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Current clinical approaches for septic shock increasingly incorporate bundle treatment, a multi-component approach that uses a collection of tests and agents to assist in the identification and treatment of infection. The present study analyzed completion rates of 3 h and 6 h bundle treatment among patients with septic shock in intensive care units (ICUs) of hospitals in Jiangsu Province from 2016 to 2020, using data from the Jiangsu Provincial Intensive Care Medical Quality Control Center. Current approaches and factors affecting treatment completion were assessed.The completion rates of 3 h and 6 h bundle treatment in ICUs of all medical units in Jiangsu Province and in ICUs of hospitals of different levels were recorded. Analyses show that the completion rate of 3 h and 6 h bundle treatment for patients with septic shock in ICUs in Jiangsu Province increased year by year from 2016 to 2020.The completion rate of 3 h bundle treatment increased from 69.82% (3 604/5 162) to 82.47% (8 915/10 775) (all P< 0.001). The completion rate of 6 h bundle treatment increased from 62.69% (3 236/5 162) to 72.54% (7 816/10 775) (all P< 0.001). In addition, year by year, the completion rate of 3 h bundle treatment in ICUs in tertiary hospitals increased, from 69.80% (3 596/5 152) to 82.23% (7 375/8 969), while the completion rate of 6 h bundle treatment increased from 62.69% (3 230/5 152) to 72.18% (6 474/8 969) (all P< 0.001). Completion rates in secondary hospitals also increased year by year, from 80.00% (8/10) to 85.27% (1 540/1 806) for 3 h treatment and from 60.00% (6/10) to 74.31% (1 342/1 806) (all P< 0.001) for 6 h treatment. Completion rates for 3 h treatment in first-tier cities (83.99% (2 099/2 499)) and second-tier cities (84.68% (3 952/4 667)) was higher than in third-tier cities (79.36% (2 864/3 609)). The completion rate of 6 h bundle treatment gradually decreased in first-line (77.19% (1 929/2 499)), second-line (74.37% (3 471/4 667)), and third-line (66.94% (2 416/3 609)) cities (all P< 0.001). The data collectively show that from 2016 to 2020, the completion rate of bundle treatment in septic shock patients in ICUs in Jiangsu Province improved significantly.

Acute respiratory distress syndrome (ARDS) is a common critical disease, which often leads to poor prognosis in critically ill patients. The excessive respiratory drive in ARDS is related to lung injury. Control of excessive respiratory drive is helpful to reduce lung injury and mortality of ARDS. The mechanisms of abnormal increase in respiratory drive in ARDS include hypoxemia, hypercapnia, stretch reflex caused by alveolar collapse and inflammatory stimulation. Respiratory drive should be evaluated by clinical manifestations, physiological parameters and respiratory mechanics indexes. It is particularly important to make individual therapy strategies according to the evaluation of respiratory drive. Analgesia and sedation combined with muscle relaxation, high positive end-expiratory pressure (PEEP) and prone position can be used to control excess respiratory drive. This article reviews the evaluation and management of excess respiratory drive in ARDS patients.

Objective: To investigate the relationship between the levels of exosomes in bronchoalveolar lavage fluid (BALF) and plasma and the severity of lung injury and its outcome in patients with acute respiratory distress syndrome (ARDS). Methods: Patients who were admitted to the Department of Critical Care Medicine, Zhongda Hospital Affiliated to Southeast University and received invasive mechanical ventilation were selected from August 2020 to April 2021, and they were divided into ARDS group and non-ARDS group. Finally, 33 ARDS patients were included, including 18 males and 15 females, aged (65.5±15.5) years; 10 non-ARDS patients, 8 males and 2 females, aged (57.2±15.3) years. The BALF and plasma of the two groups of patients were collected within 24 hours after enrollment, and the total exosomes of the samples were collected by ultracentrifugation. Nanoparticle tracking analysis (NTA) was used to detect and compare the differences in exosome content between the two groups. Correlation of content with the severity and prognosis of lung injury in ARDS patients. Results: There was no significant difference in gender and age between ARDS group and non-ARDS group (both P >0.05). The exosome in plasma of ARDS group was significantly higher than that of non-ARDS group [(25.3±1.2)/ml vs (24.2±1.6)/ml, P =0.031], while the exosomes in BALF of ARDS group was also higher than that of non-ARDS group [(26.5±1.6)/ml vs (24.6±1.1)/ml, P =0.001]. The exosomes in BALF of patients with ARDS caused by intrapulmonary causes was higher than that in ARDS group caused by extrapulmonary causes [(26.9±1.5)/ml vs (25.2±0.9)/ml, P =0.01], and the infection caused by bacterial shows that the highest exosome level in BALF. The exosomes in the BALF of the mild ARDS group was significantly lower than that of the severe ARDS group [(25.7±1.3)/ml vs (27.2±1.5)/ml, P =0.038]; the exosomes in BALF of ARDS patients was negatively correlated with P/F ratio ( r =-0.38, P =0.03); and it was positively correlated with Murray lung injury score ( r =0.47, P =0.01). However, the static compliance levels, length of hospital stay, duration of mechanical ventilation, and 28-day outcome were not associated with the exosomes in BALF. Conclusion: Compared with non-ARDS patients, ARDS patients have significantly higher levels of exosomes in BALF and plasma, there is a certain correlation between exosomes derived from BALF and the severity of lung injury in ARDS.

Objective: To develop an area under curve (AUC)-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill patients. Methods: This retrospective cohort study included adult patients treated with vancomycin in the intensive care unit at a tertiary teaching hospital from January 2015 to December 2017. Baseline clinical characteristics before vancomycin treatment and pharmacokinetic parameters were collected to establish a prediction model of nephrotoxicity. Univariate analysis was used to screen variables, and multivariate logistic regression analysis was used to establish the prediction model and nomogram. Results: A total of 159 patients met the inclusion criteria, sixty-four were included in the final analysis. Sixteen patients (25%, 16/64) developed vancomycin-associated nephrotoxicity. The following variables were incorporated into the prediction model: vancomycin AUC, estimated glomerular filtration rate (GFR), and combined nephrotoxic drugs. The following equation was established to calculate the probability of nephrotoxicity: logit (P)=-4.83+0.009×AUC-2.87×1 (if GFR>60 ml/min)+2.53×1 (if number of combined nephrotoxic drugs≥2). A nomogram was generated based on the equation. The receiver-operating characteristic curve demonstrated that the AUC of the prediction model was 0.927 (95% CI 0.851-1.000). The cut-off value of the probability of nephrotoxicity was 26.48%. The sensitivity and specificity were 87.5% and 87.5% respectively. Conclusion: The incidence of vancomycin-associated nephrotoxicity is high. The AUC-based nomogram can effectively predict vancomycin-associated nephrotoxicity in critically ill patients.

Objective: To evaluate the effects of neuromuscular blocking agents (NMBA) on oxygenation and respiratory conditions in patients with acute respiratory distress syndrome(ARDS). Methods: English databases such as MEDLINE, Embase and Web of Science were searched online, as well as Chinese databases such as China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database and Wanfang Database. Randomized controlled trials (RCTs) of NMBA therapy for ARDS with publication date up to May 2020 were retrieved. Literature was screened according to inclusion and exclusion criteria, and the main analysis indicators were oxygenation index. Results: A total of 5 RCTs were included, and 1 462 ARDS patients were enrolled. Compared with the control group, the ratio of partial arterial oxygen pressure to fraction of inspired (PaO 2 )/(FiO 2 ) significantly improved in the intervention group after 72 hours MD =14.39, (95 %CI 6.40-22.38, P= 0.000 4) and 96 hours of NMBA, but there was no difference between PaO 2 /FiO 2 at 24 and 48 hours ( P> 0.05).Positive end expiratory pressure (PEEP) significantly decreased at 72 hours ( MD =-0.45, 95 %CI -0.87--0.03, P= 0.04) and 96 hours ( MD =-0.82, 95 %CI -1.39--0.26, P= 0.004) treatment with NMBA, while there was no significant difference in PEEP between 24 and 48 hours after treatment ( P> 0.05). At 96 h, plateau pressure (Pplat) in the intervention group was significantly lower ( MD =-1.69, 95 %CI -2.64--0.75, P= 0.000 4), and there was no significant difference in Pplat between 24, 48 and 72 h after treatment ( P> 0.05). Conclusion: The early use of NMBA within 48 hours has a delayed improvement effect on oxygenation and ventilator conditions in ARDS patients.

To determine the physicians'compliance of hour-1 bundle for sepsis. A management system of hour-1 bundle for sepsis was established. The clinical data of 286 sepsis patients were collected, who were classified into 3 months before the bundle (control group), 9 months during process (observation group) and 3 months after bundle (study group). The compliance of hour-1 bundle implementation was compared in three groups. The results showed that with the application and implementation of the management system, the compliance of hour-1 bundle for sepsis in the control group, observation group and study group was 58.3%(28/48), 69.1%(105/152) and 88.4%(76/86) respectively (χ 2 =7.053, P =0.029). The 28 day mortality in sepsis patients was 41.7%(20/48), 34.9%(53/152) and 23.3%(20/86) respectively (χ 2 =5.576, P =0.062).The management system of hour-1 bundle for sepsis can effectively improve the physicians' compliance.

Objective: To investigate the role of chest wall elastic resistance in determining the effects of positive end-expiratory pressure (PEEP) on central venous pressure (CVP) in patients with mechanical ventilation (MV). Methods: In this prospective study, according to the median of ratio of chest wall elastic resistance to respiratory system elastic resistance (Ers), patients were divided into high chest wall elastic resistance group (Ecw/Ers≥0.24) and low chest wall elastic resistance group [elastance of chest wall (Ecw)/Ers<0.24]. PEEP was set at 5, 10, 15 cmH 2 O (1 cmH 2 O=0.098 kPa) respectively. Clinical data including CVP, heart rate (HR), blood pressure (BP) and respiratory mechanics were recorded. Results: Seventy patients receiving MV were included from November 2017 to December 2018. Clinical characteristics including age, BP, HR, baseline PEEP, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) and comorbidities were comparable in two groups. However, patients with high Ecw/Ers ratio presented higher body mass index (BMI) than those with low Ecw/Ers ratio[ (25.4±3.2) kg/m 2 vs. (23.4±3.2) kg/m 2 , P =0.011]. As PEEP increased from 5 cmH 2 O to 10 cmH 2 O, CVP in high Ecw/Ers group increased significantly compared with that in low Ecw/Ers group [1.75(1.00, 2.13) mmHg (1 mmHg=0.133kPa) vs. 1.50(0.50, 2.00)mmHg, P =0.038], which was the same as PEEP increased from 10 cmH 2 O to 15 cmH 2 O [2.00(1.50, 3.00)mmHg vs. 1.50(1.00, 2.00)mmHg, P =0.041] or PEEP increased from 5 cmH 2 O to 15 cmH 2 O [ 3.75(3.00,4.63)mmHg vs. 3.00(1.63, 4.00)mmHg, P =0.012]. When PEEP increased from 5 cmH 2 O to 10 cmH 2 O, 10 cmH 2 O to 15 cmH 2 O and 10 cmH 2 O to 15 cmH 2 O, there were significant correlations between Ecw/Ers and CVP elevation ( r =0.29, P =0.016; r =0.31, P =0.011; r =0.31, P =0.01 respectively). Conclusions: In patients receiving mechanical ventilation, elevation of PEEP leads to a synchronous change of CVP, which is corelated with patients' chest wall elastic resistances.

Objective: To acquire the signal of neuron excitability and blood oxygen in mouse cortex after ischemic stroke, and to clarify the relationship between the change of neurovascular function and the degree of cerebral infarction. Methods: The male C57BL/6 mouse( n= 20) about 6-8 weeks and 20 g weight were produced the embolic stroke modal by photochemical injury. The mouse cortex was scanned by the multispectral optical imaging while using electric stimulation in 1, 3 and 7 d after operation. Then several data around the infarction were acquired including neuron excitability, the total hemoglobin concentration and deoxygenated hemoglobin concentration. The ischemic cerebral infarction size was analyzed by TTC staining. Plasma TNF-α concentration was measured by enzyme-linked immunosorbent assay(ELISA). And modified neurological severity score (mNSS) was recorded after ischemic stroke( n= 30). Then correlativity analysis was used between the optical signals and three indicators of cerebral infarction degree. Results: The changes of neuron excitability signals were 1.15%±0.28%, 2.84%±1.06%, 2.21%±0.55%. The total hemoglobin concentration signals were 3.71%±2.76%,3.19%±2.70%,4.27%±3.05%. The deoxygenated hemoglobin concentration signals were 2.93%±2.33%, 3.60%±1.74%, 2.08%±1.28%. The neural signal was correlated to cerebral infarction size, plasma TNF-α concentration and mNSS( r= -0.441, -0.449,-0.404, all P< 0.05), and mNSS had a great effect on neuron excitability(β=-0.169, P< 0.05). Meanwhile, the total hemoglobin concentration was correlated to cerebral infarction size( r= 0.440, P< 0.05). Conclusion: The signal of neuron and blood oxygen is able to represent the change of neurovascular function and evaluate the progression of ischemic stroke.

Objective: To analyze the silver content, homogeneity, and cytotoxicity of silver-containing products. Methods: (1) Five kinds of silver-containing products A, B, C, D, and E were purchased from the market, and products A, B, C, and D are liquid or gel form while product E was dressing form. The silver content of each product and the homogeneity of product E were determined by flame method. The sample number was 3. (2) Human hepatocellular carcinoma cell line (HepG2) was selected as the evaluation model. Four silver-containing products A, B, C, and D were diluted with high-glucose dulbecco's modified eagle medium (DMEM) at multiple ratios of 1∶100, 1∶200, 1∶400, and 1∶800, and then they were used for cell culture. Cells cultured with high-glucose DMEM and high-glucose DMEM containing 20 μg/mL silver nitrate were used as blank control and positive control, respectively. The cell viability was determined by methyl thiazolyl tetrazolium assay, and each sample number was 5. (3) Four mass concentrations of 0.031 3, 0.062 5, 0.125 0, and 0.250 0 μg/mL were prepared from silver-containing product A, and then they were used to culture HepG2 cell. Cells cultured with high-glucose DMEM containing fetal calf serum and 294 μg/mL potassium dichromate were used as positive control, while those containing fetal calf serum were used as blank control. Hoechst 33258 staining method was used to detect apoptosis rate of cells. The tail moment, tail length, and the percentage of DNA in the tail of cells were observed by comet assay to evaluate DNA damage. The sample numbers were all 3. Data were processed with one-way analysis of variance and least significant difference- t test. Results: The silver content of products A, B, C, and D was (256.5±1.5) μg/mL, (271.5±1.3) μg/mL, (652.4±2.6) μg/g , (330.0±2.1) μg/g, which was in accordance with labelled amount. The silver content of product E was (0.158±0.013) mg/g, and the silver content of each piece of product E was (0.125±0.017) mg/g, showing good uniformity of product E. (2) Compared with the rate of blank control, the cell survival rates of product A at the dilution ratio of 1∶100, product B at the dilution ratio of 1∶100, and product C at the dilution ratio of 1∶100 and 1∶200 were significantly reduced ( t =35.506, 8.914, 37.594, 30.693, P <0.01). Compared with the rate of positive control, the cell survival rates of product A at the dilution ratio of 1∶200, 1∶400, and 1∶800, product C at the dilution ratio of 1∶400 and 1∶800, products B and D at each dilution ratio were increased significantly ( t =27.537, 18.262, 18.709, 26.333, 41.762, 15.776, 19.759, 20.443, 15.715, 26.792, 24.963, 31.803, 30.537, P <0.01). (3) The apoptosis rates of cells treated by 0.250 0 μg/mL product A and positive control were (6.1±0.4)% and (62.2±3.9)% respectively, which were significantly higher than the apoptosis rate of blank control [(3.3±0.7)%, t =13.327, 30.475, P <0.05]. The apoptosis rates of cells treated by 0.031 3, 0.062 5, 0.125 0 μg/mL product A were (2.9±0.4)%, (3.1±0.4)%, and (4.2±0.9)% respectively, which were close to the apoptosis rate of blank control ( t =1.181, 0.133, 1.097, P >0.05). (4) The tail moment, tail length, and tail DNA percentage of cells cultured with 0.125 0 and 0.250 0 μg/mL product A were significantly higher than those cultured with blank control ( t =29.026, 51.194, 21.851, 36.138, 24.721, 50.455, P <0.05 or P <0.01). However, the tail moment, tail length, and tail DNA percentage of cells cultured with 0.031 3 and 0.062 5 μg/mL product A were close to those cultured with blank control ( t =5.878, 3.429, 2.779, 1.960, 1.328, 7.763, P >0.05). Conclusions: The silver content of silver-containing products meets the requirements of the labeling. The concentration of product C is higher than that of other products, leading to a greater possibility of decreasing the survival rate of HepG2 cells. It is suggested that the products A and B should be taken as reference in the concentration setting of silver ion products. The product solution with higher concentration may have higher risk of damage to cell DNA. Therefore, it is not recommended to upregulate silver content of relevant products blindly in order to achieve better antibacterial effect.

Nowadays, antibacterial products containing silver ion are widely used in clinical wound treatment. The concentration of silver ion in products, pH value, and other factors may affect the release of silver ion and its antibacterial effects. In the treatment of clinical wound, silver ion product plays a good role in anti-infection, promoting healing and reducing medical expenses. In this paper, the related applications of silver ion products in wound surface are analyzed, and the antibacterial properties of silver ion and its therapeutic effects in wound treatment are summarized.

Objective: To explore the acute toxic effect and the cumulative target organ of silver nitrate and nano-silver with two different particle diameters in rats. Methods: Thirty-six adult SD rats were divided into small particle size nano-silver group (SNS), large particle size nano-silver group (LNS), silver nitrate group (SN), and control group (C) according to the random number table, with 9 rats in each group. The rats of the four groups were respectively injected with 10 mg/mL nano-silver solution (particle diameter of 20 nm, prepared by saline) in silver dose of 30 mg/kg by tail vein for once, 10 mg/mL nano-silver solution (particle diameter of 100 nm, prepared by saline) in silver dose of 30 mg/kg, 1.67 mg/mL silver nitrate solution (prepared by glucose solution) in silver dose of 3 mg/kg, and 30 mg/mL polyvinylpyrrolidone solution (prepared by saline) in dose of 90 mg/kg. (1) Toxicity test. The general observation was performed within 14 days after injection, and the deviation between value of body mass before injection and each of that on post injection day (PID) 1, 7, and 14 were respectively recorded. On PID 1, 7, and 14, 3 rats of each group were harvested for determination of serum content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, and albumin by fully automatic biochemical analyzer. Then the rats were sacrificed immediately, and heart tissue, liver tissue, spleen tissue, lung tissue, kidney tissue, and brain tissue were collected to calculate the organ coefficient. Organ samples with obvious changes in organ coefficient were collected for histopathological observation by HE staining, with 3 samples in each group at each time point. (2) Bio-distribution. The specimens of heart, liver, spleen, lung, and kidney of rats from groups SNS, LNS, and SN were collected for detection of silver content by inductively coupled plasma mass spectrometry, with 3 samples in each group at each time point. Data were processed with analysis of variance of factorial design, LSD test, and Dunnett's T3 test. Results: (1) The general condition of rats in groups C and SN after injection were normal. The state of rats of groups SNS and LNS was poor with black secretion in the eye and other phenomena on PID 1, which recovered from PID 3 on. (2) The deviations between values of body mass before injection and that on PID 14 in rats of groups LNS and SN were significantly decreased as compared with deviation of group C (with P values below 0.01), but deviation of group SNS was not significantly changed ( P >0.05). The deviations between values of body mass before injection and each of that on PID 1 and 7 in rats in the other three groups were similar to those in group C (with P values above 0.05). (3) Compared with those in group C, the serum content of total protein of rats in group SN on PID 1 was significantly decreased, and liver coefficient was significantly increased (with P values below 0.05). On PID 1, the serum content of ALT of rats in group LNS was (61.0±8.7) U/L, which was significantly higher than that in group C [(40.0±4.6) U/L, P <0.01]. Compared with those in group C [(126.0±3.5) U/L and 4.05±0.23], the serum content of AST of rats in groups SNS and LNS on PID 1[(249.7±107.2) and (237.0±38.3) U/L] was significantly increased, and liver coefficients (3.50±0.38 and 3.31±0.07) were significantly decreased, with P values below 0.05. Compared with those in group C [(69.2±4.8) U/L and 4.32±0.39], the serum content of AST of rats in groups SNS and LNS on PID 7 [(181.0±51.5) and (167.7±16.5) U/L] was also significantly increased, and liver coefficients (3.55±0.18 and 3.62±0.21) were also significantly decreased, P <0.05 or P <0.01. On PID 14, the four liver biochemical indexes in serum and all organ coefficients of rats in the other three groups were similar to those in group C (with P values above 0.05). (4) The liver of rats in group SN had slight degeneration on PID 1, the liver cells around the central vein of liver of rats in group SNS had slight degeneration on PID 7, and the liver cells got severely eosinophilic degeneration in liver of rats in group LNS on PID 7. There was no significant pathological change in the liver of rats in each group at the rest time points. (5) The silver content of lung and kidney in rats of group SNS on PID 1, that of spleen and kidney in rats of group LNS on PID 1, and that of heart and kidney in rats of groups LNS and SNS on PID 7 was significantly less than that of group SN (with P values below 0.05). The silver content of liver and spleen in rats of group SNS on PID 14 was significantly more than that of group SN (with P values below 0.05). Compared with that of group SN, the silver content of lung on PID 1 and liver on PID 7 in rats of group LNS was significantly increased (with P values below 0.05). On PID 14, there was no significant change in the silver content of all organs of rats between group SN and group LNS (with P values above 0.05). The silver content of heart, lung, and kidney on PID 1 and heart on PID 7 in rats of group LNS was significantly more than that of group SNS (with P values below 0.05). On PID 14, the silver content of each organ of rats in group SNS was close to that in group LNS (with P values above 0.05). Conclusions: Silver nitrate and nano-silver with two different particle diameters have a short acute toxic effect on the liver of rats, and the liver has certain ability of self-healing. Nano-silver is mainly accumulated in the liver. The distribution of nano-silver with large particle diameter in organs is more widely than that of nano-silver with small particle diameter.

With the rapid development of modern science and technology, the application of nanomaterial is ubiquitous in our daily life and medical field, in which the application related to nano-silver is more extensive. On one hand, it can make positive effects, such as anti-bacteria, anti-virus, anti-fungi, anti-parasitic infection and anti-tumor. In particular, its anti-bacterial activity in some acute or chronic treatment of infected wounds is more prominent. The application in diseases of gynecology, orthopedics, cardiovascular system, oral cavity, and ophthalmology is increasing. On the other hand, it can induce negative impacts and potential toxicity. It can be harmful to skin, gastrointestinal tract, respiratory tract, cardiovascular system, and so on. This article summarizes the antimicrobial application of nano-silver on treatment of diseases, its potential toxic effects on some organs or systems, and the possible toxic mechanism, as well as makes prospects of the research trends of nano-silver in future.

Objective: The aim of this article is to discuss the relation between serum uric acid and prehypertension, and to evaluate the influence of age, obesity, fasting plasma glucose (FPG) and lipids in Chinese adults., Methods: All the 14 451 non-hypertensive samples were analyzed for blood pressure, body mass index (BMI), FPG, lipids and serum uric acid., Results: The serum uric acid levels were stratified by quintiles, after adjustment for relevant factors, OR values of prehypertension increased with the elevated uric acid levels. Serum uric acid level was 200 - 380 µmol/L, it had a linear relationship with the risk of prehypertension, 200 µmol/L as a turning point for this linear relationship, FPG could affect their correlation (P < 0.0001)., Conclusions: Serum uric acid was associated with prehypertension, independent of metabolic risk factors. The associations were not significant in old individuals. FPG may modify the associations.

Objective: 1H magnetic resonance (1H MR) spectroscopic technique in combination with pattern recognition technique were applied to analyze toxic effects of rats which were intratracheally instilled with titanium dioxide nanoparticles (nano-TiO2) as well as to detect the target organs and biomarkers associated with the toxic effects., Methods: Twenty-four SD male rats were divided into 4 groups randomly which were high dose group (40 mg/kg nano-TiO2), moderate dose group (4 mg/kg nano-TiO2), low dose group (0.4 mg/kg nano-TiO2) and control group (0.9% NaCl solution) respectively, there were six rats per group. All rats were exposed to the object by single intratracheally instilling at a volume of 0.1 ml/100 g. After one week observation, 1H MR spectra of plasma were measured and analyzed by principal component analysis. Histopathologic examination for tissues such as heart, lung, liver, and kidney were performed simultaneously., Results: The relative content of lactate [(37.86+/-2.58)x10(-3)], citrate [(2.21+/-0.45)x10(-3)], choline [(7.74+/-0.76)x10(-3)] and creatine [(4.17+/-1.15)x10(-3)] in high dose group were significantly decreased as compared with those [(52.07+/-5.12)x10(-3), (3.01+/-0.21)x10(-3), (9.28+/-0.78)x10(-3), (8.59+/-2.64)x10(-3)] in control group (t values were -6.024, -3.177, -3.374, -4.215 respectively, P<0.05), however the relative content of glucose [(19.41+/-1.72)x10(-3)] was significantly increased compared with that [(14.45+/-2.45)x10(-3)] in control group (t value was 2.802, P<0.05). The relative content of lactate [(44.39+/-5.09)x10(-3)] and creatine [(3.67+/-0.76)x10(-3)] in moderate group was significantly decreased compared with those [(52.07+/-5.12)x10(-3), (8.59+/-2.64)x10(-3)] in control group (t values were -3.254, -4.694 respectively, P<0.05). The relative content of pyruvate [(3.84+/-0.70)x10(-3)] was significantly increased in low dose group as compared with that [(3.13+/-0.46)x10(-3)] in control group (t value was 2.787, P<0.05), however the relative content of creatine [(8.10+/-0.72)x10(-3)] was significantly decreased compared with that [(9.28+/-0.78)x10(-3)] in control group (t value was -2.602, P<0.05). No significant difference was found between other experimental groups and control group. No visible damage was found in histopathologic examination., Conclusion: Lung, liver, kidney and heart were the target organs of rats which were intratracheally instilling titanium dioxide nanoparticles. Lactate, pyruvate, glucose, citrate, choline and creatine can be presumed as the biomarkers when searching the target organs of the toxic effects.

Objective: To explore the feasibility of in vitro magnetic resonance imaging on Fe2O3-arginine labeled heNOS gene modified endothelial progenitor cells (EPCs)., Methods: Fe2O3 was incubated with arginine to form Fe2O3-arginine complex. Rabbit peripheral blood mononuclear cells (MNCs) were isolated and EPCs were isolated by adherence method, expanded and modified with heNOS gene using Lipofectamine 2000. After 48 hours, genetically modified EPCs were incubated with Fe2O3-arginine for 24 hours. Intracellular iron was detected by Prussian blue stain. The expression of heNOS gene was detected by Western blot. MTT assay was used to evaluate cell survival and proliferation of Fe2O3-arginine labeled heNOS-EPCs. Flow cytometry was used to measure cell apoptosis. The cells underwent in vitro MR imaging with various sequences., Results: Iron-containing intracytoplasmatic vesicles could be clearly observed with Prussian blue staining, and the labeling rate of labeled heNOS-EPCs were similar to that of labeled EPCs (around 100%). Survival and apoptosis rates obtained by MTT and flow cytometry analysis were similar among labeled heNOS-EPCs, labeled EPCs and unlabeled EPCs with Fe2O3-arginine. The signal intensity on MRI was equally decreased in labeled heNOS-EPCs and labeled EPCs compared with that in unlabeled cells. The percentage change in signal intensity (DeltaSI) was most significant on T2*WI and DeltaSI was significantly lower in cells labeled for 7 days than that labeled for 1 days., Conclusions: The heNOS gene can be successfully transfected into rabbit peripheral blood EPCs using Lipofectamine2000. The heNOS-EPCs can be labeled with Fe2O3-arginine without significant change in viability and proliferation capacity. The labeled heNOS-EPCs can be imaged with standard 1.5 T MR equipment. The degree of MR signal intensity may indirectly reflect the cell count, growth and division status.