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1.
J Biophotonics ; : e202400138, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952169

ABSTRACT

Neurological disorders such as Parkinson's disease (PD) often adversely affect the vascular system, leading to alterations in blood flow patterns. Functional near-infrared spectroscopy (fNIRS) is used to monitor hemodynamic changes via signal measurement. This study investigated the potential of using resting-state fNIRS data through a convolutional neural network (CNN) to evaluate PD with orthostatic hypotension. The CNN demonstrated significant efficacy in analyzing fNIRS data, and it outperformed the other machine learning methods. The results indicate that judicious input data selection can enhance accuracy by over 85%, while including the correlation matrix as an input further improves the accuracy to more than 90%. This study underscores the promising role of CNN-based fNIRS data analysis in the diagnosis and management of the PD. This approach enhances diagnostic accuracy, particularly in resting-state conditions, and can reduce the discomfort and risks associated with current diagnostic methods, such as the head-up tilt test.

2.
Gastroenterol Rep (Oxf) ; 12: goae060, 2024.
Article in English | MEDLINE | ID: mdl-38974878

ABSTRACT

Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued.

4.
ACS Omega ; 9(27): 29723-29731, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39005819

ABSTRACT

The implementation of photoelectrochemical water purification technology can address prevailing environmental challenges that impede the advancement and prosperity of human society. In this study, Cu, which is abundant on Earth, was fabricated using an electrochemical deposition process, in which the preferential orientation direction and carrier concentration of the Cu-based oxide semiconductor were artificially adjusted by carefully controlling the OH- and applied voltage. In particular, Cu2O grown with a sufficient supply of OH- ions exhibited the (111) preferred orientation, and the (200) surface facet was exposed, independently achieving 90% decomposition efficiency in a methyl orange (MO) solution for 100 min. This specialized method minimizes the recombination loss of electron-hole pairs by increasing the charge separation and transport efficiency of the bulk and surface of the Cu2O multifunctional absorption layer. These discoveries and comprehension not only offer valuable perspectives on mitigating self-photocorrosion in Cu2O absorbing layers but also provide a convenient and expeditious method for the mass production of water purification systems that harness unlimited solar energy. These properties enable significant energy saving and promote high-speed independent removal of organic pollutants (i.e., MO reduction) during the water purification process.

5.
Microorganisms ; 12(6)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38930569

ABSTRACT

This study investigated the synergistic effect of combining flavourzyme, a natural enzyme, and floating electrode-dielectric barrier discharge (FE-DBD) plasma (1.1 kV, 43 kHz, N2 1.5 m/s) treatment, a non-thermal decontamination technology, against Escherichia coli biofilms in squid. E. coli (ATCC 35150 and ATCC 14301) biofilms were formed on the surface of squid and treated with different minimum inhibitory concentrations (MICs) of flavourzyme (1/8; 31.25 µL/mL, 1/4; 62.5 µL/mL, 2/4; 125 µL/mL, and 3/4 MIC; 250 µL/mL) and FE-DBD plasma (5, 10, 30, and 60 min). Independently, flavourzyme and FE-DBD plasma treatment decreased by 0.26-1.71 and 0.19-1.03 log CFU/cm2, respectively. The most effective synergistic combination against E. coli biofilms was observed at 3/4 MIC flavourzyme + 60 min FE-DBD plasma exposure, resulting in a reduction of 1.55 log CFU/cm2. Furthermore, the combined treatment exhibited higher efficacy in E. coli biofilm inactivation in squid compared to individual treatments. The pH values of the synergistic combinations were not significantly different from those of the untreated samples. The outcomes indicate that the combined treatment with flavourzyme and FE-DBD plasma can effectively provide effective control of E. coli biofilms without causing pH changes in squid. Therefore, our study suggests a new microbial control method for microbial safety in the seafood industry.

6.
Nutrients ; 16(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38931199

ABSTRACT

Saikosaponin D (SSD), derived from Bupleurum falcatum L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.


Subject(s)
Apoptosis , Autophagy , Colorectal Neoplasms , Lung Neoplasms , Oleanolic Acid , Saponins , Saponins/pharmacology , Oleanolic Acid/pharmacology , Oleanolic Acid/analogs & derivatives , Autophagy/drug effects , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Apoptosis/drug effects , Humans , Lung Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Mice , Mice, Inbred BALB C , Antineoplastic Agents, Phytogenic/pharmacology , Xenograft Model Antitumor Assays , Cell Survival/drug effects , Mice, Nude
7.
J Clin Anesth ; 97: 111504, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851003

ABSTRACT

STUDY OBJECTIVE: To determine if single-injection bilateral posterior quadratus lumborum block (QLB) with ropivacaine would improve postoperative analgesia in the first 24 h after laparoscopic hepatectomy, compared with 0.9% saline. DESIGN: Prospective, double blinded, randomized controlled trial. SETTING: A single tertiary care center from November 2021 and January 2023. PATIENTS: A total of 94 patients scheduled to undergo laparoscopic hepatectomy due to hepatocellular carcinoma. INTERVENTIONS: Ninety-four patients were randomized into a QLB group (receiving 20 mL of 0.375% ropivacaine on each side, 150 mg in total) or a control group (receiving 20 mL of 0.9% saline on each side). MEASUREMENTS: The primary outcome was the cumulative opioid consumption during the initial 24-h post-surgery. Secondary outcomes included pain scores and intraoperative and recovery parameters. MAIN RESULTS: The mean cumulative opioid consumption during the initial 24-h post-surgery was 30.8 ± 22.4 mg in the QLB group (n = 46) and 34.0 ± 19.4 mg in the control group (n = 46, mean differences: -3.3 mg, 95% confidence interval, -11.9 to 5.4, p = 0.457). The mean resting pain score at 1 h post-surgery was significantly lower in the QLB group than in the control group (5 [4-6.25] vs. 7 [4.75-8], p = 0.035). No significant intergroup differences were observed in the resting or coughing pain scores at other time points or in other secondary outcomes. CONCLUSIONS: Preoperative bilateral posterior QLB did not reduce cumulative opioid consumption during the first 24 h after laparoscopic hepatectomy.

8.
Calcif Tissue Int ; 115(2): 124-131, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38878178

ABSTRACT

Depression and osteoporosis are common diseases in dialysis patients. In addition, patients with osteoporosis are more susceptible to depression. Contrary to previous anti-osteoporosis agents, denosumab and romosozumab could be used in dialysis patients and have similar action mechanisms for blocking RANKL. RANKL causes bone resorption after binding RANKL, but binding with OPG leads to suppress of bone resorption. In recent mice study, inhibition of RANKL with denosumab improved depressive-like phenotype. Besides, it was found that OPG was associated with depression. Therefore, this study aimed to investigate the association of depressive symptoms with RANKL and OPG in hemodialysis patients. We conducted a cross-sectional study with a total of 172 hemodialysis patients. The participants were measured for plasma RANKL, OPG, MMP-2, and MMP-9 levels. Logistic regression analysis was performed to evaluate the effect of RANKL and OPG on the presence of depressive symptoms. The depressive symptoms were observed in 90 (52.3%) subjects. RANKL tertile 3 had negative association with BDI score (ß - 4.527, 95% CI - 8.310 to - 0.743) in univariate analysis, and this association persisted even after multivariate adjustments (ß - 5.603, 95% CI - 9.715 to -1.491) in linear regression. In logistic regression between RANKL tertiles and depressive symptoms, RANKL tertile 3 had significantly lower unadjusted OR (0.40, 95% CI 0.19-0.86), and multivariate-adjusted OR (0.31, 95% CI 0.12-0.82) for depressive symptoms. OPG was not significantly associated with depressive symptoms. Higher plasma RANKL concentrations were significantly associated with lower depressive symptoms in HD patients.Trial registration WHO registry, No. KCT0003281, date: January 12, 2017.


Subject(s)
Depression , RANK Ligand , Renal Dialysis , Humans , RANK Ligand/blood , Female , Male , Renal Dialysis/adverse effects , Middle Aged , Depression/blood , Cross-Sectional Studies , Aged , Osteoprotegerin/blood , Osteoporosis/blood
9.
Ann Surg Treat Res ; 106(6): 313-321, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38868586

ABSTRACT

Purpose: Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) expectedly results in improved nutritional status and less body weight loss than conventional total gastrectomy in upper-third gastric cancer. This study aimed to investigate the food passage patterns following LPG-DTR and its effect on nutritional outcomes up to 1 year after surgery. Methods: This prospective cohort study recruited 10 patients with early gastric cancer scheduled for LPG-DTR. Nutritional indices and body composition were assessed every 3 months up to 12 months. Liquid and solid food transits were evaluated with fluoroscopic upper gastrointestinal study and radionuclide scintigraphy, respectively. Results: At 12 months, patients exhibited a body weight loss of 14.5% ± 3.6%. The main passage routes for liquid and solid foods differed, primarily via the interposed jejunum for liquids, whereas via both tracts for solids. The median half-life of solid food emptying from the remnant distal stomach was 105.1 minutes (range, 50.8-2,194.2 minutes), and duodenal passage of solid food was noted in 9 of 10 patients. Those with gastric half-emptying time >3 hours demonstrated greater weight loss (19.5% ± 1.4% vs. 12.5% ± 1.1%, P = 0.024) and more pronounced reduction in serum albumin levels (-0.5 ± 0.3 g/dL vs. 0.0 ± 0.2 g/dL, P = 0.024) after 12 months. Conclusion: LPG-DTR demonstrated varying food passage patterns depending on the food contents and delayed solid food emptying from the remnant stomach was associated with more substantial weight loss.

10.
Radiother Oncol ; 198: 110383, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38879129

ABSTRACT

BACKGROUND AND PURPOSE: No established early biomarkers currently exist to predict responses during concurrent chemoradiotherapy (CCRT) in patients with unresectable non-small cell lung cancer (NSCLC). This study investigated the potential of gross tumor volume (GTV) and its changes during CCRT as predictors of survival outcomes. MATERIALS AND METHODS: We identified 227 patients with unresectable stage III NSCLC who underwent definitive CCRT followed by durvalumab between November 2018 and December 2022. GTV was defined as the volume of the primary tumor, assessed at two time points: before starting CCRT for initial planning (GTV1), and at the fourth week of CCRT for adaptive planning (GTV2). Both relative and absolute regressions between GTV1 and GTV2 were calculated. RESULTS: The median GTV1 volume was 90 mL (range, 5-840 mL), and the median GTV2 volume was 64 mL (range, 1-520 mL), resulting in median absolute and relative regressions of 18.6 mL and 25.0 %, respectively. Among the GTV parameters, relative GTV regression exhibited the strongest predictive value, with an area under the curve (AUC) of 0.804 for in-field progression and 0.711 for overall progression. The 1-year progression-free survival rates for the high (>30 %), intermediate (0-30 %), and low (≤0%) relative regression groups were 88.0 %, 62.6 %, and 14.3 %, respectively (p = 0.006 for high vs. intermediate; p < 0.001 for intermediate vs. low). Additionally, GTV2 volume demonstrated stronger associations with survival outcomes than GTV1 volume. CONCLUSION: Relative GTV regression was identified as a promising early predictor for patients with unresectable stage III NSCLC. Further development of a multi-parametric predictive model is warranted to guide patient-tailored therapeutic approaches.

11.
Am J Ophthalmol ; 267: 19-29, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876313

ABSTRACT

PURPOSE: To investigate glaucoma progression based on Optical Coherence Tomography (OCT) Guided Progression Analysis (GPA) according to baseline ß-zone parapapillary atrophy (PPA) morphology in glaucoma patients. DESIGN: Retrospective cohort study. METHODS: Patients over 20 years of age who had been diagnosed with primary open-angle glaucoma (POAG) at Seoul National University Hospital, Seoul, Korea between 2010 and 2020. This study included POAG patients with a minimum of 5 years of follow-up. We quantitatively measured the baseline ß-zone PPA parameters, classified ß-zone PPA morphology according to new classification standard we created and analyzed the corresponding GPA progression of the retinal nerve fiber layer (RNFL). RESULTS: A total of 210 patients with POAG (mean age: 53.8 years) were enrolled in the study. The mean follow-up period was 9.8 years. The average value of the baseline mean deviation in visual field perimetry was -2.48 dB. Longer radial extent and larger angular extent of ß-zone PPA were significantly associated with progression on GPA, as was the presence of disk hemorrhage. Among the 4 classified ß-zone PPA morphologies (Crescent type 1 & 2, Solar-eclipse type 1 & 2), the Solar-eclipse type 2 group showed the highest progression. A Kaplan-Meier survival analysis demonstrated significant differences among the 4 types. CONCLUSIONS: The larger the radial and angular extents of ß-zone PPA, the more progression that was shown on OCT GPA. Furthermore, significant differences in progression were noted based on the morphological type of ß-zone PPA. Our findings indicate that baseline ß-zone PPA parameters and morphology are valuable predictors of future glaucoma progression.

12.
Int J Mol Sci ; 25(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38791159

ABSTRACT

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.


Subject(s)
Glomerulonephritis , Kidney Glomerulus , Lab-On-A-Chip Devices , Podocytes , Humans , Podocytes/metabolism , Podocytes/pathology , Kidney Glomerulus/metabolism , Kidney Glomerulus/pathology , Glomerulonephritis/metabolism , Glomerulonephritis/physiopathology , Glomerulonephritis/pathology , Glomerular Filtration Barrier/metabolism , Glomerulonephritis, Membranous/metabolism , Glomerulonephritis, Membranous/pathology , Glomerulonephritis, Membranous/physiopathology , Glomerulonephritis, IGA/metabolism , Glomerulonephritis, IGA/pathology , Glomerulonephritis, IGA/physiopathology , Permeability , Endothelial Cells/metabolism , Endothelial Cells/pathology , Lupus Nephritis/metabolism , Lupus Nephritis/pathology , Lupus Nephritis/physiopathology , Cell Survival , Nephrosis, Lipoid/metabolism , Nephrosis, Lipoid/pathology , Nephrosis, Lipoid/physiopathology
13.
Article in English | MEDLINE | ID: mdl-38755499

ABSTRACT

The hamstring tendon (HT) autograft is currently the most widely utilised autograft option for anterior cruciate ligament (ACL) reconstruction. However, recent studies endorse the peroneus longus tendon (PLT) autograft as a viable alternative. To evaluate this, we systematically reviewed randomised controlled trials (RCTs) to compare the efficacy of PLT against HT autografts. Our search encompassed Cochrane, Embase, OVID, PubMed, and Scopus databases for RCTs comparing outcomes of PLT and HT autografts in ACL reconstruction. Primary outcomes included Lysholm and International Knee Documentation Committee (IKDC) scores, while secondary outcomes involved American Orthopaedic Foot and Ankle Society (AOFAS) scores, graft diameters and donor-site complications. Statistical analysis was performed using Review Manager 5.4 (Cochrane Collaboration) and heterogeneity was assessed with I2 statistics. 683 patients from 6 RCTs were included, with 338 (49.5%) patients treated with PLT autografts. Follow-up ranged from 12 to 30 months. Despite lower preoperative Lysholm scores in the PLT group, no significant differences were observed at 6 and 12 months. Although preoperative and 6-month IKDC scores were lower in the PLT group, no significant differences were found at 12 and 24 months. AOFAS scores showed no significant preoperative difference, but slightly lower scores were noted in the PLT group at 12 or 24 months. There was no significant difference in graft diameter, while donor-site complications were fewer in the PLT group. In summary, the PLT autograft is a promising and non-inferior alternative to the HT autograft, demonstrating equivalent outcomes in patient-reported knee and ankle metrics, comparable graft diameters and fewer donor-site complications.

14.
Child Neuropsychol ; : 1-10, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38781441

ABSTRACT

This study uses fNIRS to determine whether there is a difference in the relationship between intra-individual variability and frontal lobe activity between ADHD patients and typically developing children. A total of 28 subjects (14 in ADHD patient group and 14 in control group) participated in this study. The subjects were tested for K-SADS and intelligence, and then the frontal lobe activity of the subjects was measured by continuous performance test, using functional near-infrared spectroscopy (NIRSIT). Processing speed index was significantly lower in the ADHD patient group than in the control group (p = .04). The CPT test results showed a positive correlation in the activity of the right dorsolateral prefrontal region in the patient group, but not at a statistically significant level. In the control group, activity showed a significant level of negative correlation with commission and hit reaction time standard deviation (p = .023; p = .063 respectively). In contrary to ADHD patient group, activation of the right dorsolateral prefrontal area was significantly correlated with reduction of intra-individual variability. This result showing that the relationship between activation of the right dorsolateral prefrontal area of the ADHD patient group and intra-individual variability shows a different pattern from typically developing children.

15.
Int J Surg Case Rep ; 119: 109669, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38718495

ABSTRACT

INTRODUCTION AND IMPORTANCE: While the typical symptom associated with pneumorachis after an epidural block is radiculopathy in one or several corresponding segments, there has been a rare case report of significant complications such as cardiac arrest leading to death, or paraplegia. CASE PRESENTATION: We present a case of an eighty-nine-year-old male patient who developed progressive paraplegia following an upper thoracic epidural block-associated pneumorachis. The procedure was performed at a different hospital using the loss of resistance (LOR) technique. Interestingly, the onset of paraplegia was delayed, occurring six hours after the procedure. Furthermore, there was a discrepancy between the clinical symptoms and the identified lesion in imaging studies. Despite the performance of an emergency laminectomy to remove the epidural gas, the paralysis continued to progress proximally. CLINICAL DISCUSSION: Healthcare professionals should observe patients for an appropriate duration after the procedure to detect and manage any delayed symptoms. And it is crucial to recognize the potential for lesion extension beyond the symptomatic segment and perform thorough imaging examinations. CONCLUSION: These findings emphasize the importance of exercising caution during the procedure, even when using a minimal amount of air with the LOR technique in the thoracic spine.

16.
Sci Rep ; 14(1): 12065, 2024 05 27.
Article in English | MEDLINE | ID: mdl-38802493

ABSTRACT

This study investigated intraocular pressure (IOP) in Dutch belted rabbits using two different tonometers, rebound tonometry (TonoVet Plus; TVP) and a Tonopen (Tono-Pen AVIA Vet; TPA). Post-pubescent male Dutch belted rabbits aged 36 weeks (n = 10 animals) were used in the study. IOP measurements were conducted every 2 weeks for 22 weeks using TVP and TPA on both eyes of each rabbit. The average IOP measurements were compared by the paired Student's t-test. Pairwise Pearson's correlation coefficients and Bland-Altman statistics were used. The overall mean IOP measured with TPA was significantly higher than that with TVP (23.5 ± 4.9 vs. 21.8 ± 2.4 mmHg for the right eyes; P = 0.045, and 23.0 ± 4.7 vs. 21.5 ± 2.4 mmHg for the left eyes; P = 0.047). Both tonometers tended to show increased IOP readings with age, and positive correlations between IOP and age were observed with both TPA (r = 0.95, P < 0.001 for right eyes; r = 0.95, P < 0.001 for left eyes) and TVP (r = 0.91, P < 0.001 for right eyes; r = 0.64, P = 0.024 for left eyes). The average bias calculated by subtracting TPA from TVP was - 1.60 (95% confidence intervals - 1.927, - 1.281) mmHg. IOP in post-pubescent Dutch belted rabbits tended to increase with age throughout the 22 week study.


Subject(s)
Aging , Intraocular Pressure , Tonometry, Ocular , Animals , Rabbits , Intraocular Pressure/physiology , Tonometry, Ocular/methods , Male , Aging/physiology
17.
Sci Rep ; 14(1): 10143, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38698042

ABSTRACT

Sirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury.


Subject(s)
Apoptosis , Cyclosporine , Mice, Knockout , Mitochondria , Oxidative Stress , Sirtuin 3 , Animals , Sirtuin 3/metabolism , Sirtuin 3/genetics , Cyclosporine/adverse effects , Cyclosporine/toxicity , Cyclosporine/pharmacology , Mitochondria/metabolism , Mitochondria/drug effects , Mice , Dogs , Apoptosis/drug effects , Oxidative Stress/drug effects , AMP-Activated Protein Kinases/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Madin Darby Canine Kidney Cells , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Kidney Diseases/prevention & control , Kidney Diseases/pathology , Kidney Diseases/genetics , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Mice, Inbred C57BL , Male , Signal Transduction/drug effects
18.
Article in English | MEDLINE | ID: mdl-38797499

ABSTRACT

PURPOSE: This study aimed to evaluate the efficacy of local ablative therapy (LAT) combined with pembrolizumab in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) and to identify patients who would most benefit from LAT. METHODS AND MATERIALS: We retrospectively identified patients who received diagnosis of synchronous oligometastatic NSCLC (≤5 metastatic lesions and ≤3 organs involved) and were treated with first-line pembrolizumab between January 2017 and December 2022. Patients who underwent LAT, including surgery or radiation therapy at all disease sites, were compared with those who did not undergo LAT. A recursive partitioning analysis (RPA) model was developed using prognostic factors for progression-free survival (PFS). RESULTS: Among the 258 patients included, 78 received LAT with pembrolizumab, and 180 received pembrolizumab alone. The median follow-up duration was 15.5 months (range, 3.0-71.2 months). In the entire cohort, LAT was independently associated with significantly improved PFS (hazard ratio [HR], 0.64; P = .015) and overall survival (OS) (HR, 0.61; P = .020). In the propensity score-matched cohort (N = 74 in each group), the median PFS was 19.9 months and 9.6 months, respectively (P = .003), and the median OS was 42.2 months and 20.5 months, respectively (P = .045), for the LAT and non-LAT groups. Based on the RPA model, incorporating the number of metastatic lesions, performance status, and programmed cell death-ligand 1 expression level, patients were stratified into 3 risk groups with distinct PFS. LAT significantly improved PFS and OS in the low- and intermediate-risk groups; however, no difference was observed in the high-risk group. LAT was more effective as a consolidative treatment after pembrolizumab initiation than as an upfront therapy. CONCLUSIONS: LAT combined with pembrolizumab was associated with higher PFS and OS compared with pembrolizumab alone in selected patients with synchronous oligometastatic NSCLC. The RPA model could serve as a valuable clinical tool for identifying appropriate patients for LAT.

19.
Pathology ; 56(5): 653-661, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38811262

ABSTRACT

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (E20ins) are the third most frequent mutations observed in non-small cell lung cancer, accounting for approximately 1-10% of all EGFR mutations. In the era of precision medicine and targeted therapies, consistent naming of genetic alterations is crucial to avoid confusion and errors. However, the annotation of EGFR E20ins mutations has been inconsistent, leading to confusion in the scientific literature and product documentation. In this study, our primary objective was to investigate the usage of different annotation related to EGFR E20ins in independent studies. Additionally, we assessed the distribution of EGFR E20ins mutations and estimated the detection coverage expected from each available EGFR E20ins detection assay. A total of 1,418 EGFR E20ins mutations were collected from six studies (FoundationInsights, Geneseeq Technology Inc, mobocertinib phase I/II trial, poziotinib phase II trial, sunvozertinib phase I trial, and Samsung Medical Center) and reorganised according to Human Genome Variation Society (HGVS) nomenclature. Our analysis revealed that the majority of EGFR E20ins mutations requiring correction were 'insertion' or 'deletion-insertion', which should be appropriately designated as 'duplication'. Additionally, duplicated variants were reported using different annotations in each study, and furthermore, even identical variant sequences were annotated differently within the same study. In all six studies, p.A767_V769dup and p.S768_D770dup were the most frequently observed EGFR E20ins. The Oncomine Dx Target Test showed the highest patient coverage at 77.2%, followed by the Droplex EGFR Mutation Test v2 with a patient coverage of 70.5% for EGFR E20ins patients. To ensure comprehensive coverage in real-world settings, it is essential to standardise the annotations for each variant, for example using the HGVS nomenclature. The accurate classification and analysis of drug responsiveness in EGFR E20ins necessitate consideration of the nomenclature, particularly with respect to the locations where the actual mutations occur.


Subject(s)
Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Exons , Lung Neoplasms , Precision Medicine , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Exons/genetics , Mutation , Mutagenesis, Insertional/genetics , Terminology as Topic
20.
Clin Orthop Surg ; 16(2): 313-321, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38562625

ABSTRACT

Background: Although several techniques for the treatment of ulnar impaction syndrome (UIS) have been introduced, there have still been reports on various complications such as delayed union, nonunion, refracture, wrist pain, plate irritation, and chronic regional pain syndrome. This study aimed to compare the differences in radiological and clinical outcomes of patients in which intramedullary bone grafting was performed in addition to plate stabilization with those without additional bone grafting during ulnar shortening osteotomies (USOs). Methods: Between November 2014 and June 2021, 53 wrists of 50 patients with idiopathic UIS were retrospectively reviewed. Patients were divided into 2 groups according to whether intramedullary bone grafting was performed. Among the 53 wrists, USO with an intramedullary bone graft was performed in 21 wrists and USO without an intramedullary bone graft was performed in 32 wrists. Demographic data and factors potentially associated with bone union time were analyzed. Results: There was no significant difference between the 2 groups when comparing postoperative radioulnar distance, postoperative ulnar variance, amount of ulnar shortening, and postoperative Disabilities of the Arm, Shoulder and Hand score. Compared to the without-intramedullary bone graft group, bone union time of the osteotomy site was significantly shortened, from 8.8 ± 3.0 weeks to 6.7 ± 1.3 weeks in the with-intramedullary bone graft group. Moreover, there were no cases of nonunion or plate-induced symptoms. Both in univariable and multivariable analyses, intramedullary bone grafting was associated with shorter bone union time. Conclusions: USO with an intramedullary bone graft for idiopathic UIS has favorable radiological and clinical outcomes. The advantage of this technique is the significant shortening of bone union time.


Subject(s)
Joint Diseases , Wrist Joint , Humans , Retrospective Studies , Wrist Joint/diagnostic imaging , Wrist Joint/surgery , Bone Transplantation , Treatment Outcome , Ulna/diagnostic imaging , Ulna/surgery , Joint Diseases/surgery , Osteotomy/methods
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