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Background: Hereditary sensory and autonomic neuropathy (HSAN) type II with WNK1/HSN2 gene mutation is a rare disease characterized by early-onset demyelination sensory loss and skin ulceration. To the best of our knowledge, no cases of an autonomic disorder have been reported clearly in a patient with WNK/HSN2 gene mutation and only one case of a Japanese patient with the WNK/HSN2 gene mutation of HSAN type II was previously reported. Case presentation: Here we describe a 54-year-old woman who had an early childhood onset of insensitivity to pain; superficial, vibration, and proprioception sensation disturbances; and several symptoms of autonomic failure (e.g., orthostatic hypotension, fluctuation in body temperature, and lack of urge to defecate). Genetic analyses revealed compound homozygous mutations in the WNK1/HSN2 gene (c.3237_3238insT; p.Asp1080fsX1). The patient demonstrated sensory loss in the "stocking and glove distribution" but could perceive visceral pain, such as menstrual or gastroenteritis pain. She experienced frequent fainting episodes. She had undergone exenteration of the left metatarsal because of metatarsal osteomyelitis at 18 years. Sural nerve biopsy revealed a severe loss of myelinated and unmyelinated nerves. She complained of severe pain in multiple joints, even on having pain impairment. Although non-steroidal anti-inflammatory drugs are generally more effective than acetaminophen for arthritis, in our case, they were ineffective and acetaminophen (2400 mg/day) adequately controlled her pain and improved quality of life. Over 3 months, the numerical rating scale, pain interference scale of the Brief Pain Inventory, and the Pain Catastrophizing Scale decreased from 6/10 to 3/10, from 52/70 to 20/70, and from 22/52 to 3/52 points, respectively. Conclusions: This is the second reported case of a Japanese patient with WNK/HSN2 gene mutation of HSAN type II and the first reported case of an autonomic disorder in a patient with the WNK/HSN2 gene mutation. Acetaminophen adequately controlled arthropathy related pain in a patient with congenital impairment of pain sensation. [ABSTRACT FROM AUTHOR]

Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT. We also found that all four patients had characteristic neurological features of peripheral neuropathy and ataxia with cerebellar atrophy, and some patients showed leukoencephalopathy or spinal cord atrophy on MRI scans. Validated mutations were located at highly conserved residues among different species and segregated with the disease in each family. Nerve conduction studies showed axonal sensorimotor neuropathy. Sural nerve biopsies showed chronic axonal degeneration with a marked loss of large and medium myelinated fibres. An immunohistochemical assay with an anti-COA7 antibody in the sural nerve from the control patient showed the positive expression of COA7 in the cytoplasm of Schwann cells. We also observed mildly elevated serum creatine kinase levels in all patients and the presence of a few ragged-red fibres and some cytochrome c oxidase-negative fibres in a muscle biopsy obtained from one patient, which was suggestive of subclinical mitochondrial myopathy. Mitochondrial respiratory chain enzyme assay in skin fibroblasts from the three patients showed a definitive decrease in complex I or complex IV. Immunocytochemical analysis of subcellular localization in HeLa cells indicated that mutant COA7 proteins as well as wild-type COA7 were localized in mitochondria, which suggests that mutant COA7 does not affect the mitochondrial recruitment and may affect the stability or localization of COA7 interaction partners in the mitochondria. In addition, Drosophila COA7 (dCOA7) knockdown models showed rough eye phenotype, reduced lifespan, impaired locomotive ability and shortened synaptic branches of motor neurons. Our results suggest that loss-of-function COA7 mutation is responsible for the phenotype of the presented patients, and this new entity of disease would be referred to as spinocerebellar ataxia with axonal neuropathy type 3. [ABSTRACT FROM AUTHOR]

Objective: To analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from pediatric patients in a Chinese hospital. Methods: From October 2011 to May 2014, we collected 284 isolates (including 217 noninvasive and 67 invasive strains). We tested the antimicrobial susceptibility of these specimens using the Epsilomer test and disk diffusion method, and the expression of macrolide resistant genes ermB and mefA by polymerase chain reaction. Results: The most common serotype for 217 noninvasive strains was 19F (31.3%). The coverage rates of the 7-, 10-, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) were 53.9%, 53.9%, and 86.2%, respectively. For 67 invasive strains, the most common serotype was 23F (22.4%). The coverage rates of PCV7, PCV10, and PCV13 for invasive strains were 77.6%, 82.1%, and 91.0%, respectively. The susceptibility of strains isolated from nonmeningitis specimens to penicillin (PEN) was 97.2%. The rate of multidrug resistance in 284 isolates was 98.7%. All of these isolates were resistant to erythromycin (ERY) and had the ermB gene; 38.6% of those isolates had the mefA gene. Conclusions: Compared with PCV7 and PCV10, the coverage rate of PCV13 was relatively higher for the S. pneumoniae isolates from pediatric patients. This finding suggests that PCV13 probably plays the strongest role in prevention of pneumococcal diseases and control of multidrug resistance. Because pneumococci were sensitive to PEN, this drug is still the preferred choice for clinical treatment of pediatric pneumococcal diseases. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical significance of 3-phosphoinositide-dependent protein kinase-1 (PDK1) expression in hepatocellular carcinoma (HCC) and its association with clinicopathologic features and prognosis in HCC patients. Materials and methods: A total of 128 HCC patients who received radical resection were enrolled from Wenling Maternal and Child Health Care Hospital between May 2005 and December 2008, and tumor and adjacent tissue samples were collected. Expression of PDK1 was detected by immunohistochemistry method. Correlation of PDK1 expression with clinicopathological features and prognosis was determined by Spearman's correlation analysis. Impact of expression of PDK1 on overall survival and recurrence was determined by Kaplan-Meier analysis. Results: Immunohistochemistry results showed that PDK1 expression in HCC tissues was significantly higher than that in the corresponding adjacent cancer tissues. Univariate analysis showed that PDK1 messenger RNA expression can predict time to recurrence with diagnostic significance (P=0.001). Univariate analysis showed that alpha-fetoprotein level, tumor number, tumor encapsulation, microvascular invasion, and tumor-node-metastasis stage were also unfavorable prognostic variables for recurrence (P<0.05). Kaplan-Meier analysis showed that overexpression of PDK1 correlates with significantly shorter postoperative overall survival and higher recurrence rates (hazard ratio =2.68; 95% confidence interval: 2.46-4.42, P=0.001) in HCC patients after curative resection. Conclusion: Our study indicated that PDK1 may serve as a candidate pro-oncogene and a potential prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

To investigate the effects of signal transducer and activator of transcription 3 (STAT3) combined with cisplatin (CDDP) on the growth of human Wilms tumour (WT) SK-NEP-1 cell subcutaneous xenografts in nude mice and the possible mechanisms. Human WT SK-NEP-1 cells were subcutaneously transplanted to establish the BALB/c nude mice xenograft model. Mice were randomly divided into five groups: blank control group, adenovirus control group (NC group), STAT3 group, CDDP group and STAT3 plus CDDP group (combination group). Tumour volume and tumour weight were observed during the therapeutic process. The expression levels of STAT3, glucose regulatory protein 78 (GRP78) and BCL2-associated X protein (BAX) were evaluated by immunohistochemical analysis. Compared with the STAT3 group or CDDP group, the tumour weight and volume was significantly reduced in the combination group (P<0.05). No statistical significance was found in NC group compared with the blank control group (P>0.05). Immunohistochemical analysis showed that STAT3, GRP78 and BAX protein levels in the combination group were significantly higher than those in STAT3 group and CDDP group (P<0.05). Exogenous STAT3 and CDDP may synergistically inhibit the xenograft tumour growth through up-regulation of BAX protein via GRP78. [ABSTRACT FROM AUTHOR]