Rheology, physicochemical properties, and microstructure of fish gelatin emulsion gel modified by γ-polyglutamic acid.

In this work, the effect of the addition of γ-polyglutamic acid (γ-PGA) on the rheology, physicochemical properties, and microstructure of fish gelatin (FG) emulsion gel was investigated. Samples of the emulsion gel were evaluated for rheological behavior and stability prior to gelation. The mechanical properties and water-holding capacity (WHC) of the emulsion were determined after gelation. The microstructure of the emulsion gel was further examined using confocal laser scanning microscopy (CLSM). The results indicated a gradual increase in the apparent viscosity and gelation temperature of the emulsion at a higher concentration of γ-PGA. Additionally, frequency scan results revealed that on the addition of γ-PGA, FG emulsion exhibited a stronger structure. The emulsion containing 0.1% γ-PGA exhibited higher stability than that of the control samples. The WHC and gel strength of the emulsion gel increased on increasing the γ-PGA concentration. CLSM images showed that the addition of γ-PGA modified the structure of the emulsion gel, and the droplets containing 0.1% γ-PGA were evenly distributed. Moreover, γ-PGA could regulate the droplet size of the FG emulsion and its size distribution. These findings suggest that the viscoelasticity and structure of FG emulsion gels could be regulated by adjusting the γ-PGA concentration. The γ-PGA-modified FG emulsion gel also exhibited improved rheology and physicochemical properties. The results showed that γ-PGA-modified FG emulsion gel may find potential applications in food, medicine, cosmetics, and other industries.

Characterization of VOC emissions and health risk assessment in the plastic manufacturing industry.

Volatile organic compounds (VOCs) significantly contribute to ozone pollution formation, and many VOCs are known to be harmful to human health. Plastic has become an indispensable material in various industries and daily use scenarios, yet the VOC emissions and associated health risks in the plastic manufacturing industry have received limited attention. In this study, we conducted sampling in three typical plastic manufacturing factories to analyze the emission characteristics of VOCs, ozone formation potential (OFP), and health risks for workers. Isopropanol was detected at relatively high concentrations in all three factories, with concentrations in organized emissions reaching 322.3 µg/m3, 344.8 µg/m3, and 22.6 µg/m3, respectively. Alkanes are the most emitted category of VOCs in plastic factories. However, alkenes and oxygenated volatile organic compounds (OVOCs) exhibit higher OFP. In organized emissions of different types of VOCs in the three factories, alkenes and OVOCs contributed 22.8%, 67%, and 37.8% to the OFP, respectively, highlighting the necessity of controlling them. The hazard index (HI) for all three factories was less than 1, indicating a low non-carcinogenic toxic risk; however, there is still a possibility of non-cancerous health risks in two of the factories, and a potential lifetime cancer risk in all of the three factories. For workers with job tenures exceeding 5 years, there may be potential health risks, hence wearing masks with protective capabilities is necessary. This study provides evidence for reducing VOC emissions and improving management measures to ensure the health protection of workers in the plastic manufacturing industry.

An optimized short-term steroid therapy for chronic drug-induced liver injury: A prospective randomized clinical trial.

BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).

Multiscale structure changes and mechanism of polyphenol-amylose complexes modulated by polyphenolic structures.

This study was designed to investigate the effect of polyphenolic structure on the interaction strength and process between polyphenols (gallic acid (GA), epigallocatechin gallate (EGCG) and tannic acid (TA)) and amylose (AM). The results of Fourier transform infrared spectroscopy, isothermal titration calorimetry, X-ray photoelectron spectroscopy and molecular dynamic simulation (MD) suggested that the interactions between the three polyphenols and AM were noncovalent, spontaneous, low-energy and driven by enthalpy, which would be enhanced with increasing amounts of pyrogallol groups in the polyphenols. The results of turbidity, particle size and appearance of the complex solution showed that the interaction process between polyphenols and AM could be divided into three steps and would be advanced by increasing the number of pyrogallol groups in the polyphenols. At the same time, MD was intuitively employed to exhibit the interaction process between amylose and polyphenols, and it revealed that the interaction induced the aggregation of amylose and that the agglomeration degree of amylose increased with increasing number of pyrogallol groups at polyphenols. Last, the SEM and TGA results showed that TA/AM complexes had the tightest structure and the highest thermal stability (TA/AM˃EGCG/AM˃GA/AM), which could be attributed to TA having five pyrogallol groups.

Disulfidptosis characterizes the tumor microenvironment and predicts immunotherapy sensitivity and prognosis in bladder cancer.

Background: Bladder cancer (BLCA) is prone to metastasis and has poor prognosis with unsatisfactory treatment responsiveness. Disulfidptosis is a recently discovered, novel mode of cell death that is closely associated with human cancers. However, a comprehensive analysis of the relationship between disulfidptosis and BLCA is lacking. Therefore, this study aimed to explore the potential effect of disulfidptosis on BLCA and identify a biomarker for evaluating the prognosis and immunotherapy of patients with BLCA. Material and methods: We acquired BLCA RNA sequencing data from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) cohort (containing 19 normal samples and 409 tumor samples) and the GES39281 cohort (containing 94 tumor samples) which were used for external validation of the signature. Initially, we performed unsupervised consensus clustering to explore disulfidptosis-related subgroups. We then conducted functional enrichment analysis on these subgroups to gain insights into their biological significance and evaluate their immunotherapy response and chemotherapy sensitivity. Next, we conducted Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Cox regression to construct a prognostic signature in the TCGA training set for prognosis-related differentially expressed genes (DEGs) in the disulfidptosis-related subgroups. Subsequently, we used a receiver operating characteristic (ROC) curve and independent prognostic analysis to validate the predictive performance of the signature in the TCGA testing and the GES39281 cohorts. Finally, we explored the therapeutic value of this signature in patients with BLCA, in terms of immunotherapy and chemotherapy. Result: In this study, we obtained two subgroups: DRG-high (238 samples) and DRG-low (160 samples). The DRG-high group exhibited a poor survival rate compared to the DRG-low group and had a significant association with tumor grade, stage, and metastasis. Additionally, several pathways related to cancer and the immune system were enriched in the high-DRG group. Moreover, the DRG-high group exhibited higher expression of PD1 and CTLA4 and had a better response to immunotherapy in patients with both PD1 and CTLA4 positivity. Conversely, the DRG-high group was more sensitive to common chemotherapeutic agents. A prognostic signature was created, consisting of COL5A1, DIRAS3, NKG7, and POLR3G and validated as having a robust predictive capability. Patients in the low-risk-score group had more immune cells associated with tumor suppression and better immunotherapy outcomes. Conclusion: This study contributes to our understanding of the characteristics of disulfidptosis-related subgroups in BLCA. Disulfidptosis-related signatures can be used to assess the prognosis and immunotherapy of patients with BLCA.

IgG antibody response to SARS-CoV-2 infection and its influencing factors in lymphoma patients.

BACKGROUND: The ability of generating effective humoral immune responses to SARS-CoV-2 infection has not been clarified in lymphoma patients. The study aimed to investigate the antibody (Ab) production after SARS-Cov-2 infection and clarify the factors affecting the Ab generation in these patients. PATIENTS & METHODS: 80 lymphoma patients and 51 healthy controls were included in this prospective observational study. Clinical factors and treatment regimens affecting Ab positive rate (APR) and Ab levels were analyzed by univariate and multivariate methods. RESULTS: The anti-SARS-CoV-2 IgG APR and Ab levels in lymphoma patients were significantly lower than those in healthy controls. Lymphoma patients with COVID-19 vaccination had significantly higher APR and Ab levels compared with those without vaccination. Additionally, the use of dexamethasone for COVID-19 treatment had a negative impact on Ab levels. For the impact of treatment regimens on the APR and Ab levels, the results showed that patients treated with ≥ 6 times CD20 monoclonal Ab (mAb) and patients treated with autologous hematopoietic stem cell transplantation (ASCT) prior to infection produced a statistically lower APR and Ab levels compared with those treated with 1-5 times CD20 mAb and those treated without ASCT, respectively. Furthermore, multiple regression analysis indicated that the number of anti-CD20 treatment was an independent predictor for both APR and Ab levels. CONCLUSIONS: Humoral immune response to SARS-CoV-2 infection was impaired in lymphoma patients partly due to anti-CD20 and ASCT treatment. COVID-19 vaccination may be more needed for these patients.

A dynamic nomogram for predicting intraoperative brain bulge during decompressive craniectomy in patients with traumatic brain injury: a retrospective study.

OBJECTIVE: The aim of this paper is to investigate the risk factors associated with intraoperative brain bulge (IOBB), especially the computed tomography (CT) value of the diseased lateral transverse sinus, and to develop a reliable predictive model to alert neurosurgeons to the possibility of IOBB. METHODS: A retrospective analysis was performed on 937 patients undergoing traumatic decompressive craniectomy. A total of 644 patients from Fuzong Clinical Medical College of Fujian Medical University were included in the development cohort, and 293 patients from the First Affiliated Hospital of Shantou University Medical College were included in the external validation cohort. Univariate and multifactorial logistic regression analyses identified independent risk factors associated with IOBB. The logistic regression models consisted of independent risk factors, and receiver operating characteristic curves, calibration, and decision curve analyses were used to assess the performance of the models. Various machine learning models were used to compare with the logistic regression model and analyze the importance of the factors, which were eventually jointly developed into a dynamic nomogram for predicting IOBB and published online in the form of a simple calculator. RESULTS: IOBB occurred in 93/644 (14.4%) patients in the developmental cohort and 47/293 (16.0%) in the validation cohort. Univariate and multifactorial regression analyses showed that age, subdural hematoma, contralateral fracture, brain contusion, and CT value of the diseased lateral transverse sinus were associated with IOBB. A logistic regression model (full model) consisting of the above risk factors had excellent predictive power in both the development cohort [area under the curve (AUC)=0.930] and the validation cohort (AUC=0.913). Among the four machine learning models, the AdaBoost model showed the best predictive value (AUC=0.998). Factors in the AdaBoost model were ranked by importance and combined with the full model to create a dynamic nomogram for clinical application, which was published online as a practical and easy-to-use calculator. CONCLUSIONS: The CT value of the diseased lateral transverse is an independent risk factor and a reliable predictor of IOBB. The online dynamic nomogram formed by combining logistic regression analysis models and machine learning models can more accurately predict the possibility of IOBBs in patients undergoing traumatic decompressive craniectomy.

Value of preoperative controlling nutritional status score in prognosis of patients with high-risk factors for early-stage cervical cancer.

Objective: To investigate whether the preoperative controlling nutritional status (COUNT) score is a prognostic factor of patients with high-risk factors for early-stage cervical cancer after surgery and concurrent chemoradiotherapy (CCRT). Methods: This was a retrospective study. From July 2017 to March 2021, a total of 354 patients with histologically confirmed FIGO stage IB-IIA cervical cancer undergoing surgery and postoperative CCRT were included at Hunan University of Medicine General Hospital, China. According to receiver operating characteristic (ROC) curve analysis, the patients were divided into a low CONUT score (< 3) group and a high CONUT score (≥ 3) group. Overall survival (OS) was used as the primary outcome measure and disease-free survival (DFS) as the secondary outcome measure. Results: Among the 354 patients, 239(67.5%) were included in the low CONUT score group and 115 (32.5%) in the high CONUT score group. The 3, 5 and 10-year OS rates in the low CONUT score group and high CONUT score group were respectively presenting statistically significant differences (p<0.001). The 3, 5 and 10-year DFS rates in the low CONUT score group and in the high CONUT score group were respectively with statistically significant differences (p<0.001). Multivariate Cox regression analysis showed that CONUT score, histological type, PNI and lymph node metastasis were all independent predictors for OS and DFS (all p<0.05). Conclusion: High preoperative CONUT score indicates poor prognosis of patients with high-risk factors for early-stage cervical cancer after surgery and postoperative CCRT. In clinical practice, consolidation chemotherapy is recommended for patients with high CONUT scores.

Ferrocene crosslinked and functionalized chitosan microspheres towards bio-based Fenton-like system for the removal of organic pollutants.

Dye-containing wastewater treatment has been a major long-term global challenge. For this purpose, a novel bio-based microspheres (CS-FC) with high specific surface area (63.24 m2·g-1) and nano-channels (17.95 nm) was prepared using chitosan as the framework and ferrocene as a crosslinking active group. CS-FC not only has the ability to rapidly enrich methyl orange (MO) through hydrogen-bonding and electrostatic attraction, but also almost completely degrades it in the presence of H2O2/K2S2O8 through a synergistic radical/non-radical mechanism under the activating effect of ferrocene. Without H2O2/K2S2O8, the maximum MO adsorption capacity of CS-FC is in the range 871-1050 mg·g-1, and conforms to a Langmuir isothermal model with pseudo-second-order kinetics. In the presence of H2O2/K2S2O8, the removal of MO dramatically increased from 32 % to nearly 100 % after incubation for 60 min, due to the simultaneous formation of highly reactive 1O2 and ·OH. The significant contribution from 1O2 endowed CS-FC/H2O2/K2S2O8 with high universality for degrading various organic pollutants (including azo dyes and antibiotics), a wide pH window (2-8), and low sensitivity to co-existing ions. Such cost-effective, recyclable porous bio-based microspheres are suitable for heterogeneous Fenton-like catalysis in organic wastewater treatment that rely on synergistic radical/non-radical reaction pathways.

Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study.

BACKGROUND: There is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF. METHODS: Patients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients. RESULTS: Regarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients). CONCLUSIONS: Based on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.

Preoperative vascular heterogeneity based on dynamic susceptibility contrast MRI in predicting spatial pattern of locally recurrent high-grade gliomas.

OBJECTIVES: To investigate if spatial recurrence pattern is associated with patient prognosis, and whether MRI vascular habitats can predict spatial pattern. METHODS: In this retrospective study, 69 patients with locally recurrent high-grade gliomas (HGGs) were included. The cohort was divided into intra-resection cavity recurrence (ICR) and extra-resection cavity recurrence (ECR) patterns, according to the distance between the location of the recurrent tumor and the resection cavity or surgical region. Four vascular habitats, high angiogenic tumor, low angiogenic tumor, infiltrated peripheral edema, and vasogenic peripheral edema, were segmented and vascular heterogeneity parameters were analyzed. The survival and diagnostic performance under different spatial recurrence patterns were analyzed by Kaplan-Meier and ROC. A nomogram model was constructed by regression analysis and validated by bootstrapping technique. RESULTS: Progression-free survival (PFS) and overall survival (OS) were longer for ICR (n = 32) than those for ECR (n = 37) (median PFS: 8 vs. 5 months, median OS: 17 vs. 13 months, p < 0.05). MRI vascular habitat analyses showed ECR had higher median relative cerebral blood volume (rCBVmedian) at each habitat than ICR (all p < 0.01). The rCBVmedian at IPE had good diagnostic performance (AUC: 0.727, 95%CI: 0.607, 0.828). The AUC of the nomogram based on MRI vascular habitats and clinical factors was 0.834 (95%CI: 0.726, 0.913) and was confirmed as 0.833 (95%CI: 0.830, 0.836) by bootstrapping validation. CONCLUSIONS: The spatial pattern of locally recurrent HGGs is associated with prognosis. MRI vascular heterogeneity parameter could be used as a non-invasive imaging marker to predict spatial recurrence pattern. CLINICAL RELEVANCE STATEMENT: Vascular heterogeneity parameters based on MRI vascular habitat analyses can non-invasively predict the spatial patterns of locally recurrent high-grade gliomas, providing a new diagnostic basis for clinicians to develop the extent of surgical resection and postoperative radiotherapy planning. KEY POINTS: • Intra-resection cavity pattern was associated with longer progression-free survival and overall survival in locally recurrent high-grade gliomas. • Higher vascular heterogeneities in extra-resection cavity recurrence than in intra-resection cavity recurrence and the vascular heterogeneity parameters had good diagnostic performance in discriminating spatial recurrence pattern. • A nomogram model based on MRI vascular habitats and clinical factors had good performance in predicting spatial recurrence pattern.

Leveraging an efficient preparation method into magnetic resonance examinations of young children aged 3-6.

PURPOSE: To evaluate the benefits of a multifaceted concept, ANMTE (Appropriate Number of children, appropriate learning Methods, appropriate adaptive Training, and appropriate Encouragement), proposed by our group, in improving the success rate, efficiency and image quality of Magnetic Resonance (MR) examinations for children from 3 to 6 years old. METHOD: In this study, 150 participants were included from July 2019 to January 2023, including 50 non-sedated children in ANMTE group, 50 in the group with sedative, and 50 in the group with routine preparations. ANMTE refers to appropriate number of children, appropriate learning methods, appropriate adaptive training, and appropriate encouragement, developed by our group for MR examinations of children from 3 to 6 years old. Group differences in success rate, efficiency, and image quality were evaluated across the three groups using Kaplan-Meier, Log-rank and Chi-square test, respectively. RESULTS: The rates of successful MR examinations were 44/50 (88 %), 45/50 (90 %), and 36/50 (72 %) for ANMTE group, the group with sedatives and the group with routine preparations, respectively (P = 0.03). Image quality of the 3 groups showed no significant group difference (P = 0.067). In terms of the median duration of MR examinations, ANMTE group was comparable to the group with sedative (both were about 10.0 min), but better than the group with routine preparations (16.5 min) (P = 0.024). CONCLUSION: We demonstrated the feasibility of our comprehensive nursing method ANMTE in MR examinations of young children, similar to the group with sedative at the success rate and image quality as well as the durations of MR examinations. ANMTE has not only better efficiency but also higher safety as it does not require sedative, which could be promising in clinical routine MR examinations for young children aged 3-6 years old.

The Value of Sports and Functional Exercise on Preventing Falls in Elderly Patients with Cognitive Impairment: A Systematic Review and Meta-Analysis.

Objective: To explore the value of sports and functional exercises in preventing falls in elderly patients with cognitive impairment. Methods: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang Database, and China Biomedical Literature Database (CBM), from inception to January 2023, were used to search the randomized controlled trials (RCTs) of sports and functional exercises in elderly patients with cognitive impairment. Two independent researchers extracted the data and evaluated the quality of the included literature. RevMan5.4 software was adopted for data analysis. Results: The results indicated that exercise combined with functional exercise could noticeably enhance the fall effect score and shorten the Timed Up and Go Test (TUGT) time of elderly patients with cognitive impairment compared to simple drug treatment (P < .05). Our results showed that the exercise combined with functional exercise can noticeably prolong the standing time of elderly patients with cognitive impairment upon monocular eye closure. Our results also showed that exercise combined with functional exercise can noticeably improve the fear of falls in elderly patients with cognitive impairment. Conclusion: Sports and functional exercise intervention can promote the balance ability and fall self-efficacy of elderly patients with cognitive impairment and have a positive effect on enhancing patients' fear of falls. The findings need to be further verified and methodological quality needs to be improved. In addition, longer intervention times are required to verify the findings.

Clinical Research of Lupus Retinopathy: Quantitative Analysis of Retinal Vessels by Optical Coherence Tomography Angiography in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Lupus retinopathy, an ocular manifestation of systemic lupus erythematosus (SLE), is the major pathology attributed to retinal vasculopathy. Our study is to analyze the changes in retinal vessels in patients with SLE by optical coherence tomography angiography. METHODS: A total of 61 SLE patients without obvious retinal manifestation and 71 healthy people were included. The SLE patients were further divided into a lupus nephritis (LN) group and a non-LN group. The changes in central macular thickness (CMT) and the retinal vessel densities were compared between the two groups, and the correlation between retinal vascular changes and disease activity was analyzed. RESULTS: Compared with healthy control, the CMT and the retinal vascular densities in both superficial and deep retina were decreased significantly in SLE patients. There was no significant difference in retinal vascular densities between LN groups and non-LN groups. CONCLUSION: The CMT and retinal vessel densities were decreased in SLE patients without clinical manifestations, which might serve as a sensitive biomarker for early changes of lupus retinopathy in SLE patients.

Mid-term assessment of subtalar arthroereisis with Talar-Fit implant in pediatric patients with flexible flatfoot and comparing the difference between different sizes and exploring the position of the inserted implant.

Background: Subtalar arthroereisis (STA) has gained growing acceptance as a viable approach solution for the management of pediatric flexible flatfoot. However, STA still remains controversial. The purpose of this study is to assess the effect of STA using the Talar-Fit implant for treating pediatric flexible flatfoot. Specifically, the aims of the study are as follows: first, to present the mid-term outcomes of STA using the Talar-Fit implant; second, to compare the radiographic and clinical outcomes associated with varying sizes of Talar-Fit implant; and third, to analyze the optimal position of the inserted implants. Methods: A retrospective analysis was conducted on a cohort of 57 pediatric patients diagnosed with flexible flatfoot (77 feet) who underwent STA utilizing Talar-Fit between January 2014 and December 2021. The participants were categorized into five groups according to the size of the implant: Group 8, Group 9, Group 10, Group 11, and Group 12. The evaluation included the assessment of clinical function using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot score, as well as the assessment of radiographic data such as the calcaneal pitch angle (CPA), lateral Meary angle (LMA), talar declination angle (TDA), and medial longitudinal arch angle (MLAA) were evaluated. Furthermore, the position of the inserted implants was also recorded, including angle, depth, and distance. The comparison of pre- and postoperation was conducted using the paired Student's t-test, whereas the analysis of differences among subgroups was performed using the Wilcoxon rank-sum test. A P-value < 0.05 is considered statistically significant. Results: In total, 57 pediatric patients (77 feet) were successfully followed-up for an average period of 26.8 months. The overall AOFAS score significantly improved from 58.6 ± 10.9 to 85.2 ± 8.6 (P < 0.001). Furthermore, the LMA decreased from 20.3° ± 3.6° to 4.5° ± 1.3°, the CPA increased from 14.8° ± 1.6° to 23.6° ± 2.7°(P < 0.05), the TDA decreased from 40.2° ± 2.3° to 25.5° ± 3.2°(P < 0.05), and the MLAA decreased from 140.1° ± 2.8° to 121.4° ± 3.9°(P < 0.05). No statistically significant differences were observed among subgroups regarding the final outcomes. The improvements of CPA, TDA, and MLAA among different groups were significantly different; however, the adjusted P-values were all greater than 0.05. The implant were inserted at a mean angle of 89.5° ± 2.4°, a mean depth of 0.9 mm ± 2.1 mm, and a mean distance of 9.9 mm ± 0.9 mm. Eight patients experienced complications, including six cases of pain occurrence and two cases of implant dislocation. Conclusion: STA with Talar-Fit has demonstrated satisfactory mid-term outcomes. A Talar-Fit with a larger size may demonstrate a superior effect when compared with that of a smaller size. The implants were inserted in a similar position, indicating that the medial edge of the implant may be possible to transcend the midline of the talus neck.

Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging Combined with T1 Mapping Identifies Dysplastic Module and Hepatocellular Carcinoma: A Retrospective Study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading type of liver cancer in adults, often resulting in fatal outcomes for those with cirrhosis. Dysplastic nodule (DN) is a liver nodule that is substantial in size, ranging from 1-2 cm. However, accurately distinguishing between DN and HCC on imaging has posed a challenge. OBJECTIVE: The aim of this study is to assess the usefulness of Gd-EOB-DTPA-enhanced MRI T1 mapping in distinguishing between DN and HCC. METHODS: This study analyzed 66 patients with confirmed HCC or DN who underwent Gd-EOB-DTPA-enhanced MRI T1 mapping before surgery or puncture at the Army Medical Center in China. The T1 values of each lesion were measured before and after Gd-EOB-DTPA administration, and various calculations were made, including absolute and percentage reduction in T1 value and coefficient of variation. The t-test was used to compare these values between the two groups, and the efficacy of T1 mapping values for differential diagnosis of HCC and DN was evaluated using the receiver operating characteristic curve (ROC). RESULTS: The study found that T1pre, T1hp, ΔT1, ΔT1%, and CV in the HCC group were significantly higher than in the DN group (p < 0.01). The accuracy of T1hp, ΔT1, and CVT1-hp in identifying HCC from DN was high, with AUCs of 0.955, 0.910, and 0.932, respectively. ΔT1% also had some accuracy, with an AUC of 0.818. CONCLUSION: Our results provide preliminary evidence that Gd-EOB-DTPA-enhanced MRI T1, CVT1-hp mapping, can be a valuable tool in diagnosing and differentiating between HCC and DN.

ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling.

Rho GTPase-activating protein 4 (ARHGAP4) is an important Rho family GTPase-activating protein that is strongly associated with the onset and progression of some tumors. We found that ARHGAP4 mRNA and protein are overexpressed in human acute myeloid leukemia (AML) patients and are associated with a poor prognosis. ARHGAP4 knockdown significantly impairs viability and colony formation capacity and induces apoptosis in AML cells. Further results demonstrate that ARHGAP4 deletion impairs AML progression in vivo. Interestingly, DRAM1 signaling is significantly activated in AML cells with ARHGAP4 knockdown. Our results also indicated that ARHGAP4 might function in AML cells by binding with p53 to inhibit DRAM1. Moreover, knockdown of DRAM1 rescues the defects of ARHGAP4 in AML cells. This newly described role of the ARHGAP4/DRAM1 axis in regulating AML progression may have important therapeutic implications.

Preclinical Development of Brain Permeable ERß Agonist for the Treatment of Glioblastoma.

Glioblastoma (GBM) is the most prevalent and aggressive type of adult brain tumors with low 5-year overall survival rates. Epidemiologic data suggest that estrogen may decrease brain tumor growth, and estrogen receptor beta (ERß) has been demonstrated to exert antitumor functions in GBM. The lack of potent, selective, and brain permeable ERß agonist to promote its antitumor action is limiting the therapeutic promise of ERß. In this study, we discovered that Indanone and tetralone-keto or hydroxyl oximes are a new class of ERß agonists. Because of its high activity in ERß reporter assays, specific binding to ERß in polar screen assays, and potent growth inhibitory activity in GBM cells, CIDD-0149897 was discovered as a possible hit by screening a library of compounds. CIDD-0149897 is more selective for ERß than ERα (40-fold). Treatment with CIDD-0149897 markedly reduced GBM cell viability with an IC50 of ∼7 to 15 µmol/L, while having little to no effect on ERß-KO cells and normal human astrocytes. Further, CIDD-0149897 treatment enhanced expression of known ERß target genes and promoted apoptosis in established and patient-derived GSC models. Pharmacokinetic studies confirmed that CIDD-0149897 has systemic exposure, and good bioavailability in the brain. Mice tolerated daily intraperitoneal treatment of CIDD-0149897 (50 mg/kg) with a 7-day repeat dosage with no toxicity. In addition, CIDD-0149897 treatment significantly decreased tumor growth in U251 xenograft model and extended the survival of orthotopic GBM tumor-bearing mice. Collectively, these findings pointed to CIDD-0149897 as a new class of ERß agonist, offering patients with GBM a potential means of improving survival.

Inhibition of Amyloid ß Aggregation and Cytotoxicity by Berbamine Hydrochloride.

Alzheimer's disease (AD) continues to be a major global health challenge, and the recent approval of Aduhelm and Leqembi has opened new avenues for its treatment. Small-molecule inhibitors targeting Aß aggregation hold promise as an alternative to monoclonal antibodies. In this study, we evaluated the ability of berbamine hydrochloride (BBMH), a member of the bisbenzylisoquinoline alkaloids, to reduce Aß aggregation and cytotoxicity. Thioflavin T kinetics, circular dichroism spectroscopy, and atomic force microscopy results indicated that BBMH effectively inhibited Aß aggregation. Surface plasmon resonance and molecular docking results further revealed that BBMH could bind to Aß fibrils, thereby hindering the aggregation process. This physical picture has been confirmed in a quantitative way by chemical kinetics analysis, which showed BBMH tends to bind with the fibril ends and thus prevents the transition from protofibrils to mature fibrils as well as the elongation process. Additionally, our MTT results showed that BBMH was able to reduce the cytotoxicity of Aß40 on N2a cells. Our results demonstrate, for the first time, the potential of BBMH to inhibit Aß aggregation and cytotoxicity, offering a promising direction for further research and drug development efforts in the fight against Alzheimer's disease.

Redox-responsive microemulsion: Fabrication and application to curcumin encapsulation.

HYPOTHESIS: Stimulus-responsive microemulsions have aroused significant attention because of their versatile and reversible switchability between stable and unstable states. However, most stimuli-responsive microemulsions are based on stimuli-responsive surfactants. We posit that the change in the hydrophilicity of a selenium-containing alcohol triggered by a mild redox reaction could also influence the stability of microemulsions and provide a new nanoplatform for the delivery of bioactive substances. EXPERIMENTS: A selenium-containing diol (3,3'-selenobis(propan-1-ol), PSeP) was designed and used as a co-surfactant in a microemulsion with ethoxylated hydrogenated castor oil (HCO40), diethylene glycol monohexyl ether (DGME), 2-n-octyl-1-dodecanol (ODD) and water. The redox-induced transition in PSeP was characterized by 1H NMR, 77Se NMR, and MS. The redox-responsiveness of the ODD/HCO40/DGME/PSeP/water microemulsion was investigated through determination of a pseudo-ternary phase diagram, analysis by dynamic light scattering, and electrical conductivity, and its encapsulation performance was evaluated by determination of the solubility, stability, antioxidant activity, and skin penetrability of encapsulated curcumin. FINDINGS: The redox conversion of PSeP enabled efficient switching of ODD/HCO40/DGME/PSeP/water microemulsions. Addition of oxidant (H2O2), oxidized PSeP into more hydrophilic PSeP-Ox (selenoxide), disrupting the emulsifying capacity of the combination of HCO40/DGME/PSeP, markedly reducing the monophasic microemulsion region in the phase diagram, and inducing phase separation in some formulations. Addition of reductant (N2H4·H2O), reduced PSeP-Ox and restored the emulsifying capacity of the combination of HCO40/DGME/PSeP. In addition, PSeP-based microemulsions can significantly enhance the solubility in oil (by 23 times), stability, antioxidant capacity (DPPH∙ radical scavenging by 91.74 %), and skin penetrability of curcumin, showing clear potential for encapsulation and delivery of curcumin and other bioactive substances.