Clinical characteristics and prognostic analysis of pediatric hemophagocytic lymphohistiocytosis using lasso-logistic regression.

This study aims to evaluate and predict mortality risks among pediatric patients with hemophagocytic lymphohistiocytosis (HLH). We conducted a retrospective analysis of pediatric patients with HLH diagnosed at the Affiliated Hospital of Zunyi Medical University between January 2012 and April 2023. Patients were divided into a death group and a survival group based on their outcomes. Risk factors for mortality were analyzed using a lasso-logistic regression model. This study included 142 pediatric patients with HLH, with a median age of 40.5 (14.75-84) months, of whom 78 (54.93%) were male. The overall mortality rate was 34.51%. Through lasso-logistic regression analysis, five independent prognostic factors were identified: concurrent central nervous system involvement, multiple organ dysfunction syndrome involving three or more organs, platelet count ≤ 42.5 × 109/L, activated partial thromboplastin time ≥ 54.05 s, and the utilization of blood purification in conjunction with the HLH-94/2004 treatment protocol. The predictive value of the lasso-logistic regression model is better than that of the traditional logistic regression model (AUC: 0.906 vs 0.811, P = 0.001). Subsequently, a lasso-logistic regression-based predictive model incorporating these identified risk factors was developed. Our lasso-logistic regression-based prediction model may help to identify high-risk patients with HLH early, thereby enabling the timely initiation of appropriate treatment interventions.

The Acid Roles of PtSn@Al2O3 in the Synthesis and Performance of Propane Dehydrogenation.

In this study, a PtSn/Al2O3 catalyst with bimetallic uniform distribution in the sphere was synthesized. The PDH performance and characterization analyses, such as with FTIR, XPS, and NH3-TPD, were investigated. The effects of acid on the PDH performance were analyzed. Citric acid (CA) acted as a competing adsorbent in the preparation process of the PtSn/Al2O3 catalyst to synthesize the uniform catalyst. Water washing and alkali-treated samples were also studied. SEM line scanning revealed that increased the apparent concentration of Pt metal from 0.23 to 0.30 with citric acid. In contrast to the fresh PtSn/Al2O3 catalyst, the addition of citric acid increased the PDH selectivity from 74% to 93%. After alkali or water washing treatments, the catalyst's selectivity further increased to 96%. Strong acid sites promoted the breaking of C-C bonds during the PDH reaction, resulting in more methane and ethylene byproducts, and decreased catalyst selectivity for fresh PtSn/Al2O3. From the PDH reaction thermodynamic analysis, a relatively sub-atmospheric pressure environment with a lower propane pressure could be the reasonable choice.

Carvedilol exhibits anti-acute T lymphoblastic leukemia effect in vitro and in vivo via inhibiting ß-ARs signaling pathway.

An increasing number of studies have focus upon ß-adrenergic receptor blockers and their anti-tumor effects. However, the use of Carvedilol (CVD), the third generation ß-AR blocker, has not been explored for use against T-ALL. In this study, the level of ß-ARs was explored in pediatric T-ALL patients. Moreover, the antitumor effects of CVD against T-ALL were assessed in vitro and in vivo, and the underlying mechanisms were investigated. The viability of T-ALL cells following CVD treatment was detected using a CCK-8 assay, and the apoptotic and cell cycle effects were measured using flow cytometry. The protein levels of ß-ARs, cAMP, Epac, JAK2, STAT3, p-STAT3, PI3K, p-PI3K, AKT, p-AKT, mTOR, cyclin D1, PCNA, and cleaved caspase-3 were assessed by Western blotting. In vivo experiments were used to investigate the effect of CVD on T-ALL growth in mice. The results indicated that ß-ARs were highly expressed in the newly diagnosed T-ALL cells when compared to those in the control group (P < 0.05). In vitro, CVD significantly inhibited T-ALL cell viability, promoted apoptosis and blocked the G0/G1 phase of cell cycle. After CVD treatment, the protein levels of ß-ARs, cAMP, Epac, PI3K, p-PI3K, AKT, p-AKT, mTOR, JAK2, STAT3, p-STAT3, cyclin D1 and PCNA were significantly downregulated (P < 0.05); whereas cleaved caspase-3 was significantly upregulated (P < 0.05). In vivo, the volume and weight of the xenograft tumors were significantly decreased in the CVD group (P < 0.05). CVD promoted xenograft tumor apoptosis and reduced the proportion of CEM-C1 cells in murine peripheral blood and bone marrow (P < 0.05). Our results demonstrate that ß-ARs are expressed in T-ALL. CVD has a strong antitumor effect against T-ALL and inhibits ß-AR associated signaling pathways. Therefore, CVD may provide a potential therapy for T-ALL.

Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice.

BACKGROUND: Fructus mume (F. mume) has been used as a traditional treatment for ulcer, cough, and digestive problems for many years in Asian countries. Previous studies have demonstrated that F. mume extracts alleviate cognitive deficits in rats with chronic cerebral hypoperfusion and in mice with scopolamine treatments. The present experiment was conducted to examine the effects of F. mume on cognitive impairments in 5XFAD transgenic mice with five familial Alzheimer's disease (AD) mutations. METHODS: F. mume was administered daily to 5XFAD mice at 12 weeks of age and continued for 90 days. Cognitive function was evaluated using a spatial memory version of the Morris water maze task, the object/location novelty recognition test, and contextual fear conditioning at 24 weeks of age. To elucidate the possible mechanisms underlying the memory improving effects of F. mume in 5XFAD mice, we examined alterations in hippocampal cholinergic function. RESULTS: Vehicle-treated 5XFAD mice exhibited hippocampus-dependent memory impairments compared with non-transgenic littermates, which was reversed in F. mume-treated 5XFAD mice. In addition, reduced hippocampal choline acetyltransferase (ChAT) levels in 5XFAD mice were reversed by F. mume treatment, indicating that F. mume enhances the effects of cholinergic neuronal function. CONCLUSIONS: F. mume may have therapeutic effects on cognitive impairments in AD.

Conserved CO-FT regulons contribute to the photoperiod flowering control in soybean.

BACKGROUND: CO and FT orthologs, belonging to the BBX and PEBP family, respectively, have important and conserved roles in the photoperiod regulation of flowering time in plants. Soybean genome experienced at least three rounds of whole genome duplications (WGDs), which resulted in multiple copies of about 75% of genes. Subsequent subfunctionalization is the main fate for paralogous gene pairs during the evolutionary process. RESULTS: The phylogenic relationships revealed that CO orthologs were widespread in the plant kingdom while FT orthologs were present only in angiosperms. Twenty-eight CO homologous genes and twenty-four FT homologous genes were gained in the soybean genome. Based on the collinear relationship, the soybean ancestral CO ortholog experienced three WGD events, but only two paralogous gene pairs (GmCOL1/2 and GmCOL5/13) survived in the modern soybean. The paralogous gene pairs, GmCOL1/2 or GmCOL5/13, showed similar expression patterns in pair but different between pairs, indicating that they functionally diverged. GmFTL1 to 7 were derived from the same ancestor prior to the whole genome triplication (WGT) event, and after the Legume WGD event the ancestor diverged into two branches, GmFTL3/5/7 and GmFTL1/2/4/6. GmFTL7 were truncated in the N-terminus compared to other FT-lineage genes, but ubiquitously expressed. Expressions of GmFTL1 to 6 were higher in leaves at the flowering stage than that at the seedling stage. GmFTL3 was expressed at the highest level in all tissues except roots at the seedling stage, and its circadian pattern was different from the other five ones. The transcript of GmFTL6 was highly accumulated in seedling roots. The circadian rhythms of GmCOL5/13 and GmFT1/2/4/5/6 were synchronized in a day, demonstrating the complicate relationship of CO-FT regulons in soybean leaves. Over-expression of GmCOL2 did not rescue the flowering phenotype of the Arabidopsis co mutant. However, ectopic expression of GmCOL5 did rescue the co mutant phenotype. All GmFTL1 to 6 showed flower-promoting activities in Arabidopsis. CONCLUSIONS: After three recent rounds of whole genome duplications in the soybean, the paralogous genes of CO-FT regulons showed subfunctionalization through expression divergence. Then, only GmCOL5/13 kept flowering-promoting activities, while GmFTL1 to 6 contributed to flowering control. Additionally, GmCOL5/13 and GmFT1/2/3/4/5/6 showed similar circadian expression profiles. Therefore, our results suggested that GmCOL5/13 and GmFT1/2/3/4/5/6 formed the complicate CO-FT regulons in the photoperiod regulation of flowering time in soybean.

Explaining the negative effects of workplace incivility on family lives: a moderated mediation model of surface acting and resource-providing variables.

The effects of workplace incivility have been understudied in educational settings. To expand incivility research to educational professions, the present research investigates whether, how, and when workplace incivility deriving from different sources (coworkers, supervisors, and outsiders) is related to work-to-family interference (WFI) of preschool teachers. Drawing on the conservation of resources theory, the present study proposes that workplace incivility and subsequent maladaptive emotion labor strategies (i.e., surface acting) jointly create a resource-depletion mechanism contributing to elevated WFI and two resource-providing variables (supervisor work-family support and psychological detachment after hours) function as potential mitigating factors to break the resource-depletion mechanism. This study used a female-dominated sample (i.e., preschool teachers) found that workplace incivility from insiders (supervisors and coworkers respectively) and external stakeholders (child's family members) all positively linked to WFI, and surface acting mediated these relationships. Moreover, moderated mediation analyses indicated that psychological detachment buffered the mediated effect of surface acting on WFI, whereas supervisor work-family support did not. Findings deepen the understanding of why and when workplace incivility influences employees' family lives, as well as point to future intervention strategies.

Case report: A case of renal vessel rupture caused by severe vomiting in early pregnancy.

OBJECTIVE: Spontaneous renal vessel rupture is a rare clinical emergency. However, pregnancy symptoms and signs are not obvious, and the limited examination methods obscure the observation. Thus, early renal rupture is challenging to detect, leading to misdiagnosis and poor prognosis. This paper aims to improve clinicians' understanding of this disease and reduce the rate of clinical misdiagnosis. PATIENT CONCERNS: The patient, aged 23 and 11 weeks pregnant, developed severe right lumbar and abdominal pain for 14 hours after severe nausea, vomiting, and paroxysmal intensification. Color ultrasound of the urinary system at another hospital revealed right kidney stones and right ureter dilation. Thus, the patient came to our hospital for treatment. DIAGNOSES: Spontaneous renal vessel rupture. INTERVENTIONS: In this case, the diagnosis of spontaneous renal vascular rupture and hemorrhage was confirmed. Following conservative treatment such as fluid replenishment, blood transfusion, and hemostasis, the patient was given an emergency renal artery embolization due to unstable hemodynamics during treatment and poor conservative treatment effect. OUTCOMES: Nephrectomy was performed after 1-week follow-up for renal necrosis. LESSONS: To avoid missed diagnosis and misdiagnosis, patients with abdominal pain caused by severe vomiting during pregnancy must be closely monitored. Additionally, treatment should be considered individually to ensure the safety of both mother and child. Therefore, spontaneous renal vessel rupture should be considered as the differential diagnosis.

Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

[Clinical Characteristics of Children with Hemophagocytic Syndrome with Different EB Virus DNA Loads].

OBJECTIVE: To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis. METHODS: Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×102 copies/ml), low load group (>5×102-<5×105 copies/ml) and high load group (≥5×105copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group. RESULTS: The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 µg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×109/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups. CONCLUSION: The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.

Correlation between mismatch repair and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy.

BACKGROUND: Almost all adjuvant chemotherapy regimens for gastric cancer recommended by guidelines are fluorouracil (5-FU) based, and 5-FU-based adjuvant chemotherapy plays an important role in reducing the recurrence of gastric cancer after surgery. However, the effect of mismatch repair (MMR) status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer remains controversial. MATERIALS AND METHODS: We prospectively included patients with gastric cancer who underwent radical gastrectomy between March 14, 2017 and September 30, 2021. The included patients received 5-FU-based adjuvant chemotherapy or surgery alone. The MMR status of patients was divided into MMR proficient (pMMR) and MMR defective (dMMR) according to four MMR proteins. Peripheral blood was collected for systemic inflammation analysis. The main purpose of this study was to analyze the effect of MMR status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer. We also analyzed the differences in systemic inflammation levels in different MMR status and their impact on survival. RESULTS: A total of 479 patients were enrolled, with a median follow-up period of time was 36 months. In the surgery alone group, dMMR gastric cancer had better disease-free survival (DFS) (hazard ratio [HR] = 4.33, 95% confidence interval [CI] 1.25-15.02, p = 0.02) than pMMR, and in the adjuvant chemotherapy group, there was no significant difference in DFS (HR = 1.16, 95% CI 0.65-2.07, p = 0.61) between dMMR and pMMR gastric cancer. The same results were seen for overall survival (OS). In addition, the result show that in the dMMR group, there was no difference in DFS (HR = 1.62, 95% CI 0.46-5.77, p = 0.45) between patients receiving adjuvant chemotherapy and those receiving surgery alone. In the pMMR group, the DFS values (HR = 0.59, 95%CI 0.35-0.99, p = 0.04) of patients receiving adjuvant chemotherapy were better than those of patients receiving surgery alone, and the same results were observed for OS. In addition, among pMMR patients, patients with a low platelet lymphocyte ratio (PLR) who received 5-FU adjuvant chemotherapy and those with a low neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) who received surgery alone had better DFS and OS. CONCLUSION: To our knowledge, this is the first prospective study to specifically explore the correlation between MMR and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. The results showed that gastric cancer patients with pMMR can benefit from 5-FU-based adjuvant chemotherapy, but those with dMMR cannot. Among pMMR patients, lower PLR and SII values with surgery alone and lower NLRs in those receiving 5-FU-based adjuvant chemotherapy were associated with higher DFS and OS.

Effects of Fructus mume Extract on MAPK and NF-κB Signaling and the Resultant Improvement in the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion.

Fructus mume (F. mume) has been used as a medicinal food in Japan and has been reported to have anti-inflammatory effects in inflammatory bowel disease and macrophage-mediated inflammation. We investigated the effects of F. mume extracts on cognitive dysfunction in rats with chronic cerebral hypoperfusion and the molecular mechanisms underlying these effects. Chronic cerebral hypoperfusion was induced in male Wister rats by bilateral common artery occlusion (BCCAo). Daily administration of F. mume extracts was started on day 20 after post-BCCAo and continued for 40 days. The status of hippocampus-dependent memory was evaluated in control rats, rats with chronic cerebral hypoperfusion, and rats with chronic cerebral hypoperfusion that were administered F. mume. The levels of microglial activation were measured in the hippocampus and the fimbria of hippocampus, and expression levels of hippocampal mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were examined. Rats that received chronic cerebral hypoperfusion showed spatial memory impairments relative to the control rats; these impairments were reduced by daily administration of F. mume. Administration of F. mume mitigated the microglial activation and alterations of hippocampal MAPK and NF-κB signaling in the rats with chronic cerebral hypoperfusion. These results indicate that F. mume may possess therapeutic potential for the prevention of vascular dementia via inhibition of inflammatory processes.

Persistence of E. coli O157:H7 in urban recreational waters from Spring and Autumn: a comparison analysis.

People might get infected by pathogens found in urban recreational waters during water-contact activities, such as swimming, boating, bathing, and yachting. However, the persistence of pathogenic bacteria in those waters was not well documented. In this study, persistence of E. coli O157:H7 (EcO157) in 48 water samples (24 Spring samples and 24 Autumn samples) from the 3 urban recreational waters was investigated. Multivariate statistical analysis was performed to correlate survival data with water physicochemical properties and bacterial communities. Our data showed that EcO157 survived longer in Spring samples than in Autumn samples regardless of the lakes. Results revealed that recreational water physicochemical properties and bacterial community in Spring samples were different from those in Autumn samples. Mantel and Partial Mantel tests, as well as co-occurrence network analysis illustrated that EC salinity, TOC, and bacterial community were correlated with survival time (ttd) (p < 0.05). Variation partition analysis (VPA) indicated that bacterial community, EC, TOC, and TN explained about 64.81% of overall ttd variation in Spring samples, and bacterial community, EC, pH, and TP accounted for about 56.59% of overall ttd variation in Autumn samples. Structural equation model (SEM) illustrated that EC indirectly positively affected ttd through bacterial community. The correlation between bacterial community and ttd was negative in Spring samples and positive in Autumn samples. TN appeared a direct positive effect on ttd in Spring samples. TP displayed a direct negative effect on ttd in Autumn samples. Our results concluded that there was seasonal variation in environmental factors that directly or indirectly affected the survival of EcO157 in urban recreational waters.

Hsa-miR-149-5p Suppresses Prostate Carcinoma Malignancy by Suppressing RGS17.

BACKGROUND: MicroRNAs (miRNAs) are key players in the progression of human cancers. While several miRNAs have been reported to regulate the development of tumors, the molecular mechanisms and roles of miR-149-5p in prostate carcinoma (PCa) remain unclear. Our aim was to investigate the interaction and functions of miR-149-5p and RGS17 in PCa. METHODS: Microarray analysis was performed to identify the key miRNA and gene involved in PCa progression. The expression levels of miRNA and mRNA in PCa tissues and cells were verified by qRT-PCR. MTT assay, BrdU proliferation assay and wound-healing assay were applied to assess the effect of miR-149-5p and RGS17 on PCa cells' viability, proliferation, and migration ability. The association between RGS17 and miR-149-5p was identify using dual-luciferase reporter assay and Western blot assay. RESULTS: Data analysis indicated the reduction of miR-149-5p expression in PCa tissues and cells. Experimental investigations also showed that this miRNA suppressed the viability, proliferation and migration ability of PCa cells. RGS17 was found to be the target of miR-149-5p, and the low expression of miR-149-5p upregulated RGS17 in PCa tissues and cells. The results of the cell-function assays showed that RGS17 acted as an oncogene in PCa even though its promotive effect could be reversed by miR-149-5p. CONCLUSION: This research confirmed that by targeting and inhibiting RGS17, miR-149-5p could suppress PCa development.

The efficacy of cisplatin and low-temperature plasma radiofrequency ablation in advanced laryngeal cancer patients and on the serum survivin levels.

OBJECTIVE: To investigate the effect of cisplatin injections combined with low-temperature plasma radiofrequency ablation on the clinical efficacy and serum survivin levels in advanced laryngeal cancer patients. METHODS: A total of 42 patients with locally advanced laryngeal cancer treated in our hospital from January 2018 to June 2020 were recruited as the study cohort and placed in a control group (21 cases) or a treatment group (21 cases) according to the medication administered to each patient. The patients in the control group were treated with CO2 laser resections under laryngoscopy combined with cisplatin injections, and the patients in the observation group were treated with low-temperature plasma radiofrequency ablation combined with cisplatin injections. The clinical efficacies in the two groups were observed and the WHOQOL-BREF scores, tumor marker levels, and serum survivin levels were compared. RESULTS: After the treatment, the ORR and CBR in the control group were 33.3% and 61.9%, respectively, levels that were significantly lower than the 66.7% and 90.5% in the observation group (P<0.05). The observation group's physiological, psychological, and social relations dimension scores were significantly higher than the corresponding scores in the control group (P<0.05). The tumor markers in the observation group were significantly lower in the serum CA72-4, CA19-9, and SCC-Ag levels than they were in the control group (P<0.05). The observation group exhibited lower serum survivin levels than the control group (P<0.05). Conclusion Cisplatin injections combined with low-temperature plasma radiofrequency ablation has a significant effect on the treatment of locally advanced laryngeal cancer. It can improve patients' quality of life, reduce the tumor marker levels in the body, and inhibit the serum survivin levels.

Bioinformatics analysis of laryngeal squamous cell carcinoma: seeking key candidate genes and pathways.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most aggressive head and neck squamous cell carcinoma. Although much work has been done to optimize its treatment, patients with LSCC still have poor prognosis. Therefore, figuring out differentially expressed genes (DEGs) contained in the progression of LSCC and employing them as potential therapeutic targets or biomarkers for LSCC is extremely meaningful. METHODS: Overlapping DEGs were screened from two standalone Gene Expression Omnibus datasets, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. By applying STRING and Cytoscape, a protein-protein network was built, and module analysis was carried out. The hub genes were selected by maximal clique centrality with the CytoHubba plugin of Cytoscape. UALCAN and GEPIA data were examined to validate the gene expression findings. Moreover, the connection of the hub genes with LSCC patient overall survival was studied employing The Cancer Genome Atlas. Then, western blot, qRT-PCR, CCK-8, wound healing and transwell assays were bring to use for further verify the key genes. RESULTS: A total of 235 DEGs were recorded, including 83 upregulated and 152 downregulated genes. A total of nine hub genes that displayed a high degree of connectivity were selected. UALCAN and GEPIA databases verified that these genes were highly expressed in LSCC tissues. High expression of the SPP1, SERPINE1 and Matrix metalloproteinases 1 (MMP1) genes was connected to worse prognosis in patients with LSCC, according to the GEPIA online tool. Western blot and qRT-PCR testify SPP1, SERPINE1 and MMP1 were upregulated in LSCC cells. Inhibition of SPP1, SERPINE1 and MMP1 suppressed cell proliferation, invasion and migration. CONCLUSION: The work here identified effective and reliable diagnostic and prognostic molecular biomarkers by unified bioinformatics analysis and experimental verification, indicating novel and necessary therapeutic targets for LSCC.

The effects of albumin-bound paclitaxel combined with cisplatin injections on patients with advanced laryngeal cancer and serum survivin.

OBJECTIVE: To explore the effects of the TP (Taxol plus Platinol) regimen and the PF (Platinol plus fluorouracil) regimen on patients with advanced laryngeal cancer and on the patients' VEGF-C (vascular endothelial growth factor C) and survivin genes. METHODS: 42 patients with locally advanced laryngeal cancer treated in our hospital from June 2018 to October 2020 were recruited as the study cohort. The patients were assigned into a control group (21 cases) or an observation group (21 cases). The control group was administered the PF regimen, and the observation group was administered the TP regimen. Both groups were treated for four consecutive courses. The clinical efficacy of the two groups of patients was observed, and the two groups' treatment effects, their serum VEGF-C, and survivin levels, and their adverse reactions were compared. RESULTS: A superior clinical efficacy was observed in the observation group (85.7%) than in the control group (57.1%) (P<0.05). Before the treatment, the two groups' serum VEGF-C and survivin levels showed no significant differences (P>0.05). After the treatment, apparently lower serum VEGF-C and survivin levels in the observation group were measured, and both groups witnessed a decline in their levels (P<0.05). We measured higher overall survival times and tumor-free survival times in the patients in the observation group compared to the control group (P<0.05). There was no significant difference in the incidences of adverse reactions between the two groups of patients (P>0.05). CONCLUSION: The TP regimen in the treatment of laryngeal cancer can reduce the VEGF-C and survivin levels in patients and has a better therapeutic effect, so it is worthy of clinical promotion.

Prediction of the mechanism of miRNAs in laryngeal squamous cell carcinoma based on the miRNA-mRNA regulatory network.

In this study, a bioinformatics analysis is conducted to screen differentially expressed miRNAs and mRNAs in laryngeal squamous cell carcinoma (LSCC). Based on this information, we explored the possible roles of miRNAs in the pathogenesis of LSCC. The RNA-Seq data from 79 laryngeal cancer samples in the Gene Expression Omnibus (GEO) database were sorted. Differentially expressed miRNAs and mRNAs in LSCC are screened using the PERL programming language, and it was analysed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The miRNA-mRNA regulatory network of LSCC is constructed using Cytoscape software. Then, quantitative real-time PCR (QRT- PCR), Cell Counting Kit-8 (CCK8) and flow cytometry analysis we are used to further validate key miRNAs. We identified 99 differentially expressed miRNAs and 2,758 differentially expressed mRNAs in LSCC tissues from the GEO database. Four more important miRNAs displaying a high degree of connectivity are selected, these results suggest that they play an important role in the pathogenesis of LSCC. As shown in the present study, we identified specific miRNA-mRNA networks associated with the occurrence and development of LSCC through bioinformatics analysis. We found a miRNA molecule closely related to LSCC based on miRNA-mRNA network: miR-140-3p was down-regulated in LSCC. In addition, the potential antitumor effect of miR-140-3p in LSCC was verified in the experiment, and it was proved that overexpression of miR-140-3p could inhibit the proliferation of LSCC cells and promote cell apoptosis, suggesting that miR-140-3p may be a potential tumor marker in LSCC.

emPAI-assisted strategy enhances screening and assessment of Mycobacterium tuberculosis infection serological markers.

Discovering new serological markers of Mycobacterium tuberculosis (MTB) infection and establishing a rapid and efficient detection technology is of great significance for the prevention and control of tuberculosis. In this study, we established an exponentially modified protein abundance index (emPAI) value-assisted strategy to investigate and improve the screening efficiency of serological biomarkers of tuberculosis. First, we used LC-MS/MS to analyse MTB culture filtrate proteins (MTB-CFPs), and 632 MTB proteins were identified. Then, the characteristic values of MTB-CFPs - including emPAI value, molecular weight (Mw), isoelectric point (pI), grand average of hydropathy (GRAVY), transmembrane domain (TMD) and functional groups were calculated. Next, we successfully prepared 10 MTB proteins with emPAI value > 1.0 and recombinantly expressed these proteins in Escherichia coli. At the same time, 3 MTB proteins with emPAI between 0.1 and 0.5 were randomly selected as the control groups, and the immunogenicity of the recombinant MTB proteins was detected using ELISA. The sensitivity and receiver operating characteristic (ROC) curves were calculated for each recombinant MTB protein. The results showed that the areas under the curve (AUC) value of Rv2031c, Rv0577, Rv0831c, Rv0934 and Rv3248c were all higher than those of Rv3875 (AUC, 0.6643). Further analysis of the relationship between emPAI value and antibody sensitivity, AUC value and antibody affinity in mice immunized with recombinant MTB protein showed that emPAI values were positively correlated with them, and R-squared value ranged from 0.64 to 0.79. The only exception was ESAT-6 (encoded by the Rv3875 gene), which AUC value was relatively low owing to its strong immunosuppressive properties. This study provides a rationale for the serological marker screening of emPAI-assisted tuberculosis clinical test. The results also provide new technical support for the screening of candidate serological markers of infectious diseases in the future.

Impairment of long-term depression induced by chronic brain inflammation in rats.

Although deficits in synaptic plasticity have been identified in aged or neuroinflamed animals with memory impairments, few studies have examined the cellular basis of plasticity in such animals. Here, we examined whether chronic neuroinflammation altered long-term depression (LTD) and studied the underlying mechanism of LTD impairment by neuroinflammation. Chronic neuroinflammation was induced by administration of lipopolysaccharide (LPS) to the fourth ventricle. Excitatory postsynaptic potentials were recorded extracellularly in the rat hippocampal CA1 area to examine alterations in synaptic plasticity. Chronic administration of LPS induced remarkable memory impairment in the Morris water maze test. N-methyl-d-aspartate receptor (NMDAR)-dependent LTD was almost absent in LPS-infused animals. The AMPA receptor (AMPAR)-mediated synaptic response was reduced in the LPS-infused group. These results suggest that reduction in NMDAR-dependent LTD might arise because of alterations in postsynaptic AMPARs as well as NMDARs and that such changes may be present in mild and early forms of Alzheimer-type dementia.