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 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.

In May 2019, the International Diabetic Foot Working Group (IWGDF) updated and issued guidelines for the prevention and management of diabetic foot disease. This guide puts forward some suggestions for the diagnosis, treatment and effective prevention of diabetic foot: the prevention of diabetic foot should start with high-risk foot, early screening and treatment of diabetic foot infection, foot ulcer and peripheral vascular disease and early comprehensive treatment. Effective prevention and early treatment can reduce the incidence of cardiovascular and cerebrovascular events in patients with diabetes, reduce the amputation rate and mortality, and improve the prognosis and quality of life of patients.

Humans ; In Situ Hybridization, Fluorescence ; Sarcoma, Alveolar Soft Part ; diagnosis

[ABSTRACT]AIM:Toinvestigatetheinteractionandthemechanismofsphingosine-1-phosphate(S1P)and phospholipid transfer protein (PLTP) in lipoprotein.METHODS:The S1P content in the plasma and lipoprotein from 10-week-old PLTP transgenic (PLTP-Tg) mice and wild-type (WT) mice (n=8 each) was assayed.The transport of S1P by PLTP was determined by S1P transfer assay.The content of specific S1P carrier, apolipoprotein M, was detected by West-ern blotting.RESULTS:Plasma S1P contents were decreased by 21.1%in PLTP-Tg mice compared with WT mice.S1P content in high-density lipoprotein ( HDL) fraction ( HDL-S1P) from PLTP-Tg mice was decreased by 35.1% compared with WT mice, whereas the S1P in low-density lipoprotein (LDL) fraction (LDL-S1P) was increased by 127.4%.The re-sults of S1P transfer assay indicated that PLTP facilitated S 1P transport from erythrocyte to recombinant liposome at 37℃in D-Hanks buffer solution .The plasma content of apolipoprotein M was not changed in PLTP-Tg mice compared with WT mice.CONCLUSION:PLTP is a key factor to maintain plasma HDL-S1P under physical condition .Overexpression of PLTP decreases the HDL-S1P but increases LDL-S1P.The mechanism might be related to the capability of PLTP on trans-ferring S1P from erythrocyte to lipoprotein.

Aim According to various target sites of HLA-E mRNA,to design and synthesize 3 pieces of HLA-E siRNA chain,to compare quantitatively their efficiency of silencing gene in BEL-7402 with HLA-E(+)in order to select the dominant siRNA.Methods The hepatocarcinomal BEL-7402 cells,induced by 5×10~5 IU·L~(-1) IFN-γ,expressed HLA-E(+) and was pured by flow cytometry selecting as target cells for research.3 pieces of specific siRNA(A,B,C group)were designed and chemically synthesized,then the concentration of which(0.1 mmol·L~(-1))was respectively transfected through Lipofectamin 2000 into target cells.After 48 h,the gene silent effect on HLA-E gene in A,B and C groups was quantitatively observed by cytoimmunofluorence,flow cytometery,Western blot and real-time PCR,as well as on NK cytotoxicity to target cells tested by NK killing rate.Results Compared with those of control or non-specific siRNA group,HLA-E antigen,protein product,HLA-E mRNA and HLA-E molecule on cell surface were statistically down-regulated in A,B,and C group(P<0.01),whose were silenced more (above 90%) in B or C group than in A group (P<0.01).The NK killing rate in A,B and C groups was dominantly improved(P<0.01),which in B or C group was higher than in A group (P<0.01).Conclusion The targeted siRNA can specifically and high-efficiently silence HLA-E expression in hepatocarcinomal cells,and may keep them from immunoescape through non-classic HLAⅠ pathway to imply new strategy for hepatocarcinomal gene-immunotherapy.

Objective To evaluate the long-term therapeutic results and the safety of nephronsparing surgery(NSS) for the treatment of renal cell carcinoma. Methods Clinical data of 243 NSSfor renal cell carcinoma were retrospectively analysed. Of them, 159 were males and 84 were femaleswith average age of 58 years (range from 24 ?77 years). The average tumor size was 3. 4 cm (rangefrom 1.1 to 6. 7 cm). Three cases were solitary renal cell carcinoma, 11 were bilateral renal cell carcinoma; 237 cases were in stage T_(1a). and 6 cases were in stage T_(1b). No lymph node and distant metastasis, no renal vein cancer tumor embolus and inferior vena cava tumor embolus was found. Postoperative follow-up was carried out by ultrasound, CT and renal function. Cancer specific survival was estimated using Kaplan-Meier method and log-rank test. Results After a mean 31 months (1-147months) follow-up, long-term follow-up data were obtained in 232 cases because the other 11 did notlive in Dalian, 52 were treated with interferon. Four of the 232 patients treated with NSS had died:1died from lung cancer 16 months after lung cancer treatment, the other 3 died from cardiovascular diseases. The total survival rate and cancer specific survival rate were 98. 3% and 100. 0%, respectively.Local tumor recurrences were detected in 5 patients and tumor metastasis was detected in 1 patient.The recurrence rate was 2. 2%, and the metastasis rate was 0. 4%. The complications included temporary renal failure and urine leakage. The complication rate was 5. 6%. Conclusions NSS for renalcell carcinoma is a safe and feasible treatment option. It has the advantages of low local recurrence,good long-term survival rate and low complication rate. NSS can maximally reserve functional nephron, reduce the risk of chronic renal failure, preserve patient's quality of life and increase patient'ssatisfaction.

BACKGROUNDIt has been known that the growth of solid tumors is dependent on angiogenesis, and neoangiogeneses of tumor become main target to control tumor growth. The aims of this study are to investigate the inhibition effect of replicate-deficient adenovirus encoding the soluble form of mouse vascular endothelial growth factor receptor 1 (sFlt1-Adv) on angiogenesis and tumor growth in established tumor model.

METHODSMouse Lewis lung cancer cells were inoculated subcutaneously into C57 mice. sFlt1-Adv, GFP-Adv and normal saline were injected twice intravenously after establishing Lewis cancer model. Diameters of tumors were measured every other day. Tumors were resected, weighed and fixed in 3% paraformadehyde. Microvessel density of tumors was determined by immunohistochemical staining with anti-CD31 antibody.

RESULTSThe planted tumor volume and weight in sFlt1-Adv group were significantly lower compared with the two controls (P < 0.01). Its inhibition rate was 71.8%. The microvessel density in sFlt1-Adv group decreased markedly compared with that of the control groups (P < 0.01).

CONCLUSIONSsFlt1-Adv can inhibit the growth of tumor through the inhibition of tumor angiogenesis. sFlt1-Adv may be potentially valuable for clinical treatment of solid tumor.