Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

Background::The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN).Methods::In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN.Results::The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 μg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%.Conclusions::The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

Background::The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN).Methods::In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN.Results::The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 μg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%.Conclusions::The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

Gas therapy has been proven to be a promising and advantageous treatment option for cancers. Studies have shown that nitric oxide (NO) is one of the smallest structurally significant gas molecules with great potential to suppress cancer. However, there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor. Therefore, the anti-cancer mechanism of NO is the key to cancer treatment, and rationally designed NO delivery systems are crucial to the success of NO biomedical applications. This review summarizes the endogenous production of NO, its physiological mechanisms of action, the application of NO in cancer treatment, and nano-delivery systems for delivering NO donors. Moreover, it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies. The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

Background Occupational aluminum exposure may associate with cognitive impairment in workers. At present, brain functional imaging data are not available for evaluating cognitive dysfunction in workers with occupational exposure to aluminum. The role of brain functional connectivity in cognitive decline associated with occupational aluminum exposure is not clear yet. Objective To explore potential mediating effect of brain functional connectivity value on cognitive decline induced by occupational aluminum exposure, to assess the relationship between cognitive impairment and brain functional connectivity, and to identify appropriate imaging evidence of early cognitive changes induced by occupational aluminum exposure. Methods This study used a subset data from a previous cross-sectional survey. Based on the data of aluminum-exposed workers, over 40 years old, aluminum-exposed working years >1 year, Montreal International Cognitive Assessment (MoCA) (Beijing version) score <26 points, 20 workers were selected as the case group, and 40 healthy workers with the same basic conditions (age, smoking, drinking, etc.) in non-aluminum production were selected as the control group with a 1∶2 matching ratio. The basic information of the subjects was collected, plasma aluminum level and cognitive function level were evaluated, and different brain functional connectivity values of default mode network (DMN) were measured by magnetic resonance imaging. The mediating effect analysis was conducted to examine the role of brain functional connectivity in the relationship between aluminum exposure and cognitive function. Results The plasma aluminum concentration of the case group was 1.76 times higher than that of the control group [(33.04±12.02) µg·L⁻¹ vs (18.74±8.95) µg·L⁻¹, P<0.05]; the MoCA score was 9.5 points lower [(18.35±2.64) vs (27.85±0.92), P<0.05]. The mean functional connection values of DMN1 and DMN2 in the case group were lower than those in the control group (P<0.05). The mean functional connection values of the left precuneus, left middle cingulate cortex, left superior medial gyrus, left precentral gyrus, and left cerebellum also decreased in the case group compared with the control group (P<0.05). Plasma aluminum concentration was negatively correlated with DMN1 functional connectivity value and MoCA scores (b=−0.004, 95%CI: −0.008–−0.001; b=−0.15, 95%CI: −0.233–−0.067; P<0.05). The mean functional connection values of DMN1 and DMN2 were positively correlated with MoCA scores (b=10.945, 95%CI: 5.574–16.316; b=10.107, 95%CI: 2.457–17.758; P<0.05). With the increase of plasma aluminum concentration, MoCA score decreased, but when the plasma aluminum concentration exceeded 19.50 µg·L⁻¹, MoCA score decreased slowly. With the increase of the mean functional connectivity value of DMN1, MoCA score increased, but when the mean functional connectivity value of DMN1 exceeded 1.05 and continued to increase, the increase of MoCA score slowed down. The results of mediating effect analysis showed that the functional connectivity value of DMN1 partially mediated the relationship between plasma aluminum concentration and MoCA score, and the mediating effect was 25.80%. Conclusion Cognitive impairment in occupational aluminum-exposed workers is closely related to brain resting-state functional connectivity. There is a dose-response relationship of plasma aluminum concentration with DMN1 functional connectivity value and MoCA scores, and DMN1 functional connectivity value partially mediates the relationship between plasma aluminum concentration and MoCA scores. The brain functional connectivity value can be used as meaningful imaging data to study the cognitive decline induced by chronic aluminum exposure.

Background Aluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity. Objective To explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)₃]. Methods BV2 cells were assigned to five groups: one control group, three Al(mal)₃ exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L⁻¹ Al(mal)₃ respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L⁻¹ C188-9 +160 μmol·L⁻¹ Al(mal)₃]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA. Results The results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)₃ dose. Compared with the control group, the cell viability of the Al(mal)₃ high-dose group was decreased by 18% (P<0.05); compared with the Al(mal)₃ high-dose group, the cell viability of the C188-9 intervention group was significantly elevated by 14% (P<0.05). Compared with the control group, the expression levels of CD68 in the Al(mal)₃ low-, medium-, and high-dose groups were elevated by 19%, 20%, and 21%, respectively (P<0.05); the expression level of CD206 in the Al(mal)₃ high-dose group was decreased by 25% (P<0.05). Compared with the Al(mal)₃ high-dose group, the expression level of CD68 in the C188-9 intervention group was reduced by 9% (P<0.05), whereas the expression level of CD206 was elevated by 22% (P<0.05). Compared with the control group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the Al(mal)₃ high-dose group increased by 129% and 127%, respectively (P<0.05). Compared with the Al(mal)₃ high-dose group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the C188-9 intervention group were decreased by 55% and 54%, respectively (P>0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)₃ high-dose group (P<0.05), the expression levels of cleaved-casepase-1 protein increased by 28% and 35% in the Al(mal)₃ medium- and high-dose groups (P<0.05), and the expression levels of ASC increased by 22%, 25%, and 53% in the Al(mal)₃ low-, medium- and high-dose groups (P<0.05), respectively. Compared with the Al(mal)₃ high-dose group, the expression levels of NLRP3, cleaved-casepase-1, and ASC proteins in the C188-9 intervention group decreased by 30%, 19%, and 32%, respectively (P<0.05). Compared with the control group, the levels of IL-1β in the Al(mal)₃ medium- and high-dose groups increased by 18% and 21%, respectively (P<0.05), and the level of IL-18 in the Al(mal)₃ high-dose group increased by 10% (P<0.05). Compared with the Al(mal)₃ high-dose group, the IL-18 levels were reduced by 23% in the C188-9 intervention group (P<0.05). The content of anti-inflammatory factor IL-10 did not differ significantly between groups (P>0.05). Conclusion Aluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.

The aim of the present study was to explore the changes in some functional connectivity in the resting-state electroencephalogram (EEG) based functional brain network of depressed college students, and to understand the brain regions involved in the onset of depression and the electrophysiological activity of subcortical nerve cells, hoping to provide additional information for the diagnosis of depression. Twenty female college students with depressive symptoms were selected according to the Beck Depression Inventory-II (BDI-II) and the Self-rating Depression Scale (SDS). The EEG information of 20 female college students under resting-state was collected by using a 32-conduction EEG acquisition system (Neuroscan). Then Pearson correlation analysis, coherence analysis, phase locking value analysis, phase lag index analysis and weighted phase lag index analysis were used to construct the resting-state brain functional network. The results showed that, compared with the normal group, the depression group exhibited significantly increased correlation in θ and β bands of EEG (P < 0.05), and extremely significantly increased in α band (P < 0.01). Among them, the coherence in α and β bands was significantly increased (P < 0.05), mainly concentrated in the left hemisphere frontal lobe and temporal lobe region. The phase locking value in θ, α and β bands was significantly increased (P < 0.05), mainly concentrated in the prefrontal region and the left hemisphere from the frontal region to the temporal region, and the connectivity in α band was the most obvious. Correlation analysis showed a significant positive correlation between indicators of differential functional connectivity (coherence and phase locking value) and BDI-II scores in the depression group, and the receiver operating characteristics (ROC) curve indicated a high specificity of 85% for the differential indicators. These results suggest that the abnormal brain function of the depressed college students is related to the change of functional connectivity in the left hemisphere, especially α frequency band in the frontal region, which is of great significance for the diagnosis of depression in the future.
Brain/physiology* ; Brain Mapping/methods* ; Depression ; Electroencephalography ; Female ; Humans ; Students

Objective: To investigate the current situation of cell phone use and sleep quality among college students, establish a sleep quality trajectory model and explore the influence of cell phone use on the sleep quality trajectory. Methods: Based on data from the College Student Behavior and Health Cohort Study 2019-2020, a latent class growth modeling was used to establish a sleep quality trajectory model among college students. The baseline influencing factors of sleep quality trajectories among college students were analyzed by χ² test, and the effects of cell phone use on sleep quality trajectories were analyzed by binary logistic regression. Results: A total of 1 092 college students were included in the analysis. The detection rates of cell phone use and poor sleep quality were 24.5% and 13.3%. Latent class growth model identified two groups of sleep quality trend trajactories: an improved sleep quality group (86.0%) and a decreased sleep quality group (14.0%). The result of binary logistic regression showed that the cell phone use was a risk factor of sleep quality trajectories. Conclusion: The cell phone use during college period could increase the risk of poor sleep quality. Targeted intervention measures about cell phone use should be adopted to improve the sleep quality among college students.
Humans ; Sleep Quality ; Cohort Studies ; Cell Phone Use ; Surveys and Questionnaires ; Students ; Sleep Initiation and Maintenance Disorders ; Cell Phone ; Sleep

Objective: To construct a multi-state Markov model and analyze the disease outcomes and its influencing factors in HIV infected individuals receiving antiretroviral therapy. Methods: A retrospective cohort analysis was conducted in HIV infected individuals receiving antiretroviral therapy in Luzhou of Sichuan province from 2010 to 2021. The disease status was divided into CD4⁺T lymphocytes (CD4) counts >500 cells/μl, 350-500 cells/μl, 200-349 cells/μl, ≤199 cells/μl and death indicated by S1-S5 in turn. A reversible continuous-time discrete-state multi-state Markov model was constructed for the analysis of disease progression features. Results: A total of 7 542 HIV infected individuals receiving antiretroviral therapy were included, and the median age (Q₁, Q₃) was 53.4 (41.2, 64.5) years old. The transition intensity of S3→S2 was higher. During follow-up, the transition probability of S4→S5 increased gradually. Influencing factors analysis of disease outcomes in HIV infected individuals receiving antiretroviral therapy showed that compared with individuals 15-24 years old, the transition intensities of S2→S1, S3→S2 and S4→S3 were lower and the transition intensity of S3→S4 was higher in individuals ≥45 years old. Compared with single individuals, the transition intensities of S3→S2 and S4→S3 were higher and the transition intensities of S3→S4 and S4→S5 were lower in married individuals. The transition intensity of S1→S2 was higher in individuals with baseline CD4 counts ≤500 cells/μl than in individuals with baseline CD4 counts >500 cells/μl. The transition intensity of S3→S4 in individuals diagnosed during 2011-2015 was lower than that in individuals diagnosed in 2010 and before. Conclusions: HIV infected individuals receiving antiretroviral therapy tended to shift to the previous disease status, suggesting that antiretroviral therapy was conducive to immune reconstitution. Older age (≥45 years old), being married, low baseline CD4 counts and being diagnosed in 2010 and before were the risk factors for disease progression.
Adolescent ; Adult ; CD4 Lymphocyte Count ; China/epidemiology* ; Disease Progression ; HIV Infections/drug therapy* ; Humans ; Middle Aged ; Retrospective Studies ; Young Adult

Objective: To analyze the clinical characteristics of 6 children with TTC21B-related nephronophthisis to provide reference for early clinical diagnosis. Methods: The general condition, clinical manifestations, laboratory tests and other clinical data of 6 children from 4 families diagnosed with nephronophthisis by genetic testing in Shanghai Children's Hospital from January 2015 to December 2020 were analyzed retrospectively. Results: A total of 6 children (3 males and 3 females) developed proteinuria and progressive renal dysfunction in early infancy. The onset age of proteinuria was 18 (6, 25) months. The age at the onset of renal impairment was 22 (10, 36) months. All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. Five children had hypertension, 3 children with abnormal liver function, 2 children with visceral translocation and 1 child with growth retardation. The genetic results suggested that all children carried variations TTC21B gene p.C518R. Conclusions: Children with TTC21B gene p.C518R nephronophthisis had proteinuria and progressed to ESRD at the early stage of life. These nephronophthisis patients commonly presented with liver and renal dysfunction.
China ; Female ; Humans ; Kidney Diseases, Cystic/genetics* ; Kidney Failure, Chronic/genetics* ; Male ; Phenotype ; Proteinuria/genetics* ; Retrospective Studies