RNADisease v4.0: an updated resource of RNA-associated diseases, providing RNA-disease analysis, enrichment and prediction.

Numerous studies have shown that RNA plays an important role in the occurrence and development of diseases, and RNA-disease associations are not limited to noncoding RNAs in mammals but also exist for protein-coding RNAs. Furthermore, RNA-associated diseases are found across species including plants and nonmammals. To better analyze diseases at the RNA level and facilitate researchers in exploring the pathogenic mechanism of diseases, we decided to update and change MNDR v3.0 to RNADisease v4.0, a repository for RNA-disease association (http://www.rnadisease.org/ or http://www.rna-society.org/mndr/). Compared to the previous version, new features include: (i) expanded data sources and categories of species, RNA types, and diseases; (ii) the addition of a comprehensive analysis of RNAs from thousands of high-throughput sequencing data of cancer samples and normal samples; (iii) the addition of an RNA-disease enrichment tool and (iv) the addition of four RNA-disease prediction tools. In summary, RNADisease v4.0 provides a comprehensive and concise data resource of RNA-disease associations which contains a total of 3 428 058 RNA-disease entries covering 18 RNA types, 117 species and 4090 diseases to meet the needs of biological research and lay the foundation for future therapeutic applications of diseases.

Transformation of 2D Flakes to 3D Hollow Bowls: Matthew Effect Enables Defects to Prevail in Electromagnetic Wave Absorption of Hollow rGO Bowls.

High-efficiency electromagnetic (EM) wave (EMW)-absorbing materials have attracted extensive scientific and technical interest. Although identifying the dominant EM loss mechanism in dielectric-loss materials is indispensable, it is challenging due to a complex synergism between dipole/interfacial polarization and conduction loss. Modulation of defects and microstructures can be a possible approach to determine the dominant EM loss mechanism and realize high-efficiency absorption. Herein, 2D reduced graphene oxide (rGO) flakes are integrated into a 3D hollow bowl-like structure, which increases defect sites (i.e., oxygen vacancy and lattice defect) and reduces the stacked thickness of rGO. Despite their lower stacked thicknesses, the hollow rGO bowls with more defects exhibit lower conductivities but higher permittivities. Accompanied by the transformation from 2D flakes to 3D hollow bowls, the dominant EM loss mechanism of rGO transforms from conduction loss to defect-induced polarization. Furthermore, the defect engineering and structural design endow rGO with well-matched impedance and strong EMW-absorbing capacity. A minimum reflection loss of -41.6 dB (1.3 mm) and an effective absorption bandwidth of 4.8 GHz (1.5 mm) is achieved at a filler loading of 5 wt%. This study will provide meaningful insights into the development of materials with superior EMW-absorbing performances via defect engineering and structural design.

Comprehensive Analysis of PKD1 and PKD2 by Long-Read Sequencing in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by heterogeneous variants in the PKD1 and PKD2 genes. Genetic analysis of PKD1 has been challenging due to homology with 6 PKD1 pseudogenes and high GC content. METHODS: A single-tube multiplex long-range-PCR and long-read sequencing-based assay termed "comprehensive analysis of ADPKD" (CAPKD) was developed and evaluated in 170 unrelated patients by comparing to control methods including next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification. RESULTS: CAPKD achieved highly specific analysis of PKD1 with a residual noise ratio of 0.05% for the 6 pseudogenes combined. CAPKD identified PKD1 and PKD2 variants (ranging from variants of uncertain significance to pathogenic) in 160 out of the 170 patients, including 151 single-nucleotide variants (SNVs) and insertion-deletion variants (indels), 6 large deletions, and one large duplication. Compared to NGS, CAPKD additionally identified 2 PKD1 variants (c.78_96dup and c.10729_10732dup). Overall, CAPKD increased the rate of variant detection from 92.9% (158/170) to 94.1% (160/170), and the rate of diagnosis with pathogenic or likely pathogenic variants from 82.4% (140/170) to 83.5% (142/170). CAPKD also directly determined the cis-/trans-configurations in 11 samples with 2 or 3 SNVs/indels, and the breakpoints of 6 large deletions and one large duplication, including 2 breakpoints in the intron 21 AG-repeat of PKD1, which could only be correctly characterized by aligning to T2T-CHM13. CONCLUSIONS: CAPKD represents a comprehensive and specific assay toward full characterization of PKD1 and PKD2 variants, and improves the genetic diagnosis for ADPKD.

Amide Proton Transfer-Weighted Magnetic Resonance Imaging for Application in Renal Fibrosis: A Radiological-Pathological-Based Analysis.

INTRODUCTION: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.

A finite element analysis of a low-profile femoral neck system of screws in sleeves in a vertical femoral neck fracture model.

BACKGROUND: Femoral neck system (FNS) has exhibited some drawbacks, such as non-fit of the plate with the lateral femoral cortex, postoperative pain, and the potential risk of subtrochanteric fractures. We have developed a low-profile FNS system that addresses some compatibility issues in FNS. In this study, we conducted finite element analysis on the 1-hole FNS (1 H-FNS), 2-holes FNS (2 H-FNS), and low-profile FNS (LP-FNS) and compared their biomechanical performance. METHODS: After the mesh convergence analysis, we established three groups of 1 H-FNS, 2 H-FNS, and LP-FNS. The interfragmentary gap, sliding distance, shear stress, and compressive stress and the bone-implant interface compression stress, stiffness, and displacement were determined under the neutral, flexion, or extension conditions of the hip joint, respectively. The stress and displacement of the femur after the implant removal were also investigated. RESULTS: (1) There were no obvious differences among the three FNS groups in terms of the IFM distance. However, the LP-FNS group showed less rotational angle compared with conventional FNS (neutral: 1 H-FNS, -61.64%; 2 H-FNS, -45.40%). Also, the maximum bone-implant interface compression stress was obviously decreased under the neutral, flexion, or extension conditions of the hip joint (1 H-FNS: -6.47%, -20.59%, or -4.49%; 2 H-FNS: -3.11%, 16.70%, or -7.03%; respectively). (2) After the implant removal, there was no notable difference in the maximum displacement between the three groups, but the maximum von Mises stress displayed a notable difference between LP-FNS and 1 H-FNS groups (-15.27%) except for the difference between LP-FNS and 2 H-FNS groups (-4.57%). CONCLUSIONS: The LP-FNS may not only provide the same biomechanical stabilities as the 1 H-FNS and 2 H-FNS, but also have more advantages in rotational resistance especially under the neutral condition of the hip joint, in the bone-implant interface compression stress, and after the implant removal. In addition, the 1 H-FNS and 2 H-FNS have similar biomechanical stabilities except for the maximum von Mises stress after the implant removal. The femur after the LP-FNS removal not only is subjected to relatively little stress but also minimizes stress concentration areas.

Muscone promotes functional recovery by facilitating microglia polarization into M2 phenotype through PPAR-γ pathway after ischemic stroke.

Exploring regimens to facilitate microglia transformation from M1 to M2 phenotype is a feasible strategy to suppress neuroinflammation, therefore reinforcing functional recovery after ischemic stroke. Muscone easily crosses the blood brain barrier (BBB) and distributes throughout the brain. Here, the results illustrated the administration of 8 mg/kg muscone promoted functional recovery through reducing the infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) staining after ischemic stroke in mice. Then, the expression of pro-inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), was significantly decreased, whereas the level of anti-inflammatory agents including C-X-C Motif Chemokine Ligand 1 (CXCL1), transforming growth factor-ß (TGF-ß) and interleukin-10 (IL-10) was obviously elevated in penumbra with the treatment of 8 mg/kg muscone using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), western blot and enzyme-linked immunosorbent assay (ELISA) tests. Subsequently, the results showed the application of muscone upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) to facilitate microglia transformation into M2 phenotype using RT-qPCR, western blot and immunofluorescence analysis. Collectively, the present study provides evidence for our hypothesis that muscone intensifies microglia transformation into M2 phenotype via activating PPAR-γ signaling pathway in penumbra after ischemic stroke. These findings demonstrate muscone is a promising candidate for the treatment of ischemic stroke.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Novel Information-Driven Smoothing Spline Linearization Method for High-Precision Displacement Sensors Based on Information Criterions.

A noise-resistant linearization model that reveals the true nonlinearity of the sensor is essential for retrieving accurate physical displacement from the signals captured by sensing electronics. In this paper, we propose a novel information-driven smoothing spline linearization method, which innovatively integrates one new and three standard information criterions into a smoothing spline for the high-precision displacement sensors' linearization. Using theoretical analysis and Monte Carlo simulation, the proposed linearization method is demonstrated to outperform traditional polynomial and spline linearization methods for high-precision displacement sensors with a low noise to range ratio in the 10-5 level. Validation experiments were carried out on two different types of displacement sensors to benchmark the performance of the proposed method compared to the polynomial models and the the non-smoothing cubic spline. The results show that the proposed method with the new modified Akaike Information Criterion stands out compared to the other linearization methods and can improve the residual nonlinearity by over 50% compared to the standard polynomial model. After being linearized via the proposed method, the residual nonlinearities reach as low as ±0.0311% F.S. (Full Scale of Range), for the 1.5 mm range chromatic confocal displacement sensor, and ±0.0047% F.S., for the 100 mm range laser triangulation displacement sensor.

TRIM3 facilitates estrogen signaling and modulates breast cancer cell progression.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. More than 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha-negative breast cancer, which is more aggressive and has a shorter survival time, ER alpha-positive breast cancer could benefit from endocrine therapy. Selective estrogen receptor modulators, such as tamoxifen, are widely used in endocrine therapy. Approximately half of ER alpha-positive breast cancer patients will eventually develop endocrine resistance, making it a major clinical challenge in therapy. Thus, decoding the throughput of estrogen signaling, including the control of ER alpha expression and stability, is critical for the improvement of breast cancer therapeutics. METHODS: TRIM3 and ER alpha protein expression levels were measured by western blotting, while the mRNA levels of ER alpha target genes were measured by RT-PCR. A CCK-8 assay was used to measure cell viability. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling activity was accomplished with luciferase assays, RT-PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect ER alpha protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the ER alpha protein. RESULTS: In our current study, we found that TRIM3, an E3 ligase, can promote ER alpha signaling activity and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and migration, while unbiased RNA sequencing data indicated that TRIM3 is required for the activity of estrogen signaling on the -genome-wide scale. The immunoprecipitation assays indicated that TRIM3 associates with ER alpha and promotes its stability, possibly by inducing K63-linked polyubiquitination of ER alpha. In conclusion, our data implicate a nongenomic mechanism by which TRIM3 stabilizes the ER alpha protein to control ER alpha target gene expression linked to breast cancer progression. CONCLUSION: Our study provides a novel posttranslational mechanism in estrogen signaling. Modulation of TRIM3 expression or function could be an interesting approach for breast cancer treatment. Video abstract.

Long noncoding RNA NEAT1 decreases polycystic ovary syndrome progression via the modulation of the microRNA-324-3p and BRD3 axis.

Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is believed to be involved in many gynecological and obstetrics disorders. Nevertheless, the role of NEAT1 in polycystic ovary syndrome (PCOS) is scarcely investigated. Our study aimed to investigate the role of NEAT1, microRNA (miR)-324-3p, and bromodomain containing 3 (BRD3) in PCOS. First, 80 women with PCOS and 80 healthy (non-PCOS) women were included, and their serum hormone levels were tested. Next, the PCOS mouse model was established by dehydroepiandrosterone injection, and then NEAT1, miR-324-3p, and BRD3 expression levels were detected in the PCOS mice. Lentivirus carrying short hairpin-NEAT1 or miR-324-3p agomir was injected into the PCOS mice to determine the change in biochemical indices and pathology. Moreover, a rescue experiment was conducted, after which, the binding relationships among NEAT1, miR-324-3p, and BRD3 were analyzed. NEAT1 and BRD3 were expressed at a high level while miR-324-3p was expressed at a low level in women with PCOS and PCOS mice. Reduced levels of NEAT1 or elevated levels of miR-324-3p mitigated metabolic disorders and alleviated ovarian pathological changes in PCOS mice. Mechanistically, NEAT1 sponged miR-324-3p and miR-324-3p targeted BRD3. In the rescue experiment, elevated miR-324-3p or reduced BRD3 level reversed the effects of the enhanced NEAT1 on metabolic disorders and ovarian pathological changes in PCOS mice. NEAT1 exacerbates metabolic disorders and ovarian pathological changes in PCOS mice by downregulating miR-324-3p and upregulating BRD3. This study gives a novel direction in PCOS treatment.

Self-Assembly of a Pd4Cu8L8 Cage for Epoxidation of Styrene and Its Derivatives.

Herein we report a discrete heterometallic Pd4Cu8L8 cage with a tubular structure, which was synthesized by the assembly of copper metalloligands and PdII ions in a stepwise manner. The Pd4Cu8L8 cage has been unequivocally characterized by single-crystal X-ray diffraction, electrospray ionization-mass spectroscopy, and energy dispersive spectroscopy. The cage showed excellent catalytic activity in the epoxidation of styrene and its derivatives under conditions without using additional solvent, providing potential material for catalyzing the oxidation reactions.

Isolated adrenocorticotropic hormone deficiency associated with sintilimab therapy in a patient with advanced lung adenocarcinoma: a case report and literature review.

BACKGROUND: Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy. CASE PRESENTATION: A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level. CONCLUSIONS: Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.

Should cannulated screws be removed after a femoral neck fracture has healed, and how? A finite element analysis of the femur before and after cannulated screw removal.

PURPOSE: The removal of three inverted triangular parallel cannulated screws after the femoral neck fracture healing is sometimes accompanied by osteonecrosis of the femoral head (ONFH) or its refracture. The purpose of this study was to determine the biomechanical changes of the femur before and after the screw removal using a finite element analysis. METHODS: The CT data of the femurs were obtained from a 69-year-old healthy female to establish the femur models. The established finite element models consisted of N, C, and R groups: N group, the normal femur; C group (to simulate the femoral neck fracture healing after the internal fixation), the normal femur with three inverted triangular parallel cannulated screws (C1) or with two upper parallel screws (C2). For the R1 or R2 groups, the screws in the model of the C1 or C2 individuals were gradually removed in seven or three types of different screw combinations, respectively. The stresses and displacements of the femur were determined. RESULTS: (1) Compared with the N group, a uniform stress distribution was stopped by the addition of three screws in the C1 group; in contrast, all screw removals resulted in the stress concentration on the screw holes and the disappearance of stress shielding. Moreover, the average stress of the femoral head in C1 group increased by 37.85%, while that of the femoral neck decreased by 23.03%. (2) Compared with the C1 group, while only the lowest femoral calcar screw was removed, there was a similar stress distribution in the proximal femur, and the average stress of the femoral head increased only by 0.35% although that of the femoral neck increased by 63.62%; however, removal by any other means resulted in a significant stress concentration in the proximal femur and a significant increase in the average stresses of the femoral head and neck (5.96-40.95% and 12.82-75.46%, respectively). (3) Compared with the N or C1 group, there was a significant stress concentration on the screws and its surrounding proximal femur in the C2 group. (4) Compared with the C2 group, the simultaneous removal of two upper screws not only did not cause a significant stress concentration on the proximal femur but also significantly reduced the average stresses of the femoral head and neck by 87.49% and 65.51% respectively. On the contrary, the gradual removal of two screws caused a significant stress concentration on the screw and its surrounding proximal femur although the average stresses of the femoral head and neck decreased by 88.79-89.06% and 67.00-67.22%, respectively. (5) Compared with the N group, the average displacements of the femoral head and neck in the C1 group increased only by 3.12% and 3.37%, respectively. Additionally, compared with the C1 group, while three, two, or one screw was simultaneously removed, the average displacements of the femoral head and neck only fluctuated - 5.51-1.65% and 1.78-9.03%, respectively. CONCLUSIONS: Residual internal fixation after femoral neck fracture healing may lead to stress concentration on screws and stress shielding around screws. The first removal of the lowest femoral calcar screw and then the second removal of two upper residual screws have a minimum effect on the stress concentration on the proximal femur and the average stress on the femoral head. The incorrect screw removal and resulting femoral load may well be closely related to occurrence in ONFH or its refracture.

Characterization of Neodymium Speciation in the Presence of Fulvic Acid by Ion Exchange Technique and Single Particle ICP-MS.

It has been well known that the free ion concentration of metals plays a vital role in metal bioavailability. However, measurement of this fraction is still not easy over years of development. Nowadays, rare earth elements (REEs) are drawing more attentions as an emerging contaminant due to their wide applications in our daily life. To analyze the free ion concentration of neodymium (Nd), we adopted ion-exchange technique (IET) to investigate the changes on Nd free ion concentration in the presence of fulvic acid (FA). With the dynamic mode of IET analysis, the concentrations of Nd free ion were in the range of 0.85-36.8 × 10-8 M at the total Nd concentration of 5 × 10-7 M when FA varied from 0.4 to 10 M. However, these concentrations were 3-58 times higher than the one calculated by WHAM 7.0, which may be due to the particulate Nd spontaneously formed in solution. With single particle ICP-MS analysis, we found 0.25%-2.36% of Nd was in the form of colloids when the total Nd concentrations varied from 8.5 × 10-9 to 4.7 × 10-7 M, with the average particle sizes in the range of 26.5-39.2 nm. The presence of FA significantly decreased the number of Nd colloids, but increased the average particle size. Under the TEM, we found that Nd colloids were amorphous, with the size less than 200 nm. The present study provided a relatively new perspective on REE speciation in water. The natural organic matters not only affect the free ion concentration of Nd, but also influenced the size and numbers of Nd colloids in solution.

[Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs].

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,ß-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 µmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.

Preparation and evaluation of alendronate sodium solid lipid nanoparticles with high oral bioavailability in rats.

Low oral bioavailability of alendronate sodium (ALE) significantly limits its clinical application. However, few studies focus on preparing ALE solid lipid nanoparticles (ALE-SLNs) and investigating its oral bioavailability in vivo due to highly hydrophilic property of ALE. In this study, ALE-SLNs were prepared through high-speed shearing combined with ultrasonic treatment method. ALE-SLNs were evaluated by average particle size, electric potential, encapsulation efficiency (EE), and drug loading (DL). Our results showed that the average EE and DL reached 62.56±0.94% and 6.26±0.09% (n=3), respectively. 120.27±1.17nm, 0.29±0.13 and -19.1±0.27 mV (n=3) were obtained in the average particle size, polydispersity index and zeta potential, respectively. The stability test showed that ALE-SLNs remained stable for more than 2 months at 4°C. After oral administration of ALE-SLNs (4.5mg/kg), the bioavailability was 2.17 times higher than that of ALE solution (86.82±3.6 vs 40.1±1.3µg) in rats. Our results indicate that high-speed shearing combined with the ultrasound method is simple and rapid to prepare ALE-SLNs. SLNs can improve the oral delivery of ALE in rats, which may exert beneficial effects in clinical applications.

Association between Procalcitonin and Acute Kidney Injury in Patients with Bacterial Septic Shock.

OBJECTIVE: The objective of this study was to assess the relationship between serum procalcitonin (PCT) and acute kidney injury (AKI) induced by bacterial septic shock. METHODS: A retrospective study was designed which included patients who were admitted to the ICU from January 2015 to October 2018. Multiple logistic regression and receiver operating characteristic (ROC) as well as smooth curve fitting analysis were used to assess the relationship between the PCT level and AKI. RESULTS: Of the 1,631 patients screened, 157 patients were included in the primary analysis in which 84 (53.5%) patients were with AKI. Multiple logistic regression results showed that PCT (odds ratio [OR] = 1.017, 95% confidence interval [CI] 1.009-1.025, p < 0.001) was associated with AKI induced by septic shock. The ROC analysis showed that the cutoff point for PCT to predict AKI development was 14 ng/mL, with a sensitivity of 63% and specificity 67%. Specifically, in multivariate piecewise linear regression, the occurrence of AKI decreased with the elevation of PCT when PCT was between 25 ng/mL and 120 ng/mL (OR 0.963, 95% CI 0.929-0.999; p = 0.042). The AKI increased with the elevation of PCT when PCT was either <25 ng/mL (OR 1.077, 95% CI 1.022-1.136; p = 0.006) or >120 ng/mL (OR 1.042, 95% CI 1.009-1.076; p = 0.013). Moreover, the PCT level was significantly higher in the AKI group only in female patients aged ≤75 years (p = 0.001). CONCLUSIONS: Our data revealed a nonlinear relationship between PCT and AKI in septic shock patients, and PCT could be used as a potential biomarker of AKI in female patients younger than 75 years with bacterial septic shock.

Effects of dexmedetomidine on intraoperative hemodynamics, recovery profile and postoperative pain in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: To investigate the optimal dose of dexmedetomidine to maintain hemodynamic stability, prevent of cough and minimize postoperative pain for patients undergoing laparoscopic cholecystectomy. METHODS: One hundred twenty patients were randomly divided into D1, D2, D3 and NS groups, and dexmedetomidine 0.4, 0.6, 0.8µg/kg and normal saline were administrated respectively. Patients' heart rate, systolic blood pressure and diastolic blood pressure were measured at T1-T7. The incidence of cough was recorded. Other parameters were noted, the time of spontaneous respiratory recovery and extubation, visual analogue scale scores and dosage of tramadol. RESULTS: The heart rate, systolic blood pressure and diastolic blood pressure of D2 and D3 groups has smaller fluctuations at T2-3 and T7 compared with NS and D1 groups (P < 0.05). The incidence of cough was lower in D2 and D3 groups than NS group (P < 0.05). The visual analogue scale scores and tramadol dosage of D2 and D3 groups were lower than NS group (P < 0.05). The time of spontaneous respiratory recovery and extubation in D3 group was longer than that in D1 and D2 groups (P < 0.05). CONCLUSIONS: Intravenous infusion of 0.6µg/kg dexmedetomidine before induction can maintain hemodynamic stability, decrease cough during emergence, relieve postoperative pain of patients undergoing laparoscopic cholecystectomy. TRIAL REGISTRATION: ChiCTR1900024801 , registered at the Chinese Clinical Trial Registry, principal investigator: Qin Ye, date of registration: July 28, 2019.

Chromatically multi-focal optics based on micro-lens array design.

CCD arrays encode color information via uniformly distributed red, green and blue pixels. Therefore, even a perfectly achromatic system projecting an image onto a CCD plane cannot possibly associate a single object point with the 3 or more discrete pixels encoding color content. Here, we propose and demonstrate a micro-lens array (MLA) design that simultaneously corrects chromatic aberrations and separates color channels to spatially distinct pixels. Starting from a commercially available aspheric condenser lens, methods to design and assess the performance of a few microns deep MLA etched on the convex optical surface are detailed. Actual fabrication is carried out by fluid jet polishing, with an optical form deviation of 0.24 µm rms. Finally, the MLA is assessed with a narrowly collimated beam containing two wavelengths, which produces distinct spots of diameter 10-15 µm as expected.

Anti-Infective and Pro-Coagulant Chitosan-Based Hydrogel Tissue Adhesive for Sutureless Wound Closure.

Multifunctional tissue adhesives with excellent adhesion, antibleeding, anti-infection, and wound healing properties are desperately needed in clinical surgery. However, the successful development of multifunctional tissue adhesives that simultaneously possess all these properties remains a challenge. We have prepared a novel chitosan-based hydrogel adhesive by integration of hydrocaffeic acid-modified chitosan (CS-HA) with hydrophobically modified chitosan lactate (hmCS lactate) and characterized its gelation time, mechanical properties, and microstructure. Tissue adhesion properties were evaluated using both pigskin and intestine models. In situ antibleeding efficacy was demonstrated via the rat hemorrhaging liver and full-thickness wound closure models. Good antibacterial activity and anti-infection capability toward S. aureus and P. aeruginosa were confirmed using in vitro contact-killing assays and an infected pigskin model. The result of coculturing with 3T3 fibroblast cells indicated that the hydrogels have no significant cytotoxicity. Most importantly, the biocompatible and biodegradable CS-HA/hmCS lactate hydrogel was able to close the wound in a sutureless way and promote wound healing. Our results demonstrate that this hydrogel has great promise for sutureless closure of surgical incisions.