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.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To explore the value of using computed tomography(CT)values to distinguish fresh and old fractures vertebral bodies in osteoporotic vertebral compression fractures(OVCF).Methods:Retrospective analysis of clinical data of 101 OVCF patients in our hospital from September 2022 to September 2023.Kappa test for consistency between magnetic resonance imaging(MRI)and vertebral CT values in distinguished fresh or old OVCF.The difference of CT values between fresh,old fractures and adjacent normal vertebral bodies were compared.The diagnostic efficiency was analyed by receiver operating characteristic(ROC)curve.Results:There was a high consistency between vertebral CT values and MRI in the diagnosis of OVCF in fresh and old fractures(Kappa value=0.934).There was a difference in difference of CT values between adjacent normal vertebral bodies and fresh fractures vertebral bodies(P＜0.05).There was a difference in difference of CT values of fresh fractures vertebral bodies and old fractures vertebral bodies(P＜0.05).The ROC curve analysis results showed that,the combined measurement of CT values of fresh and old fractured vertebral bodies has an area under the curve(AUC)of 0.723,which was higher than alone measurement of the CT values of fresh fractured vertebral bodies and old fractured vertebral bodies of 0.536 and 0.610(Z=2.548,2.605,2.841,P＜0.05).Conclusion:CT values of vertebral bodies show high consistency in distinguish fresh and old fractures of OVCF compared to MRI findings,and the diagnostic efficiency of combine detection is relatively high.

Objective:To explore the diagnostic value of conventional computed tomography(CT)combined with enhanced CT scan in bone metastases.Methods:This study was a retrospective observational study,84 suspected bone metastases patients admitted to our hospital from January 2022 to August 2024 were selected,All patients underwent conventional CT and enhanced CT scan and pathological examination,Using pathological examination results as the"gold standard"for diagnosis.The imaging manifestations of bone metastases using conventional CT combined with enhanced CT scan examination were observed;The detection rate and bone metastases types of conventional CT and enhanced CT scan were analyzed;The bone metastases location in different types of malignant tumors were analyzed;The detection results of bone metastases between conventional CT and enhanced CT scan were compared;the diagnostic efficacy of conventional CT and enhanced CT scan alone and in combination for bone metastases were analyzed by Receiver operating characteristic(ROC)curve.Results:The detection rate of osteogenic,osteolytic,cystic and mixed bone metastases by conventional CT combined with enhanced CT scan was supered to that of conventional CT and enhanced CT scan alone(P＜0.05).Bone metastases from lung cancer,breast cancer and other tumors mainly occur in the spine,limbs and ribs,while esophageal cancer,gastric cancer,liver cancer,prostate cancer,thyroid cancer,renal cancer,and nasopharyngeal cancer had relatively fewer bone metastases.The positive detection cases of bone metastases used conventional CT combined with enhanced CT scan were supered to those used conventional CT and enhanced CT scan alone.The sensitivity,specificity and accuracy of conventional CT combined with enhanced CT scan for the diagnosis of bone metastases were 94.00％,94.11％and 94.04％,respectively,and the positive/negative predictive values were 95.91％and 91.42％,respectively.The sensitivity,specificity and accuracy of conventional CT scan were 84.00％,78.78％and 80.95％,respectively,and the positive/negative predictive values were 85.71％and 74.28％,respectively.The sensitivity,specificity and accuracy of enhanced CT were 89.79％,85.71％and 88.09％,respectively.and the positive and negative predictive values were 89.79％and 85.71％,respectively.The diagnostic efficacy of conventional CT combined with enhanced CT scan for bone metastases was significantly better than that of conventional CT and enhanced CT scan alone.Conclusions:Conventional CT combined with enhanced CT scan can significantly improve the diagnostic efficiency of bone metastases,and provide an important basis for clinical treatment.

This report describes the case of a 43-year-old male presenting with severe anemia (hemoglobin, HGB 35 g/L). A comprehensive evaluation encompassing bone marrow morphology (24% ring sideroblasts), genetic testing (SF3B1-negative), iron metabolism studies (ferritin 1 179 μg/L), and imaging (liver MRI T2* value 1.1 ms) was performed for diagnosis, treatment planning, and assessment of outcomes. Initially diagnosed as having myelodysplastic syndrome with ring sideroblasts (MDS-RS), the patient experienced relapse after 10 months of luspatercept treatment. Following the identification of a significant retrospective history of heavy alcohol consumption (250 g/day for 20 years), vitamin B 6 therapy resulted in a rapid increase in HGB to 85 g/L within 10 days, reaching 134 g/L after one month, confirming a diagnosis of alcohol-induced sideroblastic anemia (SA). This case highlights that in SA lacking clonal evidence, the exclusion of reversible causes such as alcoholism should be prioritized. While luspatercept demonstrated short-term efficacy in this patient with non-clonal SA, caution is warranted regarding potential masking of the underlying etiology. Concurrent monitoring of iron overload and early initiation of iron chelation therapy are crucial in alcoholic SA to prevent hepatic damage.

Objective:To explore the diagnostic value of conventional computed tomography(CT)combined with enhanced CT scan in bone metastases.Methods:This study was a retrospective observational study,84 suspected bone metastases patients admitted to our hospital from January 2022 to August 2024 were selected,All patients underwent conventional CT and enhanced CT scan and pathological examination,Using pathological examination results as the"gold standard"for diagnosis.The imaging manifestations of bone metastases using conventional CT combined with enhanced CT scan examination were observed;The detection rate and bone metastases types of conventional CT and enhanced CT scan were analyzed;The bone metastases location in different types of malignant tumors were analyzed;The detection results of bone metastases between conventional CT and enhanced CT scan were compared;the diagnostic efficacy of conventional CT and enhanced CT scan alone and in combination for bone metastases were analyzed by Receiver operating characteristic(ROC)curve.Results:The detection rate of osteogenic,osteolytic,cystic and mixed bone metastases by conventional CT combined with enhanced CT scan was supered to that of conventional CT and enhanced CT scan alone(P＜0.05).Bone metastases from lung cancer,breast cancer and other tumors mainly occur in the spine,limbs and ribs,while esophageal cancer,gastric cancer,liver cancer,prostate cancer,thyroid cancer,renal cancer,and nasopharyngeal cancer had relatively fewer bone metastases.The positive detection cases of bone metastases used conventional CT combined with enhanced CT scan were supered to those used conventional CT and enhanced CT scan alone.The sensitivity,specificity and accuracy of conventional CT combined with enhanced CT scan for the diagnosis of bone metastases were 94.00％,94.11％and 94.04％,respectively,and the positive/negative predictive values were 95.91％and 91.42％,respectively.The sensitivity,specificity and accuracy of conventional CT scan were 84.00％,78.78％and 80.95％,respectively,and the positive/negative predictive values were 85.71％and 74.28％,respectively.The sensitivity,specificity and accuracy of enhanced CT were 89.79％,85.71％and 88.09％,respectively.and the positive and negative predictive values were 89.79％and 85.71％,respectively.The diagnostic efficacy of conventional CT combined with enhanced CT scan for bone metastases was significantly better than that of conventional CT and enhanced CT scan alone.Conclusions:Conventional CT combined with enhanced CT scan can significantly improve the diagnostic efficiency of bone metastases,and provide an important basis for clinical treatment.

A young male patient was diagnosed with aplastic anemia accompanied by paroxysmal nocturnal hemoglobinuria(PNH),and achieved only partial remission after immunosuppressive therapy.Over the past year,his anemia worsened,leading to transfusion dependence,which was considered to be caused by active he-molysis of PNH.Despite switching to eculizumab treatment,his anemia continued to deteriorate.A detailed medical history revealed chronic periodontal infection,with periodontal pain,purulent discharge,and fever in the past month.Multidisciplinary discussion suggested that chronic odontogenic infection activating the comple-ment system was the primary cause of aggravated PNH hemolysis,and the acute infection affected the efficacy of eculizumab.Based on multidisciplinary consultation,a treatment plan was formulated,including intravenous antibiotics combined with periodontal irrigation and tooth extraction to control odontogenic infection,while con-tinuing regular eculizumab infusion.The patient's symptoms improved,hemoglobin levels rose rapidly,and he was no longer transfusion-dependent.This case provides an empirical reference for addressing difficulties en-countered in the treatment of rare diseases with new drugs through multidisciplinary collaborative diagnosis and treatment.

Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Nerve Regeneration/physiology* ; Mitochondria/metabolism* ; Zebrafish Proteins/genetics* ; Axons/metabolism* ; Signal Transduction/physiology* ; Axonal Transport/physiology* ; Nerve Tissue Proteins/genetics*

This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rabbits ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Signal Transduction/drug effects* ; Male ; Disease Models, Animal ; Pyroptosis/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans ; Female