Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo clarify the medication regularity of WU Zhao-dong，a famous chief physician in traditional Chinese medicine （TCM） of Jiangxi province， and investigate the potential mechanism of potential new prescriptions against chronic renal failure （CRF）. MethodThe outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform （V 2.5） to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），STRING，and Kyoto Encyclopedia of Genes and Genomes（KEGG）， followed by verification by molecular docking and experiments. ResultA total of 200 prescriptions were screened out， with 217 Chinese medicinal drugs involved， and eight new potential prescriptions were derived. To be specific， Prescription 1： Armeniacae Semen Amarum-Astragali Radix-Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma-fried Atractylodis Macrocephalae Rhizoma， Prescription 2： Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba，Prescription 3：Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba， Prescription 4：Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix， Prescription 5：Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus， Prescription 6： Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma， Prescription 7：Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix， Prescription 8：Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1，18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted， and 37 potential targets for the treatment of CRF were obtained， including interleukin （IL）-6， vascular endothelial growth factor （VEGF）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nitric oxide synthase 3 （NOS3）， and hypoxia-inducible factor-1 （HIF-1）. The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis，NF-κB， Toll-like receptors， and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen， and increased the content of NO and NOS3 in renal tissues of CRF rats. ConclusionPrescription 1 shows the multi-component and multi-target characteristics of action，and its mechanism may be related to its inhibition of renal fibrosis，anti-inflammation，improvement of intestinal microecology，and improvement of renal hypoxia and ischemia.

Effect of Paidu Baoshen Pill on renal fibrosis in 5/6 nephrectomized rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the anti-renal fibrosis effect of Paidu Baoshen Pill (PBP) on 5/6 nephrectomized rats and to explore its mechanism.</p><p><b>METHODS</b>Totally 50 SD male healthy rats were randomly divided into the normal control group (n = 10), the sham-operation group (n = 10), and the nephrectomy model group (n = 30) according to the proportion of 1:1:3. Rats in the sham-operation group had their renal capsule isolated without nephrectomy. Rats in the nephrectomy model group had their kidneys 5/6 nephrectomized. Then 24 h urine was collected and 24 h urinary protein (24 h UP) detected. Serum blood urea nitrogen (BUN) and serum creatitine (SCr) were also tested. According to the SCr level 30 rats of the model group were further randomly divided into the model group, the PBP group, and the Niaoduqing Granule (NG) group, 10 in each group. Rats in the PBP group and the NG group were respectively administered with PBP (at the daily dose of 1.0 g/kg) and NG (at the daily dose of 3.33 g/kg) by gastrogavage (they were dissolved in distilled water). At the same time, 2 mL distilled water was administered by gastrogavage to rats in the normal control group, the sham-operation group, and the nephrectomy model group, once daily for 4 successive weeks. Mental conditions, activities, hair color, shape of stool, and the body weight were observed during administration. After 4 weeks, urine was collected to detect 24 h UP. Blood was sampled to detect SCr, BUN, transforming growth factor β1 (TGF-β1), type III procollagen (PC III), collagen type IV (Col IV), laminin (LN), and fibronectin (FN). After rats were killed, their left remnant renal tissues were collected for pathological examinations. The protein expression quantity of TGF-β1 and FN was detected by immunohistochemical method. mRNA expression levels of TGF-β1 and FN were detected using real time fluorescent quantitative PCR.</p><p><b>RESULTS</b>There was no statistical difference in the above indices between the normal control group and the sham-operation group (P > 0.05). Compared with the sham-operation group, rats' general condition was poorer in the model group, their body weight grew slower, and 24 h UP increased; serum levels of BUN, SCr, TGF-β1, PC III, Col IV, LN, and FN increased; the residual renal pathological lesion was serious; expression levels of TGF-β1, TGF-β1, mRNA, FN, and FN mRNA increased in the renal tissue (all P < 0.01). Compared with the model group, rats' general condition was better, their body weight grew faster, 24 h UP reduced (P < 0.05), blood levels of BUN and SCr decreased significantly (P < 0.01), serum levels of TGF-β1, PC III, CoL IV, LN, and FN decreased (P < 0.05, P < 0.01); the residual renal pathological lesion was attenuated in the PBP group and the NG group; expression levels of TGF-β1, TGF-β1, mRNA, FN, and FN mRNA decreased (P < 0.01). Compared with the NG group, blood levels of SCr and FN, and expression levels of FN and FN mRNA decreased more in the PBP group (P < 0.05).</p><p><b>CONCLUSIONS</b>PBP had the effect of anti-renal fibro- sis in 5/6 nephrectomized rats. Down-regulating expression levels of TGF-β1, and FN from gene transcription and protein translation levels might be one of its mechanisms.</p>

Effects of vitamin A combined with other micronutrients on nutritional status of 3-6 years old children / 第二军医大学学报

Objective To explore the effects of vitamin A combined with other micronutrients on the nutritional status in children. Methods According to the method of stratified random cluster sampling, three kindergartens were randomly selected out of 7 in the suburbs of Chongqing. A total of 350 preschool children who met the eligibility criteria, aged between 3-6 years old in the selected kindergartens, were randomly assigned to 3 treatment groups: the vitamin A group (A group), the vitamin A plus Zn group (AZ group), and the vitamin A supplementation with multiple micronutrients group (AMM group). The supplementation lasted for 6 months in the three groups. The height and weight of the participants were measured and the Z-score value was calculated before and after supplementation to evaluate the incidence of malnutrition. Serumvitamin A, Zn, Fe, Ca and hemoglobin levels were also measured before and after the intervention. A questionnaire survey of the general situation, family status and dietary habit of the children was performed before the supplementation; also the dietary nutrient intake of the children during intervention was investigated by a 24-hour dietary recall method. Results The 24-hour dietary recall results showed that vitamin A, Zn and Ca were inadequate in the diet of the 3-6 years old children in our study. Compared with before supplementation, the serum Zn and Fe levels were significantly different in the three groups 6 months after supplementation (all P0.05). The increment of serum vitamin A in AMM group was significantly greater than those in A and AZ groups (all P0.05). Conclusion The effect of multiple micronutrient supplementation shows no significant difference on nutritional status in 3-6 aged children compared with the two micronutrient supplementations. Micronutrient supplement for children should be based on the main nutritional problems of them, and the best combination of nutrients should be chosen to improve nutrition and health status of children.

Effects of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on iron metabolic homeostasis / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of vitamin A, vitamin A plus iron and "7 + 1" multiple micronutrient-fortified seasoning powder on iron metabolic homeostasis in preschool children.</p><p><b>METHODS</b>This was a randomized, controlled and blinded interventional field trial. A total of 226 2 - 7 years old preschool children were recruited from three nurseries in the area, and they were randomly assigned into three different fortified diet groups for 6 months. The subjects in Group I were fortified with vitamin A; those in Group II and III were fortified with vitamin A plus iron and vitamin A plus iron, thiamine, riboflavin, folic acid, niacinamide, zinc and calcium (7 + 1), respectively. The concentration of serum vitamin A was measured by high-performance liquid chromatography (HPLC), serum ferritin (SF) was measured by enzyme-linked immunosorbent assay (ELISA), soluble transferrin receptor (sTfR) was measured by microparticle-enhanced, and hemoglobin (HB) by hemiglobincyanide, the sTfR-SF index (TFR-F index) and total body iron content were computed respectively before and after intervention. Simultaneously, children's demographic data, socio-economic status and eating habits, etc. were investigated by questionnaires.</p><p><b>RESULTS</b>A total of 226 preschool children were included in the study with age ranged from 2 to 7 years with average age (4.0 ± 0.85) (means ± standard deviation). The prevalence of anemia, deficient iron storage, vitamin A deficiency (VAD) and suspect sub-clinical vitamin A deficiency (SSVAD) were 23.5%, 15.0%, 6.3% and 25.9%, respectively. The levels of SF and sTfR significantly decreased after intervention in all groups (χ(2) = 8.3298, χ(2) = 16.1471, χ(2) = 15.1371, χ(2) = 15.1171, χ(2) = 5.2617, χ(2) = 4.8844, P < 0.05) especially in group II and group III for SF (χ(2) = 16.1471, χ(2) = 15.1371, P < 0.05) and group I for sTfR (χ(2) = 15.1171, P < 0.05). No marked change of TFR-F index and total body iron contents was observed in group I (t = 0.1817, t = 1.7736, P > 0.05), while TFR-F index decreased and total body iron contents increased in group II and group III (t = 5.3561, t = 6.5979, t = 11.1663, t = 8.7306, P < 0.05) after intervention.</p><p><b>CONCLUSION</b>Vitamin A intervention has significant effect on iron storage and mobilization but seldom effect on iron absorption in small intestine. The combination of vitamin A and other micronutrients might be a better intervention for the improvement of iron deficiency for preschool-children.</p>

Impact of antioxidant vitamins and heavy metal levels at birth on neurodevelopment of children assessed at two years of age / 中华儿科杂志

<p><b>OBJECTIVE</b>Epidemiologic study on the perinatal interaction of antioxidant vitamins and heavy metals on offspring's intellectual development is extremely limited. The aim of this prospective cohort study was to investigate the status of maternal and cord blood antioxidant vitamins (Vitamin A, E and C) and heavy metals (lead, cadmium and mercury) at delivery and correlations between these antioxidant vitamins or metals and neurodevelopment of early childhood, and to explore the protective effect of antioxidant vitamins against the injure of heavy metals to intellectual development in children in Tongliang, Chongqing, China.</p><p><b>METHOD</b>A total of 150 pairs of mothers-neonates were recruited. Serum concentrations of vitamin(V) A, vitamin E, vitamin C, lead, cadmium and mercury in maternal and cord blood after delivery were determined and intellectual development was evaluated by Gesell Development Schedule (GDS) at two years of age.</p><p><b>RESULT</b>A total of 111 pairs of maternal-neonatal subjects with completed data were included into statistical analysis. After adjusting for potential confounders, cord blood mercury level was found negatively associated with all the development quotients (DQs) (β = -0.486, β = -0.716, β = -0.846, β = -0.935, β = -0.702, P < 0.05). Cord VE level was positively correlated with motor, adaptation, language and average DQ (β = 0.475, β = 0.458, β = 0.403, β = 0.395, P < 0.05). When antioxidant vitamins and heavy metals levels were all included into the multiple regression model, cord vitamin E level was statistically positively related with motor, adaptation and average DQs (β = 0.449, β = 0.412, β = 0.349, P < 0.05). While cord blood mercury level was negatively correlated with adaptation, language, social and average DQ (β = -0.397, β = -0.727, β = -0.935, β = -0.628, P < 0.05), the relationship between cord mercury level and motor DQ was not statistically significant (P = 0.0890). The motor, adaptation, language and average DQs in high cord VE group were higher than those in low VE group (t = 2.93, t = 2.06, t = 2.13, t = 2.27, P < 0.05). Social DQ in high cord lead group was significantly lower than that in low lead group (χ(2) = 5.56, P = 0.015). Cord VC level in high cadmium group was significantly lower than that in low cadmium group (χ(2) = 7.62, P = 0.006). VA placental transport ratio in high mercury group was significantly lower than those in low mercury group (χ(2) = 8.02, P = 0.005).</p><p><b>CONCLUSION</b>Our data suggested that there may be certain interaction between antioxidant vitamin A, E, C and heavy metals lead, cadmium, mercury. Antioxidant vitamins at delivery may have protective effect on the early neurodevelopment via interaction with the heavy metals.</p>