ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

Due to the moist environment in the mouth, there are many challenges that arise, such as difficult biofilm removal, short drug retention time, and low tissue repair efficiency, while treating dental caries, periodontal disease, and other oral diseases. As a biomimetic biomaterial, polydopamine (PDA) possesses multifunctional properties, including mussel-inspired adhesion and stimuli-responsive drug release. PDA adhesion properties originate from its surface catechol and amino functional groups, which maintain strong wettability in aqueous environments. With smart responsiveness encompassing photothermal, pH, and enzymatic stimuli, PDA enables controlled drug release under specific conditions. Additionally, PDA exhibits antibacterial, anti-inflammatory, and osteoblast-promoting functions, thus demonstrating significant application potential in the treatment of oral diseases. In hard tissue therapies, specifically for dental caries, PDA promotes enamel remineralization by inducing hydroxyapatite crystal growth and enhances dentin collagen mineralization through Ca2+ chelation while inhibiting cariogenic bacteria. In mandibular defect repair, functionalized PDA coatings on bone implants facilitate mesenchymal stem cell adhesion and differentiation, activate osteogenic signaling pathways, and synergistically promote vascularization to improve bone-implant integration. For soft tissue treatments, specifically for periodontitis, PDA alleviates alveolar bone resorption via antibacterial and anti-inflammatory effects coupled with osteoclast inhibition. In denture stomatitis management, PDA’s strong wet adhesion prolongs drug retention, while its photothermal effect and reactive oxygen generation provide both broad-spectrum antibacterial activity and wound healing promotion. This review summarizes PDA’s synthesis mechanisms and biological functions, with an emphasis on its therapeutic applications in oral diseases, providing innovative strategies for oral healthcare.

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.

Antibody-negative autoimmune encephalitis （AE） in children poses certain challenges for clinical diagnosis and treatment due to the lack of characteristic autoantibodies. This study conducts a retrospective analysis of the clinical data of a boy， aged 7 years， who had the main manifestations of “irritability， vomiting， pyrexia， and lethargy”. Video electroencephalography showed diffuse slow waves， with the presence of type 2 cerebrospinal fluid oligoclonal bands， and the boy was tested negative for related autoantibodies in blood and cerebrospinal fluid. Finally the boy was diagnosed with antibody-negative AE. After admission， the boy received first-line immunotherapy with methylprednisolone and intravenous immunoglobulin， combined with tocilizumab for intensive treatment， and the symptoms were rapidly relieved. At 1 week after discharge， the boy experienced memory loss， and head MRI suggested cerebral atrophy. After 1 month of adjuvant hyperbaric oxygen therapy， the boy’s memory recovered to the level before disease onset， and reexaminations of MRI and video electroencephalography obtained normal results.No recurrence was observed during follow-up for 6 months， and the boy achieved satisfactory academic performance.This case suggests that for children with antibody-negative AE， first-line immunotherapy combined with tocilizumab can rapidly control inflammation， and the addition of hyperbaric oxygen therapy can effectively improve subsequent cerebral structural and cognitive abnormalities， with few adverse reactions， which provides a new clinical approach for the treatment of this type of disease.

Vestibular migraine （VM） is the most common cause of recurrent vertigo， and it is an overlapping disease of central vestibular disease and migraine，as well as a syndrome characterized by the simultaneous or alternating occurrence of paroxysmal vestibular symptoms and typical migraine attacks.VM is known as the “chameleon of vestibular system diseases” due to its complex and diverse symptoms， which can easily lead to missed diagnosis and misdiagnosis. In recent years， with the development of neuroimaging technology and the implementation of multi-center clinical research， the pathogenesis of VM has gradually been expanded from the classic trigeminal neurovascular theory to the aspects of neurotransmitter disorder，cortical diffusion inhibition，and abnormal vestibular-cortical pathway integration. In addition， there have been constant improvements in the diagnosis system of VM，and the treatment modality of VM is gradually shifting to the comprehensive treatment paradigm of “symptomatic treatment in the acute stage combined with preventive treatment in the remission stage and lifestyle adjustment”.This article reviews the latest research advances in this field.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

Autoimmunity diseases(AIDs) involve the entire body's tissue systems and pose a serious threat to the normal immune system and health of the human body. Researches have shown that AID is caused by the complex interaction between genetic susceptibility and environmental factors. Enterovirus(EV) infection often accompanies certain AID and is an important type of virus infection related to AID. Coxsackievirus(CV), a member of the EV family, is an important pathogen among the pathogenic factors of type 1 diabetes(T1D). EV infection causes damage to the activity of pancreatic β cells and accelerates the disease progression of T1D. In terms of treatment, recent reports have shown that antiviral therapy for T1D is effective in preserving the function of β pancreatic cells. In celiac disease and Crohn's disease(CD), EV infection can induce inflammatory pathogenic changes in the intestinal microbiota, increase intestinal barrier permeability, and may trigger the occurrence of such AIDs. However, the relationship and mechanism between EV infection and many AIDs remain unclear.This paper summarizes the research conclusions on the correlation between EV infection and AIDs to facilitate a deeper exploration of their pathogenic patterns.

ObjectiveTo investigate the expression features of HBsAg and HBcAg in liver tissue and their correlation with HBV serum markers in children with chronic hepatitis B （CHB）. MethodsA total of 257 patients who were consecutively admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to December 2023 and underwent liver biopsy to achieve a confirmed diagnosis of CHB were enrolled in this study. The NIS-Elements system was used to capture the immunohistochemical images of HBsAg and HBcAg in liver tissues， and Image J software was used for quantitative analysis. The one-sample chi-square test was used for within-group comparison of continuous data， and the Pearson/Spearman/Kendall’s Tau-b correlation analysis was used to investigate the correlation between viral antigen expression and serological markers. ResultsAmong the 257 CHB patients， there were 162 children （76 children aged<5 years and 86 children aged 5 — 18 years） and 95 adults. There were significant differences in the expression pattern， area， and intensity of HBsAg and the area and intensity of HBcAg in liver tissue between different age groups and between the children with different HBeAg statuses （all P<0.05）. In the children aged<5 years， HBsAg staining area was significantly negatively correlated with anti-HBs and HBeAg （both P<0.05）and was significantly positively correlated with ALT and AST （both P<0.05）， and HBsAg staining intensity was significantly positively correlated with qHBsAg （P<0.05） and was significantly negatively correlated with anti-HBs （P<0.05）. In the children group， HBsAg staining area was negatively correlated with anti-HBs and HBeAg （both P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg （P<0.05） and was negatively correlated with anti-HBs （P<0.05）. In the adult group， HBsAg staining area was positively correlated with ALT， AST， and liver inflammatory activity （all P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05） and was negatively correlated with liver inflammatory activity and fibrosis degree （both P<0.05）. In the children aged<5 years， HBcAg staining area was positively correlated with qHBsAg and HBV DNA （both P<0.05）， and HBcAg staining intensity was significantly positively correlated with HBV DNA （P<0.001）. In the children aged 5 — 18 years， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）. In the children group， HBcAg staining area was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）， and HBcAg staining intensity was positively correlated with qHBsAg and HBV DNA （both P<0.05）. In the adult group， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.001）， and HBcAg staining area was positively correlated with the serum level of ALT （P=0.043）. ConclusionThe expression levels of HBsAg and HBcAg in liver tissue of children with CHB are significantly correlated with serological markers， and in clinical practice， HBsAg and HBcAg combined with serological markers can help to assess the condition of the liver， determine the immune stage， and provide evidence-based guidance for treatment timing.