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Abstract Background Limb salvage surgery is an important method for treating malignant tumors of the bone involving the adjacent parts of the major joints in children. This technique allows for preservation of limb function, especially in the lower limb. However, the reconstruction of the proximal end of the tibia after removing the tumor mass with a rational scale to preserve the total knee joint and reduce limb length discrepancy presents a challenge. Case presentation We present a case of osteosarcoma of the proximal tibia. After being treated with an extended tumor resection, the proximal tibia of the child was restructured using endoprosthetic replacement with epiphyseal preservation. This procedure preserves the entire articular surface and growth plate of the knee joint of the affected limb and provides a feasible alternative protocol for retaining the function and growth potential of the affected limb. The patient remained disease-free and normal limb motor function was observed during the 3.5 year follow-up since the initial surgery. Conclusions Preservation of the epiphysis enabled our patient to perform better limb function after limb-saving surgery as a result of his undamaged knee joint and minimized limb-length discrepancy. We believe that endoprosthetic replacement with preservation of the epiphysis can provide the best strategy for reconstruction after resection of focal malignant tumors in long bones without epiphytic involvement.

IntroductionIt is well-known that altered hypothalamus–pituitary–adrenal (HPA) axis process has an important role in the neurodegenerative process in schizophrenia (SZ). However, this neurodegenerative mechanism has not been clarified in SZ. Therefore, the main purpose of this study was to determine HPA axis damage in the first-episode, unmedicated schizophrenia (FES) patients and chronic schizophrenia (CSZ) patients in comparison with healthy controls (HC) by means of quantitative analysis of the peripheral blood mRNA expression of glucocorticoid receptor (GR), GR transcripts containing exons 1B (GR-1B), and neuron specific enolase (NSE) genes and serum cortisol and NSE, a specific serum marker for neuronal damage.MethodsIn the present study, 43 FES patients, 39 CSZ, and 47 HC were included. The peripheral blood mRNA expressions for GR, GR-1B, and NSE genes were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Serum cortisol and NSE were analyzed by electrochemiluminescence immunoassay technique.ResultsLevels of GR mRNA were significantly lower in FES and CSZ than that in HC. The expression of GR-1B mRNA was significantly decreased in CSZ when compared with that in FES. Levels of NSE mRNA were significantly lower in CSZ than that in FES patients or HC patients. CSZ patients showed significantly lower cortisol concentrations than FES and HC patients. FES patients showed significantly higher NSE concentrations than CSZ and HC.ConclusionOur findings support that there is disrupted HPA axis system in the SZ and suggest that CSZ patients suffer a greater HPA axis damage than FES patients. Our research implicated underlying GR mRNA dysregulation in SZ and the potential importance of the functional GR-1B transcription in CSZ.

Voltage-gated sodium channels (VGSCs), which are abnormally expressed in various types of cancers such as breast cancer, prostate cancer, lung cancer, and cervical cancer, are involved in the metastatic process of invasion and migration. Nav1.5 is a pore-forming α subunit of VGSC encoded by SCN5A. Various studies have demonstrated that Nav1.5, often as its neonatal splice form, is highly expressed in metastatic breast cancer cells. Abnormal activation and expression of Nav1.5 trigger a variety of cellular mechanisms, including changing H+ efflux, promoting epithelial-to-mesenchymal transition (EMT) and the expression of cysteine cathepsin, to potentiate the metastasis and invasiveness of breast cancer cells in vitro and in vivo. Here, we systematically review the latest available data on the pro-metastatic effect of Nav1.5 and its underlying mechanisms in breast cancer. We summarize the factors affecting Nav1.5 expression in breast cancer cells, and discuss the potential of Nav1.5 blockers serving as candidates for breast cancer treatment.

ObjectivesCytokine activation and low complement levels are common in depression patients. This study is aimed at investigating the clinical significance of changes in serum concentrations of melatonin (MT), interleukin-6 (IL-6), homocysteine (hcy), and complement C3 and C4 in depression patients and relationships of them with depression activity.MethodsA total of 95 depression patients, including first-episode group (n = 43) and recurrent group (n = 52), and 45 age- and gender-matched healthy controls (HC) were recruited. Serum levels of MT, IL-6, hcy, C3, and C4 in all samples were measured by using enzyme-linked immunosorbent assay (ELISA), chemiluminescence method, enzyme circulation method, and immuno-scatter turbidimetric assay, respectively.ResultsThe serum MT, IL-6, and hcy levels in the first-episode group (113.08 ± 5.06 pg/ml, 2.06 ± 0.12 ng/L, and 13.87 ± 0.45 μmol/L), and recurrent group (117.63 ± 4.63 pg/ml, 2.20 ± 0.12 ng/L, and 13.61 ± 0.46 μmol/L) were significantly higher than those in the control group (89.50 ± 5.10 pg/ml, 1.57 ± 0.06 ng/L, and 11.34 ± 0.40 μmol/L). The serum levels of C3 in the first-episode group (0.95 ± 0.02 ng/L) were significantly lower than those in the recurrent group (1.05 ± 0.03 ng/L) and control group (1.12 ± 0.03 ng/L). There was no significant difference in serum C4 level between each group.ConclusionThese results suggest that higher serum MT, IL-6, and hcy levels were correlated with pathogenesis of depression.

Myotonia congenita and hypokalemic periodic paralysis type 2 are both rare genetic channelopathies caused by mutations in the CLCN1 gene encoding voltage-gated chloride channel CLC-1 and the SCN4A gene encoding voltage-gated sodium channel Nav1.4. The patients with concomitant mutations in both genes manifested different unique symptoms from mutations in these genes separately. Here, we describe a patient with myotonia and periodic paralysis in a consanguineous marriage pedigree. By using whole-exome sequencing, a novel F306S variant in the CLCN1 gene and a known R222W mutation in the SCN4A gene were identified in the pedigree. Patch clamp analysis revealed that the F306S mutant reduced the opening probability of CLC-1 and chloride conductance. Our study expanded the CLCN1 mutation database. We emphasized the value of whole-exome sequencing for differential diagnosis in atypical myotonic patients.

Schizophrenia (SZ) is a debilitating and heterogeneous disease. We hypothesized that the oxytocin (OXT) system, inflammation and one-carbon metabolism would have a link with SZ. In this study, serum OXT, OXT receptor (OXTR), interleukin-6 (IL-6), high sensitivity CRP (hsCRP) and homocysteine (Hcy) levels were measured in 52 first-episode schizophrenia (FES) patients and 41 healthy controls (HC) from the Second Xiangya Hospital of Central South University. Meanwhile, the mRNA expressions of OXT and OXTR genes were determined by real-time quantitative PCR. Serum OXT and OXTR levels were significantly lower in FES patients (518.96 ± 22.22 and 174.60 ± 17.11 pg/ml) than the HC group (711.58 ± 40.57 and 252.15 ± 20.62 pg/ml). Serum IL-6 and hsCRP levels showed no difference between the two groups (1.82 ± 0.30 vs. 1.69 ± 0.36 pg/ml, 0.66 (0.22, 1.07) vs. 0.31 (0.13, 0.91) mg/L), but serum Hcy levels were significantly higher in FES patients (20.18 ± 1.83 vs. 15.24 ± 0.82 μmol/ml). The FES patients (0.27 ± 0.02 and 0.20 ± 0.02) have relatively higher mRNA expressions of OXT and OXTR genes than the HC group (0.16 ± 0.01 and 0.14 ± 0.01). In summary, our results suggested the possible function of the OXT system and Hcy in the pathogenesis of SZ.

The aim of this study is to explore the changes and clinical significance of serum C3, C4, hypersensitive C-reactive protein (hsCRP) and uric acid (UA) in patients of bipolar disorder (BD). In this case-control study, we recruited 141 BD patients from The Second Xiangya Hospital, Central South University, and 151 age and gender matched healthy controls (HC) from the health management central of The Second Xiangya Hospital. These patients were divided into two subgroups based on medicines use: 91 patients were treated with psychiatric drugs and 50 patients were drugs free, or four subgroups based on mood states: 54 patients in manic/hypomanic phase, 30 patients in depressive phase, 52 patients in euthymic phase and 5 patients in mixed phase. Serum levels of C3, C4, hsCRP and UA were measured in all subjects. The serum C3 levels in BD patients (0.9981 ± 0.1849 g/L) were significantly lower than that in HC group (1.0637 ± 0.2186 g/L), especially the drugs free subgroup and the euthymic subgroup (0.975 ± 0.153 and 0.983 ± 0.182 g/L), while the serum UA levels were significantly higher (354.6 ± 90.4 vs. 332.9 ± 88.7 μmol/L), especially the drug-treated subgroup and manic/hypomanic subgroup (361.56 ± 93.20 and 376.70 ± 88.89 μmol/L), and rates of hyperuricaemia (31.91 vs. 17.88%) were significantly higher in BD patients than in HC group. The serum C4 and hsCRP levels in HC group showed no significant difference with BD patients in whole or those subgroups. These findings suggested that the complement and purinergic systems of BD patients might be disrupted, the UA levels could be a potential marker in manic phase and the C3 might be the marker of therapeutic evaluation of BD patients.

Abstract Background: The tarantula Chilobrachys jingzhao is one of the largest venomous spiders in China. In previous studies, we purified and characterized at least eight peptides from C. jingzhao venom. In this report, we describe the purification and characterization of Jingzhaotoxin-X (JZTX-X), which selectively blocks Kv4.2 and Kv4.3 potassium channels. Methods: JZTX-X was purified using a combination of cation-exchange HPLC and reverse-phase HPLC. The amino-acid sequence was determined by automated Edman degradation and confirmed by mass spectrometry (MS). Voltage-gated ion channel currents were recorded in HEK293t cells transiently transfected with a variety of ion channel constructs. In addition, the hyperalgesic activity of JZTX-X and the toxin´s effect on motor function were assessed in mice. Results: JZTX-X contained 31 amino acids, with six cysteine residues that formed three disulfide bonds within an inhibitory cysteine knot (ICK) topology. In whole-cell voltage-clamp experiments, JZTX-X inhibited Kv4.2 and Kv4.3 potassium channels in a concentration- and voltage-dependent manner, without affecting other ion channels (Kv1.1, 1.2, 1.3, 2.1, delayed rectifier potassium channels, high- and low-voltage-activated Ca2+ channels, and voltage-gated sodium channels Nav1.5 and 1.7). JZTX-X also shifted the voltage-dependent channel activation to more depolarized potentials, whereas extreme depolarization caused reversible toxin binding to Kv4.2 channels. JZTX-X shifted the Kv4.2 and Kv4.3 activities towards a resting state, since at the resting potential the toxin completely inhibited the channels, even in the absence of an applied physical stimulus. Intrathecal or intraplantar injection of JZTX-X caused a long-lasting decrease in the mechanical nociceptive threshold (hyperalgesia) but had no effect on motor function as assessed in the rotarod test. Conclusions: JZTX-X selectively suppresses Kv4.2 and Kv4.3 potassium channel activity in a concentration- and voltage-dependent manner and causes long-lasting mechanical hyperalgesia.

Abstract Spider venoms are known to contain proteins and polypeptides that perform various functions including antimicrobial, neurotoxic, analgesic, cytotoxic, necrotic, and hemagglutinic activities. Currently, several classes of natural molecules from spider venoms are potential sources of chemotherapeutics against tumor cells. Some of the spider peptide toxins produce lethal effects on tumor cells by regulating the cell cycle, activating caspase pathway or inactivating mitochondria. Some of them also target the various types of ion channels (including voltage-gated calcium channels, voltage-gated sodium channels, and acid-sensing ion channels) among other pain-related targets. Herein we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against the pathophysiological conditions including cancer and pain.

ABSTRACT The impact of the sulfur (S) content in lubricating oil was evaluated for four ultra-low-emission vehicles and two super-ultra-low-emission vehicles, all with low mileage. The S content in the [...]