standards for drug warehouse acceptance and storage， drug warehouse outbound delivery and pharmacy acceptance check， drug distribution and dispensing in pharmacy and intravenous admixture center， medication administration in nursing units and examination departments， as well as drug return process. Key recommendations are proposed such as improving the core functions of the drug traceability system， unifying the hospital-wide traceability code database， strengthening the management of traceability codes for backup medications， establishing a management organization and institutional framework， and optimizing the architectural design and data governance requirements of the drug traceability system. The release of the Consensus will provide scientific， standardized and implementable practical guidelines for medical institutions of Sichuan province， helping to improve closed-loop management of the drug traceability system， strengthen medication safety and fulfil medical insurance fund supervision.