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 understand the situation of dental cone beam computed tomography (CBCT) quality control testing phantoms in radiation health technical service institutions in Guangdong province, analyze the differences among different phantoms, and provide a reference for dental CBCT quality control testing. Methods The testing phantoms of 49 radiation health technical service institutions were used as the research objects. The designated CBCT equipment was used for scanning and imaging. The Z-score method was used to evaluate the high-contrast resolution, low-contrast resolution, and distance measurement deviation of each phantom. Results The satisfaction rates of various items for the phantoms in 49 institutions ranged from 85.7% to 100%. The distance measurement deviations of four institutions were “suspicious”, and the high-contrast resolution of four institutions and the distance measurement deviation of one institution were “unsatisfactory”. Conclusion The overall performance of dental CBCT quality control testing phantoms in radiological health technical service institutions in Guangdong province is satisfactory. However, there are still some phantoms with poor results in items such as distance measurement deviation and high-contrast resolution. The structural design, material selection, and manufacturing process of the phantom may all affect the results of quality control testing. Therefore, appropriate phantoms, optimized exposure conditions, and suitable reconstruction algorithms should be used in CBCT quality control testing to ensure accurate and reliable measurements.

Objective To explore the risk factors for postoperative respiratory failure (RF) in patients with esophageal cancer, construct a predictive model based on the least absolute shrinkage and selection operator (LASSO)-logistic regression, and visualize the constructed model. Methods A retrospective analysis was conducted on patients with esophageal cancer who underwent surgical treatment in the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Gansu Hospital from 2020 to 2023. Patients were divided into a RF group and a non-RF (NRF) group according to whether RF occurred after surgery. Clinical data of the two groups were collected, and LASSO-logistic regression was used to optimize feature selection and construct the predictive model. The model was internally validated by repeated sampling 1000 times based on the Bootstrap method. Results A total of 217 patients were included, among which 24 were in the RF group, including 22 males and 2 females, with an average age of (63.33±9.10) years; 193 were in the NRF group, including 161 males and 32 females, with an average age of (62.14±8.44) years. LASSO-logistic regression analysis showed that the percentage of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) to predicted value (FEV1/FVC%pred) [OR=0.944, 95%CI (0.897, 0.993), P=0.026], postoperative anastomotic fistula [OR=4.106, 95%CI (1.457, 11.575), P=0.008], and postoperative lung infection [OR=3.776, 95%CI (1.373, 10.388), P=0.010] were risk factors for postoperative RF in patients with esophageal cancer. Based on the above risk factors, a predictive model was constructed, with an area under the receiver operating characteristic curve of 0.819 [95%CI (0.737, 0.901)]. The Hosmer-Lemeshow test for the calibration curve showed that the model had good goodness of fit (P=0.527). The decision curve showed that the model had good clinical net benefit when the threshold probability was between 5% and 50%. Conclusion FEV1/FVC%pred, postoperative anastomotic fistula, and postoperative lung infection are risk factors for postoperative RF in patients with esophageal cancer. The predictive model constructed based on LASSO-logistic regression analysis is expected to help medical staff screen high-risk patients for early individualized intervention.

BACKGROUND:MXene nanoparticles,due to their unique hydrophilicity,biocompatibility,and antibacterial properties,are widely used in wound,tumor,nerve repair,and cardiovascular treatments.However,it is still unclear what effect MXene nanoparticles have on diabetic wound healing.OBJECTIVE:To investigate the in vitro antioxidant,anti-inflammatory and photothermal antibacterial properties of MXene nanoparticles Ti3C2Tx as well as their effect on wound repair in diabetic mice.METHODS:(1)In vitro experiments:The cytotoxicity of Ti3C2Tx nanoparticles on mouse fibroblasts(NIH-3T3)at various concentrations was evaluated using the methyl thiazolyl tetrazolium(MTT)assay.NIH-3T3 cells were exposed to H2O2,and the MTT assay was used to detect the protective effects of different mass concentrations of Ti3C2Tx on NIH-3T3 cells.NIH-3T3 cells were exposed to H2O2,and the effect of Ti3C2Tx(20 μg/mL)on the generation of reactive oxygen species in NIH-3T3 cells was analyzed under illumination(or no illumination)treatment.RAW264.7 macrophages were divided into three groups:control group,lipopolysaccharide group,and lipopolysaccharide+Ti3C2Tx group.Real-time quantitative PCR was used to detect the expression of specific genes(CD86,interleukin 6,CD206,arginase 1)in the cells.Escherichia coli(or Staphylococcus aureus)were divided into three groups:control group,Ti3C2Tx group,and Ti3C2Tx illumination group.The bacterial survival rate was calculated by plate colony counting method.(2)In vivo experiments:Streptozotocin was administered intraperitoneally to ICR mice to induce a diabetic condition.After successful modeling,a full-thickness skin defect wound was created on the back of the mice using a circular punch.The experiment was divided into three groups:control group(n=6),Ti3C2Tx group(n=6),and Ti3C2Tx illumination group(n=6).The wound healing was observed,and CD31 and CD206 immunohistochemical staining of wound tissue was performed on day 7 after intervention.Hematoxylin-eosin staining and Masson staining of wound tissue were performed on days 7 and 14 after intervention.Ti3C2Tx solution was injected subcutaneously into ICR mice.After illumination(or non-illumination)exposure,the toxic effects of Ti3C2Tx on mice were analyzed by blood biochemical detection.RESULTS AND CONCLUSION:(1)In vitro experiments:Ti3C2Tx showed no cytotoxicity on NIH-3T3 cells at mass concentrations ranging from 5-160 μg/mL.It increased the survival rate of NIH-3T3 cells at a mass concentration of 20 μg/mL.Ti3C2Tx at 10-80 μg/mL significantly improved the survival rate of NIH-3T3 cells under H2O2 intervention.Ti3C2Tx significantly inhibited the generation of reactive oxygen species in NIH-3T3 cells under the intervention of H2O2,and illumination treatment further enhanced the effect of Ti3C2Tx on inhibiting the generation of reactive oxygen species.Ti3C2Tx effectively inhibited macrophage inflammation induced by lipopolysaccharide and promoted the transformation of cells into M2 macrophages with anti-inflammatory properties.Both Ti3C2Tx and Ti3C2Tx illumination significantly inhibited the growth of Escherichia coli and Staphylococcus aureus,and the inhibitory effect of Ti3C2Tx illumination was more significant.(2)In vivo experiments:Gross and histological analyses of the wound surface showed that both Ti3C2Tx and Ti3C2Tx illumination promoted wound healing in diabetic mice,and the promotion effect of Ti3C2Tx irradiation was more significant.Immunohistochemical staining results showed that both Ti3C2Tx and Ti3C2Tx illumination inhibited the inflammatory response in diabetic wounds and promoted angiogenesis,and the effect of Ti3C2Tx illumination was more significant.Blood biochemical test results showed that Ti3C2Tx and illumination had no obvious toxic effects on mice.(3)These results indicate that Ti3C2Tx nanoparticles efficiently promote the healing of skin wounds in a diabetic mouse model through antioxidation,anti-inflammation,and antibacterial actions via photothermal effects.

Objective:To explore the related risk factors contributing to re-fracture after hip surgery in elderly patients.Methods:This retrospective analysis was conducted on the clinical data of 2 415 elderly individuals who underwent surgical treatment for hip fractures and were discharged from Shanghai Sixth People's Hospital between January 2016 and December 2021.Patients were grouped into re-fracture and non-re-fracture cohorts based on whether a second fracture occurred within three years after surgery.Demographics, clinical data, and postoperative functional rehabilitation outcomes of the two groups were collected, and univariate and multivariate logistic regression analyses were applied to identify the independent risk factors for re-fractures after surgery.Results:A total of 2, 000 patients who completed follow-up were included in the final analysis, aged 60~91 years, with a mean age of (75.4±8.2) years.Among them, 855 were male(42.75%), and the postoperative re-fracture incidence was 28.25% (565/2 000). Univariate analysis indicated that advanced age, fracture type at first onset, lower Harris scores, insufficient rehabilitation training, osteoporosis, diabetes, cerebrovascular disorders, visual impairment, and syncope were all significantly associated with re-fracture (all P<0.05), while gender differences were not statistically significant ( P>0.05). Multivariate regression confirmed the following as independent risk factors: age ≥75 years, postoperative Harris score <80, non-standard rehabilitation training, combined osteoporosis, diabetes, cerebrovascular disease, visual impairment, and syncope ( OR、 RR>1). Conclusions:Elderly patients are prone to re-fracture after hip surgery, and its occurrence is closely related to advanced age, inadequate functional rehabilitation, osteoporosis, and multiple internal medical comorbidities.In clinical practice, attention should be paid to standardized postoperative rehabilitation, systematic anti-osteoporotic therapy, and active intervention of comorbidities to reduce the incidence of re-fracture and improve the long-term prognosis of patients.

PURPOSE: Intrathoracic and intra-abdominal injuries in patients with rib fractures are often overlooked, leading to delayed and ineffective treatment. However, the relationship between rib fractures and organ damage has been rarely studied. The purpose of this study was to analyze the risk factors associated with intrathoracic and intra-abdominal injuries in patients with rib fractures. METHODS: This retrospective observational study included 1269 patients diagnosed with rib fractures from September 2020 to April 2023. Patient data were collected, including gender, age, body mass index, systolic blood pressure, heart rate, type of rib fracture, number of fractured ribs, location of the rib fracture, and the presence of thoracic and abdominal organ injuries. Patients without imaging examinations, the patient with rib fractures from iatrogenic causes or mental illnesses or rheumatic immune diseases was excluded. The primary outcomes were intra-thoracic and intra-abdominal injuries. Multivariate logistic regression analysis was conducted to identify the risk factors for these injuries in patients with rib fractures. RESULTS: The rib fracture characteristics in the occurrence group included bilateral fractures, higher number of fractures (≥3), and fractures located anteriorly, posteriorly, and laterally, as well as greater fracture displacement, compared to the non-occurrence group. The results of the multivariate logistic regression analysis indicated that age (p=0.016, odds ratio (OR)=0.95, 95% confidence interval (CI: 0.92-0.98), the number of rib fractures (≥3, p=0.001, OR=1.46, 95% CI: 1.13-1.89), rib type (bilateral rib fractures, p=0.043, OR=2.63, 95% CI: 2.16-3.12), and rib fracture location (lateral rib fractures, p=0.041, OR=2.85, 95% CI: 1.31-4.97; posterior rib fractures, p=0.022, OR=3.25, 95% CI: 1.46-6.92) were independent risk factors for thoracic and abdominal organ injuries in patients with traumatic rib fractures. CONCLUSIONS Patients with rib fractures resulting from blunt trauma, particularly those with lateral or posterior rib fractures, fractures involving more than 3 ribs, and bilateral rib fractures, are at an increased risk for significant intrathoracic and intra-abdominal injuries. These findings warrant attention and the implementation of appropriate preventive measures during treatment.
Humans ; Rib Fractures/complications* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Thoracic Injuries/epidemiology* ; Abdominal Injuries/epidemiology* ; Risk Factors ; Adult ; Aged ; Logistic Models ; Young Adult

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

OBJECTIVES: To evaluate the association of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). METHODS: This genetic association study was conducted among a total of 361 women aged ≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university-affiliated IVF center. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index, and follicular output rate. RESULTS: The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was 22. Based on the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), the patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL (adjusted β=1.8, 95% CI: 0.2-3.4, P=0.024) and group LL (adjusted β=1.5, 95% CI: 0.2-2.7, P=0.021). No significant difference was observed in the number of AFCs between group SL and group LL (P>0.05). Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors (P>0.05). CONCLUSIONS GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women, indicating that AR gene polymorphisms may affect ovarian reserve.
Adult ; Female ; Humans ; Genotype ; Ovarian Follicle/cytology* ; Ovarian Reserve/genetics* ; Ovulation Induction/methods* ; Polymorphism, Genetic ; Receptors, Androgen/genetics* ; East Asian People/genetics*

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry