Case report: POEMS syndrome masquerades as diabetic foot.

We present the case of a 54-year-old woman with reasonable blood sugar control who presented with a diabetic foot combined with severe peripheral neuropathy and vascular disease. Lower limb muscle weakness, muscle atrophy, skin pigmentation, and emaciation were also observed. Although her muscle strength improved after glucocorticoid treatment, it remained challenging to account for the other symptoms in this particular patient with chronic inflammatory demyelinating polyneuropathy. Plump liver and spleen, hidden bone lesions combined with seemingly unexplained cerebral infarction, and serous effusion led us to suspect polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. The abnormal proliferation of monoclonal plasma cells and a significant increase in vascular endothelial growth factor (VEGF) levels confirmed the diagnosis of POEMS syndrome. After 1 month of treatment with lenalidomide and dexamethasone, the diabetic foot ulcers healed, and the symptoms of myasthenia and fatigue improved. Diabetic feet may represent only the tip of the iceberg of an underlying POEMS syndrome. Our report aimed to increase awareness of this rare yet significant situation, advocating for the prompt identification and treatment of POEMS syndrome.

Suppressing CHD1L reduces the proliferation and chemoresistance in osteosarcoma.

Osteosarcoma (OS) is the most common bone malignant tumor. However, the genetic basis of OS pathogenesis is still not understood, and occurrence of chemo-resistance is a major reason for the high morbidity of OS patients. Recently, chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) has been identified as a gene related to malignant tumor progression. Unfortunately, its effects on OS development and drug resistance are still not understood. In the study, we attempted to investigate the effects of CHD1L on tumorigenesis and chemoresistance in OS. We found that CHD1L expression was markedly up-regulated in OS samples, especially in cisplatin (cDDP)-resistant patients. We also showed that OS cells with CHD1L knockdown were more sensitive to cDDP treatment with lower IC50 values. In addition, we found that CHD1L deletion markedly reduced cell proliferation and induced apoptosis in OS cells with cDDP resistance. Moreover, the properties of cancer stem cells were highly suppressed in cDDP-resistant OS cells following CHD1L knockdown. Furthermore, multidrug resistance protein 1 (MDR-1) expression levels were dramatically decreased in OS cells with cDDP resistance when CHD1L was suppressed. Functional analysis indicated that CHD1L knockdown clearly restrained the activation of ERK1/2, protein kinase B (AKT) and NF-κB signaling pathways in cDDP-resistant OS cells. Consistently, animal experiments suggested that CHD1L suppression mitigated cDDP resistance in the generated in vivo xenografts. Collectively, CHD1L could modulate chemoresistance of OS cells to cDDP, and thus may be inspiring findings for overcoming drug resistance in OS.

Functions of Exogenous RUNX2 in Giant Cell Tumor of Bone In Vitro.

OBJECTIVES: This research aimed to investigate the relative level of Runt-related transcription factor 2 (RUNX2) in giant cell tumor of bone (GCTB). Through the histopathological similarities between osteoporosis and GCTB, the biological functions of exogenous RUNXS were demonstrated in GCTB cell lines. This generated awareness of the molecular mechanism of the biogenesis and metastasis of GCTB, as well as showing the pathways and processes involved in this study. This research also expected to provide hints for the clinical treatment of patients with GCTB, to release the tumor burden and reduce the recurrence rate and metastasis of patients with this condition. METHODS: The expression of RUNX2 in the tumors was verified by Western Blot, qRT-PCR and immunohistochemistry, compared with the normal tissues' adjacent tumors. Subsequently, the plasmids expressing RUNX2 were constructed, amplified and transfected into the 0404 cell line through transfection kits (0.4, 0.8, 1.6, 2.4 ng/µl). After that, the proliferation, migration, invasion, cellular viability and apoptosis of 0404 cell lines were examined by EDU assay, wound healing assay, transwell assay, annexin v staining, and CCK8 assay, respectively. RESULTS: The messenger RNA (mRNA) level of RUNX2 in tumors was over 100 folds more than the normal tissues. The protein level of tumors upregulated 8.32(±4.41) folds relatively. After the transfection of RUNX2 overexpressed plasmids into the 0404 cell line, the mRNA level of RUNX2 increased approximately 530.11(±24.87), 1117.96(±77.68), 2835.09(±45.22) and 4781.51(±79.37) folds respectively, and the protein level was upregulated about 4.12(±1.15), 16.73(±1.63), 21.53(±2.41) and 23.39(±0.85) folds respectively. The proliferation of 0404 cells was inhibited by 2.13(±1.02)% of 1.6 ng/µl group and 3.03(±1.76)% of 2.4 ng/µl group. And the migration was inhibited about 45.56(±6.13)%, 50.79(±5.27)%, 63.15(±8.62)% and 93.90(±3.65)% respectively. The invasion was decreased about 14.49(±5.4)%, 37.02(±6.52)%, 42.24(±2.59)% and 48.97(±10.61)% respectively. Meanwhile, FITC Annexin V/PI apoptosis assay demonstrated that RUNX2 plasmids could promote apoptosis rate around 4.15(±0.27)%, 5.07(±0.27)%, 7.61(±0.45)% and 11.32(±1.02)% respectively, and CCK8 proved these plasmids could weaken cellular viability in a concentration-dependent manner with the time passing. CONCLUSIONS: RUNX2 is highly expressed in giant cell tumors of bone. The RUNX2 overexpressed plasmids we constructed could be successfully transfected into 0404 cell line. Far more importantly, the exogenous RUNX2 can seriously block the biological functions of 0404 cell line in a concentration-dependent manner, including proliferation, translocation, invasion, cellular viability, and apoptosis. Meanwhile, the mechanism was hypothesized and discussed in the article.

Mechanical and Biological Properties of a Biodegradable Mg-Zn-Ca Porous Alloy.

OBJECTIVES: As promising alternative to current metallic biomaterials, the porous Mg scaffold with a 3-D open-pore framework has drawn much attention in recent years due to its suitable biodegradation, biocompatibility, and mechanical properties for human bones. This experiment's aim is to study the mechanical properties, biosafety, and osteogenesis of porous Mg-Zn alloy. METHODS: A porous Mg-2Zn-0.3Ca (wt%) alloy was successfully prepared by infiltration casting, and the size of NaCl particles was detected by a laser particle size analyzer. The microstructure of the Mg-2Zn-0.3Ca alloy was characterized by the stereoscopic microscope and Sirion Field emission scanning electron microscope. X-ray computerized tomography scanning (x-CT) was used to create the 3-D image. The degradation rate was measured using the mass loss method and the pH values were determined together. The engineering stress-strain curve, compressive modulus, and yield strength were tested next. The bone marrow stromal cells (BMSC) were cultured in vitro. The CCK-8 method was used to detect the proliferation of the BMSC. Alkaline phosphatase (ALP) and alizarin red staining were used to reflect the differentiation effects. After co-culturing, cell growth on the material's surface was observed by scanning electron microscope (SEM). The cell adhesion was tested by confocal microscopy. RESULTS: The obtained results showed that by using near-spherical NaCl filling particles, the porous Mg alloy formed complete open-cell foam with a very uniform size of pores in the range of 500-600 µm. Benefitting from the small size and uniform distribution of pores, the present porous alloy exhibited a very high porosity, up to 80%, and compressive yield strength up to 6.5 MPa. The degradation test showed that both the pH and the mass loss rate had similar change tendency, with a rapid rise in the early stage for 1-2 day's immersion and subsequently remaining smooth after 3 days. In vitro cytocompatibility trials demonstrated that in comparison with Ti, the porous alloy accelerated proliferation in 1, 3, 5, and 7 days (P < 0.001), and the osteogenic differentiation test showed that the ALP activity in the experimental group was significantly higher (P = 0.017) and has more osteogenesis nodules. Cell adhesion testing showed good osteoconductivity by more BMSC adhesion around the holes. The confocal microscopy results showed that cells in porous Mg-based alloy had better cytoskeletal morphology and were larger in number than in titanium. CONCLUSIONS: These results indicated that this porous Mg-based alloy fabricated by infiltration casting shows great mechanical properties and biocompatibilities, and it has potential as an ideal bone tissue engineering scaffold material for bone regeneration.

[Impact of sacral nerve root resection on the erectile and ejaculatory function of the sacral tumor patient].

OBJECTIVE: To evaluate the erectile and ejaculatory function of sacral tumor patients after sacral nerve root resection and investigate the relationship of erectile and ejaculatory dysfunction (EED) with the level of sacral nerve injury. METHODS: This retrospective study included 47 male patients aged 16 to 63 (32.6 +/- 6.8) years treated by sacral tumor resection between January 2008 and August 2013. According to the levels of the sacral nerve roots spared in surgery, the patients were divided into four groups: bilateral S1-S3 (n=16), unilateral S1-S3 (n=21), unilateral S1-S2 (n=6), and unilateral S1 (n=4). The patients were followed up for 12 to 41 (27.2 +/- 10.9) months by questionnaire investigation, clinic review, and telephone calls about their erectile and ejaculatory function at 3, 6 and 12 months after surgery and in August 2013. RESULTS: In the bilateral S1-S3 group, the incidence rates of EED were 31.25% (5/16), 25% (4/16), and 12.5% (2/16) at 3, 6, and 12 months respectively after surgery, with recovery of erectile and ejaculatory function in August 2013. The incidence rates of EED in the unilateral S1-S3 group were 85.71% (18/21), 71.43% (15/21), 52.38% (11/21), and 42.86% (9/21) at 3, 6 and 12 months and in August 2013, respectively; those in the unilateral S1-S2 group were 100% (6/6), 83.33% (5/6), 83.33% (5/6), and 66.67% (4/6) at the four time points; and those in the unilateral S1 group were all 100% (4/4). No statistically significant differences were found in the incidence rate of EED among the patients of different ages or tumor types (P > 0.05). CONCLUSION: The incidence of postoperative EED in male patients treated by sacral tumor resection is closely related to the mode of operation. Sparing the S3 nerve root at least unilaterally in sacral tumor resection is essential for protecting the erectile and ejaculatory function of the patient.

Research progress on the livin gene and osteosarcomas.

Osteosarcoma is a common malignant tumor of bone, but mechanisms underlying its development are still unclear. At present, it is believed that the inhibition of normal apoptotic mechanisms is one of the reasons for the development of tumors, so specific stimulation of tumor cell apoptosis can be considered as an important therapeutic method. Livin, as a member of the newly discovered inhibitor of apoptosis proteins (IAPs) family, has specifically high expression in tumor tissues and can inhibit tumor cell apoptosis through multiple ways, which can become a new target for malignant tumor treatment (including osteosarcoma) and might of great significance in the clinical diagnosis of tumors and the screening of anti-tumor agents and carcinoma treatment.

Anti-fatigue effects of proteins isolated from Panax quinquefolium.

ETHNOPHARMACOLOGICAL RELEVANCE: American ginseng (Panax quinquefolium) is an obligate shade perennial plant that belongs to Araliaceae ginseng species, and is native to eastern USA and Canada. Ginseng proteins are reported to have several pharmaceutical properties. However, such properties of American ginseng proteins (AGP) have seldom been reported. Also, anti-fatigue properties of AGP have not been studied. Therefore, we examined the anti-fatigue effects of AGP in mice. MATERIALS AND METHODS: The molecular weight and protein contents of AGP were determined by SDS-PAGE, while the amino acid composition was analyzed by HPLC. The mice were divided into four groups. The control group was administered distilled water by gavage every day for 28 days. The other groups, designated as AGP treatment groups, were administered 125, 250 and 500 mg/kg of body weight, respectively of AGP by gavage every day for 28 days. Anti-fatigue activity was estimated using forced swimming test, and biochemical indices were determined using available kits. RESULTS: The subunit molecular weight of AGP ranged from 8-66 kD and the protein content measured by Bradford assay was 1.86 mg/mL. The forced swimming time of low, intermediate and high groups were found to be longer as compared to the control group. AGP significantly decreased blood lactate (BLA) and serum urea nitrogen (SUN) levels, and increased hepatic glycogen (GLU) level. Additionally, AGP lowered malondialdehyde (MDA) content and increased the levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD). CONCLUSION: AGP shows anti-fatigue activity in mice, as measured by the physiological indices for fatigue.