Endodontic microsurgery (EMS) is an oral surgical procedure that utilizes the magnification and illumination provided by a microscope. Fine instruments are used to remove periapical diseased tissues, resect the root apex, and tightly seal the root canal system, aiming to promote the healing of periapical tissues and retain the affected tooth whenever possible. Precise localization and resection of the root apex have always been challenging in EMS. The application of digital technology in EMS can address many issues in traditional endodontic microsurgery. Digital technology offers advantages such as optimizing surgical planning, providing precise positioning guidance, and enhancing operational accuracy. Currently, the commonly used digital technologies in EMS include static and dynamic navigation technologies and oral surgical robots. Static navigation technology enhances surgical predictability through precise preoperative planning and guided fabrication, yet is constrained by its inability to adjust during surgery. Dynamic navigation technology excels in real-time tracking and intraoperative flexibility but demands high hand-eye coordination from surgeons and may be hindered by bulky handheld devices. Oral surgical robots reduce hand tremors and human error in surgery with their high precision, stability, and ability to adjust in real time, but their clinical applicability is limited and their cost is high. In clinical practice, tailored combinations of these technologies can be applied based on case complexity. For simple cases with well-defined anatomy, static navigation alone may suffice. For complex anatomical cases, static navigation can provide initial planning, supplemented by dynamic navigation for real-time guidance or robotic systems for high-precision execution. This paper discusses the workflow, clinical application status and advantages and limitations of these three digital technologies in EMS. The continuous development of digital technology is expected to simplify the operation process, improve the navigation accuracy, and reduce the operation cost. It is believed that with continuous improvement and optimization, these technologies will effectively break through the current bottleneck of the cost of equipment, operation complexity, and accuracy enhancement. These technologies are also expected to further expand the application boundaries, providing more minimally invasive, precise, and time-saving personalized treatment solutions for endodontic diseases.

ObjectiveToll-like receptor 4 （TLR4）， a receptor for pathogen-associated molecular patterns of innate immunity， is associated with neurodegenerative diseases. Interleukin （IL）-6， IL-1β， and tumor necrosis factor-α （TNF-α） as common pro-inflammatory cytokines and high-sensitivity C-reactive protein （hs-CRP） are related to inflammatory responses. This study evaluated the clinical efficacy and possible mechanisms of therapeutic effects of Fengyintang on early and mid-stage PD with excessive heat generating wind by observing the effects of Fengyintang on the serum levels of TLR4， IL-6， IL-1β， TNF-α， and hs-CRP in the patients with PD. MethodsSixty-eight PD patients who met the inclusion criteria were randomly assigned into the control group and the observation group （n=34）. Both groups were treated with anti-PD Western medicine and the observation group was additionally treated with Fengyintang. Both groups were treated for 8 weeks. Before and after 8 weeks of treatment， the patients in the two groups were measured for their TCM symptom scores， International Movement Disorder Society Unified Parkinson's Disease Rating Scale （MDS-UPDRS） score， Parkinson's Disease Non-Motor Symptom Scale （NMSS） score， Patient Assessment of Constipation Symptom （PAC-SYM） score， Pittsburgh Sleep Quality Index （PSQI）， Hamilton Anxiety Scale （HAMA） score， Hamilton Depression Scale （HAMD） score， and changes in serum TLR4， IL-6， IL-1β， TNF-α， and hs-CRP levels. ResultsOne case in the control group was removed due to loss of visit， and a total of 67 PD patients （33 in the control group and 34 in the observation group） who met the criteria were included for analysis. After treatment， patients in the observation group showed decreases in scores of TCM symptoms， MDS-UPDRS， NMSS， PAC-SYM， PSQI， HAMA， and HAMD （P<0.05， P<0.01）. Moreover， the observation group had lower scores of TCM symptoms， MDS-UPDRS， NMSS， PAC-SYM， PSQI， HAMA， and HAMD than the control group （P<0.05， P<0.01）. The observation group showed higher efficacy in terms of TCM symptoms and MDS-UPDRS score than the control group （Z=-0.57， P<0.05）. The overall response rate was higher in the observation group than in the control group （Z=-0.62， P<0.05， P<0.01）. The serum TLR4， TNF-α， IL-1β， IL-6， and hs-CRP levels of the observation group were lower than those of the control group （P<0.05， P<0.01）. ConclusionFengyintang combined with Western medicine can safely and effectively alleviate the clinical symptoms， reduce the levels of inflammatory factors， improve the quality of life， and delay the disease progression of PD patients by inhibiting peripheral TLR4 expression and thus suppressing the downstream inflammatory response.

Background Against the background of global warming, frequent heatwaves pose a major threat to public health. Objective To investigate the effects of heatwaves on outpatient visits for skin diseases in Urumqi, characterize the exposure–response relationship, identify the critical temperature threshold, and provide scientific evidence for targeted prevention and control of heat-related skin diseases. Methods Data on meteorological conditions, air quality, and dermatological outpatient visits from 10 hospitals in Urumqi were collected from January 1, 2016 to December 31, 2024. A time-stratified case-crossover design combined with a distributed lag model was adopted to construct a conditional logistic regression model, with adjustment for potential confounders, including relative humidity, air pollutants, and COVID-19 lockdown measures. With a maximum lag of 14 d, single-lag and cumulative-lag effects of heatwaves were examined, and the exposure–response relationship between temperature and the risk of dermatological outpatient visit was fitted. Results A total of 385 heatwave days were identified in Urumqi from January 1, 2016 to December 31, 2024. These days were concentrated between June and September and showed an increasing annual trend. The median daily number of dermatological outpatient visits during heatwave periods (165 cases) was significantly higher than that during control periods (114 cases) (Z=−5.108, P<0.001). After adjusting for confounders, the odds of dermatological outpatient visits during heatwaves were 1.088 times higher than those of the control period (OR=1.088, 95%CI: 1.069, 1.107). Single-lag effects were statistically significant from lag0 to lag11 (P<0.05), peaking at lag0 (OR=1.088, 95%CI: 1.069, 1.107), showing an acute and immediate effect. Cumulative-lag effects were statistically significant from 1 to 14 d (P<0.05), peaking at lag04 (OR=1.117, 95%CI: 1.099, 1.136). The exposure–response relationship indicated that the OR values increased steeply with increasing temperature when the daily mean temperature exceeded 24.2 ℃, peaking at approximately 28.1 ℃ (OR=1.400, 95%CI: 1.189, 1.649). Conclusions Heatwave exposure is significantly associated with an increased risk of dermatological outpatient visits among residents in Urumqi. The impact of high temperature on skin diseases is predominantly acute, with peak risks observed on the day of exposure and within the subsequent 4 d. A daily mean temperature of 24.2 ℃ can serve as the critical threshold for heightened dermatological consultation risk. Strengthened health education and early warning systems are recommended to mitigate heatwave-related adverse dermatological outcomes.

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

OBJECTIVE To investigate the incidence of hospital-associated infections among the neurosurgery de-partment patients undergoing brain tumor resection and analyze the economic cost so as to provide scientific bases for formulating prevention strategies.METHODS Totally 1027 patients who underwent brain tumor resection in neurosurgery department of the First Affiliated Hospital of Shandong First Medical University from Jan.1,2020 to Dec.31,2024 were recruited as the research subjects.The 36 patients who had postoperative hos-pital-associated infections were assigned as the infection group,and 991 patients who did not have hospital-associ-ated infection were assigned as the no infection group.The patients of the infection group and the non-infection group were matched in a 1∶1 ratio by using propensity score matching method(caliper value 0.005).The length of hospital stay and costs of medical items were compared between the infection group and the non-infection group,and the economic burden due to the hospital-associated infections was estimated.RESULTS The incidence of hospital-associated infections was 3.51％among the patients undergoing brain tumor resection,and totally 36 pairs were matched successfully with the propensity score.The hospitalization cost of the infection group was 109,103.81(73,370.21,163,628.37)yuan after the matching,which was increased by 50,087.69 yuan as com-pared with the non-infection group(Z=-5.237,P＜0.001);the length of hospital stay was 23.00(17.25,36.00)days,which was prolonged by 8.50 days(Z=-3.764,P＜0.001).Among the costs of medical items,the medial costs of western medicine,treatment materials and clinical laboratory tests increased most.CONCLUSIONS The control of the costs of western medicine,treatment materials and clinical laboratory tests is the key to reduce the costs of brain tumor resection patients with hospital-associated infections.It is necessary to carry out the real-time monitoring of the hospital-associated infections and early warning of suspected cases and reduce the incidence of hospital-associated infections so as to reduce the economic costs.

OBJECTIVE To investigate the incidence of hospital-associated infections among the children with acute leukemia and analyze the economic burden so as to provide scientific bases for formulating the hospital infec-tion management strategies.METHODS A total of 140 children with acute leukemia who were hospitalized in pedi-atric hematology department of the First Affiliated Hospital of Shandong First Medical University and underwent hematopoietic stem cell transplantation from Jan.1,2018 to Jun.30,2024 were recruited as the research subjects.The clinical data,incidence of infections and cost data were collected.The infection group and the non-infection group were matched in a 1∶1 ratio by propensity score matching method.The length of hospital stay and costs of medical items were compared between the infection group and the non-infection group.The economic burden due to the hospital-associated infections was estimated.RESULTS Of the 140 children,59 had hospital-as-sociated infections,with the incidence of infections 42.14％.A total of 125 children who conformed to the inclu-sion and exclusion criteria were included in the study,among whom 53 pairs were matched successfully by propen-sity score matching method.The median hospitalization cost was 230,125.79 yuan in the infection group after the matching,189,880.90 yuan in the non-infection group,and there was significant difference between the two groups(Z=-2.038,P=0.042).The direct economic burden due to the hospital-associated infections in the chil-dren with acute leukemia was 40,244.89 yuan.The median costs of western medicine,self-pay and antibiotics were increased most remarkably among all the costs of medical items(all P＜0.05).CONCLUSION The targeted surveillance of hospital-associated infections and early warning of suspected cases are the major strategies to reduce the incidence of infections and relieve the economic burden.

Objective:To characterize the etiological and genetic features of pediatric influenza outbreaks in Changzhou between 2021 and 2024，with the goal of informing evidence-based prevention strategies and guiding effective management of influenza outbreaks in school settings.Methods:During the period of 2021 to 2024，throat swabs of influenza-like cases from school outbreaks in Changzhou were collected. These samples underwent real-time reverse transcription-polymerase chain reaction（RT-PCR）testing and virus isolation. Epidemiological data were integrated to conduct pathogenetic analysis. The HA genes of isolated strains were amplified and sequenced to perform genetic characterization.Results:Between 2021 and 2024，a total of 256 influenza outbreaks were reported in schools in Changzhou. A total of 3 201 specimens were collected，of which 2 245 were tested positive for influenza viruses，resulting in a positivity rate of 70.13%. The outbreak season was primarily concentrated from December to February each year，with settings predominantly distributed in primary schools（accounting for 73.83%）. The predominant epidemic strains were influenza A viruses，including 118 outbreaks caused by H1N1 and 104 by H3N2. A total of 74 influenza virus strains were successfully isolated from positive specimens，and sequencing of the hemagglutinin（HA）gene was completed. Phylogenetic analysis revealed that certain B/Victoria lineage strains（e.g.，B/Changzhou/01/2021）clustered closely with the vaccine strain B/Austria/3594/17（bootstrap support：99%）. Among influenza H1N1 strains，multiple isolates from 2023—2024 clustered within the same major branch as A/Victoria/4897/2022（bootstrap support：100%）. In contrast，the H3N2 strains exhibited a complex evolutionary pattern，showing variable genetic distances to vaccine strains from different years（e.g.，A/Massachusetts/18/2022，A/Darwin/6/2021）；some isolates were closely related to vaccine strains，while others were more distantly related and scattered across the phylogenetic tree.Conclusions:The influenza outbreak situation in schools was severe and has significant public health implications. Continuous surveillance is essential，and preventive strategies should be promptly adjusted based on the epidemiological and genetic characteristics of circulating strains.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.