GGT5: a potential immunotherapy response inhibitor in gastric cancer by modulating GSH metabolism and sustaining memory CD8+ T cell infiltration.

PURPOSE: The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs). METHODS: We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by  Multiplex immunohistochemistry (mIHC). RESULTS: Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy. CONCLUSIONS: Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.

Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling.

Triple-negative breast cancer (TNBC) exhibits the poorest outcomes among breast cancer subtypes due to the high heterogeneity and a lasting scarcity of effectual treatments. Targeted therapies based on molecular subtypes of TNBC are critical step toward tailoring treatments to improve clinical outcomes. Gastrointestinal cancer stem cell (CSC) marker DCLK1 was reported to be highly expressed in stem cell-rich subtype of TNBC. Here, we firstly explored the impacts of DCLK1 on tumor cells as well as their immune microenvironment in TNBC and potential therapeutic strategies for TNBC patients with high DCLK1 expression. Our results disclosed that DCLK1 overexpression promoted, while knockout of DCLK1 suppressed the CSC-like traits of TNBC cells and resistance to chemotherapeutics. Besides, DCLK1 supported immune escape by inhibiting intratumoral cytotoxic T cell infiltration in TNBC and hence limited immune checkpoint inhibitors efficacy. Mechanistically, bioinformatics analysis revealed that IL-6/STAT3 signaling was significantly enriched in high DCLK1-expressing patients, and our results further revealed that DCLK1 enhanced IL-6 expression and STAT3 activation in TNBC cells, which finally gave rise to upregulated CSC traits and suppressed CD8+ T-cell activity. Inhibiting IL-6/STAT3 pathway by IL-6R antagonist, Tocilizumab or STAT3 inhibitor, S31-201 could abolish DCLK1-promoted malignant phenotypes of TNBC cells. Finally, DCLK1 was identified to be specifically and highly expressed in the mesenchymal-like subtype of TNBC and targeting DCLK1 could improve chemotherapy efficacy and activate antitumor immunity. Overall, our study revealed the potential clinical benefits of targeting DCLK1 in TNBC treatment.

MTA1 localizes to the mitotic spindle apparatus and interacts with TPR in spindle assembly checkpoint regulation.

We previously identified a cell cycle-dependent periodic subcellular distribution of cancer metastasis-associated antigen 1 (MTA1) and unraveled a novel role of MTA1 in inhibiting spindle damage-induced spindle assembly checkpoint (SAC) activation in cancer cells. However, the more detailed subcellular localization of MTA1 in mitotic cells and its copartner in SAC regulation in cancer cells are still poorly understood. Here, through immunofluorescent colocalization analysis of MTA1 and alpha-tubulin in mitotic cancer cells, we reveal that MTA1 is dynamically localized to the spindle apparatus throughout the entire mitotic process. We also demonstrated a reversible upregulation of MTA1 expression upon spindle damage-induced SAC activation, and time-lapse imaging assays indicated that MTA1 silencing delayed the mitotic metaphase-anaphase transition in cancer cells. Further investigation revealed that MTA1 interacts and colocalizes with Translocated Promoter Region (TPR) on spindle microtubules in mitotic cells, and this interaction is attenuated on SAC activation. TPR is well-implicated in SAC regulation via binding the MAD1-MAD2 complex, however, no interactions between MTA1 and MAD1 or MAD2 were detected in our coimmunoprecipitation (co-IP) assays, suggesting that the MTA1-TPR may represent a distinct SAC-associated complex separate from the previously reported TPR-MAD1/MAD2 complex. Our data provide new insights into the subcellular localization and molecular function of MTA1 in SAC regulation in cancer, and indicate that intervention of the MTA1-TPR interaction may be effective to modulate SAC and hence chromosomal instability (CIN) in tumorigenesis.

The effectiveness of health education based on the 5Ts for teach-back on oral nutritional supplements compliance of post-discharge patients after surgery for gastric cancer: a randomized controlled trial.

OBJECTIVE: This study aims to explore the 5Ts teach-back(5Ts) to improve oral nutritional supplements (ONS) compliance of discharged patients after gastric cancer surgery. SETTING AND METHODS: Patients were recruited from the Bethune First Hospital of Jilin University. The patients were randomly assigned to 5Ts (n = 54) and routine health education (n = 54). Weekly ONS compliance was collected by "weekly ONS diary." ONS knowledge, health literacy, and health education satisfaction were collected at baseline and 5 weeks after discharge. Chi-square test, Mann-Whitney U test, and T test were used for data analysis. RESULTS: At the end of the intervention, there were 41 and 40 patients in intervention and control group. 5Ts significantly improve ONS compliance, ONS knowledge level (P = 0.000), health literacy level (P = 0.011), and health education satisfaction (P = 0.009) of patients. At the end of follow-up, there were 30 and 27 patients in two groups, and no significant difference in ONS compliance (P = 0.728). CONCLUSION: The 5Ts can significantly improve patients' ONS compliance and the effect of health education. TRIAL REGISTRATION NUMBER: This prospective trial was registered in the Chinese Clinical Trial Registry at ChiCTR2000040986 ( http://www.chictr.org.cn ). PATIENT OR PUBLIC CONTRIBUTION: Jia Wang and Haiyan Hu contributed to the performance of the study, analysis and interpretation the data, and drafted the manuscript; Jianan Sun and Qing Zhang contributed to the supervision of the study and interpreted the data; Zhiming Chen contributed to the analysis and interpretation the data; Qiuchen Wang contributed to the performance of the study and revised the manuscript; Mingyue Zhu contributed to interpretation the data; Jiannan Yao contributed to revise the manuscript; Hua Yuan and Xiuying Zhang contributed to the conception of the study, performed the study, interpreted the data, and significantly revised the manuscript. All authors screened the final version of the manuscript.

Reflection on the teaching of student-centred formative assessment in medical curricula: an investigation from the perspective of medical students.

BACKGROUND: Formative assessment (FA) is becoming increasingly common in higher education, although the teaching practice of student-centred FA in medical curricula is still very limited. In addition, there is a lack of theoretical and pedagogical practice studies observing FA from medical students' perspectives. The aim of this study is to explore and understand ways to improve student-centred FA, and to provide a practical framework for the future construction of an FA index system in medical curricula. METHODS: This study used questionnaire data from undergraduate students in clinical medicine, preventive medicine, radiology, and nursing at a comprehensive university in China. The feelings of medical students upon receiving student-centred FA, assessment of faculty feedback, and satisfaction were analysed descriptively. RESULTS: Of the 924 medical students surveyed, 37.1% had a general understanding of FA, 94.2% believed that the subject of teaching assessment was the teacher, 59% believed that teacher feedback on learning tasks was effective, and 36.3% received teacher feedback on learning tasks within one week. In addition, student satisfaction results show that students' satisfaction with teacher feedback was 1.71 ± 0.747 points, and their satisfaction with learning tasks was 1.83 ± 0.826 points. CONCLUSION: Students as participants and collaborators in FA provide valid feedback for improving student-centred FA in terms of student cognition, empowered participation, and humanism. In addition, we suggest that medical educators avoid taking student satisfaction as a single indicator for measuring student-centred FA and to try to build an assessment index system of FA, to highlight the advantages of FA in medical curricula.

Unsupervised Monocular Depth and Camera Pose Estimation with Multiple Masks and Geometric Consistency Constraints.

This paper presents a novel unsupervised learning framework for estimating scene depth and camera pose from video sequences, fundamental to many high-level tasks such as 3D reconstruction, visual navigation, and augmented reality. Although existing unsupervised methods have achieved promising results, their performance suffers in challenging scenes such as those with dynamic objects and occluded regions. As a result, multiple mask technologies and geometric consistency constraints are adopted in this research to mitigate their negative impacts. Firstly, multiple mask technologies are used to identify numerous outliers in the scene, which are excluded from the loss computation. In addition, the identified outliers are employed as a supervised signal to train a mask estimation network. The estimated mask is then utilized to preprocess the input to the pose estimation network, mitigating the potential adverse effects of challenging scenes on pose estimation. Furthermore, we propose geometric consistency constraints to reduce the sensitivity of illumination changes, which act as additional supervised signals to train the network. Experimental results on the KITTI dataset demonstrate that our proposed strategies can effectively enhance the model's performance, outperforming other unsupervised methods.

Preferences for oral nutritional supplement therapy among postoperative patients with gastric cancer: a discrete choice experiment.

PURPOSES: Patients after gastrectomy have poor compliance with oral nutritional supplement (ONS) therapy. Incorporating patient preferences into treatment decisions allows possible product improvements or treatment focus adjustments. The purpose of this research was to investigate the preferences for ONS therapy among postoperative patients with gastric cancer, and to provide person-centered oral nutrition management strategies. METHODS: A discrete choice experiment was designed and implemented within a Chinese cancer population. The survey was administered via paper-based questionnaires during face-to-face interviews with assistance from health professionals. A mixed logit model was used to estimate respondents' preferences for different levels of nutrition therapy attributes. RESULTS: One hundred ninety respondents valued "Adverse reactions-almost none" (ß 3.43 [SE, 0.28]) the most, followed by "Flavor-good taste" (ß 0.68 [SE, 0.13]) and "Follow-up frequency-once every 2 weeks" (ß 0.52 [SE, 0.13]), and were willing to pay more for these attribute levels. Respondents would be 93.73% more likely to accept a nutrition therapy program if there were almost no adverse reactions compared to the frequent adverse reactions. CONCLUSIONS: Health professionals should pay attention to the management and prevention of adverse reactions when prescribing nutritional products, and provide diversified ONS products when necessary to meet patient preferences. When formulating intervention strategies, health professionals should also consider the different characteristics of patients, acknowledge the importance of the role of nurse specialists in a novel model of multidisciplinary nutritional care, standardize ONS information, follow up regularly, and encourage patients' families to participate in daily nutrition care.

Factors influencing adherence to healthy eating behaviors among adult colorectal cancer survivors: a systematic mixed method review.

PURPOSE: Under the umbrella of social cognitive theory, we examined the influences of personal, environmental, and behavioral factors on adherence to healthy eating behaviors among colorectal cancer survivors. METHODS: Based on Pluye and Hong's framework, a systematic mixed studies review was conducted. An extensive search strategy was applied in PubMed, Web of Science, Embase, CINAHL, and PsycINFO (from date of record to 2022 January 22). The pillar integration process was employed to integrate the extracted data. The Mixed Methods Appraisal Tool was used to appraise the quality of all retained studies. RESULTS: Twenty-eight studies with a total sample size of 5106 were included in the analysis, with 15 quantitative studies, 12 qualitative studies, and 1 mixed method study. The critical appraisal showed that 22 of the 28 studies (79%) were rated with five stars, while 6 (21%) were rated with four stars. The personal factors influencing adherence to healthy eating behaviors among colorectal cancer survivors included outcome expectancies, self-efficacy, psychological factors, knowledge about healthy eating, demographic and disease characteristics, environmental factors incorporated outside information on healthy eating, power of surrounding people, social activities, cultural milieus, socioeconomic status, and education. The behavioral factors included self-regulation of diet, goals, and other behaviors closely related to healthy eating behaviors. CONCLUSIONS: Adherence to healthy eating behaviors among colorectal cancer survivors was influenced collectively by personal factors, environmental factors and behavioral factors.

Lymphocyte-to-monocyte ratio combined with CA19-9 for predicting postoperative recurrence of colorectal cancer in patients with diabetes.

OBJECTIVE: To investigate the significance of lymphocyte-to-monocyte ratio (LMR) combined with carbohydrate antigen (CA) 19-9 for predicting postoperative recurrence of colorectal cancer (CRC) in patients with type II diabetes. METHODS: We conducted a retrospective analysis of 106 postoperative patients with stage II-III CRC and with type II diabetes. Their clinical indexes such as LMR and CA19-9 were collected, and the patients were followed up for 5 years. RESULTS: The CA19-9 level was 119.7 U/ml at baseline in the relapsed group, while this was 24.81 U/ml in non-relapsed group (p = 0.001). On the contrary, the LMR level was 5.10 and 2.57 for non-relapsed and relapsed group (p < 0.001), respectively. Kaplan-Meier survival curves stratified by CA19-9 and LMR suggested that patients with lower CA19-9 had higher survival probability (p < 0.001), while patients with high LMR level had higher survival probability (p < 0.001). The multivariable Cox proportional hazard regression analysis with CA19-9 and LMR indicated that although the baseline CA19-9 is significantly associated with increasing risk of disease recurrence, the HR (HR = 1.0, 95% CI 1.00-1.01) was small and close to 1, whereas the high baseline LMR (HR = 0.44, 95% CI 0.32-0.61) was associated with decrease in disease recurrence. Model with continuous CA19-9 and LMR was able to better predict (AUC 73.17%) the disease recurrence. CONCLUSION: LMR combined with CA19-9 may become a new index for predicting postoperative recurrence of CRC in patients with diabetes.

Disruption of Core 1-mediated O-glycosylation oppositely regulates CD44 expression in human colon cancer cells and tumor-derived exosomes.

Aberrant O-glycosylation truncates O-glycans and is known to be closely associated with colorectal cancer (CRC), a major gastrointestinal tumor. CD44 is one of the highly post-transcriptionally modified O-glycoproteins participating in a series of physiological and pathobiological processes. In this research, we aimed to investigate whether CD44 expression in cells and exosomes can be influenced by disruption of Core 1-mediated O-glycosylation. Exosomes derived from LS174T and LSC human colon cancer cell lines were isolated from cell culture supernatant and pulled down using tetraspanin-specific antibody CD63 immunoaffinity magnetic beads. Identifications have been performed via transmission electron microscopy (TEM) and flow cytometry. CD63 immunoaffinity-purified exosomes are examined for CD44 expression by flow cytometric analyses. The percentages of CD44 in exosomes derived from abnormally O-glycosylated cells are significantly higher compared with those derived from normal ones, however, which is surprisingly contrary to the cellular expression levels of CD44. The secretion of truncated glycoproteins to the extracellular environment via microvesicles may be most likely its underlying mechanism. CD44 in exosomes might be a potential biomarker of aberrant O-glycosylation. This is the first study indicating that aberrant O-glycosylation can affect expression or delivery of O-glycoproteins via exosomes, which provides us some new sights in therapeutic strategies for human colon cancer.

Reverse engineering a predictive signature characterized by proliferation, DNA damage, and immune escape from stage I lung adenocarcinoma recurrence.

Identifying early-stage cancer patients at risk for progression is a major goal of biomarker research. This report describes a novel 19-gene signature (19-GCS) that predicts stage I lung adenocarcinoma (LAC) recurrence and response to therapy and performs comparably in pancreatic adenocarcinoma (PAC), which shares LAC molecular traits. Kaplan-Meier, Cox regression, and cross-validation analyses were used to build the signature from training, test, and validation sets comprising 831 stage I LAC transcriptomes from multiple independent data sets. A statistical analysis was performed using the R language. Pathway and gene set enrichment were used to identify underlying mechanisms. 19-GCS strongly predicts overall survival and recurrence-free survival in stage I LAC (P=0.002 and P<0.001, respectively) and in stage I-II PAC (P<0.0001 and P<0.0005, respectively). A multivariate cox regression analysis demonstrated the independence of 19-GCS from significant clinical factors. Pathway analyses revealed that 19-GCS high-risk LAC and PAC tumors are characterized by increased proliferation, enhanced stemness, DNA repair deficiency, and compromised MHC class I and II antigen presentation along with decreased immune infiltration. Importantly, high-risk LAC patients do not appear to benefit from adjuvant cisplatin while PAC patients derive additional benefit from FOLFIRINOX compared with gemcitabine-based regimens. When validated prospectively, this proof-of-concept biomarker may contribute to tailoring treatment, recurrence reduction, and survival improvements in early-stage lung and pancreatic cancers.

Alternative splice variants of DCLK1 mark cancer stem cells, promote self-renewal and drug-resistance, and can be targeted to inhibit tumorigenesis in kidney cancer.

Renal cell carcinoma (RCC) is a common and devastating disease characterized by a hypoxic microenvironment, epithelial-mesenchymal transition and potent resistance to therapy evidencing the presence of cancer stem cells (CSCs). Various CSC markers have been studied in RCC, but overall there is limited data on their role and most markers studied have been relatively nonspecific. Doublecortin-like kinase 1 (DCLK1) is a validated CSC marker in the gastrointestinal tract and evidence for an equivalent role in other cancers is accumulating. We used bioinformatics, immunohistochemistry, flow cytometry, spheroid self-renewal and chemoresistance assays in combination with overexpression and siRNA-knockdown to study the stem cell-supportive role of DCLK1 alternative splice variants (DCLK1 ASVs) in RCC. To target tumor cells expressing DCLK1 ASVs directly, we developed a novel monoclonal antibody (CBT-15) and delivered it systemically to RCC tumor xenografts. DCLK1 ASVs were overexpressed, enriched together with CSC markers and predictive of overall and recurrence-free survival in RCC patients. In vitro, DCLK1 ASVs were able to directly stimulate essential molecular and functional characteristics of renal CSCs including expression of aldehyde dehydrogenase, self-renewal and resistance to FDA-approved receptor tyrosine kinase and mTOR inhibitors, while targeted downregulation of DCLK1 reversed these characteristics. Finally, targeting DCLK1 ASV-positive cells with the novel CBT-15 monoclonal antibody blocked RCC tumorigenesis in vivo. These findings establish DCLK1 as a CSC marker with implications for therapy, disease progression and survival in RCC and demonstrate the therapeutic value of DCLK1-targeted monoclonal antibodies against renal CSCs.

Dclk1, a tumor stem cell marker, regulates pro-survival signaling and self-renewal of intestinal tumor cells.

BACKGROUND: More than 80% of intestinal neoplasia is associated with the adenomatous polyposis coli (APC) mutation. Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-renew and increased the tumor progeny in Apc Min/+ mice. However, the role of Dclk1 expression and its contribution to regulating pro-survival signaling for tumor progression in Apc mutant cancer is poorly understood. METHODS: We analyzed DCLK1 and pro-survival signaling gene expression datasets of 329 specimens from TCGA Colon Adenocarcinoma Cancer Data. The network of DCLK1 and pro-survival signaling was analyzed utilizing the GeneMANIA database. We examined the expression levels of Dclk1 and other stem cell-associated markers, pro-survival signaling pathways, cell self-renewal in the isolated intestinal epithelial cells of Apc Min/+ mice with high-grade dysplasia and adenocarcinoma. To determine the functional role of Dclk1 for tumor progression, we knocked down Dclk1 and determined the pro-survival signaling pathways and stemness. We used siRNA technology to gene silence pro-survival signaling in colon cancer cells in vitro. We utilized FACS, IHC, western blot, RT-PCR, and clonogenic (self-renewal) assays. RESULTS: We found a correlation between DCLK1 and pro-survival signaling expression. The expression of Dclk1 and stem cell-associated markers Lgr5, Bmi1, and Musashi1 were significantly higher in the intestinal epithelial cells of Apc Min/+ mice than in wild-type controls. Intestinal epithelial cells of Apc Min/+ mice showed increased expression of pro-survival signaling, pluripotency and self-renewal ability. Furthermore, the enteroids formed from the intestinal Dclk1+ cells of Apc Min/+ mice display higher pluripotency and pro-survival signaling. Dclk1 knockdown in Apc Min/+ mice attenuates intestinal adenomas and adenocarcinoma, and decreases pro-survival signaling and self-renewal. Knocking down RELA and NOTCH1 pro-survival signaling and DCLK1 in HT29 and DLD1 colon cancer cells in vitro reduced the tumor cells' ability to self-renew and survive. CONCLUSION: Our results indicate that Dclk1 is essential in advancing intestinal tumorigenesis. Knocking down Dclk1 decreases tumor stemness and progression and is thus predicted to regulate pro-survival signaling and tumor cell pluripotency. This study provides a strong rationale to target Dclk1 as a treatment strategy for colorectal cancer.

Prognostic Signature in Osteosarcoma Based on Amino Acid Metabolism-Associated Genes.

Background: Osteosarcoma (OS) is undeniably a formidable bone malignancy characterized by a scarcity of effective treatment options. Reprogramming of amino acid (AA) metabolism has been associated with OS development. The present study was designed to identify metabolism-associated genes (MAGs) that are differentially expressed in OS and to construct a MAG-based prognostic risk signature for this disease. Methods: Expression profiles and clinicopathological data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena databases. A set of AA MAGs was obtained from the MSigDB database. Differentially expressed genes (DEGs) in GEO dataset were identified using "limma." Prognostic MAGs from UCSC Xena database were determined through univariate Cox regression and used in the prognostic signature development. This signature was validated using another dataset from GEO database. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, single sample gene set enrichment analysis, and GDSC2 analyses were performed to explore the biological functions of the MAGs. A MAG-based nomogram was established to predict 1-, 3-, and 5-year survival. Real-time quantitative polymerase chain reaction, Western blot, and immunohistochemical staining confirmed the expression of MAGs in primary OS and paired adjacent normal tissues. Results: A total of 790 DEGs and 62 prognostic MAGs were identified. A MAG-based signature was constructed based on four MAGs: PIPOX, PSMC2, SMOX, and PSAT1. The prognostic value of this signature was successfully validated, with areas under the receiver operating characteristic curves for 1-, 3-, and 5-year survival of 0.714, 0.719, and 0.715, respectively. This MAG-based signature was correlated with the infiltration of CD56dim natural killer cells and resistance to several antiangiogenic agents. The nomogram was accurate in predictions, with a C-index of 0.77. The expression of MAGs verified by experiment was consistent with the trends observed in GEO database. Conclusion: Four AA MAGs were prognostic of survival in OS patients. This MAG-based signature has the potential to offer valuable insights into the development of treatments for OS.

Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

Introduction: The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

Introducción: La efectividad de una dieta elemental (DE) para prevenir eventos adversos (EA) durante la quimioterapia en pacientes con cáncer de esófago (CE) sigue sin estar clara. Este metaanálisis evalúa la eficacia de DE para prevenir EA en pacientes con CE durante quimioterapia. Se realizaron búsquedas en Medline (con PubMed), Embase, Biblioteca Cochrane y Web of Science para recuperar estudios prospectivos y aleatorios publicados antes del 12/04/2023. La razón de probabilidad (RP) de cada EA se calculó usando Review Manger 5.4.1. Se evaluó el riesgo de sesgo y se utilizó un metaanálisis basado en modelo de efectos aleatorios para analizar los datos disponibles. Después de una búsqueda sistemática, se identificaron cuatro estudios prospectivos y aleatorios con 237 pacientes. En cuanto a las toxicidades gastrointestinales, los hallazgos indicaron una tendencia hacia una disminución en el riesgo de mucositis (OM) (OR = 0,54, IC 95 %: 0,25-1,14), estreñimiento (OR = 0,87, IC 95 %: 0,49-1,53) y anorexia (OR = 0,99, IC 95 %: 0,32-3,05) y una tendencia creciente en el riesgo de diarrea (OR = 1,48, IC 95 %: 0,79-2,79) entre los pacientes tratados con DE. Sin embargo, no hubo muestras estadísticas significativas. Para toxicidades hematológicas, el riesgo de neutropenia de todos los grados (RP = 0,28; IC del 95 %: 0,14-0,57), leucopenia grado ≥ 2 (RP = 0,43; IC del 95 %: 0,22-0,84), neutropenia grado ≥ 2 (RP = 0,34; IC del 95 %: 0,17-0,67) y neutropenia grado ≥ 3 (RP = 0,28; IC del 95 %: 0,12-0,63) disminuyó significativamente. Ninguna evidencia firme confirmó el efecto preventivo de DE frente a OM o la diarrea. Una DE sería útil previniendo neutropenia y leucopenia.

Development and validation of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy: A study protocol.

AIM: This study aims to develop and validate a clinical nutrition risk screening tool to predict nutrition risk in home for the patients with gastric cancer after surgery at home so that high-risk patients can be targeted for preventive nutrition care. DESIGN: The development of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy (SNRSGC) through literature review, expert panel ratings and cognitive interview; the validation of SNRSGC is evaluated through prospective research on participants. METHODS: This research is divided into four parts: Step 1, Identification of a potential referred nutritional risk screening; Step 2, Item generation and scoring are selected through literature review methods to screen sensitive indicators which can reflect the nutritional characteristics of patients after gastric cancer surgery, establish the frame and update according to the latest guidelines; Step 3, Item reduction is determined by the rating of SNRSGC items by an expert panel and cognitive interview; Step 4, During the validation stage, we conducted research design based on the Consensus-based Standards for the selection of health Measurement Instruments checklist to evaluate the validity, reliability, interpretability and acceptability of SNRSGC. RESULTS: SNRSGC is the first screening tool specifically to predict nutrition risk for stay-at-home postoperative patients with gastric cancer, which can help patients at home detect nutritional risks at home in time and guide patients to seek medical treatment as soon as possible to improve their nutritional status.

Detection and new genetic environment of the pleuromutilin-lincosamide-streptogramin A resistance gene lsa(E) in methicillin-resistant Staphylococcus aureus of swine origin.

OBJECTIVES: To investigate the genetic basis of pleuromutilin resistance in porcine methicillin-resistant Staphylococcus aureus (MRSA) and to map the genetic environment of the identified plasmid-borne resistance gene. METHODS: Seventy porcine MRSA isolates, which exhibited high MICs of tiamulin, valnemulin and retapamulin, were investigated for pleuromutilin resistance genes and mutations. They were characterized by staphylococcal cassette chromosome mec (SCCmec) typing, spa typing and multilocus sequence typing (MLST). Plasmid DNA was extracted from the lsa(E)-positive strains and transferred to S. aureus RN4220 for selection of resistance plasmids. The plasmid-borne lsa(E) gene region was sequenced and 10 overlapping PCR assays for the analysis of the genetic environment of lsa(E) were developed. RESULTS: All 70 MRSA isolates were ST9 (MLST)-t899 (spa)-IVa (SCCmec). Sixteen isolates carried the lsa(E) gene; all others were negative for known pleuromutilin resistance mechanisms. An lsa(E)-carrying plasmid of ∼41 kb was detected in a single isolate. Sequence analysis revealed that the lsa(E) gene was located in a multiresistance gene cluster, which showed partial homology to clusters identified in MRSA, methicillin-susceptible S. aureus (MSSA) and Enterococcus faecalis. PCR analysis of the remaining isolates revealed a partly deleted multiresistance gene cluster in 6/15 isolates and solely the lsa(E) gene without the known flanking regions in 9/15 isolates. CONCLUSIONS: We identified the pleuromutilin-lincosamide-streptogramin A resistance gene lsa(E) in porcine MRSA isolates. The multiresistance gene cluster in which lsa(E) was located differed from the previously described ones found in human MRSA/MSSA or in E. faecalis. The location of lsa(E) on a multiresistance plasmid facilitates its persistence and dissemination.

Construction of a novel immune response prediction signature to predict the efficacy of immune checkpoint inhibitors in clear cell renal cell carcinoma patients.

Background: Immune checkpoint inhibitor (ICI) treatment has enhanced survival outcomes in clear cell renal cell carcinoma (ccRCC) patients. Nevertheless, the effectiveness of immunotherapy in ccRCC patients is restricted and we intended to develop and characterize an immune response prediction signature (IRPS) to forecast the efficacy of immunotherapy. Methods: RNA-seq expression profile and clinicopathologic characteristics of 539 kidney cancer and 72 patients with normal specimens, were downloaded from the Cancer Genome Atlas (TCGA) database, while the Gene Expression Omnibus (GEO) database was used as the validation set, which included 24 ccRCC samples. Utilization of the TCGA data and immune genes databases (ImmPort and the InnateDB), we explored through Weighted Gene Co-expression Network Analysis (WGCNA), along with Least Absolute Shrinkage and Selection Operator method (LASSO), and constructed an IRPS for kidney cancer patients. GSEA and CIBERSORT were performed to declare the molecular and immunologic mechanism underlying the predictive value of IRPS. The Human Protein Atlas (HPA) was deployed to verify the protein expressions of IRPS genes. Tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS) were computed to determine the risk of immune escape and value the discrimination of IRPS. A ccRCC cohort with anti-PD-1 therapy was obtained as an external validation data set to verify the predictive value of IRPS. Results: We constructed a 10 gene signature related to the prognosis and immune response of ccRCC patients. Considering the IRPS risk score, patients were split into high and low risk groups. Patients with high risk in the TCGA cohort tended towards advanced tumor stage and grade with poor prognosis (p < 0.001), which was validated in GEO database (p = 0.004). High-risk group tumors were related with lower PD-L1 expression, higher TMB, higher MSIsensor score, lower IPS, higher TIDE score, and enriched Treg cells, which might be the potential mechanism of immune dysfunction and exclusion. Patients in the IRPS low risk group had better PFS (HR:0.73; 95% CI: 0.54-1.0; P = 0.047). Conclusion: A novel biomarker of IRPS was constructed to predict the benefit of immunotherapy, which might lead to more individualized prognoses and tailored therapy for kidney cancer patients.

Selected cutaneous adverse events in patients treated with ICI monotherapy and combination therapy: a retrospective pharmacovigilance study and meta-analysis.

Introduction: Cutaneous adverse events are commonly reported immune-related adverse events (irAEs), some of which are serious or even life-threatening, and it is essential to study these specific cutaneous AEs to understand their characteristics and risk. Methods: We performed a meta-analysis of published clinical trials for immune checkpoint inhibitors (ICIs) to evaluate the incidence of cutaneous adverse events, using data from PubMed, Embase, and the Cochrane Library databases. Results: A total of 232 trials with 45,472 patients were involved. Results showed that anti-PD-1 and targeted therapy combinations were associated with higher risk for most of the selected cutaneous adverse events. In addition, a retrospective pharmacovigilance study was conducted using the Food and Drug Administration (FDA) Adverse Events System database. Reporting odds ratio (ROR) and Bayesian information components (IC) were used to perform the disproportionality analysis. Cases were extracted from January 2011 to September 2020. We identified 381 (20.24%) maculopapular rash, 213 (11.32%) vitiligo, 215 (11.42%) Stevens-Johnson syndrome (SJS), and 165 (8.77%) toxic epidermal necrolysis (TEN) cases. For vitiligo, anti-PD-1/L1 combined with anti-CTLA-4 therapy showed the strongest signal (ROR: 55.89; 95% CI: 42.34-73.78; IC025: 4.73). Palmar-plantar erythrodysesthesia (PPE) was reported with the most significant association with combined anti-PD-1/L1 and VEGF (R)-TKIs (ROR: 18.67; 95% CI: 14.77-23.60; IC025: 3.67). For SJS/TEN, antiPD-1 inhibitors showed the strongest signal (ROR: 3.07; 95% CI: 2.68-3.52; IC025: 1.39). The median onset time of vitiligo and SJS/TEN was 83 and 24 days, respectively. Conclusion: Overall, in selected cutaneous AEs, each of them showed specific characteristics. It is necessary to realize their differences and take appropriate interventions in patients with different regimens.

Design of online formative assessment of nursing humanities curriculum during the COVID-19 pandemic: A teaching practice research.

BACKGROUND: Under the digital transformation trend nursing education, online formative assessment (OFA) provides a new opportunity. However, the OFA of nursing humanities course lacks design and practice, and faces the challenge of enhancing effective communication between teachers and students, student participation and autonomous learning. OBJECTIVES: To enhance the reliability of OFA in nursing humanities courses and provide practical experience for online teaching in the nursing profession. DESIGN: A quantitative research approach was used. SETTING: This study was conducted in a comprehensive university in China. PARTICIPANTS: We conducted teaching practice on 185 nursing undergraduates, with 89 students in the experimental group, and 96 students in the control group. METHODS: In the 2020-2021 multicultural nursing course, student learning outcomes and questionnaires were analyzed through the online learning tool Superstar Learning, student feedback and satisfaction questionnaires, and descriptive analysis and independent sample t-tests were conducted using SPSS 25.0 software. RESULTS: The OFA of students using Superstar Learning differed in learning performance and time to receive feedback from teachers between the experimental and control groups, and both groups had higher satisfaction levels. The experimental group's instructional design contained a synchronous classroom discussion module with better participation. CONCLUSIONS: During the COVID-19 pandemic, the use of online learning tools can support the implementation of OFA, build an environment where teachers and students participate together, have a positive impact on the continuous updating of teachers' teaching programs and students' learning outcomes. Simultaneous classroom discussions are expected to be an effective way to improve the reliability of OFA. Our instructional design, provides best practice suggestions for future online teaching and learning.