Combination of theoretical analysis and experiments: Exploring the role of PLA2G7 in human cancers, including renal cancer.

Background: The pivotal role of phospholipase A2 group VII (PLA2G7) has been identified in specific human cancers, such as prostate cancer, diffuse large B cell lymphoma, and melanoma. Given PLA2G7's significant involvement in established tumors, exploring its role in other cancers is highly relevant. Methods: In this study, we acquired and analyzed data from The Cancer Genome Atlas database, the UCSC XENA website, and other online platforms including Gene Set Cancer Analysis, cBioPortal, Tumor Immune Estimation Resource, and TISIDB to investigate PLA2G7's role in human cancers, including renal cancer. Furthermore, in vitro experiments, including immunofluorescence, western blotting, and CCK-8 assays, were conducted to elucidate PLA2G7's role in renal cancer. Finally, the relationship between PLA2G7 and various drug sensitivity was explored. Results: Our findings demonstrate that PLA2G7 is highly expressed and may serve as a valuable candidate biomarker in pan-cancer. PLA2G7 exhibits distinct alteration frequencies across human cancers and is correlated with tumor mutation burden, tumor microenvironment, DNA stemness score, RNA stemness score, tumorigenesis, tumor immunity, and microsatellite instability in pan-cancer. Immunofluorescence and western blotting revealed a relative high level of PLA2G7 protein in renal cancer cell lines (ACHN and 786-O), predominantly localized in the cytoplasm. Treatment with a PLA2G7 gene inhibitor (darapladib) significantly decreased the viability of ACHN and 786-O cell lines. Additionally, we observed an association between PLA2G7 mRNA levels and various drug sensitivity. Conclusions: Our study suggests that PLA2G7 has the potential to serve as a valuable biomarker and therapeutic target for cancer, particularly in the context of renal cancer.

A nomogram predicting the histologic activity of lupus nephritis from clinical parameters.

BACKGROUND: The 2021 clinical guidelines of the Kidney Disease: Improving Global Outcomes emphasize the importance of the histological activity index (AI) in the management of lupus nephritis (LN). Patients with LN and a high AI have poor renal outcomes and high rates of nephritic relapse. In this study we constructed prediction models for the AI in LN. METHODS: The study population comprised 337 patients diagnosed with LN using kidney biopsy. The participants were randomly divided into training and testing cohorts. They were further divided into high-activity (AI >2) and low-activity (AI ≤2) groups. This study developed two clinical prediction models using logistic regression and least absolute shrinkage and selection operator (LASSO) analyses with laboratory test results collected at the time of kidney biopsy. The performance of models was assessed using 5-fold cross-validation and validated in the testing cohort. A nomogram for individual assessment was constructed based on the preferable model. RESULTS: Multivariate analysis showed that higher mean arterial pressure, lower estimated glomerular filtration rate, lower complement 3 level, higher urinary erythrocytes count and anti-double-stranded DNA seropositivity were independent risk factors for high histologic activity in LN. Both models performed well in the testing cohort regarding the discriminatory ability to identify patients with an AI >2. The average area under the curve of 5-fold cross-validation was 0.855 in the logistic model and 0.896 in the LASSO model. A webtool based on the LASSO model was created for clinicians to enter baseline clinical parameters to produce a probability score of an AI >2. CONCLUSIONS: The established nomogram provides a quantitative auxiliary tool for distinguishing LN patients with a high AI and helps physicians make clinical decisions in their comprehensive assessment.

Aerosol inhalation of ambroxol hydrochloride combined with terbutaline can promote recovery of children with severe pneumonia.

OBJECTIVE: This research aimed to investigate the clinical efficacy of aerosol inhalation of ambroxol hydrochloride combined with terbutaline on children with severe pneumonia, and to evaluate its influence on their immune function and inflammatory level. METHODS: Totally 113 severe pneumonia children were included. Thereinto, 55 children in the control group (CG) were treated with terbutaline aerosol inhalation, while 58 in the research group (RG) were given ambroxol hydrochloride on the basis of the CG. Their symptom alleviating time, blood gas parameters, adverse reactions during treatment, clinical efficacy, immune function and inflammatory factors were compared. RESULTS: The time of fever clearance time, disappearance of cough and pulmonary rates, chest shadow absorption and hospitalization of children in the RG were shorter than those in the CG. The combined treatment did not increase additional adverse reactions; instead, its effective rate was markedly higher than that in the CG. Further research found that after treatment, the arterial partial pressure of oxygen (PaO2), oxygenation index (OI), CD4+ and CD4+/CD8+, and interleukin-10 (IL-10) levels were dramatically increased, while the arterial partial pressure of carbon dioxide (PaCO2), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-17 (IL-17) and CD8+ levels were obviously increased. In addition, these indexes of children in the RG were obviously better than those in the CG. CONCLUSION: Aerosol inhalation of ambroxol hydrochloride combined with terbutaline has a remarkable clinical efficacy on children with severe pneumonia, which can improve their immune function and reduce inflammatory reaction.

[Association of leptin level and leptin receptor gene polymorphisms with susceptibility to severe pre-eclampsia].

OBJECTIVE: To evaluate the association of serum leptin concentrations and polymorphisms of G1019A and A223G of leptin receptor gene (LEPR) with severe pre-eclampsia. MEHTODS: A case-control study was carried out in 207 patients with severe pre-eclampsia (SPE group) and 252 healthy pregnant women (control group) during the third trimester of pregnancy. The serum leptin was determined by enzyme-linked immunosorbent assay. The polymorphisms of LEPR gene G1019A and A223G were detected by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) analysis. Miettinen's test was used to estimate the odds ratios (OR) and 95% confidence intervals (CI). RESULTS: (1) In severe pre-eclampsia group, serum leptin levels and rate of premature infant birth were significantly higher than that in normal pregnant women, and birth weight was lower than that in controls (P<0.01). (2) The frequencies of GA genotype and G allele for LEPR gene G1019A in SPE group (33.8% and 20.3%) were markedly higher than that in controls (19.8% and 15.1%) (P<0.01), and the carriers of GA genotype and G allele were more frequent in SPE group than in control group, resulting in an OR 2.04 (95%CI: 0.77-5.42) and 1.43 (95%CI: 1.02-2.01) to develop severe pre-eclampsia, compared with carriers of AA genotype and A allele. (3) AG genotype and A allele frequencies of LEPR gene A223G in SPE group (19.3% and 12.6%) were significantly lower than that in controls (34.5% and 19.2%) (P<0.01), resulting in an OR of 0.46 (95%CI: 0.30-0.71) and 0.60 (95%CI: 0.42-0.87) to develop severe pre-eclampsia, compared with subjects with GG genotype and G allele. (4) The "1019AA+223AG" genotype frequency was significantly lower in SPE group (6.8%) than in controls (24.6%) (P<0.01), resulting in an OR of 0.22 (95%CI: 0.12-0.39) to develop severe pr-eclampsia, while the "1019AA+223AG" was significantly higher in SPE group (22.2%) than in controls (11.9%) (P<0.05), resulting in an OR of 2.10 (95%CI: 0.78-3.45) to develop severe pre-eclampsia. (5) No significant differences were found in SBP, DBP, BMI and serum leptin levels in subjects with different genotypes in the two groups (P>0.05). CONCLUSION: Elevated serum leptin level and LEPR gene G1019A and A223G polymorphisms might play a role in severe pre-eclampsia, while the level of serum leptin was not associated with genotypes of LEPR gene G1019A and A223G polymorphisms. The genotypes GA and "1019AA+223AG"of G1019A may be genetic susceptibility factors to severe pre-eclampsia.