BackgroundCirculatory shock is a common syndrome with a high mortality and limited therapeutic options. Despite its discovery and use in clinical and experimental settings more than a half-century ago, angiotensin II (Ang II) has only been recently evaluated as a vasopressor in distributive shock. We examined existing literature for associations between Ang II and the resolution of circulatory shock.MethodsWe searched PubMed, MEDLINE, Ovid, and Embase to identify all English literature accounts of intravenous Ang II in humans for the treatment of shock (systolic blood pressure [SBP] ≤ 90 mmHg or a mean arterial pressure [MAP] ≤ 65 mmHg), and hand-searched the references of extracted papers for further studies meeting inclusion criteria. Of 3743 articles identified, 24 studies including 353 patients met inclusion criteria. Complete data existed for 276 patients. Extracted data included study type, publication year, demographics, type of shock, dosing of Ang II or other vasoactive medications, and changes in BP, lactate, and urine output. BP effects were grouped according to type of shock, with additional analyses completed for patients with absent blood pressure. Shock was distributive (n = 225), cardiogenic (n = 38), or from other causes (n = 90). Blood pressure as absent in 18 patients.ResultsFor the 276 patients with complete data, MAP rose by 23.4% from 63.3 mmHg to 78.1 mmHg in response to Ang II (dose range: 15 ng/kg/min to 60 mcg/min). SBP rose by 125.2% from 56.9 mmHg to 128.2 mmHg (dose range: 0.2 mcg/min to a 1500 mcg bolus). A total of 271 patients with complete data were determined to exhibit a BP effect which was directly associated with Ang II. Subgroups (patients with cardiogenic, septic, and other types of shock) exhibited similar increases in BP. In patients with absent BP, deemed to be cardiac arrest, return of spontaneous circulation (ROSC) was achieved, and BP increased by an average of 107.3 mmHg in 11 of 18 patients. The remaining seven patients with cardiac arrest did not respond.ConclusionsIntravenous Ang II is associated with increased BP in patients with cardiogenic, distributive, and unclassified shock. A role may exist for Ang II in restoring circulation in cardiac arrest.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1896-6) contains supplementary material, which is available to authorized users.

Acute kidney injury (AKI) is a common disease with a complex pathophysiology. The old paradigm of identifying renal injury based on location—prerenal, intrarenal, and postrenal—is now being supplanted with a new paradigm based on observable kidney injury patterns. The pathophysiology of AKI on a molecular and microanatomical level includes inflammation, immune dysregulation, oxidative injury, and impaired microcirculation. Treatment has traditionally been supportive, including the avoidance of nephrotoxins, judicious volume and blood pressure management, hemodynamic monitoring, and renal replacement therapy. Fluid overload and chloride-rich fluids are now implicated in the development of AKI, and resuscitation with a balanced, buffered solution at a conservative rate will mitigate risk. Novel therapies, which address specific observable kidney injury patterns include direct oxygen-free radical scavengers such as α-lipoic acid, curcumin, sodium-2-mercaptoethane sulphonate, propofol, and selenium. In addition, angiotensin II and adenosine receptor antagonists hope to ameliorate kidney injury via manipulation of renal hemodynamics and tubulo-glomerular feedback. Alkaline phosphatase, sphingosine 1 phosphate analogues, and dipeptidylpeptidase-4 inhibitors counteract kidney injury via manipulation of inflammatory pathways. Finally, genetic modifiers such as 5INP may mitigate AKI via transcriptive processes.

Splenomegaly and pancytopenia are common in Wilson’s disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson’s Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients significantly improved one year after splenectomy. Thus, we may conclude that splenectomy is a safe and effective therapeutic measure for hypersplenism in WD patients who had been preoperatively treated with DMPS for powerful anti-copper therapy.

Due to the significant differences between the shale reservoir and conventional sand reservoir in many aspects such as types and characteristics of minerals, pores and fluids, the existing rock physics models are no longer applicable for shale reservoir. In order to make a better description of the shale gas reservoir, a new rock physics effective model, which is more suitable for shale reservoir was proposed in this work. One assumption used is that clay is considered to be the background medium, and other minerals, organic matter, pores and fluids are seen as inclusions. And well A is used to verify the reliability of the new rock physics effective model. Results show that the P-wave and S-wave velocity estimation results are in good agreements with the well-logging values. Besides, a new brittle indicating factor was developed. Using the constructed rock physics effective model, from four aspects of quartz content, organic matter, porosity and fluid types, the new brittle indicating factor was compared with the routine index of rock brittleness -Young's modulus. Tests on real datasets showed that our new brittle indicating factor is more sensitive than Young's modulus when used in predicting the gas-bearing brittle shale reservoir.

Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.

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BackgroundMusculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain.ObjectivesTo investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD.MethodsWe enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain.ResultsTwo hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07–2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63–6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life.ConclusionsThe lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

We consider the problem of fluid identification and fracture detection in unconventional reservoir (tight gas sand and shale gas) characterization. We begin with a simplification of the stiffness parameters and the derivation of a linearized reflection coefficient and azimuthal elastic impedance (EI). The accuracy of the simplification is confirmed in application to gas-bearing fractured rocks with low porosity and small fracture density. We have developed a modified fluid factor that is more sensitive to fluid type and less influenced by porosity. A two-step inversion workflow is evaluated based on the derived linearized reflection coefficient and azimuthal EI, including (1) a damped least-squares inversion for azimuthal EI, constrained by an initial model, and (2) a Bayesian Markov chain Monte Carlo inversion for the modified fluid factor and dry fracture weaknesses. Stability and accuracy are examined with synthetic data, from which we conclude that the modified fluid factor and dry fracture weaknesses can be stably determined in the presence of moderate data error/noise. The stability of our approach is further confirmed on a fractured tight gas sand field data set, within which we observe that geologically reasonable parameters (Lamé constants, the modified fluid factor, and dry fracture weaknesses) are determined. We conclude that our inversion workflow and its underlying assumptions form realistic predictions/discriminations of reservoir fracture and fluid parameters.