Absence of ULK1 decreases AMPK activity in the kidney, leading to chronic kidney disease progression.

AMP-activated protein kinase (AMPK) inactivation in chronic kidney disease (CKD) leads to energy status deterioration in the kidney, constituting the vicious cycle of CKD exacerbation. Unc-51-like kinase 1 (ULK1) is considered a downstream molecule of AMPK; however, it was recently reported that the activity of AMPK could be regulated by ULK1 conversely. We demonstrated that AMPK and ULK1 activities were decreased in the kidneys of CKD mice. However, whether and how ULK1 is involved in the underlying mechanism of CKD exacerbation remains unknown. In this study, we investigated the ULK1 involvement in CKD, using ULK1 knockout mice. The CKD model of Ulk1-/- mice exhibited significantly exacerbated renal function and worsening renal fibrosis. In the kidneys of the CKD model of Ulk1-/- mice, reduced AMPK and its downstream ß-oxidation could be observed, leading to an energy deficit of increased AMP/ATP ratio. In addition, AMPK signaling in the kidney was reduced in control Ulk1-/- mice with normal renal function compared to control wild-type mice, suggesting that ULK1 deficiency suppressed AMPK activity in the kidney. This study is the first to present ULK1 as a novel therapeutic target for CKD treatment, which regulates AMPK activity in the kidney.

Usefulness of aliasing phenomenon for diagnosing venous valve stenosis of arteriovenous fistula in a hemodialysis patient.

We present venous valve stenosis, which is an uncommon cause of arteriovenous fistula (AVF) dysfunction. Owing to the thin structure in echography, venous valves are challenging to observe; however, we have found that the aliasing phenomenon is useful for diagnosing venous valve stenosis.

Pretreatment Immature Platelet Fraction as a Surrogate of Reticulated Platelets Predicts the Response to Corticosteroids in Adults with Immune Thrombocytopenia.

OBJECTIVES: Reticulated platelets circulating in the blood reflect megakaryopoietic activity and platelet turnover and can be automatically and low-invasively measured as the immature platelet fraction (IPF) using a Sysmex XN hematocytometer. The present study retrospectively investigated whether or not the IPF can predict the treatment response to corticosteroids in adult patients with primary immune thrombocytopenia (ITP). METHODS: Forty-six patients who had been newly diagnosed with primary treatment-naïve ITP and started treatment with corticosteroids were analyzed. RESULTS: Among the 46 primary ITP patients, 33 (72%) responded to the treatment and 13 (28%) did not. The percentage of IPF (IPF%) among the nonresponders was significantly lower than that of the responders (6.6 vs. 16.0%; p < 0.001). In the receiver operating characteristics analysis, the optimum IPF% cut-off value for predicting the treatment response was 12%, with a specificity of 85% and a sensitivity of 76%. CONCLUSIONS: Our findings thus suggest that measuring the IPF% as a surrogate of reticulated platelets is useful to identify patients likely to respond to corticosteroids.

Generation of a Nearly Monocycle Optical Pulse in the Near-Infrared Region and Its Use as an Ionization Source in Mass Spectrometry.

We report on the generation of an octave-spanning (600-1400 nm) nearly monocycle (1.1 cycle) ultrashort optical pulse (3.2 fs) in the near-infrared region by the Fourier synthesis of two pulses at 800 and 1200 nm, both of which were spectrally broadened by self-phase modulation and were compressed by chirp mirrors. The 3.2 fs pulse was converted into the ultraviolet by third harmonic generation, the pulse width being evaluated to 1.9 fs. The near-infrared pulse (3.2 fs) was employed as an ionization source in mass spectrometry, and the signal intensity was significantly increased for pentachlorobenzene, an environmental pollutant listed in the Stockholm Convention. The present data and the spectral properties obtained by quantum chemical calculations suggest that the method offers a potential advantage for the detection of Novichok, a chemical warfare agent that is thought to have been used in a terrorist attack.

CRT in a congenital heart disease patient with interventricular dyssynchrony due to an RV conduction delay.

We encountered a unique pattern of cardiac dyssynchrony in a patient with complex congenital heart disease (heterotaxy syndrome) with a biventricular physiology and systemic left ventricle (LV). On speckle tracking echocardiography, dyssynchrony was not detected within the LV, but was noted in an interventricular fashion between the LV and right ventricle (RV). An electrophysiologic study revealed a conduction delay in the subpulmonary RV. Cardiac resynchronization therapy provided reverse cardiac remodeling and an excellent result in our patient by placing the pacing leads around the dyssynchronous lesion.

An autopsy case of globular glial tauopathy presenting with clinical features of motor neuron disease with dementia and iron deposition in the motor cortex.

Globular glial tauopathy (GGT) is a 4-repeat (4R) tauopathy in which 4R tau accumulates to form globular glial inclusions (GGIs), predominantly in oligodendroglia. To date, little has been reported on iron deposits in patients with GGT. We report a case of GGT with iron deposits in a 78-year-old woman presenting with an 8-year history of slowly progressing limb weakness and cognitive decline. Susceptibility-weighted imaging revealed a low signal intensity in the right precentral gyrus, suggesting iron deposition. A clinical diagnosis of motor neuron disease with dementia was made 4 years after onset. At autopsy, gross pathological findings showed atrophy of the frontal and temporal lobes. A localized area of the precentral gyrus corresponding to the most severely affected limb showed the strongest atrophy, macroscopically, and displayed 4R tau-immunoreactive GGIs and microscopically many ferritin-immunoreactive neurons. We diagnosed this patient as having GGT. This is the first GGT case with iron deposition confirmed both radiologically and pathologically.

Extranodal NK/T-cell lymphoma, nasal type, manifesting as rapidly progressive dementia without any mass or enhancing brain lesion.

Among the many potential etiologies for rapidly progressive dementia (RPD), primary central nervous system extranodal NK/T-cell lymphoma, nasal-type (ENKL) is a rare entity. We present the first reported case of autopsy-proven RPD due to ENKL without any mass or enhancing lesion of the brain. A 54-year-old immunocompetent man presented with RPD, myoclonus and ataxia. The mini-mental state examination (MMSE) score was 22/30. His brain MRI revealed progressive brain atrophy without gadolinium enhancement or mass lesion. Five months after the initial evaluation, cognitive impairment further worsened with an MMSE score of 3/30. At the advanced stage, lumbar MRI showed swollen cauda equina with gadolinium enhancement. The number of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid had gradually increased. Twelve months after onset, the patient died of respiratory failure. Pathological findings revealed that lymphoma cells had diffusely invaded the meninges, parenchyma of the brain, spinal cord and cauda equina. Cells were positive for CD3, CD56 and EBV-encoded small RNAs and negative for CD20. No evidence of malignancy was identified in the visceral organs. This report indicates that ENKL should be recognized as one of the rare causes of RPD. Early testing for EBV-DNA in cerebrospinal fluid and imaging of cauda equina would be useful diagnostic tools.

Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion.

ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and ß-cell function. Elovl6 is expressed in both islets and ß-cell lines. In mice fed with chow, islets of the Elovl6(-/-) mice displayed normal architecture and ß-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6(-/-) mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6(-/-) islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per ß-cell and diabetes.

Frequency-resolved optical gating with two nonlinear optical processes.

A frequency-resolved optical gating (FROG) technique that combines autocorrelation (second-harmonic-generation FROG, SHG-FROG) and cross correlation FROG (XFROG) is reported for simultaneous characterization of two unknown optical pulses. Two SHG-FROG signals and a XFROG signal are acquired in a single measurement using a single diagnostic system. Unlike the conventional combination of SHG-FROG for reference-pulse characterization and XFROG for test-pulse characterization, the ambiguity in the direction of time in SHG-FROG is removed during phase retrieval by simultaneously analyzing the three FROG signals. Furthermore, overall characterization is faster, more robust, and highly convergent than the conventional combination of SHG-FROG and XFROG techniques.

Extensive cortical spongiform changes with cerebellar small amyloid plaques: the clinicopathological case of MV2K+C subtype in Creutzfeldt-Jakob disease.

We report a clinical case report of the MV2K+C subtype of sporadic Creutzfeldt-Jakob disease (sCJD). The patient was a 72-year-old woman who exhibited progressive dementia over the course of 22 months. Diffusion-weighted MRI during this period showed abnormal hyperintensity in the cerebral cortex in the early stage. The clinical course was similar to that of previously reported patients with the MV2K or MV2K+C subtype of sCJD. However, histopathological examination revealed unique features: severe extensive spongiform changes with perivacuolar deposits in the cerebrum and basal ganglia, plaque-like PrP deposits in the cerebrum, and only mild changes in the cerebellum with small amyloid plaques (∼20 µm in diameter), smaller than those in the MV2K subtype or variant CJD (40-50 µm in diameter). Molecular analysis showed a methionine/valine heterozygosity at codon 129 and no pathogenic mutation in the PrP gene (PRNP). Western blot analysis of the protease-resistant PrP (PrP(Sc) ) in the right temporal pole revealed the type 2 pattern, which is characterized by a single unglycosylated band, in contrast to the doublet described for the typical MV2 subtype of sCJD. The other intermediate band might exist in the cerebellum with kuru plaques. Therefore, small amyloid plaques in the cerebellum can be crucial for MV2K+C subtype.

High-pH mobile phase in reversed-phase liquid chromatography-tandem mass spectrometry to improve the separation efficiency of aminoglycoside isomers.

In chromatography, the use of extreme conditions can often lead to unique separation selectivity. In this study, a highly basic mobile phase (pH > 11), which is not typically employed for reversed-phase liquid chromatography (RPLC), was utilized in RPLC-tandem mass spectrometry (MS/MS) to achieve effective separation between electrically neutral bases of aminoglycosides (AGs). A mixture of AGs was simultaneously analyzed using 500 mmol L-1 ammonia aqueous solution (pH 11.8) as the mobile phase. A total of 11 AGs, including 2 stereoisomers of neomycin (B and C) and 5 structurally similar components of gentamicin (C1, C1a, C2, C2a, and C2b), were completely separated for the first time. The high separation performance for AGs was mainly due to two factors: First, slight differences in hydrophobicity among the AGs were significantly enhanced at a high pH by the complete acid dissociation of amines. Second, the high pH of the mobile phase minimized any electrostatic interactions between the AGs and residual silanol groups in the stationary phase, resulting in extremely sharp peaks for the AGs. The sensitivity of spectinomycin decreased by more than 20% when using the highly basic mobile phase (pH 11.8) due to its degradation, therefore, a mixture of 10 AGs was analyzed with 250 mmol L-1 ammonia aqueous solution (pH 11.5) with less degradation as the optimum condition. The developed analytical method could be used to determine the concentrations of trace AGs in milk with high accuracy and precision. Thus, RPLC-MS/MS using a high-pH mobile phase has great potential for the efficient separation of basic compounds containing amino sugars such as AGs.

A case of recurrent peritoneal dialysis-related peritonitis caused by Stenotrophomonas maltophilia during ongoing antibiotic treatment for Enterococcus faecalis-induced peritonitis.

Recurrent peritonitis is a serious complication of peritoneal dialysis (PD), which could result in PD withdrawal and mortality. However, cases of recurrent peritonitis occurring during ongoing antimicrobial therapy are rarely reported. Herein, we present a 71-year-old man who experienced initial peritonitis due to Enterococcus faecalis. Despite effective antimicrobial therapy, he developed recurrent peritonitis while on antimicrobial therapy. PD fluid culture analysis yielded Stenotrophomonas maltophilia (S. maltophilia). He was treated with multiple antimicrobials, and the peritoneal catheter was removed. To the best of our knowledge, this is the first case of recurrent peritonitis caused by S. maltophilia, which was developed during antimicrobial treatment. Our report findings suggest the importance of considering S. maltophilia infection in an atypical case of very early recurrent peritonitis.

Effect of osteosarcopenia on longitudinal mortality risk and chronic kidney disease progression in older adults.

INTRODUCTION: Chronic kidney disease (CKD) causes a progressive loss of muscle and bone mass, which frequently overlap with and affect clinical outcomes. However, the impact of sarcopenia, low bone mineral density (BMD; osteopenia or osteoporosis), and osteosarcopenia (sarcopenia and low BMD) on CKD progression is yet to be determined. We aimed to address these issues in patients with CKD without kidney replacement therapy (KRT). METHODS: This prospective cohort study included 251 outpatients aged ≥65 years with CKD without KRT enrolled in our hospital between June 2016 and March 2017. Sarcopenia was defined according to the 2014 criteria of the Asian Working Group for Sarcopenia (AWGS), and low BMD was defined as a T-score of ≤-1.0. The patients were divided into four groups: normal (no sarcopenia/normal BMD), only low BMD (no sarcopenia/low BMD), only sarcopenia (sarcopenia/normal BMD), and osteosarcopenia (sarcopenia/low BMD). The primary outcome was a composite of all-cause deaths, initiating KRT, and admissions owing to major adverse cardiovascular and cerebrovascular events (MACEs). The secondary outcome was a kidney composite outcome that included a 30 % reduction in creatinine-based estimated glomerular filtration rate (eGFR) and initiating KRT. The outcome risk was determined using the Cox regression models adjusted for potential confounders. RESULTS: Median age (25th-75th percentile) and eGFR of the outpatients (35 % women) were 76 (69-81) years and 32.1 (20.8-41.7) ml/min/1.73 m2, respectively. During a median follow-up period of 5.2 years, there were 22 deaths, 117 30 % eGFR reductions, 48 KRTs, and 18 admissions owing to MACEs. The osteosarcopenia group rather than the only low BMD or only sarcopenia groups exhibited a higher risk of the primary (hazard ratio [HR]: 3.28, 95 % confidence interval [CI]: 1.52-7.08) and kidney composite (HR: 2.07, 95 % CI: 1.10-3.89) outcomes. Among the osteosarcopenia-related body compositions and physical functions, low handgrip strength (HGS) was strongly associated with a high risk of primary and kidney composite outcomes (HR: 2.44, 95 % CI: 1.46-4.08; HR: 1.48, 95 % CI: 0.97-2.24, respectively). The increase in HGS but not the body mass index, skeletal muscle mass index, or BMD was associated with lower risks of primary and kidney composite outcomes (HR: 0.93, 95 % CI: 0.89-0.98; HR: 0.96, 95 % CI: 0.92-0.99 per 1 kg, respectively). CONCLUSIONS: Osteosarcopenia was associated with poor survival and kidney outcomes in older patients with CKD. Low HGS, which is common in patients with osteosarcopenia and CKD, was associated with increased mortality risk and kidney function decline. These findings can help the risk prediction and pathogenesis of the kidney-bone-muscle axis and improving muscle strength can help mitigate CKD progression.

Genetic Diagnosis of Adult Hemodialysis Patients With Unknown Etiology.

Introduction: Kidney disease of unknown etiology accounts for 1 in 10 adult end-stage renal disease (ESRD) cases worldwide. The aim of this study is to clarify the genetic background of patients with chronic kidney disease (CKD) of unknown etiology who initiated renal replacement therapy (RRT) in adulthood. Methods: This is a multicenter cross-sectional cohort study. Of the 1164 patients who attended 4 dialysis clinics in Japan, we first selected patients who started RRT between the ages of 20 and 49 years. After excluding patients with apparent causes of CKD (e.g., diabetic nephropathy, polycystic kidney disease (PKD) with family history, patients who underwent renal biopsy), 90 patients with CKD of unknown cause were included. The 298 genes associated with CKD were analyzed using capture-based targeted next-generation sequencing. Results: Of the 90 patients, 10 (11.1%) had pathogenic variants in CKD-causing genes and 17 (18.9%) had variant of unknown significance (VUS). Three patients had PKD1 pathogenic variants, and 1 patient had PKD1 and COL4A4 pathogenic variants. In addition, 2 patients were diagnosed with atypical hemolytic uremic syndrome (aHUS) due to C3 or CFHR5. One patient each was diagnosed with Alport syndrome due to COL4A4 and COL4A3 variants, nephronophthisis due to NPHP1 variants, Fabry disease due to GLA variants, and autosomal-dominant tubulointerstitial kidney disease due to UMOD variants. Genetic diagnoses were not concordant with clinical diagnoses, except for patients with PKD1 variant. Conclusion: This largest study on genetic analysis in hemodialysis-dependent adults revealed the presence of undiagnosed inherited kidney diseases.

A Case of Cholestatic Liver Involvement Secondary to Amyloid Light Chain Amyloidosis With New-Onset Hypercholesterolemia and Elevated Gamma-Glutamyltransferase Level.

Amyloid light chain (AL) amyloidosis is a rare disorder caused by the deposit of misfolded light chain proteins. AL amyloidosis causes multiple organ involvement and rarely causes fatal liver failure. We present a 68-year-old man who showed cholestatic liver injury and was diagnosed with AL amyloidosis. Due to rapidly progressing cholestatic liver involvement, the patient died five days after the renal biopsy. Preclinically, there was hypercholesterolemia, and levels of gamma-glutamyltransferase (GGT) were elevated. Previous studies have suggested hypercholesterolemia and elevated GGT levels in patients with AL amyloidosis and liver involvement; however, its clinical relevance remains unknown. Our report suggests that in addition to serum kappa/lambda, the combination of new-onset GGT level elevation and hypercholesterolemia could be preclinical characteristics of cholestatic liver involvement in AL amyloidosis.

Upregulation of long non­coding RNA LINC00460 in EGFR­mutant lung cancer indicates a poor prognosis in patients treated with osimertinib.

The long non-coding RNA (lncRNA) LINC00460 is involved in tumor growth, metastasis and drug resistance. The present study investigated the clinical significance of LINC00460 expression in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer treated with osimertinib. Osimertinib-resistant cells we derived from EGFR-mutant non-small-cell lung cancer (NSCLC) cell lines, after which, small interfering RNA (siRNA)-mediated silencing and in vitro-transcribed (IVT), synthetic LINC00460 RNA transfection were used to investigate the effects of LINC00460 expression on acquired resistance to osimertinib. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate LINC00460 expression in 54 samples (RNA extracted from the tumor tissues of 30 cases and cell-free RNA from 24 cases) obtained from patients with EGFR mutation-positive lung cancer who had received osimertinib as the initial treatment. The acquisition of osimertinib resistance increased the expression of LINC00460 in the EGFR-mutant NSCLC cell lines. By contrast, knockdown of LINC00460 in osimertinib-resistant cell lines increased their sensitivity to osimertinib, whereas treatment of NSCLC cells with IVT LINC00460 RNA decreased their sensitivity to osimertinib. The present study examined LINC00460 expression at the primary tumor site and demonstrated that compared with in the low-expression group (n=24), the high-expression group (n=6) had a significantly lower best overall response rate to osimertinib (16.6% vs. 60.0%; P=0.044), significantly shorter median progression-free survival (PFS; 224 days vs. 669 days; P=0.001) and significantly shorter median overall survival (724 days vs. not reached; P=0.011). Moreover, following osimertinib therapy, PFS was significantly shorter for patients with high LINC00460 expression in plasma cell-free RNA (n=12) than for those with low LINC00460 expression (n=12) (median PFS: 655 days vs. 210 days; P=0.020). In conclusion, the upregulation of LINC00460, the expression of which is implicated in osimertinib resistance, in the primary site and plasma of patients with EGFR mutation-positive lung cancer may be associated with a poor prognosis in those treated with osimertinib.

Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.

BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.

Preparation of mineralized pericardium by alternative soaking for soft-hard interregional tissue application.

Recent applications of decellularized tissues include the ectopic use of sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are modified (or fabricated) with the desired functions for application to the target (transplanted or used) tissue, including soft-hard interregional tissues, such as ligaments, tendons, and periodontal ligaments. This study aimed to prepare a mineralized decellularized pericardium to construct a soft-hard interregional tissue by 3D fabrication of decellularized pericardium, for example, rolling up to a cylindrical form. The decellularized pericardial tissue was prepared using the high hydrostatic pressurization (HHP) and surfactants method. The pericardium consisted of bundles of aligned fibers, and the bundles were slightly disordered when prepared with the surfactant decellularization method compared with that prepared using the HHP decellularization method. Mineralization of the decellularized pericardium was performed using an alternate soaking process with various cycles. The surface of the decellularized pericardium was covered with calcium phosphate precipitates, which accumulated on the surface with an increasing number of soaking cycles. The inside of the HHP decellularized pericardium was mineralized uniformly, whereas the mineralization of the decellularized pericardium decreased toward the interior. These findings suggest that the decellularization method strongly affects the structure and mineralized parts of the decellularized pericardium. The mineralized decellularized pericardium could be a candidate material for reconstructing alternative interregional tissues, such as ligaments and tendons.

In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics.

PURPOSE: To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS: SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS: The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION: SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.