Development and internal validation of a clinical prediction model for osteopenia in Chinese middle-aged and elderly men: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. METHODS: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. RESULTS: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. CONCLUSIONS: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Boron-Containing Mesoporous Silica Nanoparticles with Effective Delivery and Targeting of Liver Cancer Cells for Boron Neutron Capture Therapy.

Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.

Evaluating the learning curve of endoscopic surgery for spontaneous intracerebral hemorrhage: A single-center experience in a county hospital.

BACKGROUND: Endoscopic surgery has shown promise in treating Spontaneous Intracerebral Hemorrhage (sICH), but its adoption in county-level hospitals has been hindered by the high level of surgical expertise required. METHODS: In this retrospective study at a county hospital, we utilized a Cumulative Sum (CUSUM) control chart to visualize the learning curve for two neurosurgeons. We compared patient outcomes in the learning and proficient phases, and compared them with expected outcomes based on ICH score and ICH functional outcome score, respectively. RESULTS: The learning curve peaked at the 12th case for NS1 and the 8th case for NS2, signifying the transition to the proficient stage. This stage saw reductions in operation time, blood loss, rates of evacuation < 90 %, rebleeding rates, intensive care unit stay, hospital stay, and overall costs for both neurosurgeons. In the learning stage, 6 deaths occurred within 30 days, less than the 10.66 predicted by the ICH score. In the proficient stage, 3 deaths occurred, less than the 15.88 predicted. In intermediate and high-risk patients by the ICH functional outcome score, the proficient stage had fewer patients with an mRS ≥ 3 at three months than the learning stage (23.8 % vs. 69.2 %, P = 0.024; 40 % vs. 80 %, P = 0.360). Micromanipulating bipolar precision hemostasis and aspiration devices in the endoport's channels sped up the transition from learning to proficient. CONCLUSION: The data shows a learning curve, with better surgical outcomes as surgeons gain proficiency. This suggests cost benefits of surgical proficiency and the need for ongoing surgical education and training in county hospitals.

Hydrogen alleviates impaired lung epithelial barrier in acute respiratory distress syndrome via inhibiting Drp1-mediated mitochondrial fission through the Trx1 pathway.

Acute respiratory distress syndrome (ARDS) is an acute and severe clinical complication lacking effective therapeutic interventions. The disruption of the lung epithelial barrier plays a crucial role in ARDS pathogenesis. Recent studies have proposed the involvement of abnormal mitochondrial dynamics mediated by dynamin-related protein 1 (Drp1) in the mechanism of impaired epithelial barrier in ARDS. Hydrogen is an anti-oxidative stress molecule that regulates mitochondrial function via multiple signaling pathways. Our previous study confirmed that hydrogen modulated oxidative stress and attenuated acute pulmonary edema in ARDS by upregulating thioredoxin 1 (Trx1) expression, but the exact mechanism remains unclear. This study aimed to investigate the effects of hydrogen on mitochondrial dynamics both in vivo and in vitro. Our study revealed that hydrogen inhibited lipopolysaccharide (LPS)-induced phosphorylation of Drp1 (at Ser616), suppressed Drp1-mediated mitochondrial fission, alleviated epithelial tight junction damage and cell apoptosis, and improved the integrity of the epithelial barrier. This process was associated with the upregulation of Trx1 in lung epithelial tissues of ARDS mice by hydrogen. In addition, hydrogen treatment reduced the production of reactive oxygen species in LPS-induced airway epithelial cells (AECs) and increased the mitochondrial membrane potential, indicating that the mitochondrial dysfunction was restored. Then, the expression of tight junction proteins occludin and zonula occludens 1 was upregulated, and apoptosis in AECs was alleviated. Remarkably, the protective effects of hydrogen on the mitochondrial and epithelial barrier were eliminated after applying the Trx1 inhibitor PX-12. The results showed that hydrogen significantly inhibited the cell apoptosis and the disruption of epithelial tight junctions, maintaining the integrity of the epithelial barrier in mice of ARDS. This might be related to the inhibition of Drp1-mediated mitochondrial fission through the Trx1 pathway. The findings of this study provided a new theoretical basis for the application of hydrogen in the clinical treatment of ARDS.

The dynamic role of nucleoprotein SHCBP1 in the cancer cell cycle and its potential as a synergistic target for DNA-damaging agents in cancer therapy.

BACKGROUND: Malignant tumours seriously threaten human life and health, and effective treatments for cancer are still being explored. The ability of SHC SH2 domain-binding protein 1 (SHCBP1) to induce cell cycle disturbance and inhibit tumour growth has been increasingly studied, but its dynamic role in the tumour cell cycle and corresponding effects leading to mitotic catastrophe and DNA damage have rarely been studied. RESULTS: In this paper, we found that the nucleoprotein SHCBP1 exhibits dynamic spatiotemporal expression during the tumour cell cycle, and SHCBP1 knockdown slowed cell cycle progression by inducing spindle disorder, as reflected by premature mitotic entry and multipolar spindle formation. This dysfunction was caused by G2/M checkpoint impairment mediated by downregulated WEE1 kinase and NEK7 (a member of the mammalian NIMA-related kinase family) expression and upregulated centromere/kinetochore protein Zeste White 10 (ZW10) expression. Moreover, both in vivo and in vitro experiments confirmed the significant inhibitory effects of SHCBP1 knockdown on tumour growth. Based on these findings, SHCBP1 knockdown in combination with low-dose DNA-damaging agents had synergistic tumouricidal effects on tumour cells. In response to this treatment, tumour cells were forced into the mitotic phase with considerable unrepaired DNA lesions, inducing mitotic catastrophe. These synergistic effects were attributed not only to the abrogation of the G2/M checkpoint and disrupted spindle function but also to the impairment of the DNA damage repair system, as demonstrated by mass spectrometry-based proteomic and western blotting analyses. Consistently, patients with low SHCBP1 expression in tumour tissue were more sensitive to radiotherapy. However, SHCBP1 knockdown combined with tubulin-toxic drugs weakened the killing effect of the drugs on tumour cells, which may guide the choice of chemotherapeutic agents in clinical practice. CONCLUSION: In summary, we elucidated the role of the nucleoprotein SHCBP1 in tumour cell cycle progression and described a novel mechanism by which SHCBP1 regulates tumour progression and through which targeting SHCBP1 increases sensitivity to DNA-damaging agent therapy, indicating its potential as a cancer treatment.

Diagnosing postoperative lymph node metastasis in thyroid cancer with multimodal radiomics and clinical features.

Purpose: This study aims to evaluate the diagnostic value of texture analysis for lymph node metastasis after thyroid cancer surgery. Methods: We retrospectively analyzed patients who underwent positron emission tomography/computed tomography (PET/CT) examination before 131I treatment at Shanghai Tenth People's Hospital between 2017 and 2020. Clinical follow-up results were used as the criterion for determining the presence of lymph node metastasis. The study included 119 patients, who were then randomly divided into training and test groups in a 7:3 ratio. Regions of interest were identified, and radiomics features were extracted using LIFEx 7.3.0. Mann-Whitney U test and LASSO regression were employed to screen radiomics parameters for modeling. Subsequently, a nomogram model was built by combining radscore and clinical features. SPSS 26.0 software was utilized for statistical analysis, and p < 0.05 was considered statistically significant. Results: Follow-up confirmed 54 patients with thyroid cancer lymph node metastasis and 65 patients in the non-metastasis group. A total of 119 lymph nodes were delineated. For each lesion, 164 CT texture features and 164 PET texture features were extracted, and 107 significant parameters were identified, including 16 CT texture parameters and 91 PET texture parameters. After screening, 3 CT parameters, 4 PET parameters and 12 PET/CT parameters were selected to establish three radiomic models. The AUC values were as follows: AUC (CT) = 0.730, AUC (PET) = 0.759 and AUC (PET/CT) = 0.864. We then combined clinical features and radscore to construct a nomogram, resulting in a C-index of 0.915 in the training group. In the test group, the C-index was confirmed to be 0.868. Conclusions: Radiomics may enhance the diagnostic efficiency of lymph node metastases after thyroid cancer surgery and could potentially assist clinicians in future diagnoses. The developed nomogram, which combines radiomics and clinical features, offers relatively high accuracy in helping clinicians assess the risk of metastasis in thyroid patients after surgery.

Case report: Exploring the utility of whole-body bone scintigraphy for pediatric Langerhans cell histiocytosis: insights from clinical practice.

Purpose: This mini-review delves into the realm of Langerhans cell histiocytosis (LCH) in children, focusing on its skeletal involvement. By synthesizing pertinent literature, we sought to provide a comprehensive understanding of LCH's clinical and radiographic spectrum. Our study then demonstrates the diagnostic prowess of whole-body 99mTc-methyl diphosphonate (MDP) scintigraphy in LCH cases, underscoring its value in tandem with existing knowledge. Methods: Our approach involved an extensive literature review that contextualized LCH within the current medical landscape. Subsequently, we presented a case series featuring five pediatric instances of skeletal LCH, one accompanied by soft tissue infiltration. The principal aim was to illuminate the diagnostic and staging potential of whole-body 99mTc-MDP scintigraphy, augmenting existing insights. Results: Through meticulous literature synthesis, we highlighted pediatric LCH's protean clinical manifestations and radiological variability. Aligning with this spectrum, our case series underscored the role of 99mTc-MDP scintigraphy in diagnosing and staging LCH. Among the five pediatric cases, one demonstrated concurrent soft tissue involvement. This aligns with the multifaceted nature of LCH presentations. Conclusion: Pediatric LCH can present with a wide range of clinical and radiologic features. By amalgamating our cases with extant literature, we stress the necessity of a multimodal strategy. 99mTc-MDP scintigraphy emerged as an indispensable tool for accurate staging and soft tissue detection. Our findings collectively advocate for a holistic approach to managing LCH, ensuring informed therapeutic decisions for optimal patient outcomes.

Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway.

BACKGROUND: Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets. METHODS: Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC­1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-ß-galactosidase (SA-ß-Gal) staining. RESULTS: Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs. CONCLUSION: APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.

The D-SPECT SH reconstruction protocol: improved quantification of small left ventricle volumes.

BACKGROUND: Due to spatial resolution limitations, conventional NaI-SPECT typically overestimates the left ventricular (LV) ejection fraction (EF) in patients with small LV volumes. The purpose of this study was to explore the clinical application value of the small heart (SH) reconstruction protocol embedded in the postprocessing procedure of D-SPECT. METHODS: We retrospectively analyzed patients who undergo both D-SPECT and echocardiography (Echo) within one week. Patients with small LV volume were defined as those with a rest end-systolic volume (rESV) ≤ 25 mL and underwent reconstruction using the standard (SD) reconstruction protocol. The SH protocol was deemed successful in correcting the LVEF value if it decreased by 5% or more compared to the SD protocol. The ROC curve was used to calculate the optimal cutoff value of the SH protocol. LVEF, ESV and EDV were computed with SD and SH, respectively. Echo was performed as a reference, and Echo-LVEF, ESV, and EDV were calculated using the Teichholz formula. One-way ANOVA was used to compare these parameters among the three groups. RESULTS: The final study included 209 patients (73.21% female, age 67.34 ± 7.85 years). Compared with the SD protocol, the SH protocol significantly decreased LVEF (67.43 ± 7.38% vs. 71.30 ± 7.61%, p < 0.001). The optimal cutoff value for using the SH protocol was rESV > 17 mL (AUC = 0.651, sensitivity = 78.43%, specificity = 45.57%, p = 0.001). In the subgroup of rESV > 17 mL, there was no significant difference in LVEF (61.84 ± 4.67% vs. 62.83 ± 2.85%, p = 0.481) between the SH protocol and Echo, and no significant difference was observed in rESV (26.92 ± 3.25 mL vs. 27.94 ± 7.96 mL, p = 0.60) between the SH protocol and Echo. CONCLUSION: This pilot study demonstrated that the SH reconstruction protocol was able to effectively correct the overestimation of LVEF in patients with small LV volumes. Particularly, in the rESV > 17 mL subgroup, the time and computing power waste could be reduced while still ensuring the accuracy of the LVEF value and image quality.

The determination of the optimal threshold on measurement of thyroid volume using quantitative SPECT/CT for Graves' hyperthyroidism.

PURPOSE: To investigate the optimal threshold for measuring thyroid volume in patients with Grave's hyperthyroidism (GH) by SPECT/CT. MATERIALS AND METHODS: A 53 mL butterfly-shaped hollow container made of two 45-degree transparent elbows was put into a NEMA IEC phantom tank. The butterfly-shaped container and the tank were then filled with Na99mTcO4 of different radioactive concentrations, respectively, which could simulate thyroid gland with GH by different target-to-background ratios (T/B) (200:1, 600:1, 1000:1). The different T/B of planar imaging and SPECT/CT were acquired by a Discovery NM/CT 670 Pro SPECT/CT. With Thyroid software (Version 4.0) of GE-Xeleris workstation, the region of the thyroid gland in planar imaging was delineated. The thyroid area and average long diameter of both lobes were substituted into the Allen formula to calculate the thyroid volume. The calculation error was compared with the actual volume. Q-Metrix software was used to perform CT-based attenuation correction, scatter correction, resolution recovery. Ordered-subsets expectation maximization was used to reconstruct SPECT data. 20%, 25%, 30%, 40%, 50%, 60% thresholds were selected to automatically delineate the volume of interest and compared with the real volume, which determinated the optimal threshold. We measured the thyroid volume of 40 GH patients using the threshold and compared the volumes obtained by planar imaging and ultrasound three-dimensional. The differences of the volumes with different T/B and thresholds were compared by the ANOVA and least significant difference t test. The volumes delineated by SPECT/CT were evaluated using ANOVA, least significant difference t test, correlation analysis and, linear regression and Bland-Altman concordance test plot. The differences and consistency of thyroid volume were compared among the above three methods. RESULTS: There was no significant difference in the results between different T/B models (P > 0.05). The thyroid volume calculated by the planar imaging formula method was higher than the real volume, with an average overestimation of 22.81%. The volumes delineated by SPECT/CT threshold automatically decreased while the threshold increased. There were significant differences between groups with different thresholds (P < 0.001). With an average error of 3.73%, the thyroid volume analyzed by the threshold of 25% was close to the results of ultrasound measurement (P > 0.05). Thyroid volume measured by planar imaging method was significantly higher than ultrasound and SPECT/CT threshold automatic delineation method (P < 0.05). The agreement between the SPECT/CT 25% threshold and ultrasound (r = 0.956, b = 0.961) was better than that between the planar imaging and ultrasound (r = 0.590, b = 0.574). The Bland-Altman plot also showed that the thyroid volume measured by the 25% threshold automatic delineation method was in good agreement with the ultrasound measurement. CONCLUSIONS: The T/B has no effect on the measurement of thyroid volume in GH patients; planar imaging method can significantly overestimate thyroid volume in GH patients, and 25% threshold automatic delineation method can obtain more accurate thyroid volume in GH patients.

The impact of time to evacuation on outcomes in endoscopic surgery for supratentorial spontaneous intracerebral hemorrhage: a single-center retrospective study.

Supratentorial spontaneous intracerebral hemorrhage (SICH) can be treated with endoscopic surgery, but the optimal timing remains uncertain. We retrospectively analyzed data from 46 patients who underwent endoscopic surgery for supratentorial SICH. We examined the relationship between time to evacuation and functional outcome at 3 months, adjusting for prognostic factors. Surgical outcomes and complications were compared between patients with early (≤ 12 h) or late (> 12 h) evacuation. Median time to evacuation was 12 h, and the rate of unfavorable outcome (modified Rankin Scale > 3 at 3 months) was 32.6%. Longer time to evacuation was independently associated with unfavorable outcome (odds ratio per hour delay: 1.26). Late evacuation carried a 7.25-fold higher risk of unfavorable outcome compared to early evacuation. This association held across subgroups based on hematoma volume, location, and intraventricular extension (P for interaction > 0.05). Patients with late evacuation had fewer spot signs (24% vs. 4.8%, P = 0.035) and markers of hemorrhagic expansion (36% vs. 9.5%, P = 0.018), longer neurosurgical intensive care unit (NSICU) stay (3.2 vs. 1.9 days, P = 0.011) and hospital stay (15.7 vs. 11.9 days, P = 0.014), and higher 30-day mortality (28.6 vs. 4%, P = 0.036) and complication rates (57.1% vs. 28.0%, P = 0.023). This study suggests a potential association between early endoscopic evacuation of supratentorial SICH and improved functional outcomes, lower 30-day mortality and reduced complications. The need for timely intervention in managing supratentorial SICH is highlighted, yet further validation through multi-center prospective studies is essential to substantiate these findings and provide a higher level of evidence.

Added value of regional 18F-FDG PET/MRI-assisted whole-body 18F-FDG PET/CT in malignant ascites with unknown primary origin.

BACKGROUND: Comparing to PET/CT, integrative PET/MRI imaging provides superior soft tissue resolution. This study aims to evaluate the added value of regional delayed 18F-FDG PET/MRI-assisted whole-body 18F-FDG PET/CT in diagnosing malignant ascites patients. RESULTS: The final diagnosis included 22 patients with ovarian cancer (n = 11), peritoneal cancer (n = 3), colon cancer (n = 2), liver cancer (n = 2), pancreatic cancer (n = 2), gastric cancer (n = 1), and fallopian tube cancer (n = 1). The diagnosis of the primary tumor using whole-body PET/CT was correct in 11 cases. Regional PET/MRI-assisted whole-body PET/CT diagnosis was correct in 18 cases, including 6 more cases of ovarian cancer and 1 more case of fallopian tube cancer. Among 4 cases that were not diagnosed correctly, 1 case had the primary tumor outside of the PET/MRI scan area, 2 cases were peritoneal cancer, and 1 case was colon cancer. The diagnostic accuracy of regional PET/MRI-assisted whole-body PET/CT was higher than PET/CT alone (81.8% vs. 50.0%, κ 2 = 5.14, p = 0.023). The primary tumor conspicuity score of PET/MRI was higher than PET/CT (3.67 ± 0.66 vs. 2.76 ± 0.94, P < 0.01). In the same scan area, more metastases were detected in PET/MRI than in PET/CT (156 vs. 86 in total, and 7.43 ± 5.17 vs. 4.10 ± 1.92 per patient, t = 3.89, P < 0.01). Lesion-to-background ratio in PET/MRI was higher than that in PET/CT (10.76 ± 5.16 vs. 6.56 ± 3.45, t = 13.02, P < 0.01). CONCLUSION: Comparing to whole-body PET/CT alone, additional delayed regional PET/MRI with high soft tissue resolution is helpful in diagnosing the location of the primary tumor and identifying more metastases in patients with malignant ascites. Yet larger sample size in multicenter and prospective clinical researches is still needed.

Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet-induced oxidative damage by increasing endogenous antioxidants in HaCaT cells.

BACKGROUND: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. MATERIALS AND METHODS: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. RESULTS: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. CONCLUSION: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.

Parvalbumin interneurons dysfunction is potentially associated with FαMNs decrease and NRG1-ErbB4 signaling inhibition in spinal cord in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate the alteration of PV interneurons in ALS mainly focusing its dynamic changes and its relationship with motor neurons and ErbB4 signaling. METHODS: SOD1G93A mice were used as ALS model. ALS animals were divided into different groups according to birth age: symptomatic prophase (50~60 days), symptomatic phase (90~100 days), and symptomatic progression (130~140 days). Immunofluorescence was performed for measurement of PV-positive interneurons, MMP-9, ChAT, NeuN and ErbB4. RT-qPCR and western blot were used to determine the expression of PV and MMP-9. RESULTS: PV expression was remarkably higher in the anterior horn of gray matter compared with posterior horn and area in the middle of gray matter in control mice. In ALS mice, PV, MMP-9 and ErbB4 levels were gradually decreased along with onset. PV, MMP-9 and ErbB4 levels in ALS mice were significantly down-regulated than control mice after onset, indicating the alteration of PV interneurons, FαMNs and ErbB4. SαMNs levels only decreased remarkably at symptomatic progression in ALS mice compared with control mice, while γMNs levels showed no significant change during whole period in all mice. MMP-9 and ErbB4 were positively correlated with PV. NRG1 treatment significantly enhanced the expression of ErBb4, PV and MMP-9 in ALS mice. CONCLUSION: PV interneurons decrease is along with FαMNs and ErbB4 decrease in ALS mice.

Outcome of Sclerotherapy in a Preterm Infant with a Giant Fetal Neck Lymphatic Malformation: A Case Report.

Introduction: Lymphatic malformation (LM), most commonly present in the neck area, is benign vascular malformations of the lymphatic system. In an infant, however, LM poses a high risk of adverse outcomes. Case Presentation: We present a case with a giant fetal LM. Through ultrasonography, at 23+ weeks of gestation, a septate cystic mass 7.2×6.5×6.3 cm in size was found on the right side of the fetus's neck. After extensive counseling by the multidisciplinary team, the parents chose to continue the pregnancy. Severe fetal tracheal compression was observed at 29 weeks by magnetic resonance imaging (MRI). At 31 weeks and 5 days, owing to suspected fetal distress, an emergency cesarean section was performed and a male baby weighing 1720 g was delivered. The mass was 10×16×8 cm in size and ex utero intrapartum treatment (EXIT) was implemented. Due to progressive growth of the mass secondary to intralesional bleeding, an intralesional injection of bleomycin was administered three days later. This injection was repeated at the age of 1 month and 8 days. The baby was followed up and, by a year after his birth, LM had disappeared. The baby has since been in good health. Conclusion: Accurate prenatal diagnosis and regular monitoring of a fetus with LM may improve prognosis. It is essential to have a trained multidisciplinary team to evaluate the condition of the fetus and the neonate and to provide treatment based on the evaluation. Our experience with intralesional bleomycin injection for the treatment of a giant fetal neck LM in a preterm infant had a favorable outcome. Long-term follow-up by a multidisciplinary team is needed in such cases.

Role of endoscopic third ventriculostomy in patients undergoing resection of pulvinar area lesions: Preliminary clinical results.

BACKGROUND: Patients with pulvinar area lesions may develop hydrocephalus at any stage. The role of endoscopic third ventriculostomy (ETV) in this setting remains unclear. METHOD: We retrospectively enrolled 15 patients with a mean age of 43 years who underwent endoscopic resection of pulvinar area lesions using the supracerebellar infratentorial approach (SCITA). We compared the different modalities of hydrocephalus management and their outcomes. RESULTS: Nine of 15 patients (60.0%) had preoperative obstructive hydrocephalus. Five patients underwent ETV before tumor resection, and none developed postoperative hydrocephalus. Four patients underwent one-stage surgery for tumor removal, and one patient with a polymorphous low-grade neuroepithelial tumor of the young required postoperative ETV. Another patient with diffuse astrocytoma and hydrocephalus underwent concurrent lamina terminalis fenestration and endoscopic resection via the SCITA, which resulted in the resolution of hydrocephalus. The preoperative ETV group had no major postoperative complications, while the non-ETV group had three (0/5 vs. 3/4, P = 0.048). The ETV group also had a shorter intensive care unit stay; however, the difference was not significant (1.2 vs. 2.8; P = 0.188). ETV was effective in alleviating symptoms of postoperative hydrocephalus in patients with midbrain-invading tumors. CONCLUSION: Endoscopic surgery via the SCITA can address both tumor and hydrocephalus issues in some cases but has a higher surgical risk and postoperative hydrocephalus rate. Preoperative ETV can prevent these complications and improve postoperative outcomes.

Disulfiram suppresses epithelial-mesenchymal transition (EMT), migration and invasion in cervical cancer through the HSP90A/NDRG1 pathway.

Disulfiram (DSF) has proven to be a promising anti-tumor drug in preclinical studies. However, its anti-cancer mechanism has not yet been elucidated. As an activator in tumor metastasis, N-myc downstream regulated gene-1 (NDRG1) is involved in multiple oncogenic signaling pathways and is upregulated by cell differentiation signals in various cancer cell lines. DSF treatment results in a significant reduction in NDRG1, while down-regulated NDRG1 has a pronounced effect on invading cancer cells, as shown in our previous work. Here, in vitro and in vivo experiments confirm that DSF contributes to regulating tumor growth, EMT, and the migration and invasion of cervical cancer. Furthermore, our results show DSF binds to the ATP-binding pocket in the N-terminal domain of HSP90A, thereby affecting the expression of its client protein NDRG1. To our knowledge, this is the first report of DSF binding to HSP90A. In conclusion, this study sheds light on the molecular mechanism by which DSF inhibits tumor growth and metastasis through the HSP90A/NDRG1/ß-catenin pathway in cervical cancer cells. These findings provide novel insights into the mechanism underlying DSF function in cancer cells.

Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma: a retrospective cohort study.

Introduction: The Kasabach-Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation. Methods: The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors. Results: A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (P < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914-0.966), lesion size (P < 0.001, OR 1.944; 95% CI 1.646-2.296), mixed type (P = 0.030, OR 2.428; 95% CI 1.092-5.397), deep type (P = 0.010, OR 4.006; 95% CI 1.389-11.556), and mediastinal or retroperitoneal lesion location (P = 0.019, OR 11.864; 95% CI 1.497-94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (P < 0.001, OR 7.206, 95% CI 4.073-12.749) and a lesion diameter of 5.35 cm (P < 0.001, OR 11.817, 95% CI 7.084-19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis. Conclusion: For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.

Clinical Application of Proximal Arch Cannulation in the Surgical Treatment of Acute Type I Aortic Dissection.

Objective The goal is to determine the best location for inserting a catheter into the aortic arch of patients with a certain type of aortic dissection (DeBakey type I) by analyzing images of the patient's aortic arch before surgery. This analysis will take into account the shape and structure of the patient's aortic arch to find the most optimal location for cannulation. Methods A retrospective analysis was conducted on 100 patients with acute DeBakey type I aortic dissection diagnosed between January 2021 and February 2023, utilizing the Carestream medical imaging software Image Suite V4 (New York, USA). The study included 67 cases that underwent surgery and 33 cases that did not. The study aimed to evaluate the optimal intubation position on the patient's aortic arch by analyzing the true and false lumen classification, true and false lumen area, and hematoma thickness on the patient's aortic arch, as observed in the aortic computed tomography angiography (CTA) conducted upon admission. Results The vascular axis analysis showed a significant difference in the true lumen area among the three regions that were examined (P < 0.001). Zone 1 had a larger true lumen area of 6.40 ± 2.71 cm2 compared to zone 2 with 5.75 ± 2.13 cm2 and zone 3 with 4.85 ± 1.70 cm2, as determined by statistical analysis. In addition, the statistical analysis of hematoma thickness in the three regions where cannulation can be performed revealed a significant difference among the three groups (P = 0.027). Further analysis showed that there was no significant difference between zone 1 and zone 2 (P = 1.000), a significant difference between zone 1 and zone 3 (P < 0.046), and no significant difference between zone 2 and zone 3 (P = 0.080). The difference between zone 1 false lumen thickness of 1.55 ± 0.51 cm and zone 3 false lumen thickness of 1.33 ± 0.55 cm was found to be small. Conclusion Cannulation of the aortic arch is a common strategy used in cardiac surgery. Accurate cannulation is critical to the success of the procedure. The use of CTA provides valuable guidance for the cannulation procedure. A thorough examination of CTA and precise measurement of relevant parameters can help guide the surgeon to determine the optimal cannulation site. The study found that zone 1 of the aortic arch has the largest area and is the most suitable for cannulation, in accordance with the physiological characteristics and surgical practices of a surgeon. Furthermore, cannulation of the aortic arch has been found to be a safe and effective strategy for cannulation. Overall, careful examination of CTA and accurate measurement of relevant parameters can have a significant guiding effect on the cannulation of the aortic arch, which can lead to improved outcomes in cardiac surgery.