[Network Meta-analysis of Qi-supplementing and Yin-nourishing Chinese patent medicines in treatment of early diabetic nephropathy].

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

Mechanism of Yiqi Yangying Heluo Formula in the Treatment of IgA Nephropathy by Affecting Gd-IgA1 Based on BAFF Molecular Level and T Lymphocyte Immunity.

Background: Galactose-deficient IgA1 (Gd-IgA1) is a critical initiating factor in the pathogenesis of IgA nephropathy (IgAN), which plays an important role in the diagnosis and evaluation of this disease. Moreover, the whole pathogenesis process has an intimate association with the immune response of T and B lymphocytes and their inflammatory factors. There is no specific therapy for IgAN at present. Yiqi Yangyin Formula can significantly reduce urinary protein and hematuria in patients with IgAN. Yiqi Yangying Heluo Formula (YYHF) is optimized on the basis of the above prescription, but its specific mechanism remains to be further studied. Methods: The effect of YYHF on urinary protein and urinary red blood cell count in patients with IgAN was observed by a self-controlled clinical study before and after treatment. On this basis, flow cytometry was used to detect the proportion of T lymphocyte subsets in peripheral blood of patients with IgAN before and after treatment and healthy controls. Meanwhile, the levels of Gd-IgA1, B cell activation factor (BAFF), and their cytokines (IL-4, IL-6, and IL-17) in peripheral blood were detected by enzyme-linked immunosorbent assay. The changes in mechanism-related indicators of the two groups were observed and subject to correlation analysis. Results: (1) Compared with the levels before treatment, 24-hour urinary protein content decreased by 47.7% and urinary red blood cell number decreased by 67% in patients with IgAN intervened by YYHF after 48 weeks of follow-up. (2) Compared with the healthy control group, patients with IgAN showed a significantly increased proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg, obviously reduced proportion of Th2 cells and Treg cells, and evidently elevated levels of Gd-IgA1, BAFF, and their cytokines (IL-4, IL-6, and IL-17) in the peripheral blood. (3) Following 48 weeks of follow-up after intervention treatment with YYHF, the levels of Gd-IgA1, BAFF, IL-6, and IL-17 were significantly lower, but the level of IL-4 was higher in peripheral blood of patients with IgAN than those before treatment and after 24 weeks of treatment; simultaneously, the proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg decreased while that of Th2 cells and Treg cells increased after 48 weeks of follow-up compared with that before treatment in peripheral blood of patients with IgAN. (4) The results of correlation analysis revealed that the level of Gd-IgA1 in peripheral blood of patients with IgAN was positively correlated with the level of BAFF, as well as the proportion of Th1 cells, Th17 cells, Th1/Th2, IL-6, and IL-17 levels, and negatively correlated with the proportion of Treg cells. In addition, the level of Gd-IgA1 in peripheral blood was positively correlated with proteinuria, yet without correlation with hematuria. Conclusion: YYHF can reduce the quantitative level of 24 h urinary protein and urinary red blood cell count in patients with IgAN. Patients with IgAN have obvious T cell immune imbalance. YYHF can significantly reduce the level of Gd-IgA1 in patients with IgAN, and its mechanism may be explained by the reduced level of BAFF in peripheral blood and improved immune balance of T cells.

First record of a Takayama bloom in Haizhou Bay in response to dissolved organic nitrogen and phosphorus.

Since 1990s, harmful algal blooms (HABs) of Kareniaceae, primarily caused by species of Karenia and Karlodinium and rarely by Takayama species, have been substantially increasing in frequency and duration in the coastal waters of China. In this study, we recorded a bloom of high abundance of T. acrotrocha in the Haizhou Bay, the Yellow Sea in September 2020, which is the first record of a Takayama bloom in the temperate coastal waters of China. We found that high concentrations of DON and DOP accelerated the proliferation of T. acrotrocha in the Haizhou Bay. Intensive mariculture, and terrestrial nitrogen and phosphorus input may be responsible for the eutrophication in the Haizhou Bay featuring high concentrations of DON and DOP, and high DIN/DIP ratios. The results suggested that, under ocean warming, the HABs of Kareniaceae are becoming increasingly dominant in eutrophic temperate coasts with intensive mariculture activities.

Structural modulation of gut microbiota during alleviation of experimental passive Heymann nephritis in rats by a traditional Chinese herbal formula.

BACKGROUND: Jianpi-Qushi-Heluo formula (JQHF) has been used to treat idiopathic membranous nephropathy (IMN) in hospitals for many years. PURPOSE: Elucidating the protective effect and exploring the potential mechanism of JQHF against IMN. METHODS: Passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Then, the animals were treated with JQHF at 16.2 g/kg or 32.4 g/kg, with benzepril (10 mg/kg) as a positive control. Renal function was evaluated by biochemical measurements and pathological testing. Fecal samples were collected before and after treatment to analyze the gut microbiota composition by shotgun whole metagenome sequencing. RESULTS: JQHF exhibited potent efficacy in ameliorating PHN at both doses, as revealed by decreasing the deposition of IgG and C5b-9, relieving podocyte injury, and reducing glomerular and tubular cell apoptosis. The lower dose was corresponding to the clinical dosage and showed better therapeutic effects than the higher dose. Metagenomic analysis showed that gavage with 16.2 g/kg of JQHF shifted the structure of the gut microbiota in PHN rats and significantly increased the relative abundances of Prevotella copri, Lactobacillus vaginalis and Subdoligranulum variabile. Particularly, S. variabile was strongly negatively correlated with serum levels of TC and TG, the deposition of IgG and C5b-9, and apoptosis of glomerular cells. CONCLUSIONS: The JQHF is an effective agent for the treatment of experimental PHN. The PHN-allevating effect of JQHF is associated with specific alternation of gut microbiota.

Traditional Chinese Medicine in Treating IgA Nephropathy: From Basic Science to Clinical Research.

IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and end-stage renal disease worldwide. Currently, clinical interventions for IgAN are limited, and many patients seek out alternative therapies such as traditional Chinese medicine (TCM). In the last several years, TCM has accumulated ample application experiences and achieved favorable clinical effects. This article summarizes high-quality research from basic science to clinical applications aimed to provide more evidence-based medicine proof for the clinical treatment of IgAN. In summary, qi and yin deficiency accounted for the largest proportion in IgAN patients, and the treatment of IgAN should be based on supplementing qi and nourishing yin. Further, for patients with severe IgAN, the treatment combination of Chinese and Western medicines is better than pure Chinese medicine or hormone therapy. In addition, the pharmacological mechanism of Chinese herbal medicines is mostly based on restoring the immune function, relieving the inflammation damage, and inhibiting proliferation of the glomerular mesangial cells.

Jianpi Qushi Heluo Formula alleviates renal damages in Passive Hemann nephritis in rats by upregulating Parkin-mediated mitochondrial autophagy.

Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.

Effects of Jian Pi Qu Shi Formula on intestinal bacterial flora in patients with idiopathic membranous nephropathy: A prospective randomized controlled trial.

BACKGROUND: The incidence of idiopathic membranous nephropathy (IMN) has recently increased remarkably. Immune dysfunction caused by disordered intestinal flora might be an important factor affecting IMN. The Jian Pi Qu Shi Formula (JPQSF) shows promise in treating IMN. Here, we sequenced 16S rRNA genes to compare intestinal flora between patients with IMN and healthy persons. We also conducted a randomized controlled clinical trial to further compare the intestinal flora of patients with IMN treated with traditional Chinese medicine (TCM) and western medicine (WM). METHODS: Among 40 patients with IMN treated at Department of Nephrology in Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine between July 2016 and December 2018, we compared 30 of them with 10 healthy persons (controls). The IMN group was randomly assigned to receive JPQSF (TCM) or immunosuppressant WM therapy in (n = 15 per group) for 6 months. Intestinal microbiota diversity was analyzed using alpha diversity and beta diversity. Intestinal flora that significantly differed between the groups was analyzed using MetaStat. The effects and safety of the therapies were determined based on the values for plasma albumin, 24-h urine protein excretion, serum creatinine, urea nitrogen, estimate glomerular filtration rate (eGFR), complete blood count, and liver enzymes. All data were statistically analyzed using Statistical Package for the Social Sciences (SPSS) 20.0 statistical software. RESULTS: Baseline characteristics did not significantly differ between the IMN and healthy groups, or the TCM and WM groups. After six months of treatment, 24-h urinary protein significantly declined in the TCM and WM groups (before and after treatment: 3.24 ± 1.74 vs. 1.73 ± 1.85 g, P < 0.05 and 3.94 ± 1.05 vs. 1.91 ± 1.18 g, P < 0.05, respectively). Plasma albumin was significantly increased in the TCM group (before vs. after treatment: 32.44 ± 9.04 vs. 39.99 ± 7.03 g/L, P < 0.05), but did not significantly change in the WM group (31.55 ± 4.23 vs. 34.83 ± 9.14 g/L, P > 0.05). Values for urea nitrogen, serum creatinine, and eGFR did not significantly change in either group. The alpha diversity index for intestinal flora differed between the IMN and healthy groups, and the TCM and WM groups. Comparisons of multiple samples (beta diversity) revealed differences in intestinal flora between the IMN and healthy groups, and the TCM and WM groups. The Metastat analysis findings showed that the main genera that differed between the IMN group before treatment and the healthy group were Christensenellaceae_R-7_group, Bifidobacterium (77), Dorea, Escherichia-Shigella, Parabacteroides, Bifidobacterium, and Coprococcus_3. After TCM therapy, the main differential genera were Butyricimonas, Bacteroides, Alistipes, and Lachnospira, and after WM therapy, these were Ruminococcus_2, Lachnospiraceae_ND3007_group, Lachnospira, Bifidobacterium, Alistipes, and [Eubacterium]_ventriosum_group. CONCLUSION: Patients with IMN might have disordered intestinal flora, and JPQSF can regulate intestinal flora in patients with IMN.

Shengxuening versus Oral Iron Supplementation for the Treatment of Renal Anemia: A Systematic Review.

Shengxuening (SXN), as an effective supplement to heme-like iron, has been widely used in China to treat renal anemia. However, proof of its use for improving inflammation is scarce in the past decades. This work aimed to evaluate the effectiveness of SXN with inflammatory factors as primary endpoints. By searching PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), VIP Information/ China Science and Technology Journal Database, and WANFANG Database, we identified previous studies that met the inclusion criteria and included them in the systematic review. Analyses were performed using STATA. Nine randomized controlled trials were included in this systematic review. The results revealed that, when compared with oral iron supplementation, SXN can reduce the level of inflammatory factors, including hs-CRP (WMD -1.93 mg/L; 95% CI -2.14 to -1.72), IL-6 (P< 0.05), and TNF-α (P< 0.05), and significantly enhance the level of Hb (WMD 13.40 g/L; 95% CI 12.95 to 13.84), TSAT (WMD 6.88%; 95% CI 6.50 to 7.26), and SF (WMD 38.46 µg/L; 95% CI 23.26 to 53.67). Moreover, SXN exhibits a superior security than oral iron supplementation with less gastrointestinal adverse reactions (RR 0.14; 95% CI 0.06 to 0.32). In patients with renal anemia, SXN is more efective and safer than oral iron supplementation, especially in reducing the level of inflammation.

Analysis on diagnosis and treatment scheme of traditional Chinese medicine in treatment of COVID-19 in Chinese provinces and regions / 中草药

Since December 2019, a novel coronavirus-infected pneumonia was first detected in Wuhan, such cases had been subsequently discovered in other cities. The disease caused by the novel coronavirus was officially named COVID -19 (coronavirus disease 2019) by the world health organization. National Health Commission of China and other provinces and cities have successively performed syndrome differentiation of COVID-19 and provided corresponding Chinese medicine treatment programs. In this epidemic, the disease is a “dampness toxin”. The best principle for treatment is early detection and early treatment. Both Chinese and Western medicine have their own advantages. The advantages could be complementary and could not be replaced each other. Therefore, we collected the Chinese medicine treatment programs for the treatment of COVID-19 comprehensively, conducted a systematic analysis, and especially analyzed the pharmacological basis of traditional Chinese medicine for the treatment of COVID-19, which provided a basis for the rationality of Chinese medicine prescription for the treatment of COVID-19, and provided a reference of updating the diagnosis and treatment plan for provinces and cities.

Polymorphisms of genes related to vitamin D metabolism and transportation and its relationship with the risk of osteoporosis: protocol for a multicentre prospective cohort study in China.

INTRODUCTION: Osteoporotic fracture is one of the most common causes of disability and a major contributor to medical care costs in many regions of the world. The polymorphisms of genes related to vitamin D metabolism and transportation are associated with variation in bone mineral density and the risk of osteoporosis. METHODS AND ANALYSIS: The China Community-based Cohort of Osteoporosis study is an observational, longitudinal, multicentre, prospective cohort study for middle-aged and older permanent residents of China, which has been ongoing in six cities since 2016. Female residents aged 45-80 years old and male residents aged 50-80 years old are identified through permanent resident lists. All the enrolled participants will complete questionnaires on their personal characteristics and histories. The bone mineral density of their lumbar vertebrae and left hip will be measured and serum bone metabolism parameters assessed. Polymorphisms of genes related to vitamin D metabolism and transportation will be detected, and their relationship with the risk of osteoporosis, and osteoporotic fracture, will be analysed. About 18 000 residents will be involved in the study. ETHICS AND DISSEMINATION: The study was approved by Institutional Ethics Board of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine (2016LCSY065). Results will be published in peer-reviewed journals. The results of this study are expected to improve the understanding of the association between polymorphisms of genes related to vitamin D metabolism and transportation and the risk of osteoporosis and osteoporotic fracture among middle-aged and older residents of China. TRIAL REGISTRATION NUMBER: NCT02958020.

Characterization of genipin-crosslinked gelatin/hyaluronic acid-based hydrogel membranes and loaded with hinokitiol: In vitro evaluation of antibacterial activity and biocompatibility.

Hydrogel membranes are often used as physical barriers in oral tissue reconstruction and facial surgery to isolate connective and epithelial tissues and form a closed space for undisturbed bone healing. In this study, gelatin and hyaluronic acid were crosslinked with genipin and loaded with a hinokitiol additive as a bacteriostatic agent for potential applications as regeneration membranes. This bifunctional membrane had biocompatibility and antibacterial activities on each membrane side for proper biodegradation. Different membrane groups of gelatin/hyaluronic acid were obtained via a solution casting technique and were genipin crosslinked. The membrane groups were further loaded with adequate hinokitiol at a loading concentration of up to 0.16 g/L (hinokitiol to phosphate buffered saline). Fourier transform infrared spectroscopy showed that gelatin and hyaluronic acid were crosslinked with genipin through cross-linking amide bond (CONH) formation with a cross-linking degree of over 84%. The groups with hinokitiol showed substantial antibacterial activity. Meanwhile, the addition of hinokitiol on hydrogel membranes did not significantly affect the tensile strength. However, it decreased the solubility of the membranes by slowing down the relaxation and degradation of their molecular junctions as hinokitiol is a hydrophobic compound with low permeability. Consequently, the degradation of hydrogel membranes with hinokitiol was delayed. In vitro cytocompatibility indicated that the cell viability of the groups with hinokitiol increased with incubation time, demonstrating that cell viability and proliferation were not affected by cell culture testing.

Efficacy of complementary and integrative medicine on health-related quality of life in cancer patients: a systematic review and meta-analysis.

Complementary and integrative medicine (CIM) has been used for improving health-related quality of life (HRQOL) in patients with cancer. The objective of this review is to evaluate the effects of CIMs on the HRQOL of cancer patients. We identified randomized controlled trials (RCTs) involving patients with cancer at any stage by retrieving electronic databases from the inception to February 14, 2018 (Systematic Review Registration: PROSPERO CRD42018091609). The main outcomes were HRQOL scores and related domains such as physical well-being scores. The standardized mean difference was used for the analysis and heterogeneity was assessed with the I 2 statistic. A Bayesian framework was used to estimate the ranking order of efficacy in HRQOL change. Finally, 34 RCTs with 3,010 patients were included. As a whole, the results showed clearly superior efficacy of CIM in improving HRQOL. For different domains of HRQOL, different CIM interventions may play different roles. The ranking order of efficacy in change HRQOL was qigong plus mindfulness, Chinese herbal medicine, multimodal complementary medicine, qigong, nutritional supplement, mindfulness, acupuncture, yoga, and massage, and it was different among different domains. There was no evidence of publication bias. In conclusion, CIM may improve the HRQOL of cancer patients. More studies, especially focusing on male cancer patients, are needed to increase the confidence level of our findings.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Research progress on anti-depression effects of ginsenosides / 药学学报

Ginseng is a traditional Chinese medicine known as the "king of herbs" since ancient time in China. It was found in animal experiments that total saponins, ginsenoside monomers or glycosides from ginseng extraction all showed antidepressant effects in chronic unpredictable stress, corticosterone or lipopolysaccharide induced depression models. Taking ginsenosides as the focus, we reviewed the antidepressive mechanisms from the perspectives of various hypotheses, such as regulations of hypothalamic-pituitary-adrenal axis, monoamine neurotransmitter and neuroplasticity related to the pathogenesis of depression. The mechanism, target and pharmacodynamic targets of ginsenosides for anti-depression were summarized, in order to provide references for multi-targets and multi-level development of new anti-depression drugs, and improvement of diagnosis and treatment of depression from the perspective of traditional Chinese medicine and natural products.

Efficacy of Traditional Chinese Medicine Regimen Jian Pi Qu Shi Formula for Refractory Patients with Idiopathic Membranous Nephropathy: A Retrospective Case-Series Study.

BACKGROUND: The treatment of adult refractory idiopathic membranous nephropathy with steroid and other immunosuppressant-resistant nephrotic syndromes can be a significant challenge. We evaluated the efficacy and safety of the traditional Chinese medicine Jian Pi Qu Shi Formula (JPQSF) as a promising regimen. METHODS: We analyzed 15 consecutive patients with biopsy-proven idiopathic membranous nephropathy who failed immunosuppressive therapy from October 2013 to January 2017. JPQSF was administered orally two times per day, respectively, in the morning and at night for 6 months. All patients had at least 1 year of follow-up. The primary endpoints included complete or partial remission. Secondary endpoints included change of clinical parameters and adverse events after 12 months of treatment. RESULTS: After 12 months, complete remission was achieved in 13.3% of patients and partial remission in 66.7%, yielding a response rate of 80%. Proteinuria, serum albumin, and cholesterol were improved significantly (P<0.001, P<0.001, and P<0.05, respectively). After 1 year of treatment, proteinuria (mean ± SD) decreased from 5.93 ± 2.54 g per 24 h to 1.99 ± 1.17 g per 24 h (P<0.001). No serious adverse events occurred during the observation. CONCLUSIONS: JPQSF may be an alternative therapeutic option for steroid and general immunosuppressant-resistant membranous nephrotic syndrome patients, with a favorable safety profile. Larger and longer follow-up studies evaluating this regimen are warranted.

Dan-Lou Prescription Inhibits Foam Cell Formation Induced by ox-LDL via the TLR4/NF-κB and PPARγ Signaling Pathways.

Atherosclerosis is the major worldwide cause of mortality for patients with coronary heart disease. Many traditional Chinese medicine compound prescriptions for atherosclerosis treatment have been tried in patients. Dan-Lou prescription, which is improved from Gualou-Xiebai-Banxia decoction, has been used to treat chest discomfort (coronary atherosclerosis) for approximately 2,000 years in China. Although the anti-inflammatory activities of Dan-Lou prescription have been proposed previously, the mechanism remains to be explored. Based on the interaction between inflammation and atherosclerosis, we further investigated the effect of Dan-Lou prescription on macrophage-derived foam cell formation and disclosed the underlying mechanisms. In the oxidative low-density lipoprotein (ox-LDL) induced foam cells model using murine macrophage RAW 264.7 cells, the ethanol extract from Dan-Lou prescription (EEDL) reduced ox-LDL uptake and lipid deposition by inhibiting the protein and mRNA expression of Toll-like receptor (TLR)4 and scavenger receptor (SR)B1. After stimulation with ox-LDL, the metabolic profile of macrophages was also changed, while the intervention of the EEDL mainly regulated the metabolism of isovalerylcarnitine, arachidonic acid, cholesterol, aspartic acid, arginine, lysine, L-glutamine and phosphatidylethanolamine (36:3), which participated in the regulation of the inflammatory response, lipid accumulation and cell apoptosis. In total, 27 inflammation-related gene targets were screened, and the biological mechanisms, pathways and biological functions of the EEDL on macrophage-derived foam cells were systemically analyzed by Ingenuity Pathway Analysis system (IPA). After verification, we found that EEDL alleviated ox-LDL induced macrophage foam cell formation by antagonizing the mRNA and protein over-expression of PPARγ, blocking the phosphorylation of IKKα/ß, IκBα and NF-κB p65 and maintaining the expression balance between Bax and Bcl-2. In conclusion, we provided evidences that Dan-Lou prescription effectively attenuated macrophage foam cell formation via the TLR4/NF-κB and PPARγ signaling pathways.

[Relationship between serum 25(OH)D levels at birth and respiratory distress syndrome in preterm infants].

OBJECTIVE: To investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels at birth and respiratory distress syndrome (RDS) in preterm infants. METHODS: This retrospective study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were divided into two groups: RDS (n=72) and control (n=40). Clinical data of the two groups were collected, including gestational age, birth weight, gender, delivery mode, Apgar scores at 1 minute and 5 minutes, incidence of maternal gestational diabetes mellitus, and use of prenatal steroid hormone. Peripheral blood samples were collected and 25(OH)D levels were measured by chemiluminescence immunoassay. The association between serum 25(OH)D levels at birth and RDS was analyzed by multivariate logistic regression. RESULTS: Apgar scores at 1 minute and 5 minutes and serum 25(OH)D levels in the RDS group were significantly lower than those in the control group (P<0.05), while the rates of neonatal asphyxia and vitamin D deficiency were significantly higher than those in the control group (P<0.05). Multivariate logistic regression analysis showed that neonatal asphyxia (OR=2.633, 95%CI: 1.139-6.085) and vitamin D deficiency (OR=4.064, 95%CI: 1.625-10.165) were risk factors for RDS in preterm infants. CONCLUSIONS: Vitamin D deficiency might be associated with increased risk of RDS in preterm infants. Reasonable vitamin D supplementation during pregnancy might reduce the incidence of RDS in preterm infants.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

[Vitamin D level at birth and influencing factors in preterm infants].

OBJECTIVE: To investigate vitamin D level at birth and possible influencing factors in preterm infants. METHODS: A total of 600 preterm infants were enrolled, and venous blood samples were collected within 24 hours after birth to measure the serum level of 25-hydroxyvitamin D [25(OH)D]. The effect of sex, birth weight, birth season, gestational age, mother's age, body mass index (BMI) in early pregnancy, delivery mode, and complications during pregnancy on serum 25(OH)D level was analyzed. RESULTS: The rates of vitamin D deficiency, insufficiency, and sufficiency were 42.0%, 38.7%, and 19.3% respectively. The preterm infants born in summer and autumn had a significantly higher serum 25(OH)D level than those born in winter (P<0.05) and a significantly lower incidence rate of vitamin D deficiency than those born in spring and winter (P<0.003). Compared with those whose mothers were aged <30 years, the infants whose mothers were aged ≥30 years had a significantly higher serum 25(OH)D level (P<0.05) and a significantly lower incidence rate of vitamin D deficiency (P<0.017). Compared with those whose mothers were overweight or had normal body weight, the infants whose mothers were obese had a significantly lower serum 25(OH)D level (P<0.05) and a significantly higher incidence rate of vitamin D deficiency (P<0.006). Compared with those whose mothers had no preeclampsia, the infants whose mothers had preeclampsia during pregnancy had a significantly lower serum 25(OH)D level (P<0.05) and a significantly higher incidence rate of vitamin D deficiency (P<0.017). The multivariate analysis showed that birth in winter and spring, mother's age <30 years, and early-pregnancy BMI ≥28 kg/m2 were risk factors for vitamin D deficiency (P<0.05). CONCLUSIONS: There is a high prevalence of vitamin D deficiency in preterm infants. Vitamin D supplementation should be given to the preterm infants with high-risk factors for vitamin D deficiency.

Computational Investigation into the Interactions of Traditional Chinese Medicine Molecules of WenQingYin with GluR2.

Docking and molecular dynamics simulations have been carried out to investigate the interaction of a traditional Chinese medicine, WenQingYin, with the glutamate receptor 2 (GluR2) subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Four representative drug components of WenQingYin, namely 2-(3,4-dihydroxyphenyl)-5,6,7-trihydroxy-4H-chromen-4-one (PHF), 4-hydroxy-3-methoxybenzoic acid (HMB), 4-(2,3-dihydroxy-3-methylbutoxy)-7H-furo[3,2-g]chromen-7-one (DHMBP) and methyl 7-formylcyclopenta[c]pyran-4-carboxylate (cerbinal), and their complexes with GluR2 were simulated. Our results show that PHF, HMB, and DHMBP formed a partial hydrogen bond with GluR2 in its ligand-binding domain. However, cerbinal was not stable in the ligand-binding domain of GluR2 and induced a significant change in the structure of GluR2. Three-dimensional plots represent the contact and movement situation of the traditional Chinese medicine molecules in the ligand-binding domain. The combined results of the docking and molecular dynamics simulations provide insight into the interaction between these traditional Chinese medicine molecules and proteins.