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.

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.

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.

Purpose: This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods: From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA). Results: Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness. Conclusion Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

Objective To evaluate the incidence, prognosis and influencing factors of lower cranial nerve palsy after microvascular decompression (MVD) in patients with hemifacial spasm (HFS). Methods Clinical data of 1033 patients with HFS, admitted to our hospital from May 2014 to August 2016, were retrospectively analyzed. The incidence of lower cranial nerve palsy after procedure and prognosis of these patients were summarized; and influencing factors were analyzed by statistical method. Results In 1033 patients with HFS, 10 patients (0.97％) had lower cranial nerve palsy after procedure: 6 patients suffered hoarseness, 2 patients suffered dysphasia, and 2 patients were with both symptoms; the symptoms in 6 patients completely recovered within one month, 2 patients within one-3 months, and 2 patients within 3-6 months. No permanent low cranial nerve palsy occurred. There were no statistical significances in age, gender, clinical course, sides, or the types of offending vessels between the lower cranial nerve palsy patients (n=10) and the non-palsy patients (n=1023)(P>0.05). Conclusion Lower cranial nerve palsy is a rare complication after MVD, and type of responsible vessels is not a influencing factor in this complication

Objective:To evaluate the short-term economic effects of four kinds of premixed insulin in newly diagnosed type 2 dia-betes mellitus. Methods:A total of 120 newly diagnosed patients with type 2 diabetes mellitus were divided into four groups according to the kind of premixed insulin, group A was treated with insulin aspart 30 injection, group B was treated with insulin lispro 25 injec-tion, group C was treated with isophane protamine biosynthetic human insulin injection and group D was treated with protamine zinc re-combinant human insulin injection. The course of treatment was three months. The therapy efficacy was assessed by the remission rate in three months. The short-term economic effect was evaluated by the cost-minimization analysis method. Results:The remission rate of group A, B, C and D respectively was 48. 39%, 48. 28%, 51. 61% and 51. 72% without significant difference (P>0. 05). The average cost per person of the four groups was 1195. 52, 1202. 41, 1220. 69 and 1258. 84 yuan, and the average medicine cost per person was 750. 52, 689. 41, 754. 69 and 764. 34 yuan, respectively. There was no significant difference in cost among the four groups (P >0. 05). Conclusion:All the four kinds of premixed insulin can be used for the starting treatment with the similar total cost, and in relative terms, aspart 30 injection and insulin lispro 25 injection are better for the initial treatment of diabetes.

Since the fecal bacteria transplantation (FMT) had been exist for a long time, it attracted more attention in recent years because this therapy could adjust the bacteria disturbance rapidly in clinical settings. Recent studies demonstrated that fecal microbiota transplantation (FMT) has great clinical value in the treatment of Clostridium difficile infection, inflammatory bowel disease, Intractable functional constipation and other diseases. But the FMT is not as perfect as we expect, so we did this article to review the history and terminology of FMT, and summarized the progress in nursing methods of FMT.

Objective To evaluate the therapeutic effect of bone marrow mesenchymal stem cell (MSC) infusion transplantation via renal artery and via caudal vein in treating chronic kidney disease (CKD) in rats,and to compare the expressions of aquaporin1 (AQP1) and aquaporin2 (AQP2) between the two transplantation routes.Methods A total of 50 male SD rats were selected for this experiment.Two experimental rats were used to make preparation of bone marrow MSC.CKD model was established with infusion of adriamycin via caudal vein in 36 rats.The 36 CKD models were randomly divided into adriamycininduced renal failure model control group (A-C group,n=12),MSC transplantation through the right renal artery group (M-A group,n=12) and MSC transplantation through the caudal vein group (M-V group,n=12).The remaining 12 male SD rats were used as the blank control group (N group).One week after the last bone marrow MSC transplantation,the 24 h urine volume,24 h urinary protein content,serum sodium content and serum albumin level were measured,and AQP1 and AQP2 expressions in the kidney tissue were determined by immunohistochemistry.Results Compared with A-C group,the serum albumin level and 24h urine volume in both M-V group and M-A group were significantly increased (P＜0.05),while 24h urinary protein content and serum sodium content were remarkably decreased (P＜0.05).The 24h urinary protein content in the M-A group was obviously lower than that in the M-V group (P＜0.05).The AQP1 and AQP2 expressions in the kidney tissue in both M-V group and M-A group were strikingly lower than those in the A-C group (P＜ 0.05),but no statistically significant differences in AQP1 and AQP2 expressions existed between the M-V group and the M-A group (P＞0.05).Conclusion MSC transplantation can increase serum albumin,and lower urinary protein,serum sodium and the expressions of AQP1 and AQP2 in renal parenchymal cells,which has the effect on repairing renal injury of adriamycin-induced CKD rats.For a given period of time,the clinical curative effect of MSC transplantation via renal artery is better than that of MSC transplantation via peripheral vein,but the difference in curative effect between the two MSC transplantation pathways has no obvious correlation with AQP1 and AQP2 expressions.