Radiotherapy is a crucial treatment modality for head and neck tumors. However, while effectively killing tumor cells, it significantly disrupts the homeostasis of the oral microecology, which is closely associated with various complications such as radiation-induced oral mucositis. Literature review indicates that as radiotherapy doses accumulate and treatment durations extend, the richness and diversity of the oral microbiota show a declining trend, with the genus Streptococcus decreasing most markedly. In contrast, radiotherapy selectively promotes the proliferation of bacterial phyla such as Proteobacteria and Bacteroidetes, which are rich in opportunistic pathogens. Mechanistically, radiotherapy activates the nuclear factor-kappa B pathway, triggering chronic inflammation and oxidative stress, damaging the epithelial barrier, suppressing local immunity, and causing damage to organs such as the salivary glands. It can also induce systemic diseases via the oral-gut axis, forming a multi-level, interconnected pathogenic network. In terms of interventions, treatment strategies including probiotics and prebiotics have shown promising efficacy against side effects such as radiation-induced oral mucositis. Saliva-based oral microbiota transplantation is an emerging strategy that is expected to become widely utilized for restoring oral microecological balance. Existing interventions provide preliminary pathways for clinical practice, but this field still faces several key scientific questions. The association between oral microecology and systemic diseases remains largely correlative, lacking causal evidence. Furthermore, critical parameters for oral microbiota transplantation, such as donor screening criteria, transplantation protocols, and long-term safety, are not yet well-defined. Therefore, future research should focus on conducting large-scale clinical trials to establish standardized protocols and safety evaluation systems for oral microecological interventions, and explore combined treatment therapies such as probiotics, prebiotics, and microbiota transplantation to advance the development of personalized precision modulation. These will enable more effective management of radiotherapy-induced oral microecological dysbiosis and improve treatment outcomes and quality of life for patients with head and neck tumors.

Objective To investigate the development, role, and regulatory mechanism of macrophage efferocytosis in the liver of hosts infected with Schistosoma japonicum. Methods The expression of efferocytosis-related gene like efferocytosis receptors, efferocytosis-related bridging molecules,“eat me” signal and “don’t eat me” signal was detected in the livers of patients and mice infected with S. japonicum in the Gene Expression Omnibus (GEO) database. Ten wild-type (WT) male mice (6 ~ 8 weeks old, weighing 20 ~ 25 g) were randomly divided into a Schistosoma japonicum infection (SJ) group and a normal control (NC) group, with 5 mice in each group. The efferocytosis of neutrophils and T cells by liver macrophages was detected in mice from SJ group and NC group using flow cytometry and immunofluorescence assay, respectively. The expression of efferocytosis-related Mer receptor tyrosine kinase (MerTK) and Axl receptor tyrosine kinase (Axl) proteins was determined in mouse liver tissues using Western blotting assay, and the proportion of MerTK⁺ macrophages and the average fluorescence intensity of macrophage MerTK were detected in mouse livers using flow cytometry. Changes in liver granulomas and fibrosis were observed in mice infected with S. japonicum following injection of efferocytosis inhibitors, and S. japonicum-infected mice without injection of efferocytosis inhibitors served as controls. Bone marrow-derived macrophages (BMDMs) were isolated from macrophage scavenger receptor class A (SR-A) conditional knockout (CKO) and wild-type (WT) mice, and changes in apoptotic neutrophils were detected in SR-A CKO mouse macrophages in vitro using flow cytometry. Then, BMDMs was divided into the WT mono-culture group, the WT and apoptotic neutrophils co-culture group, the SR-A CKO mono-culture group, and the SR-A CKO and neutrophils co-culture group, and the expression of MerTK and Axl was quantified in vitro using Western blotting and real-time quantitative PCR (RT-qPCR) assays during neutrophil efferocytosis. The efferocytosis of neutrophils and T cells by mouse liver macrophages was detected in the SR-A CKO SJ group and the WT SJ group using flow cytometry and immunofluorescence assay, and the expression of MerTK and Axl proteins was determined in mouse liver tissues in both groups using Western blotting. In addition, the proportion of MerTK⁺ macrophages and the average fluorescence intensity of macrophage MerTK were detected in mouse livers in both groups using flow cytometry. Results Data from the GEO database showed that the expression of some efferocytosis receptors and efferocytosis-related bridging molecules, and “eat me” and “don’t eat me” signals all appeared a tendency towards a rise in livers of patients and mice in the SJ group relative to the NC group, suggesting that S. japonicum infection-induced liver diseases may be associated with efferocytosis. Flow cytometry detected higher proportions of Ly6G⁺ cells [(13.13 ± 0.45)% vs. (6.48 ± 0.25)%; t = 22.30, P < 0.05] and CD3⁺ cells [(7.60 ± 0.33)% vs. (3.30 ± 0.42)%; t = 13.98, P < 0.05] in mouse liver macrophages in the SJ group than in the NJ group, and the expression of MerTK protein [(2.30 ± 0.14) vs. (1.14 ± 0.46); t = 4.19, P < 0.05], the mean fluorescence intensity of macrophages [(160.67 ± 15.28) vs. (94.50 ± 19.61); t = 4.81, P < 0.05], and the proportion of MerTK⁺ macrophages [(20.78 ± 4.17)% vs. (6.85 ± 0.39)%; t = 6.57, P < 0.05] were significantly higher in mouse liver tissues in the SJ group than in the NC group. The Axl expression was lower in mouse liver tissues in the SJ group than in the NC group [(1.25 ± 0.08) vs. (1.93 ± 0.37); t = 2.79, P < 0.05], and the area of granulomas around single eggs [(9.18 ± 1.81) × 10⁴μm² vs. (5.24 ± 1.35) × 10⁴ μm²; t = 3.03, P < 0.05] and proportion of collagen fibers [(25.27 ± 3.99)% vs. (15.14 ± 4.02)%; t = 3.10, P < 0.05] were significantly greater in livers of S. japonicum-infected mice with injection of efferocytosis inhibitors than in mice without injection of efferocytosis inhibitors. The in vitro efferocytosis efficiency of BMDMs [(32.83 ± 3.17)% vs. (45.43 ± 2.34)%; t = 5.54, P < 0.05], and the proportions of Ly6G⁺ [(9.37 ± 0.48)% vs. (13.13 ± 0.72)%; t = 7.50, P < 0.05] and CD3⁺ cells [(4.95 ± 0.17)% vs. (7.64 ± 0.50)%; t = 8.87, P < 0.05] in liver macrophages post-infection with S. japonicum were significantly lower in SR-A CKO mice than in WT mice, and the expression of MerTK protein [(0.65 ± 0.25) vs. (1.96 ± 0.69); t = 3.10, P < 0.05], the average fluorescence intensity of macrophages [(138.33 ± 8.39) vs. (160.67 ± 15.28); t = 3.03, P < 0.05] and the proportion of MerTK⁺ macrophages [(13.17 ± 5.01)% vs. (22.63 ± 2.06)%; t = 3.56, P < 0.05] were significantly lower in mouse liver tissues in the SR-A CKO SJ group than in the WT group. Western blotting detected no significant difference in the Axl protein expression in mouse liver tissues between the SR-A CKO SJ group and the WT SJ group [(0.48 ± 0.07) vs. (0.68 ± 0.30); t = 1.09, P > 0.05]. There were significant differences in the relative MerTK mRNA and protein expression during efferocytosis of BMDMs among the WT monoculture group, the WT and apoptotic neutrophils co-culture group, the SR-A CKO mono-culture group, and the SR-A CKO and neutrophils co-culture group (F = 9.41 and 40.68, both P values < 0.05). In addition, there was a significant difference in the relative Axl mRNA expression during efferocytosis of BMDMs among the four groups (F = 13.62, P < 0.05); however, no significant difference was seen in the relative Axl protein expression (F = 1.27, P > 0.05). Conclusions Efferocytosis of liver macrophages is seen in mice infected with S. japonicum and inhibits liver fibrosis. SR-A may up-regulate the efficiency of macrophage efferocytosis through regulating the expression of efferocytosis receptors.

Diabetic nephropathy (DN), as one of the most common complications of diabetes, is a primary cause of end-stage renal disease. The pathogenesis of DN encompasses processes such as chronic inflammation, recruitment and activation of immune cells, tubular and glomerular injury, and renal fibrosis. These processes are highly correlated with the activation of the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome and the resulting pyroptosis it mediates. Previous studies have shown that the release of pro-inflammatory cytokines, leakage of damage-associated molecular patterns (DAMPs), recruitment and activation of immune cells can be reduced by regulating the NLRP3 inflammasome and its mediated pyroptosis, thereby slowing the diffusion of inflammatory responses in adjacentcells, fibrosis, and tissue remodeling processes. Ultimately, these process can improve renal injury and dysfunction caused by diabetic nephropathy. This article summarizes the molecular regulatory mechanisms of the NLRP3 inflammasome and its mediated pyroptosis at different pathological stages of DN, proposes potential targets for regulating their activation, aiming to provide a new direction for personalized treatment of DN.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

Objective To explore the anatomical landmarks and segmentation method for the intraoperative identification of the cervical segment of the internal carotid artery by studying cadaveric dissections with an endoscopic transoral medial pterygomandibular fold approach and to investigate its clinical significance.Methods The head specimens of five fresh frozen cadavers were dissected in the anatomical laboratory of the Surgical Treatment Technology Innovation Unit of Nasal Skull Base Tumor in Eye&ENT Hospital of Fudan University.The parapharyngeal space was dissected layer by layer through the endoscopic transoral medial pterygomandibular fold approach,and the location marks of parapharyngeal internal carotid artery(ppICA)and adjacent structures of ppICA were anatomically studied.The anatomical landmarks associated with ppICA were observed and characterized,and the ppICA was segmented anatomically according to its adjacent structures.Then,the length of each ppICA segment was measured.Results Muscle structures were essential anatomical landmarks for an endoscopic transoral pterygoid medial approach that identifies mandibular folds.The first layer of muscles included the superior pharyngeal constrictor,tensor veli palatini,and medial pterygoid muscles.The second layer includes the stylopharyngeus,styloglossus,longus capitis,and levator veli palatini muscles.The stylopharyngeal and levator veli palatini muscles were close to the ppICA and were reliable landmarks for locating the ppICA.Furthermore,the ppICA was divided into three segments according to their positional relationship with the ppICA.The first segment of ppICA(P1 ICA)was located between the greater horn plane of the hyoid bone and the intersection plane between the upper margin of stylopharyngeal muscle and ppICA.The second segment of ppICA(P2 ICA)was between the plane where the upper edge of the stylopharyngeal muscle intersected with the ppICA and the plane where the projection of inferior edge of the levator veli palatini muscle intersected with the ppICA.The third segment of ppICA(P3 ICA)was between the intersection of the lower margin projection of the levator veli palatini muscle and ppICA and the external orifice of the carotid canal.The P2 ICA was within an anatomical region bounded by the levator veli palatini muscle,longus capitis muscle,and stylopharyngeus muscle.This region was termed"ICA window"in this paper measured under the cadaver head specimen,the lengths of P1 ICA,P2 ICA,and P3 ICA were(36.5±7.3)mm,(15.5±1.6)mm,(7.4±1.7)mm respectively.Conclusion The muscular structure refers to the relatively constant anatomical reference landmarks within the endoscopic transoral medial pterygomandibular fold.The stylopharyngeus and levator veli palatini muscles are reliable landmarks for precisely locating and segmenting the ppICA,thus having essential clinical implications.

The focus of green analytical chemistry(GAC)is to minimize the negative impacts of analytical pro-cedures on human safety,human health,and the environment.Several factors,such as the reagents used,sample collection,sample processing,instruments,energy consumed,and the quantities of hazardous materials and waste generated during analytical procedures,need to be considered in the evaluation of the greenness of analytical assays.In this study,we propose a greenness evaluation metric for analytical methods(GEMAM).The new greenness metric is simple,flexible,and comprehensive.The evaluation criteria are based on both the 12 principles of GAC(SIGNIFICANCE)and the 10 factors of sample prep-aration,and the results are presented on a 0-10 scale.The GEMAM calculation process is easy to perform,and its results are easy to interpret.The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

The construction of medical ethical review is the basic guarantee for strengthening the ethical governance of medical science and technology,and mutual recognition of ethical review results serves as a pivotal approach to accelerate the construction of ethical review.This paper conducted a questionnaire survey on 30 tertiary medical and health institutions with clinical trial qualifications in Tianjin,based on the exploration of the implementation of the Notice on the Implementation of Mutual Recognition of Medical Ethics Review Results in the Beijing-Tianjin-Hebei Region jointly issued by the Health Committees of the three regions in Tianjin's tertiary medical and health institutions.By investigating and analyzing the situation of clinical trials,ethics committees,and mutual recognition from 2021 to 2023,the regular reasons affecting the promotion of mutual recognition of ethical review results in the Beijing-Tianjin-Hebei region were identified,and reasonable recommendations were proposed.These aimed to offer references for the Tianjin region in deepening the integration of Beijing-Tianjin-Hebei development and accelerating the promotion of regional ethical mutual recognition work,thereby advancing the construction and development of medical ethical review.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To explore the current therapeutic status of rhythm control versus rate control in elderly patients with atrial fibrillation(AF)and the related factors that may influence treatment decisions.Methods:A retrospective study was conducted on AF patients aged ≥75 years old who were hospitalized in the Healthcare Department of Beijing Hospital from January 2010 to May 2020.The patients were grouped and compared according to whether they underwent rhythm control or rate control.Multivariate logistic regression analysis was used to investigate the factors that may influence the treatment decision of rhythm control or rate control.Results:A total of 167 patients was included, with a median age of 90 years old.Among them, 21 patients(12.6%)received rhythm control, and 109 patients(65.3%)received rate control.Compared with the group not receiving rhythm control, the rhythm control group had a younger age, higher BMI, higher diastolic blood pressure, a higher proportion of multiple medication use, a lower proportion of chronic kidney disease stage 3 or above, and higher hemoglobin levels(all P<0.05). Compared with the group not receiving rate control, the rate control group had a lower proportion of paroxysmal AF, a faster resting ventricular rate, a higher proportion of smoking history, a higher proportion of multiple medication use, coronary heart disease, pacemaker treatment, chronic obstructive pulmonary disease and/or asthma, and a lower proportion of cognitive impairment(all P<0.05). Multivariate logistic regression analysis revealed that multiple drug use( OR=11.578, 95% CI: 1.341-99.993, P=0.026)was positively associated with rhythm control therapy, while chronic kidney disease stage 3 or above( OR=0.248, 95% CI: 0.063-0.968, P=0.045)was negatively associated with rhythm control therapy.For rate control therapy, multiple drug use( OR=5.056, 95% CI: 2.253-11.347, P<0.001), resting ventricular rate( OR =1.033, 95% CI: 1.005-1.062, P=0.021), and chronic obstructive pulmonary disease(COPD)and/or asthma( OR=2.739, 95% CI: 1.124-6.672, P=0.027)showed positive associations. Conclusions:The application rate of rhythm control therapy is low in elderly AF patients, and ventricular rate control is the main treatment.Complex clinical conditions are the main constraints, and it is urgent to optimize individualized strategies based on prospective studies and develop new treatment techniques to improve clinical practice.