Hematological factors associated with immunity, inflammation, and metabolism in patients with systemic lupus erythematosus: Data from a Zhuang cohort in Southwest China.

INTRODUCTION: Hematological parameters play important role in multiple diseases. This study was to investigate the possible association of the routine hematological parameters involved in immunity, inflammation, and metabolism with systemic lupus erythematosus (SLE) in patients of Zhuang ethnicity in Guangxi, southwest China. METHODS: The medical records of 195 Zhuang SLE patients between January 2013 and November 2018 were retrospectively reviewed. Random forest algorithm and multivariate logistic regression were used to identify the feature hematological parameters in patients with SLE. Association rules were explored between each parameter and immunity- (IgG, IgA, IgM, C3, and C4), inflammation- (ESR, hs-CRP, and CAR), and metabolism- (TG, TC, HDL-C, LDL-C, TP, PA, ALB, and UA) related indexes. RESULTS: Random forest algorithm and logistic regression analysis showed that neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width (RDW), and platelet-to-lymphocyte ratio (PLR) were the feature parameters for distinguishing SLE patients from healthy controls. According to the ROC curves, the optimal cutoff values to predict SLE were 1.98 for NLR, 13.35 for RDW, and 145.64 for PLR. Association rule analysis showed that NLR was strongly associated with C3, hs-CRP, TG, ALB, and UA; RDW was strongly associated with C3, C4, hs-CRP, TG, and ALB; PLR was strongly associated with IgG, hs-CRP, HDL-C, and UA. CONCLUSIONS: Neutrophil-to-lymphocyte ratio, RDW, and PLR may serve as effective predictors of dysregulation in immunity, inflammation, and metabolism. These three indicators may be potential for cardiovascular risk assessment in Zhuang SLE patients in southwest China.

The association of interleukin-16 gene polymorphisms with IL-16 serum levels and risk of nasopharyngeal carcinoma in a Chinese population.

Interleukin (IL)-16 plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in DNA sequence of IL16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individual's susceptibility to nasopharyngeal carcinoma (NPC). To test this hypothesis, we investigated the association of IL16 gene polymorphisms and serum IL-16 levels with NPC risk in a Chinese population. We analyzed IL16 gene rs11556218 T/G, rs4778889 T/C, and rs4072111 C/T polymorphisms using PCR-RFLP and DNA sequencing, and serum IL-16 levels were measured by ELISA. The IL16 rs11556218 T/G polymorphism was significantly associated with the susceptibility to NPC patients. The TG genotype was associated with a significantly higher risk of NPC as compared with the TT genotype (OR = 2.05, 95% CI 1.04-4.01; p = 0.037). Patients carrying the G allele had a significantly higher risk for developing NPC compared with individuals carrying the T allele (OR = 1.79, 95% CI 1.07-3.01; p = 0.027). The serum IL-16 levels were increased in NPC patients compared with controls (p < 0.01); the genotypes carrying the IL16 rs11556218 G variant allele were associated with increased serum IL-16 levels compared with the homozygous wild-type genotype in NPC patients (all p values <0.01). Our data suggested that IL16 rs11556218 T/G polymorphism was associated with increased susceptibility to NPC through increasing the production of serum IL-16 levels.

Genetic variants of LncRNAs HOTTIP and MEG3 influence nasopharyngeal carcinoma susceptibility and clinicopathologic characteristics in the Southern Chinese population.

OBJECTIVE: Recent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC. METHODS: This research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics. RESULTS: In comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers. CONCLUSION: Individuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3.

Impact of NLRP3 gene polymorphisms (rs10754558 and rs10733113) on HPV infection and cervical cancer in southern Chinese population.

OBJECTIVE: Mutations in the NLRP3gene have previously been linked to certain forms of cancer, but there have not been any specific studies examining the association between NLRP3 polymorphisms and cervical cancer (CC). This study was therefore designed to investigate the effect of NLRP3 gene polymorphisms on HPV infection and cervical cancer in southern Chinese population. METHODS: Multiplex PCR and next-generation sequencing approaches were used to assess the NLRP3 rs10754558 and rs10733113 polymorphisms in 404 cervical lesion patients, including 227 diagnosed with CC and 177 diagnosed with cervical intraepithelial neoplasia(CIN), with 419 healthy female controls being included for comparison. Correlations between the rs10754558 and rs10733113 genotypes and alleles in these patients and CC and CIN were then analyzed. RESULTS: No correlations were found between NLRP3 rs10754558 and rs10733113 and human papillomavirus(HPV) infection status. Relative to the healthy control group, the NLRP3 rs10754558 GG genotype, CG + GG genotype, and G allele frequencies were significantly increased among patients with cervical lesions (CC and CIN) (OR = 1.815,P = 0.013;OR = 1.383, P = 0.026; OR = 1.284, P = 0.014,respectively), whereas no such differences were observed for rs10733113. A higher cervical lesion risk was detected for patients over the age of 45 exhibiting the rs10754558 GG genotype (OR = 1.848, P = 0.040). Additionally, the risk of CC was elevated in patients with the rs10754558 GG genotype or the G allele relative to patients with the CC genotype or the C allele(OR = 1.830, P = 0.029; OR = 1.281, P = 0.039). The rs10733113 genotypes or alleles were not significantly associated with CC risk (P > 0.05). No association between rs10754558 and rs10733113 genotypes and CC patient clinicopathological features were observed (P > 0.05). Serum NLRP3, IL-1ß, and IL-18 levels were significantly elevated in CC patients relative to healthy controls(P < 0.05). Relative to the CC genotype, CC patients harboring the rs10754558 GG genotype exhibited significantly elevated IL-1ß and IL-18 levels(P < 0.05). CONCLUSION: The rs10754558 polymorphism in the NLRP3 gene may contribute to an elevated risk of CC, although it is not significantly correlated with HPV infection and CC progression.

N7-methylguanosine-related miRNAs predict hepatocellular carcinoma prognosis and immune therapy.

N7-methylguanosine (m7G) modification has been notably linked with the development of many tumors. However, no investigations have been conducted on whether m7G-related miRNA (m7G-miRNA) is a prognostic index of hepatocellular carcinoma (HCC). Therefore, this investigation aimed to establish a predictive m7G-miRNA signature for efficient HCC prognosis and elucidate the associated immune cell infiltration (ICI) and functions in the tumor microenvironment. RNA sequencing and clinical data on 375 HCC and 50 healthy tissue samples were acquired from The Cancer Genome Atlas database. The m7G-miRNA regulators methyltransferase-like 1 and WD repeat domain 4 were acquired from the TargetScan database. Univariate Cox regression analysis was conducted on the 63 differentially expressed m7G-miRNAs identified. A prognostic signature that consisted of seven miRNAs was identified. According to their risk scores, individuals with HCC were divided into high-risk (HR) and low-risk (LR) cohorts. A Kaplan-Meier test revealed that survival in the HR HCC patients was poorer than in the LR cohort (p < 0.001). The area under the receiver operating characteristic curves of 1-, 3-, and 5-year overall survival were 0.706, 0.695, and 0.715, respectively. A nomogram of sex, risk score, age, and stage indicated the HCC patients' overall survival. Furthermore, it was indicated that the HR and LR patients had different degrees of ICI and immune function. A pathway enrichment analysis revealed the association of several immunity-linked pathways with the risk model. In conclusion, the signature established has great prognostic value and could be used as a new immunotherapy target for individuals with HCC.

Comprehensive Identification of Bridge Genes to Explain the Progression from Chronic Hepatitis B Virus Infection to Hepatocellular Carcinoma.

BACKGROUND: Hepatitis B virus infection co-occurs in 33% of individuals with hepatocellular carcinoma worldwide. However, the molecular link between hepatitis B virus and hepatocellular carcinoma is unknown. Thus, we aimed to elucidate molecular linkages underlying pathogenesis through in-depth data mining analysis. MATERIALS AND METHODS: Differentially expressed genes were identified from patients with chronic hepatitis B virus infection, hepatocellular carcinoma, or both. Gene set enrichment analysis revealed signaling pathways involving differentially expressed genes. Protein-protein interaction networks, protein crosstalk, and enrichment were analyzed to determine whether differentially expressed gene products might serve as a bridge from hepatitis B virus infection to hepatocellular carcinoma pathogenesis. Prognostic potential and transcriptional and post-transcriptional regulators of bridge genes were also examined. RESULTS: We identified vital bridge factors in hepatitis B virus infection-associated hepatocellular carcinoma. Differentially expressed genes were clustered into modules based on relative protein function. Signaling pathways associated with cancer, inflammation, immune system, and microenvironment showed significant crosstalk between modules. Thirty-two genes were dysregulated in hepatitis B virus infection-mediated hepatocellular carcinoma. CPEB3, RAB26, SLCO1B1, ST3GAL6 and XK had higher connectivity in the modular network, suggesting significant associations with survival. CDC20 and NUP107 were identified as driver genes as well as markers of poor prognosis. CONCLUSION: Our results suggest that the sustained inflammatory environment created by hepatitis B virus infection is a risk factor for hepatocellular carcinoma. The identification of hepatitis B virus infection-related hepatocellular carcinoma bridge genes provides testable hypotheses about the pathogenesis of hepatocellular carcinoma.

[The dissemination of CMV in urine of different group from Guangxi and the relationship between CMV infection and renal disease].

OBJECTIVE: To detect Human Cytomegalovirus (HCMV) DNA in urine samples from the following groups: pregnant women, sick newborns, hospitalized nephropathy patients, renal transplant recipients and normal population. Preliminarily study the relationship of HCMV infection and renal disease. METHODS: To detect HCMV DNA in morning urine samples by Real-time fluorescence quantitative PCR (FQ-PCR). RESULTS: The positive rates of HCMV DNA in the urine of pregnant women,sick newborns, hospitalized nephropathy patients, renal transplant recipients and normal population are 8.18%, 3.45%, 18.54%, 25.42%, 0.56%. CONCLUSION: The infection rates of HCMV in the urine of pregnant women and sick newborns are very high in Guangxi, it should take serious measures to prevent and control the situation. HCMV probably participate in the injury of kidney, and worsen the disease. It should be one of the causes of renal disease.