Association of Methylenetetrahydrofolate Reductase rs1801133 Gene Polymorphism with Cancer Risk and Septin 9 Methylation in Patients with Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies, with a high incidence and mortality worldwide. Methylated Septin 9 (mSEPT9) has been used clinically as an auxiliary tool for CRC screening. The aim of the present study was to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism with the risk of CRC and the methylation status of Septin 9 in CRC. METHODS: Information of 540 patients with a confirmed diagnosis of CRC and with a physical examination were utilized to assess the association of the MTHFR rs1801133 polymorphism with CRC and the methylation of SEPT9. MTHFR rs1801133 polymorphism was genotyped using polymerase chain reaction (PCR). The commercial Septin 9 Gene Methylation(mSEPT9) Detection Kit was used for plasma SEPT9 methylation analysis. RESULTS: Among 540 patients, 61.48% were men and the median age was 54.47 ± 13.14. 65.37% of all colorectal tumors developed in the rectum. 195 patients had negative mSEPT9 methylation, while 345 had positive results. 87 individuals with stage I, 90 with stage II, 287 with stage III, and 76 with stage IV colorectal cancer were included in the sample. The results demonstrated that the positivity rate and degree of methylation of mSEPT9 were remarkably higher in patients with more advanced TNM stages than in those with less advanced stages. The frequencies of the MTHFR rs1801133 CC genotype and allele C carriers in patients with CRC were significantly higher than those in healthy individuals (P = 0.006 and P = 0.001, respectively). The positivity rate of the mSEPT9 assay was significantly higher among the MTHFR rs1801133 TT genotype and allele T carriers than among the CC and allele C carriers respectively. The MTHFR rs1801133 TT genotype and allele T carriers were positively associated with the methylation of SEPT9 (OR = 3.320, 95% CI 1.485-7.424, P = 0.003 and OR = 1.783, 95% CI 1.056-3.010, P = 0.030, respectively). CONCLUSION: In conclusion, individuals harboring the MTHFR rs1801133 CC genotype had a higher risk of CRC and the MTHFR rs1801133 TT carriers were more susceptible to Septin 9 gene methylation.

RNA virus diversity in rodents.

Many zoonotic disease emergencies are associated with RNA viruses in rodents that substantially impact public health. With the widespread application of meta-genomics and meta-transcriptomics for virus discovery over the last decade, viral sequences deposited in public databases have expanded rapidly, and the number of novel viruses discovered in rodents has increased. As important reservoirs of zoonotic viruses, rodents have attracted increasing attention for the risk of potential spillover of rodent-borne viruses. However, knowledge of rodent viral diversity and the major factors contributing to the risk of zoonotic epidemic outbreaks remains limited. Therefore, this study analyzes the diversity and composition of rodent RNA viruses using virus records from the Database of Rodent-associated Viruses (DRodVir/ZOVER), which covers the published literatures and records in GenBank database, reviews the main rodent RNA virus-induced human infectious diseases, and discusses potential challenges in this field.

Clinical, epidemiological, and genotypic characteristics of rotavirus infection in hospitalized infants and young children in Yunnan Province.

Rotaviruses are the most important pathogenic cause of non-bacterial diarrhea in infants and children. Approximately 60% of hospital admissions for acute diarrhea worldwide are caused by rotavirus infection. Rotavirus infection and hospitalization among children in China are a social burden, resulting in economic loss. The prevalence and geographical distribution of rotavirus genotypes is variable, partially due to population migration. Due to the unique geographical conditions and climate in Yunnan Province, several viruses with new genotypes have emerged, and multiple genotypes have become co-epidemic. In this study, rotavirus infection screening and genetic characterization of epidemic strains were performed in 149,492 infants and children admitted to hospitals in six representative prefectures in Yunnan Province between 2019 and 2021. The prevalence of rotavirus infection was 13.39% and was highest in January and lowest in September. G9P[8] was the main epidemic rotavirus genotype. Other epidemic genotypes included G2P[4], G8P[8], G9P[4], G2P[8], G3P[8], G4P[8], G3P[4], and G4P[6]. Phylogenetic analysis revealed that locally epidemic strains were influenced by importation of strains from neighboring provinces and other Asian countries. These findings provide a scientific basis for rotavirus prevention and control and lay a foundation for preliminary studies to establish a rotavirus surveillance network in Yunnan Province.

Increased Risk of Neurological Disease Following Pediatric Rotavirus Infection: A Two-Center Case-Control Study.

BACKGROUND: Whether pediatric rotavirus infection is associated with extraintestinal complications remains unknown. METHODS: We conducted a case-control study to investigate the incidences and risks of rotavirus-associated extraintestinal complications in hospitalized newborns, infants, and children younger than 5 years. RESULTS: A total of 1325 young inpatients with rotavirus infection (754 male and 539 newborns) and 1840 controls without rotavirus infection (1035 male and 836 newborns) were included. The incidences of neurological disease were higher among rotavirus individuals compared with controls: newborns, 7.24% (39/539) versus 2.87% (24/836), P < .001; infants and young children, 19.59% (154/786) versus 12.35% (124/1004), P < .001. The associated odd ratios (ORs) for neurological disease frequency following rotavirus infection was 2.64 (95% confidence interval [CI], 1.57-4.44) for newborns and 1.73 (95% CI, 1.34-2.24) for infants and young children, which increased to 2.56 (95% CI, 1.57-4.18) in case-control (1:1) matching analysis and 1.85 (95% CI, 1.41-2.42) in confounder adjustment. Rotavirus infection was associated with other extraintestinal complications, depending on study population and disease severity. Outcome analysis revealed rotavirus infection and its consequences had a significant impact on hospitalization and discharge. CONCLUSIONS: Rotavirus exposure was associated with a spectrum of extraintestinal complications, particularly neurological disease. Rotavirus infection and subsequent consequences resulted in poor clinical outcomes.

Prevalence and Genotype Distribution of Human Papillomavirus Infection Among 40,613 Women: An Outpatient-Based Population Study in Kunming, Yunnan.

Human Papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. The current study aimed to investigate the prevalence and genotype distribution of HPV infection among outpatient-based populations. A total of 40,613 women were recruited from the First People's Hospital of the Yunnan Province. Our study retrospectively analyzed the results of cervical HPV screening among 40,613 women. The results of study showed the prevalence and genotype distribution of HPV infection was different among various outpatient-based populations, and the prevalence of HPV infection was the highest in the gynecological outpatients (26.59%), followed by reproductive gynecological outpatients (18.51%), and the prevalence of physically examined population was the lowest (8.15%). The outpatient-based population was facing a huge threat of HPV infection, especially women from the gynecology clinic. The three most common HPV genotypes were HPV-52 (4.79%), 16 (2.95%) and 58 (2.83%). However, the distribution of HPV genotype varied by populations, especially in physically examined population, the infection rate of HPV-81 ranked third among all infections with various genotypes. Two peaks of prevalence of HPV infection were observed among women under 25 years (31.93%) and over 55 years (28.55%), while the prevalence in women aged 46-55 years (20.18%) was the lowest. Our study on the prevalence and genotype distribution of HPV infection among various outpatient-based populations will provide scientific evidence for vaccination strategies of HPV and prevention and control plans of cervical cancer in Kunming area.

Phylogenetic characteristics of HIV among female cross-border travelers in Yunnan province between 2003 and 2012.

Sexual transmission is currently the main mode of transmission of the human immunodeficiency virus (HIV). In this study, 181 HIV-infected female cross-border travelers entering Yunnan province were recruited between 2003 and 2012. HIV RNAs were extracted from their frozen serum and gag-pol gene sequences were obtained for phylogenetic and recombination analyses. In total, 131 gag-pol gene sequences were obtained successfully, at a rate of 72.4%. The most prevalent subtypes were CRF01_AE, followed by CRF08_BC, subtypes B and C. The other four subjects were classified as undefined subtypes and other recombinants. The subtype distribution of intravenous drug users was significantly different from that of sexually transmitted infections and unknown groups. The genetic distances of subtype B, C, and CRF01_AE strains were all close to the reference sequences from Yunnan province and Southeast Asian countries. Gene diversity and cocirculation of multiple subtypes were observed in female cross-border travelers, and CRF01_AE was the dominant epidemic subtype. The advantages of these subtype preferences for sexual transmission were obvious in HIV infection and transmission among this population. Our findings also suggest that close attention should be given to the HIV infection status of the female migrant population. In addition, a description of their epidemic characteristics is significant for the surveillance and prevention of acquired immunodeficiency syndrome in the Yunnan province.

IRS4 promotes the progression of non-small cell lung cancer and confers resistance to EGFR-TKI through the activation of PI3K/Akt and Ras-MAPK pathways.

IRS4 is a member of the insulin receptor substrate (IRS) protein family. It acts as a cytoplasmic adaptor protein, integrating and transmitting signals from receptor protein tyrosine kinases to the intracellular environment. IRS4 can induce mammary tumorigenesis and is usually overexpressed in non-small cell lung cancer (NSCLC). However, little is known about the role of IRS4 in the development and progression of lung cancer. In this study, we show that IRS4 knockout suppresses the proliferation, colony formation, migration, and invasion of A549 lung cancer cells, as well as tumor growth in a nude mouse xenograft model. In contrast, stable expression of IRS4 showed the opposite effects. As expected, IRS4 was found to activate the PI3K/Akt and Ras-MAPK pathways, and we also showed that IRS4 depletion significantly enhanced the sensitivity of EGFR tyrosine kinase inhibitor (EGFR-TKI)-resistant cells to gefitinib. Taken together, these results show that IRS4 promotes NSCLC progression and may represent a potential therapeutic target for EGFR-TKI-resistant NSCLC.

Rotavirus-related systemic diseases: clinical manifestation, evidence and pathogenesis.

Rotaviruses, double-stranded, non-enveloped RNA viruses, are a global health concern, associated with acute gastroenteritis and secretory-driven watery diarrhoea, especially in infants and young children. Conventionally, rotavirus is primarily viewed as a pathogen for intestinal enterocytes. This notion is challenged, however, by data from patients and animal models documenting extra-intestinal clinical manifestations and viral replication following rotavirus infection. In addition to acute gastroenteritis, rotavirus infection has been linked to various neurological disorders, hepatitis and cholestasis, type 1 diabetes, respiratory illness, myocarditis, renal failure and thrombocytopenia. Concomitantly, molecular studies have provided insight into potential mechanisms by which rotavirus can enter and replicate in non-enterocyte cell types and evade host immune responses. Nevertheless, it is fair to say that the extra-intestinal aspect of the rotavirus infectious process is largely being overlooked by biomedical professionals, and there are gaps in the understanding of mechanisms of pathogenesis. Thus with the aim of increasing public and professional awareness we here provide a description of our current understanding of rotavirus-related extra-intestinal clinical manifestations and associated molecular pathogenesis. Further understanding of the processes involved should prove exceedingly useful for future diagnosis, treatment and prevention of rotavirus-associated disease.

Prevalence and Genotypes of Human Papillomavirus among Men in Yunnan Province, China.

Human papillomavirus (HPV) infection is one of the most commonly reported sexually transmitted infections. Persistent infection is associated with the development of cervical cancer. Men may serve as a medium for HPV transmission among women, and much remains unknown about the prevalence and genotypes of HPV infection among men in Yunnan Province. This study was designed to investigate these parameters among men in this region. Clinical information was collected from January 2015 to May 2020, and 369 men who wished to undergo tests for HPV were included in this study. HPV screening was performed using the HPV GenoArray Test Kit, and the anatomical site of sample collection was the urethra. The mean age was 36.15 ± 9.08 years. Our results revealed that the prevalence of HPV infection among men was 23.85% in Yunnan Province, and there was no association between age and HPV prevalence in men. There were 72 (81.81%) individuals positive for a single HPV type, and 16 (18.19%) positive for multiple HPV types. The most prevalent oncogenic HPV types were found to be 52, 51, and 16. The most prevalent types of HPV infection were similar between men and women in this region, though the prevalence of HPV in men was relatively high.

Vaginal Microbiota and HPV Infection: Novel Mechanistic Insights and Therapeutic Strategies.

Cervical cancer is a global public health concern. The complex interaction of genetic and environmental factors is critical for the progress of cervical cancer. Growing evidence suggests that microbes, human papillomavirus (HPV), and the immune system interact closely with each other to govern homeostasis of the vaginal environment and the health of the lower genital tract of females. Certain vaginal microbial strains may play either a protective or a pathogenic role in carcinogenesis of the cervix after HPV persistent infection. Probiotics can therefore present a putative therapeutic approach for cervical cancer. However, work in this field remains limited. Recent technological developments have allowed us to identify microbes and their products using culture-independent molecular detection techniques. In this review, we discuss the composition of the vaginal bacterial community, its commensal flora and the protective impact this has on the health of the female genital tract. This review will also describe critical immune factors in lower genital tract health and summarize the role of the vaginal microbiota in cervical carcinogenesis. Knowledge in this field has provided researchers with the clues and tools to propose the use of probiotics as a potential line of treatment for cervical cancer and has provided valuable insights into host-pathogen interaction dynamics within the female genital tract.

Completely genomic and evolutionary characteristics of human-dominant G9P[8] group A rotavirus strains in Yunnan, China.

G9P[8] rotavirus A (RVA) has been identified as the predominant genotype circulating in Yunnan, China. To elucidate the molecular characteristics of its genetic composition at the whole-genome level, the genomes of 12 strains isolated from paediatric patients with diarrhoea were fully sequenced and characterized. Eleven of the 12 strains were genotyped as G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, which is closely related to the Wa-like genotype 1 constellation. In contrast, one strain was genotyped as G9-P[8]-I1-R1-C1-M1-A1-N2-T1-E1-H1, with the NSP2 gene characterized as a DS-1 like genotype. Bayesian phylogenetic analysis indicated that G9 strains had emerged in 1932 with an estimated average evolutionary rate of 1.63×10-3 substitutions/site/year. Considering the high prevalence and fast evolutionary rate of G9P[8] rotaviruses, our results suggest that G9P[8] RVA should be strictly monitored in China.

The prevalence and genotype distribution of rotavirus A infection among children with acute gastroenteritis in Kunming, China.

The aim of this study was to determine the prevalence of rotavirus A (RVA) infections in children from Kunming, China, and the RVA genotypes present. A total of 16,311 children with acute gastroenteritis were recruited for the study, and 33.1 % (5,394/16,311) were RVA positive. Children under 24 months of age were more susceptible to RVA infection, with an infection rate of 87.4 % (4,712/5,394). The most prevalent genotype was G9P[8] (85/107, 79.4 %), which showed high sequence similarity to G9P[8] strains from other regions of China and neighbouring countries, but not to the licensed vaccine strain LLR. These findings should be useful for the prevention of RVA infections.