[Association of waist-to-height ratio with sarcopenic obesity in hemodialysis patients with normal body mass index].

Objective: To explore the association between waist-to-height ratio (WHtR) and sarcopenic obesity (SO) in maintenance hemodialysis (MHD) patients with normal body mass index (BMI). Methods: A multicenter and cross-sectional study that included adult patients undergoing MHD was conducted in 20 hemodialysis centers from June 1st to August 30th, 2021. Body composition was evaluated by body composition monitor based on bioimpedance spectroscopy. According to the quartiles of WHtR, patients were divided into four groups: Q1, Q2, Q3 and Q4 group. The association of WHtR with SO was determined by multiple logistic regression models, stratified analyses, interactive analyses, and receiver operating characteristic (ROC) analyses, respectively. Results: A total of 2 207 MHD patients (1 341 males and 866 females) were included, and aged [M (Q1, Q3)] 57 (44, 68) years. The prevalence of SO was increased with increasing quartiles of WHtR [8.6% (46/533), 22.5% (141/628), 35.4% (215/608), and 44.3% (194/438) for Q1, Q2, Q3, and Q4 group, respectively]. Multivariate logistic regression analysis showed that WHtR was associated with SO. The association remained statistically significant even after adjusting for age, gender, dialysis vintage, BMI, biochemical indicators, and various medical histories. Compared with Q1 group, the odds ratios (OR) were 2.54 (95%CI: 1.69-3.83), 4.30 (95%CI: 2.88-6.42) and 5.18 (95%CI: 3.37-7.96) for Q2, Q3 and Q4 group, respectively. The interaction analysis showed that age, sex and history of diabetes had interactive roles in the association between WHtR and SO (all P<0.05). The association stably existed across subgroups, and it was more obvious in male patients, those with older age and without a history of diabetes（all P<0.05）. Furthermore, the cut-off value of WHtR identifying SO in male patients was 0.49, and the corresponding area under the curve (AUC) was 0.73 (95%CI: 0.70-0.75), with the sensitivity of 72.7% and specificity of 60.3%. In female patients, the cut-off value was 0.51, and the AUC was 0.68 (95%CI: 0.65-0.71), with the sensitivity of 70.1% and specificity of 57.8%. Conclusion: WHtR could be used as a simple index to evaluate the risk of SO in MHD patients with normal BMI.

[Endovascular abdominal aortic aneurysm repair with a new stent graft:early results from a multicenter study].

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.

[Relationship between visceral obesity and atherosclerosis in hemodialysis patients].

Objective: To evaluate the relationship between surrogate markers of visceral obesity[hypertriglyceridemic waist (HW) phenotype, visceral adiposity index (VAL), lipid accumulation product (LAP)]and atherosclerosis in hemodialysis patients. Methods: A multi-center cross-sectional study was carried out. A total of 961 maintenance hemodialysis (MHD) patients from 11 hemodialysis centers of Guizhou province between July 2016 and September 2017 were enrolled in the study. Anthropometric measures were performed in all subjects. Laboratory parameters including triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein-cholesterol were extracted from the medical records by researchers. Pearson correlation analysis was used to investigate the correlation between HW phenotype, VAI, LAP and plasma atherosclerotic index (AIP). Multivariate linear regression analysis was used to evaluate factors affecting AIP. Results: Totally, 585 men and 376 women aged 18-90 years, with a mean age of (56.08±15.42) years were recruited in the study. Pearson correlation analysis showed that VAI (men: r=0.82, women: r=0.84), LAP (men: r=0.73, women: r=0.74) and having HW phenotype (men: r=0.62, women: r=0.63) correlated positively with AIP (all P<0.001). Multivariate linear regression analysis showed that VAI (men: ß=0.77, women: ß=0.82) and LAP (men: ß=0.73, women: ß=0.73) were independent associated factors of AIP after adjustment of BMI, age, smoking and history of diabetes and hypertension (all P<0.001). Conclusions: Surrogate markers of visceral obesity such as having HW phenotype, VAI, LAP correlated positively with AIP. VAI, LAP has positive impacts on AIP independent of BMI, age, smoking and other traditional atherosclerosis risk factors.

Sulfonylurea receptor 1 contributes to the astrocyte swelling and brain edema in acute liver failure.

Astrocyte swelling (cytotoxic brain edema) is the major neurological complication of acute liver failure (ALF), a condition in which ammonia has been strongly implicated in its etiology. Ion channels and transporters are known to be involved in cell volume regulation, and a disturbance in these systems may result in cell swelling. One ion channel known to contribute to astrocyte swelling/brain edema in other neurological disorders is the ATP-dependent, nonselective cation (NCCa-ATP) channel. We therefore examined its potential role in the astrocyte swelling/brain edema associated with ALF. Cultured astrocytes treated with 5 mM ammonia showed a threefold increase in the sulfonylurea receptor type 1 (SUR1) protein expression, a marker of NCCa-ATP channel activity. Blocking SUR1 with glibenclamide significantly reduced the ammonia-induced cell swelling in cultured astrocytes. Additionally, overexpression of SUR1 in ammonia-treated cultured astrocytes was significantly reduced by cotreatment of cells with BAY 11-7082, an inhibitor of NF-κB, indicating the involvement of an NF-κB-mediated SUR1 upregulation in the mechanism of ammonia-induced astrocyte swelling. Brain SUR1 mRNA level was also found to be increased in the thioacetamide (TAA) rat model of ALF. Additionally, we found a significant increase in SUR1 protein expression in rat brain cortical astrocytes in TAA-treated rats. Treatment with glibenclamide significantly reduced the brain edema in this model of ALF. These findings strongly suggest the involvement of NCCa-ATP channel in the astrocyte swelling/brain edema in ALF and that targeting this channel may represent a useful approach for the treatment of the brain edema associated with ALF.

Significance of relaxin-2 expression in hepatocellular carcinoma: relation with clinicopathological parameters.

BACKGROUND: A number of putative roles, including the modulation of tumor growth, neovascularization, metastasis and oncogenic progression, have been correlated to relaxin-2 overexpression. However, the clinical significance of relaxin-2 expression in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the expression of relaxin-2 in HCC and determine its correlation with tumor progression and prognosis. PATIENTS AND METHODS: 180 HCC patients who had undergone curative liver resection were selected and immunohistochemistry was performed to analyze relaxin-2 expression in the respective tumors. RESULTS: Immunohistochemistry confirmed relaxin-2 overexpression in HCC tissues compared with their adjacent nonneoplastic tissues (p < 0.01). Additionally, immunostaining showed more relaxin-2 positive cells in the higher tumor grade (III) than in the lower tumor stage (I, II; p = 0.026). Moreover, HCC patients with high relaxin-2 expression were significantly associated with lower 5-year overall survival (p < 0.01) and lower 5-year disease-free survival (p < 0.01), respectively. Furthermore, immunostaining showed more relaxin-2 positive cells in the tumor recurrence (ETR) patients than non-ETR patients (p = 0.001). The Cox proportional hazards model further showed that relaxin-2 was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 1.872, 95% confidence interval [CI] = 1.18-5.146, p = 0.023) and 5-year overall survival (HR = 3.637, CI = 1.443-7.15, p = 0.001) in HCC. CONCLUSIONS: Our data suggest for the first time that the overexpression of relaxin-2 protein in HCC tissues is of predictive value on tumor progression and poor prognosis.

Brain edema in acute liver failure: role of neurosteroids.

Brain edema is a major neurological complication of acute liver failure (ALF) and swelling of astrocytes (cytotoxic brain edema) is the most prominent neuropathological abnormality in this condition. Elevated brain ammonia level has been strongly implicated as an important factor in the mechanism of astrocyte swelling/brain edema in ALF. Recent studies, however, have suggested the possibility of a vasogenic component in the mechanism in ALF. We therefore examined the effect of ammonia on blood-brain barrier (BBB) integrity in an in vitro co-culture model of the BBB (consisting of primary cultures of rat brain endothelial cells and astrocytes). We found a minor degree of endothelial permeability to dextran fluorescein (16.2%) when the co-culture BBB model was exposed to a pathophysiological concentration of ammonia (5mM). By contrast, lipopolysaccharide (LPS), a molecule well-known to disrupt the BBB, resulted in an 87% increase in permeability. Since increased neurosteroid biosynthesis has been reported to occur in brain in ALF, and since neurosteroids are known to protect against BBB breakdown, we examined whether neurosteroids exerted any protective effect on the slight permeability of the BBB after exposure to ammonia. We found that a nanomolar concentration (10nM) of the neurosteroids allopregnanolone (THP) and tetrahydrodeoxycorticosterone (THDOC) significantly reduced the ammonia-induced increase in BBB permeability (69.13 and 58.64%, respectively). On the other hand, we found a marked disruption of the BBB when the co-culture model was exposed to the hepatotoxin azoxymethane (218.4%), but not with other liver toxins commonly used as models of ALF (thioacetamide and galactosamine, showed a 29.3 and 30.67% increase in permeability, respectively). Additionally, THP and THDOC reduced the effect of TAA and galactosamine on BBB permeability, while no BBB protective effect was observed following treatment with azoxymethane. These findings suggest that ammonia does not cause a significant BBB disruption, and that the BBB is intact in the TAA or galactosamine-induced animal models of ALF, likely due to the protective effect of neurosteroids that are synthesized in brain in the setting of ALF. However, caution should be exercised when using azoxymethane as an experimental model of ALF as it caused a severe breakdown of the BBB, and neurosteriods failed to protect against this breakdown.

Role of cerebral endothelial cells in the astrocyte swelling and brain edema associated with acute hepatic encephalopathy.

Brain edema is an important complication of acute hepatic encephalopathy (AHE), and astrocyte swelling is largely responsible for its development. Elevated blood and brain ammonia levels have been considered as major etiological factors in this edema. In addition to ammonia, recent studies have suggested that systemic infection, inflammation (and associated cytokines (CKs)), as well as endotoxin (lipopolysaccharide (LPS)) are also involved in AHE-associated brain edema. As endothelial cells (ECs) are the first resident brain cells exposed to blood-borne "noxious agents" (i.e., ammonia, CKs, LPS) that are present in AHE, these cells may be in a critical position to react to these agents and trigger a process resulting in astrocyte swelling/brain edema. We therefore examined the effect of conditioned media (CM) from ammonia, LPS and cytokine-treated cultured brain ECs on cell swelling in cultured astrocytes. CM from ammonia-treated ECs when added to astrocytes caused significant cell swelling, and such swelling was potentiated when astrocytes were exposed to CM from ECs treated with a combination of ammonia, LPS and CKs. We also found an additive effect when astrocytes were exposed to ammonia along with CM from ammonia-treated ECs. Additionally, ECs treated with ammonia showed a significant increase in the production of oxy-radicals, nitric oxide (NO), as well as evidence of oxidative/nitrative stress and activation of the transcription factor nuclear factor kappa B (NF-κB). CM derived from ECs treated with ammonia, along with antioxidants (AOs) or the NF-κB inhibitor BAY 11-7082, when added to astrocytes resulted in a significant reduction in cell swelling, as compared to the effect of CM from ECs-treated only with ammonia. We also identified increased nuclear NF-κB expression in rat brain cortical ECs in the thioacetamide (TAA) model of AHE. These studies suggest that ECs significantly contribute to the astrocyte swelling/brain edema in AHE, likely as a consequence of oxidative/nitrative stress and activation of NF-κB.

Tuberculous sacroiliitis: a study of the diagnosis, therapy and medium-term results of 15 cases.

This report reviews the diagnosis, treatment and follow-up of 15 Chinese patients with tuberculous sacroiliitis (TBS) from 1997 to 2007. Buttock pain and lower back pain were the main complaints. All patients received antituberculosis chemotherapy treatment for at least 18 months; 10 also underwent surgery, with seven undergoing modified Smith-Petersen arthrodesis (evaluated using a visual analogue scale [VAS] for pain and the Oswestry Disability Index [ODI]). No simplex tuberculous synovitis existed at diagnosis. Bone-marrow oedema, cold abscess and soft-tissue oedema responded to antituberculosis treatment. Thirteen patients (86.7%) had satisfactory outcomes. There were also significant improvements in VAS and ODI scores post-operatively. In the chemotherapy plus surgery group, eight patients had solid bony fusions at 24 months post-operatively, while the five on chemotherapy alone presented with fibrous ankylosis at 24 months. Chemotherapy is the main treatment for TBS and modified arthrodesis is a feasible and effective method for treating severe joint destruction.

NF-κB in the mechanism of brain edema in acute liver failure: studies in transgenic mice.

Astrocyte swelling and brain edema are major complications of the acute form of hepatic encephalopathy (acute liver failure, ALF). While elevated brain ammonia level is a well-known etiological factor in ALF, the mechanism by which ammonia brings about astrocyte swelling is not well understood. We recently found that astrocyte cultures exposed to ammonia activated nuclear factor-κB (NF-κB), and that pharmacological inhibition of such activation led to a reduction in astrocyte swelling. Although these findings suggest the involvement of NF-κB in astrocyte swelling in vitro, it is not known whether NF-κB contributes to the development of brain edema in ALF in vivo. Furthermore, pharmacological agents used to inhibit NF-κB may have non-specific effects. Accordingly, we used transgenic (Tg) mice that have a functional inactivation of astrocytic NF-κB and examined whether these mice are resistant to ALF-associated brain edema. ALF was induced in mice by treatment with the hepatotoxin thioacetamide (TAA). Wild type (WT) mice treated with TAA showed a significant increase in brain water content (1.65%) along with prominent astrocyte swelling and spongiosis of the neuropil, consistent with the presence of cytotoxic edema. These changes were not observed in Tg mice treated with TAA. Additionally, WT mice with ALF showed an increase in inducible nitric oxide synthase (iNOS) immunoreactivity in astrocytes from WT mice treated with TAA (iNOS is known to be activated by NF-κB and to contribute to cell swelling). By contrast, Tg mice treated with TAA did not exhibit brain edema, histological changes nor an increase in iNOS immunoreactivity. We also examined astrocytes cultures derived from Tg mice to determine whether these cells exhibit a lesser degree of swelling and cytopathological changes following exposure to ammonia. Astrocyte cultures derived from Tg mice showed no cell swelling nor morphological abnormalities when exposed to ammonia for 24h. By contrast, ammonia significantly increased cell swelling (31.7%) in cultured astrocytes from WT mice and displayed cytological abnormalities. Moreover, we observed a lesser increment in iNOS and NADPH oxidase activity (the latter is also known to be activated by NF-κB and to contribute to astrocyte swelling) in astrocyte cultures from Tg mice treated with ammonia, as compared to ammonia-treated WT mice astrocytes. These findings strongly suggest that activation of NF-κB is a critical factor in the development of astrocyte swelling/brain edema in ALF.

Role of mitogen-activated protein kinases in the mechanism of oxidant-induced cell swelling in cultured astrocytes.

Cytotoxic brain edema, usually a consequence of astrocyte swelling, is an important complication of stroke, traumatic brain injury, hepatic encephalopathy, and other neurological disorders. Although mechanisms underlying astrocyte swelling are not fully understood, oxidative stress (OS) has generally been considered an important factor in its pathogenesis. To better understand the mechanism(s) by which OS causes cell swelling, we examined the potential involvement of mitogen-activated protein kinases (MAPKs) in this process. Cultures exposed to theoxidant H(2)O(2) (10, 25, 50 microM) for different time periods (1-24 hr) significantly increased cell swelling in a triphasic manner. Swelling was initially observed at 10 min (peaking at 30 min), which was followed by cell shrinkage at 1 hr. A subsequent increase in cell volume occurred at approximately 6 hr, and the rise lasted for at least 24 hr. Cultures exposed to H(2)O(2) caused the activation of MAPKs (ERK1/2, JNK and p38-MAPK), whereas inhibition of MAPKs diminished cell swelling induced by 10 and 25 microM H(2)O(2). These findings suggest that activation of MAPKs is an important factor in the mediation of astrocyte swelling following oxidative stress.

[The expression levels of GIRK1 and IRK1 in memory deficit rats].

AIM: To study the expression level of GIRK1 and IRK1 in cerebral cortex after aggregated beta-amyloid peptide25-35 injection into the rat cerebral ventricle for different times. METHODS: To test the spatial learning and memory in Morris water maze. To observe GIRK1 and IRK1 expression levels by RT-PCR. RESULTS: In Morris water maze task, the latencies of beta-amyloid peptide treated rats were longer than those of the sham rars in the 4, 5, 8, 10 training periods ("student" t-test, P < 0.05). The expression levels of GIRK1 in beta-amyloid peptide injection day 1 and day 3 groups are decreased significantly compared with sham group (Tukey's test, P < 0.05) and there is no difference between beta-amyloid peptide injection day 17 group and sham group. IRK1 expression levels are no difference among the four groups. CONCLUSION: Injection of aggregated beta-amyloid peptide25-35 into rat cerebral ventricles can induce memory and potassium channel expression changes. Beta-amyloid peptide induced inhibition of GIRK1 expression may have some relations with brain dysfunction.