The prognostic significance and potential mechanism of DBF4 zinc finger in hepatocellular carcinoma.

DBF4 zinc finger (DBF4) is a critical component involved in DNA replication and cell proliferation. It acts as a positive regulator of the cell division cycle 7 kinase. In this study, our investigation encompassed the impact of DBF4 on hepatocellular carcinoma (HCC) progression and delved into the potential mechanisms. We utilized open-access databases like TCGA and GEO to analyze the association between DBF4 and 33 different tumor types. We also conducted immunohistochemistry experiments to validate the expression of DBF4 in HCC, STAD, COAD, READ, PAAD, and LGG. Furthermore, we employed lentiviral transduction to knockdown DBF4 in HLF and SMMC cells, as well as to overexpress DBF4 in Huh7 cells. Subsequently, we evaluated the impact of DBF4 on proliferation, migration, and invasion of hepatocellular carcinoma cells. RNA sequencing and KEGG pathway enrichment analysis were also conducted to identify potential pathways, which were further validated through WB experiments. Finally, pathway inhibitor was utilized in rescue experiments to confirm whether DBF4 exerts its effects on tumor cells via the implicated pathway. Our findings revealed that DBF4 exhibited significant expression levels in nearly all examined tumors, which were further substantiated by the results of immunohistochemistry analysis. High DBF4 expression was correlated with poor overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), disease-free interval (DFI), relapse-free interval (RFI) in majority of tumor types, particularly in patients with HCC. In vitro experiments demonstrated that inhibition of DBF4 impaired the proliferative, migratory, and invasive abilities of HCC cells, whereas overexpression of DBF4 promoted these phenotypes. Sequencing results indicated that DBF4 may induce these changes through the ERBB signaling pathway. Further experimental validation revealed that DBF4 activates the ERBB signaling pathway, leading to alterations in the JNK/STAT, MAPK, and PI3K/AKT signaling pathways, thereby impacting the proliferative, migratory, and invasive abilities of tumor cells. Lastly, treatment of Huh7 cells overexpressing DBF4 with the ERBB2 inhibitor dacomitinib demonstrated the ability of ERBB2 inhibition to reverse the promoting effect of DBF4 overexpression on the proliferative, migratory, and invasive abilities of HCC cells. DBF4 plays a pivotal oncogenic role in HCC by promoting the ERBB signaling pathway and activating its downstream PI3K/AKT, JNK/STAT3, and MAPK signaling pathways. DBF4 may serve as a prognostic biomarker for patients with HCC.

Video evidence that cuckoos farm their hosts by ejecting nestlings.

When host nests are scarce, avian brood parasites would benefit from behaviours that increase the availability of suitable nests. Several studies reported ejection of host nestlings from nests by brood parasites; however, whether brood parasites do so to induce the host to re-nest and thus increase opportunities for future parasitism (i.e. 'farming' behaviour) remains unclear. Here, we report observational evidence of farming behaviour by a common cuckoo Cuculus canorus female in a Daurian redstart Phoenicurus auroreus population: (1) the cuckoo destroyed a host nest by ejecting all nestlings, (2) the host then produced a new nest and (3) the cuckoo successfully parasitized the replacement nest. We suggest that farming behaviour may be more common, but often goes undetected because it requires intense nest monitoring.

Gastric mixed neuroendocrine non-neuroendocrine neoplasms.

The uncommon tumour known as gastric mixed neuroendocrine-non-neuroendocrine neoplasms (G-MiNENs) is made up of parts of neuroendocrine carcinoma and adenocarcinoma. The biological and clinical features are different from those of gastric adenocarcinoma. Their pathophysiology, diagnostic standards, and clinical behaviour have all been the subject of lengthy debates, and their nomenclature has undergone multiple changes. Its emergence has created new challenges in the classification and diagnosis of gastric tumours. This review will update information on the topic, covering molecular aspects, diagnostic criteria, treatment, and prognostic factor discovery. It will also provide a historical context that will aid in understanding the evolution of the idea and nomenclature of mixed gastric tumours. Additionally, it will provide the reader a thorough understanding of this difficult topic of cancer that is applicable to real-world situations.

Transcription factor RELA promotes hepatocellular carcinoma progression by promoting the transcription of m6A modulator METTL3.

OBJECTIVE: To explore the biological function of RELA proto-oncogene, NF-kB subunit (RELA) in hepatocellular carcinoma (HCC) progression, and its potential regulatory effects on the regulators of m6A modification. METHODS AND MATERIALS: GEPIA, UALCAN and Human Protein Atlas databases were applied to analyze the expression characteristics of RELA in HCC tissues and non-cancer liver tissues, and its relationship with clinicopathologic indicators and prognosis. Quantitative real-time PCR (qRT-PCR) was used to examine the expression level of RELA mRNA in HCC cells. Cell counting kit-8 (CCK-8) assay, EdU assay and flow cytometry were used to examine cell growth and apoptosis. PROMO database was applied to predict the binding sequence between RELA and methyltransferase like protein 3 (METTL3) promoter region, and this prediction was verified by dual luciferase reporter gene experiment and chromatin immunoprecipitation assay. The effect of RELA on METTL3 expression was examined by Western blot and qRT-PCT, and the regulatory effects of RELA on the other m6A regulators were evaluated by qRT-PCR. RESULTS: RELA was highly expressed in HCC tissues and cell lines, and was closely associated with adverse clinicopathologic indicators and poor prognosis of patients. Overexpression of RELA promoted the growth of HCC cells and inhibited apoptosis; Knocking down RELA had the opposite effects. Overexpression of RELA promoted METTL3 transcription. Knockdown or overexpression of METTL3 reversed the effects of overexpression or knockdown of RELA on HCC cell growth and apoptosis, respectively. RELA also promoted the expression of a series of m6A regulators at mRNA expression level in HCC cell lines. CONCLUSION: RELA promotes the transcription of METTL3 by binding to METTL3 promoter region, thus promoting the malignancy of HCC cells. This study suggests NF-κB signaling contributes the dysregulation of m6A modification in HCC tumorigenesis.

Sarcopenia affects the clinical efficacy of immune checkpoint inhibitors in patients with gastrointestinal cancers.

OBJECTIVE: The impact of sarcopenia on the efficacy of immune checkpoint inhibitors (ICI) in gastrointestinal cancer (GIC) patients remains uncertain in clinical practice. Hence, this study aims to investigate the potential correlation between sarcopenia and the clinical outcomes of GIC patients treated with ICIs. METHODS: To gather pertinent studies, a systematic literature search was implemented across multiple databases, including PubMed, Embase, the Cochrane Library, and Google Scholar. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS), measured with the hazard ratio (HR). And the secondary outcomes, including disease control rate (DCR), overall response rate (ORR), and adverse events (AE), were evaluated with the odd ratio (OR). RESULTS: A total of 13 articles involving 1294 patients were collected for this analysis. The pooled results revealed that GIC patients with sarcopenia had significantly poorer OS (HR = 1.697, 95% CI = 1.367-2.106, p < 0.001) and PFS (HR: 1.551, 95% CI: 1.312-1.833, p < 0.001), and lower ORR (OR = 0.594, 95% CI = 0.388-0.909, p = 0.016) and DCR (OR: 0.553, 95% CI: 0.360-0.850, p = 0.007) compared to those without sarcopenia. However, sarcopenia did not increase the incidence of treatment-related adverse events compared with non-sarcopenia (OR = 1.377, 95% CI = 0.693-2.737, p = 0.361). According to subgroup analysis, the association between sarcopenia and the therapeutic effect of ICI on patients with primary liver cancer or gastric cancer was consistent with the above findings. CONCLUSION: Sarcopenia is significantly correlated with poorer treatment response and worse long-term efficacy in GIC patients treated with ICIs. Moreover, sarcopenia does not increase the incidence of adverse events.

Role of gonadally synthesized steroid hormones in the colorectal cancer microenvironment.

Objective: To understand the relationship between steroid hormones synthesized by the gonads and colorectal cancer as well as its tumor microenvironment, in the expectation of providing new ideas in order to detect and treat colorectal cancer. Methods: Through reviewing the relevant literature at home and abroad, we summarized that androgens promote the growth of colorectal cancer, and estrogens and progesterone help prevent bowel cancer from developing; these three hormones also have a relevant role in the cellular and other non-cellular components of the tumor microenvironment of colorectal cancer. Conclusion: The current literature suggests that androgens, estrogens, and progesterone are valuable in diagnosing and treating colorectal cancer, and that androgens promote the growth of colorectal cancer whereas estrogens and progesterone inhibit colorectal cancer, and that, in addition, the receptors associated with them are implicated in the modulation of a variety of cellular components of the microenvironment of colorectal cancer.

Low geriatric nutritional risk index as a poor prognostic biomarker for immune checkpoint inhibitor treatment in solid cancer.

Objective: In this investigation, we focused on the geriatric nutritional risk index (GNRI), a comprehensive metric that takes into account the patient's ideal weight, actual weight, and serum albumin levels to measure malnutrition. Our primary objective was to examine the predictive value of GNRI-defined malnutrition in determining the response to immunotherapy among cancer patients. Methods: Relevant articles for this study were systematically searched in PubMed, the Cochrane Library, EMBASE, and Google Scholar up to July 2023. Our analysis evaluated overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) as clinical outcomes. Results: This analysis comprised a total of eleven articles encompassing 1,417 patients. The pooled results revealed that cancer patients with low GNRI levels exhibited shorter OS (HR: 2.64, 95% CI: 2.08-3.36, p < 0.001) and PFS (HR: 1.87, 95% CI: 1.46-2.41, p < 0.001), and lower ORR (OR: 0.46, 95% CI: 0.33-0.65, p < 0.001) and DCR (OR: 0.42, 95% CI: 0.29-0.61, p < 0.001). Sensitivity analyses confirmed that the above results were stable. Egger's and Begg's tests revealed that there was no publication bias in the above results. Conclusion: Our results imply that the GNRI is a useful predictor of immunotherapy response in cancer patients.

Construction of a Nomogram to Predict Overall Survival in Patients with Early-Onset Hepatocellular Carcinoma: A Retrospective Cohort Study.

Hepatocellular carcinoma (HCC) is a widespread and impactful cancer which has pertinent implications worldwide. Although most cases of HCC are typically diagnosed in individuals aged ≥60 years, there has been a notable rise in the occurrence of HCC among younger patients. However, there is a scarcity of precise prognostic models available for predicting outcomes in these younger patients. A retrospective analysis was conducted to investigate early-onset hepatocellular carcinoma (EO-LIHC) using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2018. The analysis included 1392 patients from the SEER database and our hospital. Among them, 1287 patients from the SEER database were assigned to the training cohort (n = 899) and validation cohort 1 (n = 388), while 105 patients from our hospital were assigned to validation cohort 2. A Cox regression analysis showed that age, sex, AFP, grade, stage, tumor size, surgery, and chemotherapy were independent risk factors. The nomogram developed in this study demonstrated its discriminatory ability to predict the 1-, 3-, and 5-year overall survival (OS) rates in EO-LIHC patients based on individual characteristics. Additionally, a web-based OS prediction model specifically tailored for EO-LIHC patients was created and validated. Overall, these advancements contribute to improved decision-making and personalized care for individuals with EO-LIHC.

Effects of hormones on intestinal stem cells.

The maintenance of intestinal renewal and repair mainly depends on intestinal stem cells (ISCs), which can also contribute to the growth of intestinal tumours. Hormones, which are vital signalling agents in the body, have various effects on the growth and replacement of intestinal stem cells. This review summarises recent progress in the identification of hormones associated with intestinal stem cells. Several hormones, including thyroid hormone, glucagon-like peptide-2, androgens, insulin, leptin, growth hormone, corticotropin-releasing hormone and progastrin, promote the development of intestinal stem cells. However, somatostatin and melatonin are two hormones that prevent the proliferation of intestinal stem cells. Therefore, new therapeutic targets for the diagnosis and treatment of intestinal illnesses can be identified by examining the impact of hormones on intestinal stem cells.

The Use of Antibiotics During Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Advanced Esophagogastric Cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are effective in only a minority of patients with esophagogastric cancer (EGC). Here, we aimed to explore the impact of antibiotic use on outcomes in ICI-treated EGC patients. METHODS: Patients with advanced EGC treated with ICIs at our center were identified between 2017 and 2021. The impact of antibiotic use on overall survival (OS) and progression-free survival (PFS) was assessed by a log-rank test. Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 17, 2022. Clinical outcomes were OS, PFS, and disease control rate (DCR). RESULTS: In our cohort, 85 EGC patients were recruited. The results showed that antibiotic use significantly shortens OS (HR: 1.91, 95% CI: 1.11-3.28, P = 0.020) and PFS (HR: 2.13, 95% CI: 1.21-3.74, P = 0.009) and reduces DCR (OR: 0.27, 95% CI: 0.10-0.720, P = 0.013) in EGC patients treated with ICIs. The meta-analysis results revealed that antibiotic use was significantly associated with worse OS (HR = 2.454, 95% CI: 1.608-3.748, P < 0.001), PFS (HR = 2.539, 95% CI: 1.455-4.432, P = 0.001), and lower DCR (OR = 0.246, 95% CI: 0.105-0.577, P = 0.001). No publication bias existed, and sensitivity analysis confirmed stable results. CONCLUSION: In patients with advanced EGC undergoing ICI, the use of antibiotics, such as cephalosporins, was associated with inferior survival rates.

Blood biomarkers predict outcomes in patients with hepatocellular carcinoma treated with immune checkpoint Inhibitors: A pooled analysis of 44 retrospective sudies.

OBJECTIVE: We conducted the first meta-analysis to identify the predictive significance of baseline blood biomarkers (such as neutrophil to lymphocyte ratio (NLR), early alpha-fetoprotein (AFP) response, albumin-bilirubin (ALBI), AFP, platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), protein induced by vitamin K absence II (PIVKA-II), and lymphocyte to monocyte ratio (LMR)) in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by November 24, 2022. Clinical outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and hyperprogressive disease (HPD). RESULTS: A total of 44 articles with 5322 patients were included in this meta-analysis. The pooled results demonstrated that patients with high NLR levels had significantly poorer OS (HR: 1.951, P < 0.001) and PFS (HR: 1.632, P < 0.001), lower ORR (OR: 0.484, P < 0.001) and DCR (OR: 0.494, P = 0.027), and higher HPD (OR: 8.190, P < 0.001). The patients with high AFP levels had shorter OS (HR: 1.689, P < 0.001) and PFS (HR: 1.380, P < 0.001), and lower DCR (OR: 0.440, P < 0.001) than those with low AFP levels, however, there was no difference in ORR (OR: 0.963, P = 0.933). We also found that early AFP response was correlated with better OS (HR: 0.422, P < 0.001) and PFS (HR: 0.385, P < 0.001), higher ORR (OR: 7.297, P < 0.001) and DCR (OR: 13.360, P < 0.001) compared to non-responders. Besides, a high ALBI grade was significantly related to shorter OS (HR: 2.440, P = 0.009) and PFS (HR: 1.373, P = 0.022), lower ORR (OR: 0.618, P = 0.032) and DCR (OR: 0.672, P = 0.049) than those with an ALBI grade 1. CONCLUSION: The NLR, early AFP response, and ALBI were useful predictors of outcomes in HCC patients treated with ICIs.

Characterization of the intestinal fungal microbiome in patients with hepatocellular carcinoma.

OBJECTIVE: Gut mycobiota plays a crucial role in benign liver diseases; however, its correlation with hepatocellular carcinoma (HCC) remains elusive. This study aimed to elucidate fungal differences in patients with HCC-associated cirrhosis compared to cirrhotic patients without HCC and healthy controls. METHODS: The 72 fecal samples from 34 HCC patients, 20 cirrhotic patients, and 18 healthy controls were collected and analyzed using ITS2 rDNA sequencing. RESULTS: Our results revealed the presence of intestinal fungal dysbiosis with significant enrichment of opportunistic pathogenic fungi such as Malassezia, Malassezia sp., Candida, and C. albicans in HCC patients compared with healthy controls and cirrhosis patients. Alpha-diversity analysis demonstrated that patients with HCC and cirrhosis showed decreased fungal diversity compared to healthy controls. Beta diversity analysis indicated that the three groups exhibited significant segregated clustering. Besides, C. albicans was found to be significantly more abundant in the HCC patients with TNM stage III-IV than those with stage I-II, in contrast to the commensal organism S. cerevisiae. We also confirmed that the HCC patients were successfully classified with an area under the curve value of 0.906 based on the fecal fungal signature. Finally, our animal experiments confirm that aberrant colonization of the intestine by C. albicans and M. furfur can promote the development of HCC. CONCLUSIONS: This study indicates that dysbiosis of the gut mycobiome might be involved in HCC development. TRIAL REGISTRATION: ChiCTR, ChiCTR2100054537. Registered 19 December 2021, http://www.chictr.org.cn/edit.aspx?pid=144550&htm=4.

Experimental evidence that cuckoos choose host nests following an egg matching strategy.

The arms race between brood parasites and their hosts provides a classic model to study coevolution. Hosts often reject the parasitic egg, and brood parasites should therefore select host nests in which the colour of the eggs best matches that of their own. Although this hypothesis has received some support, direct experimental evidence is still lacking. Here, we report on a study of Daurian redstarts, which show a distinct egg-colour dimorphism, with females laying either blue or pink eggs. Redstarts are often parasitized by common cuckoos, which lay light blue eggs. First, we showed that cuckoo eggs were more similar in spectral reflectance to the blue than to the pink redstart egg morph. Second, we report that the natural parasitism rate was higher in blue than in pink host clutches. Third, we performed a field experiment in which we presented a dummy clutch of each colour morph adjacent to active redstart nests. In this set-up, cuckoos almost always chose to parasitize a blue clutch. Our results demonstrate that cuckoos actively choose redstart nests in which the egg colour matches the colour of their own eggs. Our study thus provides direct experimental evidence in support of the egg matching hypothesis.

Brood parasitism risk drives birds to breed near humans.

Urbanization is transforming ecosystems at a global scale and at an increasing rate,1,2 and its profound consequences for wildlife have been well documented.3,4,5,6 Understanding how animals thrive in the urban environment and how this environment affects (co-)evolutionary processes remains an important challenge.7 Urban environments can provide resources such as food or nest sites (e.g., cavities)10,8,9 and also reduce exposure to predators.11,12 For some species, urban environments may also affect susceptibility to brood parasitism,13,14 but this has never been tested experimentally. Here, we use a combination of field observations and experimental manipulations to show that Daurian redstarts, Phoenicurus auroreus, a common host of the common cuckoo, Cuculus canorus, nest in proximity to humans to avoid brood parasitism. First, redstarts were more likely to be parasitized with increasing distance to the nearest building. Second, redstarts adjusted their nesting location in response to a seasonally predictable change in the risk of brood parasitism. Third, experimentally simulating the presence of cuckoos during a period when they are naturally absent increased the likelihood that redstarts nested indoors or closer to human settlements. These findings suggest that redstarts actively choose to place their nest in the vicinity of a human residence as a defense against cuckoos. Our study exemplifies how animals take advantage of the urban environment by using it as a novel line of defense against detrimental interspecific interactions.

Gastric Cancer: Innovations in Screening, Diagnosis and Treatment.

Gastric cancer (GC) is an aggressive and heterogeneous malignancy that is one of the leading cancers in the world and an important global health problem due to its overall high prevalence and high mortality rate [...].

The prognostic value of the advanced lung cancer inflammation index in patients with gastrointestinal malignancy.

BACKGROUND: Systemic inflammation is crucial for the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is considered to be a better indicator of systemic inflammation than current biomarkers. However, the prognostic value of the ALI in gastrointestinal neoplasms remains unclear. We performed the first meta-analysis to explore the association between ALI and gastrointestinal oncologic outcomes to help physicians better evaluate the prognosis of those patients. METHODS: Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 29, 2022. Clinical outcomes were overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). RESULTS: A total of 18 articles with 6898 patients were included in this meta-analysis. The pooled results demonstrated that a low ALI was correlated with poor OS (HR = 1.914, 95% CI: 1.514-2.419, P < 0.001), DFS (HR = 1.631, 95% CI: 1.197-2.224, P = 0.002), and PFS (HR = 1.679, 95% CI: 1.073-2.628, P = 0.023) of patients with gastrointestinal cancers. Subgroup analysis revealed that a low ALI was associated with shorter OS (HR = 2.279, 95% CI: 1.769-2.935, P < 0.001) and DFS (HR = 1.631, 95% CI: 1.197-2.224, P = 0.002), and PFS (HR = 1.911, 95% CI: 1.517-2.408, P = 0.002) of patients with colorectal cancer. However, the ALI was not related to CSS in the patients with gastrointestinal malignancy (HR = 1.121, 95% CI: 0.694-1.812, P = 0.640). Sensitivity analysis supported the stability and dependability of the above results. CONCLUSION: The pre-treatment ALI was a useful predictor of prognosis in patients with gastrointestinal cancers.

The Prognostic Significance and Potential Mechanism of Prolyl 3-Hydroxylase 1 in Hepatocellular Carcinoma.

Background: Prolyl 3-hydroxylase 1 (P3H1) is essential for human collagen synthesis. Here, we investigated its relevance to multiple cancers, especially hepatocellular carcinoma (LIHC). Methods: We estimated the relationship of P3H1 with 33 cancers using publicly available databases. And immunohistochemistry was utilized to verify the P3H1 expression in liver, gastric, colon, pancreatic, and rectal cancer. Then, we attenuated P3H1 expression in BEL-7402 and HLF cells by lentivirus technology and assessed the effect of P3H1 on cell proliferation, migration, and invasion. Results: Bioinformatic analysis revealed a significantly higher expression of P3H1 in almost all tumors, which was consistent with the immunohistochemical findings in the liver, gastric, colon, pancreatic, and rectal cancers. P3H1 expression was associated with overall survival, progression-free interval, disease-specific survival, and disease-free interval in most cancers, particularly in LIHC. Besides, we also found that P3H1 expression was an independent prognostic factor for LIHC. And knockdown of P3H1 significantly reduced liver cancer cell proliferation, migration, and invasion in liver cancer cells. Interestingly, P3H1 expression levels showed a significant positive connection with Th2 infiltration through multiple immune infiltration algorithms. ICI treatment was less effective in LIHC patients with high P3H1 expression. Finally, we also identified an upstream regulatory mechanism of P3H1 in LIHC, namely, AL355488.1, HCG18, and THUMPD3-AS1/hsa-miR-29c-3p-P3H1 axis. Conclusion: We have systematically described for the first time that P3H1 is closely related to various tumors, particularly in LIHC, and interference with P3H1 may be a therapeutic target for patients with LIHC.

Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy.

Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising performance in improving the prognosis of urological cancer patients. The goal of this meta-analysis was to determine the impact of PPI use on the clinical outcomes of urological cancer patients receiving ICI therapy. Methods: Before 6 May 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, and Google Scholar. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of six articles met the inclusion criteria, and of the 1980 patients with advanced or metastatic urothelial cancers (UC) included. The meta-analysis displayed that PPI use could increase the risk of progression by 50.7% (HR: 1.507, 95% CI: 1.327-1.711, p < 0.001) and death by 58.7% (HR: 1.587, 95% CI: 1.367-1.842, p < 0.001), and reduce the ORR (OR: 0.503, 95% CI: 0.360-0.703, p < 0.001) in UC patients receiving ICIs. No significant heterogeneity and publication bias existed. Sensitivity analysis proved that the results were stable and reliable. Conclusion: The meta-analysis indicated that concomitant PPI use was significantly associated with low clinical benefit in UC patients.

The association between antibiotic use and outcomes of HCC patients treated with immune checkpoint inhibitors.

Objective: Recently, immune checkpoint inhibitor (ICI) treatment has shown encouraging performance in improving the prognosis of hepatocellular carcinoma (HCC) patients. The gut microbiome plays a vital role in altering the efficacy of ICIs, which may be impacted by antibiotics. The aim of the meta-analysis is to estimate the influence of antibiotic use on the survival of HCC patients treated with ICIs. Methods: The literature review was conducted using databases like PubMed, EMBASE, Cochrane Library, CNKI, WANFANG DATA, VIP, Google Scholar, and ClinicalTrials.gov before May 15, 2022. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of six retrospective studies met the inclusion criteria. 1056 patients were included in the study, of which 352 (33.33%) received antibiotic treatment. The meta-analysis results revealed antibiotic use did not affect the OS (HR: 1.41, 95% CI: 0.96-2.08, P = 0.088) and PFS (HR: 1.21, 95% CI: 0.73-2.00, P = 0.459) in HCC patients treated with ICIs. Besides, the use of antibiotics did not reduce the ORR (OR: 1.06, 95% CI: 0.69-1.64, P = 0.784) and DCR (OR: 0.42, 95% CI: 0.09-2.06, P = 0.286) in HCC patients treated with ICIs. Conclusion: Current evidence reveals that antibiotic use does alter the therapeutic efficacy of ICIs in HCC patients. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier CRD42022311948.