ObjectiveTo characterize the features of the gut microbiome and its association with clinical prognosis in patients with intermediate and advanced hepatocellular carcinoma （HCC） treated with transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy. MethodsThis retrospective study enrolled patients with intermediate and advanced HCC who received TACE combined with targeted therapy and immunotherapy at the First Affiliated Hospital of Sun Yat-sen University from February 2025 to July 2025. Baseline clinical data and fecal samples were collected from all enrolled patients before the index hospitalization and treatment. Patients were stratified using two independent criteria： ① a good-prognosis group and a poor-prognosis group， based on whether progression-free survival （PFS） reached 6 months； ② a response group and a non-response group， based on tumor response to the first TACE assessed by the modified Response Evaluation Criteria in Solid Tumors （mRECIST）. Metagenomic sequencing was performed on fecal samples. Bioinformatic analysis was conducted to evaluate the diversity and compositional differences of intestinal bacterial and fungal communities between groups in each stratification， and to screen for prognosis-associated characteristic microbial taxa. ResultsA total of 61 patients met the inclusion criteria. Analysis of α-diversity and β-diversity showed no statistically significant differences in bacterial and fungal diversity between groups under either stratification strategy （P＞ 0.05）. At the bacterial level， Lactobacillus johnsonii （prognosis stratification： P=0.048； response stratification： P=0.043）， Bifidobacterium dentium （prognosis stratification： P=0.004； response stratification： P=0.030） and Clostridioides difficile （prognosis stratification： P=0.017； response stratification： P=0.016） were significantly enriched in both the good prognosis group and the response group. At the fungal level， Cryptococcus decaguttatus （P=0.045）， Puccinia striiformis （P=0.002）， and Kwoniella quercicola （P=0.015） were enriched in the good‑prognosis group； Kwoniella bestiolae （P=0.037） was enriched in the response group； and Akanthomyces muscarius （P=0.024） was enriched in the non-response group. Survival analysis based on the common differential bacterial abundance in both groupings showed a significant correlation between the abundance of Bifidobacterium dentium and patient prognosis. ConclusionDifferences in the gut microbiota are associated with the prognosis of patients with intermediate and advanced HCC treated with TACE combined with targeted therapy and immunotherapy. Bifidobacterium dentium may serve as a potential predictive biomarker for the efficacy of this combination regimen， and represents a potential intervention target to modulate treatment response. Differences in gut fungal communities are also potentially associated with the prognosis of intermediate and advanced HCC patients receiving TACE combined with targeted therapy and immunotherapy.

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

Subgingival air polishing can effectively remove plaque and soft deposits attached to the tooth surface and implant surfaces.It is an adjunctive treatment method for periodontitis and peri-implantitis,offering good cleaning efficiency with minimal damage to the root surface and implant surface.Additionally,it promotes the reattachment of fibroblasts to the root surface and osteoblast integration on the implant surface.Subgingival air polishing can improve clinical attachment levels and also shows better therapeutic effects when combined with flap surgery.It provides higher comfort for patients and lower operational difficulty for the dentist.This article aims to an-alyze and summarize in vivo and in vitro studies,reviewing the therapeutic progress of subgingival air polishing in the treatment of peri-odontitis and peri-implantitis.

Subgingival air polishing can effectively remove plaque and soft deposits attached to the tooth surface and implant surfaces.It is an adjunctive treatment method for periodontitis and peri-implantitis,offering good cleaning efficiency with minimal damage to the root surface and implant surface.Additionally,it promotes the reattachment of fibroblasts to the root surface and osteoblast integration on the implant surface.Subgingival air polishing can improve clinical attachment levels and also shows better therapeutic effects when combined with flap surgery.It provides higher comfort for patients and lower operational difficulty for the dentist.This article aims to an-alyze and summarize in vivo and in vitro studies,reviewing the therapeutic progress of subgingival air polishing in the treatment of peri-odontitis and peri-implantitis.

Objective:To evaluate the effects of photodynamic therapy (PDT) in extraction sockets of periodontally compromised molars on soft tissue healing, postoperative pain, bone density and bone height changes.Methods:This study is a single-center, single-blind, randomized controlled superiority clinical trial. Thirty-eight periodontally compromised molars requiring extraction in patients attending the Department of Periodontology, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, from December 2022 to September 2023 were included, and randomly assigned to PDT group and control group. The control group received routine debridement after extraction, while PDT group received routine debridement followed by PDT. The bucco-lingual and mesio-distal wound distances at 7 and 14 d after extraction were measured, and then the wound closure rates were calculated. Evaluating the soft tissue healing indexes at 7 and 14 d after extraction. The visual analogue scale was used to assess the pain level at 6 h, 1 d, 2 d, and 3 d after tooth extraction. Apical radiographs were taken immediately and 2 months after extraction in order to compare the changes of the bone density and height.Results:The wound closure rate at 1 week was (78.08±5.45)% in PDT group and (71.03±6.82)% in control group, with significant differences ( P<0.01). The wound closure rate at 2 weeks in PDT group [(85.88±3.84) %] was significantly higher than that in the control group [(81.66±3.79) %] ( P<0.01), but did not reach the superiority value of the superiority test (superiority value=10%, 95% CI at 1 week: 3.00%-11.12%, 95% CI at 2 weeks: 1.71%-6.73%). The soft tissue healing index of PDT group at 1 week was significantly better than the control group ( P<0.05), but there was no significant difference between the two groups at 2 weeks ( P>0.05). There was no significant difference between the two groups in terms of postoperative pain at 6 h, 1 d, 2 d and 3 d as well as in bone density and height changes at 2 months after tooth extraction ( P>0.05). Conclusions:PDT could promote soft tissues healing to some extent, but did not provide additional assistance in the healing of extraction sockets of periodontally compromised teeth. PDT did not show benefits on postoperative pain, changes of the bone density and bone height after tooth extraction.

Objective To study the applicability and optimization of computer simulation methods during the allocation of health care providers for medical evacuation on board medical trains.Methods Using Anylogic as a simulation modeling tool,the process of mass evacuation of the injured by means of medical trains was simulated.The simulated process of rescue involved the generation,categorization,treatment and surgery of the injured individuals.The allocation of health care resources was assessed based on the different rates at which the injured arrived.Results In the carriage for mild to moderate patients,24 doctors and 36 nurses could meet the need of treatment.In the carriage for critically ill ones,4 doctors and 6 nurses could meet the need when the rate at which the injured arrived was 100-200 people/an hour.When the injured arrived at the rate of 300-476 people/an hour,4 doctors and 8 nurses were needed.Conclusion Computer simulation can be feasibly used to study the allocation of human resources for health care,which can facilitate decision-making about mass evacuation of injured personnel by means of medical trains.

Objective This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis.Methods C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide(4NQO,50 mg/L).Lingual mucosa samples,being representative of normal tissue(week 0)and early(week 12)and advanced(week 28)tumorigen-esis,were harvested for microarray and methylated DNA immunoprecipitation sequencing(MeDIP-Seq).The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1(SMAD1)were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines.Results The cytosine guanine island(CGI)methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks.The promoter methylation level at 12 weeks exceeded that at 0 weeks.Notably,208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0,12,and 28 weeks.The mRNA of SMAD1 was upregulated,con-current with a decrease in promoter methylation levels in cell lines compared to normal mucosa.Conclusion DNA methylation changed during lingual carcinogenesis.Overexpression of SMAD1 was correlated to promoter hypomethyl-ation in tongue cancer cell lines.

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn²⁺ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn²⁺, we constructed a TDN-MnO₂ complex and found that it displayed a much higher efficacy than TDN plus Mn²⁺ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO₂. These findings provide new therapeutic opportunities for cancer therapy.