Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma.

Introduction: A copper-dependent cell death, cuproptosis, involves copper binding with lipoylated tricarboxylic acid (TCA) cycle components. In cuproptosis, ferredoxin 1 (FDX1) and lipoylation act as key regulators. The mechanism of cuproptosis differs from the current knowledge of cell death, which may invigorate investigations into copper's potential as a cancer treatment. An extremely dismal prognosis is associated with gliomas, the most prevalent primary intracranial tumor. In patients with glioma, conventional therapies, such as surgery and chemotherapy, have shown limited improvement. A variety of cell death modes have been confirmed to be operative in glioma oncogenesis and participate in the tumor microenvironment (TME), implicated in glioma development and progression. In this study, we aimed to explore whether cuproptosis influences glioma oncogenesis. Methods: Gene expression profiles related to cuproptosis were comprehensively evaluated by comparing adjacent tissues from glioma tissues in The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) database. Gene expression, prognostic, clinical, and pathological data of lower-grade gliomas (LGG) and glioblastoma were retrieved from TCGA and Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) databases. The datasets were managed by "Combat" algorithm to eliminate batch effects and then combined. A consensus clustering algorithm based on the Partitioning Around Medoid (PAM) algorithm was used to classified 725 patients with LGG and glioblastoma multiforme (GBM) into two cuproptosis subtypes. According to the differentially expressed genes in the two cuproptosis subtypes, 725 patients were divided into 2 gene subtypes. Additionally, a scoring system that associated with TME was constructed to predict patient survival and patient immunotherapy outcomes. Furthermore, we constructed a prognostic CRG-score and nomogram system to predict the prognosis of glioma patients. 95 tissue specimens from 83 glioma patients undergoing surgical treatment were collected, including adjacent tissues. Using immunohistochemistry and RT-qPCR, we verified cuproptosis-related genes expression and CRG-score predictive ability in these clinical samples. Results: Our results revealed extensive regulatory mechanisms of cuproptosis-related genes in the cell cycle, TME, clinicopathological characteristics, and prognosis of glioma. We also developed a prognostic model based on cuproptosis. Through the verifications of database and clinical samples, we believe that cuproptosis affects the prognosis of glioma and potentially provides novel glioma research approaches. Conclusion: We suggest that cuproptosis has potential importance in treating gliomas and could be utilized in new glioma research efforts.

Comparison of Genomic Copy Number Variations Among Breast Cancer Subtypes / 肿瘤防治研究

Objective To compare genomic copy number variations (CNVs) among different subtypes of breast cancer and analyze specific CNVs in each subtype. Methods AIMS software was used for genotype breast cancer (BasL, Her2, LumA and LumB), and GISTIC2.0 software was used to analyze genome-wide CNVs in tumor tissues from TCGA. We collected and analyzed the information and samples of 324 cases of invasive breast cancer admitted to Jiangmen Central Hospital(JMCH). Fluorescence quantitative PCR was used to detect the CNV of ERBB2, TFDP1, MIR148B, CCND1, MDM2 and MIR139 genes in the tumor tissues, to verify TCGA analysis. Results 13q34 was specifically amplified and 12q13.13 was specifically deleted in BasL-type breast cancer. The 17q12 was specifically amplified in Her2 type. The 12q15 was specifically amplified and 11q13.4 was specifically deleted in LumB type, but LumA type had no specific amplification or deletion of chromosome region. The proportion of TFDP1 amplification or MIR148B deletion in BasL type were 57.8% (TCGA) and 71.4% (JMCH), which were significantly higher than other subtypes (P < 0.001). The proportion of ERBB2 amplification of Her2 type were 55.2% (TCGA) and 86.7% (JMCH), which were significantly higher than other subtypes (P < 0.001). The proportion of LumB type with CCND1 or MDM2 amplification or MIR139 deletion were 47.6% (TCGA) and 61.8% (JMCH), which were significantly higher than other subtypes (P < 0.05). Conclusion At the CNV level of breast cancer, Her2 type is characterized by the amplification of ERBB2, BasL type is characterized by the amplification of TFDP1 or the deletion of MIR148B, LumB type is characterized by the amplification of CCND1 or MDM2 or the deletion of MIR139, but LumA type lacks specific CNV characteristics.

[HIV-1 gene subtypes among newly reported HIV/AIDS cases in two border areas of Yunnan province].

Objective: To explore the features of distribution on HIV-1 gene subtypes among newly reported HIV/AIDS cases in the border areas of Yunnan province. Methods: A total of 233 newly reported HIV/AIDS cases aged 18 or more were consecutively included in the border counties of Dehong Dai and Jingpo autonomous prefecture (Dehong prefecture), Honghe Hani and Yi autonomous prefecture (Honghe prefecture) of Yunnan province from November 2015 to October 2016. HIV-1 RNA was extracted with pol and env genes amplified. HIV-1 gene subtypes were determined through phylogenetic analysis. Results: A total of 146 out of 233 specimens were genotyped successfully. HIV-1 was found to have had 8 gene subtypes in Dehong prefecture, with the unique recombinant forms (URFs) as the predominant (52.8%, 57/108) type, including 56.8% (21/37) of the cases with Chinese ethnicity and another 50.7% (36/71) were Myanmar citizens. Four HIV-1 gene subtypes were detected in Honghe prefecture, with CRF01_AE as predominant (71.1%, 27/38), including 81.0% (17/21) Vietnamese and 58.8% (10/17) Chinese. Differences on the distribution of HIV-1 gene subtypes were seen statistically significant between Dehong prefecture and Honghe prefecture (χ(2)=61.072, P<0.001). Conclusions: The distribution of HIV-1 gene subtypes showed big difference in the two border areas of Yunnan province, suggesting that both Chinese or non- Chinese citizens living in the area should be taken good care of, in terms of HIV/AIDS prevention and control.

[HIV gene subtypes of newly reported HIV/AIDS cases in Dehong Dai and Jingpo autonomous prefecture of Yunnan province, 2016].

Objective: To explore distribution of HIV gene subtypes among newly reported HIV/AIDS cases from China and Myanmar in Dehong Dai and Jingpo prefecture of Yunnan province in 2016. Methods: We conducted DNA extractions from newly reported HIV/AIDS cases in 2016. The gag, env and pol genes were amplified by using reverse transcription-PCR (RT-PCR) and sequenced to identify HIV subtypes. Results: A total of 1 112 newly diagnosed HIV cases were reported in Dehong in 2016, and the HIV subtypes were identified for 860 cases. Subtype C was predominant (33.6%), followed by unique recombinant forms (URFs) (28.4%), CRF01_AE (18.6%) and so on. URFs include four recombination, among which the recombination of CRF01_AE and C subtype were predominant. The HIV subtype distribution was associated with nationality and transmission route in HIV/AIDS cases from Myanmar. Conclusions: The gene subtypes of C, URFs and CRF01_AE were mainly distributed; distribution of URFs remained complex and diverse among newly reported HIV/AIDS cases in Dehong in 2016.

Analysis of human papillomavirus infection status and genotype distribution in women in Huzhou, China / 中华实验和临床病毒学杂志

Objective@#To observe the infection status and the distribution of the gene subtypes of human papillomavirus (HPV) in Huzhou.@*Methods@#Cervical exfoliated cells were collected from the women who attended the physical examination and the cervical HPV examination from June 2017 to December 2017 in Huzhou Maternal and Child Health-Care hospital. A total of 2 830 women were tested for 21 HPV genotypes (including HPV-16, 18, 31, 59, 66, 53, 33, 58, 45, 56, 52, 35, 68, 51, 39, 82, 26, 73, 6, 11, 81), using real-time polymerase chain reaction (RT-PCR), investigated the infection status and subtype distribution.@*Results@#Among the 2 830 women, 269 were positive for HPV, the total infection rate was 9.51% (269/2 830). The infection rate of single gene and double gene was 86.99% (234/269) and 11.90% (32/269), respectively. The infection rate of high-risk subtypes was 9.11% among the detected women (258/2 830), accounting for 83.77% of HPV gene detections (258/308). The HPV-58, 16, 52 were the most commonly found gene subtypes among the high-risk HPV. The rate of HPV infection and high-risk subtypes of HPV infection in women was the highest in the 56-60 year old group, and the lowest in the 31-35 year old group. In different age groups, the difference in high-risk HPV infection rate was statistically significant, the total infection rate had no statistical significance.@*Conclusions@#In Huzhou area, the HPV infection rate of women found through normal physical examination was 9.51%, the high risk type was 58, 16 and 52, and the 56-60 year old group was the high incidence group. This study provides the HPV infection status and HPV gene subtype distribution characteristics in women in Huzhou, which has important guiding value for the vaccine development and application, and for prevention of HPV infection.

HIV-1 gene subtypes among newly reported HIV/AIDS cases in two border areas of Yunnan province / 中华流行病学杂志

Objective To explore the features of distribution on HIV-1 gene subtypes among newly reported HIV/AIDS cases in the border areas of Yunnan province.Methods A total of 233 newly reported HIV/AIDS cases aged 18 or more were consecutively included in the border counties of Dehong Dai and Jingpo autonomous prefecture (Dehong prefecture),Honghe Hani and Yi autonomous prefecture (Honghe prefecture) of Yunnan province from November 2015 to October 2016.HIV-1 RNA was extracted with pol and env genes amplified.HIV-1 gene subtypes were determined through phylogenetic analysis.Results A total of 146 out of 233 specimens were genotyped successfully.HIV-1 was found to have had 8 gene subtypes in Dehong prefecture,with the unique recombinant forms (URFs) as the predominant (52.8％,57/108) type,including 56.8％ (21/37) of the cases with Chinese ethnicity and another 50.7％ (36/71) were Myanmar citizens.Four HIV-1 gene subtypes were detected in Honghe prefecture,with CRF01_AE as predominant (71.1％,27/38),including 81.0％ (17/21) Vietnamese and 58.8％ (10/17) Chinese.Differences on the distribution of HIV-1 gene subtypes were seen statistically significant between Dehong prefecture and Honghe prefecture (x2=61.072,P＜0.001).Conclusions The distribution of HIV-1 gene subtypes showed big difference in the two border areas of Yunnan province,suggesting that both Chinese or non-Chinese citizens living in the area should be taken good care of,in terms of HIV/AIDS prevention and control.

HIV gene subtypes of newly reported HIV/AIDS cases in Dehong Dai and Jingpo autonomous prefecture of Yunnan province, 2016 / 中华流行病学杂志

Objective To explore distribution of HIV gene subtypes among newly reported HIV/AIDS cases from China and Myanmar in Dehong Dai and Jingpo prefecture of Yunnan province in 2016.Methods We conducted DNA extractions from newly reported HIV/AIDS cases in 2016.The gag,env and pol genes were amplified by using reverse transcription-PCR (RT-PCR) and sequenced to identify HIV subtypes.Results A total of 1 112 newly diagnosed HIV cases were reported in Dehong in 2016,and the HIV subtypes were identified for 860 cases.Subtype C was predominant (33.6％),followed by unique recombinant forms (URFs) (28.4％),CRF01_AE (18.6％) and so on.URFs include four recombination,among which the recombination of CRF01 AE and C subtype were predominant.The HIV subtype distribution was associated with nationality and transmission route in HIV/AIDS cases from Myanmar.Conclusions The gene subtypes of C,URFs and CRF01_AE were mainly distributed;distribution of URFs remained complex and diverse among newly reported HIV/AIDS cases in Dehong in 2016.

HIV-1 gene subtypes among newly reported HIV/AIDS cases in two border areas of Yunnan province / 中华流行病学杂志

Objective To explore the features of distribution on HIV-1 gene subtypes among newly reported HIV/AIDS cases in the border areas of Yunnan province.Methods A total of 233 newly reported HIV/AIDS cases aged 18 or more were consecutively included in the border counties of Dehong Dai and Jingpo autonomous prefecture (Dehong prefecture),Honghe Hani and Yi autonomous prefecture (Honghe prefecture) of Yunnan province from November 2015 to October 2016.HIV-1 RNA was extracted with pol and env genes amplified.HIV-1 gene subtypes were determined through phylogenetic analysis.Results A total of 146 out of 233 specimens were genotyped successfully.HIV-1 was found to have had 8 gene subtypes in Dehong prefecture,with the unique recombinant forms (URFs) as the predominant (52.8％,57/108) type,including 56.8％ (21/37) of the cases with Chinese ethnicity and another 50.7％ (36/71) were Myanmar citizens.Four HIV-1 gene subtypes were detected in Honghe prefecture,with CRF01_AE as predominant (71.1％,27/38),including 81.0％ (17/21) Vietnamese and 58.8％ (10/17) Chinese.Differences on the distribution of HIV-1 gene subtypes were seen statistically significant between Dehong prefecture and Honghe prefecture (x2=61.072,P＜0.001).Conclusions The distribution of HIV-1 gene subtypes showed big difference in the two border areas of Yunnan province,suggesting that both Chinese or non-Chinese citizens living in the area should be taken good care of,in terms of HIV/AIDS prevention and control.

HIV gene subtypes of newly reported HIV/AIDS cases in Dehong Dai and Jingpo autonomous prefecture of Yunnan province, 2016 / 中华流行病学杂志

Objective To explore distribution of HIV gene subtypes among newly reported HIV/AIDS cases from China and Myanmar in Dehong Dai and Jingpo prefecture of Yunnan province in 2016.Methods We conducted DNA extractions from newly reported HIV/AIDS cases in 2016.The gag,env and pol genes were amplified by using reverse transcription-PCR (RT-PCR) and sequenced to identify HIV subtypes.Results A total of 1 112 newly diagnosed HIV cases were reported in Dehong in 2016,and the HIV subtypes were identified for 860 cases.Subtype C was predominant (33.6％),followed by unique recombinant forms (URFs) (28.4％),CRF01_AE (18.6％) and so on.URFs include four recombination,among which the recombination of CRF01 AE and C subtype were predominant.The HIV subtype distribution was associated with nationality and transmission route in HIV/AIDS cases from Myanmar.Conclusions The gene subtypes of C,URFs and CRF01_AE were mainly distributed;distribution of URFs remained complex and diverse among newly reported HIV/AIDS cases in Dehong in 2016.

Effects of the fish spawning inducer ovaprim on vasotocin receptor gene expression in brain and ovary of the catfish Heteropneustes fossilis with a note on differential transcript expression in ovarian follicles.

Ovaprim (OVP), a commercial formulation of a salmon GnRH analogue and the dopamine receptor-2 blocker domperidone, is a successful spawning inducer for fish breeding. It induces a preovulatory surge in LH, which stimulates the synthesis of a maturation-inducing steroid (MIS, 17,20ß-dihydroxy-4-pregnen-3-one) that initiates germinal vesicle breakdown (GVBD) and ovulation. Coincidently, the OVP treatment also stimulates vasotocin (VT) secretion in the brain and ovary of the catfish Heteropneustes fossilis that also stimulates the synthesis of the MIS. VT mediates its effect through V1- and V2-type receptors. In the present study in the catfish, we report that OVP stimulates the expression of VT receptor genes v1a1, v1a2 and v2a in the brain and ovary. A single intraperitoneal administration of OVP (0.5µL/g body weight) or incubation of post-vitellogenic ovarian follicles with 5µL/mL OVP, for 0, 4, 8, 12, 16, and 24h stimulated ovulation and GVBD, respectively, in a time-dependent manner. The OVP treatment in vivo stimulated brain VT receptor transcript levels 4h onwards. The peak expression was noticed at 12h (v1a1), 8 and 12h (v1a2), and 8, 12 and 16h (v2a), coinciding with FOM and ovulation. The VT receptor genes are expressed in the ovarian follicles compartmentally; both v1a1 and v1a2 are expressed in the isolated follicular layer (theca and granulosa) but absent in denuded oocytes. V2a is expressed in the denuded oocytes and not in the follicular layer. The OVP injection stimulated the v1a1 and v1a2 expression from 4h onwards in both intact follicle and isolated follicular layer, the peak expression was observed at 16h. The v2a expression was up-regulated in both intact follicles and denuded oocytes at 4h (denuded oocytes) or 8h (intact follicle) onwards with the peak expression at 12h and 16h (denuded oocytes) or at 16h (intact follicles). Under in vitro conditions, the OVP incubations elicited similar pattern of changes with the peak stimulation at 16h for all the genes. In conclusion, the VT receptor genes are differentially expressed in the ovarian follicles and OVP induced periovulatory stimulation of the VT receptor genes, coinciding with FOM and ovulation.

Chromosome-specific NOR inactivation explains selective rRNA gene silencing and dosage control in Arabidopsis.

In eukaryotes, scores of excess ribosomal RNA (rRNA) genes are silenced by repressive chromatin modifications. Given the near sequence identity of rRNA genes within a species, it is unclear how specific rRNA genes are reproducibly chosen for silencing. Using Arabidopsis thaliana ecotype (strain) Col-0, a systematic search identified sequence polymorphisms that differ between active and developmentally silenced rRNA gene subtypes. Recombinant inbred mapping populations derived from three different ecotype crosses were then used to map the chromosomal locations of silenced and active RNA gene subtypes. Importantly, silenced and active rRNA gene subtypes are not intermingled. All silenced rRNA gene subtypes mapped to the nucleolus organizer region (NOR) on chromosome 2 (NOR2). All active rRNA gene subtypes mapped to NOR4. Using an engineered A. thaliana line in which a portion of Col-0 chromosome 4 was replaced by sequences of another ecotype, we show that a major rRNA gene subtype silenced at NOR2 is active when introgressed into the genome at NOR4. Collectively, these results reveal that selective rRNA gene silencing is not regulated gene by gene based on mechanisms dependent on subtle gene sequence variation. Instead, we propose that a subchromosomal silencing mechanism operates on a multimegabase scale to inactivate NOR2.

The rate of HPV infection and HPV genotyping in women from Yingtan / 国际检验医学杂志

Objective To determine the rate of human papillomavirus virus (HPV)infection and HPV subtypes distribution in women from Yingtan,so as to provide more reliable and scientific clinical data for the prevention and control of cervical carcinoma. Methods 4 165 women were retrospectively analyzed,who were outpatients or physical examination people of Railroad Branch of People′s Hospital of Yingtan from January 2011 to June 2013.23 types of HPV genotypes were detected in cervical samples by u-sing the nucleic acid amplification and reverse dot hybridization technology.Results 1 311 HPV positive samples were found in 4 165 women (31.48%),of which 20.86% with single HPV genotype infection,6.27% with double HPV genotypes infection, 2.76% with triple HPV genotypes infection,0.84% with quadriad HPV genotypes infection,and 0.72% with more than quadriad HPV genotypes infection.HPV52 had the highest infection rate,accounting for 12.43%,following with HPV43,58,16.>20-25 age group had the highest infection rate(43.19%).Conclusion Women have high HPV infection rate in Yingtan,and HPV subtypes such as HPV52,43,58,16 are superior infection genotypes.

Subtypes of ADH2 gene in alcoholics.

Alocholism is the multifactorial disease influenced by genetic environmental interaction and genetic variation of the genes may be associated with alcohol dependence due to its modified function in behavioral and physiological responses. In the present study, genetic variation was detected in the subtypes of gene, coding for the alcohol metabolizing enzyme Alcohol Dehydrogenase 2 (ADH2). Blood samples were collected from the alcoholic and non alcoholic subjects and genotyping was performed using PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism), analysis to determine genetic polymorphisms in the ADH2 gene subtypes. The three subtypes of ADH2 gene (ADH2.1, ADH2.2 and ADH2.3) were found in both alcoholics (Family History Positive and Family History Negative) as well as non alcoholics.