Association of complement components with risk of colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Complement components could contribute to the tumor microenvironment and the systemic immune response. Nevertheless, their role in colorectal cancer (CRC) remains a contentious subject. AIM: To elucidate the relationship between complement components and CRC risk and clinical characteristics. METHODS: Searches were conducted in PubMed, the Cochrane Library, and the China National Knowledge Infrastructure database until June 1, 2023. We included cohort studies encompassing participants aged ≥ 18 years, investigating the association between complement components and CRC. The studies were of moderate quality or above, as determined by the Agency for Healthcare Research and Quality. The meta-analysis employed fixed-effects or random-effects models based on the I² test, utilizing risk ratio (RR) and their corresponding 95% confidence interval (CI) for outcomes. Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity. RESULTS: Data from 15 studies, comprising 1631 participants that met the inclusion criteria, were included in the meta-analysis. Our findings indicated that protein levels of cluster of differentiation 46 (CD46) (RR = 3.66, 95%CI: 1.75-7.64, P < 0.001), CD59 (RR = 2.86, 95%CI: 1.36-6.01, P = 0.005), and component 1 (C1) (RR = 5.88, 95%CI: 1.75-19.73, P = 0.004) and serum levels of C3 (standardized mean difference = 1.82, 95%CI: 0.06-3.58, P = 0.040) were significantly elevated in patients with CRC compared to healthy controls. Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis, whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression (P < 0.05 for all). Although specific pooled results demonstrated notable heterogeneity, subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies. CONCLUSION: Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC, emphasizing the potential significance of monitoring elevated complement component levels.

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

Role and mechanism of circ-PRKCI in hepatocellular carcinoma.

BACKGROUND: The circular RNA circ-PRKCI is an endogenous non-coding RNA that forms a covalently closed ring after reverse splicing, which plays a key role in the occurrence and development of multiple digestive system tumors. AIM: To investigate the role and mechanism of circ-PRKCI in the occurrence and development of hepatocellular carcinoma (HCC). METHODS: This study used real-time polymerase chain reaction to detect the expression of circ-PRKCI in tumor tissues, tumor adjacent tissues, and blood in patients with HCC and other digestive system tumor cells. A series of functional tests were performed to explore whether circ-PRKCI affects the growth of HCC cells and what is its mechanism in HCC. Meanwhile, fluorescence in situ hybridization was used to detect the subcellular localization of circ-PRKCI. Survival analysis was performed to predict the correlation between circ-PRKCI and the prognosis of HCC. Chi-square test and t-test were performed for statistical analyses. RESULTS: The level of circ-PRKCI was significantly higher in HCC tissues than in tumor adjacent tissues, and in HCC cell lines than in cells lines of esophageal, liver, stomach, and colon cancers. A series of functional tests showed that circ-PRKCI substantially inhibited cell apoptosis and promoted cell invasion. It was found that circ-PRKCI can act as the sponge of miRNA-545 to reduce the expression of AKT3 protein. Moreover, the result of survival analysis showed that circ-PRKCI target gene E2F7 can reduce liver cancer patients' survival rate. And clinical data suggested that the distribution of circ-PRKCI rose with the depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, indicating that circ-PRKCI may affect the survival and prognosis of patients with HCC by regulating E2E7. CONCLUSION: This study explores the role and mechanism of circ-PRKCI in HCC, which provides a new research direction and theoretical basis for the treatment of HCC.

[A validation study of national early warning score in evaluation of death risk in elderly patients with critical illness].

Objective: To verify the validity and feasibility of national early warning score (NEWS) in evaluation of death risk in elderly patients with critical illness,in order to find out which scoring method is more suitable for elderly critical illness patients. Methods: A prospective case-control study was conducted. The critical illness patients aged over 60 years old with the length of hospital stay over 24 hours, and admitted to Department of Emergency of Qingdao Municipal Hospital from January to December 2015 were enrolled. The clinical data including in emergency and the actual outcome of patients were collected, and the patients were divided into death group and survival group according to 30-day outcome. Patients in the two groups were assessed by using NEWS and risk classification according to the first results of vital signs monitoring. Multivariate logistic regression model was used to analyze the relationship between the NEWS classification and the risk of death in elderly critical ill patients. Results: 1 950 emergency elderly patients with critical illness were enrolled, with 78 cases (4.0％) dead within 30 days and 1 872 survived (96.0％).Compared with the survival group, patients in death group were older (years:79.8 ± 10.8 vs.75.3 ± 8.9,t =4.335,P ＜0.001),and had higher acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score (22.9± 4.6 vs.18.2 ± 4.8,t =8.487,P ＜ 0.001),lower Glasgow coma scale (GCS) score (12.2 ± 4.5 vs.13.4 ± 5.2,t =-2.007,P =0.045),higher incidence of respiratory system diseases (29.5％ vs.17.9％,x 2 =12.742,P =0.013),higher NEWS score (11.2 ± 5.5 vs.3.9 ± 2.7,t =22.063,P ＜ 0.001),as well as higher proportion of patients with NEWS classification of high risk and very high risk (65.4％ vs.15.8％,x 2 =263.125,P ＜ 0.001).With the increase of NEWS risk classification, mortality rate was also increased, and the mortality rate in the patients with low, medium, high and very high risk were 0.81％ (9/1 108),3.63％ (18/496),5.83％ (13/223),30.89％ (38/123),respectively, with statistically significant difference (x 2 =179.741,P ＜ 0.001).It was showed by logistic regression analysis that the NEWS score of elderly patients with critical illness were positively correlated with 30-day death. The 30-day death risk of patients with middle risk, high risk and very high risk was 4.600,9.052 and 54.598 folds of the patients with low risk respectively. Conclusion: NEWS score can be used to assess the risk of death in emergency elderly patients with critical illness. NEWS risk classification can quantify and classify the risk of death in the elderly patients with critical illness.

Concise review: induced pluripotency by defined factors: prey of oxidative stress.

Reprogramming somatic cells to pluripotency (induced pluripotent stem cells, iPSCs) via forced expression of defined factors has become one of the most fascinating areas in biomedical research because it holds a tremendous application potential for cell therapy, disease modeling, and drug screening applications. However, cellular reprogramming is a very inefficient and metabolically demanding process commonly associated with genomic instability of the resulting iPSCs. Low reprogramming efficiency and presence of de novo genomic aberrations in iPSCs may hamper their downstream applications. Here, we review mounting studies that have tackled reprogramming efficiency and genome stability of iPSCs. In particular, we focus on the effect of oxidative stress on cellular reprogramming. We will discuss how oxidative stress influences cellular reprogramming and the mechanisms by which antioxidants promote reprogramming efficiency and preserve genome integrity of iPSCs. A reduction of oxidative stress is expected to augment reprogramming efficiency and concomitantly promote the genomic integrity of the resulting iPSCs, eventually facilitating the implementation of cellular reprogramming for downstream applications. Stem Cells 2015;33:1371-1376.

Antioxidant supplementation reduces genomic aberrations in human induced pluripotent stem cells.

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using oncogenic transcription factors. However, this method leads to genetic aberrations in iPSCs via unknown mechanisms, which may limit their clinical use. Here, we demonstrate that the supplementation of growth media with antioxidants reduces the genome instability of cells transduced with the reprogramming factors. Antioxidant supplementation did not affect transgene expression level or silencing kinetics. Importantly, iPSCs made with antioxidants had significantly fewer de novo copy number variations, but not fewer coding point mutations, than iPSCs made without antioxidants. Our results suggest that the quality and safety of human iPSCs might be enhanced by using antioxidants in the growth media during the generation and maintenance of iPSCs.

Genetic polymorphisms of LMP/TAP gene and hepatitis B virus infection risk in the Chinese population.

Despite the availability of effective vaccines, hepatitis B virus (HBV) infection is still commonly seen worldwide. Several reports show that the human major histocompatibility complex (MHC) systems were involved in the elimination of HBV via the restrictive antigen-processing pathway. We investigate whether LMP/TAP gene polymorphisms coded by MHC-II region were associated with HBV infection. A total of seven polymorphisms of LMP/TAP gene were identified by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays. Three hundred fifty-six patients and 326 unrelated healthy volunteers were included in the case-control study. Of the seven polymorphisms, three of which (LMP7 codons 145, TAP1 codons 637, and TAP2 codons 651) were observed to have statistically significant association with HBV infection (P < 0.05). We analyzed the three-locus haplotype constructed with three such polymorphisms and found that the frequency of haplotypes D and E increased significantly in patients, in comparison with that in controls (OR = 3.57, 95% CI: 2.09-6.12, P < 0.001; OR = 2.74, 95% CI: 1.35-5.56, P = 0.005, respectively). The results imply that LMP7-145, TAP1-637, and TAP2-651 sites were associated with the risk of HBV infection. Haplotypes D and E might be involved in the development of HBV infection. These data suggest a potential role of LMP/TAP gene as a candidate gene for susceptibility to HBV infection.

Association analysis of hepatitis virus B infection with haplotypes of the TBX21 gene promoter region in the Chinese population.

BACKGROUND: The T-box21 (TBX21) gene encodes the transcription factor T-bet (T-box expressed in T-cells), which influences naive T-lymphocyte development and has been implicated in the pathogenesis of many diseases. METHODS: We selected 208 hepatitis B patients and 213 healthy volunteers to examine whether polymorphisms or haplotypes of the TBX21 gene promoter were associated with hepatitis B virus (HBV) infection in the Chinese population. Two polymorphisms at -1499 and -1514 located in the TBX21 promoter region were identified by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Single nucleotide polymorphism (SNP) at -1499 was significantly different between HBV patients and healthy controls [p=0.003; odds ratio (OR) 3.65, 95% confidence interval (CI) 1.58-8.45]. Similarly, our results showed a significantly higher level of haplotype D (--/AC) in HBV patients compared to control subjects (p=0.005; OR 4.82, 95% CI 1.59-14.61). CONCLUSIONS: Based on our findings, it seems that genetic variations of allele -1499 and haplotype D (--/AC) within the TBX21 promoter region contribute to susceptibility to HBV infection in the Chinese population.

Association of the -183 polymorphism in the IFN-gamma gene promoter with hepatitis B virus infection in the Chinese population.

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that plays an important role in regulating cellular immune responses. Regulation of IFN-gamma expression is considered to be strictly controlled at the transcriptional level. Two single-nucleotide polymorphisms (SNPs) within the human IFN-gamma promoter (at positions -183 and -155) are considered to influence the promoter activity by altering the acting transcription factor-1 (AP-1) binding. We sought to assess the association between the SNPs of the IFN-gamma promoter and the host susceptibility to hepatitis B virus (HBV) infection, as well as its interaction with age and gender. No polymorphism at position-155 was detected in any of the participants, but a significant difference was found in the polymorphism at position -183 between the cases and controls (G/T and T/T vs. GG; P < 0.01, odds ratio (OR) = 4.50 (95% confidence interval (CI) = 2.23-9.09). A susceptibility analysis revealed a gradually increased trend of the OR value from the young to the old group (OR = 3.03, 4.17, and 5.56). Similarly, the association of the -183 polymorphism was markedly different in females (OR = 5.71). Our data suggest that the polymorphism at position -183 of the IFN-gamma gene promoter may be associated with susceptibility to HBV infection, and age and gender factors are coordinative risk factors.

[Association between LMP2/LMP7 gene polymorphism and the infection of hepatitis B virus].

OBJECTIVE: To elucidate whether the antigen-processing gene (LMP2/LMP7) polymorphisms could influence the infection of hepatitis B virus. METHODS: Genomic DNA of 176 patients infected with HBV and 208 healthy volunteers were extracted from the peripheral blood leukocytes. Polymorphisms of LMP genes in HBV patients were determined by polymerase chain reaction-restriction fragment length polymorphism (RFLP), the controls by DNA sequencing. We used the software PHASE1.0 to construct the haplotypes of every individual. At last the unconditional Logistic regression model was used to analyze the statistical association of genotypes or haplotypes in two groups adjusted by gender and age. RESULTS: The distributions of LMP2 genes between cases and controls did not differ. However, LMP7 gene frequency in patients was higher than that in controls [odds ratio 2.11(95% confidence interval 1.36-3.26); 2.66 (95% confidence interval 1.17-6.02), heterogenous or homologous respectively]. Similarly, we found the haplotype combinated by R-K had a significant difference in two groups [odds ratio 1.81 (95% confidence interval 1.19-2.76)]. CONCLUSION: These findings suggest that polymorphisms of LMP2/LMP7 gene is one of the important host factors which independently affect on the infection of hepatitis B virus.