Effect of flexible sigmoidoscopy-based screening on colorectal cancer incidence and mortality: an updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Our objective was to estimate the effect of flexible sigmoidoscopy (FS)-based screening on colorectal cancer (CRC) incidence and mortality by conducting an updated meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Web of Science, Embase, and Cochrane Library searched for RCTs from database inception to December 2022. The methodological quality of the RCTs was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.4 was used for this meta-analysis. RESULTS: Four RCTs involving 457, 871 patients were included. This meta-analysis revealed that FS-based screening was associated with a 20% relative risk reduction in CRC incidence [RR = 0.80; 95% CI (0.75, 0.86); P < 0.00001], and a 24% reduction in CRC mortality [RR = 0.76; 95% CI (0.70, 0.82); P < 0.00001]. In addition, this meta-analysis revealed that FS-based screening reduced the incidence[RR = 0.68; 95% CI (0.60, 0.77); P < 0.00001] and mortality[RR = 0.64; 95% CI (0.49, 0.83); P = 0.0007] of distal CRC, but had no significant effect on proximal colon cancer. CONCLUSION: FS-based screening appeared to be effective in reducing distal CRC incidence and mortality in patients at average risk compared to no intervention, but had no significant effect on proximal colon cancer.

The efficacy and safety of glucocorticoid for perioperative patients with hepatectomy: a systematic review and meta-analysis.

OBJECTIVE: Glucocorticoids have been used in patients undergoing perioperative hepatectomy, however their safety and efficacy remain controversial. This meta-analysis was conducted to investigate this issue and further provide reference for clinical practice. METHODS: PubMed/MEDLINE, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) from database inception to December 2022. Literature screening and data extraction were performed independently by two reviewers. The methodological quality of the RCTs was assessed using the Jadad scale. RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 11 RCTs involving 905 patients were included. Compared with the control group, we found perioperative glucocorticoid administration significantly lowered overall complication rate [RR = 0.67; 95% CI (0.55, 0.83); P = 0.0003], infectious complication rate [RR = 0.41; 95% CI (0.21, 0.82); P = 0.01] and postoperative liver failure [RR = 0.63; 95% CI (0.41, 0.97); P = 0.03]. In addition, glucocorticoids appear to improve liver function (TBil) [MD = -0.36, 95% CI (-0.59, -0.14), P = 0.001] and reduce the release of certain inflammatory cytokines (IL-6) [MD = -48.52, 95% CI (-56.88, -40.16), P < 0.00001]. CONCLUSION: Based on the available evidence, glucocorticoids appear to be safe and effective in patients undergoing hepatectomy, but further research is needed.

Effect of primary tumor resection on survival in patients with asymptomatic unresectable metastatic colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: It remains controversial whether primary tumor resection (PTR) improves survival in patients with asymptomatic, unresectable metastatic colorectal cancer (mCRC). Therefore, we conducted a meta-analysis to assess the latest evidence on clinical outcomes. MATERIALS AND METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and Embase databases for eligible studies published between database inception and May 2022. RevMan 5.4 and Stata 16.0 were used for the meta-analysis. RESULTS: A total of nine studies were included, including four randomized controlled trials (RCTs) and five retrospective cohort studies. Meta-analysis showed that overall survival (OS) [HR = 0.89, 95%CI (0.74, 1.06), P = 0.19] and progression-free survival (PFS) [HR = 0.87, 95%CI (0.71, 1.06), P = 0.17] were not significantly different between the PTR and non-PTR groups. In the subgroup analysis, all subgroups showed no significant difference in OS between the two groups. CONCLUSION: PTR may not provide additional survival benefits over chemotherapy in asymptomatic, unresectable mCRC patients. However, in view of the limitations of this study, more well-designed RCTs are needed to validate our conclusions.

Robotic versus Laparoscopic Total Mesorectal Excision Surgery in Rectal Cancer: Analysis of Medium-Term Oncological Outcomes.

Background. Robotic systems can overcome some limitations of laparoscopic total mesorectal excision (L-TME), thus improving the quality of the surgery. So far, many studies have reported the technical feasibility and short-term oncological results of robotic total mesorectal excision (R-TME) in treating rectal cancer (RC); however, only a few evaluated the survival and long-term oncological outcomes. The following study compared the medium-term oncological data, 3-year overall survival (OS), and disease-free survival (DFS) of L-TME and R-TME in patients with rectal cancer. Methods. In this retrospective study, records of patients (patients with stage I-III rectal cancer) who underwent surgery (127 cases of L-TME and 148 cases of R-TME) at the Gansu Provincial Hospital between June 2016 and March 2018 were included in the analysis. Kaplan-Meier analysis evaluated the 3-year OS and DFS for all patients treated with curative intent. Results. The conversion rate was significantly higher, and the postoperative hospital stay was significantly longer in the L-TME group than in the R-TME group (all P<.05). Major complications were significantly lower in the robotic group (P<.05). The 3-year DFS rate (for all stages) was 74.8% for L-TME and 85.8% for R-TME (P = .021). For disease stage III, the 3-year DFS and OS were significantly higher in the R-TME group (P<.05). Conclusion. R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage III rectal cancers. Nevertheless, further randomized controlled trials and a longer follow-up period are needed to confirm these findings.

Chemotherapy plus panitumumab/cetuximab versus chemotherapy plus bevacizumab in wild-type KRAS/RAS metastatic colorectal cancer: a meta-analysis.

OBJECTIVE: It remains controversial which targeted monoclonal antibodies combined with chemotherapy can provide better efficacy in wild-type KRAS/RAS metastatic colorectal cancer (mCRC) patients. Therefore, we used this meta-analysis to assess the latest evidence of clinical outcomes. MATERIALS AND METHODS: We systematically searched PubMed, Web of Science, Cochrane Library and Embase databases for eligible studies published from database inception to May 2022. RevMan 5.4 was used to conduct the meta-analysis. RESULTS: 11 RCTs involving a total of 3575 patients were included. Meta-analysis showed that EGFR inhibitors significantly prolonged the overall survival (OS) [HR = 0.83, 95%CI (0.73, 0.94), P = 0.003] and overall response rate (ORR) [RR = 1.11, 95%CI (1.05, 1.18), P = 0.0003] compared to VEGF inhibitors in wild-type KRAS/RAS mCRC patients, but no significant difference in progression-free survival (PFS) [HR = 0.96, 95%CI (0.87, 1.07), P = 0.50]. In subgroup analysis, the survival benefit of EGFR inhibitors was limited to first-line treatment. CONCLUSION: Our study showed that EGFR inhibitors were superior to VEGF inhibitors in wild-type KRAS/RAS mCRC patients, especially in patients with first-line treatment. However, subsequent large sample, multi-center RCTs are needed to further verify our conclusions.

Metabolic Flux Enhancement and Transcriptomic Analysis Displayed the Changes of Catechins Following Long-Term Pruning in Tea Trees ( Camellia sinensis).

The tea tree is a perennial woody plant, and pruning is one of the most crucial cultivation measurements for tea plantation management. To date, the relationship between long-term pruning and metabolic flux enhancement in tea trees has not been studied. In this research, 11-year-old pruned tea trees from four different cultivars were randomly selected for transcriptome analysis and characteristic secondary metabolite analysis together with controls. The findings revealed that epigallocatechin gallate (EGCG) accumulation in pruned tea trees was significantly higher than that in unpruned tea trees. SCPL1A expression (encoding a class of serine carboxypeptidase), which has been reported to have a catalytic ability during EGCG biosynthesis, together with LAR, encoding leucoanthocyanidin reductase, was upregulated in the pruned tea trees. Moreover, metabolic flux enhancement and transcriptome analysis revealed low EGCG accumulation in the leaves of unpruned tea trees. Because of the bitter and astringent taste of EGCG, these results provide a certain understanding to the lower bitterness and astringency in teas from "ancient tea trees", growing in the wild with no trimming, than teas produced from pruned plantation trees.

Hydrogen peroxide-mediated growth of the root system occurs via auxin signaling modification and variations in the expression of cell-cycle genes in rice seedlings exposed to cadmium stress.

The link between root growth, H2O2, auxin signaling, and the cell cycle in cadmium (Cd)-stressed rice (Oryza sativa L. cv. Zhonghua No. 11) was analyzed in this study. Exposure to Cd induced a significant accumulation of Cd, but caused a decrease in zinc (Zn) content which resulted from the decreased expression of OsHMA9 and OsZIP. Analysis using a Cd-specific probe showed that Cd was mainly localized in the meristematic zone and vascular tissues. Formation and elongation of the root system were significantly promoted by 3-amino-1,2,4-triazole (AT), but were markedly inhibited by N,N'-dimethylthiourea (DMTU) under Cd stress. The effect of H2O2 on Cd-stressed root growth was further confirmed by examining a gain-of-function rice mutant (carrying catalase1 and glutathione-S-transferase) in the presence or absence of diphenylene iodonium. DR5-GUS staining revealed close associations between H2O2 and the concentration and distribution of auxin. H2O2 affected the expression of key genes, including OsYUCCA, OsPIN, OsARF, and OsIAA, in the auxin signaling pathway in Cd-treated plants. These results suggest that H2O2 functions upstream of the auxin signaling pathway. Furthermore, H2O2 modified the expression of cell-cycle genes in Cd-treated roots. The effects of H2O2 on root system growth are therefore linked to auxin signal modification and to variations in the expression of cell-cycle genes in Cd-stressed rice. A working model for the effects of H2O2 on Cd-stressed root system growth is thus proposed and discussed in this paper.

TGF-ß1 inhibits the growth and metastasis of tongue squamous carcinoma cells through Smad4.

Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine that regulates cell growth, differentiation, migration, apoptosis and extracellular matrix remodeling. TGF-ß1 transduces signals from the cell membrane to the cell nucleus through serine/threonine kinase receptors and their downstream effectors, Smad molecules. Although many studies have been focused on TGF-ß1-Smad signaling pathway, the role of TGF-ß1/Smad in tongue squamous cell carcinoma is not fully understood. In the present study, we used a series of cell function assays to examine the role of TGF-ß-Smad4 signaling in tongue squamous cell carcinoma. We observed the effects of TGF-ß1 on the growth and metastatic potential of the tongue squamous cell carcinoma cell line Ts, which expresses lower level of Smad4 protein. We found that Smad4 could decrease TGF-ß1-induced cell proliferation, and that Smad4 overexpression promoted Ts cell apoptosis. In Ts vector control cells, TGF-ß1 increased the expression of TßRII, as well as MMP-2, and enhanced cell invasion through the basement membrane, and then induced cell metastasis. However in Ts cells stably expressing Smad4, Smad4 mediated TGF-ß1-induced p21 expression promoted cell apoptosis and inhibited cell proliferation, delayed MMP-2 expression, and decreased cell metastasis. Therefore, TGF-ß1 plays distinct roles in the Smad4-dependent and -independent signaling pathways.

[Inhibitory effect of transforming growth factor-ß(1) on oral squamous cell carcinoma brain metastasis Tb cell line].

OBJECTIVE: To investigate the inhibitory effect of transforming growth factor (TGF)-ß1 on oral squamous cell carcinoma (OSCC) Tb cell line. METHODS: Cell counting method was used to examine the inhibitory effect of TGF-ß1 on Tb cell and flow cytometry (FCM) assay performed to measure the changes of cell cycle. Superarray was used to screen the changing expression of genes in TGF-ß1/Smads signaling pathway.RT-PCR method was used to detect the results of Superarray. RESULTS: TGF-ß1 showed significant inhibiting effect on OSCC Tb cell line. TGF-ß1 blocked the cell cycle at G1 phase. The expression level of activin receptor-like kinase-1 (ACVRL-1), anti-mullerian hirmine (AMH), cyclim-dependent kinase inhibitor-2B (CDKN-2B) and transforming growth factor-beta-indnced factor (TGIF) was higer in the cells treated with TGF-ß1 than in control, while TDGF-1 expression was down-regulated. ACVRL-1 and CDKN-2B gene expression was consistent with the results of Superarray. CONCLUSIONS: TGF-ß1 can inhibit the growth of OSCC Tb cell line. The mechanism may be related to the regulation of cell cycle and the expression of ACVRL-1 and CDKN-2B in TGF-ß1-Smads signaling pathway.

[Functional significance of TGF-beta1 signal transduction pathway in oral squamous cell carcinoma].

OBJECTIVE: The aim of this study was to investigate the expression of transforming growth factor-beta1 (TGF-beta1) and its signaling pathway molecules in oral squamous cell carcinoma (OSCC) and analyze the association between these factors and genesis and metastasis of OSCC. METHODS: The express of TGF-beta1, TbetaRI, TbetaRII and Smad4, a pivotal downstream molecule of its signaling, in 10 normal oral mucosa tissues and 108 OSCC was detected by SP immunohistochemistry, and thier correlation with genesis and metastasis of OSCC were assessed. RESULTS: The expressions of TbetaRII and Smad4 were lower in the tumors (34.3%, 38.9%) than those in the normal oral epithelium (80.0%, 100.0%, P < 0.05). The positive expression rates of TGF-beta1 and TbetaRI in the normal oral epithelium and OSCC were not significantly different (P > 0.05). There was an inverse correlation between TGF-beta1, Smad4, TbetaRII, TbetaRI expression and clinical stages (P < 0.01). The expression of TGF-beta1 was related with histological differentiation and tumor localization (P < 0.05). There was a relationship beteween Smad4 expression and histological differentiation and lymph node metastasis (P < 0.05). The expression of TbetaRII in the samples with lymph node metastasis was less than that in the ones without lymph node metastasis (P < 0.01), although there was no association between expression of TbetaRII and lymph node metastasis status. CONCLUSION: There is an important relationship between the abnormal TGF-beta1/Smad4 signal pathway and genesis and development of OSCC, while the low expressed Smad4 and TbetaRII may promote the metastasis of OSCC.