Effects of Active Ingredients in Alcoholic Beverages and Their De-Alcoholized Counterparts on High-Fat Diet Bees: A Comparative Study.

The mechanisms by which alcohol, alcoholic beverages, and their de-alcoholized derivatives affect animal physiology, metabolism, and gut microbiota have not yet been clarified. The polyphenol, monosaccharide, amino acid, and organic acid contents of four common alcoholic beverages (Chinese Baijiu, beer, Chinese Huangjiu, and wine) and their de-alcoholized counterparts were analyzed. The research further explored how these alcoholic beverages and their non-alcoholic versions affect obesity and gut microbiota, using a high-fat diet bee model created with 2% palm oil (PO). The results showed that wine, possessing the highest polyphenol content, and its de-alcoholized form, particularly when diluted five-fold (WDX5), markedly improved the health markers of PO-fed bees, including weight, triglycerides, and total cholesterol levels in blood lymphocytes. WDX5 treatment notably increased the presence of beneficial microbes such as Bartonella, Gilliamella, and Bifidobacterium, while decreasing Bombilactobacillus abundance. Moreover, WDX5 was found to closely resemble sucrose water (SUC) in terms of gut microbial function, significantly boosting short-chain fatty acids, lipopolysaccharide metabolism, and associated enzymatic pathways, thereby favorably affecting metabolic regulation and gut microbiota stability in bees.

Synthesis of tunable thickness-to-diameter ratio microcapsules via a diffusion-controlled process for temperature-responsive release.

Designing microcapsules with a complicated functionalized shell to respond to an external stimulus has attracted much attention for triggered release; however, simplifying the synthesis process remains a significant challenge. Herein, we initially propose a novel, simple synthesis strategy that utilizes a mixed solvent as the organic phase to control the diffusion of common monomers during interfacial polymerization, resulting in the successful preparation of microcapsules with tunable thickness-to-diameter ratios (T/D). The morphology of microcapsules is confirmed by scanning electron microscopy. We also observe that the T/D of the designed microcapsules progressively increases as the diffusion of monomers occurs, and the glass transition temperature of microcapsules is controlled. Furthermore, microcapsule-based crosslinking agents are applied to investigate the crosslinking reaction of poly(vinyl chloride). Rotational rheometer results indicate that the microcapsules exhibit an excellent external stimulus response, precisely triggering release at the predetermined temperature. This simple approach for the preparation of microcapsules with tunable physical properties has great potential for triggered release in diverse applications.

Single-incision laparoscopic transabdominal preperitoneal repair in the treatment of adult female patients with inguinal hernia.

BACKGROUND: Women have a 3% lifetime chance of developing an inguinal hernia, which is not as common in men. Due to its cosmetic benefits, single-incision laparoscopic transabdominal preperitoneal (SIL-TAPP) inguinal hernia repair is becoming increasingly popular in the management of inguinal hernia in women. However, there are no studies comparing the safety and applicability of SIL-TAPP repair with conventional laparoscopic transabdominal preperitoneal (CL-TAPP) inguinal hernia repair for the treatment of inguinal hernia in women. AIM: To compare the outcomes of SIL-TAPP and CL-TAPP repair in adult female patients with inguinal hernia and to estimate the safety and applicability of SIL-TAPP repair in adult female inguinal hernia patients. METHODS: We retrospectively compared the clinical information and follow-up data of female inguinal hernia patients who underwent SIL-TAPP inguinal hernia repair and those who underwent CL-TAPP inguinal hernia repair at the Affiliated Hospital of Nantong University from February 2018 to December 2020 and assessed the long-term and short-term outcomes of both cohorts. RESULTS: This study included 123 patients, with 71 undergoing SIL-TAPP repair and 52 undergoing CL-TAPP repair. The two cohorts of patients and inguinal hernia characteristics were similar, with no statistically meaningful difference. The rate of intraoperative inferior epigastric vessel injury was lower in patients in the SIL-TAPP cohort (0, 0%) than in patients in the CL-TAPP cohort (4, 7.7%) and was significantly different (P < 0.05). In addition, the median [interquartile range (IQR)] total hospitalization costs were significantly lower in patients in the SIL-TAPP cohort [$3287 (3218-3325)] than in patients in the CL-TAPP cohort [$3511 (3491-3599)]. Postoperatively, the occurrence rate of trocar site hernia was lower in the SIL-TAPP cohort (0, 0%) than in the CL-TAPP cohort (4, 7.7%), and the median (IQR) cosmetic score was significantly higher in the SIL-TAPP cohort [10 (10-10)] than in the CL-TAPP cohort [9 (9-10)]. CONCLUSION: SIL-TAPP repair did not increase the incidence of intraoperative and postoperative complications in female inguinal hernia patients. Moreover, female inguinal hernia patients who underwent SIL-TAPP repair had a lower probability of trocar site hernia and inferior epigastric vessel injury than female inguinal hernia patients who underwent CL-TAPP repair. In addition, female inguinal hernia patients who underwent SIL-TAPP repair reported a more aesthetically pleasing postoperative abdominal incision. Therefore, SIL-TAPP repair is a better option for the treatment of inguinal hernias in women.

Robustly federated learning model for identifying high-risk patients with postoperative gastric cancer recurrence.

The prediction of patient disease risk via computed tomography (CT) images and artificial intelligence techniques shows great potential. However, training a robust artificial intelligence model typically requires large-scale data support. In practice, the collection of medical data faces obstacles related to privacy protection. Therefore, the present study aims to establish a robust federated learning model to overcome the data island problem and identify high-risk patients with postoperative gastric cancer recurrence in a multicentre, cross-institution setting, thereby enabling robust treatment with significant value. In the present study, we collect data from four independent medical institutions for experimentation. The robust federated learning model algorithm yields area under the receiver operating characteristic curve (AUC) values of 0.710, 0.798, 0.809, and 0.869 across four data centres. Additionally, the effectiveness of the algorithm is evaluated, and both adaptive and common features are identified through analysis.

Comparison of transumbilical single-incision laparoscopic TAPP versus conventional laparoscopic TAPP in the elderly: A retrospective analysis.

BACKGROUND: To analyze and compare the clinical efficacy of transumbilical single-incision laparoscopic surgery TAPP(SILS-TAPP) and conventional laparoscopic TAPP(CL-TAPP) in the treatment of senile inguinal hernia. METHODS: From January 2019 to June 2021, a total of 221 elderly patients (≥60 years old) with inguinal hernia received SILS-TAPP and CL-TAPP in General Surgery Department of Affiliated Hospital of Nantong University. The perioperative indicators, postoperative complications and follow-up of the two groups were compared to explore the feasibility and superiority of SILS-TAPP in the treatment of inguinal hernia in the elderly. RESULTS: There was no difference in demographic characteristics between the two groups. The mean operation time (28.6 ± 4.2 min vs 28.2 ± 5.3 min) in the SILS-TAPP group was not significantly different from that in the CL-TAPP group (Ρ = 0.623), and there was no significant increase in hospital costs(Ρ = 0.748). The intraoperative blood loss (7.4 ± 3.4 ml), VAS score on the postoperative day (2.2 ± 0.7), mean time of resuming activity (8.2 ± 1.9 h) and mean postoperative hospital stay (0.8 ± 0.2 d) in the SILS-TAPP group were better than those in the CL-TAPP group (Ρ < 0. 05).There was no statistical difference in the overall incidence of intraoperative (Ρ = 0.128) and postoperative complications (Ρ = 0.125) between the two groups. CONCLUSION: Single-incision laparoscopic surgery TAPP (SILS-TAPP) is feasible and effective in elderly patients, providing a new alternative surgical method for patients who can tolerate general anesthesia.

Distinguishing common renal cell carcinomas from benign renal tumors based on machine learning: comparing various CT imaging phases, slices, tumor sizes, and ROI segmentation strategies.

OBJECTIVES: To determine whether a CT-based machine learning (ML) can differentiate benign renal tumors from renal cell carcinomas (RCCs) and improve radiologists' diagnostic performance, and evaluate the impact of variable CT imaging phases, slices, tumor sizes, and region of interest (ROI) segmentation strategies. METHODS: Patients with pathologically proven RCCs and benign renal tumors from our institution between 2008 and 2020 were included as the training dataset for ML model development and internal validation (including 418 RCCs and 78 benign tumors), and patients from two independent institutions and a public database (TCIA) were included as the external dataset for individual testing (including 262 RCCs and 47 benign tumors). Features were extracted from three-phase CT images. CatBoost was used for feature selection and ML model establishment. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the ML model. RESULTS: The ML model based on 3D images performed better than that based on 2D images, with the highest AUC of 0.81 and accuracy (ACC) of 0.86. All three radiologists achieved better performance by referring to the classifier's decision, with accuracies increasing from 0.82 to 0.87, 0.82 to 0.88, and 0.76 to 0.87. The ML model achieved higher negative predictive values (NPV, 0.82-0.99), and the radiologists achieved higher positive predictive values (PPV, 0.91-0.95). CONCLUSIONS: A ML classifier based on whole-tumor three-phase CT images can be a useful and promising tool for differentiating RCCs from benign renal tumors. The ML model also perfectly complements radiologist interpretations. KEY POINTS: • A machine learning classifier based on CT images could be a reliable way to differentiate RCCs from benign renal tumors. • The machine learning model perfectly complemented the radiologists' interpretations. • Subtle variances in ROI delineation had little effect on the performance of the ML classifier.

Research progress regarding the effect and mechanism of dietary phenolic acids for improving nonalcoholic fatty liver disease via gut microbiota.

Phenolic acids (PAs), a class of small bioactive molecules widely distributed in food and mainly found as secondary plant metabolites, present significant advantages such as antioxidant activity and other health benefits. The global epidemic of nonalcoholic fatty liver disease (NAFLD) is becoming a serious public health problem. Existing studies showed that gut microbiota (GM) dysbiosis is highly associated with the occurrence and development of NAFLD. In recent years, progress has been made in the study of the relationship among PA compounds, GM, and NAFLD. PAs can regulate the composition and functions of the GM to promote human health, while GM can increase the dietary sources of PAs and improve its bioavailability. This paper discussed PAs, GM, and their interrelationship while introducing several representative dietary PA sources and examining the absorption and metabolism of PAs mediated by GM. It also summarizes the effect and mechanisms of PAs in improving and regulating NAFLD via GM and their metabolites. This helps to better evaluate the potential preventive effect of PAs on NAFLD via the regulation of GM and expands the utilization of PAs and PA-rich food resources.

LncRNA TTN-AS1 confers tamoxifen resistance in breast cancer via sponging miR-107 to modulate PI3K/AKT signaling pathway.

OBJECTIVE: Tamoxifen resistance of breast cancer (BC) is a significant hindrance in clinical therapy. The long-noncoding RNA (lncRNA) TTN-AS1 has been reported as a crucial tumor promoting factor in various cancers. In this study, we set out to discover the specific pathologic regulatory mechanisms of tamoxifen-resistance in breast cancer. METHODS: MTT assay was conducted to evaluate the cell viability of the breast cancer cell lines MCF-7 and MCF-7/TAM. QRT-PCR and western blot assay were performed to estimate the expression of TTN-AS1, miR-107 and related proteins. Flow cytometry was conducted to identify degree of apoptosis and cell cycle. The invasive ability was estimated by transwell chamber assay. RESULTS: Our findings revealed that TTN-AS1 can enhance tamoxifen-resistance in BC cells and augment the invasive ability of tamoxifen-resistant breast cancer cells by down-regulating miR-107, and thereby encourage the development of drug-resistant BC. Further investigation indicates that lncRNA TTN-AS1 worsens the course of tamoxifen-resistant BC by regulating zinc and ring finger 2 (ZNRF2) via miR-107 and activating the PI3K/AKT pathway. CONCLUSION: Our findings suggest that the lncRNA TTN-AS1 can encourage tamoxifen-resistance in BC by modulating the miR-107/ZNRF2 axis and stimulating the PI3K/AKT pathway.

Up-regulation of long noncoding RNA MBNL1-AS1 suppresses breast cancer progression by modulating miR-423-5p/CREBZF axis.

Breast cancer is the leading cause of cancer-related death among females, which is required to be solved urgently. Recent studies have found significant changes in a large number of genes and their transcriptional levels during breast cancer development, which are often closely related to the abnormal expression of long noncoding RNAs (lncRNAs). Herein, our study found that MBNL1-AS1 was down-regulated both in breast cancer tissues and cell lines, and it functioned as a tumor suppressor to inhibit cancer cell proliferation, migration, and invasion. MiR-423-5p was found to be a target of MBNL1-AS1 with an inverse relationship: an increase in miR-423-5p could counteract the inhibitory effect induced by MBNL1-AS1 on cancer cell promotion. Further, CREBZF was negatively regulated by miR-423-5p. Accordingly, CREBZF knockdown could impair the hindrance of cancer cell growth mediated by low miR-423-5p expression. Also, MBNL1-AS1 influenced the PI3K/AKT pathway, which was associated with cell proliferation and apoptosis, by regulating CREBZF. As a result, our work illustrated the tumor suppressor role of MBNL1-AS1 in breast cancer via upregulating miR-423-5p-targeted CREBZF. Thereby, the evidence indicates the complete understanding of the role of MBNL1-AS1/miR-423-5p/CREBZF axis in the regulation of breast cancer development, which could be used as a biomarker for predicating survival among breast cancer patients.

RBM38 is negatively regulated by miR-320b and enhances Adriamycin resistance in breast cancer cells.

Breast cancer (BC) is a common type of malignant tumor that is frequently accompanied by drug resistance, which is a significant challenge in the treatment of BC. Adriamycin (ADM) is a commonly used drug for the treatment of BC. The aim of the present study was to demonstrate the association between RNA binding motif protein 38 (RBM38) and ADM resistance in BC. The results revealed that the expression levels of RBM38 were significantly upregulated in ADM-resistant BC tissues and the ADM-resistant cell line, MCF-7/A, as demonstrated using reverse transcription-quantitative PCR and western blotting. In addition, the results of the MTT assay revealed that the overexpression of RBM38 enhanced the resistance of MCF-7/A cells to ADM, promoted invasiveness, as determined using a Transwell assay, inhibited the apoptosis of resistant cells, as determined using flow cytometry, and accelerated cell cycle progression from the G0 to the S phase. The results of the dual luciferase reporter assay demonstrated the binding relationship between microRNA (miR)-320b and RBM38, and the expression levels of miR-320b were significantly downregulated in ADM-resistant BC tissues and MCF-7/A cells. Overexpression of miR-320b reversed ADM resistance, suppressed invasiveness, promoted apoptosis and arrested MCF-7/A cells in the G0 phase. In addition, RBM38 was discovered to be negatively regulated by miR-320b, which was able to restore the sensitivity of BC cells to ADM by downregulating RBM38. Further exploration of the underlying regulatory mechanism revealed that the miR-320b/RBM38 signaling axis mediated the development of ADM resistance in BC by altering the expression of cell cycle-, drug resistance- and PI3K/AKT signaling pathway-related proteins. In conclusion, the results of the present study suggested that RBM38 may be negatively regulated by miR-320b, which accelerates drug resistance in BC.

Research progress on intervention effect and mechanism of protocatechuic acid on nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has become a surge burden worldwide due to its high prevalence, with complicated deterioration symptoms such as liver fibrosis and cancer. No effective drugs are available for NALFD so far. The rapid growth of clinical demand has prompted the treatment of NAFLD to become a research hotspot. Protocatechuic acid (PCA) is a natural secondary metabolite commonly found in fruits, vegetables, grains, and herbal medicine. It is also the major internal metabolites of anthocyanins and other polyphenols. In the present manuscript, food sources, metabolic absorption, and efficacy of PCA were summarized while analyzing its role in improving NAFLD, as well as the mechanism involved. The results indicated that PCA could ameliorate NAFLD by regulating glucose and lipid metabolism, oxidative stress and inflammation, gut microbiota and metabolites. It was proposed for the first time that PCA might reduce NAFLD by enhancing the energy consumption of brown adipose tissue (BAT). However, the PCA administration mode and dose for NAFLD remain inconclusive. Fresh insights into the specific molecular mechanisms are required, while clinical trials are essential in the future. This review provides new targets and reasoning for the clinical application of PCA in the prevention and treatment of NAFLD.

Computed Tomography-Based Radiomics Nomogram: Potential to Predict Local Recurrence of Gastric Cancer After Radical Resection.

OBJECTIVE: Accurate prediction of postoperative recurrence risk of gastric cancer (GC) is critical for individualized precision therapy. We aimed to investigate whether a computed tomography (CT)-based radiomics nomogram can be used as a tool for predicting the local recurrence (LR) of GC after radical resection. MATERIALS AND METHODS: 342 patients (194 in the training cohort, 78 in the internal validation cohort, and 70 in the external validation cohort) with pathologically proven GC from two centers were included. Radiomics features were extracted from the preoperative CT imaging. The clinical model, radiomics signature, and radiomics nomogram, which incorporated the radiomics signature and independent clinical risk factors, were developed and verified. Furthermore, the performance of these three models was assessed by using the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: The radiomics signature, which was comprised of two selected radiomics features, namely, contrast_GLCM and dissimilarity_GLCM, showed better performance than the clinical model in predicting the LR of GC, with AUC values of 0.83 in the training cohort, 0.84 in the internal validation cohort, and 0.73 in the external cohort, respectively. By integrating the independent clinical risk factors (N stage, bile acid duodenogastric reflux and nodular or irregular outer layer of the gastric wall) into the radiomics signature, the radiomics nomogram achieved the highest accuracy in predicting LR, with AUC values of 0.89, 0.89 and 0.80 in the three cohorts, respectively. DCA in the validation cohort showed that radiomics nomogram added more net benefit than the clinical model within the range of 0.01-0.98. CONCLUSION: The CT-based radiomics nomogram has the potential to predict the LR of GC after radical resection.

Boric Acid-Fueled ATP Synthesis by Fo F1 ATP Synthase Reconstituted in a Supramolecular Architecture.

Significant strides toward producing biochemical fuels have been achieved by mimicking natural oxidative and photosynthetic phosphorylation. Here, different from these strategies, we explore boric acid as a fuel for tuneable synthesis of energy-storing molecules in a cell-like supramolecular architecture. Specifically, a proton locked in boric acid is released in a modulated fashion by the choice of polyols. As a consequence, controlled proton gradients across the lipid membrane are established to drive ATP synthase embedded in the biomimetic architecture, which facilitates tuneable ATP production. This strategy paves a unique route to achieve highly efficient bioenergy conversion, holding broad applications in synthesis and devices that require biochemical fuels.

A Transfer Learning Radiomics Nomogram for Preoperative Prediction of Borrmann Type IV Gastric Cancer From Primary Gastric Lymphoma.

OBJECTIVE: This study aims to differentiate preoperative Borrmann type IV gastric cancer (GC) from primary gastric lymphoma (PGL) by transfer learning radiomics nomogram (TLRN) with whole slide images of GC as source domain data. MATERIALS AND METHODS: This study retrospectively enrolled 438 patients with histopathologic diagnoses of Borrmann type IV GC and PGL. They received CT examinations from three hospitals. Quantitative transfer learning features were extracted by the proposed transfer learning radiopathomic network and used to construct transfer learning radiomics signatures (TLRS). A TLRN, which integrates TLRS, clinical factors, and CT subjective findings, was developed by multivariate logistic regression. The diagnostic TLRN performance was assessed by clinical usefulness in the independent validation set. RESULTS: The TLRN was built by TLRS and a high enhanced serosa sign, which showed good agreement by the calibration curve. The TLRN performance was superior to the clinical model and TLRS. Its areas under the curve (AUC) were 0.958 (95% confidence interval [CI], 0.883-0.991), 0.867 (95% CI, 0.794-0.922), and 0.921 (95% CI, 0.860-0.960) in the internal and two external validation cohorts, respectively. Decision curve analysis (DCA) showed that the TLRN was better than any other model. TLRN has potential generalization ability, as shown in the stratification analysis. CONCLUSIONS: The proposed TLRN based on gastric WSIs may help preoperatively differentiate PGL from Borrmann type IV GC.Borrmann type IV gastric cancer, primary gastric lymphoma, transfer learning, whole slide image, deep learning.

A Heterogeneity Radiomic Nomogram for Preoperative Differentiation of Primary Gastric Lymphoma From Borrmann Type IV Gastric Cancer.

OBJECTIVE: This study aimed to preoperatively differentiate primary gastric lymphoma from Borrmann type IV gastric cancer by heterogeneity nomogram based on routine contrast-enhanced computed tomographic images. METHODS: We enrolled 189 patients from 2 hospitals (90 in the training cohort and 99 in the validation cohort). Subjective findings, including high-enhanced mucosal sign, high-enhanced serosa sign, nodular or an irregular outer layer of the gastric wall, and perigastric fat infiltration, were assessed to construct a subjective finding model. A deep learning model was developed to segment tumor areas, from which 1680 three-dimensional heterogeneity radiomic parameters, including first-order entropy, second-order entropy, and texture complexity, were extracted to build a heterogeneity signature by least absolute shrinkage and selection operator logistic regression. A nomogram that integrates heterogeneity signature and subjective findings was developed by multivariate logistic regression. The diagnostic performance of the nomogram was assessed by discrimination and clinical usefulness. RESULTS: High-enhanced serosa sign and nodular or an irregular outer layer of the gastric wall were identified as independent predictors for building the subjective finding model. High-enhanced serosa sign and heterogeneity signature were significant predictors for differentiating the 2 groups (all, P < 0.05). The area under the curve with heterogeneity nomogram was 0.932 (95% confidence interval, 0.863-0.973) in the validation cohort. Decision curve analysis and stratified analysis confirmed the clinical utility of the heterogeneity nomogram. CONCLUSIONS: The proposed heterogeneity radiomic nomogram on contrast-enhanced computed tomographic images may help differentiate primary gastric lymphoma from Borrmann type IV gastric cancer preoperatively.

Co-assembled Supramolecular Gel of Dipeptide and Pyridine Derivatives with Controlled Chirality.

It is commonly considered that amyloid-ß (Aß) fibrils are heavily involved in the neurological diseases. Establishing an external model based on the core recognition motif (diphenylalanine, FF) of Aß would be of significance in understanding the assembly and disassembly of Aß fibrils in living system. Herein, supramolecular gels with structure transition from amyloid-like ß-sheet to different supramolecular helices were obtained through the co-assembly of a N-fluorenylmethoxycarbonyl-protected L-FF (L-FmocFF) with achiral pyridine derivatives. It is found that the different stacking modes (H- or J-aggregates) of additives and the microenvironment of chiral carbon play vital roles for the selectively chiral transfer or amplification of L-FmocFF. The dynamic process of helix formation was also captured. This work provides a convenient co-assembly way to explore the structure basis of Aß fibrils with a controlled chirality.

Self-Assembled Dipeptide Aerogels with Tunable Wettability.

Constructing supramolecular materials with tunable properties and functions is a great challenge due to the complex competition between multiple assembly pathways. Herein, we report that dipeptides can self-assemble into aerogels with entirely different surface wettability through precisely controlling the assembly pathways. Charged groups or aromatic residues are selectively exposed on the surface of their nanoscale building blocks which results either in a superhydrophilic or highly hydrophobic surface. With this special property, single component dipeptide aerogels can play diverse roles in medical care applications. This study suggests great promise in the synthesis of supramolecular materials with different targeted functions from the same molecular unit.

Estimating the instant case fatality rate of COVID-19 in China.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate the instant case fatality rate (CFR) and cure rate of COVID-19 in China. METHODS: A total of 82 735 confirmed cases released officially by the Chinese authorities from December 8, 2019 to April 18, 2020 were collected. The estimated diagnosis dates of deaths and cured cases were calculated based on the median cure time or median death time of individual cases. Following this, the instant CFR was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. RESULTS: In China, the instant CFR of COVID-19 was 3.8-14.6% from January 1 to January 17; it then declined gradually and stabilized at 5.7% in April. The average CFR in China was 6.1±2.9%, while the CFR was 1.0±0.4% in China except Hubei Province. The cure rate of COVID-19 was 93.9±2.9% in China, and stabilized at 94.3%, while it was 99.0±0.4% in China except Hubei Province. CONCLUSIONS: The instant CFR of COVID-19 in China overall was much higher than that in China except Hubei Province. The CFR of COVID-19 in China was underestimated.

Risk of Gastrointestinal Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Systematic Review and Meta-Analysis.

Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy can improve clinical outcomes in the treatment of various tumors, but may also be associated with more adverse events (AEs). We performed a systematic review and meta-analysis to characterize the risk of gastrointestinal AEs in cancer patients treated with ICI plus chemotherapy. Methods: This review was based on comprehensive search through PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) that reported gastrointestinal AEs following the use of ICI plus chemotherapy. Literature screening, data extraction, and quality evaluation were performed by two individual reviewers. Revman (version 5.3) was used for meta-analysis. Risk ratios (RR) with 95% confidence interval (CI) were calculated. Meta-analysis was conducted according to different types of ICIs [programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors]. Results: After a full-text review, 10 trials involving 5,142 patients were included in the study. Compared with chemotherapy alone, PD-1 inhibitor plus chemotherapy significantly increased the risk of diarrhea (RR = 1.38, 95% CI, 1.13-1.68, P = 0.001; I 2 = 0%) and colitis (RR = 2.90, 95% CI, 1.02-8.21, P = 0.050; I 2 = 0%), PD-L1 inhibitor plus chemotherapy significantly increased the risk of nausea (RR = 1.17, 95% CI, 1.02-1.35, P = 0.020; I 2 = 0%), while CTLA-4 inhibitor plus chemotherapy significantly increased the risk of decreased appetite (RR = 1.49, 95% CI, 1.17-1.90, P = 0.001; I 2 = 0%), diarrhea (RR = 2.23, 95% CI, 1.90-2.63, P < 0.00001; I 2 = 0%), and colitis (RR = 28.39, 95% CI, 5.59-144.24, P < 0.001; I 2 = 0%). Conclusions: This meta-analysis demonstrated that ICI plus chemotherapy is associated with a higher risk of gastrointestinal AEs. However, combining different ICIs may lead to diverse gastrointestinal toxicities. Clinicians should be aware of these AEs in the application of ICI plus chemotherapy.

lncRNA TTN-AS1 facilitates proliferation, invasion, and epithelial-mesenchymal transition of breast cancer cells by regulating miR-139-5p/ZEB1 axis.

Breast cancer is a common malignant tumor suffered predominantly by women worldwide, which results in serious levels of morbidity and mortality. To control the effects of the cancer, it is critically important to elucidate the pathophysiological processes by which it occurs and develops. Reports have demonstrated that long noncoding RNAs perform a critical role in the development and metastasis of cancers. The lncRNA TTN-AS1 is considered carcinogenic. Nevertheless, the importance and biological functions of TTN-AS1 in breast cancer require greater exploration. In the current paper, we observed that TTN-AS1 expression was significantly upregulated in breast cancer tissues/cells compared with those that are healthy. TTN-AS1 enhanced the proliferation, migration, invasion, and epithelial-mesenchymal transformation of breast cancer cells. Furthermore, a direct target of TTN-AS1, miR-139-5p was negatively regulated. In addition, zinc finger E-box binding homeobox 1 (ZEB1) is an important nuclear transcription factor, the expression of which is increased in multiple tumors. Here, we also found that ZEB1 is a target of miR-139-5p, of which TTN-AS1 could regulate the expression through competition with miR-139-5p. That is, TTN-AS1 promoted proliferation and invasion of breast cancer cells by interaction with the miR-139-5p/ZEB1 axis. In conclusion, the present study aimed to illustrate the significance of TTN-AS1 in breast cancer metastasis and contribute to potentially innovative strategies for its treatment.