Gorham-Stout disease (GSD) is a rare condition characterized by intraosseous proliferation of endothelial-lined vessels and progressive osteolysis. The precise etiology and pathophysiology of the disease remain poorly understood. Current therapeutic options for GSD include chemotherapy, radiotherapy, and surgical resection, but the surgical treatment of GSD is difficult, especially in the spinal lesion. The indication of wide-margined resection was limited because of anatomical features. Herein, we report a case of GSD of the cervical spine in which the lesions were successfully stabilized with combined conservative and surgical treatments. A 15-year-old male patient was admitted because of severe neck pain. The patient presented no neurological deficiency. However, the radiological findings revealed osteolytic lesions on the laminae and vertebrae between C1 to C5. An open biopsy confirmed an irregular, thin-walled vessel formation in the bone trabeculae, which was diagnosed as GSD. Conservative treatment was initiated with chemotherapy and radiotherapy. After one and a half year, the osteolytic condition had regressed. Spinal fusion surgery was then performed from C2 to C5 to prevent for progression of the cervical kyphotic changes, and spinal fusion was confirmed 7 months after the surgery. The patient showed no recurrence of GSD in the 5-year follow-up period after surgery. We were able to provide successful treatment by giving priority to the combined conservative treatments. If a patient has no severe deformity or progressive neurologic deficits, it might be better to prioritize conservative treatments and to perform the surgery after the osteolytic changes have stopped.

Chronic hepatitis B virus (HBV) infection is associated with lower prevalence of hyperlipidemia (HLP). However, occult HBV infection (OBI) in HLP patients has not yet been explored. OBI is defined as the presence of detectable HBV DNA in serum or liver tissue but undetectable HBV surface antigen in serum. In this study, 1,036 HLP patients and 1,134 replacement blood donor controls were recruited. Among them, 252 HLP patients and 255 blood donors with antibody to HBV core positive were selected and analyzed. HBV DNA was confirmed by nucleic acid testing assays, and nucleotide mutations were analyzed. OBI was detected in 9.5% (24/252) of HLP patients and 2.4% (6/255) of blood donors, respectively (P < 0.001). In HLP population, 41.7% of OBI and 13.6% of non-OBI carriers were associated with daily alcohol consuming > 30 g/day (P < 0.01), while in control population those rates were not statistically different between OBI and non-OBI carriers (P > 0.05). Viral load of OBI in HLP patients was higher than that of OBI in blood donors (P < 0.05), which was a positive correlation between total cholesterol and HBV viral load levels (r = 0.474 P = 0.019). HBV vaccination rate was found significantly lower in OBI HLP patients than that in non-OBI HLP patients (P < 0.01). Importantly, mutations were found in basic core promoter region of HBV among OBI HLP patients. In conclusion, the frequency of OBI is significantly higher in HLP patients, especially those patients with heavy daily alcohol consumption.

The clinical significance of detecting early atherosclerosis is now widely recognized. Measurement methods available at present are usually not suitable for use in primary care where rapid screening for a large population is needed. The Arterial Velocity-pulse Index (AVI) and Arterial Pressure-volume Index (API) are new noninvasive arterial stiffness indices that can be rapidly measured using an oscillometric device. The purpose of this study was to determine whether high AVI and API values are predictive of early atherosclerosis prior to the onset of obstructive coronary artery disease (CAD). A total of 183 patients were enrolled and allocated to the CAD group (n = 109), early atherosclerosis (AS) group (n = 34) or an apparently healthy (non-AS) group (n = 40) based on the results of angiographic examinations. Measurements for arterial blood pressure, AVI, API and brachial-ankle pulse wave velocity (baPWV) were collected. Statistical analyses revealed that AVIs were significantly lower in the non-AS group than in the AS group and the CAD group. The inter-group differences in API were not statistically significant among the 3 patient groups. As a reference, baPWV was found to be statistically higher in the CAD group than in the non-AS group, whereas there was no significant difference between the CAD group and the AS group, or between the AS group and the non-AS group. The AVI and API were both significantly correlated with baPWV. This study demonstrated that AVI was more sensitive than baPWV and API in indicating early atherosclerosis, although elevated AVI and baPWV were both predictive of CAD.

IgA nephropathy (IgAN) is the most common cause of primary renal diseases worldwide, and the early secreted antigenic target of 6 (ESAT-6) which was secreted by Mycobacterium tuberculosis (MTB) may be involved in the development and progression of IgAN. This study aimed to investigate the role of ESAT-6 for early diagnosis of IgAN caused by MTB infection. From 2011 to 2014, 21 patients with renal tuberculosis (RTB), 25 with IgAN, and 46 with IgAN infected with MTB (IgAN/MTB) were enrolled. Serum levels of antibodies against Mycobacterium tuberculosis antigen 85A (Ag85A) were measured by ELISA. Urine culture and phage amplified biologically assay were performed to detect MTB. HE staining was used to observe the morphological changes in kidney tissues. Immunohistochemistry was applied to detect the expression of ESAT-6. Immunofluorescence staining was conducted to detect IgA1. Positive rates of serum anti-Ag85A antibody and urine culture for MTB were higher in the RTB and IgAN/MTB groups than those in the IgAN group. The positive rates of plaques were also higher in RTB and IgAN/MTB groups than the positive rate in the IgAN group. By contrast, the positive rate of ESAT-6 was lower in the IgAN group than that in the RTB group or the IgAN/MTB group, whereas the expression levels of IgA1 were higher in the IgAN and IgAN/MTB groups, compared with the RTB group. Our findings suggest that ESAT-6 and IgA1 may be helpful for early diagnosis of IgAN caused by MTB infection.

The prognosis of myasthenia gravis (MG) in association with invasive or metastatic thymoma is usually worse, and therapeutic options are quite limited. Here, we retrospectively reported the therapeutic effect of docetaxel plus cisplatin (docetaxel/cisplatin) chemotherapy in 7 MG patients with metastatic thymoma. Previously, all patients underwent thymectomy at the first onset of thymoma. After the metastasis of thymoma, none of the patients received thymectomy due to unresectable conditions after surgeon’s evaluation for great risk of myasthenic crisis (n = 5) or patients’ refusal (n = 2). All patients received docetaxel (75 mg/m²) and cisplatin (70 mg/m²) on day 1 (d1) every 21 days, with the cycle ranging from 1 to 4. After docetaxel/cisplatin chemotherapy, one patient achieved partial response, and 6 with stable disease of the tumors. The clinical symptoms of MG were alleviated in all patients, 2 with complete remission and the other 5 with marked improvement. Myelosuppression was the major adverse event, occurring in 2 patients (grade II and IV). MG relapse occurred in one patient during the follow-up. Our study presented a series of MG patients with metastatic thymoma who underwent docetaxel/cisplatin chemotherapy. Besides the improved/stabilized thymoma, markedly improvement of MG with the tolerable adverse events was achieved. Docetaxel/cisplatin chemotherapy appears to be an effective treatment for selected patients with MG in association with unresectable metastatic thymoma. Further follow-up of these patients and additional subjects will be needed to determine whether the therapeutic benefits are durable.

Pancreatic ductal adenocarcinoma (PDAC) presents as an aggressive malignancy caused by environmental and genetic factors. In order to identify causal genes for PDAC, we performed whole exome sequencing (WES) to detect gene mutations in seven pairs of PDAC tissue and adjacent non-tumor tissue samples. Finally, we found a new nonsynonymous single nucleotide variant (nsSNV) in solute carrier 24 family member 2 (SLC24A2) gene resulting in the substitution of native glutamic acid (E) into aspartic acid (D) at position of 287 amino acid (E287D) in SLC24A2 protein, and confirmed this variant by Sanger gene sequencing. SLC24A2 is a potassium-dependent sodium-calcium exchanger and can transport metal ion across cell membrane. Multiple in silico variants’ effects analyses methods including SIFT, PolyPhen, PROVEAN, and PANTHER demonstrated this variant had probably damaging effects, which was consistent with the results obtained from Mutation Taster software analysis with a probability of 0.99999997 to be “disease causing.” The three dimension (3D) structure analysis results suggested this variant had little effects on the solubility and hydrophobicity of the protein; but it could decrease the protein stability by increasing the total protein structure energy (−8874.33 kJ/mol for the mutant and −8963.54 kJ/mol for the native) and by causing the mutant protein decreasing three stabilizing residues. Less stability of the mutant 287D protein than the native E287 protein was also supported by I-Mutant and Western-blotting analysis results. Overall, a new mutation in SLC24A2 gene was identified to decrease the stability of SLC24A2, which may have potential clinical usages.

Coronary artery disease (CAD) is a multifactorial disease with a genetic component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received increasing attention as a sensitive biomarker of atherosclerosis and CAD. To explore the potential association between PEDF single nucleotide polymorphisms (SNPs) and CAD, we performed this case-control study of consecutive elderly Chinese Han male patients (n = 416) and age-matched male controls (n = 528) without a history of CAD or electrocardiographic signs of CAD. The enrolled CAD patients (age ≥ 60 years) are not biologically related. A tag approach was used to examine 100% of common variations in the PEDF gene (r² ≥ 0.8, minor allele frequency > 0.1). PEDF tag SNPs (tSNPs) were selected using the HapMap Data-CHB which describes the common patterns of human DNA sequence variation and Tagger program. SNPs were genotyped using ligase detection reaction (LDR). Seven tSNPs (rs8075977, rs11658342, rs1136287, rs12603825, rs12453107, rs6828 and rs11078634) were selected. Among them, only one SNP, rs8075977 (C/T) located in the 5'-flanking region, showed the significant effect on the susceptibility to CAD. The frequency of its T allele was significantly higher in the controls (52.7%) than that in the CAD group (46.2%) (adjusted OR = 0.88, 95% CI: 0.80-0.96; P = 0.005). In conclusion, the T allele of rs8075977 in the 5'-flanking region of the PEDF gene may be protective for CAD. Conversely, the C allele at this variation site is associated with CAD in elderly Chinese Han men.

Some studies have reported that recumbent position may have advantages in patients with heart disease and in pregnancy. However, it remains controversial whether recumbent position affects autonomic nervous system activity and hemodynamics in healthy adults. The aim of this study was to evaluate alterations in heart rate variability (HRV) and hemodynamics in the supine, left recumbent and right recumbent positions in healthy young adults. A total of 80 participants aged 22.8 ± 3.1 years were enrolled in this observational study. Fifty-eight volunteers (29 men and 29 women) maintained the supine position followed by the left and right recumbent positions, while electrocardiographic data were recorded for spectral analysis of HRV to assess cardiac vagal nerve and sympathetic nerve activities. The heart rate (HR) was significantly lower in the left recumbent position than in the other positions. There were no statistically significant differences in HRV among the three positions. Considering the possibility that the echographic procedure affects autonomic nervous system (ANS) activity, the other 22 participants (11 men and 11 women) underwent an echographic evaluation of hemodynamics in the heart and inferior vena cava (IVC) across the three positions. Although a low HR was also observed, there were no statistically significant differences in the IVC or the heart blood volume between the supine and the left recumbent positions. A postural change to the left recumbent position does not affect the cardiac blood circulation or ANS activity, though it does decrease HR in healthy young adults. This finding indicates that the lower HR in the left recumbent position is not attributable to the ANS activity.

Bisphosphonates (BPs) increase bone mineral density (BMD) through the inhibition of osteoclast activity. Among BPs, ibandronate (IBN) is a strong inhibitor of bone resorption. However, the effects of a vitamin D analogue, alfacalcidol (ALF), on IBN treatment for osteoporosis is unknown. Fifty-three treatment-naïve post-menopausal women with primary osteoporosis were recruited and divided into IBN-treatment group (IBN group) and IBN with ALF group (IBN/ALF group). IBN (1.0 mg) was intravenously injected once a month, with or without oral ALF (1.0 μg/day). Ultimately, 19 subjects in IBN group and 26 in IBN/ALF group were analyzed. Bone turnover markers were examined at 4, 6, 12, and 18 months, and BMD was measured at 6, 12, and 18 months. Compared with pre-treatment, bone turnover markers significantly decreased in both groups after 4 months. The levels of serum N-terminal propeptide of type-1 procollagen and tartrate-resistant acid phosphatase-5b, and urinary N-terminal telopeptide of type-I collagen were significantly lower in IBN/ALF group than those in IBN group at 12 months. Lumbar 1-4 (L)-BMD significantly increased from 6 months in IBN/ALF group and at 18 months in IBN group. L-BMD was significantly higher in IBN/ALF group (6.6% increase) than in IBN group (3.4%) at 18 months. Total hip (H)-BMD significantly increased from 6 months in IBN/ALF group and tended to improve in IBN group. H-BMD was significantly higher in IBN/ALF group (4.8%) than in IBN group (3.2%) at 18 months. In conclusion, treatment with ALF in combination with IBN improves BMD in post-menopausal women with osteoporosis.