[Preparation, characterization and cytology study of Pluronic-PEI micelles].

Objective: To prepare and characterize Pluronic-PEI micelles as a drug/gene delivery system. Methods: We used the low-molecular-weight PEI as a cross-linking agent to prepare the Pluronic-PEI micelles. The particle size, zeta potential and critical micelle concentration (CMC) were measured by dynamic light scattering (DLS) and pyrene fluorescence probe. The cytotoxicity, transfection efficiency and the impact on the intracellular ATP and P-gp levels of Pluronic-PEI micelles were investigated at the cellular level. Results: Pluronic-PEI micelles were successfully prepared with a suitable particle size (120-180 nm), zeta potential (+6-+9 mv), and a good ability to carry the drug/gene. An in-vitro study showed that Pluronic-PEI had low cytotoxicity, and the P123-PEI600 possessed high gene transfection efficiency and could downregulate the intracellular ATP and P-gp levels. Conclusion: Pluronic-PEI is a good drug/gene delivery system, and P123-PEI600 is an ideal vector, which may be used in the combination therapy for reversing multidrug resistance.

Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation.

BACKGROUND: Ventilator-induced lung injury (VILI) is a common complication of mechanical ventilation under general anesthesia. Regular aerobic exercise before surgery improves postoperative recovery and reduces postoperative pulmonary complications, but the mechanism driving this protective effect is unclear. METHODS: To determine how aerobic exercise prevents VILI, we investigated the effects of exercise and mechanical ventilation on the lungs of male mice and the effects of AMPK stimulation (simulating exercise) and cyclic stretching on human lung microvascular endothelial cells (HLMVEC). Sirtuin 1 (Sirt1) knockdown male mice were generated to explore the regulating mechanisms of sirt1 on mitochondrial function in male mice after mechanical ventilation was explored. Western blot, flow cytometry, live cell imaging, and mitochondrial function evaluations were used to determine the protective effects of aerobic exercise in preventing mitochondrial damage in VILI. RESULTS: Mitochondrial function and cell junctions were destroyed by mechanical ventilation in male mice or cyclic stretching in HLMVEC, a model of VILI. However, mitochondrial function and cell junction dysfunction were improved by exercise before mechanical ventilation (male mice) or treatment with AMPK before cyclic stretching (HLMVEC). p66shc, a marker of oxidative stress, was increased, and PINK1, a marker of mitochondrial autophagy, was decreased by mechanical ventilation or cyclic stretching. Sirt1 knockdown increased p66shc and decreased PINK1. Increased sirt1 expression was observed in the exercise and exercise + ventilation groups, suggesting that sirt1 inhibits mitochondrial damage in VILI. CONCLUSIONS: Mechanical ventilation induces mitochondrial damage in lung cells and leads to VILI. Regular aerobic exercise before ventilation may prevent VILI by improving mitochondrial function.

Yanghe decoction attenuated pain hypersensitivity induced by michigan cancer foundation-7 injection in rats with bone metastases from breast cancer by inhibiting transient receptor potential ankyrin 1.

OBJECTIVE: To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7 (MCF-7). METHODS: Bone pain was induced in the tibia of rats injected with MCF-7 cells. The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats. The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency. Liquid chromatography-mass spectrometry, Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunohistochemical (IHC) staining were performed for analysis. RESULTS: Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1 (TRPA1) inhibitor. In morphology study, Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group. Furthermore, Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level. Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis, and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-α and interleukin-6, interleukin-1 beta by ELISA. As the cytochromec oxidase subunit II/prostaglandin E2 (PGE2) is required for cancer development, Yanghe decoction reduced the expression of PGE2 in the tissue and serum. CONCLUSION: Taken together, Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.

Pathological images for personal medicine in Hepatocellular carcinoma: Cross-talk of gene sequencing and pathological images.

Background: Considering the great heterogeneity of Hepatocellular carcinoma (HCC), more accurate prognostic models are urgently needed. This paper combined the advantages of genomics and pathomics to construct a prognostic model. Methods: First, we collected data from hepatocellular carcinoma patients with complete mRNA expression profiles and clinical annotations from the TCGA database. Then, based on immune-related genes, we used random forest plots to screen prognosis-related genes and build prognostic models. Bioinformatics was used to identify biological pathways, evaluate the tumor microenvironment, and perform drug susceptibility testing. Finally, we divided the patients into different subgroups according to the gene model algorithm. Pathological models were constructed by obtaining HE-stained sections from TCGA in corresponding subgroups of patients. Results: In this study, we constructed a stable prognostic model that could predict overall survival in HCC patients. The signature consisted of six immune-related genes (BX537318.1, TMEM147, CSPG4P12, AC015908.3, CEBPZOS, and SRD5A3). We found increased levels of infiltration of immune cells in the tumor microenvironment in patients with low risk scores, indicating significant antitumor immunity and corresponding to better clinical outcomes. We then screened nine drugs that were more sensitive in the low-risk group than in the high-risk group. Finally, we addressed the complex cellular changes and phenotypic heterogeneity in the HCC microenvironment by combining genomics and pathomics analysis methods. Conclusion: Our study showed that the prognostic evaluation model of HCC based on the immune signaling pathway is feasible and provided a reference value for potential immunotherapy for HCC.

Epidemiology of 2000 Chinese uveitis patients from Northeast China.

AIMS: To study the clinical characteristics of 2000 patients with uveitis admitted to the ophthalmology centre of the Second Hospital of Jilin University. METHODS: We retrospectively analysed 2000 patients with uveitis who were admitted to the uveitis clinic of the Second Hospital of Jilin University from July 2010 to June 2019 and analysed data on sex, onset age, onset season, anatomical classification, visual acuity and compared the results with those of other investigation studies. RESULTS: Among 2000 uveitis patients, the mean age of onset was 39.9±14.9 years. There were 946 male patients (47.3%) and 1054 female patients (52.7%). By anatomical classification, panuveitis was the most common (986 cases, 49.3%), followed by anterior uveitis (786 cases, 39.3%), posterior uveitis (119 cases, 6.0%) and intermediate uveitis (109 cases, 5.5%). Among anterior uveitis cases, ankylose spondylitis (207 cases, 26.34%), Fuchs syndrome (74 cases, 9.41%) and viral uveitis (71 cases, 9.03%) were the most common. Among panuveitis cases, Vogt-Koyanagi-Harada syndrome (372 cases, 37.73%), Behcet's disease (142 cases, 14.40%) and sympathetic ophthalmitis (33 cases, 3.35%) were the most common. Uveitis often occurs during the autumn-winter transition period. The prevalence of anterior uveitis is highest in November, and statistical analysis shows that the incidence of uveitis has a significant correlation with the month. Panuveitis has the most significant effect on vision. CONCLUSION: Panuveitis and anterior uveitis are the most common anatomical classifications of uveitis, which has a significant impact on vision, and their incidence is related to seasonal changes.

Typical CT and MRI signs of hepatic epithelioid hemangioendothelioma.

To investigate the typical magnetic resonance imaging (MRI) and computed tomography (CT) features of hepatic epithelioid hemangioendothelioma (HEH), the CT and MRI findings of 14 histopathologically confirmed cases of HEH were retrospectively analyzed. Non-contrast and dynamic contrast-enhanced scans were conducted in all cases. A total of 229 lesions were detected in the 14 cases. All cases were classified as one of three types: (i) Solitary nodular type (1 case, 7%); (ii) multifocal nodular type (11 cases, 79%); or (iii) diffuse type (2 cases, 14%). The diameter of the lesions ranged from 5 to 105 mm. For the first two types (solitary and multifocal nodular types), the CT findings included low density lesions with clear margins on non-contrast scans, centripetal enhancement in arterial phase, and homogeneous enhancement in the portal venous and delay phases. The findings of non-contrast MRI scans for these two types included low signal intensity on T1-weighted images, heterogeneous high signal intensity on T2-weighted images, and heterogeneous high signal intensity on diffusion-weighted images. The lesions were predominantly located in submarginal areas. On contrast-enhanced MRI, the findings for the first two types included peripheral ring-like enhancement with a central low signal intensity ('black target-like' sign) and a central enhanced core surrounded by a low signal intensity halo ('white target-like' sign). The findings for the third HEH type (diffuse type) on CT and MRI scans included low density or heterogeneous signal intensity lesions involving regions of part or the whole liver, coalescent lesions ('strip-like' sign), and gradual enhancement along central vessels ('lollipop' sign). Collectively, these findings indicate that the 'white target-like' sign, 'black target-like' sign, 'lollipop' sign and 'strip-like' sign, in addition to capsular contraction and submarginal location, on CT and MRI imaging may have implications for the diagnosis of HEH. Furthermore, a variety of MRI sequences may provide additional information for the differential diagnosis of HEH.

Ovarian thecoma with massive pleural effusion in postmenopausal women: A case report.

Previous clinical reports of benign ovarian thecoma, associated with hydrothorax, are rare. The present study presents the case of a 58-year-old women exhibiting right massive pleural effusions and elevated cancer antigen (CA)125, and a pelvic ultrasound revealed a hypoechoic mass. An exploratory laparotomy was subsequently performed. During the surgery, the left ovary measured 20×15×15 cm and had a smooth surface with no excrescences or papillary projections. The patient underwent right salpingo-oophorectomy. Pathological diagnosis was determined as benign ovarian thecoma. The chest radiograph revealed no pleural effusion 6 days following the surgery. The present case demonstrated a benign ovarian thecoma, associated with massive hydrothorax and elevated CA125, which mimicked an ovarian malignancy.

Antiosteoporotic effect of icariin in ovariectomized rats is mediated via the Wnt/ß-catenin pathway.

Icariin (ICA), the main active flavonoid glucoside isolated from Herba Epimedii, has been shown to prevent postmenopausal bone loss in vitro. However, the mechanisms by which ICA prevents bone loss in vivo remain poorly understood. In the present study, the effect of ICA in an ovariectomized (OVX) rat model of osteoporosis was evaluated. Sprague-Dawley rats were divided into sham-operated and OVX groups. The OVX rats were randomly divided into five groups: OVX group (water only), Fosamax (positive) group (5.04 mg/kg, weekly, administered orally), and OVX-ICA groups (125, 250 or 500 mg/kg, daily, administered orally) and treated for 12 weeks. The 125, 250 and 500 mg/kg doses of ICA were designated as low (L-ICA), medium (M-ICA) and high (H-ICA), respectively. Compared with the sham-operated group, the OVX rats had significantly decreased bone mineral density (BMD), reduced serum osteoprotegerin (OPG) and increased serum bone gla protein (BGP) concentrations. ICA significantly increased BMD, biomechanical strength, trabecular bone number and trabecular bone thickness, and reduced lumbar trabecular bone separation. Treatment with ICA also completely normalized the expression of osteoblast markers by increasing serum concentrations of OPG and BGP. Enhanced mineralization was demonstrated by increased expression of differentiation markers. Although further in vivo studies are required to investigate the efficacy of ICA in improving bone mass, this study demonstrates that ICA has strong osteogenic activity, inducing osteogenic differentiation and inhibiting resorption by osteoclasts. It also demonstrates an antiosteoporotic effect for ICA on the basis of BMD, biochemical markers, biomechanical tests and histopathological parameters. Compared with L-ICA and H-ICA, M-ICA was more effective and caused no liver or kidney damage.

Preoperative C-reactive protein as a prognostic predictor for upper tract urothelial carcinoma: A systematic review and meta-analysis.

Upper tract urothelial carcinoma (UTUC) is a relatively rare and highly aggressive tumor. However, the prognosis of UTUC is rarely predicted accurately due to the lack of reliable biomarkers. C-reactive protein (CRP) has been found to be correlated with several types of cancer. In this study, we performed a systematic review and meta-analysis to determine the association between CRP levels and prognosis in UTUC. A computerized search was conducted through PubMed, Embase, Web of Science, the Cochrane Library and CBM databases to identify clinical studies that have evaluated the association between preoperative CRP levels and prognosis of UTUC. The prognostic outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). We extracted and synthesized corresponding hazard ratios (HRs) and confidence intervals (CIs) using Review Manager 5.3 software. We identified 7 retrospective cohort studies including a total of 1,919 patients and analyzed these studies using univariate and multivariate models. Our meta-analysis results revealed that RFS and CSS were significantly different between patients with elevated CRP levels and those with low CRP levels (P<0.0001 and P<0.00001, respectively); however, that was not the case for OS (P=0.22) in the multivariate or the univariate model. The pooled HR of RFS was 2.90 (95% CI: 1.87-4.51, P<0.00001) in the univariate analysis and 1.57 (95% CI: 1.26-1.97, P<0.0001) in the multivariate analysis. The pooled HRs of CSS were 2.78 (95% CI: 1.75-4.43, P<0.0001) and 1.64 (95% CI: 1.32-2.03, P<0.00001) in the univariate and multivariate analysis, respectively. However, the pooled HRs of OS were not significant in the univariate [1.24 (95% CI: 0.72-2.15, P=0.43)] or the multivariate analysis [1.24 (95% CI: 0.88-1.75, P=0.22)]. In conclusion, our meta-analysis results suggested that CRP level may be a prognostic predictor in UTUC.

Testing of kisspeptin levels in girls with idiopathic central precocious puberty and its significance.

The aim of this study was to explore the significance of plasma kisspeptin levels in diagnosis and therapeutic evaluation through the analysis of the kisspeptin levels of girls diagnosed with idiopathic central precocious puberty (ICPP) prior to treatment and after 6-months of treatment and those with simple premature thelarche (PT). A total of 70 girls including 24 girls diagnosed with ICPP, 21 girls with PT and 25 normal girls were enrolled in the study. ELISA analysis was conducted to detect the plasma levels of kisspeptin. The kisspeptin level of the ICPP group prior to treatment (1.80±0.13 ng/ml) was significantly higher than those of the other two groups. The kisspeptin level of the ICPP group after 6 months of treatment (1.49±0.21 ng/ml) was significantly lower than that prior to treatment (P<0.05). It may be concluded that the plasma level of kisspeptin is associated with the initiation of pubertal development, and it may serve as an important parameter in the diagnosis of ICPP and the evaluation of therapeutic effects.

Association between LMP2 and LMP7 gene polymorphisms and the risk of gastric cancer: A case-control study.

The integrality of low molecular weight protein (LMP)2/LMP7 function plays an important role in the processing of GC cell antigens. The purpose of the present hospital-based case-control study was to estimate the effect of polymorphisms in the LMP2 and LMP7 genes on the risk of GC. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to distinguish the Arg to His substitution at codon 60 of LMP2 (LMP2-60) and the Gln to Lys substitution at codon 145 of LMP7 (LMP7-145) in 502 gastric cancer patients and 502 age and gender-matched cancer-free control individuals. The Lys allele of the LMP7-145 variant was more frequent in GC patients compared with control individuals [P=0.004; adjusted odds ratio (OR), 1.39; 95% confidence interval (CI), 1.11-1.74]. The Gln/Lys and Lys/Lys genotypes increased the risk of GC compared with the Gln/Gln genotype (P=0.049 and P=0.041, respectively; adjusted OR, 1.32 and 2.13, respectively; 95% CI, 1.00-1.73 and 1.03-4.39, respectively). Compared with the Gln/Gln genotype, the LMP7-145 Gln/Lys and Lys/Lys variants of the LMP7 gene were also associated with increased susceptibility to GC (P=0.017; adjusted OR, 1.38; 95% CI, 1.06-1.80). Haplotype analysis revealed that the LMP2 (Arg)-LMP7 (Lys) haplotype was associated with increased risk of GC (P=0.013, adjusted OR=1.34, 95% CI=1.06-1.70). Stratified analysis revealed that the association between the risk of GC and the variant genotypes of LMP7-145 was stronger in older individuals (>59 years), males and non-smokers. However, no association between the LMP2-60 polymorphism and the risk of GC was observed. The present results suggest that the LMP7-145 genetic variant contributes to increased susceptibility to GC, and the Lys allele is an independent risk factor for GC.

Desmoplastic small round cell tumor: A case report of a rare differential diagnosis of solid tumors of the pleura.

Desmoplastic small round cell tumor (DSRCT) presents as a rare separate clinical pathological entity, and pleural DSRCT is very rare. Following review of the English literatures it was revealed that, to date, <15 cases of primary DSRCT of the pleura have been reported worldwide. Among these, there are few computed tomography (CT) findings of pleural DSRCT which have previously been described in detail. The present study reports a pathologically proven case of pleural DSRCT, with varying contrast CT findings in a 72-year-old female, which appeared as a large (12.0×10.0×6.5 cm), smooth, oval mass in the left lower thorax with slight-moderate uniform enhancement on contrast-enhanced CT. To the best of our knowledge, the present report is the first to describe the large solid-tumor pattern and the patient is the eldest reported case of pleural DSRCT.

Multiple-phase spiral CT findings of pancreatic vasoactive intestinal peptide-secreting tumor: A case report.

The present study reports a case of pancreatic vasoactive intestinal peptide-secreting tumor (VIPoma), of 2.2 cm in diameter, arising from the region of the uncus of the pancreas with liver metastases in a 50-year-old patient, which demonstrated unusual multiple-phase spiral computed tomography (MPSCT) results. The pancreatic lesion was isodense compared with the pancreatic parenchyma. During the hepatic artery phase and portal venous phase, the mass was hypodense compared with the enhanced pancreas, with the mean CT attenuation (HU) values being 56 HU and 66 HU, respectively. During the hepatic parenchymal phase, the mass became hyperdense with the mean CT attenuation values being 74 HU. The process of contrast-enhanced MPSCT demonstrated progressive strengthening. Pancreaticoduodenectomy and wedge resection of a number of the liver metastases was performed. There are only a limited number of studies reporting CT findings of pancreatic VIPoma and no MPSCT findings have been described previously.

Effect of 4-hydroxyphenylretinamide on human cervical epithelial and cancer cell lines.

Topical trans-retinoic acid treatment produced a statistically significant regression of cervical intraepithelial neoplasia (CIN) 2, but not CIN 3, in trials. A promising oral retinoid, 4-hydroxyphenylretinamide (4-HPR) induced apoptosis through non-retinoic acid-mediated pathways and is being studied in National Cancer Institute phase II trials in several organ sites. We studied the effects of 4-HPR on cervical cancer cell lines and on cervical epithelial cell lines immortalized by human papillomavirus (HPV). Four immortalized cervical epithelial cell lines (in vitro models of precancerous CIN lesions) and nine cervical carcinoma cell lines were studied. The growth inhibitory effect of 4-HPR was tested in monolayer culture and in semisolid medium, and concentrations required for a 50% growth inhibition within 5 days were determined. The agent 4-HPR inhibited the growth of cervical carcinoma cell lines and HPV-immortalized cell lines in a dose- and time-dependent fashion. Doses of 5 and 10 microM were more effective than 1 microM. The C33A cell line was most sensitive to 4-HPR, and HeLa and HT3 were the least sensitive. Of the HPV-immortalized cell lines, Z132, an HPV-16 immortalized cell line, was sensitive; the HPV 18-immortalized cell lines (Z173, Z183, and TCL-1) were not, although they were sensitive when grown in colonies. The agent 4-HPR is active against several cervical cancer cells lines and HPV-immortalized cervical epithelial cell lines. These findings are consistent with data from other laboratories studying other organ systems. This study helps establish a relevant biologically active dose for clinical trials in the cervix, one corresponding to the 5- and 10-microM tissue doses.

Comparison of Gen-Probe DNA probe test and culture for the detection of Neisseria gonorrhoeae in endocervical specimens.

A 2-h nonisotopic DNA probe assay for the direct detection of Neisseria gonorrhoeae in urogenital specimens has recently been modified (PACE 2; Gen-Probe, San Diego, Calif.). The new assay format was developed to increase the sensitivity of the assay and simplify procedural steps. In this study, the new DNA probe test was compared with a culture reference method for the detection of N. gonorrhoeae in endocervical specimens. The results of the DNA probe test were expressed as a ratio of relative light units (RLU) of the specimen/RLU of the cutoff recommended by the manufacturer. All patient samples with sample RLU/cutoff RLU ratios less than 0.7 were interpreted as negative, and ratios greater than 2.0 were interpreted as positive for gonorrhea. Samples with sample RLU/cutoff RLU ratios between 0.7 and 2.0 were repeated until two or more consistent negative or positive ratios were obtained. A total of 469 specimens were tested with an overall disease prevalence of 6.1%. Of the 469 patients tested, 5 specimens (1.0%) fell in this borderline region and were retested. If the manufacturer's recommended cutoff value had been used, the original DNA probe results would have resulted in two false-positives. Our data were analyzed for both symptomatic (prevalence, 11.7%) and asymptomatic (prevalence, 2%) women. The study indicated that with our modification of the manufacturer's endpoint interpretation, the DNA probe test was essentially equivalent to the culture method in terms of sensitivity, specificity, and positive and negative predictive values in both symptomatic and asymptomatic patient populations. The new DNA probe test can serve as a suitable screening and diagnostic test for the diagnosis of gonorrheal genital infections in women. Additionally, it offers the advantages of rapid turnaround time and ease of use and allows simultaneous testing for Chlamydia trachomatis on the same specimen.

Detection of Chlamydia trachomatis endocervical infection in asymptomatic and symptomatic women: comparison of deoxyribonucleic acid probe test with tissue culture.

A deoxyribonucleic acid probe assay (PACE 2, Gen-Probe, San Diego) was compared with a standard tissue culture method for detection of Chlamydia trachomatis endocervical infection in both asymptomatic and symptomatic women. The results of the probe test were expressed as a ratio of relative light units of the specimen per relative light units of the cutoff recommended by the manufacturer. Samples with sample/cutoff ratios near 1.0 were repeated until two or more consistent ratios were obtained. A total of 426 specimens were obtained, with an overall disease prevalence of 10.1%. Of the 426 specimens examined, seven (1.6%) were near the cutoff and were retested. The results of 426 samples with matching cultures indicated that the manufacturer's discrete cutoff was adequate for results determination. The deoxyribonucleic acid probe test was essentially equivalent to standard tissue culture in terms of sensitivity, specificity, and positive and negative predictive values in a low-prevalence patient population.