Rare Case of Paraneoplastic Pemphigus Associated With Prostatic Cancer.

ABSTRACT: The combination of paraneoplastic pemphigus and prostate cancer is extremely unusual and has not been reported yet. Paraneoplastic pemphigus is caused by tumor-induced autoantibodies, which cause damage to the skin and mucosa. The essential treatment is active tumor control. Our patient received a robot-assisted radical prostatectomy and glucocorticoid therapy to improve his condition and relieve his skin lesions.

Computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee: outcomes of 12 cases.

BACKGROUND: To report the outcomes of computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee. METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) data were input into computer software to produce three-dimensional (3D) models of the tumor extent. Imaging data was then used to create a template for surgical resection, and development of an individualized combined allogeneic bone/endoprosthesis. Surgical simulations were performed prior to the actual surgery. RESULTS: This study included 9 males and 3 females with a mean age of 25.3 years (range, 13 to 40 years). There were 9 tumors in the distal femur and 3 in the proximal tibia. There were no surgical complications. In all cases pathologically confirmed clear surgical margins were obtained. Postoperative radiographs showed the range of tumor resection was in accordance with the preoperative design, and the morphological reconstruction of the bone defect was satisfactory with complete bilateral symmetry. The mean follow-up time was 26.5 months. Two patients died of their disease and the remaining are alive and well without evidence of recurrence. All patients are able to ambulate freely without restrictions. At the last follow-up, the average International Society of Limb Salvage score was 25.8 (range, 18 to 27), and was excellent in 8 cases and good in 4 cases. CONCLUSIONS: Computer-aided design and modeling for the surgical management of bone tumors and subsequent limb reconstruction provides accurate tumor removal with the salvage of a maximal amount of unaffected bone and precise endoprosthesis reconstruction.

[Multiomics and Multidimensional Testing for Efficacy Monitoring of Patients with Lymphoma].

OBJECTIVE: To explore the role of a new blood-based, multiomics and multidimensional method for evaluating the efficacy of patients with lymphoma. METHODS: 10 ml peripheral blood was extracted from each patient, and the genomic copy number aberrations (CNA) and fragment size (FS) were evaluated by low-depth whole genome sequencing of cfDNA, and the level of a group of plasma tumor marker (PTM) were detected at the same time. The cancer efficacy score (CES) was obtained by standardized transformation of the value of above three numerical indexes, and the changes of CES before and after treatment were compared to evaluate the patient's response to the treatment regimen. RESULTS: A total of 35 patients' baseline data were collected, of which 23 cases (65.7%) had elevated CES values. 18 patients underwent the first time test. The results showed that the CES value of 9 patients with positive baseline CES decreased significantly at the first test, and the efficacy evaluation was PR, which was highly consistent with the imaging evaluation results of the same period. At the same time, the CNA variation spectrum of all patients were evaluated and it was found that 23 patients had partial amplification or deletion of chromosome fragments. The most common amplification site was 8q24.21, which contains important oncogenes such as MYC. The most common deletion sites were 1p36.32, 4q21.23, 6q21, 6q27, 14q32.33, and tumor suppressor-related genes such as PRDM1, ATG5, AIM1, FOXO3 and HACE1 were expressed in the above regions, so these deletions may be related to the occurrence and development of lymphoma. CONCLUSION: With the advantages of more convenience, sensitivity and non-invasive, this multiomics and multidimensional efficacy detection method can evaluate the tumor load of patients with lymphoma at the molecular level, and make more accurate efficacy evaluation, which is expected to serve the clinic better.

Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis.

Varicocele, a cause of male infertility, occurs in nearly 40% of infertile males. It has been postulated that varicoceles may cause sperm DNA damage. Sperm DNA integrity has been recognized as one of the important determinants of normal fertilization and embryo growth in natural and assisted conception. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. Data were analysed using RevMan software. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). In conclusion, there is increased sperm DNA damage in patients with varicoceles and varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding. A varicocele is an important cause of male infertility and occurs in nearly 40% of infertile males. The recent understanding of the effect of varicoceles in male reproduction has led some researchers to postulate varicoceles as the possible cause of sperm DNA damage. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage by a similar method. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. The data were then entered in the RevMan software for analysis. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). Based on the results, it can be concluded that there is increased sperm DNA damage in patients with varicoceles and that varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding.

[Correlation of recurrent pregnancy loss with sperm parameters and sperm DNA fragmentation].

OBJECTIVE: To evaluate and compare standard sperm parameters and sperm DNA fragmentation in seminal ejaculates from men whose partners had a history of recurrent pregnancy loss (RPL) and a control group of men who had recently established their fertility. METHODS: Semen samples from 85 patients with a history of RPL and 20 men with proven fertility were analyzed according to World Health Organization guidelines. Sperm DNA fragmentation was detected by sperm chromatin dispersion test (SCD). RESULTS: A significant difference (P< 0.05) was observed in sperm motility but not other parameters between the two groups. The mean number of sperm cells with fragmented DNA, represented as DNA fragmentation index, was significantly increased in the RPL group [(34.99± 14.62)%] compared with controls [(10.82± 4.80)%]. CONCLUSION: This study has indicated that sperm from men with a history of RPL have a higher incidence of DNA damage and poor motility compared with fertile males.

Identification of autophagy-associated genes and prognostic implications in adults with acute myeloid leukemia by integrated bioinformatics analysis.

Acute myeloid leukemia (AML) is one of the most common malignant blood neoplasma in adults. The prominent disease heterogeneity makes it challenging to foresee patient survival. Autophagy, a highly conserved degradative process, played indispensable and context-dependent roles in AML. However, it remains elusive whether autophagy-associated stratification could accurately predict prognosis of AML patients. Here, we developed a prognostic model based on autophagy-associated genes, and constructed scoring systems that help to predicte the survival of AML patients in both TCGA data and independent AML cohorts. The Nomogram model also confirmed the autophagy-associated model by showing the high concordance between observed and predicted survivals. Additionally, pathway enrichment analysis and protein-protein interaction network unveiled functional signaling pathways that were associated with autophagy. Altogether, we constructed the autophagy-associated prognostic model that might be likely to predict outcome for AML patients, providing insights into the biological risk stratification strategies and potential therapeutic targets.

Preventive and therapeutic effects of green tea on lung cancer: a narrative review of evidence from clinical and basic research.

Background and Objective: Green tea is a popular beverage worldwide and has numerous health-promoting properties. Accumulating evidence indicates that green tea has preventive and therapeutic effects on lung cancer. This study aimed to investigate the association between green tea consumption and lung cancer. Methods: We performed a narrative review to summarized the association between green tea consumption and lung cancer. Key Content and Findings: Green tea consumption is known to decrease lung cancer risk in the general population, as indicated by meta-analyses of observational studies. Two active components of green tea, theabrownin and (-)-epigallocatechin gallate (EGCG), mediate the antitumor activity of green tea. Theabrownin promotes apoptosis, induces cell cycle arrest, and inhibits the migration, clone formation, and proliferation of lung cancer cell lines in vitro and in vivo. EGCG inhibits lung cancer cell proliferation and promotes apoptosis, agenesis, and epithelial-mesenchymal transition (EMT). In addition, EGCG sensitizes lung cancer cells to cisplatin and tyrosine kinase inhibitors (TKIs). The possible molecular mechanisms underlying the antitumor activity of EGCG and theabrownin were reviewed. Conclusions: Observational studies have indicated that green tea has preventive effects on lung cancer. In vitro and animal studies have indicated that green tea has therapeutic effects on lung cancer. Further clinical trials are needed to illustrate the therapeutic effects of green tea or its active components (i.e., theabrownin, EGCG) on lung cancer.

Tumor cell-derived exosomal microRNA-146a promotes non-small cell lung cancer cell invasion and proliferation by inhibiting M1 macrophage polarization.

Background: Tumor-associated macrophages (TAMs) affects the outcomes of non-small cell lung cancer (NSCLC). NSCLC cells released exosomes to suppress the antitumor activity of TAMs. MiR-146a is a critical regulator in TAM polarization. We hypothesized that NSCLC cells released exosomal miR-146a to regulate TAM polarization and thus affected its antitumor activity. Methods: We used H1299 cells-derived exosomes to stimulate THP-1 cells that was pretreated with phorbol 12-myristate 13-acetate (M0 macrophage). Flow cytometry and reverse transcription-quantitative polymerase chain reaction (PCR) were used to determine the polarization of macrophages. The conditioned medium of exosome-treated M0 cells was used to culture H1299 cells, and the Cell Counting Kit-8, Ki67, transwell and scratch wound assays were used to determine the biological behavior of H1299 cells. To investigate whether exosomal miR-146a regulates TAM macrophages through targeting tumor necrosis factor receptor-associated factor 6 (TRAF-6) and interleukin-1 receptor-associated kinase 1 (IRAK-1), we used small interfering RNA to knockdown the expressions of them. Results: Upregulation of miR-146a inhibited M1 polarization and thus impaired the antitumor activity of TAMs. Exosomes released by H1299 cells can be taken by M0 macrophage, and they upregulated the expression of miR-146a in M0 macrophage. The exosome suppresses M1 polarization by exosomal miR-146a. TRAF-6 and IRAK-1 mediated the inhibitive effects of exosomal miR-146a on M1 polarization. Conclusions: NSCLC cells released exosomal miR-146a to inhibit the expressions of TRAF-6 and IRAK-1 in TAMs, resulting in the impaired antitumor activity of TAMs. NSCLC cell-derived exosomal miR-146a represents a novel therapeutic target for NSCLC treatment.

[Clinical Significance of Peripheral Blood EBV-DNA Determination and Genotyping in Lymphoma Patients].

OBJECTIVE: To explore the clinical significance of Epstein-Barr virus（EBV） detection and classification in peripheral blood of lymphoma patients. METHODS: 101 lymphoma patients were enrolled, the clinical characteristics of the patients were collected, including ages, sex, types of lymphoma, Ann Arbor stages, extranodal infiltration and lactate dehyhrogenase. Fluorescent quantitative PCR technology was used to detect the EBV-DNA. Polymerase chain reaction and Agarose gel electrophoresis was used for determination of EB genotyping. The difference between curative effect in EBV-DNA+ and EBV-DNA－ patients, the correlation of adverse factors and EBV infection of the patients were analyzed. RESULTS: 68.3% (69/101) of the patients showed EBV-DNA positive. EBV-positive lymphoma patients showed more adverse prognostic factors than the patients with EBV-negative, which may lead to poorer disease outcome. Among the 46 B-cell non-Hodgkin's lymphoma patients, the overall response rate of EBV-positive patients (60.7%) was lower than EBV-negative patients(88.9%) (P<0.05); For 19 patients with Hodgkin's lymphoma, the overall response rate of EBV-positive patients (46.2%) was lower than EBV-negative patients (100%), the differences were statistically significant (P<0.05). Among 69 patients with EBV-infected lymphoma, 98.6% (68/69) showed type-2 EB virus, and 1.4% (1/69) were type-1 and type-2 mixed infections. CONCLUSION: Most of EBV-positive in lymphoma patients were EBV type 2, patients with EBV-DNA+ shows poorer efficacy than EBV-DNA－ patients.

Rapid and practical qualitative and quantitative evaluation of non-fumigated ginger and sulfur-fumigated ginger via Fourier-transform infrared spectroscopy and chemometric methods.

A strategy was developed to distinguish and quantitate nonfumigated ginger (NS-ginger) and sulfur-fumigated ginger (S-ginger), based on Fourier transform near infrared spectroscopy (FT-NIR) and chemometrics. FT-NIR provided a reliable method to qualitatively assess ginger samples and batches of S-ginger (41) and NS-ginger (39) were discriminated using principal component analysis and orthogonal partial least squares discriminant analysis of FT-NIR data. To generate quantitative methods based on partial least squares (PLS) and counter propagation artificial neural network (CP-ANN) from the FT-NIR, major gingerols were quantified using high performance liquid chromatography (HPLC) and the data used as a reference. Finally, PLS and CP-ANN were deployed to predict concentrations of target compounds in S- and NS-ginger. The results indicated that FT-NIR can provide an alternative to HPLC for prediction of active components in ginger samples and was able to work directly on solid samples.

Rapid Geographical Origin Identification and Quality Assessment of Angelicae Sinensis Radix by FT-NIR Spectroscopy.

Angelicae Sinensis Radix is a widely used traditional Chinese medicine and spice in China. The purpose of this study was to develop a methodology for geographical classification of Angelicae Sinensis Radix and determine the contents of ferulic acid and Z-ligustilide in the samples using near-infrared spectroscopy. A qualitative model was established to identify the geographical origin of Angelicae Sinensis Radix using Fourier transform near-infrared (FT-NIR) spectroscopy. Support vector machine (SVM) algorithms were used for the establishment of a qualitative model. The optimum SVM model had a recognition rate of 100% for the calibration set and 83.72% for the prediction set. In addition, a quantitative model was established to predict the content of ferulic acid and Z-ligustilide using FT-NIR. Partial least squares regression (PLSR) algorithms were used for the establishment of a quantitative model. Synergy interval-PLS (Si-PLS) was used to screen the characteristic spectral interval to obtain the best PLSR model. The coefficient of determination for calibration (R2C) for the best PLSR models established with the optimal spectral preprocessing method and selected important spectral regions for the quantitative determination of ferulic acid and Z-ligustilide was 0.9659 and 0.9611, respectively, while the coefficient of determination for prediction (R2P) was 0.9118 and 0.9206, respectively. The values of the ratio of prediction to deviation (RPD) of the two final optimized PLSR models were greater than 2. The results suggested that NIR spectroscopy combined with SVM and PLSR algorithms could be exploited in the discrimination of Angelicae Sinensis Radix from different geographical locations for quality assurance and monitoring. This study might serve as a reference for quality evaluation of agricultural, pharmaceutical, and food products.

[Detection of JAK2V617F and CALR Gene Mutations by Multiplex of Patients with Myeloproliferative Neoplasms PCR-Capillary Electrophoresis].

OBJECTIVE: To evaluate the proformance of multiplex PCR and capillary electrophoresis(MPCE) in the detection of JAK2V617F and CALR mutation in myeloproliferative neoplasms(MPN). METHODS: The specificity primers of JAK2617F gene mutation and the primers of CALR gene were designed at the same time. The JAK2V617F and CALR gene primers were labeled with Cy5 fluorescence, all the primers were mixed in one tube for multiplex PCR and the PCR prodcuts were analysised by capillary electrophoresis. Then detection limit and sensitivity of MPCE were evaluated, and compared with comercial diagnostic kit. RESULTS: JAK2V617F and CALR gene mutations could be detect by MPCE in one PCR test. JAK2V617F mutation could be detected at 0.01 ng genomic DNA, double positive JAK2V617F and CLAR gene mutations could be detected at 0.1 ng genomic DNA, at least 0.1% JAK2V617F positive mutation could be detected. The consistency between MPCE and commercial diagnostic gene mutation kit was 100%. CONCLUSION: It is developed that a new gene mutation detection method of JAK2 V617F and CLAR gene based on MPCE in our experiment and it can be used as a new reagent for molecular diagnosis of MPN patients.

Mechanism-based structure-activity relationship (SAR) analysis of aromatic amines and nitroaromatics carcinogenicity via statistical analyses based on CPDB.

Cancer is a leading cause of human mortality around the globe. In this study, mechanism-based SAR (Structure-Activity Relationship) was employed to investigate the carcinogenicity of aromatic amines and nitroaromatics based on CPDB. Principal component analysis and cluster analysis were used to construct the SAR model. Principle component analysis generated three principal components from 12 mechanism-based descriptors. The extracted principal components were later used for cluster analysis, which divided the selected 55 chemicals into six clusters. The three principal components were proposed to describe the "transport", "reactivity" and "electrophilicity" properties of the chemicals. Cluster analysis indicated that the relevant "transport" properties positively correlated with the carcinogenic potential and were contributing factors in determining the carcinogenicity of the studied chemicals. The mechanism-based SAR analysis suggested the electron donating groups, electron withdrawing groups and planarity are significant factors in determining the carcinogenic potency for studied aromatic compounds. The present study may provide insights into the relationship between the three proposed properties and the carcinogenesis of aromatic amines and nitroaromatics.