Machine learning-based identification of novel hub genes associated with oxidative stress in lupus nephritis: implications for diagnosis and therapeutic targets.

BACKGROUND: Lupus nephritis (LN) is a complication of SLE characterised by immune dysfunction and oxidative stress (OS). Limited options exist for LN. We aimed to identify LN-related OS, highlighting the need for non-invasive diagnostic and therapeutic approaches. METHODS: LN-differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus datasets (GSE32591, GSE112943 and GSE104948) and Molecular Signatures Database for OS-associated DEGs (OSEGs). Functional enrichment analysis was performed for OSEGs related to LN. Weighted gene co-expression network analysis identified hub genes related to OS-LN. These hub OSEGs were refined as biomarker candidates via least absolute shrinkage and selection operator. The predictive value was validated using receiver operating characteristic (ROC) curves and nomogram for LN prognosis. We evaluated LN immune cell infiltration using single-sample gene set enrichment analysis and CIBERSORT. Additionally, gene set enrichment analysis explored the functional enrichment of hub OSEGs in LN. RESULTS: The study identified four hub genes, namely STAT1, PRODH, TXN2 and SETX, associated with OS related to LN. These genes were validated for their diagnostic potential, and their involvement in LN pathogenesis was elucidated through ROC and nomogram. Additionally, alterations in immune cell composition in LN correlated with hub OSEG expression were observed. Immunohistochemical analysis reveals that the hub gene is most correlated with activated B cells and CD8 T cells. Finally, we uncovered that the enriched pathways of OSEGs were mainly involved in the PI3K-Akt pathway and the Janus kinase-signal transducer and activator of transcription pathway. CONCLUSION: These findings contribute to advancing our understanding of the complex interplay between OS, immune dysregulation and molecular pathways in LN, laying a foundation for the identification of potential diagnostic biomarkers and therapeutic targets.

Sema3A inactivates the ERK/JNK signalling pathways to alleviate inflammation and oxidative stress in lipopolysaccharide-stimulated rat endothelial cells and lung tissues.

Semaphorin 3A (Sema3A) is a secretory member of the semaphorin family of immune response regulators. This research focuses on its effects on inflammation and oxidative stress in acute respiratory distress syndrome (ARDS). By analysing the GEO dataset GSE57011, we obtained Sema3A as the most downregulated gene in ARDS samples. Lipopolysaccharide (LPS) was used to stimulate rat pulmonary microvascular endothelial cells (PMVECs) and rats to induce ARDS-like symptoms in vitro and in vivo, respectively. LPS induced severe damage in rat lung tissues, in which reduced immunohistochemical staining of Sema3A was detected. Sema3A overexpression reduced apoptosis and angiogenesis of LPS-induced PMVECs and alleviated lung injury and pulmonary edoema of rats. Moreover, ELISA results showed that Sema3A overexpression downregulated the levels of inflammatory cytokines and oxidative stress markers both in PMVECs and the rat lung. Activation of ERK/JNK signalling aggravated LPS-induced damage on PMVECs; however, the aggravation was partly blocked by Sema3A, which suppressed phosphorylation of ERK/JNK. Overall, this study demonstrates that Sema3A inactivates the ERK/JNK signalling to ameliorate inflammation and oxidative stress in LPS-induced ARDS models. Sema3A might therefore represent a candidate option for ARDS treatment.

Heart rate variability is associated with cerebral small vessel disease in patients with diabetes.

Objective: Low heart rate variability (HRV), an indicator of autonomic nervous system dysfunction, has been associated with increased all-cause and cardiovascular mortality and incident stroke. However, the relationship between HRV and cerebral small vessel disease (CSVD) showed contradictory results. We aimed to examine the relationship of HRV and total burden of CSVD and each of the magnetic resonance imaging (MRI) markers of CSVD. Methods: We recruited 435 patients who attended our hospital for physical examination between June 2020 and August 2021. All underwent 24-h Holter monitoring and MRI scan. The standard deviation of normal-to-normal intervals (SDNN) was selected as the method for HRV assessment. The presence of severe white matter hyperintensity, lacunes, and >10 enlarged basal ganglia perivascular spaces, and cerebral microbleeds were added for estimating the CSVD score (0-4). Multivariate logistic analyses was performed to assess whether HRV was independently associated with the burden of CSVD and each of the MRI markers of CSVD, with and without stratification by prevalent diabetes. Results: This study included 435 subjects with a mean age of 64.0 (57.0-70.0) years; 49.4% of the patients were male, and 122 (28.0%) had a history of diabetes. In multivariate analyses, lower SDNN was independently associated with total burden of CSVD and the presence of enlarged perivascular spaces in all subjects. According to diabetes stratification, lower SDNN was independently associated with total burden of CSVD and each MRI markers of CSVD separately only in the diabetic group. Conclusions: Lower HRV was associated with total burden of CSVD and each MRI markers of CSVD separately among diabetic patients, but not among non-diabetic patients.

Abnormalities of retinal structure and microvasculature are associated with cerebral white matter hyperintensities.

BACKGROUND AND PURPOSE: Whilst retinal microvasculature represents cerebral small vessels, the retinal nerve fiber layer is the extended white matter of the brain. The aim was to investigate the correlation between changes in retina and white matter hyperintensities (WMHs). METHODS: Sixty-four candidates with WMHs received an optical coherence tomography angiography examination. WMHs were divided into mild or moderate/severe groups according to the Fazekas score. After imaging the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the microvascular density parameters (vascular perfusion density [VPD], vascular length density [VLD] and fovea avascular zone area) and morphological parameters (vessel diameter index [VDI], fractal dimension [FD] and vessel tortuosity) were identified. A software algorithm measured the thickness of the peripapillary retina nerve fiber layer (PRNFL). RESULTS: Thirty-two were classified as having mild WMHs and 32 were moderate/severe. The median (interquartile range) ages of the two groups were 58 (54-64) and 61 (57-67) years, respectively. A decrease of FD, VPD and VLD in either SCP or DCP appeared with an increased risk of moderate/severe WMHs. Although changes of capillary plexus were not associated with paraventricular WMHs, decreased FD, VPD, VLD and fovea avascular zone area in either SCP or DCP were associated with an increased risk of moderate/severe deep WMHs (DWMHs). Participants with moderate/severe WMHs demonstrated reduced PRNFL thickness, particularly in the DWMHs, compared with mild WMHs. CONCLUSIONS: Abnormalities of retinal microvascular density, morphological parameters and PRNFL thickness are correlated with the incidence of moderate/severe WMHs, particularly the DWMHs, suggesting that arteriosclerosis and hypoperfusion are the causes of DWMHs.

Vaccine hesitancy among parents and its influencing factors: a cross-sectional study in Guangzhou, China.

Vaccine hesitancy is a major obstacle to the achievement of universal child vaccination, which has been studied extensively in Western countries but much less so in Asian countries, especially China. This cross-sectional survey is aimed to assess the prevalence of vaccine hesitancy and to explore the reasons for vaccine hesitancy among parents in Guangzhou. In January 2020, a questionnaire adapted to the Chinese setting from a widely-used hesitancy scale was administered to a sample of parents who brought their children aged <13 years to Community Health Service Centers for vaccination in Guangzhou. The incidence of vaccine hesitancy among those parents was 6.6% (50/755). Regression analysis showed that differences in socio-economic characteristics were not associated with the occurrence of vaccine hesitancy among parents in Guangzhou. However, strong distrust of domestic vaccine quality (OR = 10.9, 95% CI = 1.5-81.4), being required to have their children vaccinated for nursery and school entry (OR = 3.6, 95% CI = 1.7-7.7), and not being aware of which vaccines are officially required and which are optional (OR = 2.1, 95% CI = 1.1-4.3) were the risk factors significantly associated with vaccine hesitancy. In order to increase parents' trust in domestic vaccine quality and reduce the prevalence of vaccine hesitancy, it is essential to strengthen quality control in domestic vaccine manufacturing and to proactively disseminate clear and accurate information about vaccines to parents. Furthermore, advocating the value of vaccination among all citizens of Guangzhou is crucial.

Serum Cortisol Is Associated With Cerebral Small Vessel Disease-Related Brain Changes and Cognitive Impairment.

OBJECTIVE: To evaluate the relationship between serum cortisol, cerebral small vessel disease (CSVD) neuroimaging markers, and cognitive performance. METHODS: We recruited patients over 50 years old who attended our hospital for physical examination between November 2020 and July 2021. All participants were subject to brain magnetic resonance imaging (MRI), serum cortisol examination, and the Montreal cognitive function assessment (MoCA). On brain MRI, we scored the presence of each marker of CSVD, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). One point was awarded for the presence of each marker, producing a score between 0 and 4. RESULTS: In total, 158 participants were included in this study with a mean age of 60.5 (56.0-66.3) years; 55.1% were male. In the multivariable analyses, serum cortisol level was an independent predictor of WMH severity, the presence of lacunes/CMBs, moderate-severe EPVS and total CSVD burden after adjusting for confounding factors. Serum cortisol level had positive associations with periventricular/deep Fazekas score, burdens of lacunes/CMBs, moderate-severe EPVS, and total CSVD burden in dose-dependent manner, and was an independent predictor of cognitive impairment. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.745 with 64.1% sensitivity and 82.5% specificity, and an AUC of 0.705 with 52.1% sensitivity and 85.5 specificity of cortisol in detecting patients with high CSVD burden and MCI, respectively. CONCLUSIONS: Serum cortisol level is independently associated with each CSVD MRI markers, total CSVD burden and cognitive impairment. These findings provide clues for pathological mechanisms and suggest serum cortisol as a promising biomarker associated with CSVD.

Dynamic changes of peripheral blood lymphocyte subsets in acute ischemic stroke and prognostic value.

OBJECTIVE: To explore dynamic changes of peripheral blood lymphocyte subsets in patients with acute ischemic stroke (AIS) and the relationship with stroke severity and long-term outcomes. METHODS: A total of 96 consecutive patients with AIS and 28 age- and gender-matched healthy controls were recruited. Peripheral blood samples were collected, and the percentages of lymphocyte subsets were analyzed by flow cytometry. The dynamic changes in lymphocyte subsets and their correlation with clinical parameters, such as National Institutes of Health Stroke Scale (NIHSS) scores at onset and modified Rankin scale (mRS) scores 3 months later, were evaluated. RESULTS: In our study, we observed a decrease in the percentages of T-lymphocytes (T cells), helper/inducible T-lymphocytes (Th cells) and suppressor/cytotoxic T-lymphocytes (Ts cells) in AIS patients as compared to controls. The frequencies of T cells and Ts cells on day 8-14 after stroke in NIHSS ≤4 group were significantly higher than those in NIHSS >4 group. The percentages of T cells and Th cells on day 1-3 after stroke in the mRS ≤2 group were higher than those in the mRS >2 group. CONCLUSION: The frequencies of T cells, Th cells, and Ts cells in AIS are declined dramatically at least 14 days after stroke. Lower frequencies of T cells and Ts cells on day 8-14 after stroke represent more severe disease conditions, and the percentages of T cells and Th cells within 72 hr after stroke are negatively correlated with 3-month outcomes, which might have a potential for predicting long-term prognosis of stroke.

School-based sexual harassment among college students in Guangzhou, China / 中国学校卫生

Objective@#This study examined school-based sexual harassment experience among college students in Guangzhou, and to provide theoretical basis for preventing campus sexual harassment.@*Methods@#A cross-sectional survey was conducted among 1 062 college students from five universities in Guangzhou, China. A self-made questionnaire regarding awareness sexual harassment and experience of school-based sexual harassment was filled out by students voluntarily and anonymously.@*Results@#A total of 169 students reported they experienced school-based sexual harassment. The incidence of school-based sexual harassment among college students in Guangzhou was 15.91%, higher among female students (20.30%) than male students(10.2%)(χ 2=19.91, P<0.01). Verbal harassment (10.26%) was the most common type of sexual harassment, followed by physical harassment (7.16%), visual harassment (4.61%) and unwanted sexual advances (1.69%). Sexual harassment primarily took place in teaching building(58), dormitory(33) and office(17). Among the victims, 116(68.64%) were influenced by harassment. Females(n=94) being harassed were more likely to be negatively influenced compare to males(n=22).@*Conclusion@#School-based sexual harassment may result adverse psychological outcomes to students, more emphasis should be put on the prevention of sexual harassment.

[Effect of IgG3 antibody purified from sera of Microtus fortis against Schistosoma japonicum].

IgG3 antibody reaction to soluble antigens prepared from schistosomula (SSA), adult worms (SAWA) and eggs (SEA) in laboratory-bred Microtus fortis (Mf), BALB/c mice and Kunming (Km) mice challenged by cercariae of Schistosoma japonicum was detected by indirect ELISA. The effect of purified IgG3 antibody on in vitro killing schistosomula and protecting mice from infection of S. japonicum was evaluated. The IgG3 antibody level in Mf against SSA and SAWA increased significantly by 79.6 percent and 49.6 percent after the fourth week of challenge infection, but no significant increase in BALB/c mice. Purified IgG3 antibody from laboratory-bred Mf and wild Mf effectively killed schistosomula, and that of the wild Mf induced higher worm-reduction rate. The death rate of schistosomula due to IgG3 antibody purified from sera of laboratory-bred Mf and wild Mf was 2.35 and 5.88 times as high as that of Km mice respectively. The results suggest that IgG3 antibody from Microtus fortis may play an important role in immunity against S. japonicum.