A 3D-printed scaffold composed of Alg/HA/SIS for the treatment of diabetic bone defects.

Background: Diabetic bone healing remains a great challenge due to its pathological features including biochemical disturbance, excessive inflammation, and reduced blood vessel formation. In previous studies, small intestine submucosa (SIS) has been demonstrated for its immunomodulatory and angiogenic properties, which are necessary to diabetic bone healing. However, the noticeable drawbacks of SIS such as fast degradation rate, slow gelling time, and weak mechanical property seriously impede the 3D printing of SIS for bone repair. Method: In this study, we developed a novel kind of 3D-printed scaffold composed of alginate, nano-hydroxyapatite, and SIS. The morphological characterization, biocompatibility, and in vitro biological effects of the scaffolds were evaluated, and an established diabetic rat model was used for testing the in vivo biological effect of the scaffold after implantation. Results: The in vitro and in vivo results show that the addition of SIS can tune the immunomodulatory properties and angiogenic and osteogenic performances of 3D-printed scaffold, where the macrophages polarization of M2 phenotype, migration and tube formation of HUVECs, as well as osteogenic expression of ALP, are all improved, which bode well with the functional requirements for treating diabetic bone nonunion. Furthermore, the incorporation of alginate substantially improves the printability of composites with tunable degradation properties, thereby broadening the application prospect of SIS-based materials in the field of tissue engineering. Conclusion: The fabricated 3D-printed Alg/HA/SIS scaffold provides desirable immunomodulatory effect, as well as good osteogenic and angiogenic performances in vitro and in vivo, which properties are well-suited with the requirement for treating diabetic bone defects. Translational potential of this article: The incorporation of SIS and alginate acid not only provides good printability of the newly fabricated 3D-printed Alg/HA/SIS scaffold, but also improves its immunoregulatory and angiogenic properties, which suits well with the requirement for treating diabetic bone disease and opens up new horizons for the development of implants associating diabetic bone healings.

Relationship between cathepsins and cardiovascular diseases: a Mendelian randomized study.

Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) to explore the causal relationships between cathepsins and CVDs. Methods: We obtained single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study, a publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP data were sourced from seven distinct GWAS datasets, ensuring a comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, we primarily employed the inverse variance weighted (IVW) method, known for its efficiency when all SNPs are valid instruments. This was supplemented by the weighted median and MR-Egger methods to provide robustness against potential violations of MR assumptions, such as pleiotropy. The IVW method offers precision and efficiency, the weighted median method adds robustness against invalid instruments, and the MR-Egger method helps identify and correct for pleiotropic biases. Cochran's Q test was utilized to assess heterogeneity, and sensitivity analyses were conducted using MR-PRESSO and the leave-one-out approach. Results: The strength of the associations between exposure and outcome was measured using odds ratios (ORs), and results were presented with 95% confidence intervals (CIs). The cathepsin E increases the risk of myocardial infarction (MI) (OR = 1.053%, 95% CI: 1.007-1.101, p = 0.024) and ischemic stroke (IS) (OR = 1.06%, 95% CI: 1.019-1.103, p = 0.004). Conversely, cathepsin L2 decreases the risk of chronic heart failure (CHF) (OR = 0.922%, 95% CI: 0.859-0.99, p = 0.025) and atrial fibrillation (AF) (OR = 0.956%, 95% CI: 0.918-0.996, p = 0.033). Cathepsin O was associated with an increased risk of IS (OR = 1.054%, 95% CI: 1.008-1.102, p = 0.021) and AF (OR = 1.058%, 95% CI: 1.02-1.098, p = 0.002). Conclusion: Our MR analysis reveals that cathepsin E is a risk factor for MI and IS, cathepsin L2 offers protective effects against CHF and AF, and cathepsin O increases the risk for IS and AF.

The genetic duet of concurrent RASAL1 and PTEN alterations promotes cancer aggressiveness by cooperatively activating the PI3K-AKT pathway.

The significance of the prominent tumor suppressor gene for RAS protein activator-like 1 (RASAL1) could be better understood by combined genetic, clinical, and functional studies. Here, we investigated the oncogenic and clinical impacts of genetic alterations of RASAL1, particularly when coexisting with genetic alterations of the gene for phosphatase and tensin homolog (PTEN), in 9924 cancers of 33 types in the TCGA database. We found common concurrent genetic alterations of the two genes, which were cooperatively associated with activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, with cancer progression and mortality rates being 46.36% and 31.72% with concurrent gene alterations, versus 29.80% and 16.93% with neither gene alteration (HR 1.64, 95% CI 1.46-1.84 and 1.77, 95% CI 1.53-2.05), respectively. This was enhanced by additional tumor protein p53 (TP53) gene alterations, with cancer progression and mortality rates being 47.65% and 34.46% with coexisting RASAL1, PTEN, and TP53 alterations versus 25.30% and 13.11% with no alteration (HR 2.21, 95% CI 1.92-2.56 and 2.76, 95% CI 2.31-3.30), respectively. In the case of breast cancer, this genetic trio was associated with a triple-negative risk of 68.75% versus 3.83% with no genetic alteration (RR 17.94, 95% CI 9.60-33.51), consistent with the aggressive nature of triple-negative breast cancer. Mice with double knockouts of Rasal1 and Pten displayed robust Pi3k pathway activation, with the development of metastasizing malignancies, while single gene knockout resulted in only benign neoplasma. These results suggest that RASAL1, like PTEN, is a critical player in negatively regulating the PI3K-AKT pathway; defect in RASAL1 causes RAS activation, thus initiating the PI3K-AKT pathway signaling, which cannot terminate with concurrent PTEN defects. Thus, the unique concurrent RASAL1 and PTEN defects drive oncogenesis and cancer aggressiveness by cooperatively activating the PI3K-AKT pathway. This represents a robust genetic mechanism to promote human cancer.

Efficacy of the tetravalent protein COVID-19 vaccine, SCTV01E: a phase 3 double-blind, randomized, placebo-controlled trial.

Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Clinical Characteristics and Outcomes of Generalized Myasthenia Gravis in Malaysia: A Single-Center Experience.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is clinically heterogeneous and can be classified into subgroups according to the clinical presentation, antibody status, age at onset, and thymic abnormalities. This study aimed to determine the clinical characteristics and outcomes of generalized MG (GMG) patients based on these subgroups. METHODS: Medical records of MG patients from 1976 to 2023 were reviewed retrospectively. Patients with pure ocular MG were excluded. Data on demographic, clinical characteristics, laboratory features, and outcomes were analyzed. RESULTS: This study included 120 GMG patients. There was a slight preponderance of female patients over male patients (male:female ratio=1:1.3), with the age at onset exhibiting a bimodal distribution. Female patients peaked at a lower age (21-30 years) whereas male patients peaked at a higher age (61-70 years). Most (92%, 105 of 114) patients had positive anti-acetylcholine receptor antibodies. Five patients were also tested for anti-muscle-specific tyrosine kinase antibodies, with two showing positivity. Thymectomy was performed in 62 (52%) patients, of which 30 had thymoma, 16 had thymic hyperplasia, 7 had an involuted thymus, and 6 had a normal thymus. There were significantly more female patients (68% vs. 45%, p=0.011) with early-onset disease (<50 years old) and thymic hyperplasia (33% vs. 0%, p<0.025). Most (71%) of the patients had a good outcome based on the Myasthenia Gravis Foundation of America postintervention status. GMG patients with early-onset disease had a significantly better outcome than patients with a late onset in univariate (58% vs. 37%, p=0.041) and multivariate (odds ratio=4.68, 95% confidence interval=1.17-18.64, p=0.029) analyses. CONCLUSIONS: Female patients with early-onset MG and thymic hyperplasia had significantly better outcomes, but only early-onset disease was independently associated with a good outcome. These findings are comparable with those of other studies.

Bionic Potassium Ion Channel in Live Cells Repairs Cardiomyocyte Function.

The disturbance of potassium current in cardiac myocytes caused by potassium channel dysfunction can lead to cardiac electrophysiological disorders, resulting in associated cardiovascular diseases. The emergence of artificial potassium ion channels opens up a way to replace dysfunctional natural ion channels and cure related diseases. However, bionic potassium ion channels have not been introduced into living cells to regulate cell function. One of the biggest challenges is that when the bionic channel fuses with the cell, it is difficult to control the inserting angle of the bionic potassium channel to ensure its penetration of the entire cell membrane. In nature, the extracellular vesicles can fuse with living cells with a completely preserved structure of vesicle protein. Inspired by this, we developed a vesicle fusion-based bionic porin (VFBP), which integrates bionic potassium ion channels into cardiomyocytes to replace damaged potassium ion channels. Theoretical and experimental results show that the inserted bionic ion channels have a potassium ion transport rate comparable to that of natural ion channels, which can restore the potassium ion outflow in cardiomyocytes and repair the abnormal action potential and excitation-contraction coupling of cardiomyocytes. Therefore, the bionic potassium ion channel system based on membrane fusion is expected to become the research object in many fields such as ultrafast ion transport, transmembrane delivery, and channelopathies treatment.

TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.

Background/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury of HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell-membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions: The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Microwave-assisted Facile Synthesized Carbon Dots as "on-off-on" Fluorescence Probes for Mercury and Iodine Ions in Bio-samples and Cell Imaging.

A kind of nitrogen and sulfur co-doped CDs (N, S-CDs) was facilely synthesized using thiourea and citric acid as precursors, which established an "on-off-on" fluorescence probe to sequential detecting mercury and iodine ions inside water and biology samples. Under 360 nm excitation, CDs emit blue fluorescence with an optimal emission peak of 425 nm (on). The fluorescence of CDs experiences a significant quenching effect upon interaction with Hg2+ ions due to the electron transfer between CDs and Hg2+. This quenching effect is subsequently recovered upon the addition of I- owing to the formation of complexes between Hg2+ and I-. The probe exhibits high selectivity and sensitivity toward Hg2+ and I- with broad linearity in the range of 5-50 µM and 15-60 µM, respectively, and a low detection limit of 14.336 nM and 38.213 nM, respectively. The constructed fluorescence probe N, S-CDs has been successfully applied to the detection of Hg2+ and I- in water and biological samples with great recoveries. More importantly, the bioimaging study demonstrated that N, S-CDs are suitable for live monitoring in biological imaging scenarios of Hg2+ and I- in living cells.

Enhancing Lithium-Sulfur Battery Performance with MXene: Specialized Structures and Innovative Designs.

Established in 1962, lithium-sulfur (Li-S) batteries boast a longer history than commonly utilized lithium-ion batteries counterparts such as LiCoO2 (LCO) and LiFePO4 (LFP) series, yet they have been slow to achieve commercialization. This delay, significantly impacting loading capacity and cycle life, stems from the long-criticized low conductivity of the cathode and its byproducts, alongside challenges related to the shuttle effect, and volume expansion. Strategies to improve the electrochemical performance of Li-S batteries involve improving the conductivity of the sulfur cathode, employing an adamantane framework as the sulfur host, and incorporating catalysts to promote the transformation of lithium polysulfides (LiPSs). 2D MXene and its derived materials can achieve almost all of the above functions due to their numerous active sites, external groups, and ease of synthesis and modification. This review comprehensively summarizes the functionalization advantages of MXene-based materials in Li-S batteries, including high-speed ionic conduction, structural diversity, shuttle effect inhibition, dendrite suppression, and catalytic activity from fundamental principles to practical applications. The classification of usage methods is also discussed. Finally, leveraging the research progress of MXene, the potential and prospects for its novel application in the Li-S field are proposed.

Atypical Periprosthetic Femoral Fracture Might be Considered a Distinct Subtype of Atypical Femoral Fracture: A Retrospective Study.

OBJECTIVE: The exact relationship among atypical periprosthetic femoral fractures (APFFs), typical periprosthetic femoral fractures (PFFs), and atypical femur fractures (AFFs) remains unclear. This study aimed to investigate the prevalence of APFFs among PFFs and to identify the clinical characteristics, management, and prognosis that distinguish APFFs from typical PFFs and AFFs to further determine the relationship among these three fracture types. METHODS: In this retrospective study, we reviewed the clinical data of 117 consecutive patients who had PFFs after hip arthroplasty between January 2012 and December 2022 and further classified them into an APFF group and a typical PFF group according to the revised ASBMR diagnostic criteria for AFF. Moreover, patients who had subtrochanteric or femoral shaft fractures in the same period and met the diagnostic criteria for AFF were recruited and classified into the AFF group. Demographic information, minor features of AFF, comorbidities, history of medication usage, management, and complications were collected and compared among patients with typical PFFs, APFFs, and AFFs. RESULTS: Eleven PFFs were identified as APFFs, and the prevalence of APFFs among PFFs was 9.4%. Significant differences were found in generalized increase in cortical thickness (p = 0.019), prodromal symptoms (p < 0.001), and the incidence of bilateral fractures (p = 0.010) among the groups, where the incidences of these minor features in the APFF group and the AFF group were higher than those in the typical PFF group. Of note, the duration of fracture healing of APFFs was significantly longer than that of typical PFFs and AFFs (p < 0.001 and p = 0.004, respectively). In addition, the APFF group and the AFF group had higher proportions of patients with rheumatoid arthritis (p = 0.004 and p = 0.027, respectively), bisphosphonate (BP) usage (p = 0.026 and p < 0.001, respectively), and longer duration of BP usage (p = 0.003 and p = 0.007, respectively) than the typical PFF group. Furthermore, significant differences were found in management (p < 0.001) and complication rate (p = 0.020) among the groups, and the rate of complications in the APFF group and the AFF group was higher than that in the typical PFF group. CONCLUSIONS: APFFs not only fulfilled the mandatory and major diagnostic criteria for AFF but also had many clinical characteristics, management and prognosis distinguishing them from typical PFFs but resembling AFFs; hence, the diagnostic criteria for AFF might be revised to incorporate APFF as a distinct subtype of the condition.

Photochemistry of Imidazole-2-carbaldehyde in Droplets as a Potential Source of H2O2 and Its Oxidation of SO2.

Hydrogen peroxide (H2O2) plays a crucial role as an oxidizing agent within the tropospheric environment, making a substantial contribution to sulfate formation in hydrated aerosols and cloud and fog droplets. Field observations show that high levels of H2O2 are often observed in heavy haze events and polluted air. However, the source of H2O2 remains unclear. Here, using the droplets formed in situ by the deliquescence of hygroscopic compounds under a high relative humidity (RH), the formation of H2O2 by the photochemistry of imidazole-2-carbaldehyde (2-IC) under ultraviolet irradiation was explored. The results indicate that 2-IC produces IM-C•-OH and IM-C•═O radicals via H transfer itself to its excited triplet state and generates H2O2 and organic peroxides in the presence of O2, which has an evident oxidizing effect on SO2, suggesting the potential involvement of this pathway in the formation of atmospheric sulfate. H2O2 formation is limited in acidic droplets or droplets containing ammonium ions, and no H2O2 is detected in droplets containing nitrate, whereas droplets containing citric acid have an obvious promotion effect on H2O2 formation. These findings provide valuable insights into the behaviors of atmospheric photosensitizers, the source of H2O2, and the formation of sulfate in atmospheric droplets.

Anti-hair loss effect of a shampoo containing caffeine and adenosine.

BACKGROUND: Hair loss is a widespread health problem that affects numerous individuals and is associated with age, lack of sleep, stress, endocrine problems, and other problems. Caffeine exerts various pharmacological effects, particularly after ingestion. The caffeine-induced inhibition of phosphodiesterases can increase intracellular cAMP concentrations, ultimately resulting in stimulatory effects on cell metabolism and proliferation. Hence, caffeine has been confirmed to inhibit hair loss caused by premature termination of the hair growth phase. Adenosine also improves hair loss by stimulating hair growth and thickening hair shafts. However, further empirical evidence is required to comprehensively assess the efficacy of hair loss treatment and prevention using a formulation of caffeine and adenosine in specific proportions in shampoos. OBJECTIVES: This study aimed to evaluate a shampoo with caffeine and adenosine as a daily scalp care product for hair loss in 77 subjects aged 18-60 years. METHODS: The overall and local hair densities were assessed using professional cameras and dermoscopes at different magnifications and distances. Five hairs that came off the participant's head were randomly selected to measure hair diameter. The self-assessment questionnaires were filled on third month of product use. RESULTS: The combination of caffeine and adenosine in the shampoo significantly enhanced hair density compared to that of the baseline. The results revealed a significant reduction in hair loss. The hair diameters of the subjects did not change significantly. Most of the participants (71.05%) were satisfied with their hair after using the product. CONCLUSIONS: Shampoos containing caffeine and adenosine have been demonstrated to exert therapeutic benefits for reducing hair loss.

A randomized, double-blind, placebo-controlled phase I clinical trial of rotavirus inactivated vaccine (Vero cell) in a healthy adult population aged 18-49 years to assess safety and preliminary observation of immunogenicity.

We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).

Less Acetabular Coverage Predicts the Failure of Core Decompression for Osteonecrosis of the Femoral Head: A Retrospective Cohort Study.

OBJECTIVE: It is unclear whether less acetabular coverage is associated with the failure of core decompression (CD) for osteonecrosis of the femoral head (ONFH). This study aimed to investigate the clinical outcomes of CD for ONFH with small- or medium-sized pre-collapse lesions, and determine what factors, especially acetabular anatomical parameters, predict the failure of CD. METHODS: Between January 2010 and December 2022, we retrospectively reviewed 269 consecutive CDs in 188 patients diagnosed with ONFH with small- or medium-sized pre-collapse lesions. The Kaplan-Meier method was used to evaluate the survival rate of CD for ONFH with progression of collapse or conversion to total hip arthroplasty (THA) as the endpoint. Univariate and multivariate logistic regression analyses were conducted to identify the potential risk factors for the failure of CD. Receiver operating characteristic (ROC) curve analysis was further performed with conversion to THA as the endpoint to determine the predictive value of these factors. RESULTS: The overall 5-year survival rate of CD for ONFH with small- or medium-sized pre-collapse lesions was 74.3% (95% confidence interval (CI) 69.0%-81.1%) with progression of collapse as the endpoint and 83.9% (95% CI 79.3%-88.7%) with conversion to THA as the endpoint. Univariate logistic regression analysis showed that bilateral affected hips was significantly associated with progression of collapse, and center-edge angle (CEA), sharp angle, acetabular head index (AHI), as well as acetabular depth ratio (ADR) were significantly associated with both progression of collapse and conversion to THA. Multivariate logistic regression analysis further indicated that CEA and AHI were independent risk factors for both progression of collapse and conversion to THA. ROC curve analysis with conversion to THA as the endpoint revealed that the cutoff values for CEA and AHI were 26.8° (sensitivity = 74.4%, specificity = 78.6%, area under the curve (AUC) = 0.809) and 79.8 (sensitivity = 78.4%, specificity = 73.8%, AUC = 0.818), respectively. CONCLUSIONS: CD showed satisfactory clinical outcomes for ONFH with small- or medium-sized pre-collapse lesions where less acetabular coverage with a CEA < 26.8° or AHI < 79.8 was identified as an independent risk factor for the failure of CD.

Comprehensive comparison between conservative therapy and surgical management for completely displaced and comminuted mid-shaft clavicle fractures.

PURPOSE: It is still controversial whether complete displaced mid-shaft clavicle fractures should be treated with internal fixation or conservative therapy. This retrospective study aims to compare clinical outcomes of two treatment protocols. MATERIALS AND METHODS: 105 patients with displaced and comminuted mid-shaft clavicle fractures were included in this study, among which 55 patients were treated conservatively and 50 patients accepted surgical fixation and were followed up for over 20 months on average. Rate of union, malunion, time taken for union, functional outcome, self-reported satisfaction and complications were compared. RESULTS: Union rate of operative group (n=49, 98.0%) was higher than the non-operative group (n=48, 87.3%). Time taken for union in operative group (2.37±1.06 months) was shorter than the non-operative group (3.69±1.01 months). Malunion and asymmetric were only seen in the conservative group. Numbness of the shoulder was only reported in the operative group (n=23, 46.0%). Most of patients in the operative group (n=45, 90%) accepted a second operation to remove the implant. No statistically difference was found in self-reported satisfaction, Quick-DASH and Constant-Murley score. The operative group returned to work faster (1.47±0.89 to 3.34±1.37 months), regained full range of motion earlier (1.66±0.78 to 3.83±1.24 months) and regained strength faster (3.86±2.45 to 8.03±2.78 months) than the non-operative group. CONCLUSION: Complete displaced and comminuted mid-shaft clavicle fractures treated surgically have more reliable union and faster recovery when compared to conservatively treated fractures.

Bulk Segregant Analysis Sequencing and RNA-Seq Analyses Reveal Candidate Genes Associated with Sepal Color Phenotype of Eggplant (Solanum melongena L.).

Eggplant is a highly significant vegetable crop and extensively cultivated worldwide. Sepal color is considered one of the major commercial traits of eggplant. Eggplant sepals develop from petals, and sepals have the ability to change color by accumulating anthocyanins, but whether the eggplants in sepal and their biosynthetic pathways are the same as those in petals is not known. To date, little is known about the underlying mechanisms of sepal color formation. In this study, we performed bulked segregant analysis and transcriptome sequencing using eggplant sepals and obtained 1,452,898 SNPs and 182,543 InDel markers, respectively, as well as 123.65 Gb of clean data using transcriptome sequencing. Through marker screening, the genes regulating eggplant sepals were localized to an interval of 2.6 cM on chromosome 10 by bulked segregant analysis sequencing and transcriptome sequencing and co-analysis, combined with screening of molecular markers by capillary electrophoresis. Eight possible candidate genes were then screened to further interpret the regulatory incentives for the eggplant sepal color.

A case report of secondary B-cell acute lymphoblastic leukemia treated with a combination of FLT3 inhibitor and decitabine.

Secondary acute lymphoblastic leukemia (s-ALL) refers to acute lymphoblastic leukemia that occurs after a previous malignant tumor, including therapy-related acute lymphoblastic leukemia (t-ALL) and prior malignant tumor acute lymphoblastic leukemia (pm-ALL). We report a case of a 51-year-old female patient who developed acute lymphoblastic leukemia 14 years after being diagnosed with diffuse large B-cell lymphoma (DLBCL). The patient was unresponsive to conventional chemotherapy for acute lymphoblastic leukemia (ALL) and achieved remission with a combination of sorafenib and decitabine based on the molecular biology characteristics of her B-ALL.

The moderating role of work environment in the relationship between proactive personality and personal growth initiative among nurses: a cross-sectional study.

BACKGROUNDS: Personal growth initiative (PGI) is regarded as a meaningful concept with potential value at both the individual and organizational levels, but little is known about the factors that contribute to nurses' PGI. This study aimed to explore how proactive personality and hospital work environment affect PGI of clinical nurses. METHODS: A cross-sectional study was conducted between September and October 2022 among 4414 nurses from 10 tertiary general hospitals in 10 cities in Sichuan, China, using a two-stage sampling method. Self-reported anonymous online questionnaires, such as sociodemographic information survey, personal growth initiative scale II, the 10-item proactive personality scale, and practice environment scale-nursing work index were used to collect data. Multiple hierarchical regression analyses were performed to examine research hypotheses. RESULTS: Among the control variables in this study, nurses' self-perceptions of general health status and professional title positively predicted PGI (ß = 0.462, 95%CI = 0.272-0.653; ß = 1.078, 95%CI = 0.508-1.648). After adding control variables, both proactive personality (ß = 1.143, 95%CI = 1.096-1.190) and work environment (ß = 3.391, 95%CI = 2.904-3.879) positively predicted PGI. The work environment positively moderated the association between proactive personality and PGI (ß = 0.108, 95%CI = 0.025-0.191). These predictors jointly explained 50.3% of the variance in PGI. CONCLUSIONS: Nurses with a greater tendency to have a typical proactive personality have higher levels of personal growth initiative, and this positive effect will be better highlighted in a healthier work environment. Nursing managers should prioritize the employment of people with proactive personality traits, focus on the development and stimulation of proactive personality traits in nurses, and establish a supportive work environment to maximize the personal growth initiative of nurses.

In vitro modeling of recurrent Dermatofibrosarcoma Protuberans: Assessment of 5-aminolevulinic acid photodynamic therapy efficacy.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.