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Objective: Operative hysteroscopy is a common gynecologic procedure, but it carries the risk of complications. Spontaneous small intestine perforation is rare and fatal, especially in young adults. We present a spontaneous small intestine perforation after operative hysteroscopy with mimicking sign of uterine perforation after operation hysteroscopy. Case report: A 30-year-old nulligravida woman underwent Truclear® hysteroscopic polypectomy in the morning in LMD. She suffered from upper abdominal pain in the afternoon. Subsequently, progressive abdominal distention and imminent shock occurred the next morning. Initially, it was supposed to be a case of uterine rupture with internal bleeding. She was transferred to the emergency department of our hospital. Complete biochemistry data and abdominal CT were performed. The CT revealed pneumoperitoneum and ascites. Emergent laparoscopy was arranged. The abdominal cavity was full of intestinal fluid and the myomatous uterus was intact. The surgeon performed a laparotomy, two sites of spontaneous perforation of the small intestine were detected. The patient underwent laparotomic segmental resection and anastomosis and was discharged 14 days after surgery without incident. Conclusions: The risk of uterine perforation during hysteroscopy is up to 1.6%. The use of non-thermal intrauterine morcellator device (Truclear®) has been shown to significantly reduce the risk of perforation and thermal injury. As this case highlights, we suspected the possibility of uterine perforation immediately after hysteroscopic surgery. However, it happened to be rare spontaneous perforation of small bowel. The patient recovered well after timely transfer and management. Hysteroscopy is a very common procedure in gynecologic clinics, but even relatively safe intrauterine morcellator devices carry risk of complications. As a healthcare provider, we should beware of any comorbidity, for sometimes it would be catastrophic.

Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes.

Abstract Neuroendocrine neoplasm (NEN) is a common gastrointestinal (GI) tract tumor divided into the neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) according to mitosis and Ki-67 index. However, the objective discordance between interobserver may cause unsuitable diagnosis and misleading treatment. Nowadays, aberrant glycosylation of glycoconjugates inducing further populations of elongated complex oligosaccharide covalent attached to glycoconjugates anchored in the cell membrane by neo-synthesis of cancer-associated alteration of carbohydrate determinants were observed during cancer development. This study aimed to demonstrate the wax physisorption kinetics coupled with Fourier transform infrared (WPK-FTIR) imaging between NET and NEC in the rectum, colon, and stomach by utilizing two wax reagents (beeswax and paraplast) as glycan adsorbents for physical binding glycans of glycoconjugates based on dipole-induced dipole interaction. Results showed greater physisorption with beeswax than that of paraplast, suggesting highly populated elongated glycans of glycoconjugates adhering onto the tumor surfaces of NETs than that of adjacent benign mucosa in the rectum and colon. Besides, the WPK results of gastric NEN tissue sections showed a higher infrared absorbance ratio of beeswax-remnant to paraplast-remnant remains onto the tissue sections referring to a higher population of elongated glycans in gastric NET as compared with that of gastric NEC. Based on our findings, different anatomical locations could share similar phenomena with minor variance. In conclusion, WPK-FTIR imaging may have the potential to be employed as an alternative diagnostic method in GI NENs in the future.

Abstract Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge on how the virus remodels the metabolic and immune response toward hepatic pathologic environment is limited. The transcriptomic and multiple evidences reveal that the HCV core protein–intestine‐specific homeobox (ISX) axis promotes a spectrum of metabolic, fibrogenic, and immune modulators (e.g., kynurenine, PD‐L1, and B7‐2), regulating HCV‐infection relevant pathogenic phenotype in vitro and in vivo. In a transgenic mice model, the HCV core protein–ISX axis enhance metabolic disturbance (particularly lipid and glucose metabolism) and immune suppression, and finally, chronic liver fibrosis in a high‐fat diet (HFD)‐induced disease model. Mechanistically, cells with HCV JFH‐1 replicons upregulate ISX and, consequently, the expressions of metabolic, fibrosis progenitor, and immune modulators via core protein‐induced nuclear factor‐κB signaling. Conversely, cells with specific ISX shRNAi inhibit HCV core protein‐induced metabolic disturbance and immune suppression. Clinically, the HCV core level is significantly correlated with ISX, IDOs, PD‐L1, and B7‐2 levels in HCC patients with HCV infection. Therefore, it highlights the significance of HCV core protein–ISX axis as an important mechanism in the development of HCV‐induced chronic liver disease and can be a specific therapeutic target clinically.

Chronic inflammation and cancer stem cells are known risk factors for tumorigenesis. The aetiology of hepatocellular carcinoma (HCC) involves a multistep pathological process that is characterised by chronic inflammation and hepatocyte damage, but the correlation between HCC, inflammation and cancer stem cells remains unclear. In this study, we examined the role of hepatic progenitor cells in a mouse model of chemical-induced hepatocarcinogenesis to elucidate the relationship between inflammation, malignant transformation and cancer stem cells. We used diethylnitrosamine (DEN) to induce liver tumour and scored for H&E and reticulin staining. We also scored for immunohistochemistry staining for OV-6 expression and analysed the statistical correlation between them. DEN progressively induced inflammation at week 7 (40%, 2/5); week 27 (75%, 6/8); week 33 (62.5%, 5/8); and week 50 (100%, 12/12). DEN progressively induced malignant transformation at week 7 (0%, 0/5); week 27 (87.5%, 7/8); week 33 (100%, 8/8); and week 50 (100%, 12/12). The obtained data showed that DEN progressively induced high-levels of OV-6 expression at week 7 (20%, 1/5); week 27 (37.5%, 3/8); week 33 (50%, 4/8); and week 50 (100%, 12/12). DEN-induced inflammation, malignant transformation and high-level OV-6 expression in hamster liver, as shown above, as well as applying Spearman’s correlation to the data showed that the expression of OV-6 was significantly correlated to inflammation (p = 0.001) and malignant transformation (p < 0.001). There was a significant correlation between the number of cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis in the hamster.

Background: CXCL13 may act as a mediator of tumor-associated macrophage immunity during malignant progression.Objective: The present study clarifies the clinicopathological significances of CXCL13 and its corresponding trend with M2 macrophage in human astrocytoma.Methods: The predictive potential of CXCL13 was performed using 695 glioma samples derived from TCGA lower-grade glioma and glioblastoma (GBMLGG) dataset. CXCL13 and M2 biomarker CD163 were observed by immunohistochemistry in 112 astrocytoma tissues.Results: An in-depth analysis showed that CXCL13 expression was related to the poor prognosis of glioma patients (p = 0.0002) derive from TCGA analysis. High level of CXCL13 was detected in 43 (38.39%) astrocytoma and CXCL13/CD163 coexpression was expressed in 33 (29.46%) cases. The immunoreactivities of CXCL13 and CXCL13/CD163 were found in the malignant lesions, which were both significantly associated with grade, patient survival, and IDH1 mutation. Single CXCL13 and CXCL13/CD163 coexpression predicted poor overall survival in astrocytoma (p = 0.0039 and p = 0.0002, respectively). Multivariate Cox regression analyses manifested CXCL13/CD163 phenotype was a significant independent prognostic indicator of patient outcome in astrocytoma (CXCL13, p = 0.0642; CXCL13/CD163, p = 0.0368).Conclusion: CXCL13 overexpression is strongly linked to CD163+ M2 infiltration in malignant astrocytoma. CXCL13/CD163 coexpression would imply M2c-related aggressive characteristics existing in astrocytoma progression could also provide predictive trends of patient outcomes.

Abstract Background Total mesorectal excision (TME) with or without neoadjuvant concurrent chemoradiotherapy (CCRT) is the treatment for rectal cancer (RC). Recently, the use of conventional laparoscopic surgery (LS) or robotic-assisted surgery (RS) has been on a steady increase cases. However, various oncological outcomes from different surgical approaches are still under investigation. Methods This is a retrospective observational study comprising 300 consecutive RC patients who underwent various techniques of TME (RS, n = 88; LS, n = 37; Open surgery, n = 175) at a single center of real world data to compare the pathological and oncological outcomes, with a median follow-up of 48 months. Results Upon multivariate analysis, histologic grade (P = 0.016), and stage (P

Muscle loss and weakness after a burn injury are typically the consequences of neuronal dysregulation and metabolic change. Hypermetabolism has been noted to cause muscle atrophy. However, the mechanism underlying the development of burn-induced motor neuropathy and its contribution to muscle atrophy warrant elucidation. Current therapeutic interventions for burn-induced motor neuropathy demonstrate moderate efficacy and have side effects, which limit their usage. We previously used a third-degree burn injury rodent model and found that irisin—an exercise-induced myokine—exerts a protective effect against burn injury-induced sensory and motor neuropathy by attenuating neuronal damage in the spinal cord. In the current study, spinal irisin gene delivery was noted to attenuate burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation. Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues and thereby modulates the Akt/mTOR pathway and metabolic derangement and prevents muscle atrophy.

Background: Neurological deficits following subarachnoid hemorrhage (SAH) are caused by early or delayed brain injuries. Our previous studies have demonstrated that hyperglycemia induces profound neuronal apoptosis of the cerebral cortex. Morphologically, we found that hyperglycemia exacerbated late vasospasm following SAH. Thus, our previous studies strongly suggest that post-SAH hyperglycemia is not only a response to primary insult, but also an aggravating factor for brain injuries. In addition, mitochondrial fusion and fission are vital to maintaining cellular functions. Current evidence also shows that the suppression of mitochondrial fission alleviates brain injuries after experimental SAH. Hence, this study aimed to determine the effects of mitochondrial dynamic modulation in hyperglycemia-related worse SAH neurological prognosis. Materials and methods: In vitro, we employed an enzyme-linked immunosorbent assay (ELISA) to detect the effect of mitochondrial division inhibitor-1 (Mdivi-1) on lipopolysaccharide (LPS)-induced BV-2 cells releasing inflammatory factors. In vivo, we produced hyperglycemic rats via intraperitoneal streptozotocin (STZ) injections. Hyperglycemia was confirmed using blood-glucose measurements (>300 mg/dL) 7 days after the STZ injection. The rodent model of SAH, in which fresh blood was instilled into the craniocervical junction, was used 7 days after STZ administration. We investigated the mechanism and effect of Mdivi-1, a selective inhibitor of dynamin-related protein (Drp1) to downregulate mitochondrial fission, on SAH-induced apoptosis in a hyperglycemic state, and evaluated the results in a dose–response manner. The rats were divided into the following five groups: (1) control, (2) SAH only, (3) Diabetes mellitus (DM) + SAH, (4) Mdivi-1 (0.24 mg/kg) + DM + SAH, and (5) Mdivi-1 (1.2 mg/kg) + DM + SAH. Results: In vitro, ELISA revealed that Mdivi-1 inhibited microglia from releasing inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. In vivo, neurological outcomes in the high-dose (1.2 mg/kg) Mdivi-1 treatment group were significantly reduced compared with the SAH and DM + SAH groups. Furthermore, immunofluorescence staining and ELISA revealed that a high dose of Mdivi-1 had attenuated inflammation and neuron cell apoptosis by inhibiting Hyperglycemia-aggravated activation, as well as microglia and astrocyte proliferation, following SAH. Conclusion: Mdivi-1, a Drp-1 inhibitor, attenuates cerebral vasospasm, poor neurological outcomes, inflammation, and neuron cell apoptosis following SAH + hyperglycemia.

Spinal venous malformations are vascular malformations of the central nervous system. Progressive or sudden neurological deficits can result in the deterioration of the quality of life, owing to the nature of the disease. Surgery is recommended after 2–6 weeks in patients with acute symptoms, to facilitate better surgical planning. Steroids are administered during the preoperative planning and rehabilitation period. However, the patient reported in this study developed a perforated peptic ulcer 1 week after surgery and died due to sepsis. Therefore, we questioned the optimum time for surgery, i.e., we considered whether early or delayed surgery would result in better patient outcomes.

Background: Pulmonary arterial hypertension (PAH) is a life-threatening and deteriorating disease with no promising therapy available currently due to its diversity and complexity. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism of PAH. Angiotensin-converting enzyme 2 (ACE2), which catalyzes the hydrolysis of the vasoconstrictor angiotensin (Ang) II into the vasodilator Ang-(1-7), has been shown to be an important regulator of blood pressure and cardiovascular diseases. Herein we hypothesized diminazene aceturate (DIZE), an ACE2 activator, could ameliorate the development of PAH and pulmonary vascular remodeling.Methods: A murine model of PAH was established using left pneumonectomy (PNx) on day 0 followed by injection of a single dose of the VEGF receptor-2 inhibitor SU5416 (25 mg/kg) subcutaneously on day 1. All hemodynamic and biochemical measurements were done at the end of the study on day 42. Animals were divided into 4 groups (n = 6–8/group): (1) sham-operated group, (2) vehicle-treatment group (SuPNx42), (3) early treatment group (SuPNx42/DIZE1−42) with DIZE at 15 mg/kg/day, subcutaneously from day 1 to day 42, and (4) late treatment group (SuPNx42/DIZE29−42) with DIZE from days 29–42.Results: In both the early and late treatment groups, DIZE significantly attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, and right ventricle brain natriuretic peptide (BNP), as well as reversed the overexpression of ACE while up-regulating the expression of Ang-(1-7) when compared with the vehicle-treatment group. In addition, the early treatment group also significantly decreased plasma BNP and increased the expression of eNOS.Conclusions: ACE2 activator has therapeutic potentials for preventing and attenuating the development of PAH in an animal model of left pneumonectomy combined with VEGF inhibition. Activation of ACE2 may thus be a useful therapeutic strategy for the treatment of human PAH.

Phytochemical investigation and chromatographic separation of extracts from one new actinobacteria strain Amycolatopsis taiwanensis that was isolated from soil of Yilan township, in the north of Taiwan, led to the isolation of nine new compounds, amycolataiwanensins A–I (1–9, resp.), and one new natural product, namely amycolataiwanensin J (10). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic-data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3, 5, 7 and 8 exhibited potent anti-NO production activity, with IC50 values of 17.52, 12.31, 17.81 and 13.32 μM, respectively, compared to that of quercetin, an iNOS inhibitor with an IC50 value of 35.94 μM. This is the first report on indole metabolite from the genus Amycolatopsis.

Phytochemical investigation and chromatographic separation of extracts from the actinobacteria strain Saccharomonospora piscinae that was isolated from dried fishpond sediment of Kouhu township, in the south of Taiwan, led to the isolation of three new compounds, saccharpiscinols A–C (1–3, respectively), and three new natural products, namely (2S)-5,7,3′,4′-tetrahydroxy-6,8-dimethylflavanone (4), methyl-4-hydroxy-2-methoxy-6-methylbenzoate (5), and (±)-7-acetyl-4,8-dihydroxy-6-methyl-1-tetralone (6). Compounds 4–6 were reported before as synthesized products, herein, they are reported from nature for the first time. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Saccharpiscinol A showed inhibitory activities against LPS-induced NO production.

Arsenic is a well-known toxic element and carcinogenic agent. The aim of this study was to investigate p63, E-cadherin, and β-catenin proteins in urothelial carcinoma (UC) in both arsenic contaminated areas [so-called blackfoot disease (BFD) area] and non-BFD areas. The expressions of p63, E-cadherin, and β-catenin proteins in 20 UC cases of blackfoot disease and 22 UC cases in non-BFD areas were detected using immunohistochemical methods. The results revealed a high p63 expression in 20 (47.6%) UC cases and high E-cadherin expression in six (14.3%) UC cases. Expressions of p63 and E-cadherin showed no significant correlations with clinicopathologic parameters. However, all 20 BFD cases and 12 of 22 (54.5%) non-BFD cases showed aberrant β-catenin expression. Ten out of 22 (45.5%) non-BFD cases also had normal membranous immunoreactivity. The β-catenin staining pattern significantly differed between cases in endemic and nonendemic areas of BFD (p=0.001). Tumor sites also significantly correlated with β-catenin expression (p=0.044). In addition, membranous localization of β-catenin was lower in UC from BFD-endemic areas compared with those from non-BFD endemic areas. In conclusion, it is suggested that relocalization of β-catenin from membrane to cytoplasm may be involved in the tumorigenesis of UC from BFD-endemic areas.

Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found that MMP-2 and MMP-9 expression in PSP, especially male PSP patients, was significantly correlated with recurrence. In the univariate and multivariate analyses, MMP-2 and MMP-9 were statistically significant risk factors for overall recurrence in PSP patients. Therefore, high expression levels of MMP-2 and MMP-9 in type II pneumocytes show a positive correlation with PSP recurrence risk. Further studies are needed to validate whether reduction of MMP-2 and MMP-9 expression may be a promising way for decreasing the risk of PSP recurrence in the future.

Transforming growth factor-β (TGF-β) is an important target for treating systemic sclerosis (SSc). However, our study revealed three levels of TGF-β1 expression in SSc patients, indicating that inhibiting TGF-β is not sufficient to treat SSc. A previous clinical trial also displayed disappointing results. Thus, our study attempted to search for a potential novel approach. Ingenuity Pathway Analysis (IPA) indicated that the SSc pathological pathways were closely associated with store-operated Ca2+ entry (SOCE)-regulated signals, and SOCE activity was found to be increased in SSc fibroblasts. Further treatment of SSc fibroblasts with SOCE inhibitors, 2APB, and associated calcium channel inhibitors SKF96365, and indomethacin, showed that the SOCE inhibitors selectively decreased fibrosis markers and altered the cell morphology. Consequently, SOCE inhibitors, especially 2APB and indomethacin, caused the dedifferentiation of SSc fibroblasts via cytoskeleton remodeling and altered collagen secretion and restored the cell mobility. We further explained SSc pathogenesis as fibroblast differentiation with SOCE. Treatment with exogenous factors, gelatin-1, FAM20A and human albumin, which were identified from the conditioned medium of SSc fibroblasts, was important for regulating the differentiation of fibroblasts with higher levels of SOCE and α-SMA. Conclusively, to treat SSc, blockage of the increased SOCE activity in SSc induces the dedifferentiation of SSc fibroblasts and simultaneously changes the extracellular matrix (ECM) structure to limit SSc pathogenesis.

BackgroundBehçet's disease (BD) is a recurrent, multisystemic, inflammatory disorder that mainly affects blood vessels. Because recurrent inflammation of blood vessels in the brain plays a crucial role in the development of ischemic stroke, we hypothesized that patients with BD might have an elevated risk of ischemic stroke. This potential association has been suggested in a few case reports, but not epidemiological studies. Hence, the present study aimed to examine the relation between BD and subsequent ischemic stroke in Taiwan using a nationwide, population-based database.MethodsTo establish a study cohort, the longitudinal data of 306 patients newly diagnosed with BD during 2000-2010 were extracted from the National Health Insurance Research Database, Taiwan. For comparison of ischemic stroke incidence, a control cohort of 1224 subjects without BD was established using a frequency-matched ratio of 1:4 for age, sex, and pre-existing comorbidities.ResultsDuring the 10-year follow-up, 13 (4.2%) patients with BD and 20 (1.6%) control subjects experienced ischemic stroke. Kaplan-Meier analysis revealed the higher prevalence of ischemic stroke in the BD group (log-rank test, p = 0.001). After adjusting for comorbidities and demographic characteristics, Cox regression analysis revealed that patients with BD had a 2.77-fold risk of ischemic stroke (95% confidence interval, 1.38-5.57) compared to control subjects.ConclusionsPatients with BD have an elevated risk of ischemic stroke. Hence, BD may affect the vascular system in the brain, resulting in a stroke event.

In Taiwan, the average prevalence of congenital heart disease (CHD) is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelin-1 (ET-1), and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n = 11), cyanotic CHD (n = 3), CHD associated with chromosomal abnormalities (n = 3), and complex CHD (n = 2). Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%), VEGF (89.5%), iNOS (78.9%), and ET-1 (84.2%) expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Patients with HCC usually have poor prognosis and high mortality. It has been shown that carcinoembryonic antigen-related cell adhesion molecule 1 (CD66a) regulates cell signaling, proliferation, and tumor growth. The aim of this study is to analyze the expression and possible role of CD66a in HCC. Immunohistochemical staining of CD66a was performed on 86 HCC cases, and microvessel density was evaluated by CD34 immunostaining. The results were further correlated with clinicopathological parameters. For 47 of 86 HCC cases, the CD66a expression showed diffuse membrane or cytoplasmic staining. The other 39 HCC cases revealed loss of CD66a expression. Loss of CD66a expression was statistically significantly associated with large tumor size (p=0.016), fatty change (p=0.039), patients with transcatheter arterial embolization (p=0.007), and high microvessel density (p=0.036). CD34 expression had no significant association with tumor size, virus infection, histological grade, and capsular invasion. The diffuse and cytoplasmic expression of CD66a may involve the early stage of the HCC, and the loss of CD66a expression indicates tumor progression.

Glioma is characterized by a high heterogeneity in the brain tumor. Abundant tumor-associated macrophages (TAMs) exist as neoplastic tissues, implicating tumor plasticity and thus leading to therapeutic challenges. Vascular adhesion protein (VAP-1) potentially serves as a mediator for TAM immunity in tumor milieu. We previously demonstrated that VAP-1 could contribute to tumor malignancy, but its characteristics in TAM immunity of glioma progression are still unclear. This study explored the association of VAP-1 expression with TAM distribution as well as the resulting clinical significance and prognostic value in human gliomas. An in-depth analysis of AOC3 (VAP-1) gene expression was performed using 695 glioma samples derived from the cancer genome atlas (TCGA)-lower grade glioma and glioblastoma (GBMLGG) cohort. Bioinformatic analysis confirmed that VAP-1 expression is associated with poor prognosis of glioma patients (p = 0.0283). VAP-1 and TAM biomarkers (CD68, iNOS, and CD163) were evaluated by immunohistochemistry in 108 gliomas from Kaohsiung Medical University Hospital. VAP-1+ was expressed in 56 (51.85%) cases and this phenotype revealed a significant association with overall survival in Kaplan–Meier analysis (p < 0.0001). Immunohistochemical double staining showed that VAP-1 immunoreactivity was present around CD163+ M2 infiltration location, including aggressive lesions and neighboring neovasculature. We demonstrated that high VAP-1 expression levels positively correlated with CD163+ M2 activation and coexpression of these two proteins was associated with worse survival in gliomas (p < 0.0001). Multivariate analysis indicated that VAP-1 alone and co-expressed with CD163 were the significantly independent indicators (both p < 0.0001). Furthermore, VAP-1/CD163 coexpression exhibited excellent diagnostic accuracy in gliomas (AUC = 0.8008). In conclusion, VAP-1 and TAM CD163 M2 coexpression was found in glioma tissues belonging to a highly malignant subgroup that was associated with poor prognosis. These results implied VAP-1 abundance is closely linked to alternative M2 activation during glioma progression. From the aforementioned data, a reasonable inference is that VAP-1 combined with targeting M2 immunity might be an effective therapeutic target for human gliomas.

Burn-induced neuromuscular dysfunction may contribute to long-term morbidity; therefore, it is imperative to develop novel treatments. The present study investigated whether erythropoietin (EPO) administration attenuates burn-induced motor neuron apoptosis and neuroinflammatory response. To validate our hypothesis, a third-degree hind paw burn rat model was developed by bringing the paw into contact with a metal surface at 75°C for 10 s. A total of 24 male Sprague-Dawley rats were randomly assigned to four groups: Group A, sham-control; Group B, burn-induced; Group C, burn + single EPO dose (5000 IU/kg i.p. at D0); and Group D, burn + daily EPO dosage (3000 IU/kg/day i.p. at D0-D6). Two treatment regimens were used to evaluate single versus multiple doses treatment effects. Before sacrifice, blood samples were collected for hematological parameter examination. The histological analyses of microglia activation, iNOS, and COX-2 in the spinal cord ventral horn were performed at week 1 post-burn. In addition, we examined autophagy changes by biomarkers of LC3B and ATG5. The expression of BCL-2, BAX, cleaved caspase-3, phospho-AKT, and mTOR was assessed simultaneously through Western blotting. EPO administration after burn injury attenuated neuroinflammation through various mechanisms, including the reduction of microglia activity as well as iNOS and COX-2 expression in the spinal cord ventral horn. In addition, the expression of phospho-AKT, mTOR and apoptotic indicators, such as BAX, BCL-2, and cleaved caspase-3, was modulated. Furthermore, the activity of burn-induced autophagy in the spinal cord ventral horn characterized by the expression of autophagic biomarkers, LC3B and ATG5, was reduced after EPO administration. The present results indicate that EPO inhibits the AKT-mTOR pathway to attenuate burn-induced motor neuron programmed cell death and microglia activation. EPO can modulate neuroinflammation and programmed cell death and may be a therapeutic candidate for neuroprotection.

Ascorbic acid bound to KMUP-1 and sildenafil were examined for their antioxidant effects on vascular endothelium growth factor (VEGF) and endothelium nitric oxide synthase (eNOS) in hypoxic pulmonary artery (PA). Inhaled KMUP-1 and oral sildenafil released NO from eNOS. The effect of buffered l-ascorbic acid, alone and bound to KMUP-1 or sildenafil, for treating pulmonary arterial hypertension (PAH) is unclear. In this study, the antioxidant capacity of ascorbic acid increased the beneficial effects of KMUP-1 on PAH. KMUP-1A and sildenafil-A (5 mg/kg/d) were administered to hypoxic PAH rats. Pulmonary artery blood pressure, and VEGF, Rho kinase II (ROCK II), eNOS, soluble guanylate cyclase (sGC-α), and protein kinase G expression in lung tissues were measured to link PAH and right ventricular hypertrophy. Hypoxic rats had higher pulmonary artery blood pressure, greater PA medial wall thickness and cardiac weight, and a higher right ventricle/left ventricle + septum [RV/(LV+S)] ratio than normoxic rats. Oral KMUP-1A or sildenafil-A for 21 days in hypoxia prevented the rarefaction of eNOS in immunohistochemistry (IHC), reduced the IHC of VEGF in PAs, restored eNOS/protein kinase G/phosphodiesterase 5A; unaffected sGC-α and inactivated ROCK II expression were also found in lung tissues. In normoxic PA, KMUP-1A/Y27632 (10μM) increased eNOS and reduced ROCK II. ROCK II/reactive oxidative species was increased and eNOS was reduced after long-term hypoxia for 21 days. KMUP-1A or Y27632 blunted ROCK II in short-term hypoxic PA at 24 hours. l-Ascorbic acid + l-sodium ascorbate (40, 80μM) buffer alone directly inhibited the IHC of VEGF in hypoxic PA. Finally, KMUP-1A or sildenafil-A reduced PAH and associated right ventricular hypertrophy.

Expressions of human p16 and p27 were tested for correlations with clinicopathologic features of urothelial carcinoma (UC). Tissue microarrays (TMA) constructed from paraffin-embedded specimens from 78 patients with UC were analyzed by immunohistochemical staining. In 49 of the 78 tumors (63%), high p16 expression was associated with absence of tumor invasiveness and low-grade carcinoma (p = 0.003 and p = 0.046, respectively). The p27 expression was high in 33 of the 78 tumors (42%) and showed a significant negative association with invasiveness, carcinoma grade, and tumor size (p = 0.016, p = 0.046, and p = 0.014, respectively). Kaplan–Meier analysis indicated that patients with high p27 levels had longer than average overall survival (p = 0.021). This study demonstrates that p16 and p27 are prognostic indicators of tumor stage and grade in UC and that they provide clinicians with the ancillary information needed for selecting suitable therapeutic strategies.

Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.

Hyperbaric oxygen treatment (HBOT) has been used to reduce neuropathic pain. Melatonin and opioid receptors are involved in neuropathic pain, but it is not known if HBOT works through these pathways to achieve its antinociceptive effect. We divided anesthetized rats into two treatment and three sham groups. The two treatment groups received third-degree burns on their right hind paws, one treated in a hyperbaric chamber for a week and the other for two weeks. We evaluated the mechanical paw-withdrawal threshold (MWT) and expression of melatonin receptor 1 (MT1), melatonin receptor 2 (MT2), μ (MOR) and κ (KOR) opioid receptor, brain-derived neurotrophic factor (BDNF), Substance P, and calcitonin gene-related peptide (CGRP) in cuneate nucleus, dorsal horn, and hind paw skin by immunohistochemical, immunofluorescence assays and real-time quantitative polymerase chain reaction (RT-PCR). The group receiving one-week HBOT had increased expressions of MT1, MT2, MOR and KOR and decreased expressions of BDNF, Substance P, and CGRP. Their mechanically measured pain levels returned to normal within a week and lasted three weeks. This anti-allodynia effect lasted twice as long in those treated for two weeks. Our findings suggest that increasing the duration of HBOT can reduce burn-induced mechanical allodynia for an extended period of time in rats. The upregulation of melatonin and opioid receptors observed after one week of HBOT suggests they may be partly involved in attenuation of the mechanical allodynia. Downregulation of BDNF, substance P and CGRP may have also contributed to the overall beneficial effect of HBOT.

Administration of antioxidants and anti-inflammatory agents is an effective strategy for preventing ultraviolet (UV) irradiation-induced skin damage. Artocarpus communis possesses several pharmacological activities, such as antioxidant, anticancer and anti-inflammation. However, the photoprotective activity of methanol extract of A. communis heartwood (ACM) in ultraviolet irradiation-induced skin damage has not yet been investigated. The present study was performed using ultraviolet absorption, histopathological observation, antioxidant and anti-inflammation assays to elucidate the mechanism of the photoprotective activity of ACM. Our results indicated that ACM displayed a UVA and UVB absorption effect and then effectively decreased scaly skin, epidermis thickness and sunburn cells during ultraviolet irradiation in hairless mice. ACM not only decreased ultraviolet irradiation-mediated oxidative stress, including lowering the overproduction of reactive oxygen species and lipid peroxidation (p < 0.05), but also reduced the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin 1β. Additionally, ACM can decrease the synthesis of cytosolic phospholipase A2, cyclooxygenase, inducible nitric oxide synthase and vascular cell adhesion molecular-1 via inhibiting TNF-α-independent pathways (p < 0.05) in UVB-mediated inflammation and formation of sunburn cells. Consequently, we concluded that ACM extract has a photoprotective effect against UVB-induced oxidative stress and inflammation due to its sunscreen property, and its topical formulations may be developed as therapeutic and/or cosmetic products in further studies.

Ocular chemical burn is a severe injury with poor outcomes. Immediate and appropriate management is highly related to prognosis. We studied the effect of cultured human adipose tissue-derived stem cells on the regeneration of the rabbit cornea after alkaline chemical burn, using used human adipose tissue-derived stem cells as the source material. Immediately after the chemical burn, the experimental eye received a single subconjunctival injection of a stem cell suspension (1.3 × 105 cells/0.2 mL), with the other eye serving as control. Rabbits were sacrificed and specimens taken 30 days after injection. The experimental group showed faster wound healing than the control group, and the result for the experimental group was clearer cornea medium. Histologically, there were five to six epithelial cell layers on the corneas of the experimental group as compared to two to three cell layers on the corneas of the control group. Wilcoxon signed rank test showed a significant difference in the epithelial cell layers between the two groups. Surface markers for connexin 43 (Cx43), β-catenin, E-cadherin, and P63 were analyzed. Cx43 and β-catenin showed significant change, as determined by the Wilcoxon signed rank test, which indicated good cell renewal during repair of the corneal epithelium damaged by the chemical burn. E-cadherin and P63 showed no significant change during the epithelium healing process. Transplantation of cultured human adipose tissue-derived stem cells as a treatment for a corneal chemical burn promotes cell renewal and assists in damage repair.

Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that MMP had an additive effect on the formation of recurrent nasal polyp. We also investigated the association between the functional promoter polymorphism of MMPs and the intensity of labeling index. Expressions of MMP-2 and MMP-9 were assessed via immunohistochemical staining and compared between different groups, including recurrent nasal polyps, nonrecurrent nasal polyps, and control nasal mucosa. Two promoter functional single-nucleotide polymorphisms (rs3918242 for MMP-9 and rs243865 for MMP-2) were selected to correlate with staining intensity. Expression of MMP-9 was significantly enhanced in gland for recurrent nasal polyp (p = 0.016) and nonrecurrent nasal polyp (p = 0.005) compared to the control. MMP-2 positivity was significantly increased in surface epithelium for recurrent nasal polyp (p = 0.004) compared to the control (p = 0.061). However, there was no significant difference in MMP-9 and MMP-2 expressions between recurrent and nonrecurrent nasal polyps. Genetic polymorphism of MMP-2 and MMP-9 functional promoters was not associated with the intensity of labeling index. These results suggested that up-regulation of MMP-9 in gland and MMP-2 in surface epithelium was characteristic of both recurrent and nonrecurrent nasal polyps. Pathogenesis of recurrent nasal polyps may involve a mechanism other than MMP.

This study aims to explore whether certain occupations were associated with the risk of esophageal squamous cell carcinoma (ESCC) in Taiwan. In a hospital-based case-control study, we collected 326 newly diagnosed ESCC patients and 386 age-matched controls (the ratio of case patients: controls = 1:1–2). All respondents completed a questionnaire, including 33 occupations in which environments potential exposure to cancer-related hazards are present. Workers with dust and metal exposure were categorized into Groups A and B, respectively. Relative risks for ESCC were estimated by odds ratios adjusting for covariates (AOR). Compared with the controls, farmer/gardener (AOR = 2.08, 95% CI = 1.02–4.24) and workers in Group A (AOR = 2.80, 95% CI = 1.21–6.47) had significantly higher risk for developing ESCC. A tendency of increased risk was also found in workers in group B (OR = 5.72 95% CI = 2.33–14.03), but such association was not significant after adjusting for other covariates (AOR = 1.57, 95% CI = 0.54–6.61). Our results suggested that farmer/gardener and workers with exposure to dust had a significant excess risk of ESCC. This study added further evidence to the current knowledge that occupational hazards are important in the development of ESCC.

The aims of this study were to investigate the risk of hip fracture and contributing factors in patients with erectile dysfunction(ED). This population-based study was performed using the Taiwan National Health Insurance Research Database. The analysis included 4636 patients aged ≥ 40 years who had been diagnosed with ED (International Classification of Diseases, Ninth Revision, Clinical Modification codes 302.72, 607.84) during 1996-2010. The control group included 18,544 randomly selected age-matched patients without ED (1:4 ratio). The association between ED and hip fracture risk was estimated using a Cox proportional hazard regression model. During the follow-up period, 59 (1.27%) patients in the ED group and 140 (0.75%) patients in the non-ED group developed hip fracture. After adjusting for covariates, the overall incidence of hip fracture was 3.74-times higher in the ED group than in the non-ED group (2.03 vs. 0.50 per 1000 person-years, respectively). The difference in the overall incidence of hip fracture was largest during the 3-year follow-up period (hazard ratio = 7.85; 95% confidence interval = 2.94-20.96; P

Modulation of nuclear factor-kappa B (NF-κB) expression has important clinical implications including anti-inflammation. Recently, we have shown that direct regulation of NF-κB/p65 subunit may account for tacrolimus ointment’s remarkable clinical efficacy on treating inflammatory dermatoses. However, NF-κB is a dimeric transcription factor formed by hetero- or homodimeration of the five Rel family proteins. The complete operational scheme of different NF-κB subunits remains obscure. It has been shown that homodimers consist of NF-κB/p50 may serve an inhibitory role in suppressing inflammation while dimers consisting of NF-κB/p65 activate inflammatory pathway. Our current study aimed to explore the effects of ultraviolet B (UVB) on epidermal keratinocytes in terms of specific NF-κB subunits NF-κB/p50 and NF-κB/p65. Additionally, the effects of tacrolimus on differential regulation of NF-κB subunits of UVB irradiated keratinocytes were also investigated. Our result showed that UVB sequentially regulated the activities of different subunits of NF-κB: the activity of NF-κB/p50 was downregulated in the early stage (6 hours), followed by upregulation of NF-κB/p65 in the later stage (12 hours). The results from immunofluorescence, immunocytochemical, and immunohistochemical analyses indicated that the nuclear expression of NF-κB/p50 could be seen constitutively while the nuclear expression of NF-κB/p65 could only be seen after UVB irradiation. Furthermore, treatment with tacrolimus didn’t affect the nuclear activation and translocation of NF-κB/p50, while the UVB induced NF-κB/p65 nuclear expression was suppressed by tacrolimus. In summary, we have shown that UVB irradiation sequentially regulated different NF-κB subunits. The clinical efficacy of tacrolimus may be attributed to its specific regulatory effect on NF-κB/p65 but not NF-κB/p50 of the NF-κB pathway.

Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are the spindle cell mesenchymal neoplasms of the dermis and subcutis. Their histogenesis still remains uncertain and controversial. Traditionally, CD34 and factor XIIIa or other markers have been widely used to distinguish these two diseases. However, the results of these markers reveal overlapping and they lack specificity. Formalin-fixed, paraffin-embedded blocks were collected from the biopsied cases in Kaohsiung Medical University Hospital in Taiwan between 2004 and 2006. This study included 19 cases of DF and 17 cases of DFSP. Immunohistochemical analysis using antibodies CD34, matrix metalloproteinases (MMP)-2, MMP-9, and MMP-11 was performed. We found that the expression of CD34, MMP-2 and MMP-11 shows significant statistical differences in Immunohistochemistry (IHC) study positive or negative reactivity (positive of CD34 in DFSP and positive of MMP-2 and MMP-11 in DF; p=0.03, p

A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient’s neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.

This study investigates the expression of annexin 1 in urothelial carcinoma (UC) and its relation with clinicopathologic factors, and evaluates its potential clinical significance. Annexin 1 expression was analyzed by immunohistochemical staining with manual tissue microarrays and Western blot in UC. Immunohistochemical analysis of UC in tissue microarrays showed that annexin 1 protein was 76.5% (150/196) positive, which was markedly increased compared with that in the normal urothelium 20.8% (5/24) (p

Breast cancer has become the second leading cancer among females in Taiwan. Even though the etiology of breast cancer is multifactorial, oxidative stress plays an important role in the carcinogenesis. The purpose of this study was to investigate the expression of manganese superoxide dismutase (MnSOD), one of the major antioxidant enzymes that is involved against oxidative stress, in adjacent cancer-free breast tissues and neoplasm tissues within the same patient. Sixty-five breast cancer patients’ formalin-fixed tissue blocks, including ductal carcinoma in situ (DCIS) tissues, invasive ductal carcinoma (IDC) tissues, and adjacent cancer-free tissues, were evaluated by immunohistochemical stain. Meanwhile, their demographic and clinical information was also collected. The combined scores of MnSOD-positive cell proportion and MnSOD staining intensity were compared for different tissues within the same patient. The results showed that the mean combined scores of MnSOD expression in adjacent cancer-free tissues (6.33), IDC (5.30), and DCIS (3.78) were significantly different when assessed by repeated-measurement analysis of variance (F=14.17, p

Eosinophilic granuloma (EG) refers to the most common and benign form of the disorder known as Langerhans’ cell histiocytosis. The disease is typically found in children and adolescents and rarely affects adults. We present a case of EG in the occipital bone in a 36-year-old man, who visited our hospital with the chief complaint of left occipital palpable tumor mass with local tenderness and pain for one month. An X-ray of the skull revealed a rounded osteolytic lesion. A computed tomography scan revealed a shadow of soft tissues in the left occipital site involving the entire thickness of the calvaria, which was indicative of marked destruction of the bone. The soft mass was successfully removed. The margins of the skull lesion were excised, and cranioplasty was performed simultaneously with bone cement. A definitive diagnosis of EG was made by histopathology and immunohistochemical detection of S-100 antigen in the tissue samples. With respect to management, we believe surgery is the best option for most accessible cranial lesions of EG. A cranioplasty with bone cement or autologous bone can be performed in the same session to repair the cranial defect.

Lercanidipine, a calcium channel antagonist, is currently employed in the treatment of essential hypertension and angina pectoris. The purpose of this study was to elucidate the anti-proliferative effect of lercanidipine and to investigate the molecular role of this agent. Both in vitro studies and in a balloon injury rat carotid artery model were employed to study the effect of lercanidipine on smooth muscle cell proliferation. Lercanidipine-inhibited rat vascular smooth muscle cell (VSMC) proliferation and migration in a dose-dependent manner following stimulation of VSMC cultures with 10% fetal bovine serum (FBS) and 20 ng/ml platelet-derived growth factor (PDGF)-BB. FBS- and PDGF-BB-stimulated intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), and Akt activations were significantly inhibited by lercanidipine; however, lercanidipine did not affect FBS- and PDGF-BB-induced STAT3 phosphorylation. Lercanidipine also inhibited PDGF-receptor b chain phosphorylation and reactive oxygen species (ROS) production induced by PDGF-BB. Lercanidipine blocked the FBS-inducible progression through the G0/G1 to the S-phase of the cell cycle in synchronized cells. In vivo, 14 days after balloon injury, treatment with 3 and 10 mg/kg lercanidipine resulted in significant inhibition of the neointima/media ratio. Suppression of neointima formation by lercanidipine was dependent on its influence on ERK1/2 phosphorylation. These results demonstrate that lercanidipine can suppress the proliferation of VSMCs via inhibiting cellular ROS, Ras-MEK1/2- ERK1/2, and PI3K-Akt pathways, and suggesting that it may have therapeutic relevance in the prevention of human restenosis.

Various parotid gland diseases are seen clinically, including inflammation, sialolithiasis, and benign and malignant tumors. It is important to differentiate between these to make a correct diagnosis and for proper management. Here, we investigated the relationship between tumor characteristics and pathology, and considered whether the former could be used to differentiate malignant from benign parotid gland diseases. We retrospectively reviewed the charts and data of 316 patients who underwent surgery in Kaohsiung Medical University Chung-Ho Memorial Hospital from January 1, 1998 to December 31, 2008. Two hundred and eighty-one patients (88.9%) had benign disease, and 35 (11.1%) had malignant disease. The most common benign disease was pleomorphic adenoma (115 cases, 36.4%), but the most common disease in male patients was Warthin's tumor, a finding which, as far as we aware, has not been previously been reported in the literature. The incidence of Warthin's tumor seems to be increasing. In malignant disease, the most common was acinic cell carcinoma (8 cases, 22.9%). Compared with benign disease, malignant parotid gland disease more often presents as a hard, painful, fixed and large mass (> 3 cm), and more often involves the deep lobe of the parotid gland. Partial parotidectomy was adequate for most tumors, including pleomorphic adenoma. The most common postoperative complication was temporary facial palsy, followed by permanent facial palsy. However, there was no difference in transient facial palsy rate between benign and malignant parotid gland disease, although parotid gland cancer had a higher incidence of permanent facial palsy postoperatively.

Hyperbaric oxygen (HBO) treatment has been proven to decrease neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague-Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment; (2) sham burn with HBO treatment; (3) burn with one-week sham HBO treatment; (4) burn with two-week sham HBO treatment; (5) burn with one-week HBO treatment; and (6) burn with two-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting. A behavior test was also conducted, which revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared to the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor α (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis showed that the expression of Gal-3, TLR-4, CD68 and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia and macrophage activation in a rat model.

We report a rare case of postoperative colon cancer recurrence who presented with hematuria 13 years after resection of the primary colonic cancer. The patient was 72 years of age and underwent surgical resection of sigmoid colon cancer at another regional hospital in 1994. Since June 2007, this patient has complained of hematuria and bloody stool. On physical examination, tenderness and a hard, indurated mass was palpable in the lower mid-abdomen. Abdominal computed tomography showed a metastatic tumor at the lower midline peritoneum with invasion of the adjacent abdominal wall. Her serum carcinoembryonic antigen level was elevated to 32 ng/dL. Histopathology revealed metastatic colonic adenocarcinoma in the jejunum and abdominal wall.

Background: Burn scar pain is considered as neuropathic pain. The anti-inflammation and anti-neuroinflammation effects of adipose-derived stem cells (ASCs) were observed in several studies. We designed a study using a murine model involving the transplantation of autologous ASCs in rats subjected to burn injuries. The aim was to detect the anti-neuroinflammation effect of ASC transplantation and clarify the relationships between ASCs, scar pain, apoptosis and autophagy. Methods: We randomized 24 rats into 4 groups as followings: Group A and B, received saline injections and autologous transplantation of ASCs 4 weeks after sham burn, respectively; Group C and D, received saline injections and autologous transplantation 4 weeks after burn injuries. A designed behavior test was applied for pain evaluation. Skin tissues and dorsal horn of lumbar spinal cords were removed for biochemical analysis. Results: ASC transplantation significantly restored the mechanical threshold reduced by burn injury. It also attenuated local inflammation and central neuroinflammation and ameliorated apoptosis and autophagy in the spinal cord after the burn injury. Conclusion: In a rat model, autologous ASC subcutaneous transplantation in post-burn scars elicited anti-neuroinflammation effects locally and in the spinal cord that might be related to the relief of post-burn neuropathic pain and attenuated cell apoptosis. Thus, ASC transplantation post-burn scars shows the potential promising clinical benefits.

In this study, we investigated the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) Tyr705 and suppressor of cytokine signaling 3 (SOCS3) in urothelial carcinoma (UC). p-STAT3 (Tyr705) and SOCS3 were analyzed by immunohistochemistry using tissue microarray and Western blotting. Our results showed that p-STAT3 (Tyr705) was frequently detected in high-grade and infiltrating UC. However, there was no difference in p-STAT3 (Tyr705) staining between UC of the upper and lower urinary tracts. In addition, there was no significant correlation between expression of SOCS3 and histological differentiation and invasiveness of UC. These findings suggest that overexpression of p-STAT3 (Tyr705) occurs in UC, and that pathways other than SOCS3 may contribute to its activation in this cancer.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare neoplasm that commonly arises in the deep soft tissues of the lower extremities, particularly in the thigh. LGFMS occurs preferentially in young male adults. The microscopic appearance of LGFMS exhibits bland fibroblastic spindle cells with a whorled or linear arrangement in fibrous and myxoid areas. Although LGFMS has a deceptively benign histologic appearance, local recurrence and late metastases have frequently been reported. Diagnosis of LGFMS is still difficult because of its characteristic bland-looking histologic features that can be confused with other benign or low-grade fibromyxoid lesions. Although immunohistochemical staining can offer an overview of the differential diagnosis of myxoid tumors of soft tissue, it is sometimes limited for diagnosis of LGFMS. However, recent cytogenetic and molecular analyses have provided significant improvements in the diagnosis of LGFMS. Such analyses have demonstrated that most cases of LGFMS have a characteristic t (7,16) (q33;p11) translocation, resulting in the FUS-CREB3L2 fusion gene. We report a 29-year-old female who presented with a LGFMS located in the soleus muscle of her left lower leg. Preoperative imaging suggested the possibility of an intramuscular histiocytoma of the left soleus muscle. In conclusion, diagnosis of LGFMS can be challenging in routine practice in surgical pathology because of its bland-looking features. The immunohistochemical and ultrastructural findings were consistent with the fibroblastic properties of LGFMS. Cytogenetic and/or molecular genetic analyses can be used as ancillary diagnostic tools for LGFMS.

Primary effusion lymphoma (PEL) is an unusual and rare type of non-Hodgkin's lymphoma characterized by lymphomatous effusion of pleural, pericardial or peritoneal cavities without lymphadenopathy or organomegaly. It is associated with human herpes virus-8 (HHV-8) and occurs most often in immunodeficient patients. We present a case of PEL in a 69-year-old male presenting with pleural effusion and ascites. Fluid aspiration showed a monomorphic population of atypical lymphoid cells, which were medium- to large-sized, with mono- or binucleated hyper-chromatic nuclei and a small to moderate amount of basophilic cytoplasm containing cytoplasmic vesicles. Immunohistochemically, the lymphoid cells expressed CD138 and multiple myeloma oncogene 1, were positive for HHV-8, and were monoclonal for immunoglobulin heavy chain gene rearrangement. They were negative for Epstein-Barr virus by in situ hybridization. Unfortunately, the patient died during the first course of chemotherapy with cyclophosphamide, vincristine and prednisone.

This study aimed to investigate if zinc compound would have effects on body weight loss and bone marrow suppression induced by total body irradiation (TBI). ICR mice were divided randomly into two groups and treated with test or control compounds. The test compound contained zinc (amino acid chelated with bovine prostate extract), and the control was reverse osmosis pure water (RO water). One week after receiving the treatment, mice were unirradiated, or irradiated with 6 or 3 Gy by 6MV photon beams to the total body. Body weight changes were examined at regular intervals. Three and 5 weeks after the radiation, animals were sacrificed to examine the histologic changes in the bone marrow. Lower body weight in the period of 1-5 weeks after radiation and poor survival rate were found after the 6 Gy TBI, as compared with the 3 Gy groups. The median survival time after 6 Gy and 3 Gy TBI for mice given the test compound were 26 and 76 days, respectively, and the corresponding figures were 14 and 70 days, respectively, for mice given the control compound (p < 0.00001). With zinc supplement, the mean body weight in mice which received the same dose of radiation was 7-8 g heavier than in the water-supplement groups during the second and third weeks (p < 0.05). Hence, there was no statistically significant difference in survival rate between zinc and water supplement in mice given the same dose of irradiation. Histopathologically there was less recovery of bone marrow cells in the 6Gy groups compared with the 3Gy groups. In the 3 Gy water-supplement group, the nucleated cells and megakaryocytes were recovered in the fifth week when recovery was still not seen in the 6Gy group. With zinc supplement, these cells were recovered in the third week. In this study, we found that zinc is beneficial to body weight in mice treated with TBI. Histologic examination of bone marrow showed better recovery of bone marrow cells in groups of mice fed with zinc. This study suggests that zinc can be used as supplements in cancer patients receiving radiotherapy to reduce radiation-induced complications.

The objectives of this study were firstly to compare the immunostaining patterns of antibodies against caveolin-1, thyroid transcription factor-1 (TTF-1), cytokeratin 7 (CK7) and cytokeratin 20 (CK20) in primary and secondary pulmonary adenocarcinomas of breast or colonic origin, and secondly, to investigate their use alone and in combination, in distinguishing between primary and secondary lung adenocarcinomas from breast or colonic origin. Of the 49 lung adenocarcinoma specimens that were enrolled in this study, 30 were primary pulmonary adenocarcinomas, and 19 (9, breast origin; 10, colonic origin) were metastatic pulmonary carcinomas. Immunohistochemical staining was used to detect the expression of caveolin-1, TTF-1, CK7, and CK20. Primary pulmonary adenocarcinoma most often had the CK7-positive/CK20-negative immunohistochemical phenotype and was either TTF-1 positive or caveolin-1 negative. Secondary pulmonary adenocarcinoma of breast origin most often had the CK7-positive/CK20-negative immunohisto-chemical phenotype and was either TTF-1 negative or caveolin-1 positive, while secondary pulmonary adenocarcinoma of colonic origin most often had the CK20-positive/CK7-negative immunohistochemical phenotype and was either TTF-1 negative or caveolin-1 positive. The results suggest that caveolin-1, TTF-1, or CK7/CK20 alone did not distinguish reliably between primary and secondary pulmonary adenocarcinomas originating from breast or colon. The use of a panel of antibodies that includes TTF-1, caveolin-1, and CK7/CK20 may have higher sensitivity in discriminating between primary adenocarcinomas and metastatic lung adenocarcinomas from breast or colonic origin.

Leukemoid reaction is defined as a reactive leukocytosis in response to infection, inflammation, or therapeutic agents such as growth factors and malignancy. We report a case of leukemoid reaction resulting from granulocyte colony-stimulating factor producing urothelial carcinoma of the renal pelvis as evidenced on immunohistochemical analysis.

Burn-induced neuropathic pain is complex, and fat grafting has reportedly improved neuropathic pain. However, the mechanism of fat grafting in improving neuropathic pain is unclear. Previous investigations have found that neuroinflammation causes neuropathic pain, and anti-inflammatory targeting may provide potential therapeutic opportunities in neuropathic pain. We hypothesized that fat grafting in burn scars improves the neuropathic pain through anti-inflammation. Burn-induced scar pain was confirmed using a mechanical response test 4 weeks after burn injuries, and autologous fat grafting in the scar area was performed simultaneously. After 4 weeks, the animals were sacrificed, and specimens were collected for the inflammation test, including COX-2, iNOS, and nNOS in the injured skin and spinal cord dorsal horns through immunohistochemistry and Western assays. Furthermore, pro-inflammatory cytokines (IL-1 β and TNF-α) in the spinal cord were collected. Double immunofluorescent staining images for measuring p-IκB, p-NFκB, p-JNK, and TUNEL as well as Western blots of AKT, Bax/Bcl-2 for the inflammatory process, and apoptosis were analyzed. Fat grafting significantly reduced COX2, nNOS, and iNOS in the skin and spinal cord dorsal horns, as well as IL-1β and TNF-α, compared with the burn group. Moreover, regarding the anti-inflammatory effect, the apoptosis cells in the spinal cord significantly decreased after the fat grafting in the burn injury group. Fat grafting was effective in treating burn-induced neuropathic pain through the alleviation of neuroinflammation and ameliorated spinal neuronal apoptosis.

Signal transducer and activator of transcription 3 (STAT3) has been regarded as an oncogene in many types of cancers. However, its role in cervical carcinogenesis is not well determined. The purpose of this study was to evaluate the expression patterns of STAT3 in cervical intraepithelial neoplasia (CIN), normal cervix (NC), and squamous cell carcinoma (SCC) to explore its possible role in cervical carcinogenesis. Paraffin-embedded sections from 83 patients including 20 CIN 1, 10 CIN 2, 26 CIN 3, and 27 comparative cases of 10 NC and 17 stage Ib SCC were collected in this study. Immunohistochemistry was performed to analyze the expression patterns of STAT3, and the results obtained were categorized by a semiquantitative method and were further correlated with the CIN histopathologic grade and the proliferation marker, Ki-67, using the c2 test. Our results showed that nuclear STAT3 expression was predominantly in the squamous epithelial cells, and that high-grade CIN and stage Ib SCC lesions had a higher nuclear STAT3 expression when compared with NC and CIN 1. Furthermore, the nuclear STAT3 expression in CIN was significantly correlated with Ki-67 expression (p= 0.025), but not CIN lesion grade. In summary, our results indicate that an altered STAT3 expression in CIN is correlated with cell proliferation but may not have a direct contribution to cervical carcinogenesis.