Migration characteristics of microplastics in riparian soils and groundwater.

Investigations have revealed the presence of microplastics in both soil and groundwater, but the migration characteristics from soil to groundwater remain incompletely understood. In this study, two sampling sections consisting of soil-groundwater-river water were established near Lianxi Bridge and Xilin Bridge along the Jiuxi River in Xiamen. A total of 22 soil samples, 36 groundwater samples, and 18 river water samples were collected. Microplastics were detected in all samples with an abundance range of 392-836 n/kg in soil (mean, 655 ± 177 n/kg), 0.58-2.48 n/L groundwater (mean, 1.23 ± 0.42 n/L), and 0.38-1.80 n/L in river water (mean, 0.86 ± 0.41 n/L). Flakes predominantly constituted the shape of microplastics found in soil, while fibers dominated those present in water. Black, yellow, and red were the dominant color types. Polyamide (PA) and polyethylene (PE) were the main components of microplastics within soils, whereas polyethylene terephthalate (PET), polypropylene (PP), and PA prevailed within water. Microplastic particle sizes ranged from 39 to 2498 µm in soils, mainly from 29 to 3394 µm in water. The upstream section displayed higher abundances of microplastic compared to the downstream, revealing the soil particles having an intercepting effect on microplastics. The distribution and migration of microplastics in soil and groundwater are affected by many factors, including natural and anthropogenic factors, such as soil depth, soil properties, pore structure, hydrodynamics, hydraulic connections between groundwater and surface water, the extensive utilization and disposal of plastics, irrational exploitation of groundwater, and morphology and types of microplastics. These research findings contribute to a better understanding of the pathways, migration capacity, and influencing factors associated with microplastic entry into groundwater, thereby providing valuable technical support for the development of strategies aimed at controlling microplastic pollution.

Clinical significance of FBXW7 tumor suppressor gene mutations and expression in human colorectal cancer: a systemic review and meta-analysis.

BACKGROUND: Various studies investigating the clinical significance of FBXW7 mutation and/or expression have yielded inconclusive results in colorectal cancer (CRC) patients. Therefore, the present meta-analysis summarizes previous evidence and evaluates the clinical significance, including the prognostic role, of FBXW7 status in CRCs. METHODS: The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Web of Science, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the relationships between FBXW7 status and clinicopathological features and survival in CRC, respectively. RESULTS: Ten studies involving 4199 patients met the inclusion criteria and included in our meta-analysis. FBXW7 mutation/low expression was obviously correlated with advanced T stage (OR = 0.44, 95% CI: 0.27-0.74, P <  0.01) and lymph node metastasis (OR = 1.88, 95% CI: 1.40-2.53, P <  0.01), but was not associated with other parameters. Further investigation found that FBXW7 mutation/low expression predicted poor OS (HR = 1.25, 95% CI: 1.06-1.47, P <  0.01), but not DFS in CRC (HR = 1.04, 95% CI: 0.60-1.82, P = 0.88). Subgroup analysis found that FBXW7 status was obviously correlated with OS in cohorts recruited after 2009 (HR = 1.32, 95% CI: 1.17-1.50, P <  0.01), from eastern Asia (HR = 1.27, 95% CI: 1.04-1.55, P = 0.02), detected by immunohistochemistry/qRT-PCR (HR = 1.39, 95% CI: 1.22-1.59, P <  0.01), and analysed with multivariate method (HR = 1.47, 95% CI: 1.25-1.74, P <  0.01). CONCLUSIONS: This study indicates that FBXW7 status, expression level especially, is associated with OS but not DFS in CRC. FBXW7 expression level may function as a prognostic biomarker in CRC.

Reconstruct the proximal radius with iliac graft and elastic intramedullary nail fixation after tumor resection.

BACKGROUND: This study aims to introduce a novel technique in treating benign bone tumors of the proximal radius by elastic intramedullary nail fixation and iliac graft after tumor resection. METHOD: In this retrospective case series, the treatment outcomes of 17 patients with benign bone tumor involving the proximal radius were reported from January 2010 to August 2014. All the patients received reconstruction surgery with iliac graft and elastic intramedullary nail fixation after tumor resection. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was assessed using the SF-30 scoring system. In addition, functional outcome was assessed with the Musculoskeletal Tumor Society score and the Disabilities of the Arm, Shoulder, and Hand score. RESULTS: The mean follow-up was 16 months (range, 10-22). The average bone consolidate time was 19.2 weeks (range, 16-24 weeks). The pre- and postoperative pain scores were 5.47 ± 1.58 and 1.18 ± 0.39, respectively. The pain symptom was significantly ameliorated after the operation (t = 13.50, p < 0.01). The pre- and postoperative and the quality of life scores were 48.29 ± 6.58 and 77.47 ± 5.89, respectively; the quality of life score was dramatically improved (t = -20.11, p < 0.01). The mean Musculoskeletal Tumor Society score was 83.41 % (range, 63-93 %) and the mean Disabilities of the Arm, Shoulder, and Hand score was 14.1 (range, 5.8-38.3). CONCLUSION: Taken together, the application of iliac graft and elastic intramedullary nail fixation after excision of lesions might be associated to a significant reduction of the pain and improvement of QOL (quality of life) and limb function of patients with benign bone tumors of proximal radius.

Efficacy of limb salvage with primary tumor resection simultaneously for solitary bone metastasis in limbs.

BACKGROUND: This study aims to evaluate the efficacy of limb salvage with primary tumor resection on patients with solitary bone metastasis. METHODS: A retrospective treatment outcome review was performed on 20 patients with solitary bone metastasis as the primary clinical symptom who were admitted to the hospital between 2006 and 2010. With primary tumor resection, 18/20 patients received limb salvage surgery simultaneously. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was performed before and 3 months after surgery using the SF-30 scoring system. In addition, limb function was assessed 3 months after the operation using the Scoring System of American Musculoskeletal Tumor Society system (MSTS). RESULTS: The pain symptom was significantly ameliorated after the operation (t=26.653, P<0.001), and the quality of life dramatically improved (t=-20.581, P<0.001). The postoperative MSTS scores ranged from 18 to 27. The average score was 23.10±2.36. The Kaplan-Meier analysis showed that no significant differences (χ2=1.589, P=0.207) were observed in the tumor-free survival time between the wide and marginal resections. CONCLUSIONS: The application of the wide or marginal excision for the primary lesion and bony metastasis focus, based on the principles of primary bone tumors, can significantly relieve the pain and improve the quality of life and limb function of patients whose solitary bone metastasis was manifested as the first sign.

High Expression of XRCC6 Promotes Human Osteosarcoma Cell Proliferation through the ß-Catenin/Wnt Signaling Pathway and Is Associated with Poor Prognosis.

Increasing evidences show that XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6) was upregulated and involved in tumor growth in several tumor types. However, the correlation of XRCC6 and human osteosarcoma (OS) is still unknown. This study was conducted with the aim to reveal the expression and biological function of XRCC6 in OS and elucidate the potential mechanism. The mRNA expression level of XRCC6 was measured in osteosarcoma cells and OS samples by quantitative transcription-PCR (qRT-PCR). The expression of XRCC6 protein was measured using Western blot and immunohistochemical staining in osteosarcoma cell lines and patient samples. Cell Counting Kit 8 (CCK8), colony-forming and cell cycle assays were used to test cell survival capacity. We found that XRCC6 was overexpressed in OS cells and OS samples compared with the adjacent non-tumorous samples. High expression of XRCC6 was correlated with clinical stage and tumor size in OS. Reduced expression of XRCC6 inhibits OS cell proliferation through G2/M phase arrest. Most importantly, further experiments demonstrated that XRCC6 might regulate OS growth through the ß-catenin/Wnt signaling pathway. In conclusion, these findings indicate that XRCC6 exerts tumor-promoting effects for OS through ß-catenin/Wnt signaling pathway. XRCC6 may serve as a novel therapeutic target for OS patients.

Factors Affecting the Recurrence of Giant Cell Tumor of Bone After Surgery: A Clinicopathological Study of 80 Cases from a Single Center.

BACKGROUND/AIMS: This aim of the present study was to identify specific markers determining the recurrence of the giant cell tumor of bone (GCTB). METHODS: This study involved the clinicopathological analysis of 80 cases. All of the clinical features, pathological fracture, Campanacci grade, histological features and surgical methods were reviewed. Immunohistochemistry was used to detect the expression of Ki-67, CD147, mutant p53 and p63 in GCTB. Comparisons between different groups were performed using the Chi-square test. The risk factors affecting recurrence were analyzed using a binary logistic model. Kaplan-Meier analysis was employed for the survival analysis between the groups. Cell proliferation assays, migration and invasion assays were used to detect the function of CD147 on GCTB in vitro. RESULTS: The univariate analysis showed that Ki-67 and CD147 expression, pathological fracture, Campanacci grade and surgical method were associated with recurrence. The multivariate analysis revealed that CD147 expression, Campanacci grade and surgical method were the factors affecting GCTB recurrence. In addition, the Kaplan-Meier analysis revealed that these factors affected tumor-free survival time. In vitro study revealed that the CD147 knockdown by small interfering RNA (siRNA) technique dramatically reduced the proliferation, migration and invasion of GCTB. CONCLUSION: Our results suggest that CD147 may serve as an adequate marker for GCTB recurrence. Campanacci grade is a risk factor for GCTB recurrence, which is also affected by the surgical method used.

Overexpression of X-Box Binding Protein 1 (XBP1) Correlates to Poor Prognosis and Up-Regulation of PI3K/mTOR in Human Osteosarcoma.

Increasing evidence demonstrates that dysregulation of XBP1 function contributes to tumorigenesis in some cancers. However, little is known about the role of XBP1 in the progression of osteosarcoma (OS). The expression of XBP1 in OS samples was measured by quantitative RT-PCR and Western blotting assays. Cell cycle analysis and cell counting kit 8 (CCK8) assays were performed to determine the effects of XBP1 expression on cells growth capacity. Cell apoptosis coassay was applied to determine cell survival. The expression of genes affected by XBP1 was examined by quantitative RT-RCR and validated by Western blotting assays. XBP1 was overexpressed in OS clinical samples compared with corresponding non-cancerous tissues. Overexpression of XBP1 was significantly associated with advanced clinical stages, high degree of malignancy and low tumor necrosis rate. Furthermore, hypoxia activated XBP1, and silencing XBP1 significantly enhanced OS cell apoptosis. Knock-down of XBP1 resulted in inhibition of OS growth. Most importantly, knockdown of XBP1 led to down-regulation of PIK3R3 and mTOR. Taken together, XBP1 is up-regulated and has a pro-tumor effect in OS with activation of PI3K/mTOR signaling. Thus, targeting XBP1 may provide a new potential therapeutic method for OS.

GSK3ß negatively regulates HIF1α mRNA stability via nucleolin in the MG63 osteosarcoma cell line.

Hypoxia-inducible factor 1α (HIF1α) is a transcription factor involved in the growth, invasion and metastasis of malignant tumors. Glycogen synthase kinase 3 beta (GSK3ß) is a protein kinase involved in a variety of signaling pathways, such as the Wnt and NF-κB pathways; this kinase can affect tumor progress through the regulation of transcription factor expression and apoptosis. Recent studies showed that GSK3ß was involved in the expression of HIF1α. However, the effect of GSK3ß on HIF1α expression in osteosarcoma cells remains unknown. To understand the relationship between GSK3ß and HIF1α comprehensively, small RNA interference techniques, Western blot analyses, quantitative real-time PCR analyses and luciferase assays were used in our study. Experimental data revealed that inhibition of GSK3ß could increase HIF1α protein levels and expression of its target genes by increasing the stability of the HIF1α mRNA, not by affecting the HIF1α protein stability, and that this process could be mediated by nucleolin.

Mometasone furoate inhibits tumor progression and promotes apoptosis through activation of the AMPK/mTOR signaling pathway in osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in adolescents. While treatments for osteosarcoma have improved, the overall survival has not changed for three decades, and thus, new targets for therapeutic development are needed. Recently, glucocorticoids have been reported to have antitumor effects. Mometasone furoate (MF), a synthetic glucocorticoid, is of great value in clinical application, but there are few reports on its antitumor effect. Here, we verified the effect of MF on osteosarcoma in vitro and in vivo. In vitro, cell proliferation, cell cycle progression, apoptosis and cell metastasis were detected using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound-healing and transwell assays, respectively. In vivo, we generated a xenograft mouse model. To examine the potential role of the AMPK pathway, an AMPK-specific inhibitor (dorsomorphin) was used. The expression levels of factors related to the cell cycle, apoptosis and activation of the AMPK/mTOR pathway were assessed by immunohistochemistry and Western blotting. MF inhibited proliferation and metastasis and induced S phase arrest and apoptosis in osteosarcoma cells in a dose-dependent manner. In vivo, MF effectively inhibited osteosarcoma cell growth and pulmonary metastasis; however, it had no negative effect on the internal organs. Additionally, MF could activate the AMPK/mTOR pathway in osteosarcoma. Dorsomorphin significantly attenuated MF-induced antitumor activities. In summary, MF can inhibit osteosarcoma proliferation and metastasis and promote osteosarcoma cell apoptosis through the AMPK/mTOR signaling pathway in vitro and in vivo, which can provide a new rationale for subsequent academic and clinical research on osteosarcoma treatment.

Avermectin B1 mediates antitumor activity and induces autophagy in osteosarcoma through the AMPK/ULK1 signaling pathway.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Conventional chemotherapy remains unsatisfactory due to drug toxicity and resistance issues. Therefore, there is an urgent need to develop more effective treatments for advanced osteosarcoma. In the current study, we focused on evaluating the anticancer efficacy of avermectin B1, a novel avermectin analog, against osteosarcoma cells. METHODS: The half-inhibitory concentration of avermectin B1 was calculated in three osteosarcoma cell lines. Then, functional experiments were conducted to evaluate the effects of avermectin B1 on cell proliferation, the cell cycle, apoptosis and autophagy. Moreover, the AMPK/ULK1 signaling pathway was detected by Western blot assay. Finally, the in vivo effect of avermectin B1 on tumor growth and metastasis was investigated using the xenograft mouse model. To examine the role of the AMPK/ULK1 pathway, an AMPK-specific inhibitor (dorsomorphin) was used in combination with avermectin B1. RESULTS: Avermectin B1 inhibited the proliferation of osteosarcoma cells in a dose-dependent manner based on CCK8 and colony formation assays. Then, it was found to inhibit migration and invasion by wound healing assay and cell migration and invasion assay. In addition, avermectin B1 induced osteosarcoma cell apoptosis and autophagy. In vivo, avermectin B1 effectively inhibited osteosarcoma cell growth and pulmonary metastasis. Mechanistically, avermectin B1 activated the AMPK/ULK1 pathway to exert antitumor activity in vitro and in vivo. Dorsomorphin significantly attenuated the Avermectin B1-induced antitumor activities. CONCLUSION: Our study suggests that avermectin B1 is a potential agent to treat osteosarcoma cells through the AMPK/ULK1 signaling pathway.

The water-retaining functional slow-release fertilizer modified by carboxymethyl chitosan.

To solve the problem of shortage of agricultural water resources and low utilization rate of fertilizer, a slow-release fertilizer based on chitosan modified water retention function was developed. Solution polymerization and semi-interpenetrating network technology were used to load urea aldehyde into carboxymethyl chitosan superabsorbent resin network. This technology realizes the simultaneous slow release of nutrients and water by using modified chitosan, which has important implications for the application of chitosan in agriculture to regulate the soil water and fertilizer conditions. The optimal preparation conditions were: MBA 0.07 %, KPS 0.8 %, AM to AA mass ratio of 0.3:1, CMC content of 10 %, AA neutralization degree 85 %, UF 20 %, AA+AM mass sum of 10 g, reaction temperature 70 °C and reaction time 2 h. The maximum water absorption rate of the optimized NC reached 172.3 g/g. The cumulative release of nitrogen in 30 days was 83.67 %. The application of NC in sandy soil promoted seed germination and growth. The comprehensive results indicate that NC has broad application prospects in arid areas based on its excellent water retention and nutrient release performance.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint: A Retrospective Analysis.

OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

MiR-184-3p in the paraventricular nucleus participates in the neurobiology of depression via regulation of the hypothalamus-pituitary-adrenal axis.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for the pathogenesis of depression, and increased activity of cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) plays a critical role. As a well-investigated microRNA (miRNA), miR-184 has two forms, miR-184-3p and miR-184-5p. Recently, miRNAs target genes predictive analysis and dual-luciferase reporter assays identified an inhibitory role of miR-184-3p on CRTC1 expression. Therefore, we speculated that miR-184-3p regulation was responsible for the effects of chronic stress on CRTC1 in the PVN. Various methods, including the chronic social defeat stress (CSDS) model of depression, behavioral tests, Western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer, were used. CSDS evidently downregulated the level of miR-184-3p, but not miR-184-5p, in the PVN. Genetic knockdown and pharmacological inhibition of miR-184-3p in the PVN induced various depressive-like symptoms (e.g., abnormal behaviors, HPA hyperactivity, enhanced CRTC1 function in PVN neurons, downregulation of hippocampal neurogenesis, and decreased brain-derived neurotrophic factor (BDNF) signaling) in naïve male C57BL/6J mice. In contrast, genetic overexpression and pharmacological activation of miR-184-3p in the PVN produced significant beneficial effects against CSDS. MiR-184-3p in the PVN was necessary for the antidepressant actions of two well-known SSRIs, fluoxetine and paroxetine. Collectively. miR-184-3p was also implicated in the neurobiology of depression and may be a viable target for novel antidepressants.

K-Means Clustering With Natural Density Peaks for Discovering Arbitrary-Shaped Clusters.

Due to simplicity, K-means has become a widely used clustering method. However, its clustering result is seriously affected by the initial centers and the allocation strategy makes it hard to identify manifold clusters. Many improved K-means are proposed to accelerate it and improve the quality of initialize cluster centers, but few researchers pay attention to the shortcoming of K-means in discovering arbitrary-shaped clusters. Using graph distance (GD) to measure the dissimilarity between objects is a good way to solve this problem, but computing the GD is time-consuming. Inspired by the idea that granular ball uses a ball to represent the local data, we select representatives from a local neighborhood, called natural density peaks (NDPs). On the basis of NDPs, we propose a novel K-means algorithm for identifying arbitrary-shaped clusters, called NDP-Kmeans. It defines neighbor-based distance between NDPs and takes advantage of the neighbor-based distance to compute the GD between NDPs. Afterward, an improved K-means with high-quality initial centers and GD is used to cluster NDPs. Finally, each remaining object is assigned according to its representative. The experimental results show that our algorithms can not only recognize spherical clusters but also manifold clusters. Therefore, NDP-Kmeans has more advantages in detecting arbitrary-shaped clusters than other excellent algorithms.

A Fast Granular-Ball-Based Density Peaks Clustering Algorithm for Large-Scale Data.

Density peaks clustering algorithm (DP) has difficulty in clustering large-scale data, because it requires the distance matrix to compute the density and δ -distance for each object, which has O(n2) time complexity. Granular ball (GB) is a coarse-grained representation of data. It is based on the fact that an object and its local neighbors have similar distribution and they have high possibility of belonging to the same class. It has been introduced into supervised learning by Xia et al. to improve the efficiency of supervised learning, such as support vector machine, k -nearest neighbor classification, rough set, etc. Inspired by the idea of GB, we introduce it into unsupervised learning for the first time and propose a GB-based DP algorithm, called GB-DP. First, it generates GBs from the original data with an unsupervised partitioning method. Then, it defines the density of GBs, instead of the density of objects, according to the centers, radius, and distances between its members and centers, without setting any parameters. After that, it computes the distance between the centers of GBs as the distance between GBs and defines the δ -distance of GBs. Finally, it uses GBs' density and δ -distance to plot the decision graph, employs DP algorithm to cluster them, and expands the clustering result to the original data. Since there is no need to calculate the distance between any two objects and the number of GBs is far less than the scale of a data, it greatly reduces the running time of DP algorithm. By comparing with k -means, ball k -means, DP, DPC-KNN-PCA, FastDPeak, and DLORE-DP, GB-DP can get similar or even better clustering results in much less running time without setting any parameters. The source code is available at https://github.com/DongdongCheng/GB-DP.

Network interpenetrating slow-release nitrogen fertilizer based on carrageenan and urea: A new low-cost water and fertilizer regulation carrier.

Modern agriculture presents new requirements of low cost, high water retention and degradability for superabsorbent and slow-release fertilizers. In this study, carrageenan (CG), acrylic acid (AA), N, N '-methylene diacrylamide (MBA), urea and ammonium persulfate (APS) were used as raw materials. A kind of high water absorption, water retention, nitrogen slow release and biodegradable carrageenan superabsorbent (CG-SA) was prepared by grafting copolymerization. The optimal CG-SA was obtained with a water absorption rate of 680.45 g/g by orthogonal L18(3)7 experiments and single-factor experiments. The water absorption behavior of CG-SA in deionized water and salt solution were studied. The CG-SA was characterized before and after degradation by FTIR, SEM. The nitrogen release behavior and kinetic characteristics of CG-SA were investigated. In addition, CG-SA degraded 58.33 % and 64.35 % in soil at 25 °C and 35 °C after 28 days. All the results indicated that the low-cost and degradable CG-SA can achieve simultaneous slow release of water and nutrients, which is expected to be widely used as a new water-fertilizer integration technology in arid and poor areas.

[Application of absorbable anchor combined with Kirschner wire in reconstruction of extension function of old mallet finger].

Objective: To investigate the feasibility and effectiveness of absorbable anchor combined with Kirschner wire fixation in the reconstruction of extension function of old mallet finger. Methods: Between January 2020 and January 2022, 23 cases of old mallet fingers were treated. There were 17 males and 6 females with an average age of 42 years (range, 18-70 years). The cause of injury included sports impact injury in 12 cases, sprain in 9 cases, and previous cut injury in 2 cases. The affected finger included index finger in 4 cases, middle finger in 5 cases, ring finger in 9 cases, and little finger in 5 cases. There were 18 patients of tendinous mallet fingers (Doyle type Ⅰ), 5 patients were only small bone fragments avulsion (Wehbe type ⅠA). The time from injury to operation was 45-120 days, with an average of 67 days. The patients were treated with Kirschner wire to fix the distal interphalangeal joint in a mild back extension position after joint release. The insertion of extensor tendon was reconstructed and fixed with absorbable anchors. After 6 weeks, the Kirschner wire was removed, and the patients started joint flexion and extension training. Results: The postoperative follow-up ranged from 4 to 24 months (mean, 9 months). The wounds healed by first intention without complications such as skin necrosis, wound infection, and nail deformity. The distal interphalangeal joint was not stiff, the joint space was good, and there was no complication such as pain and osteoarthritis. At last follow-up, according to Crawford function evaluation standard, 12 cases were excellent, 9 cases were good, 2 cases were fair, and the good and excellent rate was 91.3%. Conclusion: Absorbable anchor combined with Kirschner wire fixation can be used to reconstruct the extension function of old mallet finger, which has the advantages of simple operation and less complications.

A Retrospective Study of the Functional Outcomes in Patients with Proximal Humeral Bone Defect after Shoulder Fusion or Prosthetic Replacement.

AIMS: The reconstruction of proximal humeral defects resulting from tumor resection is challenging. The purpose of this work was to retrospectively study the functional outcomes in patients with large bone defects after the resection of proximal humeral tumors. METHODS: We performed a retrospective analysis of 49 patients with malignant or aggressive benign tumors in the proximal humerus at our institution between 2010 and 2021. Forty-nine patients were included in the study (prosthetic replacement, n = 27; shoulder arthrodesis, n = 22). The mean follow-up was 52.8 months (range, 14-129 months). The factors evaluated included the Musculoskeletal Tumor Society (MSTS) functional score, Constant Murley Score (CMS), and complications. RESULTS: Of the 49 patients enrolled in the study, 35 were disease-free by the time of the latest follow-up, and 14 died because of the disease. Adjuvant therapies and medical comorbidities were similar between the two groups. Osteosarcoma was the most common abnormality among all the patients. The mean MSTS scores for surviving patients in the prosthesis and arthrodesis groups were 57.4% and 80.9%, respectively. The mean CMS score for the surviving patients in the prosthesis group was 43.47, and it was 61.44 for arthrodesis cases. Patients with shoulder arthrodesis demonstrated evidence of bony union at a mean of 4.5 months. CONCLUSIONS: Shoulder arthrodesis is a reliable reconstructive procedure in patients with large bone defects after the resection of proximal humeral tumors for pediatric osteosarcoma patients. Moreover, prosthetic replacement with anatomical implants results in poor function in older metastasis patients with large bone defects and resection of the deltoid muscle.

Ebastine exerts antitumor activity and induces autophagy by activating AMPK/ULK1 signaling in an IPMK-dependent manner in osteosarcoma.

Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in osteosarcoma cells. In addition, ebastine treatment exerted obvious effects on cell cycle arrest, metastasis inhibition, apoptosis and autophagy induction both in vitro and in vivo. Mechanistically, we observed that ebastine treatment triggered proapoptotic autophagy by activating AMPK/ULK1 signaling in osteosarcoma cells. Treatment with the AMPK inhibitor dorsomorphin reversed ebastine-induced apoptosis and autophagy. More importantly, we found that IPMK interacted with AMPK and functioned as a positive regulator of AMPK protein in osteosarcoma cells. A rescue study showed that the induction of autophagy and activation of the AMPK/ULK1 signaling pathway by ebastine treatment were reversed by IPMK knockdown, indicating that the activity of ebastine was IPMK dependent. We provide experimental evidence demonstrating that ebastine has antitumor activity in osteosarcoma and promotes autophagy by activating the AMPK/ULK1 signaling pathway, which is IPMK dependent. Our results provide insight into the clinical application potential of ebastine, which may represent a new potential therapeutic candidate for the treatment of osteosarcoma.

Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Objectives: The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM) through meta-analysis. Methods: As of June 2023, we searched PubMed, Web of Science, Embase and the Cochrane Library. Randomized controlled trials (RCTs) which compared the clinical outcomes of anti-CD38 mAbs plus immunomodulatory drugs (IMiDs) or proteasome inhibitors (PIs) plus dexamethasone and IMiDs (or PIs) and dexamethasone alone for RRMM patients were included. Efficacy outcomes were mainly evaluated with progression-free survival (PFS) and overall survival (OS). The safety was analyzed with hematologic and nonhematologic treatment-emergent adverse events (TEAEs). All results were pooled using hazard ratio (HR), relative risk (RR), and their 95% confidence interval (CI) and prediction interval (PI). Results: This meta-analysis included 11 RCTs in total. Compared with IMiDs (or PIs) and dexamethasone alone, anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone significantly prolonged PFS (HR: 0.552, 95% CI = 0.461 to 0.659, 95% PI = 0.318 to 0.957) and OS (HR: 0.737, 95% CI = 0.657 to 0.827, 95% PI = 0.626 to 0.868) in patients with RRMM. Additionally, RRMM patients receiving anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone achieved higher rates of overall response (RR: 1.281, 95% CI = 1.144 to 1.434, 95% PI = 0.883 to 1.859), complete response or better (RR: 2.602, 95% CI = 1.977 to 3.424, 95% PI = 1.203 to 5.628), very good partial response (VGPR) or better (RR: 1.886, 95% CI = 1.532 to 2.322, 95% PI = 0.953 to 3.731), and minimum residual disease (MRD)-negative (RR: 4.147, 95% CI = 2.588 to 6.644, 95% PI = 1.056 to 16.283) than those receiving IMiDs (or PIs) and dexamethasone alone. For TEAEs, the rates of hematologic and nonhematologic TEAEs, including thrombocytopenia, neutropenia, upper respiratory tract infection (URTI), pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension, were higher in the anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone group than in the IMiDs (or PIs) and dexamethasone group. Conclusion: Our study showed that anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone improved PFS and OS, and achieved higher rates of overall response, complete response or better, VGPR or better, and MRD-negative, as well as higher rates of thrombocytopenia, neutropenia, URTI, pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension in RRMM patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431071.