Qiditangshen Granules Alleviates Diabetic Nephropathy Podocyte Injury: A Network Pharmacology Study and Experimental Validation in Vivo and Vitro

BACKGROUND: QiDiTangShen granules (QDTS), a traditional Chinese medicine (TCM) compound prescription, have remarkable efficacy in diabetic nephropathy (DN) patients, and their pharmacological mechanism needs further exploration. METHODS: According to the active ingredients and targets of the QDTS in the TCMSP database, the network pharmacology of QDTS was investigated. The potential active ingredients were chosen based on the oral bioavailability and the drug similarity index. At the same time, targets for DN-related disease were obtained from GeneCards, OMIM, PharmGKB, TTD, and DrugBank. The TCM-component-target network and the protein-protein interaction (PPI) network were constructed with the Cytoscape and STRING platforms, respectively, and then the core targets of DN were selected with CytoNCA. GO and KEGG enrichment analysis using R software. Molecular docking to identify the core targets of QDTS for DN. In vivo, db/db mice were treated as DN models, and the urine microalbuminuria, the pathological changes in the kidney and the protein expression levels of p-PI3K, p-Akt, JUN, nephrin and synaptopodin were detected by immunohistochemistry, immunofluorescence method and Western blotting. After QDTS was used in vitro, the protein expression of mouse podocyte clone-5 (MPC5) cells was detected by immunohistochemistry, immunofluorescence and Western blot. RESULTS: Through network pharmacology analysis, 153 potential targets for DN in QDTS were identified, 19 of which were significant. The KEGG enrichment analysis indicated that QDTS might have therapeutic effects on IL-17, TNF, AGE-RAGE, PI3K-Akt, HIF-1, and EGFR through interfering with Akt1 and JUN. The main active ingredients in QDTS are CONCLUSION: Through network pharmacology, in vivo and in vitro experiments, QDTS has been shown to improve the urine microalbuminuria and renal pathology in DN, and to reduce podocyte damage via the PI3K/Akt pathway

Association and dose–response relationship of plasma magnesium with metabolic syndrome in Chinese adults older than 45 years

PurposeMagnesium (Mg) is an essential nutrient for the maintenance of vital physiological functions. Magnesium deficiency is associated with diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS); however, conclusions have been inconsistent, and there is a particular lack of evidence regarding this association in Chinese population older than 45 years. This study aimed to assess the association between plasma magnesium and the risk of MetS and its components, the dose–response relationship, and the threshold effect relationship in a Chinese population involving older than 45 years.MethodsA total of 2,101 individuals were randomly selected from the China Nutrition and Health Surveillance (CNHS) (2015–2017) by considering monitoring points. We used the joint statement of the International Diabetes Federation (IDF) in 2009 to define participants with MetS. The plasma magnesium was tested by inductively coupled plasma mass spectrometry (ICP-MS). The logistic regression and restricted cubic spline (RCS) models were used to analyze the association and dose–response relationship between plasma Mg and MetS and its components.ResultsCompared with the lowest quintile (Q1) for plasma Mg, the odds ratios (ORs) and 95% confidence intervals (95% CI) for MetS, impaired fasting glucose (IFG), hypertension, and triglyceride (TG) elevation at the highest quintile (Q5) were 0.419 (0.301, 0.583), 0.303 (0.221, 0.415), 0.446 (0.322, 0.618), and 0.526 (0.384, 0.720), respectively, with all p < 0.05. However, in the components of decreased high-density lipoprotein cholesterol (HDL-C) and central obesity, no trend toward lowering with higher plasma magnesium was observed (p = 0.717, p = 0.865). These associations were not altered by further adjustment for potential confounding variables, including age, gender, education, nationality, area, residence, body mass index (BMI), and heart rate. The RCS analysis showed that, when plasma magnesium was lower than 0.85 mmol/L, the curve was leveled off, and then, the curve showed a decreasing trend with the increase in plasma magnesium.ConclusionTherefore, plasma Mg was negatively associated with MetS and its components (including IFG, hypertension, and elevated TG) in people older than 45 years. In addition, plasma Mg greater than or equal to 0.85 mmol/L, which is higher than the commonly used threshold of 0.75 mmol/L, may be protective against MetS and its components (including elevated FPG, elevated blood pressure, and elevated TG). More prospective studies, such as randomized controlled trials, are necessary to confirm the effective impact of Mg on MetS and its components. Plasma Mg levels in the MetS population older than 45 years require attention

Free and bioavailable 25-hydroxyvitamin D thresholds for bone metabolism and their associations with metabolic syndrome in Chinese women of childbearing age

ObjectiveThe free hormone hypothesis suggests that free and bioavailable 25-hydroxyvitamin D [25(OH)D] may better reflect vitamin D bioactivity. This study aimed to determine the free and bioavailable 25(OH)D characteristics, estimate their thresholds based on parathyroid hormone (PTH) and bone turnover markers (BTMs), assess their associations with the risk of metabolic syndrome (MetS), and evaluate their potential advantages.MethodsA cross-sectional study was conducted using a nationally representative database (n = 1,505, female, 18–45 years). Serum total 25(OH)D, vitamin D-binding protein, albumin, PTH, and BTMs [osteocalcin, β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and procollagen type 1 N-terminal propeptide (P1NP)] were measured. Free 25(OH)D and bioavailable 25(OH)D were calculated. The threshold associations of 25(OH)D with PTH and BTMs were analyzed. The relationship between 25(OH)D and MetS risk was examined. An intervention study was then performed in 39 women (18–47 years) to assess the associations of increasing 25(OH)D with PTH and BTMs after vitamin D supplementation.ResultsIn the cross-sectional study, the three forms of 25(OH)D were found to have similar distribution characteristics. Free and bioavailable 25(OH)D correlated well with total 25(OH)D. Significant total 25(OH)D cutoffs were observed for PTH (14.19 ng/mL and 18.03 ng/mL), osteocalcin (15.14 ng/mL), β-CTX (14.79 ng/mL), and P1NP (15.08 ng/mL). Free and bioavailable 25(OH)D cutoffs were only found for P1NP (3.47 pg/mL and 1.66 ng/mL, respectively). A total 25(OH)D of <15.14 ng/mL was marginally associated with a higher risk of reduced high-density lipoprotein cholesterol (HDL-C) [odd ratios (OR) = 1.371 (0.991–1.899)]. The ORs of higher versus lower free and bioavailable 25(OH)D levels for reduced HDL-C were 0.770 (0.621–0.956) and 0.772 (0.622–0.958), respectively. The results of the intervention study indicated that PTH and BTMs responded more sensitively to total 25(OH)D than to free or bioavailable 25(OH)D.ConclusionFree and bioavailable 25(OH)D only had a threshold effect on P1NP. The active 25(OH)D thresholds could be used for risk assessment of reduced HDL-C. However, no superiority of free or bioavailable 25(OH)D was found based on the response of PTH and BTMs to changes in 25(OH)D in Chinese women of childbearing age following vitamin D supplementation.Clinical trial registrationhttp://www.chictr.org.cn, ChiCTR2200058290

B Cell-Related Circulating MicroRNAs With the Potential Value of Biomarkers in the Differential Diagnosis, and Distinguishment Between the Disease Activity and Lupus Nephritis for Systemic Lupus Erythematosus

Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls (P < 0.05) and could act as the diagnostic signature to distinguish SLE patients from healthy donors. Six miRNAs (miR-92a, miR-27a, miR-19b, miR-23a, miR-223, and miR-16) expressed in plasma were significantly lower in SLE patients than in RA patients (P < 0.05), revealing the potentially diagnostic signature to distinguish SLE patients from RA patients. Furthermore, the downregulated expression of miR-19b, miR-25, miR-93, and miR-15b was associated with SLE disease activity (P < 0.05) while miR-15b and miR-22 expressions were significantly lower in SLE patients with low estimate glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) (P < 0.05). The diagnostic potential of miR-15b for SLE disease activity and lupus nephritis (LN) with low eGFR was validated on an independent validation set with 69 SLE patients and a cross-validation set with 80 SLE patients. In summary, the signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and evaluation of disease activity and LN

Magnesium Nutritional Status, Risk Factors, and the Associations with Glucose Parameters of Childbearing Women in the China Adult Chronic Disease and Nutrition Surveillance (2015)

Magnesium is an essential element and participates in many metabolic pathways. Inadequate magnesium levels may lead to various health problems such as type 2 diabetes (T2DM), hypertension, and cancer. But the role of Mg in childbearing women of China is still a relatively narrow researched field. We aimed to assess the Mg nutritional status, explore the risk factors of Mg deficiency, and the associations between Mg and glucose parameters among childbearing women in a nationally representative sample. A total of 1895 18–44 years childbearing women were recruited from the China Adult Chronic Disease and Nutrition Surveillance (2015). Multivariate logistic regression was used to explore the risk factors for Mg deficiency and estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the risk of hyperglycemia. The mean value of Mg was 0.87 mmol/L and the prevalence of deficiency was 4.69%. The risk factors of Mg deficiency (Mg < 0.75 mmol/L) was city-type of rural (p = 0.045), while calcium (p = 0.001), LDL-C (p = 0.024), age group of 26–35 years (p = 0.016), 36–44 years (p = 0.006), and CNNM2 rs3740393 genotypes of GC (p = 0.027) were protective factors. It was also found that magnesium deficiency induces an increase in plasma glucose (p = 0.001). Compared with the reference range, Mg < 0.75 mmol/L would have a 6.53 fold risk for T2DM, a 5.31 fold risk for glucose-hyperglycemia, and a 9.60 fold risk for HbA1c-hyperglycemia. Consistently, there was a negative association between plasma Mg and blood glucose parameters in the dose–response study. More attention should be paid to the nutritional status of magnesium and the impact of magnesium deficiency on human health

Anti-Seismic Behavior of Welded Box Section Column Considering Welding Residual Stress at High Temperature

To study the anti-seismic performance of steel structure under high temperature, the finite element analysis software ABAQUS was used to study the seismic performance of Q235 steel welded box section column at service stage under normal temperature and high temperature fire. The effects of welding residual stress, slenderness ratio, width thickness ratio and axial load level on the hysteretic behavior of columns were analyzed and the stable bearing capacity and hysteretic performance of the column under high temperature were investigated. The results show that the maximum bearing capacity of the column decreases with the increase of the residual stress peak value. With the increase of temperature, a decrease in the maximum bearing capacity of columns under constant axial force and horizontal cyclic load and an increase in the ductility occur

Application of cosmic‐ray neutron probes for measuring soil moisture in rocky areas of the Taihang Mountains, North China

Abstract The cosmic‐ray neutron probe (CRNP) is a mesoscale and noninvasive method for measuring soil moisture and has been widely studied and applied. However, studies of its applicability in rocky mountainous areas are still challenging in complex topography and high gravel content. In this study, a field experiment was carried out to assess the applicability of the CRNP for measuring soil moisture in rocky areas of Taihang Mountains of North China. The results showed that the Pearson correlation coefficient and the root mean square error between the soil moisture from CRNP and the drying method are 0.911 and 0.025 m3 m−3, respectively, indicating that the CRNP can estimate the average soil moisture well in the study area. Compared with the capacitive sensor, the CRNP overestimated soil moisture when small rainfall events occurred, which was caused by the interception of canopy and litter. The nonlinear weighting method performed better than the linear weighting method in representing average soil moisture within the CRNP footprint. The high gravel content that contained high lattice water content reduced the penetration depth of CRNP. Biomass reduces the accuracy of the CRNP by affecting the neutron intensity. In summary, CRNP can measure soil moisture accurately in rocky areas of the Taihang Mountains, especially in dry environments with low biomass

Study on Reference Range of Zinc, Copper and Copper/Zinc Ratio in Childbearing Women of China

Background: Copper and zinc are both essential elements in humans, that play various biological roles in body functions. Population-based reference values have not yet been established in China especially in childbearing women. The aim of this study is to establish a reference value of Zn, Cu and Cu/Zn ratios in childbearing women aged 18–44 from a representative population in China. Method: A total of 191 healthy childbearing women aged 18–44 years old were enrolled from the China Adult Chronic Disease and Nutrition Surveillance (2015) in this study with a series strict inclusion criteria. Basic biological indicators (weight, height, waist, blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein, total cholesterol, triglyceride, fast glycose, HbA1c, blood pressure, uric acid) and elements levels in plasma and whole blood were collected. The 2.5th to 97.5th was used to represent the reference range of Cu, Zn and Cu/Zn ratio. Results: The reference range of Zn, Cu and Cu/Zn ratio in plasma were 70.46–177.53 µg/dL, 74.30–170.68 µg/dL and 0.54–1.68, respectively. The reference range of Zn, Cu and Cu/Zn ratios in whole blood were 402.49–738.05, 74.63–124.52 and 0.13–0.25 µg/dL, respectively. Conclusion: The reference range of Zn, Cu and Cu/Zn ratios in plasma and whole blood of healthy Chinese childbearing women could be used as an indicator to evaluate the status of element deficiency and overload