Ibrutinib versus bendamustine plus rituximab for first-line treatment of 65 or older patients with untreated chronic lymphocytic leukemia without del(17p)/TP53 mutation in China: a lifetime economic research study.

BACKGROUND: The incidence and mortality rates of patients with chronic lymphocytic leukemia (CLL) in China have recently increased. This study performed a long-term economic evaluation of the first-line treatment strategies ibrutinib (IB) or bendamustine (BE) plus rituximab (RI) for previously untreated older patients with CLL without the del(17p)/TP53 mutation in China. METHODS: Based on clinical data from large, randomized trials, a Markov model including four disease states (event-free survival, treatment failure, post-treatment failure, and death) was used to estimate the incremental costs per quality adjusted-life year (QALY) gained from the first-line IB strategy versus the BE plus RI strategy over a 10-year period. All costs were adjusted to 2022 values based on the Chinese Consumer Price Index, and all costs and health outcomes were discounted at an annual rate of 5%. Sensitivity analysis was performed to confirm the robustness of base-case results. RESULTS: Compared to the first-line BE plus RI strategy, first-line IB treatment achieved 1.17 additional QALYs, but was accompanied by $88,046.78 (estimated in 2022 US dollars) in decremental costs per patient over 10 years. Thus, first-line treatment with IB appeared to have absolute dominance compared to the BE plus RI strategy. Sensitivity analysis confirmed the robustness of these results. CONCLUSIONS: The first-line treatment with IB is absolutely cost-effective compared to the first-line BE plus RI treatment strategy for 65 or older patients with CLL without the del (17p)/TP53 mutation from the Chinese payer perspective. Therefore, it is strongly recommended that Chinese health authorities select the former strategy for these CLL patients.

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.

Genetic Polymorphism of Lipoprotein-Associated Phospholipase A2 Influences Susceptibility to Gestational Diabetes Mellitus in Chinese Population.

Purpose: This paper aims to study the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and GDM (gestational diabetes mellitus) by detecting Lp-PLA2 level and its gene polymorphism. Patients and Methods: From January to June 2022, 82 GDM patients treated in our hospital were included as an experimental group, and 89 healthy pregnant women during the same period were selected as the control group. Lp-PLA2 concentration and TG, TC, HDL-C, and LDL-C levels were tested with specialized instruments in clinical laboratories. The PLA2G7 gene polymorphisms (rs1805017, rs1805018, and rs76863441) were detected by fluorescent probe method and sequencing. Results: Lp-PLA2 concentration was significantly higher in GDM group than control group (P<0.05). Among three polymorphism loci of PLA2G7 gene (rs1805017, rs1805018, and rs76863441) the significant associations were only found in GT genotype of rs76863441 loci (P<0.05). Conclusion: Pregnant women with high levels of Lp-PLA2 concentration are more likely to develop GDM, especially those with PLA2G7 rs76863441 polymorphism. Lp-PLA2 concentration and PLA2G7 rs1805017 polymorphism may be a novel marker for GDM diagnosis and prediction.

[Application of homemade antibiotic bone cement rod in tibial screw canal osteomyelitis].

Objective: To investigate the effectiveness of homemade antibiotic bone cement rod in the treatment of tibial screw canal osteomyelitis by Masquelet technique. Methods: A clinical data of 52 patients with tibial screw canal osteomyelitis met the criteria between October 2019 and September 2020 was retrospectively analyzed. There were 28 males and 24 females, with an average age of 38.6 years (mean, 23-62 years). The tibial fractures were treated with internal fixation in 38 cases and external fixation in 14 cases. The duration of osteomyelitis was 6 months to 20 years with a median of 2.3 years. The bacterial culture of wound secretions showed 47 positive cases, of which 36 cases were infected with single bacteria and 11 cases were infected with mixed bacteria. After thorough debridement and removal of internal and external fixation devices, the locking plate was used to fixed the bone defect. The tibial screw canal was filled with the antibiotic bone cement rod. The sensitive antibiotics were given after operation and the 2nd stage treatment was performed after infection control. The antibiotic cement rod was removed and the bone grafting in the induced membrane was performed. After operation, the clinical manifestations, wound, inflammatory indexes, and X-ray films were monitored dynamically, and the postoperative bone infection control and bone graft healing were evaluated. Results: Both patients successfully completed the two stages of treatments. All patients were followed up after the 2nd stage treatment. The follow-up time was 11 to 25 months (mean, 18.3 months). One patient had poor wound healing and the wound healed after enhanced dressing change. X-ray film showed that the bone grafting in the bone defect healed and the healing time was 3-6 months, with an average of 4.5 months. The patient had no recurrence of infection during the follow-up period. Conclusion: For the tibial screw canal osteomyelitis, the homemade antibiotic bone cement rod can reduce the recurrence rate of infection and obtain a good effectiveness, and has the advantages of simple operation and less postoperative complications.

The prevalence and genotype distribution of human papillomavirus among women in Guangxi, southern China.

BACKGROUND: Human papillomavirus is a primary cause of cervical cancer and genital warts. HPV vaccine can prevent high-grade cervical lesions as well as cervical cancer. The aim of this study was to analyze the prevalence and genotype distribution of human papillomavirus among women in Guangxi before and after the HPV vaccine was approved for use in China. METHODS: From January 2016 to May 2021, 41,140 women were tested for HPV infection. HPV genotyping included 15 high-risk HPV (HR-HPV) and 6 low-risk HPV (LR-HPV) genotypes. Total prevalence, annual trend, and specific age group prevalence and genotype distribution were analyzed. RESULTS: The overall HPV infection rate was 18.10% among Guangxi women self-referred to clinic for gynecologic problems in southern China. During 2016-2018, the prevalence of HPV infection showed an upward trend, from 18.21% in 2016 to 21.99% in 2018, and later it showed a downward trend, from 18.35% in 2019 to 12.26% in May 2021. Pure HR-HPV genotypes (14.36%) were found in more infections than pure LR-HPV genotypes (2.77%) and mixed genotypes (0.97%). Two peaks of HPV infection were found in the ≤ 25 years (22.94%) and 56-65 years (21.25%) groups. The six most prevalent HR-HPV genotypes were HPV 52 (4.06%), 16 (2.70%), 58 (2.24%), 51 (1.87%), 39 (1.52%), and 53 (1.52%). The three most prevalent LR-HPV genotypes were HPV 6 (1.31%), CP8304 (1.01%), and 11 (0.82%). Infection with a single HR-HPV genotype was the most common type of infection, with an overall infection rate of 12.30%. Infection with two HPV genotypes was the most common multiple HR-HPV infection type, with an infection rate of 2.35%. CONCLUSIONS: The cervical HPV infection rate of women in Guangxi is very high, and there is significant age specificity. There is a need to increase HPV vaccination of young people and the screening of middle-aged and elderly people.

The correlation between vitamin D and inflammatory indicators in middle-aged and elderly patients with idiopathic membranous nephropathy.

This study investigates the relationship between vitamin D and inflammatory indicators in middle-aged and elderly patients with idiopathic membranous nephropathy (IMN). In this study, 100 middle-aged and elderly patients with IMN were enrolled in the nephropathy group and 100 healthy people were enrolled as a control group. The clinical data and test specimens were collected. The patients were categorized into deficiency group and lack group based on vitamin D level. The levels of serum vitamin 25 (OH) D, inflammatory indicators and clinical indicators were compared between the nephrotic group and the control group. The levels of inflammatory indicators and clinical indicators were compared. Pearson correlation analysis was applied to detect the correlation degree between serum vitamin 25 (OH) D, inflammatory indicators and clinical indicators in IMN patients. The outcomes compared with the control group, the levels of vitamin 25 (OH) D, IL-10, IFN-γ and ALB in the nephrotic group were significantly lower and CRP, IL-6, TNF-α, Cr, CysC, ß2-MG were significantly higher (all p<0.05). Compared with the vitamin D deficiency group, the levels of IL-10, IFN-γ and ALB were significantly lower and NLR, CRP, IL-4, IL-6, TNF-α, 24 urinary protein, Cr, CysC, ß2-MG were significantly higher in the vitamin D lack group (p<0.05). Vitamin 25 (OH) D level was negatively correlated with CysC, ß2-MG, 24hUP, CR (r=-0.412, -0.387, -0.382, -0.429, all p<0.05) and was positively correlated with ALB (r=0.463, p<0.001). the conclusion Low vitamin D level in middle-aged and elderly patients with IMN is common and vitamin D supplementation can improve the clinical symptoms and delay the development of IMN.

Comprehensive analysis of prognostic genes in gastric cancer.

BACKGROUND: Gastric cancer is associated with high mortality, and effective methods for predicting prognosis are lacking. We aimed to identify potential prognostic markers associated with the development of gastric cancer through bioinformatic analyses. METHODS: Gastric cancer-associated gene expression profiles were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The key genes involved in the development of gastric cancer were obtained by differential expression analysis, coexpression analysis, and short time-series expression miner (STEM) analysis. The potential prognostic value of differentially expressed genes was further evaluated using a Cox regression model and risk scores. Hierarchical clustering was applied to validate the impact of key genes on the overall survival of gastric cancer patients. RESULTS: A total of 1381 genes were consistently dysregulated in the development of gastric cancer. Among them, 186 genes affected the overall survival of gastric cancer patients. The following genes had areas under the receiver operating characteristic curve greater than 0.9 in both datasets and were therefore considered key genes: ADAM12, CEP55, LRFN4, INHBA, ADH1B, DPT, FAM107A, and LOC100506388. LRFN4, DPT, and LOC100506388 were identified as potential prognostic genes for gastric cancer through a nomogram. Overexpression of LRFN4 and LOC100506388 was associated with a higher risk of gastric cancer. Finally, we found that tumors were infiltrated with high levels of Th2 cells and mast cells, and the infiltration levels were associated with overall survival in gastric cancer patients. CONCLUSIONS: We found that key dysregulated genes may have a prognostic value for the development of gastric cancer.

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 economic research of arsenic trioxide for the treatment of newly diagnosed acute promyelocytic leukemia in China.

BACKGROUND: The objective of this study was to conduct the first systematic evaluation of the long-term economic impact of arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) for the treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) from the perspective of the Chinese health care system. METHODS: On the basis of clinical data from a randomized phase 3 trial, a time-dependent Markov model with 4 health states (complete remission, relapse or treatment failure, post-treatment failure, and death) was used to evaluate the incremental costs per quality-adjusted life-year (QALY) gained from the ATO plus ATRA regimen compared with the ATRA plus chemotherapy (CT) regimen over a 30-year period. All costs were adjusted to 2018 levels based on the Chinese Consumer Price Index. Both costs and health outcomes were discounted by 3% annually. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: Compared with the ATRA plus CT strategy, the ATO plus ATRA strategy was associated with 1.38 additional QALYs gained and $392.05 (estimated in 2018 US dollars) in incremental costs per patient over 30 years. Consequently, the incremental cost-effectiveness ratio was $284.02 per QALY gained, which was far below the Chinese willingness-to-pay threshold of $29,306 per QALY gained. Sensitivity analyses demonstrated the robustness of these results. CONCLUSIONS: From the perspective of the Chinese health care system, the ATO plus ATRA strategy is cost-effective for patients with newly diagnosed APL compared with the ATRA plus CT strategy. Therefore, the authors strongly suggest that China's health authorities choose the former strategy for these patients, whether for the elderly or for young people.

GSTM1 and GSTT1 Gene Polymorphisms, Gene-Gene Interaction, and Esophageal Carcinoma Risk: Evidence from an Updated Meta-Analysis.

BACKGROUND: Published data regarding the association between GSTM1 and/or GSTT1 gene polymorphisms and esophageal cancer (EC) susceptibility remain inconclusive. To clarify these associations, a meta-analysis was conducted. METHODS: We conducted a comprehensive search in PubMed, Embase, and the China National Knowledge Infrastructure (CNKI) for all such manuscripts published as of May 1, 2017. The pooled odds ratio (ORs) with confidence intervals (95% CI) were estimated for each study to assess the strength of the association. A subgroup analysis, a sensitivity analysis, and a publication bias analysis were also performed. RESULTS: Data from 41 studies comprising 5291 EC cases and 8191 controls were available for analysis of the GSTM1 polymorphism, and data from 31 studies comprising 4330 EC cases and 6558 controls were available for analysis of the GSTT1 polymorphism. Analyses of the GSTM1 polymorphisms demonstrated that there was a significantly increased EC risk in GSTM1 null genotype carriers (OR = 1.319, 95% CI = 1.125-1.546, p for heterogeneity <0.001). In subgroup analyses by ethnicity, and categories of EC, a significantly increased EC risk was found in Asians (OR = 1.457, 95% CI = 1.212-1.751, p for heterogeneity <0.001) and patients whose histological type was unknown. Analyses of the GSTT1 polymorphisms indicated a positive correlation between the GSTT1 null genotype and the EC risk (OR = 1.233, 95% CI = 1.044-1.455, p for heterogeneity <0.001). In subgroup analyses stratified by ethnicity and categories of EC, similar statistical associations were observed in Asians, esophageal squamous cell carcinoma (ESCC) patients, and ESCC on Asian population. In the GSTM1-GSTT1 interaction analysis, we discovered remarkably enhanced EC risk for patients with the GSTM1 and GSTT1 dual null genotypes (OR = 1.962, 95% CI = 1.178-3.268, p for heterogeneity <0.001) compared with the reference GSTM1 and GSTT1 dual positive genotype. CONCLUSIONS: We conclude that the GSTM1 and GSTT1 null genotypes are associated with increased genetic susceptibility to EC in the overall human population, particularly among Asians. In addition, our findings suggest that persons with a null genotype for both the GSTM1 and GSTT1 genes are at higher risk of developing EC. Further well-designed studies are needed to confirm these associations.

An epidemiological investigation of leukemia incidence between 2003 and 2007 in Nanjing, China.

BACKGROUND: There has been little literature about leukemia epidemiology in Nanjing in recent years. We aimed to explore the incidence rate, gender and age distribution of leukemia in Nanjing using the leukemia database of the city. RESULTS: The average yearly incidence rate of leukemia was 3.68/105 during 2003 - 2007 in Nanjing. There were no significant difference in gender (x2 = 3.266, p > 0.05) or seasons (x2 = 11.36, p > 0.05). The incidence rate was the highest in group aged 80~ years (18.64/105). AML accounted for approximately 36.8% of all leukemias. CONCLUSIONS: The incidence rate of leukemia, especially in the aged population, was relatively high in Nanjing. Leukemia is the major malignant tumor in children. Therefore, more attention should be paid to leukemia in children and the aged people.