Objective To investigate the diagnostic value of serum silent information regulator factor 2-re-lated enzyme 1(SIRT1)and histone deacetylase 4(HDAC4)levels in sepsis complicated with acute kidney in-jury(AKI).Methods From January 2019 to December 2023,120 patients with sepsis complicated with AKI(AKI group)and 60 patients with simple sepsis(non-AKI group)were selected as the study objects.Clinical data of the two groups were collected,and serum SIRT1 and HDAC4 levels were detected by enzyme-linked immunosorbent assay.With sepsis complicated with AKI as the dependent variable,multivariate Logistic re-gression was used to analyze the influencing factors,and receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of serum SIRT1 and HDAC4 levels in sepsis complicated with AKI.Results Compared with non-AKI group,serum SIRT1 level was decreased and HDAC4 level was increased in AKI group,the differences were statistically significant(P＜0.05).Compared with non-AKI group,the pro-portion of septic shock,kidney replacement therapy,sequential organ failure assessment(SOFA)score and se-rum creatinine level in AKI group were higher,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that the independent risk factors of sepsis complicated with AKI were septic shock,increased SOFA score,increased serum creatinine and increased HDAC4(P＜0.05),and the independent protective factor was increased SIRT1(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum SIRT1 and HDAC4 combined diagnosis of sepsis complicated with AKI was 0.891,which was larger than the AUC of serum SIRT1 and HDAC4 alone diagnosis(Z=3.681,3.081,P＜0.001,P=0.002).Conclusion The decrease of serum SIRT1 level and the increase of HDAC4 level are related to sepsis complicated with AKI,and the combination of serum SIRT1 and HDAC4 level has high diagnostic value.

Objective To investigate the effects of Yiqi Wenyang Lishui Formula(derived from Wuling San combined with Astragali Radix and Descurainiae Semen Lepidii Semen)on cardiac function and remodeling in heart failure(HF)patients with yang deficiency and fluid retention syndrome and to analyze risk factors for influencing therapeutic efficacy.Methods A total of 120 HF patients with yang deficiency and fluid retention syndrome admitted to Liaocheng Hospital of Traditional Chinese Medicine from February 2022 to January 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random number table.The control group received conventional western therapy,while the observation group received Yiqi Wenyang Lishui Formula additionally.Both groups were treated for 2 months.Changes in cardiac function indicators and remodeling markers were observed.Clinical efficacy was evaluated,and univariate and binary logistic regression analyses were performed to identify independent risk factors affecting treatment outcomes.Results(1)The total effective rate was 81.67％(49/60)in the observation group versus 70.00％(42/60)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P＜0.05).(2)After treatment,both groups showed significant reductions compared to those before treatment in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(P＜0.01).The reduction in LVEDD,LVESD,and serum NT-proBNP levels in the observation group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(3)Univariate analysis revealed that New York Heart Association(NYHA)functional classification,LVEDD,LVESD,and NT-proBNP levels were significantly associated with the therapeutic efficacy of the Yiqi Wenyang Lishui Formula in heart failure patients with yang deficiency and fluid retention syndrome(P＜0.05).(4)Logistic regression identified NYHA classification,LVEDD,LVESD,and NT-proBNP as independent risk factors(P＜0.05)in affecting therapeutic effect of Yiqi Wenyang Lishui Formula in treating HF with yang deficency and fluid retention syndrome,increasing the risk of ineffective treatment by 4.12-fold,1.21-fold,1.19-fold,and 1.00-fold,respectively.Conclusion Yiqi Wenyang Lishui Formula effectively improves cardiac function and remodeling in HF patients with yang deficiency and fluid retention syndrome.NYHA classification,LVEDD,LVESD,and NT-proBNP are independent risk factors for influencing efficacy,warranting close monitoring for optimized therapeutic adjustments.

Objective To investigate the identification of octreotide(OCT)modified chitosan(CS)miR-155 molecular beacon nanoparticles(CS-miR-155-MB-OCT)and imaging of lung cancer cells for the early screening of lung cancer.Methods A nude mouse model of lung transplantation tumor was established by injecting A549 lung cancer cells into tail veins to establish lung xenograft models.Cre adenovirus was injected through nasal cavity,and mice were killed at 4,6,8 and 12 weeks after adenovirus injection to establish lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and adenocarcinoma of lung in LSL K-ras G12D transgenic mice at different pathological stages.Lung tissue samples were taken and observed by HE staining.Immunohistochemistry were used to detect the expression of somatostatin receptor 2(SSTR2).Real-time fluorescence quantitative PCR was used to detect miR-155 expression levels in lung xenograft models and transgenic mice at different stages of lung cancer.Then CS-miR-155-MB and CS-miR-155-MB-OCT were injected via tail vein in lung xenograft models.CS-miR-155-MB-OCT was injected via tail vein in transgenic mice models.The fluorescence signals of lung in nude mice and transgenic mice at different disease stages were imaged by living imaging system.Frozen slices of lung tissue were made.The source of fluorescence signal was detected by laser confocal scanning microscope(CLSM).Results HE staining showed that lung transplantation tumor models and lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and lung adenocarcinoma at different pathological stages were successfully constructed.Immunohistochemical analysis showed somatostatin receptor 2(SSTR2)was expressed in transplanted lung tumor and tissue at different pathological stages.In transgenic mouse models,the expression of miR-155 was gradually increased as the disease progressed(P＜0.05).In lung xenograft models,the fluorescence signals were significantly higher in the CS-miR-155-MB-OCT group than those of the CS-miR-155-MB group(P＜0.05).In transgenic mouse models,the fluorescence signals gradually increased with the gradual progression of lesions(P＜0.05).After re-imaging the lung tissue,it was found that the fluorescence signal came from lung,and CLSM showed that the fluorescence signal came from cancer cells and some normal alveolar epithelial cells.Conclusion CS-miR-155-MB-OCT can dynamically reflect the occurrence and development of lung cancer according to changes of different fluorescence intensity,thus providing a new technology for the early diagnosis of lung cancer.

Objective:To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR.Methods:A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m 2 day 1, cisplatin 25 mg/m 2 days 1-3, and capecitabine 800 mg/m 2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results:A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm 3. The T stage ( OR=12.71, 95% CI: 1.4-112.5, P=0.022) and the volume ( OR=7.1, 95% CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion:The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Objective:To explore the application effect of micro-video combined with scenario simulation teaching in the training of orthopedic surgery posture placement for intern nursing students, so as to lay a foundation for improving the operation skills of nursing interns.Methods:A total of 86 nursing students in the operating room of Xijing Hospital of Air Force Military Medical University from June 2019 to June 2020 were selected as the research objects. They were divided into the control group ( n=42) and the intervention group ( n=44) according to the time of enrollment. The control group adopted the traditional clinical teaching and learning method, while the intervention group adopted the micro-video combined with scenario simulation teaching method. The effect of intervention was evaluated by theoretical assessment scores, skill operation assessment scores, medical education environmental scores and two-way teaching satisfaction. Results:The theoretical and technical performance assessment scores of the intervention group were higher than those of the control group ( P<0.05) . In addition, the correct rate of surgical positioning in the intervention group increased, while the time required to complete the positioning was reduced ( P<0.05) . In terms of medical education environment scores, students' perception of learning, students' perception of teachers, students' perception of the environment, and students' social self-perception scores and total scores of the intervention group were all higher than those of the control group ( P<0.05) . However, there was no statistically significant difference in academic self-perception of students between the two groups ( P>0.05) . At the same time, the two-way teaching satisfaction of nursing students and teachers in the intervention group was improved ( P<0.05) . Conclusions:The application of micro-video combined with scenario simulation teaching in the training of orthopedic surgical position placement of intern nursing students can effectively improve the teaching quality.

Objective:To prepare a progressive gradient-aperture scaffold composed of silk fibroin(SF)-chitosan(CS)-nano-hydroxyapatite(nHAp)for osteochondral repair.Method:The SF solution, CS solution and nHA suspension were mixed in vitro at equal proportions.The progressive gradient osteochondral(OC)scaffold-1(2%), scaffold-2(3%)and scaffold-3(4%)was respectively prepared by using centrifugation, vacuum freeze-drying, chemical cross-linking and three shaping steps.General conditions, porosity, hot water dissolution rate, water swelling rate, compression water swelling rate, water swelling rate after dissolution, mechanical properties, internal structure observation and pore size were measured.Rat bone marrow mesenchymal stem cells(BMSCs)were cultured and the scaffold extract was prepared.The effect of scaffold extract on the proliferation of BMSCs was detected by the cell counting kit-8(CCK-8)method.BMSCs were co-cultured with the scaffold, and the distribution and morphology of the cells around the scaffold were observed.Results:The structure of scaffold was regular in each group and the porosity was more than 80%.Along with the increase of the material concentration, the water swelling rate of the scaffold was decreased gradually( P<0.05). Compared with before compression, the water swelling rate of scaffold-1 was decreased after compression( P<0.05). There was no significant difference in the hot water dissolution rate among all groups( all P>0.05), and the complete dissolution of the scaffold-1, scaffold-2 and scaffold-3 in vitro required 65.9, 60.9, and 73.9weeks, respectively.The elastic modulus of scaffolds in above three groups were 0.0955, 0.1762 and 0.3468 MPa, respectively.The examination results of scanning electron microscope(SEM)showed that the internal structure of scaffold was honeycomb in each group, the pore shape was regular, which showed an inter-connected pore network.The pore distribution was gradually dense and the pore diameter gradually decreased from the cartilage side to the osteogenic side( P<0.05), and the nHAp content increased gradually.The scaffold extract had no obvious toxicity to the growth and proliferation of BMSCs in each group.After BMSCs were seeded on scaffolds and co-cultured for 5 days, the cells grew well without obvious cell death or morphological abnormalities. Conclusions:In this study, a progressive gradient pore size OC scaffold is successfully prepared with good physical properties and biocompatibility, which is expected to be a new bio-mimetic composite scaffold material for repairing OC defects.

The impact of maintenance therapy on progression?free survival and overall survival as well as quality of life of Chi?nese patients with metastatic colorectal cancer has long been under discussion. Recently, some phase III clinical trials have revealed that maintenance therapy can signiifcantly prolong the progression?free survival while maintain an acceptable safety proifle. Based on this evidence and common treatment practice in China, we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the neces?sity of maintenance therapy, suitable candidates for such treatment, and appropriate regimens.

BACKGROUNDAnticoagulation treatments are an important aspect of hemodialysis; however, few reports have addressed these treatments. This investigation intends to increase the understanding of the current status and improvements of hemodialysis-related anticoagulation treatments in China.

METHODSIn this study, an epidemiological investigation was conducted that examined 842 patients in 2007 and 1 175 patients in 2012 who underwent hemodialysis anticoagulation treatments in seven blood purification centers in northern Chinese cities.

RESULTSHeparin was the most commonly used anticoagulant, although the percentage of use of low-molecular-weight heparin (LMWH) increased from 26.5% in 2007 to 42.1% in 2012. In 2007, there were no significant differences in anticoagulant selection among either patients with various primary diseases or patients with hemorrhage, thrombosis, thrombocytopenia, or a low hemoglobin level. However, compared with patients with other diseases, significantly lower doses of LMWH were administered to patients with hypertension (55.5 U/kg vs. 67.3 U/kg, P < 0.05) or diabetes (58.5 U/kg vs. 67.3 U/kg, P < 0.05), and patients with hemorrhage received lower doses of heparin than the other patients (61.6 U/kg vs. 71.8 U/kg, P < 0.01). In 2012, patients with diabetic nephropathy (51.5% vs. 36.5%, P < 0.01), hemorrhage (43.4% vs. 31.7%, P < 0.01), or a hemoglobin level below 90 g/L (57.2% vs. 37.1%, P < 0.01) experienced significantly higher doses of LMWH administration; patients with hemorrhage received significantly reduced LMWH dosages (50.4 U/kg vs. 57.8 U/kg, P < 0.05), and patients with thrombosis received significantly higher doses of heparin (73.8 U/kg vs. 62.1 U/kg, P < 0.01) or LMWH (57.8 U/kg vs. 52.6 U/kg, P < 0.05). Antiplatelet drugs were administered to 20.4% of the examined patients in 2007 and 20.7% in 2012. In 2012, patients with hypertension (25.9% vs. 18.5%, P < 0.01) and thrombosis (36.6% vs. 16.1%, P < 0.01) had a higher rate of using antiplatelet drugs than patients with other primary diseases and complications. Patients receiving antiplatelet drugs also received higher doses of heparin than patients without using antiplatelet drugs (74.4 U/kg vs. 65.9 U/kg, P < 0.01). However, the use of the drugs was not correlated with thrombocytopenia. The rate at which coagulation indices were determined increased from 45.7% in 2007 to 64% in 2012.

CONCLUSIONThese findings suggested that hemodialysisrelated anticoagulation treatments in China have gradually become more standardized and individualized.

Adult ; Aged ; Anticoagulants ; therapeutic use ; China ; Cities ; Female ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Male ; Middle Aged ; Renal Dialysis ; methods

OBJECTIVEThe aim of this study was to investigate the use of the lesion-specific endonucleases-modified comet assay for analysis of DNA oxidation in cell lines.

METHODSDNA breaks and oxidative damage were evaluated by normal alkaline and formamidopyrimidine-DNA-glycosylase (FPG) modified comet assays. Cytotoxicity were assessed by MTT method. The human bronchial epithelial cell (16HBE) were treated with benzo (a) pyrene (B(a)P), methyl methanesulfonate (MMS), colchicine (COL) and vincristine (VCR) respectively, and the dose is 20 µmol/L, 25 mg/ml, 5 mg/L and 0.5 mg/L for 24 h, respectively. Oxidative damage was also detected by levels of reactive oxygen species in treated cells.

RESULTSFour genotoxicants give higher cytotoxicity and no significant changes on parameters of comet assay treated by enzyme buffer. Cell survival rate were (59.69 ± 2.60) %, (54.33 ± 2.81) %, (53.11 ± 4.00) %, (51.43 ± 3.92) % in four groups, respectively. There was the direct DNA damage induced by test genotoxicants presented by tail length, Olive tail moment (TM) and tail DNA (%) in the comet assay. The presence of FPG in the assays increased DNA migration in treated groups when compared to those without it, and the difference was statistically significant which indicated that the clastogen and aneugen could induce oxidative damage in DNA strand. In the three parameters, the Olive TM was changed most obviously after genotoxicants treatment. In the contrast group, the Olive TM of B(a) P,MMS, COL,VCR in the contrast groups were 22.99 ± 17.33, 31.65 ± 18.86, 19.86 ± 9.56 and 17.02 ± 9.39, respectively, after dealing with the FPG, the Olive TM were 34.50 ± 17.29, 43.80 ± 10.06, 33.10 ± 12.38, 28.60 ± 10.53, increased by 58.94%, 38.48%, 66.86% and 68.21%, respectively (t value was 3.91, 3.89, 6.66 and 3.87, respectively, and all P < 0.05), and the correlation between Olive TM and reactive oxygen species was better than other parameters (r = 0.77, P < 0.05).

CONCLUSIONThis study indicates that FPG-comet assay appears more specific for detecting oxidative DNA damage induced by genotoxicants exposure, and the application of comet assay will be expanded. The endonuclease modified comet assay will be used widely in the toxicology and molecular epidemiology study.

Cell Line ; Comet Assay ; methods ; DNA Damage ; Endonucleases ; Humans ; Mutagens ; toxicity ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; metabolism

OBJECTIVE To find the infla mmation bio markers induced by coke oven e missions (COE),we investigated the changes of T helper 17 (Th17 )cytokines in hu man bronchial epithelial (16HBE)cells.METHODS 16HBE cells were exposed to organic extracts of COE collected fro m co-king plant at the concentrations of 5,10 and 20 mg·L -1 for 24 h or 5 d to establish short-term and long-term cell models,respectively.Cell viability was measured by MTT assay and infla mmatory da mage was assessed by lactate dehydrogenase assay (LDH).The cytokines in culture supernatant sa mples was detected by co mmercial hu man Th17 cytokine panel kit.RESULTS COE Can induce infla mmation in COE 20 mg·L -1 group and no expression on IL-17 F and IL-1 β.The concentration of IL-10 was 1 .25 ± 0.54,1 .39 ±0.13 and (1 .90 ±0.73)pg·mL -1 in COE 5,10 and 20 mg·L -1 group showing good con-centration-effect relationship (r=0.98,P <0.05 ).IL-23 expression was found only higher at 10 and 20 mg·L -1 and the concentrations were 3.38 ±3.90 and (1 .74 ±2.00 )pg·mL -1 ,respectively.In 16HBE cells treated by COE for 5 d,elevated expression of IL-17A was found in COE 5 and 10 mg·L -1 group,and there was statistically sigificant difference between COE 10 mg·L -1 and DMSO group (P<0.05).Elevated concentration of IL-17F of 10.2 ±1 1 .78 and (6.79 ±7.84)pg·mL -1 was found in COE 5 and 10 mg·L -1 group.The concentration of IL-10 was 1 .71 ±0.02,1 .49 ±0.25 and (2.82 ± 0.33)pg·mL -1 in COE 5,10 and 20 mg·L -1 group,respectively.We found increased IL-1 βexpression with concentration of 2.72 ±0.62,2.25 ±0.33 and (0.93 ±0.21 )pg·mL -1 in COE 5,10 and 20 mg·L -1 group with negative dose-response relationship.We also found more elevated TNF-αlevels in the 5 d than in the 24 h model with no COE specific relationship.CONCLUSION COE induces expression changes of Th17 cytokines profile in 16HBE cells,including IL-23 and IL-1 βfor early and long-term infla mmation,respectively.IL-10 may be a candidate marker for population study on COE induced infla mmatory injury.