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 analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

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.

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

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

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.

Objective We propose a motion artifact correction algorithm(DMBL)for reducing motion artifacts in reconstructed dental cone-beam computed tomography(CBCT)images based on deep blur learning.Methods A blur encoder was used to extract motion-related degradation features to model the degradation process caused by motion,and the obtained motion degradation features were imported in the artifact correction module for artifact removal.The artifact correction module adopts a joint learning framework for image blur removal and image blur simulation for treatment of spatially varying and random motion patterns.Comparative experiments were conducted to verify the effectiveness of the proposed method using both simulated motion data sets and clinical data sets.Results The experimental results with the simulated dataset showed that compared with the existing methods,the PSNR of the proposed method increased by 2.88%,the SSIM increased by 0.89%,and the RMSE decreased by 10.58%.The results with the clinical dataset showed that the proposed method achieved the highest expert level with a subjective image quality score of 4.417(in a 5-point scale),significantly higher than those of the comparison methods.Conclusion The proposed DMBL algorithm with a deep blur joint learning network structure can effectively reduce motion artifacts in dental CBCT images and achieve high-quality image restoration.

BACKGROUND:Artificially synthesized hydroxyapatite ceramic granules are widely used in clinical practice to repair large-volume bone defects.However,the osteogenic effect of hydroxyapatite ceramic granules prepared by high-temperature sintering is limited by their low degradability and bioactivity. OBJECTIVE:To prepare biomimetically precipitated nanocrystalline calcium phosphate granules by a novel low-temperature deposition technique,and to characterize their physicochemical properties and cytocompatibility. METHODS:Biomimetically precipitated nanocrystalline calcium phosphate granules were prepared using a modified supersaturated calcium phosphate mineralization solution and a repeated settling and decantation washing method.Hydroxyapatite bioceramic granules were used as the control.The morphology and phase composition of the granules were characterized by scanning electron microscopy,X-ray diffraction,and Fourier transform infrared spectroscopy.The specific surface area,porosity distribution,hardness and hydrophilicity of the granules were characterized by BET-N2 method,hardness test,and contact angle test.The adsorption properties of the granules for bovine serum albumin and fetal bovine serum protein were determined by bicinchoninic acid assay.The two kinds of granules or granule extracts were co-cultured with human umbilical cord mesenchymal stem cells,and the cell proliferation was detected by MTT assay. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two kinds of particles was slightly rough and accompanied by tiny particles,the surface of the hydroxyapatite bioceramic particles was dense and smooth,and the biomimetically precipitated nanocrystalline calcium phosphate granules were mainly composed of needle/plate crystals with non-uniform nanometer size,and formed a nanopore structure between the crystals.X-ray diffraction and Fourier transform infrared spectroscopy exhibited that compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules had smaller crystalline particles,lower crystallinity,and more binding water and carbonic acid groups.Compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules had higher specific surface area,better hydrophilicity,lower hardness,and higher protein adsorption capacity.(2)The results of MTT assay showed that the two kinds of granule extracts had no cytotoxicity,human umbilical cord mesenchymal stem cells survived well on the surface of the two kinds of granules,and the biomimetically precipitated nanocrystalline calcium phosphate granules had stronger cell proliferation activity.(3)These findings indicate that compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules have better physicochemical properties and cytocompatibility.

Objective:To investigate the perinatal outcomes and risk factors of perinatal complications in preg-nant women with hypertrophic cardiomyopathy(HCM).Methods:A retrospective analysis was carried out on clini-cal data of 100 pregnant women with HCM who delivered in Obstetrical Cardiology Intensive Care Center of Shanghai Renji Hospital between Jan.2000 and Dec.2022.Analyze the incidence of perinatal complications inclu-ding miscarriage,premature birth,small for gestational age infants,neonatal asphyxia,neonatal cardiac malforma-tions and perinatal mortality.Independent risk factors of perinatal complications in pregnant women with HCM were identified using univariate and multivariate Logistic regression.Results:①The mean age was 29.21±4.41 years old,the average gestational age upon admission is 34.46±6.43 weeks.There were 16 patients with a fam-ily history of cardiomyopathy(16％),21 cases with obstructive HCM(21％)and 79 cases of non-obstructive HCM(79％),91 cases with abnormal ECG(91％),mainly with ST-T changes(77 cases,77％).The average in-terventricular septum was 19.39±6.13mm by echocardiography.②Among the 100 pregnancies of 100 HCM pa-tients,6 cases(6％)were miscarriages,94 newborns survived(94％),including 91 cases of cesarean section(91％)and 3 cases of vaginal delivery(3％).The predominant perinatal complications were preterm delivery(39 cases,39％),small for gestational age(5 cases,5％),neonatal asphyxia(3 cases,3％)and neonatal cardiac malformation(2 cases,2％).There were no perinatal deaths.③Univariate Logistic regression analysis showed that pre pregnancy heart function ≥ Grade Ⅱ,increased left atrial diameter,and concomitant pulmonary hyperten-sion were risk factors for perinatal complications in pregnant women with HCM(OR＞1,P＜0.05).Multivariate Lo-gistic regression analysis found that pre pregnancy heart function ≥ Grade Ⅱ was an independent risk factor for predicting the occurrence of perinatal complications in pregnant women with HCM(OR 6.270,P＜0.05).Conclu-sions:HCM during pregnancy can induce poor perinatal outcome.More attention should be paid to risk assess-ment and pregnancy management.Early detection of risk factors can reduce the incidence of perinatal complica-tions.