Breast cancer prognosis and immunological characteristics are predicted using the m6A/m5C/m1A/m7G-related long noncoding RNA signature.

According to statistics, breast cancer (BC) has replaced lung cancer as the most common cancer in the world. Therefore, specific detection markers and therapeutic targets need to be explored as a way to improve the survival rate of BC patients. We first identified m6A/m5C/m1A/m7G-related long noncoding RNAs (MRlncRNAs) and developed a model of 16 MRlncRNAs. Kaplan-Meier survival analysis was applied to assess the prognostic power of the model, while univariate Cox analysis and multivariate Cox analysis were used to assess the prognostic value of the constructed model. Then, we constructed a nomogram to illustrate whether the predicted results were in good agreement with the actual outcomes. We tried to use the model to distinguish the difference in sensitivity to immunotherapy between the two groups and performed some analyses such as immune infiltration analysis, ssGSEA and IC50 prediction. To explore the novel anti-tumor drug response, we reclassified the patients into two clusters. Next, we assessed their response to clinical treatment by the R package pRRophetic, which is determined by the IC50 of each BC patient. We finally identified 11 MRlncRNAs and based on them, a risk model was constructed. In this model, we found good agreement between calibration plots and prognosis prediction. The AUC of ROC curves was 0.751, 0.734, and 0.769 for 1-year, 2-year, and 3-year overall survival (OS), respectively. The results showed that the IC50 was significantly different between the risk groups, suggesting that the risk groups can be used as a guide for systemic treatment. We regrouped patients into two clusters based on 11 MRlncRNAs expression. Next, we conducted immune scores for 2 clusters, which showed that cluster 1 had higher stromal scores, immune scores and higher estimated (microenvironment) scores, demonstrating that TME of cluster 1 was different from cluster 2. The results of this study support that MRlncRNAs can predict tumor prognosis and help differentiate patients with different sensitivities to immunotherapy as a basis for individualized treatment for BC patients.

MIR-518a-5p Targets ZEB2 to Suppress the Migration and Invasion of Breast-cancer Cells.

Context: Although great progress has occurred in breast cancer (BC) treatment, including chemotherapy, chemoradiotherapy, and surgical resection, the rate of patients' survival is still unsatisfactory. Multiple genes and factors have proven to contribute to BC's occurrence. Thus, it's urgent to explore the molecular mechanisms in the development and progression of BC and find possible targets for therapy. Objective: The study intended to assess the mechanisms of miR-518a-5p's effect on BC by targeting the zinc finger E-box-binding homeobox 2 (ZEB2) gene. Design: The research team designed a laboratory study and retrospective analysis. Setting: The study took place in the Department of Breast Surgery at the Xingtai People's Hospital in Xingtai, Hebei, China. Outcome Measures: The study measured the miR-518a-5p expression in BC tissues and normal tissues using a real-time quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) test. The research team purchased the BC cells MDA-MB-231 and MCF-7 and measured the effects of the miR-518a-5p on BC cell activity as well as epithelial-mesenchymal transition (EMT) ability, using cell scratch tests and Transwell assays. The team assessed the ZEB2 protein expression and verified the targeting relationship using a Dual-Luciferase Reporter assay. Results: The miR-518a-5p expressed was low in the BC tissues and cell lines compared with adjacent normal tissues (P < .05). Overexpressing the miR-518a-5p inhibited BC-cell migration and invasion (P < .05). Moreover, the ZEB2 was the target gene for the miR-518a-5p. The Luciferase assay verified that the miR-518a-5p directly targeted the ZEB2 in BC cells (P < .05). The Transwell invasion assay, western blot analysis, and wound healing assay also showed that the miR-518a-5p inhibited BC cells by targeting ZEB2 (P < .05). Conclusions: The miR-518a-5p suppressed BC migration, invasion, and process of EMT by regulating ZEB2. In the future, this method may be a new option for BC diagnosis and treatment. An in-depth understanding of the role of the miR-518a-5p in BC can help clinicians to understand the pathogenic mechanism of breast cancer more accurately.

The Safety of Neoadjuvant Therapy with Polyethylene Glycol Liposome Adriamycin Combined with Docetaxel in Patients with Breast Cancer Complicated by Axillary Lymph Node Metastasis.

Objective: To evaluate the safety of the combination of pegylated liposomal doxorubicin and docetaxel in neoadjuvant therapy for breast cancer (BC) with axillary lymph nodes metastasis. Methods: In this single-arm study, 91 patients with clinical stage IIA-IIIc BC received 6 cycles of pegylated liposomal doxorubicin plus docetaxel as neoadjuvant chemotherapy (NAC). Trastuzumab was allowed in patients with human epidermal growth factor receptor 2-positive tumors. The effects of new anthracycline-polyethylene glycol liposomal doxorubicin on the patients' hearts were studied. The changes in left ventricular ejection fraction (LVEF) before and after treatment were evaluated by echocardiography, and the levels of cardiac-specific biomarker troponin I (cTnI) and N terminal B natriuretic peptide (NT-pro-BNP) were noted before and after treatment. Result: In our study, 88 patients completed 6 cycles of neoadjuvant chemotherapy. LVEF was within normal range; average LVEF was 67% at baseline, 66% after NAC. The difference was not statistically significant. However, LVEF decreased by more than 10% in 44.4% of patients. There was no significant difference in troponin I or NT-pro-BNP levels before or after treatment. No cardiac events with clinical symptoms were reported. Conclusion: The combination of polyethylene glycol liposome adriamycin and docetaxel in neoadjuvant chemotherapy in patients with early BC with axillary lymph node metastasis has certain cardiac safety. And in the human epidermal growth factor receptor-2 (HER-2) positive population, polyethylene glycol liposome adriamycin combined with docetaxel and trastuzumab also has certain cardiac safety.

Safety and Immunogenicity of SARS-CoV-2 Vaccines in Patients With Chronic Liver Diseases (CHESS-NMCID 2101): A Multicenter Study.

BACKGROUND & AIMS: We aimed to assess the safety and immunogenicity of inactivated whole-virion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver diseases (CLD) in this study. METHODS: This was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. RESULTS: A total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (n = 36; 8.2%) was the most frequently reported adverse event. Three participants had grade 3 aminopherase elevation (defined as alanine aminopherase >5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only 1 of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in the noncirrhotic CLD group, 78.9% in the compensated cirrhotic group, 76.7% in the decompensated cirrhotic group (P = .894 among CLD subgroups), and 90.3% in healthy controls (P = .008 vs CLD group). CONCLUSION: Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunologic response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in noncirrhotic CLD, compensated cirrhosis, and decompensated cirrhosis.

Analysis of the genetic architecture of maize ear and grain morphological traits by combined linkage and association mapping.

KEY MESSAGE: Using combined linkage and association mapping, 26 stable QTL and six stable SNPs were detected across multiple environments for eight ear and grain morphological traits in maize. One QTL, PKS2, might play an important role in maize yield improvement. In the present study, one bi-parental population and an association panel were used to identify quantitative trait loci (QTL) for eight ear and grain morphological traits. A total of 108 QTL related to these traits were detected across four environments using an ultra-high density bin map constructed using recombinant inbred lines (RILs) derived from a cross between Ye478 and Qi319, and 26 QTL were identified in more than two environments. Furthermore, 64 single nucleotide polymorphisms (SNPs) were found to be significantly associated with the eight ear and grain morphological traits (-log10(P) > 4) in an association panel of 240 maize inbred lines. Combining the two mapping populations, a total of 17 pleiotropic QTL/SNPs (pQTL/SNPs) were associated with various traits across multiple environments. PKS2, a stable locus influencing kernel shape identified on chromosome 2 in a genome-wide association study (GWAS), was within the QTL confidence interval defined by the RILs. The candidate region harbored a short 13-Kb LD block encompassing four SNPs (SYN11386, PHM14783.16, SYN11392, and SYN11378). In the association panel, 13 lines derived from the hybrid PI78599 possessed the same allele as Qi319 at the PHM14783.16 (GG) locus, with an average value of 0.21 for KS, significantly lower than that of the 34 lines derived from Ye478 that carried a different allele (0.25, P < 0.05). Therefore, further fine mapping of PKS2 will provide valuable information for understanding the genetic components of grain yield and improving molecular marker-assisted selection (MAS) in maize.

Time-lag and accumulation responses of vegetation growth to average and extreme precipitation and temperature events in China between 2001 and 2020.

Climate change is often closely related to vegetation dynamics; time lag (Tlag) and accumulative effects (Tacc) are non-negligible phenomena when studying the interaction between climate and vegetation. But, amidst the escalating frequency of extreme climatic events, the quantification of temporal effects (Teffects) of such extremes on vegetation remains scarce. This research quantifies the Tlag and Tacc responses of China's vegetation to episodes of extreme temperature and precipitation since the early 2000s, utilizing daily meteorological data series. Overall, the precipitation in China has become wetter, and nighttime temperatures have risen significantly. The proportion of areas with Teffects ranged from 1.15 % to 15.95 %, and the correlation coefficient between the climate indices and the Normalized Difference Vegetation Index (NDVI) increased by 0.05 to 0.38 when considering the Teffects, compared to not considering it. The Tacc of vegetation had the strongest response (70.74-88.01 %) to extreme events among all the tested climate indices. Moreover, the Tacc of consecutive climate events had a greater impact on vegetation growth than individual climate event. The average Tacc for extreme temperature and extreme precipitation was 1.7-3.09 months and 2.17-3.25 months, respectively. Events like the over 95 % (R95p) and 99 % (R99p) percentile heavy precipitation and the maximum precipitation amount in one day (Rx1day) caused significant Teffects on NDVI. In addition, 90 % of grasslands exhibit Tacc, mainly contributed by the extreme precipitation indices (55.7 %), while the Teffects of forests were stronger than those of extreme temperature. Furthermore, NDVI was more affected by annual precipitation than by extreme precipitation, but the opposite was true for temperature. The results of this study highlight the importance of considering the Tlag and Tacc when predicting the effects of climate change on vegetation dynamics.

Integrin ß4 Regulates Cell Migration of Lung Adenocarcinoma Through FAK Signaling.

The role of the integrin family in malignancy has received increasing attention. Many studies have confirmed that ITGB4 could activate multiple signal pathways and promote cell migration in various cancers. However, the regulatory role of integrin ß4 (ITGB4) in lung adenocarcinoma (LUAD) is still unclear. Examination of the expression or survival analysis of ITGB4 in cells, pathological samples, and bioinformatics lung adenocarcinoma databases showed ITGB4 was highly expressed in LUAD and significantly associated with poor prognosis. Small interfering RNA and plasmids were performed to investigate the effect of changes in ITGB4 expression on lung adenocarcinoma. Focal adhesion kinase (FAK) inhibitor defactinib was used to further explore the molecular mechanism of ITGB4. The results showed depletion of ITGB4 inhibited migration and activation of FAK signaling pathways in lung adenocarcinoma cells. Moreover, increased ITGB4 expression activated FAK signaling and promoted cell migration, which can be reversed by defactinib. In addition, ITGB4 could interact with FAK in lung adenocarcinoma cells. ITGB4 may promote cell migration of lung adenocarcinoma through FAK signaling pathway and has the potential to be a biomarker for lung adenocarcinoma.

Nanofibrous polycaprolactone/amniotic membrane facilitates peripheral nerve regeneration by promoting macrophage polarization and regulating inflammatory microenvironment.

Appropriate levels of inflammation are an important part of functional repair of nerve damage. However, excessive inflammation can cause the continuous activation of immune inflammatory cells and degeneration of nerve cells. Regulating the temporal and spatial changes in M1/M2 macrophages can regulate the local inflammatory immune environment of the tissue to promote its transformation to a direction conducive to tissue repair.In the present study, a multi-layer multifunctional nanofiber composite membrane of polycaprolactone(PCL) and amniotic membrane (AM) was constructed using electrospinning. In vitro studies have shown that the PCL/AM composite promoted the axon growth of SH-SY5Y cells and induced their differentiation into neurons. The PCL/AM composite wrapped the nerve stump to form a microenvironment that was conducive to nerve regeneration, blocked the invasion of scar tissue, promoted the recruitment of macrophages and moderate polarization to M2, enhanced the expression of anti-inflammatory factors IL-10 and IL-13, inhibited the expression of pro-inflammatory factors IL-6 and TNF-α, and induced myelin sheath and axon regeneration. By releasing various bioactive substances to regulate the polarization of M2 macrophages and formation of anti-inflammatory factors, the PCL/AM composite can enhance axonal regeneration and improve nerve repair.

Multilayer amnion-PCL nanofibrous membrane loaded with celecoxib exerts a therapeutic effect against tendon adhesion by improving the inflammatory microenvironment.

Tendon adhesion is a common complication after tendon surgery. The inflammatory phase of tendon healing is characterized by the release of a large number of inflammatory factors, whose mediated excessive inflammatory response is an important cause of tendon adhesion formation. Nonsteroidal anti-inflammatory drugs(NSAIDs) were used to prevent tendon adhesions by reducing the inflammatory response. However, recent studies have shown that the NSAIDs partially impairs tendon healing. Therefore, optimizing the anti-adhesive membrane loaded with NSAIDs to mitigate the effects on tendon healing requires further in-depth study. Amniotic membranes(AM) are natural polymeric semi-permeable membranes from living organisms that are rich in matrix, growth factors, and other active ingredients. In this study, we used electrostatic spinning technology to construct multifunctional nanofiber membranes of the PCL membrane loaded with celecoxib and AM. In vitro cellular assays revealed that celecoxib-loaded PCL membranes significantly inhibited the adhesion and proliferation of fibroblasts with increasing concentrations of celecoxib. In a rabbit tendon repair model, biomechanical tests further confirmed that the PCL membrane loaded with celecoxib had better anti-adhesion effects. Further experimental studies revealed that the PCL/AM membrane improved the inflammatory microenvironment by downregulating the expression of pro-inflammatory factors such as COX-2, IL-1ß, and TNF-α proteins; and inhibiting the synthesis of COL I and COL Ⅲ. The PCL/AM membrane can continuously release celecoxib to reduce the inflammatory response and deliver growth factors to the damaged area to build a suitable microenvironment for tendon repair, which provides a new direction to improve the repair efficiency of tendon.

A Signature Constructed Based on the Integrin Family Predicts Prognosis and Correlates with the Tumor Microenvironment of Patients with Lung Adenocarcinoma.

As an important element in regulating the tumor microenvironment (TME), integrin plays a key role in tumor progression. This study aimed to establish prognostic signatures to predict the overall survival and identify the immune landscape of patients with lung adenocarcinoma based on integrins. The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus datasets were used to obtain information on mRNA levels and clinical factors (GSE72094). The least absolute shrinkage and selection operator (LASSO) model was used to create a prediction model that included six integrin genes. The nomogram, risk score, and time-dependent receiver operating characteristic analysis all revealed that the signatures had a good prognostic value. The gene signatures may be linked to carcinogenesis and TME, according to a gene set enrichment analysis. The immunological and stromal scores were computed using the ESTIMATE algorithm, and the data revealed, the low-risk group had a higher score. We discovered that the B lymphocytes, plasma, CD4+ T, dendritic, and mast cells were much higher in the group with low-risk using the CiberSort. Inflammatory processes and several HLA family genes were upregulated in the low-risk group. The low-risk group with a better prognosis is more sensitive to immune checkpoint inhibitor medication, according to immunophenoscore (IPS) research. We found that the patients in the high-risk group were more susceptible to chemotherapy than other group patients, according to the prophetic algorithm. The gene signatures could accurately predict the prognosis, identify the immune status of patients with lung adenocarcinoma, and provide guidance for therapy.

CD4+ conventional T cells-related genes signature is a prognostic indicator for ovarian cancer.

Introduction: It is believed that ovarian cancer (OC) is the most deadly form of gynecological cancer despite its infrequent occurrence, which makes it one of the most salient public health concerns. Clinical and preclinical studies have revealed that intratumoral CD4+ T cells possess cytotoxic capabilities and were capable of directly killing cancer cells. This study aimed to identify the CD4+ conventional T cells-related genes (CD4TGs) with respect to the prognosis in OC. Methods: We obtained the transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD4TGs were first identified from single-cell datasets, then univariate Cox regression was used to screen prognosis-related genes, LASSO was conducted to remove genes with coefficient zero, and multivariate Cox regression was used to calculate riskscore and to construct the CD4TGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), decision curve analysis (DCA), nomogram, and calibration were made to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. The role of riskscore has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy. A risk signature with 11 CD4TGs in OC was finally established in the TCGA database and furtherly validated in several GEO cohorts. Results: High riskscore was significantly associated with a poorer prognosis and proven to be an independent prognostic biomarker by multivariate Cox regression. The 1-, 3-, and 5-year ROC values, DCA curve, nomogram, and calibration results confirmed the excellent prediction power of this model. Compared with the reported risk models, our model showed better performance. The patients were grouped into high-risk and low-risk subgroups according to the riskscore by the median value. The low-risk group patients tended to exhibit a higher immune infiltration, immune-related gene expression and were more sensitive to immunotherapy and chemotherapy. Discussion: Collectively, our findings of the prognostic value of CD4TGs in prognosis and immune response, provided valuable insights into the molecular mechanisms and clinical management of OC.

PCGF6/MAX/KDM5D facilitates MAZ/CDK4 axis expression and pRCC progression by hypomethylation of the DNA promoter.

Polycomb group RING finger protein 6 (PCGF6) plays an important role as a regulator of transcription in a variety of cellular processes, including tumorigenesis. However, the function and expression of PCGF6 in papillary RCC (pRCC) remain unclear. In the present study, we found that PCGF6 expression was significantly elevated in pRCC tissues, and high expression of PCGF6 was associated with poor survival of patients with pRCC. The overexpression of PCGF6 promoted while depletion of PCGF6 depressed the proliferation of pRCC cells in vitro. Interestingly, myc-related zinc finger protein (MAZ), a downstream molecular of PCGF6, was upregulated in pRCC with hypomethylation promoter. Mechanically, PCGF6 promoted MAZ expression by interacting with MAX and KDM5D to form a complex, and MAX recruited PCGF6 and KDM5D to the CpG island of the MAZ promoter and facilitated H3K4 histone demethylation. Furthermore, CDK4 was a downstream molecule of MAZ that participated in PCGF6/MAZ-regulated progression of pRCC. These results indicated that the upregulation of PCGF6 facilitated MAZ/CDK4 axis expression and pRCC progression by hypomethylation of the MAZ promoter. The PCGF6/MAZ/CDK4 regulatory axis may be a potential target for the treatment of ccRCC.

Gallbladder neuroendocrine carcinoma: A report of two cases and literature review.

Gallbladder neuroendocrine carcinoma (GB-NEC) is a rare, aggressive neuroendocrine carcinoma that arises from the gallbladder. Patients with GB-NEC usually have a poor prognosis. The present study described two cases diagnosed with GB-NEC and reviewed the literature to improve knowledge of GB-NEC. The present study reported on two cases of GB-NEC in male patients aged 65 and 66 years, respectively. Both patients underwent surgical resection. Postoperative pathology confirmed that one case had mixed adeno-neuroendocrine carcinoma and the other had large cell neuroendocrine carcinoma. In addition, both patients had uneventful recoveries following surgery and received cisplatin-etoposide combination chemotherapy. The present study summarized the two cases and reviewed the literature to improve understanding of GB-NEC. The results revealed that radiological findings of GB-NEC are non-specific. The present study demonstrated that surgical resection was still the most effective therapy and that postoperative adjuvant chemotherapy could markedly improve the prognosis of patients with GB-NEC.

Construction and validation of a histone acetylation-related lncRNA prognosis signature for ovarian cancer.

Ovarian cancer (OC) leads to the most deaths among gynecological malignancies. The various epigenetic regulatory mechanisms of histone acetylation in cancer have attracted increasing attention from scientists. Long non-coding RNA (lncRNA) also plays an important role in multiple biology processes linked to OC. This study aimed to identify the histone acetylation-related lncRNAs (HARlncRNAs) with respect to the prognosis in OC. We obtained the transcriptome data from Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA); HARlncRNAs were first identified by co-expression and differential expression analyses, and then univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) were used to construct the HARlncRNAs risk signature. Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analysis (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. A risk signature with 14 HARlncRNAs in OC was finally established and further validated in the International Cancer Genome Consortium (ICGC) cohort; the 1-, 3-, and 5-year ROC value, nomogram, and calibration results confirmed the good prediction power of this model. The patients were grouped into high- and low-risk subgroups according to the risk score by the median value. The low-risk group patients exhibited a higher homologous recombination deficiency (HRD) score, LOH_frac_altered, and mutLoad_nonsilent. Furthermore, consensus clustering analysis was employed to divide OC patients into three clusters based on the expression of the 14 HARlncRNAs, which presented different survival probabilities. Principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) were also performed to evaluate the three clusters. In conclusion, the risk signature composed of 14 HARlncRNAs might function as biomarkers and prognostic indicators with respect to predicting the response to the anti-cancer drugs in OC.

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma.

Long noncoding RNAs (lncRNAs) are closely associated with a variety of tumors, including stomach adenocarcinoma (STAD). However, the role of 5-methylcytosine- (m5C-) related lncRNAs in STAD is still uncertain. This study investigated the value of m5C-related lncRNAs in prognostic evaluation and immunotherapy of STAD. STAD transcriptome sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database, and m5C-related lncRNAs were screened by Pearson correlation analysis. A prognostic m5C-related lncRNA signature (m5CRLSig) associated with STAD was established using univariate and multivariate Cox regression analysis. We constructed a prognostic risk model for STAD with six m5C-related lncRNAs. The receiver operating characteristic (ROC) curve was used to examine the predictive efficacy. Univariate and multifactorial Cox regression analysis and principal component analysis (PCA) validated m5CRLSig as an independent factor of STAD prognosis. The clinicopathological characteristics of the model showed higher risk scores for stages II-IV, grade 3, N1-3, and death status. The calibration curve of a nomogram revealed that the nomogram had an excellent predictive function for survival risk. Furthermore, the expression of six m5C-related lncRNAs in STAD and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR), which verified the feasibility of the m5CRLSig as a prognostic marker for STAD. m5C-related lncRNAs were linked to multiple immune-associated pathways, according to gene set enrichment analysis (GSEA). CIBERSORT analysis indicated that m5CRLSig was involved in immune cell infiltration. Risk score was associated with immune checkpoint gene expression, immune function scores, and chemotherapeutic drug sensitivity. Therefore, m5CRLSig can efficiently assess the prognosis of STAD patients and can be used as a biological marker for immunotherapy.

Deciphering the expression patterns of homologous recombination-related lncRNAs identifies new molecular subtypes and emerging therapeutic opportunities in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading killer among women with gynecologic malignancies. Homologous recombination deficiency (HRD) has attracted increasing attention due to its significant implication in the prediction of prognosis and response to treatments. In addition to the germline and somatic mutations of homologous recombination (HR) repair genes, to widely and deeply understand the molecular characteristics of HRD, we sought to screen the long non-coding RNAs (lncRNAs) with regard to HR repair genes and to establish a prognostic risk model for EOC. Herein, we retrieved the transcriptome data from the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA) databases. HR-related lncRNAs (HRRlncRNAs) associated with prognosis were identified by co-expression and univariate Cox regression analyses. The least absolute shrinkage and selection operator (LASSO) and multivariate stepwise Cox regression were performed to construct an HRRlncRNA risk model containing AC138904.1, AP001001.1, AL603832.1, AC138932.1, and AC040169.1. Next, Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), nomogram, calibration, and DCA curves were made to verify and evaluate the model. Gene set enrichment analysis (GSEA), immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) in the risk groups were also analyzed. The calibration plots showed a good concordance with the prognosis prediction. ROCs of 1-, 3-, and 5-year survival confirmed the well-predictive efficacy of this model in EOC. The risk score was used to divide the patients into high-risk and low-risk subgroups. The low-risk group patients tended to exhibit a lower immune infiltration status and a higher HRD score. Furthermore, consensus clustering analysis was employed to divide patients with EOC into three clusters based on the expression of the five HRRlncRNAs, which exhibited a significant difference in checkpoints' expression levels and the tumor microenvironment (TME) status. Taken together, the results of this project supported that the five HRRlncRNA models might function as a biomarker and prognostic indicator with respect to predicting the PARP inhibitor and immune treatment in EOC.

PD-1 and CTLA-4 inhibitors in combination vs. alone for the treatment of advanced melanoma: A systematic review and meta-analysis.

BACKGROUND: Metastatic melanoma treatment has drastically changed during the past decade with the advent of immunotherapy. We conducted a meta-analysis, to assess PD-1 and CTLA-4 inhibitors in combination vs. alone for the treatment of advanced melanoma. METHODS: The EMBASE, Medline via PubMed, Scopus, Cochrane Central, and Web of Science databases were searched. The records retrieved were screened for eligibility. Odds ratio (OR) was applied to compare dichotomous variables. All the results were reported with 95% confidence intervals (CI). Mantel-Haenszel method was used to estimate pooled OR and 95% confidence intervals for dichotomous data. RESULTS: We retrieved 3092 citations of which we included 3 randomized controlled trials and 2 retrospective, cohort studies. The pooled OR was 2.144 (95% CI: 1.650-2.786, I2 = 80.38% P = .000) for overall response and 2.117 (95% CI: 1.578-2.841, I2 = 70.17% P = .000) for the complete response (CR). Subgroup analysis in nivolumab category showed that the pooled OR was 1.766 (95% CI: 1.324-2.355, I2 = 0.0% P = .000) for the overall response and was 1.284 (95% CI: 0.889-1.855, I2 = 0.0% P = .182) for the CR and in the ipilimumab category the pooled OR was 5.440 (95% CI: 2.896-10.220, I2 = 70.89% P = .001) for the overall response and was 5.169 (95% CI: 3.163-8.446, I2 = 0.0% P = .000) for the CR. The incidence of any treatment-related adverse events was significantly higher in the combination group than that of the nivolumab monotherapy 4.044 (95% CI: 1.740-9.403, I2 = 91.64% P = .001) or the ipilimumab monotherapy 2.465 (95% CI: 0.839-7.236, I2 = 93.02 % P = .101). CONCLUSION: Combination therapy with ipilimumab plus nivolumab is a promising strategy in the treatment of patients with advanced melanoma with superior overall and complete responses over either monotherapies.

Development and validation of AKI prediction model in postoperative critically ill patients: a multicenter cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common complication, especially among postoperative critically ill patients. Early identification of AKI is essential for reducing mortality. METHODS: Multicenter data were used to develop an AKI prediction model for critically ill postoperative patients. A total of 1731 patients admitted to intensive care units (ICUs) were divided into a development set (n=1196) and a validation set (n=535) according to the principle of 7:3 randomization. Multivariate logistic regression analysis was performed on the predictors identified by univariate analysis, and a nomogram was created based on the predictors. The area under the receiver operating characteristic curve (AUROC) was used to assess the discrimination of the model. Calibration curves were generated, and the Hosmer-Lemeshow (HL) goodness of fit test was carried out. Decision curve analysis (DCA) was performed to assess the net clinical benefit. RESULTS: The final model included 7 predictors: age, emergency surgery, abnormal basal creatinine level (BCr), chronic kidney disease (CKD), use of nephrotoxic drugs, diuretic use, and the Sequential Organ Failure Assessment (SOFA) score. A nomogram was drawn based on the predictors. The AUROC of the model in the development set was 0.725 (95% confidence interval (CI): 0.696-0.754). In the validation set, the AUROC was 0.706 (95% CI: 0.656-0.744). The model showed good discrimination (>70%) in both sets, and the HL test indicated that the model fit was good (P>0.05). DCA showed that our model is clinically useful. CONCLUSION: The novel prediction model can be used to identify high-risk postoperative patients and provide a scientific and effective basis for clinicians to identify AKI early with a nomogram.