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 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.

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.

Correlation between nonlinear subharmonic scattering of ultrasound contrast agent microbubbles and ambient pressure is expected to be used for local brain tissue pressure monitoring. Although high-frequency ultrasound has achieved high-resolution imaging of intracranial microvessels, the research on high-frequency subharmonic scattering characteristics of microbubbles is insufficient at present, which restricts the research progress of estimating local brain tissue pressure based on high-frequency subharmonic scattering of microbubbles. Therefore, under the excitation of 10 MHz high-frequency ultrasound, the effects of different acoustic pressures and ambient pressures on the high-frequency subharmonic scattering characteristics of three different ultrasound contrast agents including SonoVue, Sonazoid and Huashengxian were investigated in this in vitro study. Results showed that the subharmonic scattering amplitudes of the three microbubbles increased with the increase of ambient pressure at the peak negative acoustic pressures of 696, 766 and 817 kPa, and there was a favorable linear correlation between subharmonic amplitude and ambient pressure. Under the above three acoustic pressures, the highest correlation coefficient of SonoVue was 0.948 ( P = 0.03), the highest sensitivity of pressure measurement was 0.248 dB/mm Hg and the minimum root mean square error (RMSE) was 2.64 mm Hg. Sonazoid's highest correlation coefficient was 0.982 ( P < 0.01), the highest sensitivity of pressure measurement was 0.052 dB/mm Hg and the minimum RMSE was 1.51 mm Hg. The highest correlation coefficient of Huashengxian was 0.969 ( P = 0.02), the highest sensitivity of pressure measurement was 0.098 dB/mm Hg and the minimum RMSE was 2.00 mm Hg. The above in vitro experimental results indicate that by selecting ultrasound contrast agent microbubbles and optimizing acoustic pressure, the correlation between high-frequency subharmonic scattering of microbubbles and ambient pressure can be improved, the sensitivity of pressure measurement can be upgraded, and the measurement error can be reduced to meet the clinical demand for local brain tissue pressure measurement, which provided an important experimental basis for subsequent research in vivo.
Contrast Media ; Microbubbles ; Ultrasonography/methods*

OBJECTIVE: To investigate the efficacy of a novel artificial perfusate based on oxygen-carrying perfluoronaphthalene-albumin nanoparticles in normothermic machine perfusion (NMP) for preservation of porcine liver donation after cardiac death. METHODS: Artificial perfusate with perfluoronaphthalene-albumin nanoparticles was prepared at 5% albumin (w/v) and its oxygen carrying capacity was calculated. The livers of 16 Landrace pigs were isolated after 1 h of warm ischemia, and then they were divided into 4 groups and preserved continuously for 24 h with different preservation methods: cold preservation with UW solution (SCS group), NMP preservation by whole blood (blood NMP group), NMP preservation by artificial perfusate without nanoparticles (non-nanoparticles NMP group) and NMP preservation by artificial perfusate containing nanoparticles (nanoparticles NMP group). Hemodynamics, tissue metabolism, biochemical indices of perfusate and bile were monitored every 4 h after the beginning of NMP. Liver tissue samples were collected for histological examination (HE and TUNEL staining) before preservation, 12 h and 24 h after preservation. RESULTS: The oxygen carrying capacity of nanoparticles in 100 mL artificial perfusate was 6.94 μL/mmHg (1 mmHg=0.133 kPa). The hepatic artery and portal vein resistance of nanoparticles NMP group and blood NMP group remained stable during perfusion, and the vascular resistance of nanoparticles NMP group was lower than that of blood NMP group. The concentration of lactic acid in the perfusate decreased to the normal range within 8 h in both nanoparticles NMP group and blood NMP group. There were no significant differences in accumulated bile production, alanine aminotransferase and aspartate aminotransferase in perfusate between nanoparticles NMP group and blood NMP group (all P>0.05). After 24 h perfusion, the histological Suzuki score in blood NMP group and nanoparticles NMP group was lower than that in SCS group and non-nanoparticles NMP group (all P<0.05), and the quantities of TUNEL staining positive cells in blood NMP group and non-nanoparticles NMP group was higher than those in nanoparticles NMP group and SCS group 12 h and 24 h after preservation (all P<0.05). CONCLUSION Artificial perfusate based on oxygen-carrying nanoparticles can meet the oxygen supply requirements of porcine livers donation after cardiac death during NMP preservation, and it may has superiorities in improving tissue microcirculation and alleviating ischemia-reperfusion injury.
Swine ; Animals ; Liver Transplantation ; Organ Preservation ; Liver ; Perfusion ; Death ; Oxygen/metabolism*

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 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 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 systematically evaluate the safety and efficacy of laparoscopic surgery versus conservative treatment for appendiceal abscess. METHODS: The databases of CNKI, Wangfang, VIP, PubMed, EMBASE and Cochrane Library were searched to retrieve randomized controlled trials (RCT) or clinical controlled trials (CCT) comparing laparoscopic surgery with conservative treatment for appendiceal abscess published before June 2018. The search terms were Chinese or English. Chinese search terms included appendix, abscess, and laparoscopy; English search terms included appendix, abscess, and laparoscope. References of the resulted papers, related reviews or meta-analysis references were also induded. Literature inclusion criteria: (1)RCT or CCT, whether or not to assign concealment or blinding; (2) appendiceal abscess was diagnosed at admission; (3) laparoscopic group: laparoscopic appendectomy or laparoscopy surgical methods, such as irrigation and drainage, for appendiceal abscess; conservative treatment group: conservative methods, such as antibiotics or percutaneous abscess drainage were used to treat appendiceal abscess. EXCLUSION CRITERIA: (1) review, case report, single cohort study and other non-controlled studies literature; (2) single study sample size ≤ 20; (3) subjects with simple appendicitis or perforation of appendix to form diffuse peritonitis; (4) no valid data available for extraction; (5) repeated publication of the literature. Data were extracted from the included studies, and the Cochrane Collaboration RevMan 5.1.0 version software was used for this meta-analysis. RESULTS: Three RCTs and four CCTs with a total of 591 patients were included in this study. There were 312 patients in the laparoscopic group and 279 patients in the conservative group. Compared with the conservative group, the laparoscopic group had higher uneventful recovery rate (OR=11.91, 95%CI: 4.59 to 30.88, P<0.05), shorter hospital stay (WMD=-2.98, 95%CI: -5.96 to -0.01, P=0.05), lower incidence of recurrent or residual abscess (OR=0.07, 95%CI:0.03 to 0.20, P<0.05), and shorter time to recover to normal condition for body temperature and white blood cell respectively (SMD=-2.12, 95%CI:-2.49 to -1.75, P<0.05; SMD=-2.07, 95%CI: -3.84 to -0.29, P<0.05). However, no significant difference was found in hospital charge(P>0.05). CONCLUSIONS Laparoscopic surgery for appendiceal abscess is safe and feasible. It can improve the recovery with shorter postoperative hospital stay and less recurrent or residual abscess.
Abdominal Abscess ; surgery ; therapy ; Appendix ; surgery ; Cohort Studies ; Conservative Treatment ; Humans ; Laparoscopy ; Length of Stay ; Treatment Outcome

Gastrointestinal dysfunction is a common and major complication after surgery. The syndrome covers a wide spectrum of clinical signs, ranges from mild feeling to severe discomfort and varies from person to person. The mild patients need no care, but severe ones may have long hospital stay, and even suffer from multiple organ dysfunction syndrome, severely affecting postoperative rehabilitation. However, the etiology of postoperative gastrointestinal dysfunction has not been fully elucidated. Much research demonstrates that many factors, such as operative procedures, surgical operation, homeostasis disturbance, anesthesia and analgesia, blood perfusion, inflammation, and neuroendocrine factors, are responsible for the development and progression of postoperative gastrointestinal dysfunction. This study therefore reviewed the causes of postoperative gastrointestinal dysfunction in the published literatures.
Digestive System Surgical Procedures ; adverse effects ; Gastrointestinal Tract ; physiopathology ; Humans ; Postoperative Complications ; Postoperative Period