OBJECTIVE: To investigate the impact of early antimicrobial therapy on the prognosis of patients with suspected sepsis in emergency and outpatient settings. METHODS: A prospective cohort study was conducted. Patients with suspected sepsis admitted to the emergency department of Taizhou Hospital, Zhejiang Province, from May 1, 2022, to July 31, 2023, were enrolled. Participants were divided into an early group (0-1 hour) and a delayed group (> 1 hour) according to duration from admission to antimicrobial administration. General information, initial vital signs, laboratory parameters within 24 hours after admission, disease severity scores, vasoactive drug usage, and clinical outcomes of the patient were collected. Kaplan-Meier survival curve was used to analyze 28-day survival. Multivariate Cox proportional hazards regression was performed to identify independent risk factors for prognosis of the patients with suspected sepsis in emergency and outpatient settings. Sensitivity analyses were conducted through subgroup analyses. RESULTS: A total of 143 patients with suspected sepsis were enrolled in the analysis, with 66 patients in the early group and 77 in the delayed group. No statistically significant differences were observed in baseline characteristics (age, gender, vital signs, laboratory parameters, disease severity scores) or clinical outcomes [vasoactive drug usage rate, mechanical ventilation duration, length of intensive care unit (ICU) stay, total hospitalization duration] between the two groups. The 28-day mortality, multidrug resistance rate and sepsis confirmation rate did not differ significantly between the early group and delay group [28-day mortality: 18.2% (12/66) vs. 20.8% (16/77), multidrug resistance rate: 3.0% (2/66) vs. 2.6% (2/77), sepsis confirmation rate: 87.9% (58/66) vs. 88.3% (68/77), all P > 0.05]. Kaplan-Meier survival curve analysis showed no difference in 28-day cumulative survival between the two groups (Log-Rank test: χ² = 2.528, P = 0.112). Multivariate Cox proportional hazards regression identified vasoactive drug usage [hazard ration (HR) = 2.465, 95% confidence interval (95%CI) was 1.019-5.961, P = 0.045] and endotracheal intubation (HR = 5.516, 95%CI was 2.195-13.858, P < 0.001) as independent risk factors for 28-day death of the patients with suspected sepsis in emergency and outpatient settings. Further exploration of the impact of early antimicrobial therapy on 28-day death in different subgroups of the patients with suspected sepsis in emergency and outpatient settings was conducted through subgroup analysis. The results showed that in the patients with different ages (< 60 years old: HR = 1.214, 95%CI was 0.535-2.751, P = 0.643; ≥ 60 years old: HR = 2.085, 95%CI was 0.233-18.668, P = 0.511), sequential organ failure assessment (SOFA) scores (< 6: HR = 1.411, 95%CI was 0.482-4.128, P = 0.530; ≥ 6: HR = 0.869, 95%CI was 0.292-2.587, P = 0.801), shock indexes (< 1: HR = 1.095, 95%CI was 0.390-3.077, P = 0.863; ≥ 1: HR = 1.364, 95%CI was 0.458-4.059, P = 0.577) and whether diagnosed with sepsis or not (yes: HR = 0.943, 95%CI was 0.059-15.091, P = 0.967; no: HR = 1.207, 95%CI was 0.554-2.628, P = 0.636) subgroups, early usage of antibiotics had not shown any advantage in improving prognosis compared with delayed usage. CONCLUSION Early antimicrobial therapy does not improve the prognosis of patients with suspected sepsis in emergency and outpatient settings.
Humans ; Sepsis/drug therapy* ; Prospective Studies ; Prognosis ; Emergency Service, Hospital ; Outpatients ; Female ; Male ; Anti-Infective Agents/therapeutic use* ; Middle Aged ; Aged ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

Objective:To investigate the effect of intravenous prophylactic administration of dezocine before anesthesia induction on choking during induction period in patients undergoing general anesthesia.Methods:A total of 92 patients with tracheal intubation surgery under general anesthesia from November 2020 to May 2021 in the Zhejiang Taizhou Hospital were selected and randomly divided into the observation groupand the control group by random number table, with 46 cases in each group. The observation group was intravenously injected with 0.1 mg/kg dezocine while the control group was intravenously injected with 0.9% sodium chloride 5 ml before anesthesia induction. Anesthesia induction was performed at 10 min after injection in the two groups. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and catecholamine, interleukin-6 (IL-6) levels were recorded at before anesthesia induction (T 0), 1 min before endotracheal intubation (T 1), 1 min after intubation (T 2), and 5 min after endotracheal intubation (T 3). The incidence and degree of choking, the agitation score, visual analog scale (VAS) score, Ramsay sedation score and the incidence of adverse reactions in the two groups were compared. Results:The levels of HR, SBP and DBP at T 0, T 1, T 2 and T 3 in the two groups had no significant differences ( P>0.05). The levels of catecholamine and IL-6 in the control group were higher than those in the observation group: (120.49 ± 15.13) ng/L vs.(113.53 ± 17.14) ng/L, (16.80 ± 2.61) ng/L vs. (13.46 ± 1.55) ng/L, there were statistical differences ( P<0.05). The recovery time to spontaneous breathing in the observation group was shorter than that in the control group: (8.76 ± 2.14) min vs. (9.87 ± 2.09) min, there was statistical difference ( P<0.05). The incidence of choking in the observation group was lower than that in the control group: 2.17%(1/46) vs. 21.74%(10/46), there was statistical difference ( P<0.05). The scores of agitation score and VAS in the observation group were lower than that in the control group, and the scores of Ramsay sedation score was higher than that in the control group: (1.43 ± 0.26) scores vs. (2.11 ± 0.14) scores, (3.55 ± 1.03) scores vs. (4.86 ± 1.15) scores, (3.13 ± 0.76) scores vs. (1.54 ± 0.32) scores, there were statistical differences ( P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group: 6.52%(3/46) vs. 23.91% (11/46), there was statistical differences ( χ2 = 5.39, P<0.05). Conclusions:For patients with tracheal intubation under general anesthesia, preventive injection of dezocine before anesthesia induction can effectively inhibit the stress response of patients, with little impact on the patients′ circulatory system and respiratory system, and can also effectively reduce the incidence of choking in the induction period.

Objective:To evaluate immune response of murine peritoneal macrophage challenging by methicillin-resistant S.aureus(MRSA)after pretreatment with Pam3Csk4(TLR2 agonist).Methods: Murine peritoneal macrophage was pretreated with Pam3Csk4(1 μg/ml).Following pretreatment 12 h later,heat-killed MRSA( HK-MRSA) was added and incubated for another 2 or 6 hours.The protein and mRNA level of TNF-α, IL-6 and IL-1 were determined by ELISA and Q-PCR, respectively.To estimate phagocytosis of macrophage,HK-MRSA/MSSA labeled with FITC( FITC-HK-MRSA/MSSA) were added to well and incubated for 30 min.After washing 5 times with PBS,intracellular FITC-HK-MRSA was detected by flow cytometry.To estimate antimicrobal activity of macrophage,live MRSA and MSSA were added to well and incubated at indication time,the CFU of s.aureus was estimated via a 10-fold serial dilution on agar media.cDNA was further quantitative assessed using primers for mouse FCR-Ⅰ,FCR-Ⅲ,CR-1,CR-3,iNOS and LL37 by Q-PCR .Results: Compared with saline-pretreated cell, the protein and mRNA level of TNF-α, IL-6 and IL-1 were markely reduced, respectively.However, both the phagocytosis and antimicrobal activity to S.aureus were significantly increased in macrophages pretreated with Pam3Csk4.Further study found that the macrophages had higher FCR-Ⅰ,FCR-Ⅲ,CR-1,CR-3,iNOS and LL37 expression at 6 h and 12 h post-stimulation Pam3Csk4.Conclusion: The results suggest that Pam3Csk4 could activate murine antimicrobal activity of peritoneal macrophage challenging by methicillin-resistant Saureus via increasing opsonophagocytosis in depended antibodies, complements manners.The results suggest Pam3Csk4 probably be a novel immunotherapy candidate against MRSA.

Objective To study the effects of miR?21 on the proliferation,apoptosis and MMP2 expression of HeLa cells. Methods The miR?21 or the miRNA scramble control was transfected into Hela cells. The cell proliferation was detected by the Celltiter?GloTM assay 72 h after the transfection,and the apoptosis was evaluated by the Caspase3/7 Glo? Kit. The MMP2 RNA expression was quantified by quantitative real time PCR. Results The proliferation of HeLa cells transfected with miR?21 was significantly increased compared to that of the cells transfected with miRNA scramble control. The caspase 3/7 activity in HeLa cells transfected with miR?21 was downregulated compared to that of the cells transfect?ed with miRNA negative control. The MMP2 RNA expression in HeLa cells transfected with miR?21 was increased significantly compared to the cells transfected with miRNA negative control. Conclusion miR?21 can significantly promote the proliferation of HeLa cells. In addition,it ex?hibits the anti?apoptosis effect in HeLa cells. The transfection of miR?21 significantly increased the MMP2 RNA expression,which suggests that miR?21 may promote the tumor invasion and might be a therapeutic intervention target.

This paper presents an approach to GPU-based ray-casting of a shader model 3.0 compatible graphics card. In addition, a software toolkit is designed using the proposed algorithm to make the full benefit of GPU by extending VTK. Experimental results suggest that remarkable speedups are observed using GPU-based algorithm, and high-quality renderings can be achieved at interactive framerates above 60 fps. The toolkit designed provides a high level of usability and extendibility.
Algorithms ; Image Interpretation, Computer-Assisted ; methods ; Software Design

Objective　To observe the response rate, survival time and toxicity of docetaxel and cisplatin in weekly schedule in the treament of stage Ⅲ-Ⅳ non-small cell lung cancer. Methods　A total of 30 cases of stage Ⅲ-Ⅳ non-small cell lung cancer was included in this study. Docetaxel 25*!mg／m2 and cisplatin 25*!mg／m2 were given through intravenous dripping for the 1st, 8th, and 15th days. The chemotherapy was repeated every 28 days. Each patient was given at least 2 cycles. Results　The overall response rate was 43.3％ (13／30，all were partial response). Quality of life of the patients was improved (there were 66.7％ of the patients with Karnofsky score increased or unchanged). Median remission duration was 7 months. 40％ of the patients survived for more than 1 year. The main toxicity was hematological: Grade Ⅲ-Ⅳ leucopenia was 16.7％; Grade Ⅲ thrombocytopenia was 6.7％. The non-hematological toxicity was mild. Conclusion　The regimen of docetaxel and cisplatin in weekly schedule is effective and tolerable in the treatment of non-small cell lung cancer.