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BackgroundCognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients.MethodsThis single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment.ResultsThe mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV)

AbstractIntroduction Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future.Methods A total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses.Results The prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including Firmicutes, Actinobacteriota, Proteobacteria, and Bacteroidota. The microbial diversity in the high AAC score group had a decreasing trend (p = 0.050), and the species abundance was significantly lower (p = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of Proteobacteria and decreased abundances of Bacteroidota and Synergistota at the phylum level; increased abundances of Escherichia-Shigella, Ruminococcus_gnavus_group, and Lactobacillus; and decreased abundances of Ruminococcus and Lachnospiraceae_NK4A136_group at the genus level (p

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L−1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L−1), phycoerythrin (102.95 mg L−1), and polysaccharide (1.42 g L−1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.

IntroductionAs a pigment protein, phycocyanin has been widely used in the fields of food, nutraceutical and biotechnology due to its excellent biological activities of antioxidant. So far, Arthrospira has been generally considered as a great species for phycocyanin production.MethodsIn this study, independent and interactive effect of three factors, NaCl, Bainengsi (BS) and Bainengtai (BT) on microalgae growth and phycocyanin production were explored by response surface methodology (RSM). Using Box-Behnken design (BBD) method, the well-fitting quadratic models were established based on experimental results.ResultsMoreover, the maximum phycocyanin concentration reached 704.66 mg L-1 at the optimal condition (185 mM NaCl, 200 mg L-1 BS, and 20 mg L-1 BT), while the maximum phycocyanin content of 19.03% was obtained at another optimal condition (136 mM NaCl, 200 mg L-1 BS, and 50 mg L-1 BT). Compared to control, the concentration and content of phycocyanin were increased by 22.98% and 16.73%, respectively.DiscussionOverall, this study demonstrated that addition of exogenous substances (BS, BT) into culture medium optimized by RSM was an effective approach to increase phycocyanin production, which paved a potential way to realizing high efficient production of algal biomass and bioactive substances.

Thin structural elements such as large-scale covering plates of aerospace protection structures and vertical stabilizers of aircraft are strongly influenced by gravity (and/or acceleration); thus, exploring how the mechanical behaviors of such structures are affected by gravitational field is necessary. Built upon a zigzag displacement model, this study establishes a three-dimensional vibration theory for ultralight cellular-cored sandwich plates subjected to linearly varying in-plane distributed loads (due to, e.g., hyper gravity or acceleration), with the cross-section rotation angle induced by face sheet shearing accounted for. For selected boundary conditions, the theory enables quantifying the influence of core type (e.g., close-celled metal foams, triangular corrugated metal plates, and metal hexagonal honeycombs) on fundamental frequencies of the sandwich plates. For validation, three-dimensional finite element simulations are carried out, with good agreement achieved between theoretical predictions and simulation results. The validated theory is subsequently employed to evaluate how the geometric parameters of metal sandwich core and the mixture of metal cores and composite face sheets influence the fundamental frequencies. Triangular corrugated sandwich plate possesses the highest fundamental frequency, irrespective of boundary conditions. For each type of sandwich plate considered, the presence of in-plane distributed loads significantly affects its fundamental frequencies and modal shapes.

A herbal prescription in traditional Chinese medicine (TCM) has great complexity, with multiple components and multiple targets, making it extremely challenging to determine its bioactive compounds. Yinchenhao Tang (YCHT) has been extensively used for the treatment of jaundice disease. Although many studies have examined the efficacy and active ingredients of YCHT, there is still a lack of an in-depth systematic analysis of its effective components, mechanisms, and potential targets—especially one based on clinical patients. This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform. The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method. Moreover, a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis (IPA). We found that eight active components could modulate five key targets. These key targets were further verified by enzyme-linked immunosorbent assay (ELISA), which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7α-hydroxylase (CYP7A1), multidrug-resistance-associated protein 2 (ABCC2), multidrug-resistance-associated protein 3 (ABCC3), uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and farnesoid X receptor (FXR), and by regulating metabolic pathways including primary bile acid biosynthesis, porphyrin and chlorophyll metabolism, and biliary secretion. Eight main effective compounds were discovered and correlated with the key targets and pathways. In this way, we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.

Purpose: We studied the expression of urotensin II (UII) and its relationships with markers of pyroptosis in preeclampsia. Methods: 48 pregnant subjects were recruited consisting of 28 severe preeclampsia pregnancies (SPE) and 20 healthy pregnancies. We detected expressions of UII and markers of pyroptosis such as NLR-family pyrin domain (PYD)-containing 3 (NLRP-3), caspase-1/4/5, interleukin-1β (IL-1β), and gasdermin D (GSDMD) in placentas of patients with SPE and healthy pregnancies. Results: SPE group have higher expression of UII and NLRP-3, caspase-1, interleukin-1β (IL-1β), and GSDMD than that normal controls by IHC, real-time PCR, and western blot. IHC analysis manifests that the expressions of UII and pyroptosis-related molecules are mainly located in the placental cytotrophoblasts. Expressions of UII mRNA and protein are significantly positively correlated with pyroptosis marker such as NLRP3, caspase-1, GSDMD mRNA and protein by Pearson correlation analysis. Moreover, UII, NLRP-3, caspase-1, interleukin-1β (IL-1β), and GSDMD are positively related with systolic blood pressure, meanwhile caspase-1 and GSDMD are positively correlated with urine protein in SPE patients. We firstly verify that UII has a positive correlation with pyroptosis markers in placentas of preeclampsia patients; besides, pyroptosis-related proteins are positively correlated with systolic blood pressure and urine protein in patients with severe preeclampsia.

Background: Damp-heat jaundice syndrome (DHJS) is a diagnostic model of traditional Chinese medicine (TCM) that refers to jaundice caused by damp-heat pathogen invasion. DHJS is the most common clinical manifestation of TCM, with yellow skin, yellow eyes and anorexia. ZhiziBaipi Decoction (ZBD) is a classic TCM formula that is effective at treating DHJS and various liver diseases. However, the effective components of ZBD in the context of DHJS and the underlying mechanism are unclear.Purpose: This study of ZBD using the DHJS rat model aimed to elucidate the pathobiology of DHJS and the metabolic targets of therapeutic ZBD, construct the network relationship between the components of ZBD and endogenous biomarkers, and clarify the underlying mechanism of ZBD in preventing and treating DHJS.Methods: Using chinmedomics as the core strategy, an animal model was generated, and the therapeutic effect of ZBD was evaluated based on behavioral, histopathological and biochemical indicators. Metabonomics tools were used to identify biomarkers of DHJS, TCM-based serum pharmacochemistry was used to analyze the effective constituents of ZBD, and chinmedomics technology was used to identify ZBD components highly related to DHJS biomarkers.Results: A total of 42 biomarkers were preliminarily identified, and ZBD significantly affected the levels of 29 of these biomarkers. A total of 59 compounds in ZBD were characterized in vivo. According to chinmedomics analysis, the highly correlated components found in blood were isoformononetin, 3-O-feruloylquinic acid, glycyrrhizic acid, oxyberberine, obaculactone and five metabolites.Conclusions: Chinmedomics combined with UPLC-MS/MS was used to study the targets and effective constituents of ZBD for the treatment of DHJS.

Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.

Diabetic retinopathy is one of the serious complications of diabetes, which the leading causes of blindness worldwide, and its irreversibility renders the existing treatment methods unsatisfactory. Early detection and timely intervention can effectively reduce the damage caused by diabetic retinopathy. Metabolomics is a branch of systems biology and a powerful tool for studying pathophysiological processes, which can help identify the characteristic metabolic changes marking the progression of diabetic retinopathy, discover potential biomarkers to inform clinical diagnosis and treatment. This review provides an update on the known metabolomics biomarkers of diabetic retinopathy. Through comprehensive analysis of biomarkers, we found that the arginine biosynthesis is closely related to diabetic retinopathy. Meanwhile, creatine, a metabolite with arginine as a precursor, has attracted our attention due to its important correlation with diabetic retinopathy. We discuss the possibility of the arginine-creatine metabolic pathway as a therapeutic strategy for diabetic retinopathy.

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The etiology and pathogenesis of CRC remain unclear. A growing body of evidence suggests dysbiosis of gut bacteria can contribute to the occurrence and development of CRC by generating harmful metabolites and changing host physiological processes. Metabolomics, a systems biology method, will systematically study the changes in metabolites in the physiological processes of the body, eventually playing a significant role in the detection of metabolic biomarkers and improving disease diagnosis and treatment. Metabolomics, in particular, has been highly beneficial in tracking microbially derived metabolites, which has substantially advanced our comprehension of host-microbiota metabolic interactions in CRC. This paper has briefly compiled recent research progress of the alterations of intestinal flora and its metabolites associated with CRC and the application of association analysis of metabolomics and gut microbiome in the diagnosis, prevention, and treatment of CRC; furthermore, we discuss the prospects for the problems and development direction of this association analysis in the study of CRC. Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.

Si-Miao-Yong-An-Tang (SMYAT) is a classic prescription for the treatment of thromboangiitis obliterans (TAO). However, the effect and mechanism are still unclear. This experiment aims to evaluate the therapeutic effect and mechanism of SMYAT on sodium laurate solution induced thromboangiitis obliterans model rats using urine metabolomics. The therapeutic effect of SMYAT was evaluated by histopathology, hemorheology and other indexes. The urine metabolomic method, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for clustering group and discriminant analysis to screen urine differential metabolic biomarkers, and explore new insight into pathophysiological mechanisms of SMYAT in the treatment of TAO. SMYAT has significant antithrombotic and anti-inflammatory effects, according to the results of urine metabolomic analysis, and regulate the metabolic profile of TAO rats, and its return profile is close to the state of control group. Through metabolomics technology, a total of 35 urine biomarkers of TAO model were characterized. Among them, SMYAT treatment can regulate 22 core biomarkers, such as normetanephrine and 4-pyridoxic acid. It is found that the therapeutic effect of SMYAT is closely related to the tyrosine metabolism, vitamin B6 metabolism and cysteine and methionine metabolism. It preliminarily explored the therapeutic mechanism of SMYAT, and provided a scientific basis for the application of SMYAT.

Introduction: Vascular calcification (VC), with the mechanisms remaining unclear, is closely related with dialysis patients’ cardiovascular mortality and all-cause mortality. Irisin is a newly identified myokine. This study aims to evaluate the serum irisin levels of peritoneal dialysis (PD) patients and their relationship with VC. Methods: This cross-sectional study enrolled stable PD patients in Peking University Third Hospital who were followed for >6 months. We used plain X-ray films of abdomen to quantitatively evaluate VC of abdominal aorta. VC was evaluated by abdominal aortic calcification (AAC) scores, and PD patients were divided into the high AAC score group (AAC score ≥4) and the low AAC score group (AAC score 2.54 mmol/L) rate, serum ultrasensitive C reactive protein, and AAC scores were significantly higher in the high AAC score group than those of the low AAC score group (p < 0.05). The high AAC score group had lower diastolic blood pressure, serum albumin, and serum carbon dioxide combining power compared with the low AAC score group (p < 0.05). Serum irisin levels of PD patients with a high AAC score were significantly lower than those of PD patients with a low AAC score (109.7 ± 13.1 ng/mL vs. 115.9 ± 10.1 ng/mL, p = 0.010). The multivariate logistic regression analyses showed that serum irisin, diabetic mellitus, serum ultrasensitive C reactive protein, and age were independent factors influencing the occurrence of VC in PD patients. Conclusion: Our results are the first to provide a clinical evidence of the association between serum irisin and abdominal aortic calcification in PD patients. Lower irisin levels, diabetic mellitus, higher serum ultrasensitive C reactive protein, and older age could be potential predictive factors for VC in PD patients.

Background: Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN. Objective: Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients. Method: PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis. Results: Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (−) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (−) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer. Conclusion: In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.

Adding organic compounds to wastewater can improve the carbon/nitrogen ratio and benefit microalgae growth. We studied microalgal growth, nutrient removal and lipid accumulation of Chlorella pyrenoidosa cultured in a mixture of swine wastewater (SW) and furfural wastewater (FW). The mix ratio of SW:DFW (diluted furfural wastewater) had a significant effect on microalgae growth. As the mix ratio of SW:DFW decreased from 1:0.5 to 1:19, the maximum microalgal biomass increased, while the specific growth rate initially increased and then decreased. The efficiency of nutrient removal also depended on the mix ratio of wastewater. The highest chemical oxygen demand (COD) removal efficiency (57.30%) occurred at the mix ratio of SW:DFW = 1:3. The highest removal efficiencies of total phosphorous (TP) reached 61.93% when the mix ratio of SW:DFW was 1:9. Wastewater at the mix ratio of SW:DFW = 1:19 had a maximum lipid productivity of 49.48 mg L−1 d−1, which was 4.9 times higher than that at a mix ratio of SW:DFW = 1:0.5. These results showed that C. pyrenoidosa can be used to remove nutrients from mixed wastewater sources and simultaneously produce algal lipids.

Abstract Antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a group of chronic multisystem autoimmune diseases with substantial mortality and morbidity and frequent relapses. The complexity of the disease condition and treatment‐related adverse reactions as well as infections play important roles in the poor outcomes. Unfortunately, the subjective symptoms and objective indicators are not fully parallel, and manifestations between disease activity and treatment‐related adverse reactions are often similar. Here, we describe a case of pulmonary mucormycosis in an old female patient with AAV to highlight these challenges.

Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA is currently used in less than 5% of stroke patients. Natural compounds have been widely used in the treatment of IS in China and have a wide range of therapeutic effects on IS by regulating multiple targets and signaling pathways. The keywords “ischemia stroke, traditional Chinese Medicine, Chinese herbal medicine, natural compounds” were used to search the relevant literature in PubMed and other databases over the past five years. The results showed that JAK/STAT, NF-κB, MAPK, Notch, Nrf2, and PI3K/Akt are the key pathways, and SIRT1, MMP9, TLR4, HIF-α are the key targets for the natural compounds from traditional Chinese medicine in treating IS. This study aims to update and summarize the signaling pathways and targets of natural compounds in the treatment of IS, and provide a base of information for the future development of effective treatments for IS.

Background/Aims: Skeletal muscle atrophy is one of the main manifestations of protein energy wasting. We hypothesized that urotensin II (UII) can lead to skeletal muscle atrophy through upregulating autophagy and affecting Irisin precursor fibronectin type III domain containing 5 (FNDC5) expressions. Methods: Three animal models (the sham operation, wild-type C57BL/6 mice with 5/6 nephrectomy, UII receptor (UT) gene knockout (UTKO) mice with 5/6 nephrectomy) were designed. Skeletal muscle weight, cross-sectional area (CSA) along with UII, FNDC5, LC3, and p62 expression were investigated. C2C12 cells were differentiated for up to 4 days into myotubes. These cells were then exposed to different UII concentrations (10–5 to 10–7 M) for 6–12 h and analyzed for the expressions of autophagic markers. These cells were also exposed to the same predetermined UII concentrations for 48–72 h and analyzed for the FNDC5 expression. Myotube diameter was measured. Results: Upregulation of UII expression in skeletal muscle tissue was accompanied by reduced muscle weight and skeletal muscle CSA in the 2 posterior limbs, upregulated autophagy markers expression, and downregulated FNDC5 expression in 5/6 nephrectomy mice. The decrease of skeletal muscle weight, skeletal muscle CSA, downregulation of FNDC5 expression, and the upregulation of autophagy markers were inhibited in UTKO with 5/6 nephrectomy mice. Our in vitrostudy showed that UII could directly decrease myotube diameter, induce autophagy markers upregulation, and inhibit expression of FNDC5. When UII receptor gene was interfered by UT-specific siRNA, UII induced autophagy markers upregulation and FNDC5 downregulation were inhibited. Conclusion: We are the first to verify UII induces mice skeletal muscle atrophy associated with enhanced skeletal muscle autophagy and inhibited FNDC5 expression in chronic renal failure.

Background: Cardiovascular disease is the leading cause of morbidity and mortality in maintenance hemodialysis (MHD) patients. Uremic cardiomyopathy, characterized by myocardial hypertrophy and fibrosis, has a significant contribution to these adverse cardiac outcomes. The protective effect of soluble Klotho (s-Klotho) on myocardial damage was demonstrated in in vitro and animal experiments. However, data from MHD patients is limited. The present study was designed to identify potential correlations between echocardiographic parameters and serum s-Klotho levels in MHD patients. Methods: This is a cross-sectional study involving 105 MHD patients from the Dialysis Center of Capital Medical University affiliated Beijing Friendship Hospital between March and October 2014. The general information for each patient was recorded. Fasting blood samples were collected prior to hemodialysis during the mid-week session in all patients. The echocardiogram and left lateral lumbar spine radiograph were performed after the same mid-week session. The dialysis records for each session within 3 months before the blood tests were documented. According to the quartiles of s-Klotho levels, patients were divided into four groups (Group 1–4). The demographic and clinical characteristics, echocardiographic parameters, and abdominal aortic calcification scores among the groups were compared. Results: The enrolled 105 patients were predominantly male (54.3%) with an average age of 59.9 ± 11.2 years. Previous hemodialysis durations were 76 (42–133) months. Sixteen (15.2%) patients had diabetes mellitus. Mean serum s-Klotho level was 411.83 ± 152.95 pg/mL, and the 25th percentile, 50th percentile, and 75th percentile values of serum s-Klotho levels were 298.9, 412, and 498.2 pg/mL, respectively. Individuals in the bottom quartile of s-Klotho levels (Group 1) had significantly increased interventricular septal thickness (IVST) compared to those in the other three quartiles of s-Klotho levels (Group 1: 1.12 ± 0.16 cm; vs. Group 2: 1.12 ± 0.16 cm, p = 0.008; vs. Group 3: 0.94 ± 0.13 cm, p < 0.001; vs. Group 4: 1.03 ± 0.1 5 cm, p = 0.022). There were significant differences in the ratios of IVST and posterior wall thickness (PWT) between patients of Group 1 and Group 3 (1.12 ± 0.1 2 vs. 1.00 ± 0.1 4, p = 0.004). No significant differences were found for other parameters among the groups. The univariate correlation analyses showed that gender (r = –0.211, p = 0.030), Kt/V urea (r = –0.240, p = 0.014), hypersensitive C reactive protein (hs-CRP) (r = 0.196, p = 0.045), and serum s-Klotho levels (r = –0.260, p = 0.007) significantly correlated with IVST. Ultimately, only hs-CRP and serum s-Klotho levels were entered into a multiple regression model. Conclusions: The present study showed that patients with lower circulating s-Klotho levels were more often associated with larger IVST and greater ratios of IVST and PWT. There was an independent association between s-Klotho and IVST, and lower s-Klotho levels seem to be a potential risk factor of uremic cardiomyopathy in MHD patients.

Evaluation of the efficacy of traditional Chinese medicines (TCMs) is an important prerequisite for discovering effective substances, lead compounds, and quality markers (Q markers). At present, there is an urgent need to develop a biological language that can act as abridge for the scientific elaboration of the efficacy of TCMs, and to further highlight the significant value of TCM. Chinese medicinal syndromes and formulae are two essential parts of TCM that directly relate to its efficacy. Syndromes and formulae have been taken as the research objects. The serum pharmacochemistry of the TCM approach with metabolomics were integrated to establish an innovative chinmedomics strategy, which is able to explore syndrome biomarkers and evaluate TCM efficacy in order to discover effective substances from TCMs. A great deal of concrete work in chinmedomics has already performed to bridge the gap between Chinese and Western medicine, and to provide a powerful approach to enhance the scientific value of TCM theory and clinical practice. This article summarizes the application of chinmedomics in identifying the candidate biomarkers of a syndrome and revealing the efficacy of the related formula. We also highlight the discovery of lead compounds and Q markers from TCMs. Keywords: Chinmedomics, Serum pharmacochemistry of TCM, Efficacy, Metabolomics, Syndrome, Biomarkers, Quality markers

Idiopathic pulmonary fibrosis (IPF), characterized by excessive collagen deposition, is a progressive and typically fatal lung disease without effective therapeutic strategies. Juglanin, as a natural product mainly isolated from green walnut husks of Juglans mandshuric, has various bioactivities, including anti-oxidative, anti-inflammatory and anti-fibrotic effects. Stimulator of interferon genes (Sting) is a signaling molecule and plays an essential role in meditating fibrosis. However, the effects of Jug and Sting on pulmonary fibrosis are not fully understood. In this study, we investigated the role of Jug in bleomycin (BLM)-induced inflammation and fibrosis mouse model, as well as the underlying molecular mechanism. The results here indicated that Jug-treated mice exhibited a definitively improved survival rate than that of the BLM-challenged mice. Jug administration significantly alleviated neutrophil alveolar infiltration, lung vascular permeability and pro-inflammatory response in BLM mice. Subsequently, the pulmonary fibrosis induced by BLM was markedly attenuated by Jug through reducing the expression of fibrotic hallmarks, including transforming growth factor-β1 (TGF-β1), fibronectin, matrix metallo-proteinase-9 (MMP-9), α-smooth muscle actin (α-SMA) and collagen I. Importantly, we found that BLM mice showed higher expression levels of Sting in lung tissues, which were notably restrained by Jug treatment. The role of Jug in suppressing Sting was confirmed in TGF-β-incubated cells. Notably, the in vitro analysis further showed that Sting knockdown could ameliorate TGF-β-triggered collagen accumulation. In contrast, TGF-β-induced fibrosis was accelerated by Sting over-expression. Therefore, BLM may induce lung fibrosis through activating Sting signaling, and Jug could be used therapeutically to improve tissue repair and attenuate the intractable disease.

Both plants and animals are living things made up of similar cells as well as organelles, and their essence of life is the same. However, plants face more environmental stress than animals and generate excessive reactive oxygen species (ROS), a group of small molecules that can harm proteins, necessitating distinctive metabolic processes. Secondary metabolites in plants are a group of chemical components that can eliminate ROS and can also exhibit medicinal properties; therefore, herbal medicines are often closely linked to the ecological significance of secondary metabolites. Why plants contain so many, not few, active medicinal ingredients is unknown. The root of Scutellaria baicalensis, a popular herbal medicine, is rich in various flavonoids with diverse structural features. Sodium hydrosulfite (Na2S2O4) can produce O˙-2 radicals and induce physical conditions under environmental stress. Using UHPLC-ESI-Q-TOF-MS/MS analysis, a total of 25 different compounds were identified in the roots of S. baicalensis between the Na2S2O4 groups and suitable conditions. Based on the results of the t-test (P

Background/Aims: Vascular calcification, which involves an active cellular transformation of vascular smooth muscle cells into bone forming cells, is prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that irisin, a newly identified myokine also may play roles in vascular calcification in hemodialysis patients. This study aims to evaluate serum irisin levels and establish their relation to vascular calcification and other parameters in hemodialysis patients. Methods: A total of 150 patients on maintenance hemodialysis treatment and 38 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentrations were measured by ELISA. Vascular calcification was evaluated by abdominal aortic calcification scores. Results: Serum irisin concentrations were significantly lower in hemodialysis patients than in controls [52.8 (22.0, 100.0) vs. 460.8 (434.8, 483.4) ng/ml, P

Background/Aims: Protein energy wasting (PEW) is a common medical phenomenon that is observed in maintenance dialysis patients. PEW also increases morbidity and mortality of these patients. Its pathogenesis is unclear. We hypothesize that serum irisin levels and volume overload may induce PEW in peritoneal dialysis (PD) patients. The aim of this study is to measure serum irisin levels, evaluate volume status of PD patients, and study their correlations with PEW in PD patients. Methods: This study is a cross-sectional study with 160 PD patients from the PD center of Peking University Third Hospital and 35 healthy control subjects. PD patients were divided into PEW group and non-PEW group according to PEW diagnosis criteria. Serum irisin concentrations were measured by ELISA. Volume overload status (volume overload is defined as overhydration value ≥2 liters) of PD patients was analyzed by bioelectrical impedance. Results: The serum irisin levels were significantly lower in PD patients compared with those of the controls (113.2±11.8 ng/ml vs. 464.2±37.4 ng/ml, P

Abstract Objective To evaluate the in vivo and in vitro performance of a China-made dialysis machine (SWS-4000). Methods This was a multi-center prospective controlled study consisting of both long-term in vitro evaluations and cross-over in vivo tests in 132 patients. The China-made SWS-4000 dialysis machine was compared with a German-made dialysis machine (Fresenius 4008) with regard to Kt/V values, URR values, and dialysis-related adverse reactions in patients on maintenance hemodialysis, as well as the ultrafiltration rate, the concentration of electrolytes in the proportioned dialysate, the rate of heparin injection, the flow rate of the blood pump, and the rate of malfunction. Results The Kt/V and URR values at the 1st and 4th weeks of dialysis as well as the incidence of adverse effects did not differ between the two groups in cross-over in vivo tests (P > 0.05). There were no significant differences between the two groups in the error values of the ultrafiltration rate, the rate of heparin injection or the concentrations of electrolytes in the proportioned dialysate at different time points under different parameter settings. At weeks 2 and 24, with the flow rate of the blood pump set at 300 mL/min, the actual error of the SWS-4000 dialysis machine was significantly higher than that of the Fresenius 4008 dialysis machine (P 0.05). The malfunction rate was higher in the SWS-4000 group than in the Fresenius 4008 group (P

The aims of this study are to observe irisin and urotensin II (UII) levels in serum and placenta in normal pregnant and preeclamptic women and investigate the relationship between expressions irisin and UII, and their association with blood pressure. A total of 67 pregnant subjects were recruited, including 31 healthy and 36 preeclamptic pregnant women. Serum irisin and UII concentrations were measured. Expressions of fibronectin type III domain-containing protein 5 (FNDC5) (irisin precursor) and UII in placenta specimens were performed. There was no significant difference of serum irisin levels between severe preeclamptic (SPE)) patients, mild preeclamptic (MPE) patients and normal controls, while serum UII was significantly higher in preeclamptic women than normal pregnancy. There was no relationship between serum UII and irisin levels. In patients with preeclampsia, serum irisin was negatively associated with systolic and diastolic blood pressure(r = −0.350, P = 0.004, r = −0.307, P = 0.011), while serum UII was positively associated with systolic blood pressure (r = 0.291, P = 0.031). Serum irisin, UII, urinary protein level, BMI and serum creatinine were the independent determinants of blood pressure in preeclampsia by multiple regression analysis. Protein expression of FNDC5 and UII was upregulated in placenta of patients with SPE and positively correlated with systolic blood pressure and urinary protein level. We firstly verify that serum irisin and placental irisin precursor expressions have differently correlated with blood pressure. Expressions of irisin and urotensin II have relationships with blood pressure in patients with preeclampsia

The title compound, C22H24N2O7S·0.5C2H5OH·0.5H2O {systematic name: (S)-4-acetamido-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindoline-1,3-dione ethanol hemisolvate hemihydrate}, is a novel solvatomorph of apremilast (AP), which is an inhibitor of phosphodiesterase 4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The asymmetric unit contains one molecule of AP and disordered molecules of ethanol and water, both with half occupancy. The dihedral angle between the planes of the phenyl ring and the isoindole ring is 67.9 (2)°. Extensive intra- and intermolecular hydrogen bonds help to stabilize the molecular conformation and sustain the crystal packing.

Background: Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death. Methods: Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality. Results: In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094–1.886), age (OR: 1.046, 95% CI: 1.036–1.057), and presence of DN (OR: 1.837, 95% CI: 1.322–2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346–0.989), hemoglobin (OR: 0.974, 95% CI: 0.967–0.981), albumin (OR: 0.939, 95% CI: 0.915–0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070–0.386) were protective factors based on a multivariate analysis. Conclusions: Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Traditional Chinese medicine (TCM), an ancient medical system, has the advantages of multi-targeting and multi-ingredient preparations, and is different from modern pharmacology. However, because of the complexity of TCM and the limitation of present investigation method, the research for deciphering the scientific basis and systematic features of TCM is difficult to go further. Metabolomics has a significant increased study in recent years and enables mapping of early biochemical changes in disease and hence provides an opportunity to develop predictive biomarkers. Moreover, its method and design resemble those of traditional Chinese medicine. Therefore, it can provide useful tools for exploring essence of TCM, and will help to in-depth understand Chinese medicine syndromes. In this mini-paper, particular attention will be paid to the past successes in applications of robust metabolomics to contribute to small metabolites discovery in TCM development.

Postmenopausal osteoporosis (PMOP) is a common clinical illness in postmenopausal women, but there is no effective drug at present. Metabolomics approach was used to explore the potential biomarkers of PMOP and evaluate the efficacy and therapeutic targets of total lignans in the stem of Acanthophanax senticosus (ASSL) on the ovariectomized osteoporosis model rats. UPLC/MS and pattern recognition methods were used for serum metabolites discovery to illustrate the pathological mechanism of PMOP model rats, and then revealing the intervention effect of ASSL. The pattern recognition result showed that serum metabolic profiles of the sham operation group and the model group were clustered clearly, and 16 potential biomarkers were finally identified (7 in positive ion mode and 9 in negative ion mode), and they are involved in 15 related metabolic pathways. After oral administration of ASSL, 10 biomarkers were found to be significantly up-regulated and mainly regulated metabolic pathways include unsaturated fatty acid biosynthesis, linoleic acid metabolism, and arachidonic acid metabolism, primary bile acid synthesis, tyrosine metabolism, etc. Our study demonstrated that the ASSL could affect the endogenous metabolites related metabolic mechanism, provides a pharmacological basis of the ASSL for PMOP treatment.

Background/Aims: Urotensin II (UII) and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN). The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress) and Epithelial-mesenchymal transition (EMT) in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1), fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

Aims/Introduction: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients. Materials and Methods: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. Results: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting. Conclusions: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients.

Traditional Chinese medicine (TCM) has been widely used in many oriental countries for thousands of years and played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. It is a very complex mixture containing hundreds or thousands of different components. Pharmacokinetic study on active constituents in TCM preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. In the drug discovery phases, pharmacokinetics is a key to guide medicinal chemists in the optimization process of a chemical series and to assist pharmacologists to design in vivo studies. To explore the potentially bioactive components in TCM, it is necessary to further study the in vivo pharmacokinetic characteristics of multiple absorbed components and find out the optical time-course behavior to providing more substantial research for new leads in drug discovery. Pharmacokinetics screening method could provide a reliable means of prospecting natural products in the search for new leads in drug discovery. This review summarizes the research progress of PK on TCM in the search for suitable lead compounds in recent years.

Metabolomics, an omic science in systems biology, is the comprehensive profiling of metabolic changes occurring in living systems and has been widely used in the modern research of traditional Chinese medicine (TCM). TCM is a complex medical science, which reflects rich philosophical dialectical thought, puts the human body into a large system for observation and keeps human in a healthy status. For TCM aroused great interest in the whole world, herbs and Chinese medical formulae (CMF) as treatment methods have also been widely attention. Metabolomics represents a powerful way that provides a dynamic drawing of the phenotype of biological systems via the research of endogenous metabolites, and its methods are similar to those of TCM. This review summarizes the advantages of metabolomics, highlight the key role of biomarkers for drug discovery and development of TCM.

Herbal medicines may benefit from metabolomics studies, and applying metabolomics may provide answers about which herbal interventions may be effective for individuals, which metabolic processes are triggered, and the subsequent chemical pathways of activity. Physalis pubescens L (PPL) is an herbal fruit for one year living plant and has been developed into healthy function's food. However, the mechanisms of health functions are still unclear. To comprehensively and holistically assess its anti-fatigue and antioxidant effects, a novel integrative metabolomics approach was applied. In this study, we present metabolomics analysis applying ultra performance liquid chromatography coupled to quadrupole with time-of-flight mass spectrometry (UPLC-Q/TOF-MS) to determine metabolite alterations after oral administration PPL to rats. Fifteen metabolites in urine were identified as potential biomarkers. Pattern analysis of the UPLC-Q/TOF-MS data disclosed that PPL could relieve fatigue rats by ameliorating the disturbance in amino acids metabolism and energy metabolism, alleviating the oxidative stress from reactive oxygen species and the inflammatory damage, and recovering the destructed regulation. Based on these results, we demonstrated that PPL is a promising source of natural anti-fatigue and antioxidants material for use in functional foods and medicines.

In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten (ochratoxin A, OTA) was coupled to ovalbumin (OVA) by an active ester reaction. To develop a technique for detecting the conjugation, the hapten-protein conjugate (OTA-OVA) was characterized thoroughly by immunoarray technology, ultraviolet (UV) spectroscopy and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), respectively. The molecular weight of OTA-OVA was 50 350.141 Da, and the molecular weight of OVA was 44 887.506 Da, which were determined by MALDI-TOF-MS, respectively. In OTA-OVA, the molecular coupling ratio was 13:1 by MALDI-TOF-MS while the molecular coupling ratio was 10:1 by UV. In this experiment, UV and MALDI-TOF-MS were selected as the efficient methods to evaluate the cross-linking effect and calculate the molecular coupling ratio.

With lipid level being a major contributing factor for cardiovascular health, the high cardiovascular mortality among dialysis patients has raised substantial concerns in regard to the optimal lipid level in these patient population.To explore the optimal lipid level for the survival of dialysis patients.The lipid profile was measured for each patient. All participants were followed throughout the course of the study. Cox proportional hazards analysis was performed to analyze the prognostic value of lipid level on the survival of these patients.In our study that included 311 stable maintenance dialysis patients, 54.98% of the participants had LDL-C level ≥100 mg/dl and 82.91% of the patients with triglycerides ≥200 mg/dl had non-HDL level ≥130 mg/dl. During the follow-up period of 48.0 (18.0, 55.5) months, 149 (47.91%) participants died. Among those who died, 59 patients died of cardiovascular disease (CVD) and 33 patients died of ischemic CVD (12.0, 4.7, and 2.7 events per 100 patient-years, respectively). Patients with LDL-C 100-130 mg/dl or non-HDL 130-160 mg/dl had a lower all-cause mortality rate than those who did not meet these criteria. After adjusting for the traditional and ESRD-related risk factors, non-HDL was found to be the independent risk factor for the all-cause mortality. Compared to those patients with non-HDL 130-160 mg/dl, patients with non-HDL

Astragalus membranaceus (Fisch.) Bge (AR), one of the most important medicinal plants in Asia, was found to exhibit various bioactivities. Due to limited genomic and transcriptomic data, the biosynthetic pathway of the major bioactive compound in AR, is currently unclear. In this study, 454 GS FLX technology was employed to produce a substantial expressed sequence tag (EST) dataset from the AR. In all, 742721 high-quality reads from the AR were produced using Roche GS FLX Titanium. A total of 9893 unique sequences were obtained and annotated by a similarity search against the public databases, and involved in the secondary metabolic pathway, which would facilitate deciphering the molecular mechanism of secondary metabolism in AR. The assembled sequences were annotated with gene names and Gene Ontology (GO) terms. GO revealed the unique sequences that could be assigned to 34 vocabularies. In the KEGG mapping, unique sequences were established as associated with 46 biochemical pathways. These results provided the largest EST collections in AR and will contribute to biosynthetic and biochemical studies that lead to drug improvement. With respect to the genes related to metabolism and biosynthesis pathway were also found. Our work demonstrated the utility of 454 GS FLX as a method for the rapid and cost-effective identification of AR transcriptome, and this EST dataset will be a powerful resource for further studies such as taxonomy, molecular breeding, and secondary metabolism in AR.

Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells.

Background: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS. Methods: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied. Results: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)--these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001). Conclusion: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment. [ABSTRACT FROM AUTHOR]