A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation.

BACKGROUND: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. CASE PRESENTATION: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient's mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled, and the albumin level was recovered. CONCLUSION: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient's symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES.

BACKGROUND: Age-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults. METHODS: This study used a dataset derived from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman' s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients. RESULTS: Multivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (ß = 0.37, 95% confidence interval [CI] = 0.01, 0.73; ß = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (ß = 0.82, 95% CI = 0.36, 1.3 and ß = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests. CONCLUSIONS: The study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study.

AIM: Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS: Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS: By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION: In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

Process and applications of alginate oligosaccharides with emphasis on health beneficial perspectives.

Alginates are linear polymers comprising 40% of the dry weight of algae possess various applications in food and biomedical industries. Alginate oligosaccharides (AOS), a degradation product of alginate, is now gaining much attention for their beneficial role in food, pharmaceutical and agricultural industries. Hence this review was aimed to compile the information on alginate and AOS (prepared from seaweeds) during 1994-2020. As per our knowledge, this is the first review on the potential use of alginate oligosaccharides in different fields. The alginate derivatives are grouped according to their applications. They are involved in the isolation process and show antimicrobial, antioxidant, anti-inflammatory, antihypertension, anticancer, and immunostimulatory properties. AOS also have significant applications in prebiotics, nutritional supplements, plant growth development and others products.

Hemodynamic Mimic Shear Stress for Platelet Membrane Nanobubbles Preparation and Integrin αIIbß3 Conformation Regulation.

Platelet (PLT) membrane biomimetic nanomaterials have become promising theranostic platforms due to their good biocompatibility and effectiveness. However, in order to achieve precise regulation of cell membrane components, novel controllable construction approaches need to be developed. Inspired by the interaction mechanism among platelet production, activation, and dynamic biomechanical signals in blood circulation, here a platelet nanobubbles (PNBs) with reassembled platelet membrane with ideal echogenicity was fabricated using an adjustable pressure-induced shear stress method. The results demonstrate that the high shear stress during PNBs fabrication led to the enrichment of platelet membrane lipid rafts and proteins, as well as their reassembly on the gas-liquid interface. More importantly, the conformation of platelet integrin αIIbß3 was transformed into a shear stress-induced intermediate affinity state, which gives PNBs enhanced adhesion ability to the vascular endothelial injury. Taken together, these PNBs have great application potential in the specifically targeted ultrasound diagnosis of vascular endothelial injury.

Magnetic Nanobubble Mechanical Stress Induces the Piezo1-Ca2+ -BMP2/Smad Pathway to Modulate Neural Stem Cell Fate and MRI/Ultrasound Dual Imaging Surveillance for Ischemic Stroke.

Neural stem cells (NSCs) are used to treat various nervous system diseases because of their self-renewal ability and multidirectional differentiation potential. However, an insufficient ability to track their migration in vivo and poor control over their survival and differentiation efficiency are two major critical challenges for clinical application. Here, it is shown that when magnetic nanobubbles (MNBs), which are assembled from magnetic nanoparticles, are internalized by NSCs, intramembrane volumetric oscillation of the MNBs induces an increase in intracellular hydrostatic pressure and cytoskeleton force, resulting in the activation of the Piezo1-Ca2+ mechanosensory channel. This subsequently triggers the BMP2/Smad biochemical signaling pathway, leading to differentiation of NSCs into the neuronal phenotype. Signaling through the Piezo1-Ca2+ -BMP2/Smad pathway can be further accelerated by application of an external shear stress force using low-intensity pulsed ultrasound. More importantly, magnetic resonance imaging and ultrasound imaging surveillance of NSCs based on MNB labeling can be leveraged to provide NSC therapeutic outcomes. Both the in vitro and in vivo findings demonstrate that a bubble nanostructure-induced physical force can modulate and control the mechanical signaling pathway regulating stem cell development.

Dose-response association between maternal pre-pregnancy bodyweight and gestational diabetes mellitus following ART treatment: a population-based cohort study.

BACKGROUND: The impact of maternal pre-pregnancy bodyweight on gestational diabetes mellitus (GDM) following assisted reproductive technology (ART) treatment has been insufficiently investigated. The aim of this study was to investigate the association between maternal pre-pregnancy bodyweight and GDM following ART. METHODS: From January 2014 to March 2019, this population-based retrospective cohort study included pregnancies achieved by ART treatment in a pregnancy registration database in China. Multivariate regression analysis and restricted cubic splines were used to explore the association between bodyweight and GDM. RESULTS: A total of 6,598 pregnancies were included. The incidence of GDM was 26.0% (1715/6598). A total of 868 (13.2%) pregnant women were underweight, 665 (10.8%) were overweight, and 145 (2.20%) were obesity. We found a linear dose-response relation between maternal body mass index and GDM by restricted cubic splines, where one unit body mass index increase was associated with the 15% elevated risk of GDM (adjusted odds ratio [OR] 1.15, 95% CI 1.08-1.22). Compared to the normal weight group, maternal underweight was associated with lower risk of GDM (adjusted OR 0.68, 95% CI 0.57-0.82), while increased risk was found for overweight (adjusted OR 1.54 95% CI 1.29-1.84) and obesity (adjusted OR 1.74, 95% CI 1.23-2.47). CONCLUSIONS: Our study found a linear dose-effect relationship between pre-pregnancy bodyweight and GDM following ART treatment. The findings in this study support the clinical recommendation of advising women with overweight or obesity to lose weight prior to ART treatment.

Elevation of effective p53 expression sensitizes wild-type p53 breast cancer cells to CDK7 inhibitor THZ1.

BACKGROUND: The cyclin-dependent kinase 7 (CDK7) inhibitor THZ1 represses multiple cancer cells. However, its tumor-repressive efficiency in wild-type p53 breast cancer cells remains controversial. METHODS: We conducted various assays, including CCK8, colony formation, flow cytometry, western blotting, and lactate dehydrogenase release detection, to clarify whether p53 elevation sensitizes breast cancer cells to THZ1. RESULTS: We found that upregulating functional p53 contributes to the increased sensitivity of breast cancer cells to THZ1. Increased THZ1 sensitivity requires active p53 and an intact p53 pathway, which was confirmed by introducing exogenous wild-type p53 and the subsequent elevation of THZ1-mediated tumor suppression in breast cancer cells carrying mutant p53. We confirmed that p53 accumulates in the nucleus and mitochondria during cell death. Furthermore, we identified extensive transcriptional disruption, rather than solely CDK7 inhibition, as the mechanism underlying the nutlin-3 and THZ1-induced death of breast cancer cells. Finally, we observed the combined nutlin-3 and THZ1 treatment amplified gasdermin E cleavage. CONCLUSION: Enhanced sensitivity of breast cancer cells to THZ1 can be achieved by increasing effective p53 expression. Our approach may serve as a potential treatment for patients with breast cancer resistant to regular therapies. Video Abstract.

Effects of green tea polyphenol extract and epigallocatechin-3-O-gallate on diabetes mellitus and diabetic complications: Recent advances.

Diabetes mellitus is one of the major non-communicable diseases accounting for millions of death annually and increasing economic burden. Hyperglycemic condition in diabetes creates oxidative stress that plays a pivotal role in developing diabetes complications affecting multiple organs such as the heart, liver, kidney, retina, and brain. Green tea from the plant Camellia sinensis is a common beverage popular in many countries for its health benefits. Green tea extract (GTE) is rich in many biologically active compounds, e.g., epigallocatechin-3-O-gallate (EGCG), which acts as a potent antioxidant. Recently, several lines of evidence have shown the promising results of GTE and EGCG for diabetes management. Here, we have critically reviewed the effects of GTE and EGCC on diabetes in animal models and clinical studies. The concerns and challenges regarding the clinical use of GTE and EGCG against diabetes are also briefly discussed. Numerous beneficial effects of green tea and its catechins, particularly EGCG, make this natural product an attractive pharmacological agent that can be further developed to treat diabetes and its complications.

Validity of high resolution magnetic resonance imaging in detecting giant cell arteritis: a meta-analysis.

OBJECTIVES: This study was designed to evaluate the performance of high-resolution magnetic resonance imaging (HR-MRI) in detecting giant cell arteritis (GCA), evaluate superficial extracranial artery and other MRI abnormalities, and compare three-dimensional (3D) and two-dimensional (2D) techniques. METHODS: PubMed, Web of Science, and Cochrane Library were screened up to March 7, 2021, and further selection was performed according to the eligibility criteria. Quality Assessment of Diagnostic Accuracy Studies-2 was used for quality assessment, and heterogeneity assessment and statistical calculations were also performed. RESULTS: In total, 1851 records were retrieved from online databases, and 15 studies were finally included. Regarding the performance of HR-MRI, the superficial extracranial artery had 75% sensitivity and 89% specificity, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.91. Positive and negative post-test possibilities were 86% and 20%, respectively, with clinical diagnosis as reference. When referenced with temporal artery biopsy, the sensitivity was 91%, specificity was 78%, AUC was 0.92, and positive and negative post-test possibilities were 78% and 10%, respectively. 3D HR-MRI and 2D HR-MRI had 70% and 72% sensitivity, respectively, and 91% and 84% specificity, respectively. CONCLUSIONS: HR-MRI is a valuable imaging modality for GCA diagnosis. It provided high accuracy in the diagnosis of GCA and played a potential role in identifying GCA-related ischemic optic neuropathy. 3D HR-MRI had better specificity than 2D HR-MRI. KEY POINTS: HR-MRI helps clinicians to diagnose GCA. Superficial extracranial arteries and other MRI abnormalities can be assessed with HR-MRI. HR-MRI can help in assessing GCA-related optic neuropathy.

Relationship between high fructose corn syrup sweetened drinks, diet soft drinks, and serum sodium: NHANES 2003-2006.

BACKGROUND: Consumption of high fructose corn syrup sweetened drinks and diet soft drinks has increased in the United States. However, the relationship between the intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium has been scarcely studied. Our objective is to evaluate the relation between intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium, and explore the possible effect modifiers in a nationally representative sample of adults from the United States. METHODS: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey 2003-2006. The study participants included 6989 adults aged ≥18 years. Using survey-weighted generalized linear regression analyses, we investigated the relationship between high fructose corn syrup sweetened drink, diet soft drink consumption, and serum sodium. Consumption of high fructose corn syrup sweetened drinks and diet soft drinks was evaluated through a food-frequency questionnaire. RESULTS: Serum sodium levels increased as high fructose corn syrup sweetened drink intake increased. Serum sodium levels were higher in participants in the highest high fructose corn syrup sweetened drink consumption quantile, compared with those in the lowest high fructose corn syrup sweetened drink intake quantile (p = 0.020). The multivariate betas for serum sodium, according to the corresponding high fructose corn syrup sweetened drink intake quantiles, were 0.16, 0.19, and 0.21, respectively (P for trend = 0.051). We found no relationship between diet soft drink consumption and serum sodium after adjustment of confounding. (multivariate P > 0.05). CONCLUSION: There was a a step-wise increase in serum sodium concentration with increasing consumption of HFCS sweetened beverages. Even moderate HFCS sweetened soft drink intake was associated with an elevated serum sodium level - a risk factor for hypertension.

Safety and efficacy of botulinum toxin type A in preventing and treating scars in animal models: A systematic review and meta-analysis.

Previous studies have used botulinum toxin type A (BTXA) to improve postoperative and hypertrophic scars; however, there is lack of detailed verification on the safety and effectiveness of this approach. This study aimed to evaluate the therapeutic effect of BTXA on postoperative hypertrophic scars and its influence on cytokine expression in animal models. A computerised search of different databases was performed, including PubMed, Web of Science, Scopus, Cochrane, Embase, CNKI, and Wanfang, up to 10 March 2021. A meta-analysis was performed using R 4.0.0 based on hypertrophic index, epithelialisation time, wound area, and vascular endothelial growth factor (VEGF) expression. Eleven studies were included. The meta-analysis showed a significant difference in hypertrophic index (standardised mean difference [SMD] = -2.63, 95% confidence interval [CI]: -3.50 to -1.76, P < .01), wound area (SMD = -0.54, 95% CI: -1.24 to 0.16, P < .01), and VEGF expression (SMD = -2.56, 95% CI: -3.50 to -1.62, P < .01). This study shows that BTXA is safe and effective in preventing and treating scar hypertrophy in animal models, but excessive doses of BTXA and BTXA to treat large areas should be avoided.

Pharmacological preconditioning by TERT inhibitor BIBR1532 confers neuronal ischemic tolerance through TERT-mediated transcriptional reprogramming.

After a sublethal ischemic preconditioning (IPC) stimulus, the brain has a remarkable capability of acquiring tolerance to subsequent ischemic insult by establishing precautionary self-protective mechanism. Understanding this endogenous mechanism would reveal novel and effective neuroprotective targets for ischemic brain injury. Our previous study has implied that telomerase reverse transcriptase (TERT) is associated with IPC-induced tolerance. Here, we investigated the mechanism of TERT-mediated ischemic tolerance. Preconditioning was modeled by oxygen-glucose deprivation (OGD) and by TERT inhibitor BIBR1532 in primary neurons. We found that ischemic tolerance was conferred by BIBR1532 preconditioning. We used the Cleavage-Under-Targets-And-Tagmentation approach, a recently developed method with superior signal-to-noise ratio, to comprehensively map the genomic binding sites of TERT in primary neurons, and showed that more than 50% of TERT-binding sites were located at the promoter regions. Mechanistically, we demonstrated that under normal conditions TERT physically bound to many previously unknown genomic loci in neurons, whereas BIBR1532 preconditioning significantly altered TERT-chromatin-binding profile. Intriguingly, we found that BIBR1532-preconditioned neurons showed significant up-regulation of promoter binding of TERT to the mitochondrial anti-oxidant genes, which were correlated with their elevated expression. Functional analysis further indicated that BIBR1532-preconditioning significantly reduced ROS levels and enhanced tolerance to severe ischemia-induced mitochondrial oxidative stress in neurons in a TERT-dependent manner. Together, these results demonstrate that BIBR1532 confers neuronal ischemic tolerance through TERT-mediated transcriptional reprogramming for up-regulation of mitochondrial anti-oxidation gene expression, suggesting the translational potential of BIBR1532 as a therapeutic agent for the treatment of cerebral ischemic injury and oxidative stress-induced neurological disorders.

Optical Imaging and High-Accuracy Quantification of Intracellular Iron Contents.

Precise quantification of intracellular iron contents is important to biomedical applications of magnetic nanoparticles. Current approaches for iron quantification rely on specialized instruments while most only yield iron quantities averaged over plenty of cells. Here, a simple and robust approach, combining digital optical microscopy with the Beer-Lambert's law, that allows for imaging stainable iron distribution in individual cells and the quantification of stainable iron contents with an unprecedented accuracy of femtogram per pixel, is presented. It is further shown that this approach enables studying of the internalization and reduction dynamics of super-paramagnetic iron oxide nanoparticles (SPIONs) by stem cells in single cell level.

Nephrotic-range proteinuria and central nervous involvement in typical hemolytic uremic syndrome: a case report.

BACKGROUND: Hemolytic uremic syndrome (HUS), a common subtype of thrombotic microangiopathy (TMA), is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin-producing Escherichia coli infection is the most common cause of post-diarrheal HUS. Kidney and central nervous system are the primary target organs. CASE PRESENTATION: A 64-year-old male presented with HUS following bloody diarrhea. Nephrotic-range proteinuria and hypoalbuminemia were present at the acute stage and renal histology revealed common TMA features. Neurological involvement presented as confusion and impaired cognitive function. Cranial magnetic resonance imaging demonstrated bilateral T2 hyperintensities in the brainstem and insula. The patient received plasma exchange and supportive care. Both the renal and neurological impairments were completely recovered 3 months after the onset. CONCLUSION: We report an adult patient presenting with nephrotic-range proteinuria and central nervous system involvement at the acute phase of post-diarrheal HUS. The reversibility of the organ damages might predict a favorable outcome.

Effects of tea consumption on metabolic syndrome: A systematic review and meta-analysis of randomized clinical trials.

The metabolic syndrome (MetS) is one of the major health hazards and an epidemic worldwide. There is no known best remedy has been defined yet. In the current investigation, we designed a meta-analysis of randomized clinical trials (RCTs) to evaluate the beneficial effects of tea consumption in alleviating metabolic syndromes. Herein, we accumulated the relevant literature available on PubMed and EMBASE databases from January, 2000 to August, 2019. RCTs bearing impact factor of at least 1 or more were studied for the effect of tea consumption on MetS. This meta-analysis suggested that tea consumption has beneficial effects on diastolic blood pressure (DBP), and this finding was characterized of all types of tea in the current study and also for body mass index (BMI) value. Furthermore, this analysis also found that black tea consumption has protective effects on systolic SBP, green tea reduces the incidence of diabetes and lower the level of low-density lipoprotein (LDL) cholesterol. These functions required BMI value at least 28 or higher. The meta data led us to conclude that tea consumption have protective effects on MetS, however, different types of tea might have different protective mechanisms on MetS, but, exact mechanisms are not yet clear and needs to be explored.

Clinical significance of C4d deposition in renal tissues from patients with primary Sjögren's syndrome-a preliminary study.

BACKGROUND: To evaluate renal expression of C4d, a complement component in the classical/mannose binding lectin (MBL) pathway, in patients with primary Sjögren's syndrome (pSS)-associated renal impairments. METHODS: We retrospectively reviewed the clinical and pathological data from 39 patients with pSS presenting with renal impairments. C4d was examined in paraffin-embedded biopsy tissues using immunohistochemistry. Glomerular C4d positive was defined when > 75% glomeruli were globally stained. Tubulointerstitial C4d (TI-C4d) were scored semi-quantitatively as 0 (absent), 1 (spotty or weak), 2 (patchy) and 3 (diffuse). A TI-C4d score ≥ 2 was considered TI-C4d positive and included in the TI-C4d+ group and vice versa. Peritubular capillary (PTC) C4d was scored as 0 (absent), 1 (0~10%, minimal), 2 (10%~ 50%, focal), and 3 (> 50%, diffuse). RESULTS: Glomerular C4d deposition was observed in all 8 patients with pSS-related membranous nephropathy (MN) without obvious C1q deposition. Two of 5 patients with mesangial proliferative glomerulonephritis and 1 of 2 patients with IgA nephropathy had mild mesangial C4d deposition. Sixteen patients (6 glomerular dominant and 10 tubulointerstitial dominant) presented TI-C4d score ≥ 2. Patients in the TI-C4d+ group exhibited a higher serum creatinine level at the time of renal biopsy (TI-C4d+ 132.5 [89.7, 165.5] vs. TI-C4d- 83.0 [70.7, 102.0] µmol/L, P = 0.008). PTC C4d was observed in 12 patients, with each of minimal, focal and diffuse staining being noted in 4 patients. CONCLUSIONS: The MBL pathway of complement activation was potentially involved in pSS-related MN. Tubulointerstitial C4d might be a pathological marker of severe renal injury in patients with pSS-related renal impairments.

Adaptive Materials Based on Iron Oxide Nanoparticles for Bone Regeneration.

The paper provides a brief overview of the use of iron oxide nanoparticles (IONPs) in the areas of bone regenerative medicine. Reconstruction of bone defects caused by trauma, non-union, and bone tumor excision, still faces many challenges despite the intense investigations and advancement in bone-tissue engineering and bone regeneration over the past decades. IONPs have promising prospects in this field due to their controlled responsive characteristics in specific external magnetic fields and have been of great interest during the last few years. This Minireview aims to summarize the relevant progress and describes the following five aspects: (i) The general introduction of IONPs, with a focus on the magnetic properties as the base of application; (ii) using IONPs as tools to study and control stem cells for better treatment efficacy in stem-cell-based bone defect repair; (iii) the use of IONPs and their complexes in the delivery of therapeutic agents, including chemical drug molecules, growth factors, and genetic materials, to promote osteogenesis-related cell function and differentiation, healthy bone tissue growth, and functional reconstruction; (iv) magneto-mechanical actuation in the regulation of cells distribution, mechano-transduction membrane receptors activation, and mechanosensitive signaling pathways regulation, and (v) fabrication, characteristics, and in vitro and in vivo osteogenic effects of magnetic composite bone scaffolds. Ongoing prospects are also discussed.