OBJECTIVE To explore a model for constructing a platform for medical institution formulation and provide insights for promoting their development. METHODS By systematically reviewing the development status and challenges of medical institution preparations in China， and based on the theory of industry-university-research collaborative innovation， the organizational structure， collaborative processes， and safeguard mechanisms of the platform were designed. RESULTS & CONCLUSIONS Medical institution formulations in China mainly faced challenges such as weak research and development （R&D） capacity， uneven quality standards， and blocked transformation pathways. This study established a full-chain， whole- industry collaborative innovation network covering the government， medical institutions， universities/research institutes， pharmaceutical enterprises， and the market， forming a new “government-industry-university-research-application” five-in-one platform model for medical institution formulations. By establishing mechanisms such as multi-entity collaborative cooperation， full- chain intellectual property management， contribution-based benefit distribution， staged risk-sharing， and third-party evaluation， the model clarified the responsibilities and collaborative pathways of all parties. The new model highlights the whole-process transformation of clinical experience-based prescriptions， enabling precise alignment between clinical needs and technological R&D， as well as between preparation achievements and industrial transformation. While breaking down the barriers of traditional platform construction， it effectively achieves optimal resource allocation and complementary advantages， addresses problems emerging in the development of medical institution preparations， and provides reference value for the formulation of relevant systems.

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 investigate whether membrane vesicles (MVs) of Streptococcus mutans （S.mutans） contain autoinducer-2 (AI-2) and to preliminarily explore the effects of these MVs on the growth and biofilm formation of S. mutans. Methods: MVs were isolated from the S. mutans UA159 strain using differential centrifugation. The isolated MVs were characterized by nanoparticle tracking analysis for particle size and concentration and observed by transmission electron microscopy. The presence of AI-2 was identified using the Vibrio harveyi BB170 bioluminescence assay: the BB170 diluent was supplemented with AB medium (control group), MV extract (MVs group), pre-ultrafiltration supernatant (Sup group), or post-ultrafiltration supernatant (Sup-af group). The effects of MVs on growth and biofilm formation were assessed using the S.mutans UA159 strain or a luxS deletion mutant as the control group, compared with experimental groups stimulated with gradient concentrations of MVs (MVs-2.0E+7, MVs-2.0E+8, and MVs-2.0E+9 groups). Growth curves, MTT assay, and colony-forming unit (CFU) counts were used to determine changes in growth capacity. Biofilm formation was evaluated using crystal violet staining, confocal laser scanning microscopy, and the anthrone method for polysaccharide quantification. Results: Enriched S. mutans MVs were successfully obtained, with an average particle size of approximately 94.19 nm and a concentration of 1.87E+11 particles/mL. The bioluminescence assay showed that the luminescence intensity of the Sup group was higher than that of the Sup-af group, and the MVs group exhibited higher intensity than the control group. Assessments via growth curves, MTT assay, and CFU counts indicated no significant differences in the growth capacity of the various S. mutans strains after treatment with different concentrations of MVs. Crystal violet staining quantification and confocal laser scanning microscopy observations revealed that high-concentration MV treatment (2.0E+9 particles/mL group) resulted in lower biofilm mass compared to the control. The anthrone method showed that the production of both water-soluble and water-insoluble polysaccharides was significantly lower in the high-concentration MV group than in the control. Conclusion S. mutans MVs contain the quorum sensing signal molecule AI-2. These MVs do not significantly affect the growth of S. mutans, but they can regulate biofilm formation and exhibit an inhibitory effect at high concentrations.

Objective: To evaluate the performance of 5T magnetic resonance imaging (MRI) in visualizing dental pulp and periodontal ligament (PDL) tissues in vivo in the young adult population, thereby providing a basis for the application of high-field MRI technology in clinical oral examinations. Methods: The study was approved by the Ethics Committee of the hospital. A total of 15 healthy volunteers (413 permanent teeth altogether) were recruited and underwent full-mouth 5T MRI scans. Among them, six volunteers (168 permanent teeth) also received both 3T MRI and cone-beam computed tomography (CBCT) scans. Two dental specialists independently evaluated the imaging quality of the dental pulp and PDL on the images using a 5-point Likert scale and recorded the number of detectable root canals for each tooth. Inter-rater agreement was assessed using weighted kappa statistics and intraclass correlation coefficient (ICC). Non-parametric tests were employed to compare differences in imaging performance among different tissue structures, tooth positions, and imaging modalities. Results: 5T MRI can achieve in vivo imaging for most dental pulp tissues and partial periodontal membrane structures. There was a high level of agreement between the two raters in their imaging scores for the dental pulp and PDL (dental pulp κ = 0.934, PDL κ = 0.737). The imaging scores for dental pulp were significantly higher than those for PDL (P < 0.001), and the scores for molar dental pulp were lower than those for premolars and anterior teeth. In the multimodal comparison involving six volunteers, the raters showed good consistency in scoring dental pulp and PDL imaging across 5T MRI, 3T MRI, and CBCT, as well as in root canal counts (5T MRI for dental pulp κ = 0.971, 3T MRI for dental pulp κ = 0.933, CBCT for dental pulp κ = 0.964; 5T MRI for PDL κ = 0.625, 3T MRI for PDL κ = 0.667, CBCT for PDL κ = 0.571; ICC for root canal counts all ≥ 0.990). The imaging scores for dental pulp and PDL using 5T MRI were significantly higher than those using 3T MRI (dental pulp: P < 0.001; PDL: P = 0.022), but there was no statistically significant difference in the detection rate of the number of root canals between the two (P > 0.05). Although the imaging scores for dental pulp and PDL as well as the detection rate of the number of root canals with 5T MRI were inferior to those with CBCT (dental pulp: P < 0.001; PDL: P = 0.02; number of root canals: P < 0.05), 5T MRI can truly achieve "direct imaging" of these two soft tissues. Conclusion 5T MRI enables effective in vivo direct imaging of dental pulp and PDL tissues in the young adult population, indicating its potential clinical application value in the diagnosis and treatment of pulp and periodontal diseases.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Functional cure is currently recommended by guidelines as the ideal treatment goal for the prevention and treatment of chronic hepatitis B （CHB） in China and globally， and it is defined as sustained and undetectable serum HBsAg and HBV DNA， HBeAg clearance， and presence or absence of HBsAg seroconversion， accompanied by resolution of liver inflammation， histopathological improvements， and a significant reduction in the incidence rate of end-stage liver disease. HBV can integrate into the host genome and contribute to the continuous production of HBsAg， which can occur in the early stage of chronic HBV infection. In addition to the covalently closed circular DNA that is hard to be eliminated in liver tissue， HBsAg derived from HBV integration independent of viral replication may be the most important factor for the difficulty in achieving functional cure after antiviral therapy in patients with hepatitis B. This article reviews the research advances in HBV integration in recent years and discusses its impact on functional cure.

ObjectiveFor prepubertal and urgently treated malignant tumor patients, ovarian tissue cryopreservation and transplantation represent more appropriate fertility preservation methods. Current clinical practices often involve freezing ovarian tissue with high concentrations of cryoprotectants (CPAs) and thawing with water baths. These processes lead to varying degrees of toxicity and devitrification damage to ovarian tissue. Therefore, this paper proposes optimized methods for vitrification of ovarian tissues based on sodium alginate hydrogel encapsulation and magnetic induction nanowarming technology. MethodsFirstly, the study investigated the effects of sodium alginate concentration, the sequence of hydrogel encapsulation and CPAs loading on vitrification efficiency of encapsulated ovarian tissue. Additionally, the capability of sodium alginate hydrogel encapsulation to reduce the required concentration of CPAs was validated. Secondly, a platform combining water bath and magnetic induction nanowarming was established to rewarm ovarian tissue under various concentrations of magnetic nanoparticles and magnetic field strengths. The post-warming follicle survival rate, antioxidant capacity, and ovarian tissue integrity were evaluated to assess the efficacy of the method. ResultsThe study found that ovarian tissue encapsulated with 2% sodium alginate hydrogel exhibited the highest follicle survival rate after vitrification. The method of loading CPAs prior to encapsulation proved more suitable for ovarian tissue cryopreservation, effectively reducing the required concentration of CPAs by 50%. A combination of 8 g/L Fe₃O₄ nanoparticles and an alternating magnetic field of 300 Gs showed optimal warming effectiveness for ovarian tissue. Combining water bath rewarming with magnetic induction nanowarming yielded the highest follicle survival rate, enhanced antioxidant capacity, and preserved tissue morphology. ConclusionSodium alginate hydrogel encapsulation of ovarian tissue reduces the concentration of CPAs required during the freezing process. The combination of magnetic induction nanowarming with water bath provides an efficient method ovarian tissue rewarming. This study offers novel approaches to optimize ovarian tissues vitrification.

In the field of oral medicine, 3D-printed individualized titanium mesh technology is gradually becoming an important means for the treatment of severe alveolar bone defect augmentation. This article provides a comprehensive analysis of the advantages of this technology, the evaluation of osteogenic effects, and the progress of research in clinical applications. In response to the current issue of variability in bone augmentation outcomes, this paper delves into multiple factors affecting bone augmentation effects, including individualized titanium mesh design (involving the thickness, pore size, pore shape, porosity, contour shape, selection of titanium alloy materials, and 3D printing technology), intraoperative procedures (the accuracy of placement during 3D-printed individualized titanium mesh surgery), and postoperative care (including the prevention of complications, formation of pseudoperiosteum, and stability of the titanium mesh). By integrating the clinical experience and research findings of our team, we propose a series of targeted optimization strategies, including designing, manufacturing, and clinically applying self-positioning individualized titanium meshs (positioning wings + individualized titanium meshs) to improve the positioning accuracy of the titanium mesh; propose individualized treatment processes and titanium mesh design schemes based on specific conditions of alveolar bone defects and soft tissue status; and emphasize the importance of long-term stable fixation of the titanium mesh to reduce the risk of postoperative mesh loosening and displacement. In addition, we appropriately summarize the evaluation methods for the bone augmentation effects of 3D-printed individualized titanium meshes, covering the following key indicators: (1) vertical bone augmentation and horizontal bone augmentation; (2) changes in bone contour morphology; (3) bone volume increase; (4) clinical indicators (surgical success rate, titanium mesh exposure, infection rate, and postoperative recovery); (5) aesthetic effect evaluation; (6) long-term stability; (7) radiological assessment; (8) patient satisfaction; and (9) precision of surgical operation, aiming to assist doctors in comprehensively assessing and in-depth analyzing the surgical outcomes to achieve the best therapeutic effects. The purpose of this article is to provide a reference for the optimization and clinical application of 3D-printed individualized titanium mesh technology and to lay a theoretical foundation for achieving the best osteogenic effects.

Objective To analyze the causal relationship between immune cell phenotype and gastric cancer. Methods Bidirectional two-sample Mendelian randomization (MR) analysis was used to select 731 genetic variants involving immune cell phenotypes from the GWAS dataset as instrumental variables. Inverse-variance weighting method (IVW), weighted median method (WM), and MR-Egger regression were used for sensitivity analysis. Cochran Q test, MR-Egger regression, MR-PRESSO method, and remain-one method were also conducted. Results Changes in the absolute count of IgD+ B cells and CD14-CD16- cells were significantly associated with the risk of gastric cancer. A lower proportion of IgD+ B cells was associated with a lower risk of gastric cancer (OR=0.86, 95%CI: 0.79-0.94), while an increased number of CD4-CD8-T cells was associated with an increased risk of gastric cancer (OR=1.2, 95%CI: 1.1-1.3). Conclusion A causal relationship exists between immune cell phenotype and the risk of gastric cancer. Changes in specific immune markers may regulate the development of gastric cancer by affecting the tumor microenvironment.

Objective To investigate the characteristics of imprinted differentially methylated regions (iDMRs) in placentas and their correlation with preeclampsia (PE). Methods A total of 43 healthy pregnant women (control group) and 33 pregnant women with PE (PE group) at Shanghai Putuo Maternity and Infant Hospital and International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University School of Medicine from September 2021 to September 2023 were selected. A total of 3 362 CpG sites in 62 iDMRs were analyzed in 76 placenta and 5 maternal blood samples using BisCap targeted bisulfite resequencing (BisCap-seq) assays. The CpG sites in the CpG islands of the iDMRs were assessed for their methylation levels and methylation linkage disequilibrium (MLD). Imprinted methylation haplotype blocks (iMHBs) were constructed based on MLD. The methylation levels and variablility of CpG sites and iMHBs were compared among the healthy placenta, PE placenta and blood samples. Results The CpG sites in the CpG islands of the iDMRs exhibited intermediate methylation, with adjacent sites displaying high MLD (methylation levels: 0.35-0.65, D’ ＞ 0.8). A total of 185 iMHBs were constructed using these coupled CpG sites, 60 placenta-specific iMHBs and 38 somatic iMHBs were found to be differentially methylated in the placenta compared with maternal blood (P_adj＜0.05). Twenty-seven iMHBs were identified with differentially variable methylation patterns in the placenta. The iMHBs methylation was unchanged in the PE placentas compared to the healthy placentas. Twenty-seven differentially methylated cytosines (DMCs) were identified outside the iMHBs structure, among which the methylation levels of 19 CpG sites showed statistically significant differences between the PE group and the control group (P_adj＜0.05). The quantitative results of placental compositions of maternal plasma cell-free DNA (cfDNA) using placenta-specific haplotype (PSH) were highly correlated with those estimated by a deconvolution methodology (r＝0.973, P＜0.01). Conclusions The genomic imprinting features in the PE placentas were obvious, and PSH could be a potential marker of the placenta to quantify the placental compositions of maternal plasma cfDNA.