Objective To make a genetic diagnosis of sporadic neurofibromatosis type 1 with café-au-lait spots as the only presentation in a child.Methods Blood samples were collected from an 8-year-old child patient,his parents,and 100 healthy human controls.The mutation of NF1 gene was detected by PCR and direct sequencing.Results No mutation was detected in the NF1 gene of the parents or the healthy controls.There was a de novo nonsense mutation c.3520C ＞ T (p.Q1174X) in the NF1 gene of the patient,which leaded to a premature termination codon.Conclusions The child with café-au-lait spots as the only manifestation is diagnosed with sporadic neurofibromatosis type 1 by genetic testing.The mutation c.3520C ＞ T (p.Q1174X) may be an underlying cause of neurofibromatosis type 1.

Objective To review the diagnosis and treatment of basal cell carcinoma of the scrorum. Methods Clinical data of 7 patients with basal cell carcinoma of the scrotum were analyzed retrospectively. The mean age of the patients was 66 years. The most common presenting symptom was a plaque or nodular lesion with pruritis on the scrotum. The lesions ranged from 1.5 cm to 4.5 cm in diameter. Five of the 7 patients had a history of misdiagnosis. The diagnosis was established by biopsy of the lesion in all the patients. All of the 7 patients had no distant metastasis at the time of diagnosis and were treated by wide surgical resection.Results Histopathologic examination of the specimens confirmed the negative surgical margins in all cases.The most common histological feature was lobules, columns, bands and cords of basaloid cells associated with a surrounding loose fibromucinous stroma.One patient developed left inguinal lymph node metastasis at 21 months postoperatively,and was treated by bilateral inguinal lymph node dissection.The patient was free of cancer for 36 months after that. Another patient developed lung metastasis 48 months after the first operation.He was treated by systemic chemotherapy with cyclophosph amide, epirubicin and cisplatin for 6 cycles and obtained complete remission.This patient was free of cancer for 13 months after the chemotherapy.The remaining 5 patients were all free of cancer after the operation. Conclusions Basal cell carcinoma of the scrotum is rare.Wide surgical resection alone is usually considered to be curative. Because of its potential of metastasis, long-term followup is indicated for this disease.

Hepatic encephalopathy (HE) is a common and complex neuropsychiatric complication in patients with liver cirrhosis and has the features of high incidence, recurrence, and mortality rates, and it is also an important factor for the increased risk of hospitalization and rehospitalization. At present, there are still no effective drugs for HE. Recent studies have found that intestinal microecological changes are associated with the development, progression, and prognosis of HE, and the regulation of intestinal flora has a certain preventive effect on HE. This article summarizes the research on the association between intestinal microecology and HE in recent years and hopes to provide new ideas for clinical prevention and treatment of HE.

Objective To establish the surveillance and risk assessment system of schistosomiasis in Jiangsu Province,so as to provide technical support for timely understanding of the risk of schistosomiasis transmission and implementation of target-ed control measures. Methods The surveillance sites of schistosomiasis were assigned according to the epidemic status and en-demic type of schistosomiasis as well as the characteristics of the water system,and the prevalence of Schistosoma japonicum in humans and domestic animals,and snail status were investigated. In addition,the quality control of serum detection of S. japon-icum infections was performed. The prevalence of human and animal S. japonicum infections,snail status and missing diagnosis of serum detection were analyzed and compared among regions. Results A total of 27 surveillance sites of schistosomiasis were set up in 26 counties of 10 cities,Jiangsu Province,including 14 sites in transmission-interrupted villages and 13 sites in trans-mission-controlled villages,and 15 sites in marshland and lake regions,9 sites in plain regions with water network and 3 sites in mountainous region. In the 27 surveillance sites,a total of 16 617 residents were screened for S. japonicum infection by using dipstick dye immunoassay(DDIA),and 326 were sero-positive,with a sero-prevalence of 1.96%(2.17%for men and 1.8%for women). Of the 326 individuals undergoing parasitological examination,2 positive cases were detected in the marshland and lake region,with a S. japonicum human prevalence of 0.01%. Of the 762 floating population detected,10 were positive for blood test,with a sero-prevalence of 1.31%,and no egg-positive individuals were detected. No infection was found in the 476 do-mestic animals. Of the 746 settings surveyed,a total of 240.7 hm2 snail area was detected,with a mean snail density of 0.06 snails/0.1 m2,and no infected snails were found. There were 780 quality-control sera detected in 26 surveillance sites of schisto-somiasis,and the gross coincidence rate was 95.13%,with misdiagnosis rate of 1.28%and missing diagnosis rate of 19.23%. Conclusion The surveillance sites of schistosomiasis show reasonable distribution in Jiangsu Province,and the endemic situa-tion of schistosomiasis appears a low level in the whole province.

Ultraviolet light(UV)-sensitive disorders refer to a group of diseases due to damages to the nucleotide excision repair mechanism which cannot effectively repair DNA damage caused by ultraviolet radiation. The inheritance pattern of such diseases, mainly including xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy, is autosomal recessive and known to involve 13 genes. As proteins encoded by such genes are involved in DNA repair and transcription pathways. There is overlap between the symptoms of such diseases, and their genotype - phenotype correlations are quite complex. To facilitate genetic and prenatal diagnosis for such diseases, a summary of the research progress is provided, which mainly focused on mutation research and genotype - phenotype correlation studies. We also propose a strategy for their genetic diagnosis based on recent findings of our group.
Biomedical Research ; methods ; trends ; Cockayne Syndrome ; genetics ; DNA Damage ; DNA Repair ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Skin ; metabolism ; pathology ; radiation effects ; Trichothiodystrophy Syndromes ; genetics ; Ultraviolet Rays ; Xeroderma Pigmentosum ; genetics

OBJECTIVETo investigate the impact of androgen receptor splice variant 7 (AR-V7) expression on overall survival for patients with metastatic prostate cancer.

METHODSThe data of 113 diagnosed metastatic prostate cancer patients from January 2002 to June 2010 were collected retrospectively, including patient's age at diagnosis, prostate-specific antigen (PSA) level at diagnosis,Gleason score, clinical stage, PSA nadir during hormonal therapy, the time to PSA nadir, vital status, survival time and cause of death. The expression of AR-V7 in prostate cancer tissue was detected by using immunohistochemical staining. The correlation of AR-V7 expression and patient clinicopathological characteristics in all patients were analysed using Student t-test or Chi-square test. Cox proportional hazards regression models were used to evaluate the predictive role of AR-V7 expression and patient characteristics for overall survival.

RESULTSThe median PSA nadir was 0.7 µg/L (ranged from 0.0 to 143.0 µg/L). The median time to PSA nadir was 8.1 months (ranged from 0.9 to 71.0 months). The follow-up was performed until March 12, 2014. During the follow-up period, 67 of 113 metastatic prostate cancer patients (59.3%) died and the median overall survival was 96 months (ranged from 5 to 135 months). The AR-V7 detection rate was 20.4% (23/113). The serum PSA level in patients with positively expression of AR-V7 was significantly higher than that without AR-V7 expression (t = 2.521, P = 0.013). Multivariate Cox regression analysis indicated that the expression of AR-V7 (HR = 2.421, P = 0.002) and time to PSA nadir (HR = 1.019, P = 0.022) were independent prognostic factors of overall survival for metastatic prostate cancer patients.

CONCLUSIONSThe expression of AR-V7 in prostate cancer tissues and time to PSA nadir during hormonal therapy are independent prognostic factors of overall survival for metastatic prostate cancer patients. Therapy targeting AR-V7 may improve prognosis of metastatic prostate cancer patients.

Adult ; Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Proportional Hazards Models ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; metabolism ; pathology ; Protein Isoforms ; metabolism ; Receptors, Androgen ; metabolism ; Retrospective Studies

ObjectiveTo explore the effect of Ganoderma leucocontextum ethanol extract (GLE) on silicosis and its potential molecular mechanism using network pharmacology, molecular docking technology and animal experiments. Methods i) The components of GLE were analyzed using ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS) method. The active components, potential molecular pathways and targets of GLE in the intervention of inflammation process of silicosis was explored using network pharmacology and molecular docking technology. ii) Specific pathogen free male C57BL6/J mice were divided into four groups with 10 mice in each group. The mice in the silicosis model group and GLE intervention group were given a dose of 80 μL silica suspension with a mass concentration of 50 g/L once by non-exposed tracheal instillation, and the mice in the blank control group and GLE control group were given an equal volume of sterile 0.9% sodium chloride solution. From the second day after modeling, GLE control group and GLE intervention group were given GLE at a dose of 200 mg/(kg•d) by gavage, while blank control group and silicosis model group were given the same volume of 0.9% sodium chloride solution by gavage, once per day for 35 days. After that, the histopathological changes of lung tissues of mice were observed, the lung mass coefficient, inflammation score and the ratio of collagen deposition area were calculated, and the levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in the lung tissues of mice were detected by enzyme-linked immunosorbent assay. Results i) A total of 76 active components of GLE were detected by UPLC-QE-MS. Among them, 36 ingredients met the screening criteria of the five principles of drug-like components. A total of 67 potential targets of the 36 GLE active ingredients to improve the inflammatory response of silicosis were screened based on the network pharmacology theory. The result of Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Ontology functional analysis showed that IL signaling and cytokine signaling of immune cells played a key role in the process of anti-silicosis of GLE. The results of molecular docking showed that the top 10 targets based on the 67 intersection targets were TNF, IL6, B-cell lymphoma 2, cellular tumor antigen p53, Caspase-3 subunit p12, JUN, epidermal growth factor receptor, IL1B, 67 kDa matrix metalloproteinase-9 and prostaglandin G/H synthase 2. The result of protein-protein interaction analysis showed that glycyrrhetinic acid had the strongest affinity with the key targets TNF-α, IL-1β and IL-6, followed by ganoderma acid DM, alismatol C, ganoderma acid β and red sapogenin. ii) The results of histopathological examination showed that the inflammatory response and collagen deposition were alleviated in the lungs of mice with silicosis. The lung mass coefficient, inflammation score, ratio of collagen deposition area and IL-6 expression in lung were lower in mice of the GLE intervention group (all P<0.05), compared with the silicosis model group. However, there was no significant difference in the levels of TNF-α and IL-1β in lung tissues between the two groups (all P>0.05). Conclusion GLE may reduce silica-induced lung inflammation and fibrosis by inhibiting the IL-6 level in lung tissues of mice. Its mechanism is associated with the synergistic action of multi-components, multi-targets and multi-pathways.

Objective: To investigate the expression and function of the TNF signaling pathway in the early stage of orthodontic tooth movement with periodontitis and to provide evidence to study the early inflammatory response in patients with periodontitis orthodontic treatment. Methods: Sixteen SD rats were randomly divided into four groups: group A--12 h of orthodontic tooth movement of the bilateral maxillary first molars in rats with periodontitis; group B--periodontitis model of the bilateral maxillary first molars without orthodontic tooth movement; group C--12 h of orthodontic tooth movement of the same teeth in rats with healthy periodontium; group D--control group without operations. The bilateral maxillary first molars and surrounding periodontal tissue of each group were collected for gene chip detection. Pathway enrichment analysis, qRT-PCR and GO (gene ontology) analysis were performed to identify differential genes involved in the TNF signaling pathway. Results : Gene chip results showed that the TNF signaling pathway was significantly upregulated in group A, group B and group C (P <0.01). Among the differential genes involved in the pathway, 28 were upregulated and 5 were downregulated in group A, 12 were upregulated and 4 were downregulated in group B, and 12 were upregulated and 1 was downregulated in group C (P <0.05). The most significant GO items included "response to lipopolysaccharide", "inflammatory response", "positive regulation of NF-κB transcription factor activity", "positive regulation of NF-κB import into nucleus" and "response to hypoxia"(P <0.001). qRT-PCR results showed no significant difference in TNF-α mRNA expression in group C compared with that in group D, TNF-α was upregulated in both groups A and B (P <0.01), and mRNA expression decreased in the following order: group A > group B > group C (P <0.05). Compared with group D, the expression levels of prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 ( IL-6) in groups A, B and C were significantly upregulated (P <0.05), but the expression levels of PTGS2 and IL-6 in group A were lower than those in group B (P < 0.05). Conclusion The TNF signaling pathway is activated in the early stage of orthodontic tooth movement in rats with periodontitis. The pathway products participate in many biological processes and play an important role in the inflammatory response and bone absorption.