Objective To study the effects of fluid loading during fluid resuscitation on hemodynamics and cerebral perfusion(CPP)under different levels of intra-abdominal pressure(IAP).Methods Forty swine were employed in the study.Hypovolemia was made by blood withdrawal of 30% of estimated blood volume from each animal through the carotid artery line.All swine were randomized(random number) into four groups, namely IAPL0, IAPL15, IAPL25 and IAPL35.Then N2 gas was used to inflate in the abdomen slowly for elevating the IAP to 0,15, 25 and 35 mmHg.Fluid loading were performed with 500 mL hydroxyethyl starch within 30 minutes.Hemodynamic variables were evaluated by PiCCO.Heart rate (HR),mean arterial pressure(MAP), central venous pressure(CVP), cardiac output(CO), global end-diastolic volume index(GEDVI) and stroke volume index(SVI)were measured 30 minutes before fluid loading and 30 minutes after fluid loading.After placement of intracranial pressure optical fiber probe in the ventricle connected to intracranial pressure monitor for continuous monitoring of ICP changes, cerebral perfusion pressure (CPP) could be calculated.Results (1)HR decrease, MAP increased, SVI, CI and GEDVI significantly increased after fluid loading in all four groups (IAPL0,IAPL15,IAPL25 and IAPL35)(P<0.05),and there were not significant changes in CVP and EVLWI(P>0.05).SVRI decreased significantly in group IAPL15,IAPL25 and IAPL35 respectively(P<0.05).(2) ICP increased significantly in group IAPL15, IAPL25 and IAPL35(P<0.05), and CPP increased significantly in group IAPL25 and IAPL35(P<0.05) while CPP only slightly increased in group IAPL15(P>0.05).Conclusion When combined with intra-abdominal hypertension,fluid loading could improve the circulation of swine due to increase in CO and improve CPP.

Objective To evaluate the validity of stroke volume variation (SVV) for predicting fluid responsiveness in different grades of intra-abdominal pressure (IAP).Methods Forty pigs were involved in the study.Hypovolemia was made by blood withdraw of 30% of estimated blood volume from each animal via carotid artery.All the pigs were randomized into four groups namly 0 mm Hg (L0), 15 mm Hg (L15), 25 mm Hg (L25) and 35 mm Hg (L35).Nitrogen was inflated slowly till IAP to 0, 15, 25 and 35 mm Hg.Fluid loading was performed with 500 ml hydroxyethyl starch within 30 minutes.Hemodynamic parameters were evaluated by the thermodilution technique of pulse induced continuous cardiac output (PiCCO).SVV and stroke volume (SV) were measured before and after fluid loading.Results In groups L0 and L15, SVV was positive correlated with changes in SV (r=0.888, 0.942, respectively, P<0.05).In groups L25 and L35, there were poor correlations between SVV and changes in SV(r=0.068,-0.114, respectively).Conclusion When IAP was slightly increased up to 15 mm Hg, SVV remains an effectiveness index to predict fluid responsiveness index, however it failed to assess fluid responsiveness effectively when IAP is further raised up to 25 mm Hg or more.

Objective: To explore the impact of augmented renal clearance (ARC) on vancomycin pharmacokinetic target attainment in severe infective patients, and to analyze the initial dose of vancomycin based on the measured 12-hour urinary creatinine clearance (12 h-CL_CR). Methods: A retrospective observational study was conducted. The patients with severe infection, who receiving vancomycin empiric or targeted therapy, admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from February 2013 to December 2017 were enrolled. All patients were treated with vancomycin intravenously by intermittent bolus every 6-12 hours. After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CL_CR was calculated. ARC was defined as 12 h-CL_CR > 130 mL·min^-1·1.73 m^-2. According to 12 h-CL_CR before treatment, the patients were divided into ARC group and non-ARC group. The basic renal function of the patients was monitored, and the dosage of vancomycin and the dosage of vancomycin when the blood concentration reached the target were recorded. The correlations between 12 h-CL_CR and the dosage of vancomycin when the blood concentration reached the target as well as the blood concentration of vancomycin were analyzed by Spearman correlation analysis. Dosage stratification analysis was carried out according to different 12 h-CL_CR. The predictive value of 12 h-CL_CR for vancomycin dosage when the blood concentration reached the target was evaluated by using the receiver operator characteristic curve (ROC). Results: Data was provided from a total of 135 patients with severe infection, in which 102 patients met the inclusion criteria. The patients with vancomycin treatment duration less than 72 hours, chronic kidney disease Ⅴ phase, vancomycin treatment before entering ICU and those with incomplete data were excluded. The mean 12 h-CL_CR was (114.31±73.38) mL·min^-1·1.73 m^-2. The 12 h-CL_CR in ARC group (n = 44, 43.14%) was significantly higher than that in non-ARC group (n = 58, 56.86%) (mL·min^-1·1.73 m^-2: 179.37±59.04 vs. 65.95±35.71, P < 0.01). Target Cmin of vancomycin was achieved in 50.98% of patients (52/102), the target rate in ARC group was significantly lower than that in non-ARC group [29.55% (13/44) vs. 67.24% (39/58), P < 0.01], and the Cmin of vancomycin in ARC group was significantly lower than that in non-ARC group (mg/L: 10.98±6.09 vs. 14.67±6.20, P < 0.01). Spearman correlation analysis showed that there was a significantly negative correlation between 12 h-CL_CR and initial Cmin of vancomycin (n = 102, r = -0.436, P < 0.001), but a positive correlation was found between 12 h-CL_CR and vancomycin dosage when the blood concentration reached the target (n = 52, r = 0.275, P = 0.048). The patients with ARC need higher dosage for blood concentration reaching the target than those without ARC (mg·kg^-1·d^-1: 42.47±13.17 vs. 31.53±14.43, P < 0.01). According to 12 h-CL_CR, the patients with initial treatment reaching the target were divided into five subgroups, < 40, 40-70, 71-100, 101-130 and > 130 mL·min^-1·1.73 m^-2. The results showed that as 12 h-CL_CR increased, the attained dosage of vancomycin was also increased correspondingly. ROC curve analysis showed that when 12 h-CL_CR≥69.83 mL·min^-1·1.73 m^-2, the attained dose of vancomycin when the blood concentration reached the target was greater than conventional dosage of 30 mg·kg^-1·d^-1. Conclusions Patients with ARC have low concentrations of vancomycin and often fail to achieve therapeutic target. The initial dose of vancomycin can be selected according to 12 h-CL_CR, the higher the 12 h-CL_CR, the more the dosage of vancomycin is. When 12 h-CL_CR is greater than or equal to 69.83 mL·min^-1·1.73 m^-2, the dosage of vancomycin should be higher than the conventional dosage.

Efficient and safe delivery of drugs, proteins or genes to the targeted sites has been the focus of pharmaceutical research. Inorganic nanomaterials are ideal materials for drug delivery systems due to their good stability, excellent biocompatibility and high drug loading capacity.Inorganic nanomaterials are ideal materials for drug delivery systems due to their good stability, high biocompatibility and excellent drug loading capacity. In this review, we started with reported researches and clinical trials to discuss the researches and clinical transformation of these inorganic nanoparticles in application of drug delivery, including carbon nanomaterials, silica nanoparticles, calcium nanomaterials, gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and quantum dots, providing theoretical reference for application of inorganic drug delivery carriers in the development of new drugs, looking to the prospects of inorganic nanomaterials in clinical application.

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 analyze the clinical characteristics of bloodstream infection in patients with immune function inhibition. Methods A retrospective analysis was conducted. 234 patients with bloodstream infection admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 1st in 2015 to December 31st in 2017 were enrolled. According to the immune function on the day of bloodstream infection, they were divided into normal immune function group [human leukocyte antigen DR (HLA-DR) > 30%, n = 144] and immunosuppression group (HLA-DR ≤30%, n = 90). The gender, age, primary disease, complication, acute physiology and chronic health evaluationⅡ (APACHEⅡ) with 24 hours after ICU admission, sequential organ failure assessment (SOFA) score, etiology, infection parameters on the day of bloodstream infection [peak temperature, white blood count (WBC), neutrophils ratio, procalcitonin (PCT), and C-reactive protein (CRP)] and prognosis parameters (bacterial clearance time, the length of ICU and hospital stay, 28-day mortality) between the two groups were analyzed. Results 234 patients were enrolled in the final analysis, including 132 males and 102 females, with an average age of (60.5±18.4) years old. Severe pneumonia and abdominal infection were the main causes of primary diseases. There was no significant difference in gender composition, age, APACHEⅡ, SOFA score, other complications and primary morbidity between the two groups except that the proportion of malignant tumors in the immunosuppressive group was higher than that in the normal immune function group [43.3% (39/90) vs. 41.7% (60/144), P < 0.05]. Compared with the normal immune function group, the Gram-positive cocci infection rate in the immunosuppressive group was significantly lowered [40.0% (36/90) vs. 56.2% (81/144)], Gram-negative bacilli infection rate [50.0% (45/90) vs. 39.6% (57/144)] and fungus infection rate [10.0% (9/90) vs. 4.2% (6/144)] were significantly increased (both P < 0.05). The levels of WBC, neutrophils ratio, and PCT on the day of bloodstream infection in the immunosuppressive group were significantly lower than those of normal immune function group [WBC (×109/L): 10.2±2.1 vs. 13.5±3.6, neutrophils ratio: 0.87±0.17 vs. 0.96±0.22, PCT (μg/L): 1.3±1.1 vs. 4.7±2.1, all P < 0.05], but no significant difference in the peak temperature (℃: 38.5±1.7 vs. 38.9±1.3) or CRP (mg/L: 134.0±42.6 vs. 164.0±55.8) was found as compared with normal immune function group (both P > 0.05). Compared with the normal immune function group, the bacterial clearance time in the immunosuppressive group was significantly prolonged (days: 16.0±10.1 vs. 12.3±4.7), 28-day mortality was significantly increased [61.1% (55/90) vs. 44.4% (64/144)] with statistical significances (both P < 0.05), but no significance was found in the length of ICU stay (days: 21.0±17.1 vs. 18.7±10.4) or the length of hospital stay (days: 36.0±28.1 vs. 33.8±16.8, both P > 0.05). Conclusion Gram-negative bacilli was the main pathogen of bloodstream infection in immunosuppressive patients, and the fungal infection rate was high, inflammation reaction was not obvious, bacterial clearance time was long, and prognosis was poor.

OBJECTIVE: To explore the impact of augmented renal clearance (ARC) on vancomycin pharmacokinetic target attainment in severe infective patients, and to analyze the initial dose of vancomycin based on the measured 12-hour urinary creatinine clearance (12 h-CL_CR). METHODS: A retrospective observational study was conducted. The patients with severe infection, who receiving vancomycin empiric or targeted therapy, admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from February 2013 to December 2017 were enrolled. All patients were treated with vancomycin intravenously by intermittent bolus every 6-12 hours. After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CL_CR was calculated. ARC was defined as 12 h-CL_CR > 130 mL×min^-1×1.73 m^-2. According to 12 h-CL_CR before treatment, the patients were divided into ARC group and non-ARC group. The basic renal function of the patients was monitored, and the dosage of vancomycin and the dosage of vancomycin when the blood concentration reached the target were recorded. The correlations between 12 h-CL_CR and the dosage of vancomycin when the blood concentration reached the target as well as the blood concentration of vancomycin were analyzed by Spearman correlation analysis. Dosage stratification analysis was carried out according to different 12 h-CL_CR. The predictive value of 12 h-CL_CR for vancomycin dosage when the blood concentration reached the target was evaluated by using the receiver operator characteristic curve (ROC). RESULTS: Data was provided from a total of 135 patients with severe infection, in which 102 patients met the inclusion criteria. The patients with vancomycin treatment duration less than 72 hours, chronic kidney disease V phase, vancomycin treatment before entering ICU and those with incomplete data were excluded. The mean 12 h-CL_CR was (114.31±73.38) mL×min^-1×1.73 m^-2. The 12 h-CL_CR in ARC group (n = 44, 43.14%) was significantly higher than that in non-ARC group (n = 58, 56.86%) (mL×min^-1×1.73 m^-2: 179.37±59.04 vs. 65.95±35.71, P < 0.01). Target Cmin of vancomycin was achieved in 50.98% of patients (52/102), the target rate in ARC group was significantly lower than that in non-ARC group [29.55% (13/44) vs. 67.24% (39/58), P < 0.01], and the Cmin of vancomycin in ARC group was significantly lower than that in non-ARC group (mg/L: 10.98±6.09 vs. 14.67±6.20, P < 0.01). Spearman correlation analysis showed that there was a significantly negative correlation between 12 h-CL_CR and initial Cmin of vancomycin (n = 102, r = -0.436, P < 0.001), but a positive correlation was found between 12 h-CL_CR and vancomycin dosage when the blood concentration reached the target (n = 52, r = 0.275, P = 0.048). The patients with ARC need higher dosage for blood concentration reaching the target than those without ARC (mg×kg^-1×d^-1: 42.47±13.17 vs. 31.53±14.43, P < 0.01). According to 12 h-CL_CR, the patients with initial treatment reaching the target were divided into five subgroups, < 40, 40-70, 71-100, 101-130 and > 130 mL×min^-1×1.73 m^-2. The results showed that as 12 h-CL_CR increased, the attained dosage of vancomycin was also increased correspondingly. ROC curve analysis showed that when 12 h-CL_CR≥69.83 mL×min^-1×1.73 m^-2, the attained dose of vancomycin when the blood concentration reached the target was greater than conventional dosage of 30 mg×kg^-1×d^-1. CONCLUSIONS Patients with ARC have low concentrations of vancomycin and often fail to achieve therapeutic target. The initial dose of vancomycin can be selected according to 12 h-CL_CR, the higher the 12 h-CL_CR, the more the dosage of vancomycin is. When 12 h-CL_CR is greater than or equal to 69.83 mL×min^-1×1.73 m^-2, the dosage of vancomycin should be higher than the conventional dosage.
Anti-Bacterial Agents ; Creatinine ; Humans ; Infections ; Intensive Care Units ; Kidney Function Tests ; Retrospective Studies ; Vancomycin/administration & dosage*

BACKGROUND: Chronic kidney disease is a severe threat to human health with no ideal treatment strategy. Mature mammalian kidneys have a fixed number of nephrons, and regeneration is difficult once they are damaged. For this reason, developing an efficient approach to achieve kidney regeneration is necessary. The technology of the combination of decellularized kidney scaffolds with stem cells has emerged as a new strategy; however, in previous studies, the differentiation of stem cells in decellularized scaffolds was insufficient for functional kidney regeneration, and many problems remain. METHODS: We used 0.5% sodium dodecyl sulfate (SDS) to produce rat kidney decellularized scaffolds, and induce adipose-derived stem cells (ADSCs) into intermediate mesoderm by adding Wnt agonist CHIR99021 and FGF9 in vitro. The characteristics of decellularized scaffolds and intermediate mesoderm induced from adipose–derived stem cells were identified. The scaffolds were recellularized with ADSCs and intermediate mesoderm cells through the renal artery and ureter. After cocultured for 10 days, cells adhesion and differentiation was evaluated. RESULTS: Intermediate mesoderm cells were successfully induced from ADSCs and identified by immunofluorescence and Western blotting assays (OSR1 + , PAX2 +). Immunofluorescence showed that intermediate mesoderm cells differentiated into tubular-like (E-CAD + , GATA3 +) and podocyte-like (WT1 +) cells with higher differentiation efficiency than ADSCs in the decellularized scaffolds. Comparatively, this phenomenon was not observed in induced intermediate mesoderm cells cultured in vitro. CONCLUSION: In this study, we demonstrated that intermediate mesoderm cells could be induced from ADSCs and that they could differentiate well after cocultured with decellularized scaffolds.
Animals ; Blotting, Western ; Fluorescent Antibody Technique ; Humans ; In Vitro Techniques ; Kidney ; Mesoderm ; Nephrons ; Rats ; Regeneration ; Renal Artery ; Renal Insufficiency, Chronic ; Sodium Dodecyl Sulfate ; Stem Cells ; Ureter

Hypertriglyceridemia （HTG） is the second leading cause of acute pancreatitis in China and can be caused by primary factors， namely gene mutations， which may lead to recurrent hypertriglyceridemic acute pancreatitis （HTG-AP） and difficulties in effective control of triglyceride. This article reports an adult Chinese male patient who experienced eight attacks of HTG-AP and was found to carry a de novo heterozygous mutation， p.K327N， of the GPD1 gene， which may cause the persistent high level of triglyceride and recurrent attacks of HTG-AP.

Objective: To summarize the status of immediate breast reconstruction (IBR) after mastectomy in Beijing City, Tianjin City and Hebei Province. Methods: A retrospective analysis was made on the data of 382 cases with breast cancer who were treated and followed up successfully with immediate breast reconstruction after mastectomy from January 2012 to December 2016 in Beijing City, Tianjin City and Hebei Province. Clinic data of the followed-up 382 cases (all female, age (38.5±4.2) years (range: 24 to 70 years)), including general information, tumor information, sugery methods, and treatments after surgery were collected. The survival status, metastasis,complications and prognosis were followed up. Cosmetic effcet was evalated by Harris method, and life quality by Functional Assessment of Cancer Therapy-Breast scale (FACT-B). χ² test was used to compare the difference between year 2012 and year 2013 to 2016. Bonferroni method was used to correct the inspection level, which was 0.05/10=0.005. The trend of IBR rate (ratio of IBR to modified radical mastectomy) from 2013 to 2016 was analyzed by trend χ² test. Results: There was 46 cases in stage 0, 152 cases in stage Ⅰ, 165 cases in stage Ⅱ, 19 cases in stage Ⅲ. Twenty-five cases was treated by neoadjuvant chemotherapy, 231 by chemotherapy and 35 by radiotherapy. The proportion of implant reconstruction was 48.7% (186/382), more than expanded of 21.5% (82/382), with latissimus dorsi of 12.0% (46/382), TRAM of 8.9% (34/382), DIEP of 2.1% (8/382), and latissimus plus implant of 6.8% (26/382). According to the Harris standard, the excellent and good rate of the cosmetic effect of the reconstructed breast was 93.7%. The score of FACT-B was 108.20±16.9 (range: 67 to 144) 1 year postoperatively. Compared with 2012, the IBR rate was significant increased, till 2015, the IBR rate was 153/10 000 cases (χ²=47.028, P=0.000). Conclusions There is a significant increase on IBR rate in Beijing City, Tianjin City and Hebei province by year. Most of cases received IBR is stage Ⅰ to Ⅱ. Implant reconstruction is the main reconstructive method. Postoperative cosmetic effects and quality of life are both meet patients′ demon.