The clinical trajectory of peripheral blood immune cell subsets, T-cell activation, and cytokines in septic patients.

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.

Paraneoplastic myelitis associated with durvalumab treatment for extensive-stage small cell lung cancer.

Paraneoplastic neurologic syndromes(PNSs) caused by immune checkpoint inhibitors(ICIs) is rare and requires clinicians to differentiate between disease progression and immune-related adverse effects(irAEs). We hereby report the case of immune-related myelitis accompanied by positive paraneoplastic autoantibodies following durvalumab treatment for extensive-stage small cell lung cancer (ES-SCLC). A 70-year-old Chinese woman with ES-SCLC was administered durvalumab with etoposid-platinum(EP) as first-line treatment. Four cycles after treatment with EP plus ICI, she developed immune-related myelitis with positive paraneoplastic autoantibodies (CV2, SOX1, ZIC4). Spinal MRI showed diffuse abnormal signal shadow in the cervicothoracic spinal cord. She was discontinued for chemotherapy, and treated with high-dose steroids, intravenous immunoglobulin and plasmapheresis, maintenance therapy with steroids resulted in a favorable neurologic outcome. This is the first report of durvalumab-related PNSs. We supposed that the development of paraneoplastic myelitis was causally related to immune activation by durvalumab. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of paraneoplastic myelitis.

Sarcopenia is associated with the presence of nonalcoholic fatty liver disease in Zhejiang Province, China: a cross-sectional observational study.

BACKGROUND: Currently, both non-alcoholic fatty liver disease (NAFLD) and sarcopenia have attracted extensive attention in public health. However, the relationship between NAFLD and sarcopenia remains unclear. This study aimed to clarify the sex-specific association between sarcopenia and NAFLD according to the Asian Working Group for Sarcopenia (AWGS). METHODS: Dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography were measured in 578 participants (92 men and 486 women) during their annual health examinations. Multivariate logistic regression models were used to explore the association between NAFLD and sarcopenia with its two components. RESULTS: A total of 154 participants (30 men and 124 women) had NAFLD. The prevalence of sarcopenia was higher among the participants with NAFLD than among those without NAFLD (men: 20.0% vs. 9.7%, P = 0.295, women: 15.3% vs. 8.0%, P = 0.019). Low muscle mass (LMM) was independently associated with NAFLD in both men and women (men: odds ratio [OR], 2.88; 95% confidence interval [CI] 1.52-5.46; women: OR, 2.08; 95% CI 1.63-2.67). However, low muscle strength (LMS) was independently associated with NAFLD only in male participants, with an OR of 1.15 (95% CI 1.02-1.28). CONCLUSION: The occurrence of sarcopenia was associated with a higher risk of NAFLD, especially in men, as demonstrated by lower muscle mass and lower muscle strength.

Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies.

BACKGROUND: Although cardiac troponin is the cornerstone in diagnosis of acute myocardial infarction (AMI), the accuracy is still suboptimal in the early hours after chest pain onset. Due to its small size, heart-type fatty acid-binding protein (H-FABP) has been reported accurate in diagnosis of AMI, however, this remains undetermined. The aim is to investigate the diagnostic performance of H-FABP alone and in conjunction with high-sensitivity troponin (hs-Tn) within 6 hours of symptom onset. Furthermore, accuracy in 0h/3h algorithm was also assessed. METHODS: Medline and EMBASE databases were searched; sensitivity, specificity and area under ROC curve (AUC) were used as measures of the diagnostic accuracy. We pooled data on bivariate modelling, threshold effect and publication bias was applied for heterogeneity analysis. RESULTS: Twenty-two studies with 6602 populations were included, pooled sensitivity, specificity and AUC of H-FABP were 0.75 (0.68-0.81), 0.81 (0.75-0.86) and 0.85 (0.82-0.88) within 6 hours. Similar sensitivity (0.76, 0.69-0.82), specificity (0.80, 0.71-0.87) and AUC (0.85, 0.82-0.88) of H-FABP were observed in 4185 (63%) patients in 0h/3h algorithm. The additional use of H-FABP improved the sensitivity of hs-Tn alone but worsened its specificity (all p<0.001), and resulted in no improvement of AUC (p>0.99). There was no threshold effect (p=0.18) and publication bias (p=0.31) in this study. CONCLUSIONS: H-FABP has modest accuracy for early diagnosis of AMI within 3 and 6 hours of symptom onset. The incremental value of H-FABP seemed much smaller and was of uncertain clinical significance in addition to hs-Tn in patients with suspected AMI. Routine use of H-FABP in early presentation does not seem warranted.

The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis.

In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95% CI 0·50, 1·67; P< 0·001). No difference was found between the groups in relation to lean body mass (pooled standardised difference in mean changes 0·18, 95% CI - 0·18, 0·54; P= 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95% CI - 0·32, 0·44; P= 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate.

Gastrodia elata and parishin ameliorate aging induced 'leaky gut' in mice: Correlation with gut microbiota.

BACKGROUND: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. METHODS: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice. RESULTS: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut. CONCLUSIONS: These results suggested that G. elata and parishin could prevent gut aging and ameliorate the "leaky gut" of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

Puerarin protects differentiated PC12 cells from H2O2-induced apoptosis through the PI3K/Akt signalling pathway.

Oxidative stress has been implicated as a major mechanism underlying the pathogenesis of neurodegenerative disorders. ROS (reactive oxygen species) can cause cell death via apoptosis. NGF (nerve growth factor) differentiated rat PC12 cells have been extensively used to study the differentiation and apoptosis of neurons. This study has investigated the protective effects of puerarin in H2O2-induced apoptosis of differentiated PC12 cells, and the possible molecular mechanisms involved. Differentiated PC12 cells were incubated with 700 µM H2O2 in the absence or presence of different doses of puerarin (4, 8 and 16 µM). Apoptosis was assessed by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) analysis and Annexin V-PI (propidium iodide) double staining flow cytometry. Protein levels of phospho-Akt and phospho-BAD (Bcl-2/Bcl-XL-antagonist, causing cell death) were assayed by Western blotting. After stimulation with H2O2 for 18 h, the viability of differentiated PC12 cells decreased significantly and a large number of cells underwent apoptosis. Differentiated PC12 cells were rescued from H2O2-induced apoptosis at different concentrations of puerarin in a dose-dependent manner. This was through increased production of phospho-Akt and phospho-BAD, an effect that could be reversed by wortmannin, an inhibitor of PI3K (phosphoinositide 3-kinase). The results suggest that puerarin may have neuroprotective effect through activation of the PI3K/Akt signalling pathway.

[Atorvastatin inhibits the H2O2-induced apoptosis of human vascular endothelial cells through a down-regulation of cleaved caspase-9/caspase-3].

OBJECTIVE: To investigate the effect and potential mechanism of atorvastatin against H2O2-induced apoptosis of human umbilical vein endothelial cells (ECV-304). METHODS: ECV-304 cells were pretreated with different concentrations of atorvastatin (0.1, 1 and 10 µmol/L) for 2 h, followed by an exposure to 100 µmol/L H2O2 for 18 h. Cellular morphology was observed under fluorescence microscope. Cellular viability and apoptosis were evaluated by methyl thiazolyl tetrazolium (MTT) and flow cytometry. Finally the expressions of cleaved caspase-3 and caspase-9 were measured by Western blot. RESULTS: H2O2 treatment caused an obvious apoptosis of ECV-304 cells and significantly decreased the cellular viability as characterized by a high percentage (50.71%) of apoptotic cells. Atorvastatin pretreatment inhibit cellular apoptosis induced by H2O2 (39.45%, 20.53% and 7.83%). Western blot assay showed that H2O2 treatment caused a high expression of cleaved caspase-3 and caspase-9 while atorvastatin pretreatment obviously inhibited the expression in a dose-dependent manner. CONCLUSIONS: Atorvastatin inhibits the H2O2-induced apoptosis of ECV-304 cells in a dose-dependent manner. This effect may be associated with the down-regulation of cleaved caspase-9/caspase-3.

[Plasma gamma-glutamyl transpeptidase level as a cardiovascular risk factor in elderly patients with hypertension or hypertension with diabetes mellitus].

OBJECTIVE: To investigate plasma gamma-glutamyl transpeptidase (γ-GGT) level as a cardiovascular risk factor in elderly patients with hypertension or hypertension with diabetes mellitus. METHODS: Forty-nine elderly patients of hypertension and 42 elderly patients of hypertension with diabetes mellitus and 39 healthy elderly subjects were enrolled in the study. The height, weight and blood pressure of patients were measured, serum C reactive protein and other biochemical indicators were detected. The relation between plasma γ-GGT and cardiovascular risk factors in three groups were analyzed. RESULTS: There was no significant difference in plasma γ-GGT levels among three groups. There was a positive correlation of plasma γ-GGT levels with systolic pressure, pulse pressure, hemoglobin A1c and CRP in control group. While in hypertension with diabetes mellitus group, plasma γ-GGT levels were correlated with systolic pressure, mean arterial pressure, fasting blood sugar and cystatin. CONCLUSION: Plasma γ-GGT might be a risk factor for cardiovascular diseases, and may be used as a predictive indicator for kidney injury in early patients with hypertension with diabetes mellitus.

Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis.

Progressive immune dysfunction associated with aging is known as immunosenescence. The age-related deterioration of immune function is accompanied by chronic inflammation and microenvironment changes. Immunosenescence can affect both innate and acquired immunity. Sepsis is a systemic inflammatory response that affects parenchymal organs, such as the respiratory system, cardiovascular system, liver, urinary system, and central nervous system, according to the sequential organ failure assessment (SOFA). The initial immune response is characterized by an excess release of inflammatory factors, followed by persistent immune paralysis. Moreover, immunosenescence was found to complement the severity of the immune disorder following sepsis. Furthermore, the immune characteristics associated with sepsis include lymphocytopenia, thymus degeneration, and immunosuppressive cell proliferation, which are very similar to the characteristics of immunosenescence. Therefore, an in-depth understanding of immunosenescence after sepsis and its subsequent effects on the organs may contribute to the development of promising therapeutic strategies. This paper focuses on the characteristics of immunosenescence after sepsis and rigorously analyzes the possible underlying mechanism of action. Based on several recent studies, we summarized the relationship between immunosenescence and sepsis-related organs. We believe that the association between immunosenescence and parenchymal organs might be able to explain the delayed consequences associated with sepsis.

A Combination of Serum Biomarkers in Elderly Patients with Sarcopenia: A Cross-Sectional Observational Study.

BACKGROUND: The pathogenesis of sarcopenia in the elderly has not yet been fully understood. This study aimed to explore the relationship between sarcopenia and several serum biomarkers in elderly population. METHODS: It was an observational cross-sectional study of data collected from 70 patients. According to the criteria of the Asian Working Group for Sarcopenia (AWGS), subjects were divided into the sarcopenia group and nonsarcopenic group. We compared age, body mass index (BMI), biochemical indexes, smoking status, underlying disease, muscle mass, handgrip strength (HS), gait speed (GS), skinfold thickness, muscle thickness, and IL-6, IL-10, IL-17A, and TNF-α levels between these groups. RESULTS: Of the 70 subjects, 35 patients were diagnosed with sarcopenia. The number of men was higher than that of women in both groups. The patients with sarcopenia were older and had lower BMI and muscle thickness but higher SARC-F questionnaire scores. However, the difference in smoking status and skinfold thickness between these two groups were not statistically significant. Higher IL-6, IL-17A, and TNF-α levels were observed in participants with sarcopenia (P < 0.05). Patients with sarcopenia had a lower IL-10 level. Positive associations were present between the severity of sarcopenia and IL-6, IL-17A, and TNF-α levels, while there was an inverse correlation between the presence of sarcopenia and IL-10 level. CONCLUSIONS: Our research found that in sarcopenic elderly subjects, the serum levels of several biomarkers, such as IL-6, IL-17A, and TNF-α, were higher than those in nonsarcopenic elderly persons. Further studies are needed to explore the possible molecular mechanisms and discover new therapeutic targets.

TLR3 inhibitor and tyrosine kinase inhibitor attenuate cigarette smoke/poly I:C-induced airway inflammation and remodeling by the EGFR/TLR3/MAPK signaling pathway.

Tobacco smoke is the major risk factor for developing chronic obstructive pulmonary disease (COPD). Viral infection is a major cause of COPD exacerbation, which lacks effective drug treatments. In the present study, to mimic the pathogenesis of COPD, we employed a TLR3 ligand [Poly (I:C), PIC] to mimic viral infection to determine whether it enhances the effects of cigarette smoke (CS)-induced airway inflammation and remodeling. Our results showed that PIC enhanced the effects of cigarette smoke extract (CSE)-induced inflammatory cytokine IL-1ß, TNF-α and IL-8 mRNA expression and remodeling factor E-cadherin, α-SMA and TGF-ß1 mRNA expression with TLR3 upregulation and EGFR phosphorylation in pulmonary epithelial NCI-H292 cells. These responses were inhibited by a TLR3/dsRNA complex inhibitor (TLR3i) or a tyrosine kinase inhibitor icotinib (Ico). Similarly, in the PIC-enhanced CS-induced airway inflammation and remodeling mouse model, treatment with TLR3i or Ico reduced the mRNA and protein expression of the inflammatory cytokines IL-1ß and TNF-α and keratinocyte chemoattractant (KC) and the remodeling factors α-SMA, TGF-ß1, MMP-9 and MUC5AC, while increasing E-cadherin mRNA and protein expression. Furthermore, we found that TLRi and Ico can attenuate the airway hyperreactivity induced by PIC, which is enhanced by CS. Finally, PIC enhanced the effects of CS on TLR3 upregulation and EGFR phosphorylation and significantly increased Erk1/2 and P38 phosphorylation, whereas TLR3i and Ico markedly suppressed TLR3 upregulation and EGFR, Erk1/2 and P38 phosphorylation in the model. Our findings suggest that TLR3/EGFR may be a potential target for the treatment of airway inflammation and remodeling in COPD.

Gut microbiota signatures in Schistosoma japonicum infection-induced liver cirrhosis patients: a case-control study.

BACKGROUND: Several studies have assessed the role of gut microbiota in various cirrhosis etiologies, however, none has done so in the context of Schistosoma japonicum infection in humans. We, therefore, sought to determine whether gut microbiota is associated with S. japonicum infection-induced liver cirrhosis. METHODS: From December 2017 to November 2019, 24 patients with S. japonicum infection-induced liver cirrhosis, as well as 25 age- and sex-matched controls from the Zhejiang Province, China, were enrolled. Fecal samples were collected and used for 16S rRNA gene sequencing (particularly, the hypervariable V4 region) using the Illumina MiSeq system. Wilcoxon Rank-Sum and PERMANOVA tests were used for analysis. RESULTS: Eight hundred and seven operational taxonomic units (OTUs) were detected, of which, 491 were common between the two groups, whereas 123 and 193 were unique to the control and cirrhosis groups, respectively. Observed species, Chao, ACE, Shannon, Simpson, and Good's coverage indexes, used for alpha diversity analysis, showed values of 173.4 ± 63.8, 197.7 ± 73.0, 196.3 ± 68.9, 2.96 ± 0.57, 0.13 ± 0.09, and 1.00 ± 0.00, respectively, in the control group and 154.0 ± 68.1, 178.6 ± 75.1, 179.9 ± 72.4, 2.68 ± 0.76, 0.19 ± 0.18, and 1.00 ± 0.00, respectively, in the cirrhosis group, with no significant differences observed between the groups. Beta diversity was evaluated by weighted UniFrac distances, with values of 0.40 ± 0.13 and 0.40 ± 0.11 in the control and cirrhosis groups, respectively (P > 0.05). PCA data also confirmed this similarity (P > 0.05). Meanwhile, the relative abundance of species belonging to the Bacilli class was higher in cirrhosis patients [median: 2.74%, interquartile range (IQR): 0.18-7.81%] than healthy individuals (median: 0.15%, IQR: 0.47-0.73%; P < 0.01), and that of Lactobacillales order was also higher in cirrhosis patients (median: 2.73%, IQR: 0.16-7.80%) than in healthy individuals (median: 0.12%, IQR: 0.03-0.70%; P < 0.05). CONCLUSIONS: Cumulatively, our results suggest that the gut microbiota of S. japonicum infection-induced liver cirrhosis patients is similar to that of healthy individuals, indicating that bacterial taxa cannot be used as non-invasive biomarkers for S. japonicum infection-induced liver cirrhosis.

Expression, purification, and characterization of recombinant lumbrokinase PI239 in Escherichia coli.

Lumbrokinase (LK) is an important fibrinolytic enzyme derived from earthworms. It has been found that LK is composed of a group of isoenzymes. To construct and express the mature peptide of LK PI239 in Escherichia coli, we amplified and optimized the gene of LK which was then cloned into the prokaryotic expression vector pET-22b(-). The recombinant LK (rLK) protein was expressed as inclusion bodies and we have developed a purification process of rLK from these inclusion bodies. A step-down urea concentration strategy was applied to the rLK renaturation process. The purified and renatured rLK apparently ameliorated the conditions of the model thrombosis rats used, and may be developed into a therapeutic agent for thrombotic-associated diseases.

Construction of a recombinant adenovirus vector expressing IL-18BP/IL-4 fusion gene and the anti-inflammatory effect induced by this gene on lipopolysaccharide-stimulated synovial fibroblasts.

OBJECTIVE: To construct a recombinant adenovirus vector for expressing the IL-18 binding protein (IL-18BP)/IL-4 fusion gene and confirm the anti-inflammatory effect of this gene. MATERIALS AND METHODS: The recombinant virus expressing IL-18BP/IL-4 fusion protein (AD-IL-18BP/IL-4) was constructed. AD-IL-18BP/IL-4 was used to infect synovial fibroblasts (SF). ELISA and Western blot analysis were used to determine the expressions of the proteins IL-4 and IL-18BP. To investigate the protective effects of this vector on rheumatoid arthritis, SF were infected with AD-IL-18BP/IL-4 and stimulated by LPS (1 microg/ml) 4 h later. The expression levels of TNF-alpha, IL-6, IL-8, and IL-18 in the culture supernatant were detected by ELISA and production of PGE2 and NO was estimated. The protein expression of COX-2, iNOS, and NF-kappaB p50 in treated SF was analyzed by Western blot. RESULTS: AD-IL-18BP/IL-4 can effectively express the IL-18BP/IL-4 fusion protein. The expressions of TNF-alpha, IL-6, IL-8, and IL-18 were significantly inhibited in LPS-stimulated SF after treatment with AD-IL-18BP/IL-4. The production of PGE2 and NO was significantly decreased. Moreover, NF-kappaB p50, COX-2, and iNOS levels in SF were markedly suppressed by AD-IL-18BP/IL-4. CONCLUSION: AD-IL-18BP/IL-4 can suppress the production and expression of inflammatory cytokines such as COX-2, iNOS, and NF-kappaB in LPS-stimulated SF.

[Changes of blood pressure, blood glucose and blood lipids levels after intensive treatment in incipient diabetes II patients].

OBJECTIVE: To evaluate the effect of intensive treatment on the blood sugar, blood lipids and blood pressure levels in incipient diabetes II patients. METHODS: One hundred and sixty incipient diabetes patients were allocated into two groups according to chronological order: 80 cases received routine treatment and 80 cases received intensive treatment. Fasting blood-glucose (FBG), glycosylated hemoglobin (HbA1C), blood pressure, blood cholesterol (TC), triglyceride (TG), LDL cholesterol-C (LDL-C), alanine aminotransferase (ALT) and aspertate aminotransferase (AST) were tested before treatment. For intensive treatment group blood pressure, blood sugar and blood lipids were regularly tested, and the therapeutic protocols were adjusted according to the test results until the therapeutic target reached. After six months, HbA1C, blood pressure, TC, LDL-C, ALT and AST were tested again and comparison was made between the two groups. RESULTS: There was a significant decrease in TC and LDL-C in the intensive treatment group compared with those in the routine treatment group (P <0.05). CONCLUSION: The intensive treatment on the incipient diabetes II patients facilitate the control of the blood lipids and blood sugar.

Multidisciplinary treatment of a patient with necrotizing fasciitis caused by Staphylococcus aureus: A case report.

BACKGROUND: Necrotizing fasciitis is a severe bacterial skin infection that spreads quickly and is characterized by extensive necrosis of the deep and superficial fascia resulting in the devascularization and necrosis of associated tissues. Because of high morbidity and mortality, accurate diagnosis and early treatment with adequate antibiotics and surgical intervention are vital. And timely identification and treatment of complications are necessary to improve survival of patient. CASE SUMMARY: We report a case of necrotizing fasciitis caused by Staphylococcus aureus in a patient using high doses of glucocorticoid and suffering from secondary diabetes mellitus. He was admitted to our hospital due to redness and oedema of the lower limbs. After admission, necrotizing fasciitis caused by Staphylococcus aureus was considered, and he was discharged after B-ultrasound drainage and multiple surgical operations. In the process of treatment, multiple organ functions were damaged, but with the help of multi-disciplinary treatment, the patient got better finally. CONCLUSION: The key to successful management of necrotizing fasciitis is an early and accurate diagnosis. The method of using vacuum sealing drainage in postoperative patients can keep the wound dry and clean, reduce infection rate, and promote wound healing. Interdisciplinary collaboration is a vital prerequisite for successful treatment.

Multiorgan Drug Action of Levosimendan in Critical Illnesses.

Cardiotonic drugs mainly include digitalis, catecholamines, phosphodiesterase inhibitors, and calcium sensitizers, which have been successively discovered and applied in clinical practice. However, there are only a few new drugs available in this field, and the selection is very limited. Digitalis, catecholamines, and phosphodiesterase inhibitors increase myocardial contractility by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and this increase in intracellular calcium ion concentration enhances myocardial oxygen consumption and causes arrhythmia. For these reasons, the research focus on positive inotropic agents has shifted from calcium mobilization to calcium sensitization. Intracellular calcium sensitizers are more effective and safer drugs because they do not increase the intracellular concentration of calcium ions. However, only three calcium sensitizers have been fully developed and used in the past three decades. One of these drugs, levosimendan, has multiple molecular targets and exerts its pharmacological effects by not only increasing myocardial contractility, but also enhancing respiratory muscle function and liver and kidney protection, and it is useful for patients with severe sepsis and septic shock. Recently, more than 60 randomized controlled clinical trials of levosimendan have been reported; however, these clinical trials have occasionally shown different findings. This article reviews the research progress of levosimendan in critical illnesses in recent years.

Resistin does not down-regulate the transcription of insulin receptor promoter.

OBJECTIVE: To detect the effect of resistin on the transcription of insulin receptor promoter. METHODS: Luciferase reporter gene was fused downstream of human insulin receptor promoter and the enzymatic activity of luciferase was determined in the presence or absence of resistin. The resistin expressed with plasmid was stained with antibody against Myc tag which was in frame fused with resistin coding sequence, and then imaged with confocal microscopy. RESULTS: The treatment of pIRP-LUC transfected cells with recombinant resistin did not result in significant difference in the enzymatic activity of luciferase compared to the untreated cells. Cell staining showed that green fluorescence could be observed in the cytoplasm, but not in the nucleus. CONCLUSION: The results suggest that the endogenous resistin may functionally locate in the cytoplasm, but does not enter the nucleus and not down-regulate the transcription of insulin receptor promoter.