Investigating the prognostic value of constructing disulfidptosis-related gene models for lung adenocarcinoma patients.

OBJECTIVE: Disulfidptosis is a novel mode of cell death, a programmed mode of intracellular disulfide accumulation due to solute carrier family 7 member 11 (SLC7A11)-mediated abnormalities in the cell membrane cystine transport system. Numerous studies have confirmed the prominent role played by SLC7A11 in tumors, but the involvement of SLC7A11 as an important mediator of disulfidptosis in the death process of lung adenocarcinoma cells remains unclear. MATERIALS AND METHODS: We obtained 4,107 SLC7A11-related genes and analyzed them using a total of 1,040 lung adenocarcinoma transcriptome sequencing data from The Cancer Genome Atlas (TCGA) cohort and GEO (Gene Expression Omnibus) cohort and 991 relevant clinical data. First, we screened for differential genes and identified molecular subtypes for assessing characteristic differences between lung adenocarcinoma subtypes under the influence of SLC7A11-associated genes. Then, risk score models were constructed to assess the prognosis, immune infiltration, tumor microenvironment, and drug treatment effects in lung adenocarcinoma patients. Finally, we also analyzed the distribution of cell types and expression of characteristic genes within the tumor using a single-cell database. In addition, relevant drug sensitivities were predicted. RESULTS: We screened 956 genes with significant differences and identified 2 molecular subtypes and found significant differences in their prognosis and that subtype B had a significantly better survival prognosis than subtype A. In addition, we found that pathways associated with cell proliferation division and DNA repair were enriched in the high-risk type A samples. Finally, we constructed a robust risk-scoring system, and our risk analysis revealed a general reduction of various immune cell components and tumor stromal components in the immune microenvironment of high-risk lung adenocarcinoma and a distinct immune infiltration pattern of immune cells, which was associated with a lower survival rate. CONCLUSIONS: Our comprehensive analysis of SLC7A11-related genes suggests that disulfidptosis has a potential value in the tumor microenvironment, immunity, clinical outcome, and prognosis of lung adenocarcinoma. These findings may increase our understanding of disulfidptosis as a novel cell death paradigm and provide ideas for assessing the prognosis of lung adenocarcinoma and developing new diagnostic and therapeutic strategies.

[Analysis on the effect of sound insulation reconstruction in operation room of steel rolling production line in a steel plant].

Objective: To investigate the effect of sound insulation improvement on the noise exposure of workers in the operation room of hot rolling line for wide and heavy plate. Methods: From September 2019 to September 2017, based on the occupational health Survey, the data of 25 fixed operation rooms and workers in operation rooms of a steel rolling production line were collected retrospectively, the noise exposure levels before and after the improvement of sound insulation were statistically analyzed. Results: The noise exposure value of the workers, the qualified rate of 0 Grade 8 hours equivalent noise (L(EX, 8 h)) ≤85 dB (A) and the qualified rate of the design limit value of the operation room were all higher than those before the modification, the difference was statistically significant (P<0.01) , after the renovation, the Class II and above noise hazards were eliminated, the equivalent continuous a sound level (L(Aeq, 8 h)) >75 dB (A) of the workers in the operation room was 8h, and the noise level in the operation room still did not meet the Ergonomics limit standard. Conclusion: The improvement of sound insulation can effectively improve the working environment of noise workplace operating room and reduce the workers'noise exposure level.

[Retrospective investigation on explosive hearing loss of injured persons in explosion accidents involving a steel enterprise].

Objective: Through the investigation of the injured persons in explosion accidents, the impact of wearing the ear protectors device (anti-noise earplugs) on the auditory organs and hearing loss of the injured person was understood, which could provide reference for the clinical diagnosis, treatment and prevention of the explosive hearing impairment. Methods: A retrospective survey was conducted on 39 directly injured persons who were injured in 23 explosion accidents involving a steel plant from 1990 to 2016 as the explosive hearing loss, taking the time of the patient＇s injury and 3-6 months after the injury as the time of investigation and evidence collection, and according to whether to wear the ear protectors device for group comparison and statistical analysis. Results: There was no significant difference between the two groups in hearing loss, tinnitus, earache, headache, some patients with dizziness and craniocerebral injury, regardless of whether the injured person wore anti-noise earplugs or not (P=0.444-1) , the shock (coma) patients in the non-protected group were more common (34.8%, 8/23) , and the difference was statistically significant (P=0.012) ; Although auricle injury was detected in both groups and there was no significant difference between the two groups (P=1) , but the external ear canal injury, tympanic membrane perforation were more common in the non-protected group, and there was no external ear canal and tympanic membrane perforation in the wearing earplug group, and the difference between the two groups was significant (P=0.000) . After 3-6 months, the rehabilitation of auditory system and other symptoms in patients showed that the hearing loss, tinnitus, earache, headache, dizziness and other symptoms all disappeared in patients wearing earplugs, while the above symptoms in the non-protected group were improved but more persisted, and the difference between the two groups was statistically significant (P=0.000-0.012) , and there was no significant difference in rehabilitation conditions such as craniocerebral injury between the two groups (P=1) ; There were patients with unhealed auricle injury in both groups in 3-6 months after the injury, and there was no significant difference between the two groups (P=1) , however, in the non-protected group, 69.57% (16/23) of the patients with external auditory canal injury were still unhealed and none of the patients with tympanic membrane perforation recovered, and the difference between the two groups was obvious (P=0.000~0.001) ; Pure tone air conduction examination showed that the hearing of the earplugs wearers was well recovered at the time of the explosion, while irreversible hearing impairment was common in the non-protective group, the difference was statistically significant (P=0.000) . Conclusion: Ear protector plays an important role in protecting the auditory organs and hearing of workers in explosion accident, and it is an effective protective measure to prevent and reduce the damage of external ear canal, perforation of tympanic membrane and explosive hearing loss caused by explosion accidents.

[Preparation of folate-targeted magnetic nanocomposites loaded with TFPI-2 plasmid and cisplatin and evaluation of its targeting and inhibitory effect on nasopharyngeal carcinoma HNE-1 cells in vitro].

OBJECTIVE: To prepare a novel folate-targeted magnetic nanocomposites loaded with tissue facor pathway inhibitor 2 (TFPI-2) and cisplatin (CDDP) and to investigate its targeting ability and anti-tumor effect on nasopharyngeal carcinoma HNE-1 cells in vitro. METHODS: The copolymer folic acid-polyethylene glycol-polyethyleneimine (FA-PEG-PEI) was synthesized through amidation reaction, and then FA-PEG-PEI/ magnetic nanoparticles-CDDP/TFPI-2 (MNP-CDDP/TFPI-2) nanocomposites was obtained by electrostatic adsorption between TFPI-2 plasmid and magnetic nanoparticles loaded with CDDP (MNP-CDDP) with vortex FA-PEG-PEI. (1)H Nuclear Magnetic Resonance ((1)H NMR ) was used to determine if FA-PEG-PEI was synthesized. The particle size, zeta potential and morphology were detected by dynamic light scattering (DLS) and transmission electron microscope (TEM). The content of Fe and CDDP was measured by phenanthroline and o-phenylenediamine (OPDA) colourimetry. Agarose gel electrophoresis was used to analyze the binding ability of FA-PEG-PEI/MNP-CDDP to TFPI-2 plasmid. Molecular targeted uptake of FA-PEG-PEI/ MNP-CDDP/TFPI-2 coupling with green fluorescent protein (GFP) in NPC cells were observed by Prussian-blue iron staining and fluorescence microscope. The levels of TFPI-2 protein expression after transfection were evaluated by Western blot. The effects of nanocomposites on HNE-1 cells proliferation and apoptosis were measured with Cell Counting Kit-8(CCK-8) and flow cytometry. RESULTS: Special peak value of FA, PEG and PEI were showed on (1)H NMR spectrogram. The mean size and zeta potential of FA-PEG-PEI/MNP-CDDP/TFPI-2 were 141.1 nm and 21.5 mV. The nanocomposites showed a good monodispersity and an insufficient size uniformity under TEM. The content of Fe and CDDP were 116.2 µg/ml and 92.88 µg/ml, respectively. Agarose gel electrophoresis showed TFPI-2 could be encapsulated completely and protected from digestion of DNA enzyme as the mass ratio of FA-PEG-PEI/ MNP-CDDP and TFPI-2 plasmid was equal or higher than 1∶1. More blue-stained magnetic granulars and green fluorescence were seen in folate receptor (FR)-positive HNE-1 cells than in FR-negative CNE-2 (P<0.05) under microscope and fluorescence microscope. The level of TFPI-2 protein expression in HNE-1cells increased significantly after transfection by FA-PEG-PEI/ MNP-CDDP/TFPI-2, compared with other control groups (FA-PEG-PEI/MNP-CDDP group and TFPI-2 group), all P<0.05. The nanocomposites inhibitory effect on HNE-1 including cell growth inhibition rate (64.00%) and apoptosis rate (49.61%) were significantly higher than that in FA-PEG-PEI/MNP group (8.19%, 9.26%), FA-PEG-PEI/TFPI-2 group (40.35%, 19.85%) and FA-PEG-PEI/MNP-CDDP group(56.15%, 36.46%)(P<0.05). CONCLUSION: FA-PEG-PEI/MNP-CDDP/TFPI-2 nanocomposites was successfully synthesized using amidation and electrostatic adsorption technology and has a good molecular targeting and inhibitory effect on FR-positive HNE-1cells in vitro.

The NAD(+) salvage pathway modulates cancer cell viability via p73.

The involvement of the nicotinamide adenine dinucleotide (NAD(+)) salvage pathway in cancer cell survival is poorly understood. Here we show that the NAD(+) salvage pathway modulates cancer cell survival through the rarely mutated tumour suppressor p73. Our data show that pharmacological inhibition or knockdown of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD(+) salvage pathway, enhances autophagy and decreases survival of cancer cells in a p53-independent manner. Such NAMPT inhibition stabilizes p73 independently of p53 through increased acetylation and decreased ubiquitination, resulting in enhanced autophagy and cell death. These effects of NAMPT inhibition can be effectively reversed using nicotinamide mononucleotide (NMN), the enzymatic product of NAMPT. Similarly, knockdown of p73 also decreases NAMPT inhibition-induced autophagy and cell death, whereas overexpression of p73 alone enhances these effects. We show that the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) harbour significantly higher levels of NAMPT and lower levels of p73 than does the normal cell line (MCF-10A), and that NAMPT inhibition is cytotoxic exclusively to the cancer cells. Furthermore, data from 176 breast cancer patients demonstrate that higher levels of NAMPT and lower levels of p73 correlate with poorer patient survival, and that high-grade tumours have significantly higher NAMPT/p73 mRNA ratios. Therefore, the inverse relationship between NAMPT and p73 demonstrable in vitro is also reflected from the clinical data. Taken together, our studies reveal a new NAMPT-p73 nexus that likely has important implications for cancer diagnosis, prognosis and treatment.

Result and pedigree analysis of spontaneously abortion villus chromosome detecting by FISH.

The aim of this study was to evaluate the relationship between fetal karyotype and parental chromosomal abnormalities, and to provide a basis for clinical diagnosis and therapy in Northeast China. A total of 144 spontaneously aborted fetuses were analyzed by FISH to test for chromosome number and to recall couples for peripheral blood karyotype analysis. The rate of abnormal chorionic villus chromosomes was 35.42%. Villus chromosome abnormality rate of the first spontaneous abortion and repeated abortions were 40.54 and 33.64%, respectively (P < 0.05). The rate of chromosome abnormality in women with advanced maternal age and women younger than 35 years old were 46.43 and 32.76%, respectively (P < 0.05). In a recall of 112 couples for peripheral blood karyotype analysis, just 3 cases of 7 patients with peripheral blood chromosome abnormality showed abnormal FISH results in their abortion villi. Fetal chromosome number abnormality is a major cause of early abortion, and parental chromosomal abnormality is not the main factor in abnormal fetal karyotype. A complete evaluation and special treatment should be provided to couples with a history of recurrent miscarriage.

Prevalence of immunoglobulin A deficiency in Chinese blood donors and evaluation of anaphylactic transfusion reaction risk.

OBJECTIVES/AIMS: We investigated the incidence of immunoglobulin A (IgA) deficiency in Chinese population. BACKGROUND: The frequency of IgA deficiency, defined as a serum IgA level of <0.05 mg dL(-1) , has been broadly studied in different ethnic groups. Individuals with IgA deficiency may form specific antibodies against IgA, which can cause an anaphylactic response when the patient receives an IgA-containing blood transfusion. METHODS: A sandwich enzyme-linked immunosorbent assay was performed to screen for IgA deficiency and particle gel immunoassay used for confirmation. IgA antibodies were further detected by the DiaMed anti-IgA test in IgA-deficient blood donors. RESULTS: Of the total 22,609 healthy blood donors screened, only seven cases were confirmed as having IgA deficiency (<0.05 mg dL(-1) ). Another seven cases displayed relative IgA deficiencies, with mean IgA concentrations ranging from 0.39 to 3.70 mg dL(-1) . Anti-IgA was identified in 2 of the 14 IgA-deficient blood donors whose IgA levels were <5 mg dL(-1) . Estimation of the theoretical risk for IgA anaphylactic transfusion reaction was 0.009%. CONCLUSION: The prevalence of IgA deficiency in Chinese is low. However, potential risks exist in performing blood transfusion to IgA-deficient persons, and measures should be taken to reduce IgA anaphylaxis.

Seminal plasma zinc level may be associated with the effect of cigarette smoking on sperm parameters.

The aim of this study was to investigate the effect of cigarette smoking on seminal plasma zinc levels and sperm parameters, and to examine the role of seminal plasma zinc. Semen samples from 79 non-smokers and 68 smokers were obtained. There was a significant decrease in seminal plasma zinc in smokers and a clear correlation between seminal plasma zinc levels and the extent of smoking. Sperm parameters (concentration, motility and morphology) among smokers were significantly lower in comparison to non-smokers. These parameters were also significantly decreased among smokers with abnormal zinc levels, while there was no significant difference between non-smokers with normal zinc and non-smokers with abnormal zinc levels. As previous studies have shown that seminal plasma zinc is associated with a decrease of anti-oxidant defences, seminal plasma zinc could be a contributor to the effects of cigarette smoking on sperm parameters. In conclusion, cigarette smoking can affect sperm parameters and this study may help towards providing a mechanistic explanation.

Tumor-associated macrophages and CD3-zeta expression of tumor-infiltrating lymphocytes in human esophageal squamous-cell carcinoma.

The clinical significance of tumor-associated macrophages (TAMs) and CD3-zeta chain expression of tumor-infiltrating lymphocytes (TILs), and their correlation in human esophageal squamous cell carcinoma (SCC) are not very clear. Serial histological slides from 137 esophageal SCC patients who had undergone tumor resection were immunohistochemically studied with anti-CD68, anti-CD3-zeta and anti-CD3-epsilon antibodies. TAMs infiltration (expressed as macrophage index, M(phi)I) and CD3-zeta expression (judged by Z/E = CD3-zeta+ cells/CD3-epsilon+ cells ratio) in different tissue compartments were observed. We found that the total tumor tissue region had significantly higher macrophage density and lower CD3-zeta expression (mean +/- SD: M(phi)I(normal): 225.3 +/- 85.9; Z/E(total): 0.52 +/- 0.25; n = 137) relative to adjacent histologically normal esophageal squamous epithelium (M(phi)I(normal): 60.5 +/- 31.7, P < 0.001; Z/E(normal): 0.79 +/- 0.35, P = 0.001; n = 70). Significantly higher M(phi)I(stroma) (P = 0.006) and lower Z/E(total) (P = 0.016) were detected in patients with lymph node metastasis than in those without. Patients with high M(phi)I(total) and M(phi)I(cancer) but low Z/E(total) had poorer surgical outcomes. Univariate analysis of M(phi)I(total) and multivariate analysis of M(phi)I(total) with specific clinico-pathological parameters demonstrated M(phi)I(total) to be an independent prognostic factor for survival in esophageal SCC patients (Cox proportional hazard model, P = 0.029 and P = 0.031, respectively).

A survey of cigarette smoking among middle school students in 1988.

A survey of the prevalence of smoking in middle school students aged 13-21 years in Harbin city, China, was undertaken in the Spring of 1988. A random sample of 4712 students was selected using proportional stratified clustering. A self-administered confidential questionnaire relating to smoking habits and certain family and school factors was administered. The results showed that 1.29% of the students (2.21% boys and 0.38% girls) smoked regularly, 5.62% (10.52% boys and 0.76% girls) were light smokers and 13.77% (24.29% boys and 2.92% girls) smoked only occasionally. Smoking habits were related to the type of school and to age, there being a higher proportion of smoking in senior grade students. Students were significantly more likely to smoke if they were male and if their siblings smoked. Prevalence of regular smoking was not related to parental occupation or family income. It is suggested that anti-smoking education in the school curriculum should be directed towards students in middle school.