High-intensity focused ultrasound alone or combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with unsuitable indications for hepatectomy and radiofrequency ablation: a phase II clinical trial.

OBJECTIVES: This study aims to evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) alone or combined with transcatheter arterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) but were contraindicated for hepatectomy and radiofrequency ablation (RFA). METHODS: Patients between 20 and 80 years of age with 1-3 foci of HCC were selected. Included patients have had primary or recurrent liver lesions with no evidence of extra-hepatic metastasis prior to the study. Patients were treated with ultrasound-guided HIFU alone or HIFU combined with TACE (treated with TACE once within 4 weeks prior to receiving HIFU). RESULTS: Thirty-seven patients were enrolled, for a total of 45 lesions. The 2-year local control (LC) rate was 73.0% and the median LC time was 22 months. The 2-year progression-free survival (PFS) was 29.7% and the median PFS time was 9 months. Finally, the 2-year overall survival (OS) was 70.3%, and the median OS time was 24 months. The most common adverse events (AEs) were elevated liver enzymes, followed by fatigue, and pain, no grade 4 AEs or death occurred. Multivariate analysis showed that age, Child-Pugh class, and the number of tumors were independent prognostic factors for PFS and that the AFP levels and the number of tumors were significantly correlated with the OS. CONCLUSIONS: This study indicates that the HIFU/HIFU combined with TACE treatment is safe, and is capable of achieving both a good LC rate and a considerably good prognosis. The procedure should be considered for patients who were deemed unsuitable for other local treatments.

Efficacy of Neoadjuvant Therapy in Improving Long-Term Survival of Patients with Resectable Rectal Cancer: A Meta-Analysis.

BACKGROUND: The impact of neoadjuvant therapy on long-term prognosis of patients with resectable rectal cancer is currently unknown. OBJECTIVE: This study aimed to explore the long-term prognosis of patients with resectable rectal cancer following treatment with neoadjuvant therapy. METHODS: Four major databases (PubMed, Web of Science, Embase, Cochrane library) were searched to identify relevant articles published between January 2000 and July 2020. The main outcome indicators were the 5-year Overall Survival (OS) and Disease-Free Survival (DFS). RESULTS: The meta-analysis revealed that 5-year OS (HR: 0.88, 95% Cl: 0.83-0.93) and DFS (HR: 0.95, 95% Cl: 0.91- 0.98) were higher in patients with resectable rectal cancer after receiving neoadjuvant therapy than those treated with upfront surgery. Subgroup analysis demonstrated that the long-term survival of patients in Asia and Europe could benefit from neoadjuvant therapy. The neoadjuvant short-course radiotherapy (SCRT) and neoadjuvant chemoradiotherapy (CRT) improved the 5-year OS and DFS of patients with stage II-III rectal cancer and mid/low rectal cancer. Further research found that patients with stage II only had an increase in OS, while patients with stage Ⅲ have improved 5-year OS and DFS. CONCLUSION: Neoadjuvant therapy improved the long-term survival of patients with mid/low rectal cancer in stage Ⅱ-Ⅲ (especially stage Ⅲ). Additionally, patients in Asia and Europe seemed to be more likely to benefit from neoadjuvant therapy. For the treatment, we recommend neoadjuvant SCRT and neoadjuvant CRT for resectable rectal cancer.

The Role of Hepatic Arterial Infusion Chemotherapy in the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). METHODS: The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). RESULTS: A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients' OS (HR, 0.49; 95% CI: 0.37-0.61) and PFS (HR, 0.52; 95% CI: 0.36-0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27-0.88) and DFS (HR, 0.49; 95% CI: 0.31-0.68). CONCLUSION: HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies.

Probiotics and synbiotics show clinical efficacy in treating gestational diabetes mellitus: A meta-analysis.

BACKGROUND: This study performed a systematic and meta-analysis of randomized controlled trials (RCTs) to explore the efficacy of probiotic- and symbiotic-based supplements in the treatment of gestational diabetes mellitus (GDM). METHODS: We performed a meta-analysis to evaluate the efficacy of probiotics/synbiotics in GDM treatment, following a systematic search in Web of Science, PubMed, Cochrane Library, and EBSCO databases for articles published up to July 2020. RESULTS: In total, 12 RCTs comprising 894 participants, were analyzed. Compared to the placebo, patients administered with probiotic and synbiotic supplements benefited more with regards to glucose and lipid metabolism as well as anti-inflammation and antioxidant capacity including insulin of change (WMD: 3.57, 95%CI: -5.26, -1.88), very-low-density lipoprotein (VLDL) (WMD: -5.03, 95%CI: -8.26, -1.79), nitric oxide (NO) at the end of trial (WMD: 2.31, 95%CI: 0.91, 3.70), total antioxidant capacity (TAC) at the end of trial (SMD: 0.74, 95%CI: 0.21, 1.27), high-sensitivity C-reactive protein (hsCRP) at the end of trial (SMD: -1.23, 95%CI: -1.97, -0.49). Besides, probiotic and synbiotic supplements improved outcomes on fetal hyperbilirubinemia risk (RR: 0.26, 95%CI: 0.12, 0.55), fetal macrosomia risk (RR: 0.47, 95%CI: 0.27, 0.83) and newborn weight (SMD: -0.29, 95%CI: -0.50, -0.09). CONCLUSIONS: Findings from this work demonstrate that probiotic/symbiotic-based interventions improve glucose and lipid metabolism, anti-inflammatory and antioxidant ability in diet-controlled GDM patients, and exert beneficial outcomes on fetal hyperbilirubinemia, fetal macrosomia, and newborn weight.

Regulatory Network Analysis of Mutated Genes Based on Multi-Omics Data Reveals the Exclusive Features in Tumor Immune Microenvironment Between Left-Sided and Right-Sided Colon Cancer.

Left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have distinct characteristics in tumor immune microenvironment (TIME). Although existing studies have shown a strong association between gene mutations and TIME, whether the regulatory mechanisms between gene mutations and TIME are different between RCC and LCC is still unclear. In this study, we showed the fractions of CD8+ T cells were higher while those of regulatory T cells were lower in RCC. Besides, a stronger association between gene mutations and TIME was observed in RCC. Specifically, using multi-omics data, we demonstrated the mutations of most top mutated genes (TMGs) including BRAF, PCLO, MUC16, LRP2, ANK3, KMT2D, RYR2 made great contributions to elevated fraction of immune cells by up-regulating immune-related genes directly or indirectly through miRNA and DNA methylation, whereas the effects of APC, TP53 and KRAS mutations on TIME were reversed in RCC. Remarkably, we found the expression levels of several immune checkpoint molecules such as PD-1 and LAG3 were correlated with corresponding DNA methylation levels, which were associated with the mutations of TMGs in RCC. In contrast, the associations between gene mutations and TIME were less significant in LCC. Besides, survival analyses showed APC mutation had adverse impact on immunotherapy while patients with BRAF mutation were more suitable for immunotherapy in colon cancer. We hope that our results will provide a deeper insight into the sophisticated mechanism underlying the regulation between mutations and TIME, and thus boost the discovery of differential immunotherapeutic strategies for RCC and LCC.

HIFU for the treatment of gastric cancer with liver metastases with unsuitable indications for hepatectomy and radiofrequency ablation: a prospective and propensity score-matched study.

BACKGROUND: The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). METHODS: This is a prospective, observational study on GCLM patients with 1-3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). RESULTS: Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. CONCLUSION: The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients. Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI). Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97-1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02-3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46-6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45-0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05-1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99-2.21, P = 0.05). Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.

The role of FOLFIRINOX in metastatic pancreatic cancer: a meta-analysis.

BACKGROUND: The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC. METHODS: We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS). RESULTS: We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67-0.86, p<0.001) but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than monochemotherapy (HR 0.59, 95% Cl 0.52-0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR 0.76, 95% Cl 0.61-0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR 0.91, 95% Cl 0.82-1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea. CONCLUSION: These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors.

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis.

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73-0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.

Maintenance Long-Term Multiple Cycles Treatment with Docetaxel in Metastatic Castration-Resistant Prostate Cancer: A Report of Three Cases.

Prostate cancer (PCa) is one of the most common types of malignancy, most patients with PCa will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), which has a poor prognosis. Since 2004, chemotherapy has been approved by the FDA as the first-line treatment for mCRPC, and docetaxel-based regimens have been shown to improve both the patients' symptoms and overall survival (OS). 10 cycles of docetaxel therapy are usually given to patients with mCPRC, but there is still no consensus on the optimal number of treatment cycles. Here, we present three cases of mCRPC patients that received maintenance long-term multiple-cycles docetaxel treatment. We believe that this new treatment strategy may benefit carefully selected mCRPC patients and provide several key advantages such as maximum exposure to drugs, improvements in drug efficacy, and reduce the risk of developing drug resistance.

Medical evaluation and pharmacotherapeutical strategies in management of urolithiasis.

Treatment of urolithiasis depends on several important factors which include stone location, size, composition, and patient symptoms. Although significant advancements have been made in the surgical management of urolithiasis in the last decade, pharmacotherapy which can prevent the formation of new stones and decrease the recurrence of urolithiasis has not experienced the same level of success. Currently, urolithiasis is regarded as a complicated syndrome that is determined by numerous factors, and any treatment plan for urolithiasis should be individualized while considering any potential damage arising from stone-forming factors. This review introduces the most popular methods currently used to evaluate urolithiasis and the pharmacotherapy of urolithiasis based on patient-specific factors.

The effect of vitamin D on the occurrence and development of colorectal cancer: a systematic review and meta-analysis.

PURPOSE: There has been a lot of controversies about the correlation between vitamin D and colorectal cancer (CRC). In this meta-analysis, we purposed to explore the relationship between vitamin D and the incidence of CRC/the prognosis of CRC. METHODS: A systematic search for articles in databases (Pubmed, Web of Science, EBSCO and Cochrane Library) was terminated in April 2020. The primary outcomes were the incidence rate of CRC and the long-term survival of patients with CRC. RESULTS: According to the estimated pooled OR from 21 eligible studies, covering 904,152 people, the use of vitamin D was inversely associated with the incidence of CRC [OR = 0.87, (0.82-0.92)]. Among the four studies included in this meta-analysis, covering 7486 patients, compared the overall survival (OS) of CRC between the vitamin D users and the non-users. Based on the estimated pooled HR, vitamin D potentially improved the long-term survival of CRC patients [HR = 0.91, (0.83-0.98)]. CONCLUSION: This meta-analysis demonstrates that vitamin D not only has a positive impact on the incidence of CRC from either the dietary or supplemental sources but also benefits clinical outcomes and improves the long-term survival of CRC patients. However, further studies are recommended to clarify the above phenomena.

The Efficacy and Safety of Additional Anti-HER2-Targeting Drugs in the Treatment of HER2-Positive Advanced Breast Cancer: A Meta-Analysis.

BACKGROUND: HER2-positive breast cancer patients account for one-fifth of the total breast cancer population. Besides, more anti-HER2-targeting drugs have appeared clinically. OBJECTIVE: This study aimed to analyze the efficacy and safety of additional anti-HER2 (Human Epidermal growth Factor Receptor 2)-targeting drugs in the treatment of HER2-positive advanced breast cancers. METHODS: The following databases were searched for published articles containing data on the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancer from the time of their inception until December 2019: PubMed, Web of Science, EBSCO, and Cochrane library. The primary outcomes were Progression-Free Survival (PFS) and Overall Survival (OS). RESULTS: The additional anti-HER2-targeting drugs significantly improved the PFS (HR: 0.66, p<0.001) and OS (HR: 0.77, p<0.001) of HER2-positive advanced breast cancer patients. Regarding drug types, lapatinib was the most effective (HR: 0.53, 95% Cl: 0.39-0.67, p<0.001), followed by pertuzumab (HR: 0.72, 95% Cl: 0.55-0.89, p=0.001). Trastuzumab was the least beneficial (HR: 0.87, 95% Cl: 0.31-1.44, p=0.594). Concerning treatment regimen, first-line treatment (HR: 0.67, 95% Cl: 0.52-0.82, p<0.001) was more effective than non-first-line treatment (HR: 0.82, 95% Cl: 0.71-0.94, p=0.004). The main Adverse Events (AEs) observed were diarrhea and decreased ejection fraction. CONCLUSION: Additional anti-HER2-targeting drugs can improve long-term prognosis in HER2-positive advanced breast cancers. Besides, they are associated with fewer AEs and are tolerable. Lapatinib is the most effective drug, followed by pertuzumab, whereas trastuzumab is the least effective. Concerning treatment, we recommend the use of anti-HER2-targeting drugs in first-line therapy of HER2-positive advanced breast cancers.

HIFU for the treatment of difficult colorectal liver metastases with unsuitable indications for resection and radiofrequency ablation: a phase I clinical trial.

BACKGROUND: The goal of this study is to evaluate the safety and efficacy of high intensity focused ultrasound (HIFU) for patients with colorectal liver metastases (CRLM) but were contraindicated for resection and radiofrequency ablation. METHODS: Patients between 20 and 80 years of age with 1-3 liver metastases from colorectal cancer were selected. Included patients have had their primary lesions removed with no evidence of extrahepatic metastasis prior to the study. Ultrasound-guided HIFU was employed and target regions' ablation was achieved with repeated sonications from the deep to shallow regions of the tumors section by section. RESULTS: Thirteen patients were enrolled. The most common adverse events (AEs) were pain (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase (ALT) (n = 5), and skin edema (n = 4). No grade ≥ 3 AEs occurred and while most patients (76.9%) achieved a complete response, three patients achieved a partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but the tumors were mostly isolated to the liver (8/9). The median follow-up period was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and the median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and the median OS was 25 months. CONCLUSION: This study indicates that the HIFU treatment is safe, is able to achieve a good tumor response rate and long-term prognosis even when the foci were in high-risk locations, and should be considered for patients who were considered unsuitable for other local treatments.

Differences in the effects of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass on gut hormones: systematic and meta-analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures are becoming more popular in the world of bariatric surgery. OBJECTIVES: This study investigates how LSG and LRYGB affect gut hormones and examines their differences. SETTING: Systematic review and meta-analysis. METHODS: The literature was retrieved from PubMed, Web of Science, Embase, and the Cochrane Library database before April 2020. RESULTS: We included 53 articles in our meta-analysis. After bariatric surgery, the patients' ghrelin, fasting acyl-ghrelin, fasting peptide YY (PYY), and their AUC in the LSG group were significantly lower than those in LRYGB group. Fasting ghrelin levels were significantly reduced in patients who received LSG. After LRYGB, the postoperative fasting PYY was higher than at baseline, and the results were statistically significant. Additionally, we found an increase in fasting ghrelin levels after LRYGB. Lastly, insulin levels were both reduced after LSG and LRYGB with no significant difference. CONCLUSIONS: In terms of gut hormones, ghrelin decreased significantly after LSG, while PYY increased after LRYGB. However, the impacts caused by the change in gut hormones after undergoing either LSG and LRYGB on patients are complicated, therefore, the results should be interpreted cautiously.

Clinical significance of peripheral blood-derived inflammation markers in advanced gastric cancer after radical resection.

BACKGROUND: The prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis. METHODS: A prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly. RESULTS: The optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397 ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC). Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ≥154, but chemotherapy had no significant effect on the survival of patients with PLR < 154. CONCLUSIONS: Our findings show that higher PLR (≥154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer.

BACKGROUND: KLF5 is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. KLF5 functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated by KLF5 in CRC are currently unknown. METHODS: In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of KLF5 in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of KLF5 were then searched for through bioinformatics analysis. We also constructed a regulatory network for KLF5 and annotated its functions. Finally, one of the KLF5 lncRNA targets, SNHG12, was selected to further explore its expression pattern and functions in CRC. RESULTS: We were able to identify 19 lncRNA targets of KLF5 and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors AR and HSF1 as the regulatory co-factors of KLF5 through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that KLF5 may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the SNHG12 up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that SNHG12 may play a critical part in CRC tumorigenesis and progression. Additionally, expression of SNHG12 was found to be down-regulated in CRC cell lines when KLF5 expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of SNHG12 and KLF5, further alluding to their regulatory relationship. CONCLUSIONS: In conclusion, the network analysis of KLF5 targets indicates that SNHG12 may be a significant lncRNA in CRC.

Multi-omics Data Analyses Construct TME and Identify the Immune-Related Prognosis Signatures in Human LUAD.

Lung cancer has been the focus of attention for many researchers in recent years for the leading contribution to cancer-related death worldwide, in which lung adenocarcinoma (LUAD) is the most common histological type. However, the potential mechanism behind LUAD initiation and progression remains unclear. Aiming to dissect the tumor microenvironment of LUAD and to discover more informative prognosis signatures, we investigated the immune-related differences in three types of genetic or epigenetic characteristics (expression status, somatic mutation, and DNA methylation) and considered the potential roles that these alterations have in the immune response and both the immune-related metabolic and neural systems by analyzing the multi-omics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step strategy based on lasso regression and Cox regression was used to construct the prognostic prediction model. For the prognostic predictions on the independent test set, the performance of the trained models (average concordance index [C-index] = 0.839) is satisfied, with average 1-year, 3-year, and 5-year areas under the curve (AUCs) equal to 0.796, 0.786, and 0.777. Finally, the overall model was constructed based on all samples, which comprised 27 variables and achieved a high degree of accuracy on the 1-year (AUC = 0.861), 3-year (AUC = 0.850), and 5-year (AUC = 0.916) survival predictions.

The efficacy and safety of the addition of poly ADP-ribose polymerase (PARP) inhibitors to therapy for ovarian cancer: a systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. METHODS: The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events. RESULTS: The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34-0.53, p < 0.001; HR, 0.79, 95% CI 0.65-0.94, p < 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p < 0.001), and the HR was 0.51 (p < 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p < 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p < 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system. CONCLUSIONS: PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs.

Advantages of retrograde flexible ureteroscopy in determining the etiology of painless hematuria originating from the upper urinary tract.

The present study investigated the use of retrograde flexible ureteroscopy (RFU) in the discrimination of the etiology of hematuria that originates from the upper urinary tract (UUT). The present study collected retrospective data for patients who presented with hematuria and cystoscopy-detected bleeding from the UUT between June 2006 and August 2018 in Ningbo First Hospital. All patients accepted RFU to determine the etiology of hematuria. Data regarding imaging examinations, surgery, pathology and complications were also collected and analyzed. In total, 65 patients (males, 38; females, 27) with a mean age of 63 years underwent RFU to determine the etiology of hematuria originating from the UUT. Using RFU, UUT tumors were found in 29 cases. Stones, polyps and atypical hyperplasia were found in two cases, and a definite diagnosis was not found in three cases. There were 17 cases without obvious abnormalities and nine cases were unable to undergo RFU due to ureteral stenosis. In patients who could not be diagnosed by imaging examination, 34.4% (11/32) were diagnosed with urothelial carcinoma by RFU, and these results were also confirmed by postoperative pathology. In the present study, no patient had severe complications after RFU. The present results suggested RFU may be used as a sensitive method to diagnose UUT tumors (78.4%; 29/37) and has strong specificity. RFU could be performed as a routine examination for patients with hematuria from the UUT.