[Investigation and analysis of social security in patients with lung diseases in Kaizhou district of Chongqing].

Objective: To analyze the social insurance guarantee of pneumoconiosis patients in Kaizhou from 2006 to 2018, and to provide basis for the prevention and treatment of pneumoconiosis in the future. Methods: The social security situation of pneumoconiosis patients in Kai Zhou District in 2006-2018 years was analyzed. Results: There were 3357 cases of pneumoconiosis in Kaizhou District, with a social security rate of 99%; 79.4% of the coal mine pneumoconiosis patients, 87.5% of whom enjoy industrial injury insurance; the majority of the Xiangyu Railway pneumoconiosis patients were over 60 years old, accounting for 3.4%, all enjoy special treatment of Xiangyu Railway; the former township enterprises restructure pneumoconiosis patients, mainly under 60 years old, accounting for 3.4%. Among them, 79% enjoy work-related injury insurance, and 15.2% were rural poverty victims. Conclusion: Kaizhou district provides better social security for pneumoconiosis patients in this area, which can provide basis for formulating social security policies for pneumoconiosis patients in other areas.

[Analysis on social security of pneumoconiosis patients in two areas of Chongqing from 2006 to 2018].

Objective: To investigate the current status of social security among pneumoconiosis patients from two areas of Chongqing, China with different economic levels from 2006 to 2018, and to provide a reference for the development of security policy for pneumoconiosis patients. Methods: The current status of social security was analyzed for pneumoconiosis patients from A and B counties of Chongqing who were diagnosed from 2006 to 2018, and a comparative analysis was performed. Results: From 2006 to 2017, there was a significant increase in the number of newly diagnosed pneumoconiosis patients in A county, while the number of newly diagnosed pneumoconiosis patients remained relatively stable in B county. As of May 2018, there were 5738 pneumoconiosis patients in A county and 4155 pneumoconiosis patients in B county. Among the 5738 pneumoconiosis patients in A county, 5335 (93%) had employers, and among these patients, 2729 (47.6%) received one-time compensation from occupational injury insurance, and currently 1884 (32.8%) were covered by the insurance. Among the 4155 pneumoconiosis patients in B county, 2482 (59.7%) received one-time compensation from occupational injury insurance, and currently 3062 (73.7%) were covered by the insurance. The social security rate of pneumoconiosis patients was 71.0% in A county and 81.4% in B county, and there was a significant difference in the distribution of social security among pneumoconiosis patients between the two counties (χ(2)=4704.9, P<0.01) . Conclusion: Strict implementation of social security policies for pneumoconiosis patients by local governments is the key to solving social assistance for pneumoconiosis patients and improving their quality of life and social security level.

Gene therapy research in Asia.

Gene therapy has shown great potential for the treatment of diseases that previously were either untreatable or treatable but not curable with conventional schemes. Recent progress in clinical gene therapy trials has emerged in various severe diseases, including primary immunodeficiencies, leukodystrophies, Leber's congenital amaurosis, haemophilia, as well as retinal dystrophy. The clinical transformation and industrialization of gene therapy in Asia have been remarkable and continue making steady progress. A total of six gene therapy-based products have been approved worldwide, including two drugs from Asia. This review aims to highlight recent progress in gene therapy clinical trials and discuss the prospects for the future in China and wider Asia.

Cost analysis of adjuvant therapy with XELOX or FOLFOX4 for colon cancer.

AIM: XELOX and FOLFOX4 have both been recommended as adjuvant therapy for stage III colon cancer. This study compared the two regimens in terms of monetary costs, assuming equal efficacy of the therapies. METHOD: A retrospective financial audit was conducted of the medical records of patients treated with XELOX or FOLFOX4. All itemized expenses were classified as direct (chemotherapy, hospitalization, venous access and tests), related to adverse effects due to the adjuvant therapy, or societal (travel and time costs). The cost of supportive care was not included. RESULTS: XELOX involved less total cost to the patient than FOLFOX4 (a difference of US$2857.68), fewer costs related to adverse effects ($668.97), and less travel ($26.07) and time ($390.93) expenditure per patient. CONCLUSION: The results indicate that, overall, XELOX is a more affordable option than FOLFOX4 in China.

Regulation of epidermal growth factor receptor signaling by plasmid-based microRNA-7 inhibits human malignant gliomas growth and metastasis in vivo.

MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate genes expression by binding to the 3' untranslated region (UTR) of targets mRNAs and play critical roles in cancer pathways. Malignant glioma is the most common and highly lethal central nervous system tumor for which little effective treatment is available over several decades. The purpose of this study was to explore the therapeutic potential of plasmid-based microRNA-7 (miR-7) for gliomas in vivo. Enhancing miR-7 levels in vitro could significantly induce cell apoptosis, and inhibit cell proliferation, cell migration and invasion. Western blotting analysis was performed, which indicated that miR-7 directly inhibited epidermal growth factor receptor (EGFR) and further antagonized the downstream protein kinases including ERK, Akt and Stat3. Furthermore, systemic administration of miR-7 encapsulated in cationic liposome resulted in glioma xenografts growth arrest and the metastatic nodules decrease effectively in a sequence-specific manner. In this study, miR-7 was applied in glioma treatment for the first time in vivo. Our findings suggested that the plasmid-mediated gene therapy with miR-7 appeared to be a promising candidate for the development of new antitumor and anti-metastasis treatment for human glioma.

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).

Inhibition of hepatitis B virus gene expression by small interfering RNAs targeting cccDNA and X antigen.

To test the possible inhibition of hepatitis B virus (HBV) replication and expression by small interfering RNAs (siRNAs) targeting simultaneously covalenthy closed circular DNA (dnacccDNA) and X antigen, corresponding recombinant plasmids were transfected into HepG2.2.15 cells and the levels of cccDNA, HBXAg, HBcAg, and HBeAg were assayed at various times post transfection. As expected, the single siRNAs showed marked inhibitory effects but their combination was even more efficient. These results provide a new insight into the development of a potential anti-HBV strategy of enhancing the efficacy of individual antivirals and overcoming the high mutation rate of HBV.

[Cell heterogeneity of laryngeal carcinoma and evolution trajectory of epithelial cells].

Objective: To analyze the classification and functions of cell subsets in laryngeal carcinoma and metastatic lymph nodes, and to explore the evolution trajectory of epithelial cells to tumor cells. Methods: Single-cell RNA sequencing was performed on 5 cases of laryngeal cancer, matched metastatic lymph nodes and 3 normal tissues. Patients were admitted to Ningbo Medical Center Lihuili Hospital from October 22, 2019 to December 16, all patients were male, aged 53-70 years old. Cell subsets of the above-mentioned tissues were analyzed by the Seurat, and the biological functions of cell subpopulation were investigated by functional enrichment analysis. Malignant epithelial cells were identified using copy number variation (CNV). The evolutionary trajectory of epithelial cells to cancer cells was analyzed by cell trajectory analysis, and cancerous transitional cells were identified. The highly expressed genes in transitional cells were analyzed by the FindAllMarker of the Seurat and verified by immunohistochemistry. Results: A total of 66 969 high-quality cells were obtained in 9 major clusters: epithelial cells, T cells, B cells, fibroblasts, endothelial cells, myeloid cells, mast cells, plasmacytoid dendritic cells and nerve cells. The first 5 cell clusters were divided into 8, 6, 4, 3 and 2 subgroups, respectively. Four epithelial cell subsets (C0, C1, C2 and C5) were derived from tumor tissues and metastatic lymph nodes, and had high levels of CNV and tumor cell content. Cell trajectory analysis showed that the evolution trajectory of epithelial cells was from normal epithelial subpopulation C4 to early cancerous cell population C0, which differentiated into three major malignant cell subsets C1, C3, and C5. Epithelial cell C0 may represent the transitional cell population of carcinogenesis, and were enriched in biological processes such as epithelial-mesenchymal transformation and angiogenesis. C0 highly expressed sulforaphane (SFN) which may be related to the occurrence and development of cancer. Immunohistochemistry confirmed that SFN was highly expressed in tumor tissues and metastatic lymph nodes compared with paracancerous tissues. Conclusion: Single-cell sequencing may be used to elucidate the diversity of cells and functions in laryngeal carcinoma tissues and metastatic lymph nodes, and cell population C0 plays a key role in the evolution of cells.

Intestinal epithelium-derived BATF3 promotes colitis-associated colon cancer through facilitating CXCL5-mediated neutrophils recruitment.

Inflammation is a critical player in the development and progression of colon cancer. Basic leucine zipper transcription factor ATF-like 3 (BATF3) plays an important role in infection and tumor immunity through regulating the development of conventional type 1 dendritic cells (cDC1s). However, the function of BATF3 in colitis and colitis-associated colon cancer (CAC) remains unclear. Here, BATF3 wild-type and knockout mice were used to construct an AOM/DSS-induced CAC model. In addition, DSS-induced chronic colitis, bone marrow cross-transfusion (BMT), neutrophil knockout, and other animal models were used for in-depth research. We found that BATF3 deficiency in intestinal epithelial cells rather than in cDC1s inhibited CAC, which was depended on inflammatory stimulation. Mechanistically, BATF3 directly promoted transcription of CXCL5 by forming a heterodimer with JunD, and accelerated the recruitment of neutrophils through the CXCL5-CXCR2 axis, ultimately increasing the occurrence and development of CAC. Tissue microarray and TCGA data also indicated that high expression of BATF3 was positively correlated with poor prognosis of colorectal cancer and other inflammation-related tumors. In summary, our results demonstrate that intestinal epithelial-derived BATF3 relies on inflammatory stimulation to promote CAC, and BATF3 is expected to be a novel diagnostic indicator for colitis and CAC.

Quantum theory for cold avalanche ionization in solids.

A theory of photon-assisted impact ionization in solids is presented. Our theory makes a quantum description of the new impact ionization-cold avalanche ionization recently reported by P. P. Rajeev, M. Gertsvolf, P. B. Corkum, and D. M. Rayner [Phys. Rev. Lett. 102, 083001 (2009)]. The present theory agrees with the experiments and can be reduced to the traditional impact ionization expression in the absence of a laser.

Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.

Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.

Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase.

Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). Complete screening of the SOD1 coding region revealed that the mutation Ala4 to Val in exon 1 was the most frequent one; mutations were identified in exons 2, 4, and 5 but not in the active site region formed by exon 3. The 2.4 A crystal structure of human SOD, along with two other SOD structures, established that all 12 observed FALS mutant sites alter conserved interactions critical to the beta-barrel fold and dimer contact, rather than catalysis. Red cells from heterozygotes had less than 50 percent normal SOD activity, consistent with a structurally defective SOD dimer. Thus, defective SOD is linked to motor neuron death and carries implications for understanding and possible treatment of FALS.

Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2.

Matrix metalloproteinase-2 (MMP-2) has been used as a target for cancer immunotherapy. The activation of immunization by breaking immune tolerance to self-MMP-2 may be one of the promising approaches for the treatment of MMP-2-positive tumors. In this study, we constructed the xenogeneic tumor cell vaccine c-MMP-2 by transfecting CT26 and LLC cells with chicken MMP-2 cDNA constructs. MMP-2-specific autoantibodies in sera and tumor cells were found in mice immunized with c-MMP-2. Protection against tumor growth was evaluated in respect of the relative contributions of autoantibodies, CD4+, and CD8+ T cells. Treatment with this vaccine (c-MMP-2) also prolonged the survival time of mice bearing cancer. The specific cytotoxic T-cell responses suggested that the treatment increased CD8+ T-cell activity. The antitumor activity of c-MMP-2 was abrogated by in vivo depletion of CD4+ and CD8+ T-lymphocytes and improved by adoptive transfer of CD4+ and CD8+ T-lymphocytes from the mice treated with c-MMP-2. An alternative DNA vaccination strategy for cancer therapy was identified in this study by eliciting humoral and cellular immunoresponse with a crossreacting transfectant.

Survey of indoor sarcosaphagous insects.

Entomological evidence provides valuable information for estimating postmortem interval and location of death in criminal or legal investigations. The colonization of sarcosaphagous insects are commonly discovered in the decomposed corpses in most indoor cases. Therefore, by analyzing the growth patterns and behavioral rhythms of these insects, the application of indoor sarcosaphagous insects in actual cases can be investigated. This study classifies the common species of indoor sarcosaphagous insects and analyzes the characteristics of these insects (such as foraging, oviposition, and growth). It further discusses the effect of micro-environment on their behavior. In addition, the research status of the application of indoor sarcosaphagous insects in forensic investigations is summarized.

Systemic inhibition of tumor growth by soluble Flk-1 gene therapy combined with cisplatin.

Soluble Flk-1, a soluble vascular endothelial growth factor (VEGF) receptor, is a potent inhibitor of angiogenesis, which could restrain growth and metastasis of some experimental tumors. However, antiangiogenic agents alone cannot eradicate tumor completely, and should be combined with other therapy to enhance their effects. In this study, we evaluated the antitumor activity of the combination therapy in the immunocompetent BALB/c mice bearing H22 hepatoma and Meth A fibrosarcoma, respectively. Mice were treated with either msFlk-1 i.m. at 100 microg/mouse once every 3 days for four times from day 3 after the tumor cell injection, cisplatin cycled twice (2 mg/kg i.p. on days 4 and 11 after the tumor cell inoculation), or both agents together. Tumor growth and survival time were continually observed. Antiangiogenesis in vivo was determined by CD31 immunohistochemistry. Assessment of apoptotic cells and histological analysis was also conducted in tumor tissues. Our results showed that the combination therapy could evidently improve antitumor efficacy, including tumor growth suppression, mice survival prolongation, tumor cell apoptosis augmentation as well as neovascularization inhibition as compared with controls, without serious adverse effects. Our data suggest that the combination of DDP with msFlk-1 is more effective to suppress tumor growth in mice than either agent alone, and this combination regimen showed its potential for future clinical application.

Identification of a locus for disseminated superficial actinic porokeratosis at chromosome 12q23.2-24.1.

Disseminated superficial actinic porokeratosis is an autosomal dominant cutaneous disorder characterized by many uniformly small, minimal, annular, anhidrotic, and keratotic lesions. The genetic basis for this disease is unknown. Using a genomewide search in a large Chinese family, we identified a locus at chromosome 12q23.2-24. 1 responsible for disseminated superficial actinic porokeratosis. The fine mapping study indicates that the disseminated superficial actinic porokeratosis gene is located within a 9.6 cM region between markers D12S1727 and D12S1605, with a maximum two-point LOD score of 20.53 (theta = 0.00) at D12S78. This is the first locus identified for a genetic disease where the major phenotype is porokeratosis. The study provides a map location for isolation of a gene causing disseminated superficial actinic porokeratosis.

Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement.

This report concerns retrospective immunohistochemical and immunoelectron microscopic studies on superoxide dismutase-1 (SOD1) in intracytoplasmic hyaline inclusions (IHIs) of the anterior horn cells of three patients with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. All of the patients were members of the American "C" family. Almost all of the IHIs, present in the soma and cordlike swollen neurites of some affected neurons of the three patients, were intensely stained by an antibody to human SOD1. By contrast, the cytoplasm of anterior horn cells of the ALS patients and of ten control individuals reacted only weakly with the antibody or not at all. Immunoelectron microscopy revealed that the granule-associated thick linear structures that composed the IHIs were intensely labeled by the antibody to SOD1. The IHIs were also positively stained by antibodies to ubiquitin and phosphorylated neurofilament protein, with the distribution of immunoreactivity resembling that seen with the anti-SOD1 antibody. The DNA analysis disclosed a single-site GCC to GTC substitution at codon 4 (Ala4 --> Val) in the SOD1 gene from the brain samples of the patients and from the peripheral blood of their family members. Our results suggest that SOD1 is a component of IHIs and may interact with Ubiquitin and neurofilament protein, and point to the possibility that the presence of intense SOD1 immunoreactivity in the IHIs may be of relevance in processes involving structurally altered SOD1 molecules encoded by the mutated gene.

Novel mutations in spastin gene and absence of correlation with age at onset of symptoms.

Autosomal dominant hereditary spastic paraplegia is genetically heterogeneous, with at least five loci identified by linkage analysis. Recently, mutations in spastin were identified in SPG4, the most common locus for dominant hereditary spastic paraplegia that was previously mapped to chromosome 2p22. We identified five novel mutations in the spastin gene in five families with SPG4 mutations from North America and Tunisia and showed the absence of correlation between the predicted mutant spastin protein and age at onset of symptoms.

Isolation of 24 novel cDNA fragments from microdissected human chromosome band.

The strategy of isolating the band-specific expression fragments from a probe pool generated by human chromosome microdissection was reported. A chromosome 14q24.3 band-specific single copy DNA pool was constructed based on this probe pool. Using total DNA of the pool as probe to hybridize the human marrow cDNA library, 68 primary positive clones were selected from 5 x 10(5) cDNA clones. Among these primary clones, 32 secondary clones were obtained after second-round screening and designed as cFD14-1-32. Finally, 24 band-specific expression fragments were identified from these 32 positive clones by DNA hybridization. Those band-specific clones can hybridize to both 14q24.3 DNA and human genomic DNA but can't hybridize to 17q11-12 DNA. Partial sequences of 13 fragments of them were sequenced and identified as novel cDNA sequences, and these sequences were proved to have some homology with known genes in NCBI database. Analysis of expression spectrum of cFD14-1 suggested that the cDNA fragments thus obtained should be used to isolate the genes can not been cloned in 14q24.3 region.

Penta X syndrome: a case report with review of the literature.

We describe a 6 month-old girl with a 49, XX-XXX chromosome constitution. The patient had a characteristic round face, a low hairline, hypertelorism, epicanthus, a long philtrum, high-arched palate, short and webbed neck, small hands and feet, clinodactyly of the fifth fingers, overlapping toes, and separation between the first and the second toes. She also had atrial septal defect and patent ductus arteriosus complicated by myocarditis which exacerbated the course of her congestive heart failure. Psychomotor development was retarded with opisthotonoid posture, axial hypotonia, and with a borderline abnormal EEG. A densitometric, transmission analysis on X-linked polymorphic DNA-fragments of the Southern blots of the patient and the parents, using P20/MspI and pERT87-1/XmnI as probe/enzyme combinations, showed that the pentasomy X had resulted from 3 successive nondisjunctions at maternal meiosis. Clinical manifestations among 22 previously reported penta X syndrome patients are also reviewed.