Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors.

Sortase A (SrtA) is a membrane-associated cysteine transpeptidase required for bacterial virulence regulation and anchors surface proteins to cell wall, thereby assisting biofilm formation. SrtA is targeted in antivirulence treatments against Gram-positive bacterial infections. However, the development of potent small-molecule SrtA inhibitors is constrained owing to the limited understanding of the mode of action of inhibitors in the SrtA binding pocket. Herein, we designed and synthesized a novel class of covalent SrtA inhibitors based on the binding mode detailed in the X-ray crystal structure of the ML346/Streptococcus pyogenes SrtA complex. ML346 analog Y40 exhibited 2-fold increased inhibitory activity on Staphylococcus aureus SrtA and showed superior inhibitory effects on biofilm formation in vitro. Y40 protected Galleria mellonella larvae fromS. aureusinfections in vivo while minimally attenuating staphylococcal growth in vitro. Our study indicates that the covalent SrtA inhibitor Y40 is an antivirulence agent that is effective againstS. aureusinfections.

Explore the durability of repetitive transcranial magnetic stimulation in treating post-traumatic stress disorder: An updated systematic review and meta-analysis.

The objective was to synthesize results from studies that assessed symptom relief after repetitive transcranial magnetic stimulation (rTMS) treatment for post-traumatic stress disorder (PTSD) and investigate the long-term effectiveness of rTMS for treating PTSD. We searched multiple databases for relevant randomized controlled trials of rTMS for PTSD treatment up to 1 January 2023. Two researchers evaluated the studies and focused on the CAPS and PCL as outcome indicators. We used STATA17 SE software for the data analysis. Eight articles involving 309 PTSD patients were analysed in a meta-analysis, which found that rTMS had a significant and large effect on reducing core post-traumatic symptoms [Hedges'g = 1.75, 95% CI (1.18, 2.33)]. Both low and high-frequency rTMS also significantly reduced symptoms, with the latter having a greater effect. rTMS was shown to have a long-term effect on PTSD, with all three subgroup analyses demonstrating significant results. Interestingly, no significant difference in symptom relief was found between the follow-up and completion of treatments [Hedges'g = 0.01, 95% CI (-0.30, 0.33)], suggesting that the treatment effect of rTMS is stable. The meta-analysis provides strong evidence that rTMS is effective in reducing the severity and symptoms of PTSD in patients, and follow-up studies confirm its long-term stability.

Preservation vs. dissection of inferior pulmonary ligament for thoracoscopic upper lobectomy: a prospective randomized controlled trial.

OBJECTIVES: The proper procedure for inferior pulmonary ligament (IPL) during upper lobectomy remains a topic of debate. To address this matter, we carried out a trial comparing the clinical outcomes of IPL preservation versus IPL dissection during thoracoscopic upper lobectomy (TUL). METHODS: Patients undergoing thoracoscopic left/right upper lobectomy (TLUL/TRUL) were assigned to either the dissection group (Group D) or the preservation group (Group P). Our primary objective was to quantify and compare the alterations in postoperative residual bronchial angle and lung volume changes between the two groups. Our secondary objective encompassed the assessment of various other intraoperative and postoperative outcomes. RESULTS: Following adherence to the inclusion and exclusion criteria, we enrolled 100 patients (41 left and 59 right) in Group P and 108 patients (41 left and 67 right) in Group D for the study. Our findings revealed that in TLUL, Group P was able to reduce the degree of postoperative residual bronchial angle change (P < 0.05). Conversely, the situation was distinct for TRUL. We found no notable disparity between the two groups (P > 0.05) with regard to alterations in lung volume or the occurrence of postoperative complications-except for the duration of postoperative hospital stay (P < 0.05). CONCLUSIONS: Our study suggests IPL preservation especially for TLUL when compared to TRUL, which have important implications for the clinical management of patients undergoing upper lobectomy.

Gasdermin D protects against Streptococcus equi subsp. zooepidemicus infection through macrophage pyroptosis.

Streptococcus equi subsp. zooepidemicus (S. zooepidemicus, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. Gasdermin D (GSDMD) is involved in cytokine release and cell death, indicating an important role in controlling the microbial infection. This study investigated the protective role of GSDMD in mice infected with SEZ and examined the role of GSDMD in peritoneal macrophages in the infection. GSDMD-deficient mice were more susceptible to intraperitoneal infection with SEZ, and the white pulp structure of the spleen was seriously damaged in GSDMD-deficient mice. Although the increased proportion of macrophages did not depend on GSDMD in both spleen and peritoneal lavage fluid (PLF), deficiency of GSDMD caused the minor release of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) during the infection in vivo. In vitro, SEZ infection induced more release of IL-1ß, IL-18, and lactate dehydrogenase (LDH) in wild-type macrophages than in GSDMD-deficient macrophages. Finally, we demonstrated that pore formation and pyroptosis of macrophages depended on GSDMD. Our findings highlight the host defense mechanisms of GSDMD against SEZ infection, providing a potential therapeutic target in SEZ infection.

Caspase-1 deficiency impairs neutrophils recruitment and bacterial clearance in Streptococcus equi ssp. zooepidemicus infected mice.

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus, SEZ) is a zoonotic bacterial pathogen that can cause various inflammation, including pneumonia. As the most abundant leukocytes in the circulation, neutrophils are the first wave of leukocytes to arrive in the lung upon infection. This study aims to evaluate the effect of caspase-1 on the host response to SEZ infection in a mouse model. Intranasal exposure to SEZ induced the expression of caspase-1 in wild-type mice lung, and increased the number of neutrophils in the alveolar cavity and alveolar wall. In addition, caspase-1 deficiency reduced the transcription levels of IL-1α, IL-1ß, IL-6, and TNF-α in the lungs of infected mice, which was accompanied by decreased recruitment of pulmonary neutrophils. Moreover, knocking out caspase-1 decreased the bactericidal activity of neutrophils and promoted the pulmonary bacterial load. In line with this, the mortality of caspase-1-/- mice infected with SEZ was significantly increased compared with those of caspase-1+/+ mice. Collectively, recruiting neutrophils and enhancing the bactericidal ability of neutrophils are important means for caspase-1 to promote bacterial clearance.

Risk Factors Associated With Abnormal Urinalysis in Children.

Background: Targeted urinalysis has been suggested to improve screening efficiency in adults. However, there is no well-defined target population in children yet, with limited information on the risk factors for urinalysis abnormalities. Methods: Children from infants to 17 years old were randomly selected. Dipstick urinalysis was initially performed. Among those who were abnormal, a repeat dipstick or dipstick with microscopic urinalysis was performed for confirmation. Results: In total, 70,822 children were included, with 37,866 boys and 32,956 girls. Prevalence of abnormal urinalysis was 4.3%. Age was significantly associated with abnormal urinalysis, with the highest prevalence among 12-14-year-olds. Girls were 2.0 times more likely to exhibit abnormalities. Compared with children whose guardians had a college degree or higher, those whose guardians had a high school degree or lower had a higher likelihood of abnormalities. Geographic location was also associated with abnormal results. Conclusion: Girls, children aged 12-14 years old, and children whose guardians had a low educational level and children in certain geographic locations were significantly associated with abnormal urinalysis. Identification of children at high risk would contribute to targeted urinalysis screening.

Performance of zinc oxide quantum dots coated paper and application of fluorescent anti-counterfeiting.

Fluorescent anti-counterfeiting is one of the most widely used anti-counterfeiting technologies at present. The demand to develop new anti-counterfeiting materials and technology is more and more urgent. Zinc oxide quantum dots (ZnO QDs) have superior fluorescent properties under ultraviolet light, making them a suitable replacement for traditional phosphors for anti-counterfeiting printing, which is environmentally friendly and meets the needs of sustainable development. In this paper, water-soluble ZnO QDs with an average particle size of 5.64 nm were prepared. Paper coated by ZnO QDs was obtained after ultrasonic treatment, which could emit bright yellow fluorescence when excited by ultraviolet light. As the concentration of ultrasonic solution is increased, the loading amount of ZnO QDs on the coated paper increased gradually, reaching the maximum when the concentration is increased to 1molL-1, which then does not change with an increase in concentration. The fluorescent intensity of the coated paper was consistent with the changing trend of the loading amount. The coated paper has excellent optical stability, is easy to recycle, and provides simple identification of authenticity by ultraviolet light and anti-copy functionality. Their application in packaging and printing is of great significance to the development of complex, concealed and non-repeatable anti-counterfeiting technology.

Synthesis and performance of ZnO quantum dots water-based fluorescent ink for anti-counterfeiting applications.

In this study, the ZnO quantum dots (QDs) water-based fluorescent anti-counterfeiting ink was prepared with the polyvinylpyrrolidone (PVP) content of 0.15-0.17 g/mL, the ZnO QDs concentration of 4% and water as the solvent, which has good fluorescence, printability and resistance. According to the halftone technology, fluorescence quenching of the ZnO QDs by acid, and acid resistance of the organic fluorescent ink, a high-quality anti-counterfeiting method of fluorescent discoloration was proposed. The QDs ink has broad application prospects in the field of anti-counterfeiting green packaging.

Noninvasive Prediction of TERT Promoter Mutations in High-Grade Glioma by Radiomics Analysis Based on Multiparameter MRI.

OBJECTIVES: To investigate the predictors of telomerase reverse transcriptase (TERT) promoter mutations in adults suffered from high-grade glioma (HGG) through radiomics analysis, develop a noninvasive approach to evaluate TERT promoter mutations. METHODS: 126 adult patients with HGG (88 in the training cohort and 38 in the validation cohort) were retrospectively enrolled. Totally 5064 radiomics features were, respectively, extracted from three VOIs (necrosis, enhanced, and edema) in MRI. Firstly, an optimal radiomics signature (Radscore) was established based on LASSO regression. Secondly, univariate and multivariate logistic regression analyses were performed to investigate important potential variables as predictors of TERT promoter mutations. Besides, multiparameter models were established and evaluated. Eventually, an optimal model was visualized as radiomics nomogram for clinical evaluations. RESULTS: 6 radiomics features were selected to build Radscore signature through LASSO regression. Among them, 5 were from necrotic VOIs and 1 was from enhanced ones. With univariate and multivariate analysis, necrotic volume percentages of core (CNV), Age, Cho/Cr, Lac, and Radscore were significantly higher in TERTm than in TERTw (p < 0.05). 4 models were built in our study. Compared with Model B (Age, Cho/Cr, Lac, and Radscore), Model A (Age, Cho/Cr, Lac, Radscore, and CNV) has a larger AUC in both training (0.955 vs. 0.917, p = 0.049) and validation (0.889 vs. 0.868, p = 0.039) cohorts. It also has higher performances in net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) evaluation. Conclusively, Model A was visualized as a radiomics nomogram. Calibration curve shows a good agreement between estimated and actual probabilities. CONCLUSIONS: Age, Cho/Cr, Lac, CNV, and Radscore are important indicators for TERT promoter mutation predictions in HGG. Tumor necrosis seems to be closely related to TERT promoter mutations. Radiomics nomogram based on multiparameter MRI and CNV has higher prediction accuracies.

Evaluating the inflammatory activity in Crohn's disease using magnetic resonance diffusion kurtosis imaging.

OBJECTIVES: To explore the feasibility of diffusion kurtosis imaging (DKI) for evaluating inflammatory activity in Crohn's disease (CD). MATERIALS AND METHODS: In all, 51 CD patients were included, who were performed with consecutive enteroscopy, MR and DKI (b values = 0-2000 mm2/s). The lesions of bowel segments were graded as inactive (0-2), mild (3-6), and moderate-severe group (> 6) based on simplified endoscopic activity score for Crohn's disease (SES-CD), The abilities of the parameters of DKI and DWI in grading different activity lesions were compared. RESULTS: One hundred and twenty-seven bowel segments including inactive (15), mild (45) and moderate-severe (67) were analyzed. ADC (r = - 0.627, p < 0.001), Dapp (r = - 0.381, p < 0.001) and Kapp (r = 0.641, p < 0.001) were correlated with SES-CD. These parameters were significantly different among the three groups (all p < 0.001). ROC analysis found ADC had the highest accuracy (AUC = 0.884, p < 0.001) to differentiate inactive from active group with the threshold at 0.865 × 10-3 mm2/s, which was slightly higher than Kapp (AUC = 0.867, p < 0.001) with the threshold at 0.645, and was obviously higher than Dapp (AUC = 0.726, p = 0.005). Similarly, ADC also had the highest accuracy (AUC = 0.846, p < 0.001) to differentiate inactive-mild from moderate-severe group with the threshold at 0.825 × 10-3 mm2/s, and minimally higher than Kapp (AUC = 0.843, p < 0.001) with the threshold at 0.695, and obviously higher than Dapp (AUC = 0.690, p < 0.001). CONCLUSION: DKI is feasible and comparable to conventional DWI for the evaluation of inflammatory activity in CD.

Diagnostic value of negative enrichment and immune fluorescence in situ hybridization for intraperitoneal free cancer cells of gastric cancer.

OBJECTIVE: To explore the intraperitoneal free cancer cell (IFCC) detection value of negative enrichment and immune fluorescence in situ hybridization (NEimFISH) on chromosomes (CEN) 8/17. METHODS: To verify the reliability of NEimFISH, 29 gastric cancer tumors, their adjacent tissues and greater omental tissues were tested. Our study then included 105 gastric cancer patients for IFCC. We defined patients as IFCC-positive if a signal was detected, regardless of the detailed cancer cell numbers. A comparison of clinicopathological features was conducted among IFCC groups. We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods. The comparison of IFCC number was also conducted among different groups. RESULTS: A cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97% of malignant tissue samples in our study. Compared to intestinal gastric cancer, patients with diffuse gastric cancer tended to have more IFCCs (6 vs. 4, P=0.002). The IFCC counts were often higher in the lymphovascular invasion positive group than negative group (3 vs. 1, P=0.022). All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH. When compared to conventional cytology and paraffin pathology, NEimFISH had a higher IFCC positive rate (68.9%) and higher one-year peritoneal recurrence predictive value with area under the curve (AUC) of 0.922. CONCLUSIONS: Gastric cancer could be effectively diagnosed by NEimFISH. The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer. NEimFISH is a reliable detection modality with a higher positive detection rate, higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.

Corrigendum to "Computed Tomography Enterography: Quantitative Evaluation on Crohn's Disease Activity".

[This corrects the article DOI: 10.1155/2018/7351936.].

Computed Tomography Enterography: Quantitative Evaluation on Crohn's Disease Activity.

OBJECTIVE: To explore the feasibility of computed tomography enterography (CTE) in the quantitative evaluation of the activity of Crohn's disease (CD). METHODS: There were 49 CD patients with whole clinical, enteroscopy, and CTE data to be analyzed retrospectively. The patients were graded as inactive (0-2), mild (3-6), and moderate-severe group (>6) based on simplified endoscopic activity score for Crohn's disease (SES-CD). The differences in bowel wall thickening, mural hyperenhancement in the portal vein period, and the ΔCT values were analyzed among groups using ANOVA (analysis of variance) and q test. Then, the parameters were correlated with SES-CD, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: In the 49 patients, 13 ones were inactive, 19 ones were mild, and 17 ones were moderate-severe; the thickness of bowel wall, mural hyperenhancement in the portal vein period, and ΔCT value among groups were all significantly different (P < 0.001 in all). Correlative analysis showed that compared with the SES-CD, the bowel wall thickening (r = 0.564, P < 0.001), mural hyperenhancement in the portal vein period (r = 0.585, P < 0.001), and ΔCT value (r = 0.533, P < 0.001) were moderately correlated. CONCLUSION: The mural hyperenhancement in the portal vein period, bowel wall thickening, and ΔCT value can accurately and quantitatively assess the activity of CD lesions and are potential visual biomarkers of CD lesions.

Inadequate iron stores in early term neonates.

OBJECTIVE: To characterize neonatal iron stores depending on gestational age (GA) at term. STUDY DESIGN: Participants were 751 mother-newborn pairs from the placebo arm of a randomized clinical trial of prenatal iron-folate supplementation in China. We compared mean cord serum ferritin (SF) by weeks GA and, following the general linear model, assessed whether maternal iron deficiency (ID) influenced relations between GA and cord SF. RESULTS: Controlling for covariates, cord SF increased between 37 and 41 weeks (ps < 0.05-0.01). Cord SF was lower in infants of ID vs. non-ID mothers (geometric mean 96.3 [95% CI: 91.3-101.6] µg/L vs. 115.9 [95% CI: 105.0-127.8] µg/L, effect size = 0.33 SD, p = 0.0012). There was no significant increase with GA among infants of ID mothers. For non-ID mothers, cord-blood SF increased sharply with GA until 38 5/7 weeks, after which it plateaued. CONCLUSIONS: The findings emphasize that neonates at 37-38 weeks, although considered term, are not fully mature.

Transferrin and tocopheryl-polyethylene glycol-succinate dual ligands decorated, cisplatin loaded nano-sized system for the treatment of lung cancer.

Nanocarriers decorated with different ligands were used to achieve lung cancer treatment. Surface decoration of nanoparticulate system will assist in targeting the drug to specific tumor cells and tissues. The aim of this research was to develop a dual ligands decorated nanocarriers (NCs), which could increase the cell uptake and anti-tumor efficiency. Two different ligands: Transferrin (Tf) and D-α-tocopheryl polyethylene glycol succinate (TPGS) containing ligands were synthesized. Dual ligands decorated nanocarriers (DL-NCs) was constructed. The in vitro cytotoxicity, in vivo biodistribution, and in vivo antitumor efficacy of the DL-NCs were evaluated. DL-NCs can efficiently deliver cisplatin (CDDP) into lung cancer cells in vitro and reduced xenograft tumor size in vivo. The encapsulation of CDDP in the DL-NCs significantly improved the cytotoxicity and antitumor efficacy. DL-NCs held great potential for achieving an optimal therapeutic effect in the treatment of lung cancer.

Towards Integrating Distributed Energy Resources and Storage Devices in Smart Grid.

Internet of Things (IoT) provides a generic infrastructure for different applications to integrate information communication techniques with physical components to achieve automatic data collection, transmission, exchange, and computation. The smart grid, as one of typical applications supported by IoT, denoted as a re-engineering and a modernization of the traditional power grid, aims to provide reliable, secure, and efficient energy transmission and distribution to consumers. How to effectively integrate distributed (renewable) energy resources and storage devices to satisfy the energy service requirements of users, while minimizing the power generation and transmission cost, remains a highly pressing challenge in the smart grid. To address this challenge and assess the effectiveness of integrating distributed energy resources and storage devices, in this paper we develop a theoretical framework to model and analyze three types of power grid systems: the power grid with only bulk energy generators, the power grid with distributed energy resources, and the power grid with both distributed energy resources and storage devices. Based on the metrics of the power cumulative cost and the service reliability to users, we formally model and analyze the impact of integrating distributed energy resources and storage devices in the power grid. We also use the concept of network calculus, which has been traditionally used for carrying out traffic engineering in computer networks, to derive the bounds of both power supply and user demand to achieve a high service reliability to users. Through an extensive performance evaluation, our data shows that integrating distributed energy resources conjointly with energy storage devices can reduce generation costs, smooth the curve of bulk power generation over time, reduce bulk power generation and power distribution losses, and provide a sustainable service reliability to users in the power grid.

Emergency control system based on the analytical hierarchy process and coordinated development degree model for sudden water pollution accidents in the Middle Route of the South-to-North Water Transfer Project in China.

Water transfer projects are important for realizing reasonable allocation of water resources, but once a water pollution accident occurs during such a project, the water environment is exposed to enormous risks. Therefore, it is critical to determine an appropriate emergency control system (ECS) for sudden water pollution accidents that occur in water transfer projects. In this study, the analytical hierarchy process (AHP) integrated with the coordinated development degree model (CDDM) was used to develop the ECS. This ECS was developed into two parts, including the emergency risk assessment and the emergency control. Feasible emergency control targets and control technology were also proposed for different sudden water pollution accidents. A demonstrative project was conducted in the Fangshui to Puyang channel, which is part of the Beijing-Shijiazhuang Emergency Water Supply Project (BSP) in the Middle Route of the South-to-North Water Transfer Project (MR-SNWTP) in China. However, we could not use an actual toxic soluble pollutant to validate our ECS, so we performed the experiment with sucrose to test the ECS based on its concentration variation. The relative error of peak sucrose concentration was less than 20 %.

Low-Dose Iron Supplementation in Infancy Modestly Increases Infant Iron Status at 9 Mo without Decreasing Growth or Increasing Illness in a Randomized Clinical Trial in Rural China.

BACKGROUND: Previous trials of iron supplementation in infancy did not consider maternal iron supplementation. OBJECTIVE: This study assessed effects of iron supplementation in infancy and/or pregnancy on infant iron status, illnesses, and growth at 9 mo. METHODS: Enrollment occurred from December 2009 to June 2012 in Hebei, China. Infants born to women in a pregnancy iron supplementation trial were randomly assigned 1:1 to iron [∼1 mg Fe/(kg · d) as oral iron proteinsuccynilate] or placebo from 6 wk to 9 mo, excluding infants with cord ferritin <35 µg/L. Study groups were pregnancy placebo/infancy placebo (placebo/placebo), pregnancy placebo/infancy iron (placebo/iron), pregnancy iron/infancy placebo (iron/placebo), and pregnancy iron/infancy iron (iron/iron). The primary outcome was 9-mo iron status: iron deficiency (ID) by cutoff (≥2 abnormal iron measures) or body iron <0 mg/kg and ID + anemia (hemoglobin <110 g/L). Secondary outcomes were doctor visits or hospitalizations and weight or length gain from birth to 9 mo. Statistical analysis by intention to treat and dose-response (between number of iron bottles received and outcome) used logistic regression with concomitant RRs and general linear models, with covariate control as applicable. RESULTS: Of 1482 infants randomly allocated, 1276 had 9-mo data (n = 312-327/group). Iron supplementation in infancy, but not pregnancy, reduced ID risk: RRs (95% CIs) were 0.89 (0.79, 0.998) for placebo/iron compared to placebo/placebo, 0.79 (0.63, 0.98) for placebo/iron compared to iron/placebo, 0.87 (0.77, 0.98) for iron/iron compared to placebo/placebo, and 0.86 (0.77, 0.97) for iron/iron compared to iron/placebo. However, >60% of infants still had ID at 9 mo. Receiving more bottles of iron in infancy was associated with better infant iron status at 9 mo but only among iron-supplemented infants whose mothers were also iron supplemented (i.e., the iron/iron group). There were no group differences in hospitalizations or illnesses and no adverse effects on growth overall or among infants who were iron sufficient at birth. CONCLUSIONS: Iron supplementation in Chinese infants reduced ID at 9 mo without adverse effects on growth or illness. Effects of iron supplementation in pregnancy were observed only when higher amounts of iron were distributed in infancy. This trial was registered at clinicaltrials.gov as NCT00613717.

Validation of chronic kidney disease risk categorization system in Chinese patients with kidney disease: A cohort study.

AIM: To validate the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines risk stratification system based on the combination of estimated glomerular filtration rate (eGFR) and proteinuria. METHODS: This was a cohort study. A total of 1219 study population were recruited. Estimated GFR and proteinuria measured by using 24 h urine protein excretion rate (PER) were predictors. Adverse outcomes included all-cause mortality (ACM) and end-stage renal disease (ESRD). Follow-up was done by regular visit, telephone interview and electronic medical records. RESULTS: Over a median follow-up of 4.6 years, 153 (12.6%) and 43 (3.5%) patients experienced ESRD and ACM, respectively. On multivariable analysis, the adjusted hazard ratio for ESRD and ACM (compared with patients with eGFR > 60 mL/min per 1.7 m²) was of 29.8 and 3.6 for those with eGFR of 15-29 mL/min per 1.73 m², respectively. The adjusted hazard ratio for ESRD and ACM (compared with patients with PER < 150 mg/24h) was of 15.9 and 3.9 for those with PER > 500 mg/24h. Higher KDIGO guidelines risk categories (indicating lower eGFR or higher proteinuria) were associated with a graded increase in the risk for the ESRD (P < 0.001) and ACM (P < 0.001). Reclassification of KDIGO guidelines risk categories yielded net reclassification improvements for those with ESRD or ACM event (NRIevents ) of 33.3% or 30.2%. CONCLUSION: Lower eGFR and higher proteinuria are risk factors for ESRD and ACM in Chinese patients. The KDIGO guidelines risk categorization system assigned patients who went on to have the event to more appropriate CKD risk categories.

Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates.

BACKGROUND: Previous trials of prenatal iron supplementation had limited measures of maternal or neonatal iron status. OBJECTIVE: The purpose was to assess effects of prenatal iron-folate supplementation on maternal and neonatal iron status. METHODS: Enrollment occurred June 2009 through December 2011 in Hebei, China. Women with uncomplicated singleton pregnancies at ≤20 wk gestation, aged ≥18 y, and with hemoglobin ≥100 g/L were randomly assigned 1:1 to receive daily iron (300 mg ferrous sulfate) or placebo + 0.40 mg folate from enrollment to birth. Iron status was assessed in maternal venous blood (at enrollment and at or near term) and cord blood. Primary outcomes were as follows: 1) maternal iron deficiency (ID) defined in 2 ways as serum ferritin (SF) <15 µg/L and body iron (BI) <0 mg/kg; 2) maternal ID anemia [ID + anemia (IDA); hemoglobin <110 g/L]; and 3) neonatal ID (cord blood ferritin <75 µg/L or zinc protoporphyrin/heme >118 µmol/mol). RESULTS: A total of 2371 women were randomly assigned, with outcomes for 1632 women or neonates (809 placebo/folate, 823 iron/folate; 1579 mother-newborn pairs, 37 mothers, 16 neonates). Most infants (97%) were born at term. At or near term, maternal hemoglobin was significantly higher (+5.56 g/L) for iron vs. placebo groups. Anemia risk was reduced (RR: 0.53; 95% CI: 0.43, 0.66), as were risks of ID (RR: 0.74; 95% CI: 0.69, 0.79 by SF; RR: 0.65; 95% CI: 0.59, 0.71 by BI) and IDA (RR: 0.49; 95% CI: 0.38, 0.62 by SF; RR: 0.51; 95% CI: 0.40, 0.65 by BI). Most women still had ID (66.8% by SF, 54.7% by BI). Adverse effects, all minor, were similar by group. There were no differences in cord blood iron measures; >45% of neonates in each group had ID. However, dose-response analyses showed higher cord SF with more maternal iron capsules reported being consumed (ß per 10 capsules = 2.60, P < 0.05). CONCLUSIONS: Prenatal iron supplementation reduced anemia, ID, and IDA in pregnant women in rural China, but most women and >45% of neonates had ID, regardless of supplementation. This trial was registered at clinicaltrials.gov as NCT02221752.