Analysis of the global burden of cervical cancer in young women aged 15-44 years old.

BACKGROUND: Understanding the burden of cervical cancer (CC) in young women aged 15-44 years old are essential for formulating effective preventive strategies. METHODS: Utilizing the Global Burden of Disease 2019 Study, we estimated incidence, disability-adjusted life-years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) due to CC among young women from 1990 to 2019. Additionally, we evaluated the temporal trends using estimated annual percentage changes (EAPCs) during this period. We conducted a decomposition analysis to assess the absolute contributions of three components: population growth, population age structure and epidemiologic changes. RESULTS: Globally, there were 187 609.22 incident cases of CC worldwide, resulting in 2621 917.39 DALYs in 2019. From1990 to 2019, the age-standardized rates were decline, only the age-standardized YLDs rate (EAPC = 0.02; 95% CI: -0.02 to 0.05) showed a stable trend. The largest increase in age-standardized incidence rate (ASIR) and age-standardized YLDs rate observed in the high-middle social demographic index (SDI) quintiles. Population growth and age structure changes were associated with substantial changes in cases of CC, especially in South Asia and East Asia. CONCLUSIONS: Globally, the burden of CC in young women continues to increase, as measured by the absolute number. As populations are growing and age structure changes were associated with substantial changes in cases of CC, governments will face increasing demand for treatment, and support services for CC, especially in South Asia and East Asia.

Treatment of landfill leachate by black soldier fly (Hermetia illucens L.) larvae and the changes of intestinal microbial community.

Black soldier fly larvae (BSFL) (Hermetia illucens) are commonly used to treat organic waste. This work aims to evaluate the transformation effect, heavy metal migration, and alterations in the gut microbiota of BSFL in addition to treating landfill leachate (LL) with BSFL. We found that BSFL may grow in various landfill leachate concentrations without obvious toxicity and growth inhibition. In addition, the results indicated a significant increase in the content of ammonia nitrogen and the activity of urease and ß-glucosidase (ß-GC) in LL, increased from 2570.17 mg/L to 5853.67 mg/L, 1859.17 mg/(g·d) to 517,177.98 mg/(g·d), 313.73 µg/(g·h) to 441.91 µg/(g·h) respectively. Conversely, the content of total nitrogen (TN) and total organic carbon (TOC) decreased in LL, decreasing by 31.24% and 29.45% respectively. Heavy metals are accumulated in the leachate by the BSFL to differing degrees, the descending sequence of accumulation is Cd > As > Cu > Cr. As dropped by 26.0%, Cd increased by 22.6%, Cu reduced by 5.23%, and Cr increased by 317.1% in the remaining matrix. The concentration of heavy metals satisfies the organic fertilizers' limit index (NY/T1978). The diversity of intestinal microorganisms in BSFL decreased, from 2819 OTUs to 2338 OTUs, with Providencia and Morganella emerging as the core flora. The gene abundance of nitrogen metabolism in the microbiota increased significantly. The TOC, ß-GC, and Copper (Cu) content in BSFL correlated significantly with the gut microbiota. In Summary, this study revealed the treatment effect of BSFL on LL, the migration of heavy metals, and changes in the intestinal microorganisms of BSFL. The content of heavy metals in BSFL was found to be much lower than the upper limit of feed protein raw materials, demonstrating that BSFL is a sustainable method to treat LL.

Biological variation estimates obtained from Chinese subjects for 32 biochemical measurands in serum.

OBJECTIVES: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) have established a program of work to make available, and to enable delivery of well characterized data describing the biological variation (BV) of clinically important measurands. Guided by the EFLM work the study presented here delivers BV estimates obtained from Chinese subjects for 32 measurands in serum. METHODS: Samples were drawn from 48 healthy volunteers (26 males, 22 females; age range, 21-45 years) for 5 consecutive weeks at Chinese laboratory. Sera were stored at -80 °C before triplicate analysis of all samples on a Cobas 8000 modular analyzer series. Outlier and homogeneity analyses were performed, followed by CV-ANOVA, to determine BV estimates with confidence intervals. RESULTS: The within-subject biological variation (CVI) estimates for 30 of the 32 measurands studied, were lower than listed on the EFLM database; the exceptions were alanine aminotransferase (ALT), lipoprotein (a) (LP(a)). Most of the between-subject biological variation (CVG) estimates were lower than the EFLM database entries. CONCLUSIONS: This study delivers BV data for a Chinese population to supplement the EFLM BV database. Population differences may have an impact on applications of BV Data.

[MicroRNA-204 Carried by Exosomes of Human Umbilical Cord-derived Mesenchymal Stem Cells Regulates the Polarization of Macrophages in a Mouse Model of Myocardial Ischemia-reperfusion Injury].

Objective To explore the role and mechanism of microRNA-204(miR-204) carried by the exosomes of human umbilical cord-derived mesenchymal stem cells(hUC-MSC) in regulating the polarization of macrophages in a mouse model of myocardial ischemia-reperfusion(I/R) injury. Methods After the hUC-MSCs were isolated,cultured,and identified,their adipogenic and osteogenic differentiation capabilities were determined.The exosomes of hUC-MSCs were separated by ultracentrifugation,and the expression of CD81,CD63,tumor susceptibility gene 101(Tsg101),and calnexin in the exosomes was determined by Nanoparticle Tracking Analysis software,transmission electron microscopy,and Western blotting.Three groups(hUC-MSC,miR-204 mimic,and negative control) were designed for the determination of the expression of miR-204 in the cells and their exosomes by qRT-PCR.The C57BL/6J mice were randomly assigned into a sham operation group,an I/R group,a hUC-MSC exosomes group,a negative control group,and a miR-204 mimic group.Except the sham operation group,the I/R model was established by ligating the left anterior descending artery.The echocardiography system was employed to detect the heart function of mice.HE staining was employed to observe the pathological changes of mouse myocardium.ELISA was employed to determine the levels of interleukin-1ß(IL-1ß),tumor necrosis factor-α(TNF-α),arginase 1(Arg-1),and IL-10 in the myocardial tissue.After the macrophages of mouse myocardial tissue were isolated,flow cytometry was employed to determine the expression of CD11c and CD206,and ELISA to measure the levels of IL-1ß,TNF-α,Arg-1,and IL-10 in the macrophages. Results hUC-MSCs had adipogenic and osteogenic differentiation capabilities,and the exosomes were successfully identified.Compared with the negative control group,the miR-204 mimic group showed up-regulated expression of miR-204 in hUC-MSCs and their exosomes(P<0.001,P<0.001).Compared with the sham operation group,the modeling of I/R increased the left ventricular end-diastolic diameter(LVEDD)(P<0.001),left ventricular end-systolic diameter(LVESD)(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P<0.001),and CD11c(P<0.001).Meanwhile,it lowered the left ventricular ejection fraction(LVEF)(P<0.001),left ventricular fractional shortening(LVFS)(P<0.001),Arg-1(P<0.001),IL-10(P<0.001),and CD206(P<0.001).Compared with those in the I/R group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P=0.010),and CD11c(P<0.001) reduced,while LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.028),and CD206(P=0.022) increased in the hUC-MSC exosomes group.Compared with those in the negative control group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P=0.001),and the levels of IL-1ß(P=0.048),TNF-α(P<0.001),and CD11c(P=0.007) reduced,while the LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.001),and CD206(P=0.001) increased in the miR-204 mimic group. Conclusion The hUC-MSC exosomes overexpressing miR-204 can inhibit the polarization of macrophages in the I/R mouse model to M1-type and promote the polarization to M2-type.

[Course Design and Discussions of Integrating Ideological and Political Theories Education in Medical Laboratory Pathways and Their Clinical Application].

Specialty courses are an important carrier for driving forward the education reform of integrating ideological and political theories education in all courses and implementing the philosophy of fostering character through moral education. Medical Laboratory Pathways and Their Clinical Applicationis an undergraduate specialty course offered by the Department of Laboratory Medicine, West China Hospital, Sichuan University. The paper is based on the campaign of Integrating Ideological and Political Theories Education in All Courses and takes into consideration the features of the medical laboratory technology specialty. The paper proposes the organic unity of knowledge and skills teaching objectives and emotions and value-guided teaching objectives. In regard to the teaching content, horizontal integration was carried out, transforming the design of the course content from being laboratory test-centered to being disease-centered. Ideological and political theories education was organically incorporated in the content of the specialty course, assigning to the course the important task of values guidance. In addition, we made discussions on course design and instruction of Medical Laboratory Pathways and Their Clinical Application mainly in regard to the instruction, teaching methodology, and the form of classroom instruction of the course. We hope that the paper will provide useful information and reference for the ongoing education reform of the medical laboratory technology specialty under the new circumstances.

A genetic variant in the promoter of CD46 is associated with the risk and prognosis of hepatocellular carcinoma.

CD46 (also known as membrane cofactor protein), which is a member of the membrane-bound complement regulatory protein family, has been reported to cause cancer cells to escape complement-dependent cytotoxicity. However, the association between CD46 polymorphisms and the risk of hepatocellular carcinoma (HCC) has not been investigated. This two-stage association study was conducted to assess the relationship between the tagging single nucleotide polymorphisms (tagSNPs) of CD46 and HCC risk and prognosis. A series of functional analyses were performed to study the underlying mechanisms. Among the eight tagSNPs, rs2796267 (P = .003) and rs2796268 (P = .011) were found to modify HCC risk in the discovery set. Only rs2796267 (P < .0001) was confirmed to be associated with HCC susceptibility in the validation set. Compared with the wild-type AA genotype, the GG genotype significantly increased the HCC risk (adjusted odds ratio [OR] = 2.03; 95% confidence interval [CI], 1.34-3.08; P = .001). Moreover, subgroups analysis suggested a positive correlation among male and younger patients, especially among drinkers, smokers, and hepatitis B surface antigen-positive individuals. In functional analyses, we found that the rs2796267 G allele in the promoter region of CD46 could increase the expression of CD46 by affecting the binding affinity of STAT5a. Furthermore, Cox regression analysis revealed that the rs2796267 AG/GG genotype was significantly associated with worse prognosis of resected patients with HCC (hazard ratio = 2.27; 95% CI, 1.27-4.05; P = .006). These results suggest that the CD46 rs2796267 polymorphism may contribute to susceptibility and prognosis of HCC by altering promoter activity.

Pathogenic Leptospira Species in Insectivorous Bats, China, 2015.

PCR amplification of the rrs2 gene indicated that 50% (62/124) of insectivorous bats from eastern China were infected with Leptospira borgpetersenii, L. kirschneri, and several potentially new Leptospira species. Multilocus sequence typing defined 3 novel sequence types in L. kirschneri, suggesting that bats are major carriers of Leptospira.

The influence of living donor SHROOM3 and ABCB1 genetic variants on renal function after kidney transplantation.

OBJECTIVE: A genome-wide association study has identified several gene polymorphisms associated with loss of renal function. The effect of these variants on renal function in kidney transplant recipients receiving immunosuppressive treatment is unknown. MATERIALS AND METHODS: A cohort of 189 kidney transplant recipients and their living donors were recruited from West China Hospital of Sichuan University, on whom we assessed the association of five single nucleotide polymorphisms with renal function after kidney transplantation. RESULTS: Glomerular filtration rate estimated by serum creatinine was significantly higher in recipients carrying allograft with the A allele at rs17319721 in SHROOM3 (shroom family member 3) than those in the group with the GG genotype from month 1 to month 6 after transplantation (P=0.020). Covariate adjustment analysis showed that the variant at rs17319721 in SHROOM3 was an independent risk factor for renal dysfunction after the first month after transplantation (P=0.022). The estimated glomerular filtration rate was the lowest in recipients with allograft carrying both the A allele at rs17319721 in SHROOM3 and the CC genotype at rs1045642 in ABCB1 (P<0.05). CONCLUSION: The genetic variants in SHROOM3 and ABCB1 in donors were associated closely with renal function after kidney transplantation.

Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population.

Cell death pathway plays an important role in apoptosis, and corruption of this signaling pathway has been shown to participate in carcinogenesis. We aimed at determining whether genetic variants in CASP8, CASP10 and CFLAR influence the development and clinical outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A hospital-based case-control study, including 600 HCC cases and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk and prognosis in a Chinese Han population. Among the 11 polymorphisms, only CASP8 rs3834129 (-652 6N ins/del) modified HCC risk. Compared with CASP8 -652 insins genotype, the deldel (adjusted OR 0.717, 95% CI 0.553-0.930) and insdel (adjusted OR 0.731, 95% CI 0.554-0.964) genotypes had a significantly decreased HCC risk. Furthermore, this polymorphism was significantly associated with decreased portal vein tumor thrombosis (adjusted OR 0.554; P = 0.044) and reduced postoperative recurrence (adjusted OR 0.356; P < 0.001) of resected HCC. In addition, the multivariate analysis showed that the -652 6N ins/del polymorphism was significantly associated with improved overall survival and recurrence-free survival of resected HCC patients. The expression levels of CASP8 in HCC tumor tissues were significantly lower than those in paracancerous liver tissues, although no significant association between -652 6N ins/del genotypes and the expression levels of CASP8 were observed in these tissues. These results suggest that the CASP8 -652 6N ins/del polymorphism may play a protective role in the development, progression, and survival of HBV-related HCC among the Chinese Han population.

Effects of Codonopsis pilosula water extract on MicroRNA expression profile in D-galactose-induced senile mice.

This paper aims to observe and analyze effects of Codonopsis pilosula water extract on micro RNA (miRNA) expression profile in liver tissue of senile mice. The 110 Konminmice were randomly divided into five groups, including D-galactose-induced senile model group, normal control group, and low, middle and high dose intervention groups. Continuous modeling lasted 40 days. General symptoms and changes of body mass of the model mice were monitored and observed. The levels of serum glutamic pyruvic transaminase (ALT) and alkaline phosphatase (ALP) of mice were compared, and miRNA of differential expression during aging of D-galactose-induction and high-dose Codonopsis pilosula intervention was analyzed. The serum ALT and ALP levels in the aging model group were significantly higher than those in the normal control group (P<0.05). The serum ALT and ALP levels of Codonopsis pilosula intervention group were lower than those of aging model group, and decrease in ALP value of high dose intervention group was higher (P<0.05). The expression profile of miRNA in the aging model group was significantly different from that in normal control group and high-dose Codonopsis pilosula intervention group, and miRNA expression profile in high-dose Codonopsis pilosula intervention group was clustered with that in the normal control group. The differentially expressed miRNAs of D-galactose-induced senescence and Codonopsis pilosula anti-aging usually belong to 7 miRNA clusters. The target gene function of the differentially expressed miRNAs during senescence process was enriched in 29 signal pathways. There were 67 regulatory signal pathways in differentially expressed miRNA target genes during Codonopsis pilosula intervention. The effect of miRNA targeting may play an important role during D-galactose-induced senescence and Codonopsis pilosula anti-aging period.

CASP 3 genetic polymorphisms and risk of Hepatocellular carcinoma: a case-control study in a Chinese population.

Caspase (CASP) 3 is an important caspase in the apoptosis pathway and plays an important role in the development and progression of cancer. We hypothesized that genetic variants in CASP 3 may modify individual susceptibility to hepatocellular carcinoma (HCC). Five hundred HCC cases in West China Hospital were selected, and 500 healthy cases with the same gender, age (±5 years), and residence place were selected as control group, with proportion of 1:1. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method was performed to detect these polymorphisms. Among the 500 cases and 500 controls with DNA samples, the genotyping was successful for the CASP3 polymorphisms (rs6948, rs1049216, and rs12108497) in 486 HCC cases and 495 controls, which were included in the final analyses.The results showed that the genotype frequencies of the CASP3 did not differ significantly between the HCC patients and the control group (P > 0.05). However, when stratifying by age, sex, smoking, drinking, HBV carrier status, and family history of cancer, we found that the variant genotypes (CT + TT) of the CASP3 rs12108497 were associated with a significant increased risk of HCC among smoking individuals (adjusted OR = 2.31, 95 % CI = 1.11-4.79). No significant association was observed between the other two polymorphisms of the CASP3 gene and risk of HCC in any stratification analysis. These results suggest that the CASP3 rs12108497 polymorphism may play a role in the development of HCC among smoking individuals in the Chinese population.

Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia caused by SFTS virus (SFTSV), a newly discovered phlebovirus. The Haemaphysalis longicornis tick has been suspected to be the vector of SFTSV. To determine whether SFTSV can be transmitted among ticks, from ticks to animals, and from animals to ticks, we conducted transmission studies between developmental stages of H. longicornis ticks and between ticks and mice. Using reverse transcription PCR, we also analyzed the prevalence of SFTSV infection among H. longicornis ticks collected from vegetation in Shandong Province, China. Our results showed a low prevalence of SFTSV among collected ticks (0.2%, 8/3,300 ticks), and we showed that ticks fed on SFTSV-infected mice could acquire the virus and transstadially and transovarially transmit it to other developmental stages of ticks. Furthermore, SFTSV-infected ticks could transmit the virus to mice during feeding. Our findings indicate ticks could serve as a vector and reservoir of SFTSV.

Enhancing pili assembly and biofilm formation in Acinetobacter baumannii ATCC19606 using non-native acyl-homoserine lactones.

BACKGROUND: Quorum Sensing (QS) systems influence biofilm formation, an important virulence factor related to the bacterial survival and antibiotic resistance. In Acinetobacter baumannii, biofilm formation depends on pili biosynthesis, structures assembled via the csuA/BABCDE chaperone-usher secretion system. QS signaling molecules are hypothesized to affect pili formation; however, the mechanism behind this remains unclear. This study aimed to demonstrate the possible role of QS signaling molecules in regulating pili formation and mediating the ability to form biofilms on abiotic surfaces. RESULTS: Real-time quantitative PCR analysis showed the expression of the csuA/BABCDE genes distinctly increased when co-cultured with C6-HSL (P < 0.05). Under the same experimental conditions, expression of BfmS and BfmR was significantly higher than the control strain (P < 0.05). A subsurface twitching assay showed a switch from a small to a large and structured clone that may result from enhanced twitching motility (P < 0.05). Transmission electron microscopy analysis of cells lifted from a MH broth co-cultured with C6-HSL showed more abundant pili-like structures than the control strain. We then tested the idea that the addition of a QS signal, and therefore induction of chaperone-usher secretion system genes, provides a greater benefit at higher biofilm densities. An assay for the total fluorescence intensity of the biofilm using Confocal Laser Scanning Microscopy revealed an obvious increase. CONCLUSION: Our study demonstrated that, increased transcription of the BfmS and BfmR genes, QS signaling molecules enhance the expression of the chaperone-usher secretion system, and this expression is required for twitching motility in A. baumannii. The concomitant pili expression and strain twitching allowed A. baumannii to attach easily to abiotic surfaces and form biofilms at an earlier timepoint.

Incorporating the inflammation-related parameters enhances the performance of the nomogram for predicting local control in lung cancer patients treated with stereotactic body radiation therapy.

PURPOSE: The study aims to investigate whether including the inflammation-related parameters would enhance the accuracy of a nomogram for local control (LC) prediction in lung cancer patients undergoing stereotactic body radiation therapy (SBRT). METHODS: 158 primary or metastatic lung cancer patients treated with SBRT were retrospectively analyzed. The clinical, dosimetric and inflammation-related parameters were collected for the Cox regression analysis. The ACPB model was constructed by employing the clinical and dosimetric factors. And the ACPBLN model was established by adding the inflammation-related factors to the ACPB model. The two models were compared in terms of ROC, Akaike Information Criterion (AIC), C-index, time-dependent AUC, continuous net reclassification index (NRI), integrated discrimination improvement (IDI), calibration plots and decision curve analysis (DCA). RESULTS: Multivariate Cox regression analysis revealed that six prognostic factors were independently associated with LC, including age, clinical stage, planning target volume (PTV) volume, BED of the prescribed dose (BEDPD), the lymphocyte count and neutrocyte count. The ACPBLN model performed better in AIC, bootstrap-corrected C-index, time-dependent AUC, NRI and IDI than the ACPB model. The calibration plots showed good consistency between the probabilities and observed values in the two models. The DCA curves showed that the ACPBLN nomogram had higher overall net benefit than the ACPB model across a majority of threshold probabilities. CONCLUSION: The inflammation-related parameters were associated with LC for lung cancer patients treated with SBRT. The inclusion of the inflammation-related parameters improved the predictive performance of the nomogram for LC prediction.

CCR2+TREM-1+ monocytes promote natural killer T cell dysfunction contributing towards HBV disease progression.

Natural killer T (NKT) cells are amongst the most important innate immune cells against hepatitis B virus (HBV) infection. Moreover, previous studies have shown that HBV infection induced TREM-1+ expression in monocyte and secretion of inflammatory cytokines. Thus, this prompted us to elucidate the role of TREM-1+ monocytes in regulating the function of iNKT cells. Ninety patients and 20 healthy participants were enrolled in the study. The percentage and phenotype of iNKT cells and TREM-1+ monocytes were measured in the peripheral blood of healthy controls (HC), patients with chronic HBV infection (CHB), HBV-related liver cirrhosis (LC), and HBV-related acute-on-chronic liver failure (ACLF) via flow cytometry. Moreover, co-culture experiments with iNKT cells and TREM-1 overexpressing THP-1 cells were performed to determine the role of TREM-1 in the regulation of NKT cell function. We observed that the percentage of iNKT cells and CD4-iNKT cells gradually decreased, whereas the percentage of CCR2+TREM-1+ monocytes increased with the progression of the disease. In addition, activation of the TREM-1 signaling pathway induced the secretion of inflammatory cytokines leading to pyroptosis of iNKT cells and secretion of IL-17 contributing towards disease progression. Therefore, this study suggests that blocking the activation of TREM-1 in monocytes could promote the elimination of HBV by inhibiting pyroptosis of iNKT cells and restoring their function. However, further studies are required to validate these results that would help in developing new treatment strategies for patients with HBV infections.

Blood and CSF findings of cellular immunity in anti-NMDAR encephalitis.

OBJECTIVES: To investigate the immunopathogenic mechanisms of anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) by characterizing the changes of immune cells in both peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with NMDAR-E. METHODS: Cytology and flow cytometry were used to explore and compare different immunological parameters in PB and CSF of patients with NMDAR-E, viral encephalitis (VE) and healthy volunteers. Moreover, different models were established to assess the possibility of identifying NMDAR-E patients based on PB and CSF parameters. RESULTS: The neutrophil counts and monocyte-to-lymphocyte ratios (MLR) in PB are higher in NMDAR-E patients than in both VEs and controls (P < 0.001, respectively), while the percentages of CD3 + T, CD4 + T lymphocytes, and the leukocytes count in CSF were lower in NMDAR-Es than in VEs (P < 0.01, respectively). The higher percentages of CD8 + T cells in blood and CSF were both correlated with more severe NMDAR-E (P < 0.05, respectively). The poor neurological status group had significantly higher PB leukocytes but lower CSF leukocyte count (P < 0.05). Longitudinal observations in patients with NMDAR-E showed a decreasing trend of leukocyte count, neutrophils count, neutrophil-to-monocyte ratios (NMR), and neutrophil-to-lymphocyte ratios (NLR) with the gradual recovery of neurological function. CONCLUSIONS: The expression patterns of T lymphocyte subsets were different in patients with NMDAR-E and viral encephalitis. The changing trends of leukocyte and lymphocyte populations in peripheral blood and cerebrospinal fluid may provide clues for the diagnosis of different types of encephalitides, including NMDARE, and can be used as immunological markers to assess and predict the prognosis.

Genetic variants of p21 and p27 and hepatocellular cancer risk in a Chinese Han population: a case-control study.

The p21 (Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members of the Cip/Kip family of cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumour suppressors. We hypothesized that genetic variants in p21 and p27 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T in p21 and C-79T and Gly109Val in p27, as well as their combinations, with HCC risk in a case-control study of 476 HCC cases and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry method was performed to detect these polymorphisms. We found that the variant genotypes of p21 Ser31Arg and p27 C-79T were individually associated with a significantly increased risk of HCC, but no associations were observed for other variant genotypes. Moreover, the combined variant genotypes of the four loci were associated with a significantly increased HCC risk (adjusted OR = 2.24, 95% CI = 1.72, 2.91 among subjects carrying 3 or more variant alleles), especially among HbsAg-positive individuals (adjusted OR = 3.09, 95% CI = 1.86, 5.14). Furthermore, the combined variant genotypes of the four loci (carrying three or more variant alleles) increased a 1.93-fold (95% CI = 1.20, 3.09) and 1.76-fold (95% CI = 1.17, 2.64) risk of HCC among smokers and nonsmokers. The variant genotypes of the two genes in this study have negative correlation with the clinicopathologicals observed. These results suggest that p21 polymorphisms individually or in combination with p27 polymorphisms increases risk of HCC, particularly among HbsAg-positive individuals.

Association of a p73 exon 2 G4C14-to-A4T14 polymorphism with risk of hepatocellular carcinoma in a Chinese population.

P73, a p53 homolog, has some p53-like activities and plays an important role in modulating cell cycle, apoptosis, and DNA repair. A potentially functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the 5' untranslated region of exon 2 of the p73 gene, which may theoretically form a stem-loop structure and affect gene expression. We hypothesized that genetic variants in p73 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis that these two common variants play a role in HCC susceptibility, we conducted a hospital-based case-control study of 476 HCC patients and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method was performed to detect these polymorphisms. The results showed that the genotype and allele frequencies of the p73 G4C14-A4T14 did not differ significantly between the HCC patients and the control group (all P values are above 0.05). However, with stratification analysis by age, sex, smoking status, drinking status, HBV carrier state, and family history of cancer, we found that the variant genotypes (GC/AT + AT/AT) of the p73 G4C14-A4T14 was associated with a significant increased risk of HCC among HbsAg-positive individuals (adjusted OR = 2.19, 95 % CI = 1.25-3.83) and among women (adjusted OR = 2.62, 95 % CI = 1.47, 4.66). These results suggest that the p73 G4C14-to-A4T14 dinucleotide polymorphism may play a role in the development of chronic HBV-infected HCC in the Chinese population, especially among women.

A functional NQO1 609C>T polymorphism and risk of hepatocellular carcinoma in a Chinese population.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, thus protecting cells from oxidative damage. A single base substitution (C→T) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Thus, the lack of enzymatic activity in the homozygous C609T NQO1 polymorphism (rs1800566) may play a pivotal role in tumor development. We hypothesized that a genetic variant in NQO1 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis that the variant may play a role in HCC susceptibility, we conducted a hospital-based case-control study of 476 HCC patients and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method was performed to detect the polymorphism. The results showed that the variant alleles and genotypes of NQO1 C609T were more common among cases than those among controls (P = 0.003 and P = 0.024). Compared with the NQO1 609CC genotype, there was a significantly greater risk of HCC associated with the variant NQO1 609TT [adjusted odds ratio (OR) = 1.60, 95 % confidence interval (CI) = 1.12-2.28] and combined NQO1 609TC/TT (adjusted OR = 1.37, 95 % CI = 1.04-1.80) genotypes. Moreover, when subgroup analyses were performed, we found that the increase in risk was more evident among younger subjects, men, HbsAg-positive individuals, never smokers, never drinkers, and subjects without family history of cancer. These results suggest that the presence of the NQO1 C609T polymorphism may be a marker of genetic susceptibility to HCC.

MYL9 promotes squamous cervical cancer migration and invasion by enhancing aerobic glycolysis.

OBJECTIVE: This study explored the mechanism of squamous cervical cancer (SCC) progression. METHODS: Reverse transcription-quantitative polymerase chain reaction and western blotting were used to evaluate the expression of myosin light chain 9 (MYL9) in SCC tissues and cell lines. Furthermore, Transwell and Boyden assays were used to assess the function of MYL9 in SCC progression. In addition, the levels of lactate and aerobic glycolysis were used to explore the detailed mechanism of MYL9 in SCC. RESULTS: The mRNA and protein levels of MYL9 were elevated in SCC tissues, and MYL9 knockdown inhibited the migration and invasion of SCC cell lines. A mechanistic study demonstrated that MYL9 promotes SCC migration and invasion by enhancing aerobic glycolysis and increasing the activity of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. CONCLUSIONS: MYL9 was upregulated in SCC, and it enhanced JAK2/STAT3 pathway activity and promoted metastasis and glycolysis in SCC.