Related Factors of CRKP Infection in Neurosurgery and Comparison of Therapeutic Effects of Tigecycline Versus Polymyxin B for CRKP Infection.

Objective: This paper aimed to identify the factors related to Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in neurosurgical patients, and to compare the therapeutic effects of tigecycline versus polymyxin B against CRKP infection, so as to provide a reliable reference for neurosurgery in future prevention and treatment of CRKP infection. Methods: One hundred and fifty cases of KPN treated in the neurosurgery department of our hospital from January 1, 2019 to December 31, 2021 were selected, 50 of which were found to be infected with CRKP and the other 100 were detected with carbapenem-sensitive Klebsiella pneumoniae (CSKP) by culture, analysis of factors associated with infection with CRKP. Subsequently, CRKP-infected patients were randomized into a group treated with Ti (group Ti) and a group treated with PB (group PB). The clinical efficacy, bacterial clearance, adverse reactions, and pre- and post-treatment hepatorenal function were comparatively analyzed. Results: Based on the Logistic regression analysis, tracheal intubation (or mechanical ventilation), combination of multiple underlying diseases, presence of impaired consciousness, and use of carbapenem antibiotics are independent risk factors for CRKP infection (P < .05). Ti and PB groups had no evident differences in clinical efficacy and bacterial clearance (P > .05); however, Ti group presented a worse hepatorenal function and a higher incidence of adverse reactions than PB group (P < .05). Conclusions: Tracheal intubation (or mechanical ventilation), multiple underlying diseases, consciousness disturbance, and use of carbapenem antibiotics are related factors affecting CRKP infection in neurosurgical patients. Both Ti and PB have excellent therapeutic efficacy, but the former has more obvious toxicity and side effects.

Characterization of caspase gene family in Sebastes schlegelii and their expression profiles under Aeromonas salmonicida and Vibrio anguillarum infection.

The caspase, functioning as a proteinase, plays a crucial role in eukaryotic cell apoptosis, regulation of apoptosis, cellular growth, differentiation, and immunity. The identification of caspase gene family in Sebastes schlegelii is of great help to understand its antimicrobial research. In S. schlegelii, we totally identified nine caspase genes, including four apoptosis initiator caspases (caspase 2, caspase 8, caspase 9 and caspase 10), four apoptosis executioners (caspase 3a, caspase 3b, caspase 6, and caspase 7) and one inflammatory executioner (caspase 1). The duplication of caspase 3 genes on chr3 and chr8 may have been facilitated by whole genome duplication (WGD) events or other complex evolutionary processes. In general, the number of caspase genes relatively conserved in high vertebrates, while exhibiting variation in teleosts. Furthermore, syntenic analysis and phylogenetic relationships analysis supported the correct classification of these caspase gene family in S. schlegelii, especially for genes with duplicated copies. Additionally, the expression patterns of these caspase genes in different tissues of S. schlegelii under healthy conditions were assessed. The results revealed that the expression levels of most caspase genes were significantly elevated in the intestine, spleen, and liver. To further investigate the potential immune functions of these caspase genes in S. schlegelii, we challenged individuals with A. salmonicida and V. anguillarum, respectively. After infection with A. salmonicida, the expression levels of caspase 1 in the liver and spleen of S. schlegelii remained consistently elevated throughout the infection time points. The expression levels of most caspase family members in the intestine exhibited significant divergence following V. anguillarum infection. This study provides a comprehensive understanding of the caspase gene families in S. schlegelii, thereby establishing a solid foundation for further investigations into the functional roles of these caspase genes.

Comprehensive analysis of circRNA-miRNA-mRNA networks in the kidney of snakehead (Channa argus) response to Nocardia seriolae challenge.

Non-coding RNAs (ncRNAs) play vital roles in regulating the expression levels of genes that control essential biological functions, including immune response to bacterial infections in teleost. To dissect the roles of ncRNAs in the Channa argus (snakehead), a systematic analysis of the expression profiles of circRNA, miRNA and mRNA, as well as competing endogenous RNAs (ceRNA) regulatory networks in the kidney of snakehead following Nocardia seriolae infection were performed in the present study. A total of 111 differentially expressed circRNAs, 706 differentially expressed miRNAs, and 2548 differentially expressed mRNAs were identified in the N. seriolae infected snakehead. Based on these differently expressed RNAs, we identified 55 circRNA-mRNA pairs, 124 miRNA-mRNA pairs, and 35 circRNA-miRNA-mRNA regulatory networks, including dre-miR-103-CD302, dre-miR-27e-IGSF3, novel_circ_0005462/novel_403-IGKC, novel_circ_0001750/novel_circ_0002162-novel_477-OCLN, and novel_circ_0003847-novel_4-KCNAB3. In addition, luciferase reporter assay was employed to detect the target relationships of several circRNA-miRNA-mRNA pairs. Taken together, this study demonstrates that the genes associated with immunity and structures in the kidney of snakehead can be regulated by circRNAs and miRNAs at post-transcription levels, and provided theoretical guidance for ncRNAs studies for other teleost. However, further studies are still in great need to validate the regulatory mechanisms of ncRNAs in snakehead.

Development and validation of a nomogram for predicting the overall survival of patients with testicular cancer.

BACKGROUND: The purpose of this study was to develop and validate a nomogram to predict survival in testicular cancer patients. METHODS: Testicular cancer patients diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were selected for this study. A random sampling method was used to divide patients into training and validation cohorts, which accounted for 30% and 70% of the total sample, respectively. The nomogram was developed using the training cohort and evaluated using the C index, calibration chart, and area under the receiver operating characteristic curve (AUC). RESULTS: Seven risk factors that affect the survival of testicular cancer patients (AJCC stage, marital status, age at diagnosis, race, SEER historic stage A, surgery status, and origin) were identified using Cox proportional hazard regression analysis. The nomogram has a higher C index (0.897) and AUC when compared with the AJCC staging system. The results of the calibration chart of the nomogram show that the predicted survival of testicular cancer patients at 3, 5, and 10 years after diagnosis is very close to their actual survival. CONCLUSIONS: We developed and validated a nomogram for predicting the survival rate of testicular cancer patients at 3, 5, and 10 years after diagnosis. This nomogram has better discrimination, calibration, and clinical validity than the AJCC staging system. This indicates that the nomogram can be used to predict the survival of testicular cancer patients effectively, and provide a reference for patient treatment strategies.

Comprehensive analysis of long noncoding RNAs and lncRNA-mRNA networks in snakehead (Channa argus) response to Nocardia seriolae infection.

Evidence has been demonstrated that lncRNAs are involved in a variety of immune responses in vertebrate. It has been demonstrated that immune-related lncRNAs play vital functions in immune regulation against infections in teleost. Nocardia seriolae, as one of the Gram-positive bacteria, can cause chronic systemic granulomatous disease for snakehead (Channa argus). However, how lncRNAs function in the immune regulation process once snakehead was infected with N. seriolae infection has not been studied so far. Accordingly, transcription landscapes of lncRNAs and mRNAs in snakehead were investigated. A total of 1,991 lncRNA were obtained. Totally, we predicted 57,584 co-expression and 16,047 co-location lncRNA-mRNA pairs. To further analyze the potential function of these lncRNAs, GO enrichment analysis and KEGG signal pathways were performed on the target mRNAs of these differently expressed lncRNAs, suggesting that lncRNAs may play essential roles in modulating mRNA expression levels, and subsequently trigger downstream immune signaling pathways to regulate the immune response in snakehead. In addition, 9 DEmRNA and 3 lncRNAs were randomly selected for qRT-PCR analyzed, which confirmed the accuracy of transcriptome data. These results can provide novel knowledge about lncRNAs in immune responses process in snakehead, and can serve as important resources for further investigating the roles of lncRNAs during pathogen infections in teleost.

Analysis of suicide risk in adult US patients with squamous cell carcinoma: a retrospective study based on the Surveillance, Epidemiology and End Results database.

OBJECTIVES: The purpose of this study was to determine the risk factors for suicide in patients with squamous cell carcinoma (SCC) in the USA. SETTING: Patients with SCC diagnosed between 1975 and 2017 from the Surveillance, Epidemiology and End Results (SEER) database were selected for this study. PARTICIPANTS: This study included patients with SCC older than 20 years who were diagnosed between 1975 and 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: The general population included in data from the US Centers for Disease Control and Prevention were used to calculate the suicide rate and standardised mortality rate (SMR) of SCC patients. Univariate and multivariate Cox regression analyses were used to identify risk factors for suicide in patients with SCC. RESULTS: There were 415 268 SCC patients registered in the SEER database, among which 1157 cases of suicide were found, comprising a total of 2 289 772 person-years. The suicide rate for patients with SCC was 50.53 per 100 000 person-years, and the SMR was 4.13 (95% CI 3.90 to 4.38). The Cox regression analyses showed that the factors related to a high risk of suicide among patients with SCC included being male (vs female: HR 5.36, 95% CI 4.51 to 6.38, p<0.001), older at the diagnosis (70-79 vs ≤39 years: HR 1.46, 95% CI 1.09 to 2.08, p=0.012; ≥80 vs ≤39 years: HR 1.48, 95% CI 1.05 to 2.08, p=0.025) and white (vs black, HR 2.97, 95% CI 2.20 to 4.02, p<0.001) and surgery (vs not performed: HR 0.65, 95% CI 0.57 to 0.74, p<0.001). CONCLUSIONS: Compared with the general population, patients with SCC in the USA have a higher risk of suicide. Being male, older at the diagnosis, white and having a higher histological grade are risk factors for suicide in patients.

Deep-learning model for predicting the survival of rectal adenocarcinoma patients based on a surveillance, epidemiology, and end results analysis.

BACKGROUND: We collected information on patients with rectal adenocarcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a model that combined deep learning with a multilayer neural network (the DeepSurv model) for predicting the survival rate of patients with rectal adenocarcinoma. METHODS: We collected patients with rectal adenocarcinoma in the United States and older than 20 yearswho had been added to the SEER database from 2004 to 2015. We divided these patients into training and test cohortsat a ratio of 7:3. The training cohort was used to develop a seven-layer neural network based on the analysis method established by Katzman and colleagues to construct a DeepSurv prediction model. We then used the C-index and calibration plots to evaluate the prediction performance of the DeepSurv model. RESULTS: The 49,275 patients with rectal adenocarcinoma included in the study were randomly divided into the training cohort (70%, n = 34,492) and the test cohort (30%, n = 14,783). There were no statistically significant differences in clinical characteristics between the two cohorts (p > 0.05). We applied Cox proportional-hazards regression to the data in the training cohort, which showed that age, sex, marital status, tumor grade, surgery status, and chemotherapy status were significant factors influencing survival (p < 0.05). Using the training cohort to construct the DeepSurv model resulted in a C-index of the model of 0.824, while using the test cohort to verify the DeepSurv model yielded a C-index of 0.821. Thesevalues show that the prediction effect of the DeepSurv model for the test-cohort patients was highly consistent with the prediction resultsfor the training-cohort patients. CONCLUSION: The DeepSurv prediction model of the seven-layer neural network that we have established can accurately predict the survival rateand time of rectal adenocarcinoma patients.

Risk factors associated with suicide among leukemia patients: A Surveillance, Epidemiology, and End Results analysis.

Previous studies have found that the risk of suicide is higher in patients diagnosed with cancer than in the general population. We aimed to identify potential risk factors associated with suicide in leukemia patients by analyzing data obtained from the Surveillance, Epidemiology, and End Results (SEER) database. We screened the SEER database for leukemia patients added between 1975 and 2017, and calculated their suicide rate and standardized mortality rate (SMR) relative to the total United States population from 1981 to 2017 as a reference. Univariate and multivariate Cox regression analyses were used to determine the risk factors for suicide in leukemia patients. We collected 142,386 leukemia patients who had been added to the SEER database from 1975 to 2017, of whom 191 patients committed suicide over an observation period of 95,397 person-years. The suicide rate of leukemia patients was 26.41 per 100,000 person-years, and hence the SMR of the suicided leukemia patients was 2.16 (95% confidence interval [CI] = 1.85-2.47). The univariate and multivariate Cox regression analyses showed that a high risk of suicide was associated with male sex (vs. female: hazard ratio [HR] = 4.41, 95% CI = 2.93-6.63, p < 0.001), older age at diagnosis (60-69 years vs. ≤39 years: HR = 2.60, 95% CI = 1.60-4.23, p < 0.001; 70-79 years vs. ≤39 years: HR = 2.84, 95% CI = 1.72-4.68, p < 0.001; ≥80 years vs. ≤39 years: HR = 2.94, 95% CI = 1.65-5.21, p < 0.001), white race (vs. black: HR = 6.80, 95% CI = 1.69-27.40, p = 0.007), acute myeloid leukemia (vs. lymphocytic leukemia: HR = 1.59, 95% CI = 1.09-2.33, p = 0.016), unspecified and other specified leukemia (vs. lymphocytic leukemia: HR = 2.72, 95% CI = 1.55-4.75, p < 0.001), and living in a small city (vs. large city: HR = 2.10, 95% CI = 1.23-3.60, p = 0.007). Meanwhile, being a non-Hispanic black (vs. Hispanic: HR = 0.06, 95% CI = 0.01-0.62, p = 0.019) was a protective factor for suicide. Male sex, older age at diagnosis, white race, and acute myeloid leukemia were risk factors for suicide in leukemia patients, while being a non-Hispanic black was a protective factor. Medical workers should, therefore, provide targeted preventive measures to leukemia patients with a high risk of suicide.

Upregulation of miR-34a-5p antagonizes AFB1-induced genotoxicity in F344 rat liver.

Aflatoxin B1 (AFB1) is a well-known human hepatotoxicant and genotoxicant. Recent studies demonstrated that aberrant miRNA expression patterns were correlated with the cellular and genetic lesions induced by chemicals. To explore the role of miRNAs in AFB1-induced hepatotoxicity and genotoxicity, we examined alterations in miRNA expression patterns in F334 rat livers after exposure to 100 µg/kg or 200 µg/kg AFB1 for 28 days. Using high-throughput sequencing, we discovered that rno-miR-34a-5p, rno-miR-200b-3p, and rno-miR-429 were up-regulated and that rno-miR-130a-3p was down-regulated in liver tissue from rats that received 200 µg/kg of AFB1; this finding was validated by real-time PCR. AFB1 treatment resulted in the upregulation of rno-miR-34a-5p and rno-miR-200b-3p in the rat H-4-II-E cell line similar to our in vivo observations. Moreover, rno-miR-34a-5p was transcriptionally elevated via p53 activation after AFB1 exposure. Upregulation of rno-miR-34a-5p suppressed the expression of the cell cycle-related genes CCND1, CCNE2 and MET and led to cell cycle arrest in the G0-G1 phase. The CBMN assay indicated that inhibition of rno-miR-34a-5p and p53 expression aggravated the DNA damage induced by AFB1, which might be associated with shortening of the DNA damage repair period. Circulating miR-34a-5p in rat sera preceded a significant increase in ALT activity and other miRNAs in the 100 µg/kg AFB1 group. These observations demonstrated that rno-miR-34a-5p responded sensitively to AFB1 exposure and facilitated p53 repair of DNA damage by impacting the cell cycle. Thus, circulating rno-miR-34a-5p may be a sensitive indicator for the induction of hepatic genotoxicity by AFB1 in rats.