0.05). There was no significant difference in radiation reaction and squeal between two groups. Conclusions The clinical results of LCAH radiotherapy may be improve the three year of local control rate than conventional CF in stage Ⅲ~Ⅳa but do not improve the survival rate of three years.The radiation reaction and sequela was similar,is worth further study.

Objective To study the differences of clinical manifestations,etiology and hospitalized outcomes of purulent meningitis in preterm and term infants.Method All preterm and term infants with purulent meningitis hospitalized in the Hospital from 2006 to 2015 were enrolled in this study.The data of neonate's condition,maternal condition,clinical manifestations,complications,etiology,treatment and outcomes of the preterm and term infants groups were compared.Result During the study period,44 preterm infants and 118 term infants were included.The time of onset for purulent meningitis of preterm infants group was statistically earlier than that of term infants group [11.2 (3.2,19.8) d vs.14.3 (5.6,23.9) d,P ＜ 0.05].The prognosis of preterm infants group was statistically worse than that of term infants group (P ＜ 0.05).Among them,the incidences of clinical manifestations in preterm infants group compared to term infants group were:fever (54.5％ vs.78.8％),seizure (11.4％ vs.26.3％),lethargy and poor response (59.1％ vs.38.1％),slow weight gain (9.1％ vs.0％),apnea (45.5％ vs.0.8％) and cyanosis (15.9％ vs.4.2％);all the differences between two groups were significant (P ＜ 0.05).The time of onset for purulent meningitis with complications was statistically earlier than those without complications [9.5 (4.1,20.5) d vs.13.8 (5.9,22.0) d,P＜0.05].The duration of treatment for purulent meningitis with complications was longer than that without complications [(42.2 ± 8.8) d vs.(28.7 ± 7.1) d,P ＜ 0.05],and the positive rate of pathogens was also statistically higher than those without complications (73.8％ vs.26.7％,P ＜0.05).Coagulase-negative staphylococcus was the main pathogen for both preterm and term infants group.Klebsiella pneumoniae was more common in preterm infants group than in term infants group (40.0％ vs.10.4％,P ＜0.05).Conclusion Preterm infants with purulent meningitis had early onset time,atypical clinical manifestations,and poor prognosis.The treatment course for purulent meningitis with complications is prolonged.The pathogens for neonatal purulent meningitis have already changed.The detection rate of conditional pathogens is increasing yearly,for which the clinicians should take note seriously.

Objective:To investigate the incidence and risk factors of polymyxin B-associated acute kidney injury (AKI) in patients with severe infections caused by extensive drug resistance Gram negative bacteria (XDR-GNB)in intensive care unit (ICU).Methods:A retrospective study of adult patients with severe infection who received polymyxin B for more than 3 days in the department of critical care medicine of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from April 1st 2018 to January 31st 2020 were performed. AKI was diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The baseline data, indicators during treatment period and prognostic factors were compared between AKI group and non-AKI group. Factors with statistically significant difference in univariate analysis and important clinical factors were included in the Logistic regression model to analyze the risk factors of AKI.Results:Seventy-two patients were treated with polymyxin B for more than 3 days. Forty-nine patients were finally enrolled, with 32 patients developing polymyxin B-associated AKI, and the incidence was 44.4%. The baseline data was balanced in AKI group and non-AKI group, and there was no significant difference in the prognosis [death or discharge without medial order (cases): 14 vs. 6, discharged for improvement (cases): 18 vs. 11, χ 2 = 0.329, P = 0.566]. Polymyxin B-associated AKI occurred from 1 day to 14 days after treatment, with an average of (6.8±3.8) days. Among the 32 AKI patients, 2 cases were lost to follow up after discharge, while renal function recovered in 18 cases and unrecovered in 12 cases. The prognosis of patients without recovery of renal function was significantly worse than that of patients with renal function recovery [death or discharge without medial order (cases): 12 vs. 2, discharged for improvement (cases): 0 vs. 16, P = 0.000]. Single factor analysis showed that daily dosage of polymyxin B in AKI group was higher than that in non-AKI group (mg: 151.6±23.7 vs. 132.4±30.3), numbers of patients with daily polymyxin B dose ≥ 150 mg, using vasoactive drugs, or severe hypoalbuminemia (albumin≤25 g/L) were higher than those in non-AKI group (cases: 29 vs. 10, 18 vs. 4, 9 vs. 0), with statistically significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that daily dosage of polymyxin B ≥ 150 mg and use of vasoactive drugs were independent risk factors for polymyxin B-associated AKI [odds ratio ( OR) = 37.466, 95% confidence interval (95% CI) was 2.676-524.586, P = 0.007; OR = 22.960, 95% CI was 1.710-308.235, P = 0.018]. Conclusions:Comparing with non-AKI patients, more patients with polymyxin B-associated AKI had severe hypoalbuminemia, and the probability of using vasoactive drugs and the daily dose of polymyxin B were higher than non-AKI patients. Daily dose of polymyxin B ≥ 150 mg and using vasoactive drugs were independent risk factors for polymyxin B-associated AKI.

Objective:To investigate the protective effects and mechanisms of targeted inhibition of type 3 deiodinase (Dio3) on skeletal muscle mitochondria in sepsis.Methods:① In vivo experiments: adeno-associated virus (AAV) was employed to specifically target Dio3 expression in the anterior tibial muscle of rats, and a septic rat model was generated using cecal ligation and puncture (CLP). The male Sprague-Dawley (SD) rats were divided into shNC+Sham group, shD3+Sham group, shNC+CLP group, and shD3+CLP group by random number table method, with 8 rats in each group. After CLP modeling, tibial samples were collected and Western blotting analysis was conducted to assess the protein levels of Dio3, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), and silence-regulatory protein 1 (SIRT1). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to examine mRNA expression of genes including thyroid hormone receptors (THRα, THRβ), monocarboxylate transporter 10 (MCT10), mitochondrial DNA (mtDNA), and PGC1α. Transmission electron microscopy was employed to investigate mitochondrial morphology. ② In vitro experiments: involved culturing C2C12 myoblasts, interfering with Dio3 expression using lentivirus, and constructing an endotoxin cell model by treating cells with lipopolysaccharide (LPS). C2C12 cells were divided into shNC group, shD3 group, shNC+LPS group, and shD3+LPS group. Immunofluorescence colocalization analysis was performed to determine the intracellular distribution of PGC1α. Co-immunoprecipitation assay coupled with Western blotting was carried out to evaluate the acetylation level of PGC1α. Results:① In vivo experiments: compared with the shNC+Sham group, the expression of Dio3 protein in skeletal muscle of the shNC+CLP group was significantly increased (Dio3/β-Tubulin: 3.32±0.70 vs. 1.00±0.49, P < 0.05), however, there was no significant difference in the shD3+Sham group. Dio3 expression in the shD3+CLP group was markedly reduced relative to the shNC+CLP group (Dio3/β-Tubulin: 1.42±0.54 vs. 3.32±0.70, P < 0.05). Compared with the shNC+CLP group, the expression of T3-regulated genes in the shD3+CLP group were restored [THRα mRNA (2 -ΔΔCt): 0.67±0.05 vs. 0.33±0.01, THRβ mRNA (2 -ΔΔCt): 0.94±0.05 vs. 0.67±0.02, MCT10 mRNA (2 -ΔΔCt): 0.65±0.03 vs. 0.57±0.02, all P < 0.05]. Morphology analysis by electron microscopy suggested prominent mitochondrial damage in the skeletal muscle of the shNC+CLP group, while the shD3+CLP group exhibited a marked improvement. Compared with the shNC+Sham group, the shNC+CLP group significantly reduced the number of mitochondria (cells/HP: 10.375±1.375 vs. 13.750±2.063, P < 0.05), while the shD3+CLP group significantly increased the number of mitochondria compared to the shNC+CLP group (cells/HP: 11.250±2.063 vs. 10.375±1.375, P < 0.05). The expression of mtDNA in shNC+CLP group was markedly reduced compared with shNC+Sham group (copies: 0.842±0.035 vs. 1.002±0.064, P < 0.05). Although no difference was detected in the mtDNA expression between shD3+CLP group and shNC+CLP group, but significant increase was found when compared with the shD3+Sham group (copies: 0.758±0.035 vs. 0.474±0.050, P < 0.05). In the shD3+CLP group, PGC1α expression was significantly improved at both transcriptional and protein levels relative to the shNC+CLP group [PGC1α mRNA (2 -ΔΔCt): 1.49±0.13 vs. 0.68±0.06, PGC1α/β-Tubulin: 0.76±0.02 vs. 0.62±0.04, both P < 0.05]. ② In vitro experiments: post-24-hour LPS treatment of C2C12 cells, the cellular localization of PGC1α became diffuse; interference with Dio3 expression promoted PGC1α translocation to the perinuclear region and nucleus. Moreover, the acetylated PGC1α level in the shD3+LPS group was significantly lower than that in the shNC+LPS group (acetylated PGC1α/β-Tubulin: 0.59±0.01 vs. 1.24±0.01, P < 0.05), while the expression of the deacetylating agent SIRT1 was substantially elevated following Dio3 inhibition (SIRT1/β-Tubulin: 1.04±0.04 vs. 0.58±0.03, P < 0.05). When SIRT1 activity was inhibited by using EX527, PGC1α protein expression was notably decreased compared to the shD3+LPS group (PGC1α/β-Tubulin: 0.92±0.03 vs. 1.58±0.03, P < 0.05). Conclusion:Inhibition of Dio3 in skeletal muscle reduced the acetylation of PGC1α through activating SIRT1, facilitating nuclear translocation of PGC1α, thereby offering protection against sepsis-induced skeletal muscle mitochondrial damage.

Objective To investigate the effects of protein intake in the early phase and later phase on the outcomes of critically ill patients.Methods A total of 326 critically ill patients admitted in intensive care unit of our hospital from September 2016 to March 2018 were enrolled in this prospective observational study.According to the 28-day prognosis of patients,they were divided into death group and survival group.Early protein target (EPT) was defined as the daily protein intake≥0.8 g/ (kg · d) on days 1-3,and late protein target (LPT) was defined as the daily protein intake≥0.8 g/ (k · d) on days 4-7.Results Daily protein intakes on day 1 and day 3 and cumulative protein intakes on days 1-3 were significantly higher in non-survivors than in the survivors (P＜0.05),but daily protein intakes on day 2,4,5,6 and 7 and cumulative protein intakes on days 4-7 and 1-7 showed no significant difference between two groups (P＞0.05).Hospital mortality was the lowest in the LPT group,the highest in the EPT,and in the middle in the EPT+LPT group and non-EPT+non-LPT group (P＜0.05).The survival curve analysis showed that the survival time of the EPT-only group was significantly lower than that of the LPT-only group (P＜0.05).Multivariate analysis showed that age,sex,cumulative protein and caloric intakes on days 1-7 were the independent risk factors for mortality.Conclusion Early low protein intake is benefit for the outcomes of critically ill patients,and combined with adequate intake of protein in the later stage may further improve the outcomes.

Objective:To explore the predictive value of lipoproteins on the progression of critically ill patients to chronic critical illness (CCI).Methods:A retrospective cohort study was conducted to analyze clinical data of patients admitted to the intensive care unit (ICU) of Nanjing Drum Tower Hospital from January 1, 2020, to December 31, 2022. The levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apolipoproteins (ApoA-Ⅰ, ApoB) at 1, 3, 7, 14 and 21 days after admission to ICU were collected. The progression to CCI was recorded. CCI was defined as the length of ICU stay ≥14 days with sustained organ dysfunction [sequential organ failure assessment (SOFA) score ≥2]. Differences in lipoprotein levels between the patients with and without CCI were compared. Multivariate Logistic regression was used to analyze risk factors for critically ill patients progressing to CCI. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of lipoproteins on critically ill patients progressing to CCI.Results:A total of 200 patients were enrolled in the final analysis. 137 patients (68.5%) progressed to CCI, and 63 patients (31.5%) did not. The lipoprotein indicators in the CCI group showed a decrease after the acute phase, while the lipoprotein indicators in the non-CCI group showed an increase. The levels of HDL, LDL, ApoA-Ⅰ, and ApoB at various time points in the CCI group were significantly lower than those in the non-CCI group. HDL at 7 days in the CCI group was significantly lower than that in the non-CCI group [mmol/L: 0.44 (0.31, 0.61) vs. 0.67 (0.49, 0.75), P < 0.01]. Multivariate Logistic regression analysis showed that 7-day HDL was an independent risk factor for critically ill patients progressing to CCI [odds ratio ( OR) = 0.033, 95% confidence interval (95% CI) was 0.004-0.282, P = 0.002]. ROC curve analysis showed that the area under the ROC curve (AUC) of 7-day HDL for predicting critically ill patients progressing to CCI was 0.702, with a 95% CI of 0.625-0.779, P < 0.001. When the optimal cut-off value was 0.59 mmol/L, the sensitivity was 69.8%, and the specificity was 72.4%. Conclusions:The low level of lipoproteins is closely related to the progression of critically ill patients, and 7-day HDL has a certain predictive value for critically ill patients progressing to CCI. Continuously observation of the change trend of lipoprotein level is helpful to judge the progression of CCI in critically ill patients.