Poly[bis­[μ-1-cyclo­propyl-6-fluoro-4-oxido-7-(1-piperazin­yl)-1,4-dihydro­quinoline-3-carboxyl­ato]nickel(II)]

In the title compound, [Ni(C17H17FN3O3)2]n, the NiII atom exists in a distorted trans-NiN2O4 octa­hedral geometry defined by two monodentate N-bonded and two bidentate O,O-bonded 1-cyclo­propyl-6-fluoro-4-oxido-7-(1-piperazin­yl)-1,4-dihydro­quinoline-3-carboxyl­ate (ciprofloxacinium) monoanions. The extended two-dimensional structure is a square grid. The Ni atom lies on a center of inversion

Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men.

BackgroundThe aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude.MethodsA total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured.ResultsResults showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P<0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28-1.51, P<0.001).ConclusionThe present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects

Disruption of Smad4 impairs TGF-β/Smad3 and Smad7 transcriptional regulation during renal inflammation and fibrosis in vivo and in vitro

The mechanism by which TGF-β regulates renal inflammation and fibrosis is largely unclear; however, it is well accepted that its biological effects are mediated through Smad2 and Smad3 phosphorylation. Following activation, these Smads form heteromeric complex with Smad4 and translocate into the nucleus to bind and regulate the expression of target genes. Here we studied the roles of Smad4 to regulate TGF-β signaling in a mouse model of unilateral ureteral obstruction using conditional Smad4 knockout mice and in isolated Smad4 mutant macrophages and fibroblasts. Disruption of Smad4 significantly enhanced renal inflammation as evidenced by a greater CD45+ leukocyte and F4/80+ macrophage infiltration and upregulation of IL-1β, TNF-α, MCP-1, and ICAM-1 in the obstructed kidney and in IL-1β-stimulated macrophages. In contrast, deletion of Smad4 inhibited renal fibrosis and TGF-β1-induced collagen I expression by fibroblasts. Further studies showed that the loss of Smad4 repressed Smad7 transcription, leading to a loss of functional protein. This, in turn, inhibited IκBα expression but enhanced NF-κB activation, thereby promoting renal inflammation. Interestingly, deletion of Smad4 influenced Smad3-mediated promoter activities and the binding of Smad3 to the COL1A2 promoter, but not Smad3 phosphorylation and nuclear translocation, thereby inhibiting the fibrotic response. Thus, Smad4 may be a key regulator for the diverse roles of TGF-β1 in inflammation and fibrogenesis by interacting with Smad7 and Smad3 to influence their transcriptional activities in renal inflammation and fibrosis

N-(2-Chloro­benzo­yl)-N′-(3-pyrid­yl)thio­urea

In the mol­ecule of the title compound, C13H10ClN3OS, the dihedral angles between the plane through the thio­urea group and the pyridine and benzene rings are 53.08 (3) and 87.12 (3)°, respectively. The mol­ecules are linked by inter­molecular N—H⋯N hydrogen-bonding inter­actions to form a supra­molecular chain structure along the a axis. An intra­mol­ecular N—H⋯O hydrogen bond is also present

KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.

Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway. Knockdown of KMT2A markedly inhibited the promoter activity and expression of hTERT, and hTERT overexpression rescued the viability inhibition caused by KMT2A knockdown. Moreover, KMT2A knockdown suppressed tumorsphere formation and the expression of cancer stem cell markers, which was also reversed by hTERT overexpression. In addition, the results from a xenograft mouse model confirmed that KMT2A promoted melanoma growth via hTERT signaling. Finally, analyses of clinical samples demonstrated that the expression of KMT2A and hTERT were positively correlated in melanoma tumor tissues, and KMT2A high expression predicted poor prognosis in melanoma patients. Collectively, our results indicate that KMT2A promotes melanoma growth by activating the hTERT signaling, suggesting that the KMT2A/hTERT signaling pathway may be a potential therapeutic target for melanoma

Traditional Chinese Medicine for Refractory Nephrotic Syndrome: Strategies and Promising Treatments

Refractory nephrotic syndrome (RNS) is an immune-related kidney disease with poor clinical outcomes. Standard treatments include corticosteroids as the initial therapy and other immunosuppressants as second-line options. A substantial proportion of patients with RNS are resistant to or dependent on immunosuppressive drugs and often experience unremitting edema and proteinuria, cycles of remission and relapse, and/or serious adverse events due to long-term immunosuppression. Traditional Chinese medicine has a long history of treating complicated kidney diseases and holds great potential for providing effective treatments for RNS. This review describes the Chinese medical theories relating to the pathogenesis of RNS and discusses the strategies and treatment options using Chinese herbal medicine. Available preclinical and clinical evidence strongly supports the integration of traditional Chinese medicine and Western medicine for improving the outcome of RNS. Herbal medicine such as Astragalus membranaceus, Stephania tetrandra S. Moore, and Tripterygium wilfordii Hook F can serve as the alternative therapy when patients fail to respond to immunosuppression or as the complementary therapy to improve therapeutic efficacy and reduce side effects of immunosuppressive agents. Wuzhi capsules (Schisandra sphenanthera extract) with tacrolimus and tetrandrine with corticosteroids are two herb-drug combinations that have shown great promise and warrant further studies

Vascularized fibular graft combined with vacuum assisted closure in the reconstruction of tibial defects

Background: To investigate the application of Flow-through free vascularized fibular graft combined with Vacuum Assisted Closure for the patients suffering from tibial defects caused by chronic osteomyelitis.Methods: We retrospectively analysed 20 cases of patients who accepted this operation in the treatment of tibial defects. Among the tibial defects, six cases resulted from blood stream infection while 14 cases resulted from comminuted fractures. All the patients included in the study were accompanied with 1 to 3 sinuses. The length of the defects ranged from 6cm to 16cm, with an average of 11.3cm. 6 patients were also faced with soft tissues defects combined with tendon or bone exposures, and the defects areas ranged from 11cm×7cm to 19cm×14cm. There were 5 patients suffering from fibular fractures at the same side of the defects. The courses of this disease were 5.5 -15 months, with an average of 9.8 months.Results: The patients included in the study were followed up from 10 months to 4 years, with an average of 1.9 years. Sinuses of 18 patients healed within 4 weeks, giving a primary healing rate of 90%. We undertook debridement of the remaining sinuses and they healed within 2 weeks. All skin flaps grafted to the patients survived, thus the survival rate was 100%. The radiographs indicated that 18 patients had good prognosis and the primary union time of grafting fibula were from 4 to 8 months, with average of 6.3 months. The healing patients achieved an average of 25.6 points based on the Enneking evaluation system which was used to evaluate the function of limbs after the operation, indicating that 85.9% of the limb function recovered. 4 patients required revision surgery for complications resulting from the operation: 1 wound breakdown, 2 bone non-unions, 1 graft fracture. Infection occurred only as a pin-tract infection, and was controlled with oral antibiotics and repeated dressing; there was no deep infection out of control in any of these patients.Conclusion: The flow-through free vascularized fibular graft did not only repair tibial defects, but retained the continuity of trunk vessels. The flowthrough fibular graft combined with Vacuum Assisted Closure (VAC) controlled the infection, shortened the course of treatment, and effectively restored limb function when applied to the treatment of tibial defects.Keywords: Tibial defect, Flow-through fibular graft, Vacuum Assisted Closure, Chronic Osteomyeliti