Strengthening Mechanism of Polyurea to Anti-Penetration Performance of Spherical Cell Porous Aluminum.

A composite structure containing a metallic skeleton and polyurea elastomer interpenetrating phase was fabricated, and its anti-penetration performance for low-velocity large mass fragments was experimentally studied. The protection capacity of three polyurea was compared based on the penetration resistance force measurement. Results show that the polyurea coating layer at the backside improves the performance of the polyurea-filled spherical cell porous aluminum (SCPA) plate due to its backside support effect and phase transition effect, which are accompanied by a large amount of energy absorption. The frontal-side-coated polyurea layer failed to shear and provided a very limited strengthening effect on the penetration resistance of the interpenetrating phase composite panel. The filling polyurea in SCPA increased the damage area and formed a compression cone for the backside coating layer, leading to a significant stress diffusion effect. The anti-penetration performance was synergistically improved by the plug block effect of the interpenetrating phase composite and the backside support effect of the PU coating layer. Compared with SCPA, the initial impact failure strength and the average resistance force of the composite plate were improved by 120-200% and 108-274%, respectively.

Effect of O-arm on reduction quality and functional recovery of acetabular dome impaction fractures: a retrospective clinical study.

BACKGROUND: Acetabular dome impaction fractures (ADIF) are difficult to reduce and have a high failure rate. Consistency between the acetabulum and the femoral head is usually assessed using intraoperative X-ray fluoroscopy to evaluate the quality of fracture reduction. This study examines the effects of intraoperative mobile 2D/3DX imaging system (O-arm) on the reduction quality and functional recovery of ADIF. METHODS: We retrospectively analysed the data of 48 patients with ADIF treated at Honghui Hospital between October 2018 and October 2021.The patients were divided into the X-ray and O-arm groups. The residual step-off and gap displacements in the acetabular dome region were measured, and fracture reduction quality was evaluated. Hip function was evaluated using the modified Merle d'Aubigné and Postel scoring systems. RESULTS: There were no significant intergroup differences in the preoperative general data (p > 0.05). The mean residual average step displacement in the acetabular dome region was 3.48 ± 2.43 mm and 1.61 ± 1.16 mm (p < 0.05), while the mean gap displacement was 6.72 ± 3.69 mm and 3.83 ± 1.67 mm (p < 0.05) in the X-ray and the O-arm groups, respectively. In the X-ray group, according to the fracture reduction criteria described by Verbeek and Moed et al., one case was excellent, 13 cases were good, 11 cases were poor; 56% were excellent or good. In the O-arm group, seven cases were excellent, 12 cases were good, and four cases were poor; overall in this group, 82.6% were excellent or good (p < 0.05). A total of 46 patients achieved fracture healing at the last follow-up. In the X-ray group, according to the modified Merle d'Aubigné and Postel function score, three cases were excellent,12 cases were good, six cases were middle, three cases were poor; 62.5% were excellent or good, In the O-arm group, 15 cases were excellent, four cases were good, two cases were middle, one case was poor; 86.4% were excellent or good (p < 0.05). CONCLUSIONS: The application of O-arm in ADIF can improve fracture reduction quality and functional recovery.

Collagen-EGCG Combination Synergistically Prevents UVB-Induced Skin Photoaging in Nude Mice.

Ultraviolet (UV) radiation is a major cause of skin photoaging through generating excessive oxidative stress and inflammation. One of the strategies is to use photo-chemoprotectors, such as natural products with antioxidant and anti-inflammatory properties, to protect the skin from photo damage. The present study investigates the photoprotective potentials of topical administration of unhydrolyzed collagen, epigallocatechin gallate (EGCG), and their combination against ultraviolet B (UVB)-induced photoaging in nude mice. It is found that both the solo and combined pretreatments could recover UVB-induced depletion of antioxidative enzymes, including superoxide dismutase and glutathione peroxidase (GSH-Px), as well as an increase of lipid peroxide malondialdehyde and inflammatory tumor necrosis factor-α. Meanwhile, the UVB-stimulated skin collagen degradation is attenuated significantly with drug treatments, which is evidenced by expression analysis of matrix metalloproteinase-1 and hydroxyproline. Additionally, the mouse skin histology shows that the drug-pretreated groups possess decreased epidermis thickness and normal collagen fiber structure of the dermis layer. These results demonstrate that both EGCG and collagen can protect the skin against UVB-induced skin photoaging. Synergistically, the combination of them shows the maximum prevention to skin damage, showing its potential in the application of anti-photoaging formulation products.

Prevalence of osteoporosis in spinal surgery patients older than 50 years: A systematic review and meta-analysis.

INTRODUCTION: In spine surgery, poor bone condition is associated with several complications like adjacent segment fractures, proximal junctional kyphosis, and screw loosening. Our study explored the prevalence of osteoporosis in spinal surgery patients older than 50 years through a systematic review and meta-analysis. METHODS: This systematic review and meta-analysis were conducted according to the PRISMA criteria. Three electronic databases, including PubMed, EMBASE, and Web of Science, were searched from inception to August 2022. We used the random-effects model to calculate the overall estimates, and the heterogeneity was measured using Cochran's Q and I2 tests. Meta-regression and subgroup analyses were used to determine the source of the heterogeneity. RESULTS: Based on the inclusion and criteria, we chose ten studies with 2958 individuals for our analysis. The prevalence of osteoporosis, osteopenia, and osteoporosis/osteopenia in the spinal surgery patients was 34.2% (95%CI: 24.5%-44.6%), 43.5% (95%CI: 39.8%-47.2%), and 78.7% (95%CI: 69.0%-87.0%), respectively. Regarding different diagnoses, the prevalence was highest in patients with lumbar scoliosis (55.8%; 95%CI: 46.8%-64.7%) and the lowest in patients with cervical disc herniation (12.9%; 95%CI: 8.1%-18.7%). In age groups 50-59, 50-69,70-79, the prevalence was 27.8%, 60.4%, 75.4% in females, and 18.9%, 17.4%, 26.1% in males. CONCLUSIONS: This study showed a high prevalence of osteoporosis in patients undergoing spine surgery, especially in females, people of older age, and patients who received degenerative scoliosis and compression fractures. Current osteoporosis screening standards for patients undergoing spine surgery may not be adequate. Orthopedic specialists should make more efforts regarding preoperative osteoporosis screening and treatment.

Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants.

Background: Vitamin D deficiency causes the bone hypomineralization disorder osteomalacia in humans and is associated with many non-skeletal disorders. We aim to estimate the global and regional prevalence of vitamin D deficiency in people aged 1 year or older from 2000 to 2022. Methods: We systematically searched Web of Science, PubMed (MEDLINE), Embase, Scopus, and Google databases on December 31, 2021, and updated them on August 20, 2022, without language and time restrictions. Meanwhile, we identified references of relevant system reviews and eligible articles and included the latest and unpublished data from the National Health and Nutrition Examination Survey (NHANES, 2015-2016 and 2017-2018) database. The studies investigating the prevalence of vitamin D deficiency in population-based studies were included. A standardized data extraction form was used to collect information from eligible studies. We used a random-effects meta-analysis to estimate the global and regional prevalence of vitamin D deficiency. We stratified meta-analyses by latitude, season, six WHO regions, the World Bank income groups, gender, and age groups. This study was registered with PROSPERO (CRD42021292586). Findings: Out of 67,340 records searched, 308 studies with 7,947,359 participants from 81 countries were eligible for this study, 202 (7,634,261 participants), 284 (1,475,339 participants), and 165 (561,978 participants) studies for the prevalence of serum 25(OH)D <30, <50, and <75 nmol/L, respectively. We found that globally, 15.7% (95% CrI 13.7-17.8), 47.9% (95% CrI 44.9-50.9), and 76·6% (95% CrI 74.0-79.1) of participants had serum 25-hydroxyvitamin D levels less than 30, 50, and 75 nmol/l, respectively; the prevalence slightly decreased from 2000-2010 to 2011-2022, but it was still at a high level; people living in high latitude areas had a higher prevalence; the prevalence in winter-spring was 1.7 (95% CrI 1.4-2.0) times that in summer-autumn; the Eastern Mediterranean region and Lower-middle-income countries had a higher prevalence; females were vulnerable to vitamin D deficiency; gender, sampling frame, detection assays, sampling region, time of data collection, season, and other factors contributed to heterogeneity between the included studies. Interpretation: Globally, vitamin D deficiency remained prevalent from 2000 to 2022. The high prevalence of vitamin D deficiency would increase the global burden of disease. Therefore, governments, policymakers, health workers, and individuals should attach importance to the high prevalence of vitamin D deficiency and take its prevention as a public health priority. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021292586, PROSPERO CRD42021292586.

Genetically engineered sheep: A new paradigm for future preclinical testing of biological heart valves.

BACKGROUND: Heart valve implantation in juvenile sheep to demonstrate biocompatibility and physiologic performance is the accepted model for regulatory approval of new biological heart valves (BHVs). However, this standard model does not detect the immunologic incompatibility between the major xenogeneic antigen, galactose-α-1,3-galactose (Gal), which is present in all current commercial BHVs, and patients who universally produce anti-Gal antibody. This clinical discordance leads to induced anti-Gal antibody in BHV recipients, promoting tissue calcification and premature structural valve degeneration, especially in young patients. The objective of the present study was to develop genetically engineered sheep that, like humans, produce anti-Gal antibody and mirror current clinical immune discordance. METHODS: Guide RNA for CRISPR Cas9 nuclease was transfected into sheep fetal fibroblasts, creating a biallelic frame shift mutation in exon 4 of the ovine α-galactosyltransferase gene (GGTA1). Somatic cell nuclear transfer was performed, and cloned embryos were transferred to synchronized recipients. Cloned offspring were analyzed for expression of Gal antigen and spontaneous production of anti-Gal antibody. RESULTS: Two of 4 surviving sheep survived long-term. One of the 2 was devoid of the Gal antigen (GalKO) and expressed cytotoxic anti-Gal antibody by age 2 to 3 months, which increased to clinically relevant levels by 6 months. CONCLUSIONS: GalKO sheep represent a new, clinically relevant advanced standard for preclinical testing of BHVs (surgical or transcatheter) by accounting for the first time for human immune responses to residual Gal antigen that persists after current BHV tissue processing. This will identify the consequences of immune disparity preclinically and avoid unexpected past clinical sequelae.

Early developmental phenotypes in the cystic fibrosis sheep model.

Highly effective modulator therapies for cystic fibrosis (CF) make it a treatable condition for many people. However, although CF respiratory illness occurs after birth, other organ systems particularly in the digestive tract are damaged before birth. We use an ovine model of CF to investigate the in utero origins of CF disease since the sheep closely mirrors critical aspects of human development. Wildtype (WT) and CFTR -/- sheep tissues were collected at 50, 65, 80, 100, and 120 days of gestation and term (147 days) and used for histological, electrophysiological, and molecular analysis. Histological abnormalities are evident in CFTR-/- -/-  animals by 80 days of gestation, equivalent to 21 weeks in humans. Acinar and ductal dilation, mucus obstruction, and fibrosis are observed in the pancreas; biliary fibrosis, cholestasis, and gallbladder hypoplasia in the liver; and intestinal meconium obstruction, as seen at birth in all large animal models of CF. Concurrently, cystic fibrosis transmembrane conductance regulator (CFTR)-dependent short circuit current is present in WT tracheal epithelium by 80 days gestation and is absent from CFTR -/- tissues. Transcriptomic profiles of tracheal tissues confirm the early expression of CFTR and suggest that its loss does not globally impair tracheal differentiation.

Clinical Significance of Fusobacterium nucleatum and Microsatellite Instability in Evaluating Colorectal Cancer Prognosis.

Objective: Both genetic and microbial factors play important roles in colorectal cancer (CRC) development. The effects of Fusobacterium nucleatum (F. nucleatum) and microsatellite instability (MSI) on CRC prognosis require more clinical evidence. We aimed to investigate the role of F. nucleatum and MSI as biomarkers in predicting the prognosis of CRC. Methods: CRC patients in various TNM stages were enrolled. MSI status and F. nucleatum were detected by immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) specimens. The associations between MSI status and F. nucleatum and clinical parameters were analyzed. Results: MSI tumors were more frequently observed in the colon than in the rectum. Cancerous tissues had higher levels of F. nucleatum than adjacent noncancerous tissues. There were no significant differences in F. nucleatum abundance in different age, sex, tumor stage, location, and tumor marker groups. MSI status was associated with tumor location and stage. Survival analyses revealed that disease-free survival (DFS) was significantly longer in the F. nucleatum-negative, younger age, and TNM stage I-II groups (p< 0.05), and age, advanced TNM stage (III and IV), and F. nucleatum status were independent factors for poor prognosis. Multivariate Cox regression and receiver operating characteristic (ROC) curve analyses showed that conventional tumor biomarkers of CRC had more prognostic value than F. nucleatum and MSI. Conclusion: Age, advanced TNM stage, and F. nucleatum positivity were independent factors of poor prognosis, suggesting that F. nucleatum and MSI may contribute to the identification of new strategies for the prevention and treatment of CRC.

Evaluation of the Dielectric and Insulating Properties of Newly Synthesized Ethylene/1-Hexene/4-Vinylcyclohexene Terpolymers.

Terpolymerizations of newly synthesized ethylene (E), vinylcyclohexene (VCH), and 1-hexene were carried out with symmetrical metallocene catalysts rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2 (catalyst A) and rac-Et(Ind)2ZrCl2 (catalyst B). X-ray diffractometry (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), high-temperature gel permeation chromatography (GPC), and nuclear magnetic resonance (NMR) spectroscopy were used to evaluate the behavior and microstructure of the polymers. The activity of catalyst B was 1.49 × 106 gm/mmolMt·h), with a T m of 73.45 (°C) and ΔH m of 43.19 (J/g), while catalyst A produced first higher 1-hexene, 19.6 mol %, and VCH contents with a narrow molecular weight distribution (MWD). In previous reports, ethylene propylene monomer dienes (EPDM) had a low content and were used for dielectric and insulating properties with nanomaterials. Second, this paper presents a kind of elastomeric polymers based on E/1-hexene and VCH with a high dielectric constant (k = 6-4) and mechanical properties. In addition, low dielectric loss suggests the suitable application potential of these polymeric materials for the fabrications of capacitors. Also, this work reveals that these polymers can be a better candidate for high-voltage electrical insulation due to their enhanced dielectric, mechanical, and thermal characteristics. To examine the insulating property, the interface characteristics of the polymer were evaluated using electrochemical impedance spectroscopy (EIS) with a frequency range of 1 × 105-0.01 Hz and an amplitude of 5.0 mV. EIS is an effective method to investigate the polymers' interfacial electron transfer characteristics. The EIS Nyquist plot showed high Warburg impedance features in the low-frequency domain with straight lines without a semicircle, suggesting that the property of the polymer owing to the high electrical resistance and poor conductivity for ionic kinetics in the electrolyte may have surpassed that of the semicircle. Although the slope of low frequencies in polymers holding potent exoelectrogenic bacteria (Shewanella oneidensis MR-1) as a charge carrier in the electrolyte could significantly reduce the Warburg resistance, it still could not improve the conductivity, which demonstrated that the external charge supply could not alter the insulating property in the used polymers.

Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-ß1/SMAD pathway.

BACKGROUND: The biological activity and regenerative medicine of bone marrow mesenchymal stem cells (BMSCs) have been focal topics in the broad fields of diabetic wound repair. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated during BMSC treatment. Our previous studies have shown that hypoxia is not only a typical pathological phenomenon of wounds but also exerts a vital regulatory effect on cellular bioactivity. In this study, the beneficial effects of hypoxic BMSCs on the cellular behaviors of epidermal cells and diabetic wound healing were investigated. METHOD: The viability and secretion ability of hypoxic BMSCs were detected. The autophagy, proliferation and migration of HaCaT cells cultured with hypoxic BMSCs-derived conditioned medium were assessed by estimating the expression of autophagy-related proteins, MTS, EdU proliferation and scratch assays. And the role of the SMAD signaling pathway during hypoxic BMSC-evoked HaCaT cell autophagy was explored through a series of in vitro gain- and loss-of-function experiments. Finally, the therapeutic effects of hypoxic BMSCs were evaluated using full-thickness cutaneous diabetic wound model. RESULTS: First, we demonstrated that hypoxic conditions intensify HIF-1α-mediated TGF-ß1 secretion by BMSCs. Then, the further data revealed that BMSC-derived TGF-ß1 was responsible for the activation of epidermal cell autophagy, which contributed to the induction of epidermal cell proliferation and migration. Here, the SMAD signaling pathway was identified as downstream of BMSC-derived TGF-ß1 to regulate HaCaT cell autophagy. Moreover, the administration of BMSCs to diabetic wounds increased epidermal autophagy and the rate of re-epithelialization, leading to accelerated healing, and these effects were significantly attenuated, accompanied by the downregulation of Smad2 phosphorylation levels due to TGF-ß1 interference in BMSCs. CONCLUSION: In this report, we present evidence that uncovers a previously unidentified role of hypoxic BMSCs in regulating epidermal cell autophagy. The findings demonstrate that BMSC-based treatment by restoring epidermal cell autophagy could be an attractive therapeutic strategy for diabetic wounds and that the process is mediated by the HIF-1α/TGF-ß1/SMAD pathway.

The design and application of an individualized 3D printing assisted guide plates in assisting sacroiliac screws insertion.

OBJECTIVE: Currently, the sacroiliac screws insertion still faces several challenges in the fixation of pelvic and acetabular injuries. This study was aimed to design a personalized three-dimensional (3D) printing assisted guide plates to assist sacroiliac screws insertion, so as to provide a reference for further clinical applications. METHODS: Eight pelvic specimens (5 males and 3 females) of normal adults were used to simulate actual operation. After thin-layer CT scanning, the 3D models of pelvis were established based on the images data. Furthermore, in Mimics 17.0 software, the screw entry points and screw channels of sacroiliac screws were further simulated and designed, and the appropriate range of the posterior superior iliac spine was selected to establish and print the virtual guide plates. Then, the simulated screws insertion was performed in vitro, the pelvic specimens after screws insertion were scanned again by CT, and the effect of screws insertion was further evaluated. RESULTS: A total of 16 sacroiliac screw guide plates were designed and printed, and 48 screws were inserted on both sides. Therein, 45 screws were completely located in the sacral vertebra, which was determined as grade 0, with an accuracy rate of 93.2%. The other 3 screws penetrated the anterior cortex or sacral canal of sacral vertebra, including 2 screws in Grade 1 (4.1%) and 1 screw in Grade 2 (2.1%). Compared with the simulated screw channels, the anterior and posterior offset angles of the cross section were (0.912 ± 0.625) ° and (0.802 ± 0.681) ° respectively, with no significant difference (p > 0.05). The upper and lower offset angles of coronal plane were (1.158 ± 0.823) ° and (1.034 ± 0.908) ° respectively, and there was no significant difference (p > 0.05). CONCLUSIONS: 3 D printing guide plates assisted sacroiliac screws insertion can enhance the stability of pelvic posterior ring fixation and assist surgeons to reduce the difficulty of operation.

Impairment characteristics of static balance and plantar load distribution of patients undergoing tibial cortex transverse distraction for diabetic foot ulcers.

OBJECTIVE: Tibial cortex transverse distraction (TCTD) has been recently reported for the treatment of diabetic foot ulcers. Herein, we explored the characteristics of the impairments in static balance and plantar load distribution in patients. METHODS: We performed a retrospective study of 21 patients with diabetic foot ulcers who underwent TCTD, who were regularly followed up for > 1 year after surgery, and 20 healthy individuals (control group). A pressure platform was used to assess the standing balance functions of the lower extremities and the plantar load distribution. RESULTS: One patient underwent amputation because of severe infection. In patient group, center of pressure (COP) ellipse sway area, COP path length and angle θ were all larger, compared with those of control group (250.15 ± 98.36 mm2 vs. 135.67 ± 53.21 mm2, 145.15 ± 67.43 mm vs. 78.47 ± 34.15 mm, 39.75 ± 17.61° vs. 22.17 ± 14.15°), with statistically significant differences (P < 0.01). The average plantar load and backfoot load of the unaffected side was significantly larger than that of the affected side (58.4 ± 5.5% vs. 41.6 ± 5.5%, 45.3 ± 6.4% vs. 36.5 ± 5.6%), but they were similar for the two feet of members of the control group. CONCLUSIONS: Although TCTD may represent an appropriate method for the treatment of diabetic foot ulcers, postoperative impairments in static balance and plantar load distribution remain in the long term. These potential long-term problems should be taken into account in further rehabilitation planning. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Methods for Predicting Ethylene/Cyclic Olefin Copolymerization Rates Promoted by Single-Site Metallocene: Kinetics Is the Key.

In toluene at 50 °C, the vinyl addition polymerization of 4-vinyl-cyclohexene (VCH) comonomers with ethylene is investigated using symmetrical metallocene (rac-Et(Ind)2ZrCl2) combined with borate/TIBA. To demonstrate the polymerizations' living character, cyclic VCH with linear-exocyclicπ and endocyclicπ bonds produces monomodal polymers, but the dispersity (Ɖ) was broader. The copolymers obtained can be dissolved in conventional organic solvent and have excellent thermal stability and crystalline temperature (ΔHm), and their melting temperature (Tm) varies from 109 to 126 °C, and ΔHm ranges from 80 to 128 (J/g). Secondly, the distribution of polymeric catalysts engaged in polymer chain synthesis and the nature of the dormant state are two of the most essential yet fundamentally unknown aspects. Comprehensive and exhaustive kinetics of E/VCH have shown numerous different kinetic aspects that are interpreted as manifestations of polymeric catalysts or of the instability of several types of active center [Zr]/[C*] fluctuations and formation rates of chain propagation RpE, RpVCH, and propagation rate constants kpE and kpVCH, the quantitative relationship between RpE, RpVCH and kpE, kpVCH and catalyst structures, their constituent polymer Mw, and their reactivity response to the endocyclic and exocyclic bonds of VCH. The kinetic parameters RpE, RpVCH, kpE, and kpVCH, which are the apparent rates for the metallocene-catalyzed E/VCH, RpE, and kpE values, are much more significant than RpVCH and kpVCH at 120 s, RpE and RpVCH 39.63 and 0.78, and the kpE and kpVCH values are 6461 and 93 L/mol·s, respectively, and minor diffusion barriers are recommended in the early stages. Compared with previously reported PE, RpE and kpE values are 34.2 and 7080 L/mol·s. VCH increases the RpE in the initial stage, as we are expecting; this means that the exocyclic bond of VCH is more active at the initial level, and that the chain transfer reaction of cyclic internal π double is increased with the reaction time. The tp versus Rp, kp, and [Zr]/[C*] fraction count may be fitted to a model that invokes deactivation of growing polymer chains. At tp 120-360 s higher, the incorporation rate of VCH suppresses E insertion, resulting in reduced molecular weight.

Bacteriological Investigation and Drug Resistance Analysis of Chronic Refractory Wound Secretions.

BACKGROUND: Chronic refractory wounds were common and the treatments were complicated for burn and plastic surgeons. This study was to investigate the bacterial distribution characteristics and bacterial drug resistance of chronic refractory wound secretions. METHODS: The authors retrospectively analyzed 425 patients with chronic refractory wound infection. The results of bacterial culture of wound secretions and drug sensitivity test were retrospectively analyzed. Further, the location area of the wound was divided into 4 regions, and the difference of the bacterial culture results between different regions was analyzed. RESULTS: The wound secretions were cultured into 401 bacterial strains, including 206 gram-positive bacteria strains, accounting for 51.4%, with the highest detection rate of Staphylococcus aureus at 26.2% (105/401). There were 195 gram-negative bacteria strains, accounting for 48.6%, with the highest detection rate of Pseudomonas aeruginosa at 14.2% (57/401). There were 6 fungal strains. The proportion of gram-negative bacteria in the III region of the wound zone was significantly greater than that in the other 3 regions. CONCLUSIONS: The detection rate of gram-positive bacteria and gram-negative bacteria of chronic refractory wound secretions is not much different. However, in the area close to the perineum (III region), gram-negative bacteria is significantly higher, which has a certain reference value for the use of antibiotics in clinical practice. LEVEL OF EVIDENCE: Level 4.

Analysis of the clinical characteristics of lamotrigine-induced haemophagocytic lymphohistiocytosis.

WHAT IS KNOWN AND OBJECTIVE: Lamotrigine is currently known to be related to haemophagocytic lymphohistiocytosis (HLH). Knowledge regarding the association between HLH and lamotrigine is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics of lamotrigine-induced HLH. METHODS: We collected literature from 1994 to 31 August 2020 in Chinese and English on HLH induced by lamotrigine for retrospective analysis. RESULTS AND DISCUSSION: A total of 17 patients (12 men and 5 women) from 15 studies were included, with a median age of 29 years old (range 4-47). Symptoms of lamotrigine-induced HLH were reported to have occurred within 6-24 days following treatment initiation. Six cases reported doses that ranged from 25 mg every other day to 800 mg once daily. The major clinical features of lamotrigine-induced HLH are fever, cytopenia, rash and hyperferritinaemia. Bone marrow showed haemophagocytosis. Fifteen patients improved with drug discontinuation, and 2 patients eventually died. WHAT IS NEW AND CONCLUSION: Hemophagocytic lymphohistiocytosis is a potentially serious adverse reaction to lamotrigine (LTG). Patients should be informed that if they experience any symptoms of HLH while taking lamotrigine, they should immediately seek medical attention.

Establishment of Bovine-Induced Pluripotent Stem Cells.

Pluripotent stem cells (PSCs) have been successfully developed in many species. However, the establishment of bovine-induced pluripotent stem cells (biPSCs) has been challenging. Here we report the generation of biPSCs from bovine mesenchymal stem cells (bMSCs) by overexpression of lysine-specific demethylase 4A (KDM4A) and the other reprogramming factors OCT4, SOX2, KLF4, cMYC, LIN28, and NANOG (KdOSKMLN). These biPSCs exhibited silenced transgene expression at passage 10, and had prolonged self-renewal capacity for over 70 passages. The biPSCs have flat, primed-like PSC colony morphology in combined media of knockout serum replacement (KSR) and mTeSR, but switched to dome-shaped, naïve-like PSC colony morphology in mTeSR medium and 2i/LIF with single cell colonization capacity. These cells have comparable proliferation rate to the reported primed- or naïve-state human PSCs, with three-germ layer differentiation capacity and normal karyotype. Transcriptome analysis revealed a high similarity of biPSCs to reported bovine embryonic stem cells (ESCs) and embryos. The naïve-like biPSCs can be incorporated into mouse embryos, with the extended capacity of integration into extra-embryonic tissues. Finally, at least 24.5% cloning efficiency could be obtained in nuclear transfer (NT) experiment using late passage biPSCs as nuclear donors. Our report represents a significant advance in the establishment of bovine PSCs.

Sheep models of F508del and G542X cystic fibrosis mutations show cellular responses to human therapeutics.

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The F508del and G542X are the most common mutations found in US patients, accounting for 86.4% and 4.6% of all mutations, respectively. The F508del causes deletion of the phenylalanine residue at position 508 and is associated with impaired CFTR protein folding. The G542X is a nonsense mutation that introduces a stop codon into the mRNA, thus preventing normal CFTR protein synthesis. Here, we describe the generation of CFTRF508del / F508del and CFTRG542X / G542X lambs using CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). First, we introduced either F508del or G542X mutations into sheep fetal fibroblasts that were subsequently used as nuclear donors for SCNT. The newborn CF lambs develop pathology similar to CFTR -/- sheep and CF patients. Moreover, tracheal epithelial cells from the CFTRF508del / F508del lambs responded to a human CFTR (hCFTR) potentiator and correctors, and those from CFTRG542X / G542X lambs showed modest restoration of CFTR function following inhibition of nonsense-mediated decay (NMD) and aminoglycoside antibiotic treatments. Thus, the phenotype and electrophysiology of these novel models represent an important advance for testing new CF therapeutics and gene therapy to improve the health of patients with this life-limiting disorder.

In Situ Generated Novel 1H MRI Reporter for ß-Galactosidase Activity Detection and Visualization in Living Tumor Cells.

For wide applications of the lacZ gene in cellular/molecular biology, small animal investigations, and clinical assessments, the improvement of noninvasive imaging approaches to precisely assay gene expression has garnered much attention. In this study, we investigate a novel molecular platform in which alizarin 2-O-ß-d-galactopyranoside AZ-1 acts as a lacZ gene/ß-gal responsive 1H-MRI probe to induce significant 1H-MRI contrast changes in relaxation times T 1 and T 2 in situ as a concerted effect for the discovery of ß-gal activity with the exposure of Fe3+. We also demonstrate the capability of this strategy for detecting ß-gal activity with lacZ-transfected human MCF7 breast and PC3 prostate cancer cells by reaction-enhanced 1H-MRI T 1 and T 2 relaxation mapping.

Comparative Analysis of Ethylene/Diene Copolymerization and Ethylene/Propylene/Diene Terpolymerization Using Ansa-Zirconocene Catalyst with Alkylaluminum/Borate Activator: The Effect of Conjugated and Nonconjugated Dienes on Catalytic Behavior and Polymer Microstructure.

The copolymerization of ethylene‒diene conjugates (butadiene (BD), isoprene (IP) and nonconjugates (5-ethylidene-2-norbornene (ENB), vinyl norbornene VNB, 4-vinylcyclohexene (VCH) and 1, 4-hexadiene (HD)), and terpolymerization of ethylene-propylene-diene conjugates (BD, IP) and nonconjugates (ENB, VNB, VCH and HD) using two traditional catalysts of C2-symmetric metallocene-silylene-bridged rac-Me2Si(2-Me-4-Ph-Ind)2ZrCl2 (complex A) and ethylene-bridged rac-Et(Ind)2ZrCl2 (complex B)-with a [Ph3C][B(C6F5)4] borate/TIBA co-catalyst, were intensively studied. Compared to that in the copolymerization of ethylene diene, the catalytic activity was more significant in E/P/diene terpolymerization. We obtained a maximum yield of both metallocene catalysts with conjugated diene between 3.00 × 106 g/molMt·h and 5.00 × 106 g/molMt·h. ENB had the highest deactivation impact on complex A, and HD had the most substantial deactivation effect on complex B. A 1H NMR study suggests that dienes were incorporated into the co/ter polymers' backbone through regioselectivity. ENB and VNB, inserted by the edo double bond, left the ethylidene double bond intact, so VCH had an exo double bond. Complex A's methyl and phenyl groups rendered it structurally stable and exhibited a dihedral angle greater than that of complex B, resulting in 1, 2 isoprene insertion higher than 1, 4 isoprene that is usually incapable of polymerization coordination. High efficiency in terms of co- and ter- monomer incorporation with higher molecular weight was found for complex 1. The rate of incorporation of ethylene and propylene in the terpolymer backbone structure may also be altered by the conjugated and nonconjugated dienes. 13C-NMR, 1H-NMR, and GPC techniques were used to characterize the polymers obtained.

Thirty-six-month results of laparoscopic-based renal denervation plus unilateral laparoscopic adrenalectomy for the treatment of patients with resistant hypertension caused by unilateral aldosterone-producing adenoma.

The aim of this study was to explore the long-term clinical results of Renal denervation (RDN) from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy to treat patients with resistant hypertension caused by unilateral aldosterone-producing adenoma (APA). Sixty patients with resistant hypertension caused by APA who were treated at Henan Provincial People's Hospital from December 2016 to March 2018 were selected and randomly assigned to undergo RDN from the adventitia of the renal artery plus adrenalectomy (RDN group, n = 30) or adrenalectomy alone (control group, n = 30). Office blood pressure (BP), antihypertensive medication usage and other laboratory characteristics were followed every 6 months through 36 months. Follow-up data were available at 36 months for 23 of 30 subjects in the RDN group and for 21 of 30 subjects who were in the control group. At 36 months postprocedure, the reduction in the RDN group was 42.2 ± 21.6 mmHg and that in the control group was 29.8 ± 13.5 mmHg (p = .029 between the groups). During the follow-up to 36 months postprocedure, no patients in either the RDN group or the control group died due to surgical complications, and the RDN group had no procedural complications, including renal artery dissection, perforation, and renal artery stenosis. There was no change in the mean eGFR of the two groups, and no serious adverse events were reported. In conclusion, RDN from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy resulted in sustained lowering of BP at 3 years in a selected population of subjects with resistant hypertension caused by unilateral APA without serious safety concerns.