BACKGROUND:Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS:112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR. RESULTS:Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009 - 1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237 - 0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693 - 0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001). CONCLUSION:The NLR is an effective indicator for predicting clinical remission in patients with IMN.

INTRODUCTION AND IMPORTANCE:Vascular injuries during lumbar surgery are rare, but complications such as false aneurysm of the iliac artery, arteriovenous fistula, and lower limb artery embolism are even rarer. These complications can easily be misdiagnosed and result in the inability to choose an appropriate surgical approach, leading to serious consequences.CASE PRESENTATION:A 36-year-old male patient experienced swelling in both lower limbs, along with numbness, coldness, and dysfunction in his right lower limb, after undergoing a "posterior lumbar discectomy" surgery. On the 20th day post-surgery, a clear diagnosis was established through CTV: 1) Right common iliac artery injury with pseudoaneurysm formation; 2) Right iliac arteriovenous fistula; 3) Right popliteal artery embolism. The patient underwent hybrid surgery to address multiple complications simultaneously and made a good recovery after the procedure.CLINICAL DISCUSSION:Rarely, lumbar spine surgery can concurrently lead to conditions such as pseudoaneurysm, arteriovenous fistula, and lower limb artery embolism. Due to atypical symptoms and signs, it is often misdiagnosed. Hybrid surgery involves incising the femoral artery, using a thrombectomy catheter to remove clots from the iliac artery above and the popliteal artery below, and then re-implanting a covered stent to treat pseudoaneurysm and arteriovenous fistula.CONCLUSION:With a solid clinical knowledge, one can make a timely diagnosis and choose an appropriate surgical method to intervene, thereby improving the prognosis. Hybrid surgery combines the minimally invasive and safe effects of endovascular techniques with the precise effects of open surgery, and it also allows for the simultaneous treatment of multiple comorbidities.

The mechanical properties of oriented semicrystalline polymers fibers are mainly determined by the semicrystalline morphology in which lamellar crystals and disordered amorphous layers are in staggered arrangement. As a stress transmission channel, amorphous entanglement network can affect the strength and toughness of fiber together with crystalline phase. In this study, the relationship between mechanical properties and amorphous entanglement of oriented poly (L- lactic acid) fibers was clarified by studying the cyclic loading characteristics. Based on the Haward-Thakray model of semi-crystalline polymers, the energy contributions of the crystalline phase and the amorphous phase are separated. During the deformation of oriented fiber, the crystal will be broken under the action of tight entanglement network, and the entanglement network can transfer stress well without failure under the action of straight chain. Therefore, although the crystalline phase and the amorphous phase jointly bear the strength, the toughness and fracture behavior mainly affected by the entangled network of the amorphous phase.

Biodegradable polymer stents have a wide application prospect in the treatment of vascular stenosis diseases. However, weak radial performance of polymer stents hinders the treatment of the diseases with high demand for radial supporting, such as portal vein stenosis. According to previous research, the constraint mode between monofilaments is a key factor that affects the radial performance of polymer braided stent. In this work, a series of Poly(l-lactic acid) (PLLA) stents with the elastomer coating were prepared by ultrasonic spraying process to realize the constraints of monofilament cross points. The results are showed that the radial stiffness and peak force of the coated stent are significantly increased, up to 28 and 35 times higher than that of the bare stent. It is found that the cross points are constrained by the coating, which improves the constraining force between the monofilaments resulting in the increase of the radial force during the deformation process. More importantly, the mechanism of action between the radial force of the coated stent and the mechanical performance of elastic coating has been proposed, revealing a significant positive correlation between them. The radial force of the coated stent could be quantitatively regulated by the six-arm poly(l-lactide-co-epsilon-caprolactone) (6SPLCL) coating cross-linked by Hexamethylene diisocyanate (HDI) in different proportions. Finally, we build a mechanical model of stents and find that there is a consistency between the theoretical curve and the actual curve trend. This provides further research and expands the application scope for improving the radial supporting performance of the biodegradable polymer stent.

For the design of polymer stents, supportability and flexibility are two important indexes, but they are often difficult to balance. The mixed braiding of monofilaments with different diameters provides a potential solution to balance these two indices. In this study, the influence of mixed braiding on the mechanical properties of the stent was further explored by adjusting the knitting ratio of thick and thin monofilaments. By replacing the monofilaments in the stent with monofilaments with smaller diameters in turn, the changing trend of supportability and flexibility is obtained. The results show that, when the number of thick monofilaments is greater than or equal to that of thin monofilaments, the supportability of the stent can not only be maintained but also the flexibility can be greatly improved. Therefore, mixed braiding has the function of adjusting supportability and flexibility. Adjust supportability and flexibility of stent by mixed braiding.image

Annealing process has been applied to the development of thermoforming polymer braided stent and treating its basic constitute monofilaments, especially for Poly (l-lactide acid) (PLLA) condensed by lactic acid monomer made from the plant starch. In this work, high performance monofilaments were produced by melting spun and solid-state drawing methods. Inspired by the effects of water plasticization on semi-crystal polymer, PLLA monofilaments were annealed with and without constraint in vacuum and aqueous media. Then, the co-effects of water infestation and heat on the micro-structure and mechanical properties of these filaments were characterized. Furtherly, mechanical performance of PLLA braided stents shaped by different annealing methods was also compared. Results showed that annealing in aqueous media generated more obvious structure change of PLLA filaments. Interestingly, the combined effects of aqueous phase and thermal effectively increased the crystallinity, and decreased the molecular weight and orientation of PLLA filaments. Therefore, higher modulus, smaller strength, and elongation at the break for filaments could be obtained, which could furtherly realize better radial compression resistance of the braided stent. This annealing strategy could provide new perspectives between anneal and material properties of PLLA monofilaments, and provide more suitable manufacturing technics for polymer braided stent.

Albuminuria and podocyte injury are the key cellular events in the progression of diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is a nucleocytosolic enzyme responsible for the regulation of metabolic homeostasis in mammalian cells. This study aimed to investigate the possible roles of ACSS2 in kidney injury in DN. We constructed an ACSS2-deleted mouse model to investigate the role of ACSS2 in podocyte dysfunction and kidney injury in diabetic mouse models. In vitro, podocytes were chosen and transfected with ACSS2 siRNA and ACSS2 inhibitor and treated with high glucose. We found that ACSS2 expression was significantly elevated in the podocytes of patients with DN and diabetic mice. ACSS2 upregulation promoted phenotype transformation and inflammatory cytokine expression while inhibiting podocytes' autophagy. Conversely, ACSS2 inhibition improved autophagy and alleviated podocyte injury. Furthermore, ACSS2 epigenetically activated raptor expression by histone H3K9 acetylation, promoting activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Pharmacological inhibition or genetic depletion of ACSS2 in the streptozotocin-induced diabetic mouse model greatly ameliorated kidney injury and podocyte dysfunction. To conclude, ACSS2 activation promoted podocyte injury in DN by raptor/mTORC1-mediated autophagy inhibition.

The utilization of Poly-L-lactic acid (PLLA) as a biodegradable material for biovascular scaffolds (BVS) stems from its superior mechanical attributes, biodegradability, and biocompatibility. However, PLLA's challenges, such as its lack of active surface functional groups and high hydrophobicity, impede endothelial cells' (ECs) attachment and growth. These factors subsequently amplify the risk of thrombosis and restenosis in PLLA implants. To counteract this problem, we've adapted the polydopamine (PDA) coating technique, a technique commonly used for metal stents. This method has demonstrated potential for promoting EC adhesion and proliferation on PLLA surfaces. Our study involved the application of PDA coating to PLLA, which resulted in improved EC attachment and proliferation while simultaneously inhibiting macrophage activation and the release of the inflammatory factor TNF-α. Additionally, the reactive functional groups on the PDA-coated surface provide a reactive platform for immobilizing therapeutic molecules onto PLLA, thereby further enhancing the biocompatibility of PLLA cardiovascular stents.

Benefiting from their good biosafety and bioabsorbability, polymeric biodegradable stents (BDSs) have promising application prospects in the treatment of cardiovascular diseases. However, due to the low density of the polymer itself, it is difficult to visualize with medical imaging techniques such as CT and MRI, which leads to difficulties in accurate BDS localization and subsequent non-invasive evaluation. Therefore, modification of BDSs to adapt to monitoring techniques for clinical use without affecting their biocompatibility and mechanical properties is a promising strategy to support the clinical translation of BDSs. In this study, Fe3O4 superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized to modify the BDS by ultrasonic spraying. Due to the T2-weighted MR imaging enhancement capability of SPIONs, the fabricated SPION-BDS can be entirely visualized and long-term monitored under MR imaging. Further, a stent degradation assessment method based on the analysis of image gray value changes was established. In conclusion, the constructed SPION-BDS provides a possible solution for precise localization of BDSs after implantation, and furthermore, opens up opportunities for long-term non-invasive monitoring of in vivo BDS degradation and multimodal imaging assessment of vascular endothelial remodeling.

Background: G-protein-coupled receptor 43 (GPR43) is a posttranscriptional regulator involved in cholesterol metabolism. This study aimed to investigate the possible roles of GPR43 activation in podocyte lipotoxicity in diabetic nephropathy (DN) and explore the potential mechanisms. Methods: The experiments were conducted by using diabetic GPR43-knockout mice and a podocyte cell culture model. Lipid deposition and free cholesterol levels in kidney tissues were measured by BODIPY staining and quantitative cholesterol assays, respectively. The protein expression of GPR43, LC3II, p62, beclin1, low-density lipoprotein receptor (LDLR) and early growth response protein 1 (EGR1) in kidney tissues and podocytes was measured by real-time PCR, immunofluorescent staining and Western blotting. Results: There were increased LDL cholesterol levels in plasma and cholesterol accumulation in the kidneys of diabetic mice. However, GPR43 gene knockout inhibited these changes. An in vitro study further demonstrated that acetate treatment induced cholesterol accumulation in high glucose-stimulated podocytes, which was correlated with increased cholesterol uptake mediated by LDLR and reduced cholesterol autophagic degradation, as characterized by the inhibition of LC3 maturation, p62 degradation and autophagosome formation. Gene knockdown or pharmacological inhibition of GPR43 prevented these effects on podocytes. Furthermore, GPR43 activation increased extracellular regulated protein kinases 1/2 (ERK1/2) activity and EGR1 expression in podocytes, which resulted in an increase in cholesterol influx and autophagy inhibition. In contrast, after GPR43 deletion, these changes in podocytes were improved, as shown by the in vivo and in vitro results. Conclusion: GPR43 activation-mediated lipotoxicity contributes to podocyte injury in DN by modulating the ERK/EGR1 pathway.

With better biocompatibility, bioresorbable poly (L-lactic acid) (PLLA) helical stents are expected to replace the commonly used metallic stents. However, due to the great difference between the material properties of PLLA and those of metals, the current research results on mechanical properties of stents will not be applicative. In this article, the effects of i on the radial compression performance and bending stiffness of PLLA helical stents were systematically studied, and the effect of temperature on the radial compression performance of the helical stent was investigated. The findings obtained indicate that the reduction of initial pitch angle and initial diameter can enhance the radial compression performance. The reduction of initial pitch angle and the increase of initial diameter can weaken the bending stiffness of the helical stent. Moreover, the increase of temperature will reduce the radial stiffness and peak compression force of the helical stent. A favorable agreement between the theoretical and experimental results of radial compression properties was found in stents with the initial pitch angle between 14° and 21° and all initial diameters. This work can provide suggestions for the use of the theoretical formula in structure design of the helical stent.

Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the developed world. Podocyte injury is a critical cellular event involved in the progression of DN. Our previous studies demonstrated that platelet-derived microparticles (PMPs) mediated endothelial injury in diabetic rats. This study aimed to investigate whether PMPs are deposited in podocytes and to assess their potential effects on podocyte injury in DN. Methods The deposition of PMPs in podocytes was assessed by immunofluorescent staining and electron microscopy. The changes in renal pathology and ultra-microstructure were assessed by periodic acid-Schiff staining and electron microscopy, respectively. The expression of inflammatory cytokines and extracellular matrix proteins was measured by immuno-histochemical staining and western blot. Results PMPs were widely deposited in podocytes of glomeruli in diabetic patients and animal models and closely associated with DN progression. Interestingly, aspirin treatment significantly inhibited the accumulation of PMPs in the glomeruli of diabetic rats, alleviated mesangial matrix expansion and fusion of foot processes, and decreased the protein expression of inflammatory cytokines and extracellular matrix secretion. An in vitro study further confirmed the deposition of PMPs in podocytes. Moreover, PMP stimulation induced the phenotypic transition of podocytes through decreased podocin protein expression and increased protein expression of α-SMA and fibronectin, which was correlated with increased production of inflammatory cytokines. Conclusion Our findings demonstrated for the first time that the deposition of PMPs in podocytes contributed to the development of DN.

The investigation of the strength and toughness of poly(l-lactic acid) (PLLA) monofilaments is essential as the fundamental element of a biodegradable braided stent. However, the determining factor remains poorly addressed with respect to influencing the mechanical behavior of PLLA monofilaments. In this work, the electron beam (EB) with different radiation doses was utilized to sterilize PLLA monofilaments. Properties of the monofilaments, including the breaking strength, elongation at break, molecular weight, orientation, and microstructure of the fracture, were characterized. Results showed that a random chain scission of PLLA resulting from EB during this process could cause the decrease in molecular weight, which led to the decline in breaking strength. Meanwhile, the irradiated monofilaments were found to have almost the same elongation at break below a dose of 30 kGy and declined by 71.41% up to a dose of 48 kGy. It was also found that the ductile fracture connection of the monofilament translated to the brittle fracture by comparing the microstructure without and with sterilization. These phenomena could originate from the destruction of the long molecular chains connecting the crystal plates into shorter ones by radiation. PLLA monofilaments with 0, 30, and 48 kGy were used to braid carotid stents. Compared with a carotid Wallstent, the PLLA stent can better provide radial supporting to the carotid lesion. This study provides preliminary experimental references to evaluate and predict the mechanical performance of PLLA braided stents.

Organic-inorganic hybrids with multiple tunable functions are very attractive for potential applications in sensors, smart switches, etc. To investigate the effect of halogen tuning on the properties of hybrid materials, two new multifunctional organic-inorganic hybrid compounds [3-hydroxy-azetidinecation](2)SbX5 ( 1 : X = Cl; 2 : X = Br) are successfully synthesized here by replacing halogen anions. Reversible structural phase transitions accompanied by anomalous changes in dielectric constants are found when heating (T-1 = 362 K; T-2 = 373 K). Both two compounds have the same space group change from P2(1)2(1)2(1) (Low Temperature Phase) to Pnma (High Temperature Phase). When replacing Cl with Br, the phase transition temperature increases by ca. 10 K and the band gap changes from 3.21 eV to 2.75 eV. Based on the above properties, this work could provide an effective molecular design strategy for the exploration and construction of temperature-tunable, lower bandgap semiconductor hybrid materials. (C) 2022 Elsevier B.V. All rights reserved.

Background Lipid metabolism disorder, as one major complication in patients with chronic kidney disease (CKD), is tied to an increased risk for cardiovascular disease (CVD). Traditional lipid-lowering statins have been found to have limited benefit for the final CVD outcome of CKD patients. Therefore, the purpose of this study was to investigate the effect of microinflammation on CVD in statin-treated CKD patients. Methods We retrospectively analysed statin-treated CKD patients from January 2013 to September 2020. Machine learning algorithms were employed to develop models of low-density lipoprotein (LDL) levels and CVD indices. A fivefold cross-validation method was employed against the problem of overfitting. The accuracy and area under the receiver operating characteristic (ROC) curve (AUC) were acquired for evaluation. The Gini impurity index of the predictors for the random forest (RF) model was ranked to perform an analysis of importance. Results The RF algorithm performed best for both the LDL and CVD models, with accuracies of 82.27% and 74.15%, respectively, and is therefore the most suitable method for clinical data processing. The Gini impurity ranking of the LDL model revealed that hypersensitive C-reactive protein (hs-CRP) was highly relevant, whereas statin use and sex had the least important effects on the outcomes of both the LDL and CVD models. hs-CRP was the strongest predictor of CVD events. Conclusion Microinflammation is closely associated with potential CVD events in CKD patients, suggesting that therapeutic strategies against microinflammation should be implemented to prevent CVD events in CKD patients treated by statin.

This paper aims to study the radial compression performance of poly (L-lactic acid) (PLLA) helical stent and its influencing factors. The theoretical model was established and the radial compression test of PLLA helical stents with different parameters (initial pitch angle, temperature and compression rate) was carried out. The results indicated that smaller initial pitch angle can improve the radial compression performance of the stents. The temperature and compression rate during the test also affect the radial compression performance, and plastic deformation should be taken into consideration. The deformation mechanism of braided stent is different from that of helical stent. The experimental results showed good agreement with theory for the tests. This study would bring new sights to theoretical model and serve the design of PLLA stents.

Rationale: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear. Methods: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces. Results: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate. Conclusion: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity.

In this paper, the effects of annealing temperature on both radial supporting performance and axial flexibility of poly(L-lactic acid) (PLLA) braided stents are studied. Stents are annealed at a series of temperatures ranging from 80 to 160 degrees C for 1 h, then indicators of shaping effect, radial supporting performance, and axial flexibility are compared. Stents not annealed and annealed at 80 degrees C cannot be completely shaped. In contrast, stents annealed at 100 to 160 degrees C are well shaped showing radial shrinkage rate of 1.0 +/- 0.2% and almost no axial elongation. The radial compressive force and axial force are gradually increased by 51.2% and 89.2%, respectively with the annealing temperature gradually increasing from 80 to 160 degrees C, indicating that the radial supporting performance is improved but axial flexibility is weakened by a higher annealing temperature. Taken together, PLLA braided stents can be annealed at 100 to 120 degrees C to obtain sufficient radial force and lower axial force simultaneously for clinical applications. Moreover, tensile test, X-ray diffraction, and differential scanning calorimetry are performed for monofilaments annealed at different temperatures to further explore the effect mechanism of annealing temperature on the mechanical properties of stents. This study may provide helpful suggestions for the manufacture of biodegradable braided stents.

In this paper, a poly(L-lactic acid) (PLLA) braided stent with high radial force is prepared by optimizing the processes of monofilament forming and stent annealing. Firstly, three kinds of PLLA monofilaments with different diameters are prepared by melt extrusion, then two kinds of thicker monofilaments are further solid-state drawn to have diameters similar to that of the third thinner monofilament. The monofilament that is solid-state drawn at the larger draw ratio shows sufficient tensile mechanical properties and can be used for braiding stents, which is owing to the promotion of oriented crystallization. Secondly, PLLA braided stents are annealed at different temperatures. Stent not annealed shows much lower chronic outward force (COF) and much higher radial shrinkage rate (RSR) than those of annealed stents. Moreover, the COF is increased by 115% and the RSR is decreased by 59% as the annealing temperature is gradually increased from 80℃ to 160℃. Therefore, PLLA braided stents can be annealed at higher temperatures below their melting temperature to enhance the radial force. These results are due to the improved crystallinity induced by the thermal motion of molecular chains. This study may provide helpful suggestions for the preparation of biodegradable braided stents with high radial force.