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This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.Giant cell tumor of bone (GCTB) is a rare primary osteolytic bone tumor with high local recurrence rate after surgical resection. Here the authors conduct a phase Ib/II trial, evaluating the efficacy and safety of JMT103 (RANK-RANKL inhibitor) in patients with unresectable or surgically-challenging GCTB. [ABSTRACT FROM AUTHOR]

This special issue explores the relationship between digital trade and security, emphasizing the geopolitical implications for the global economy in the digital age. The rapid growth of digital trade has introduced significant challenges and opportunities, necessitating robust data governance to balance national security interests with the free flow of goods, services, and data across borders. The papers explore the different models of data governance championed by the US, China, and the EU, highlighting the complexities of cross-border data flows and their impact on international relations. Through detailed analyses of various international agreements and frameworks, this special issue provides a comprehensive overview of the current landscape of digital trade and its security implications, with a particular focus on China's evolving approach to data governance and its global influence. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors have improved the objective response rate and survival of melanoma patients. However, there are still many melanoma patients suffering from disease progression due to primary or secondary immune checkpoint inhibitor resistance, as is observed in the failure of anti-PD1/PD-L1 therapy. While the expression of valuable markers, such as TMB, MSI, and PD-L1, could serve as effective predictors of anti-checkpoint inhibitor therapies, tumor cell PD-L1 expression and its regulating mechanism would significantly affect the anti-PD-1 immunotherapy response and efficacy. Therefore, it is urgent to determine the function of PD-1/PD-L1 expression in melanoma and its associated pathways to enhance the efficacy of anti-PD-1 therapies. Methods: A cohort of 133 patients with histologically confirmed melanoma from Tianjin Medical University Cancer Institute & Hospital were included in this study. We performed immunohistochemical staining to detect the expression of Migration and invasion inhibitory protein (MIIP), HDAC6 and PD-L1. Kaplan–Meier and log-rank test were used for survival analysis. As for vitro, Western blot was used in melanoma cell lines to verify the signaling pathway that MIIP regulates PD-L1 expression. Results: MIIP expression was decreased in melanoma and that the negative expression of MIIP was correlated with worse overall survival. The positive expression of HDAC6, a molecule that is downstream of MIIP, had a positive trend with decreased overall survival. At the same time, the positive expression of PD-L1, a crucial costimulatory molecule, was associated with decreased overall survival. Furthermore, there was a positive association between HDAC6 and PD-L1 protein expression (p < 0.01), and this correlation is more prominent in cutaneous melanoma than acral melanoma. In cutaneous melanoma cell lines, we found that increasing MIIP led to decreased HDAC6, pSTAT3, and PD-L1 expression. Knocking down MIIP led to increased HDAC6, pSTAT3, and PD-L1 expression. Combining the published results, showing that HDAC6 can regulate PD-L1 expression through STAT3, our present data suggest that MIIP inhibits the expression of PD-L1 by downregulating HDAC6 in melanoma. Most importantly, methods for targeting MIIP-HDAC6-PD-L1 pathways, such as treatment with HDAC6 inhibitors, might indicate a new therapeutic approach for enhancing immune checkpoint inhibitor therapies in melanoma. Conclusions: Our findings highlight the immunomodulatory effects of MIIP in the inhibition of PD-L1 expression by downregulating HDAC6 in melanoma. Methods for targeting MIIP-HDAC6-PD-L1 pathways might be new therapeutic approaches for enhancing immune checkpoint inhibitor therapies in melanoma. [ABSTRACT FROM AUTHOR]

Purpose: To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous melanoma (ALM). Methods: This retrospective study included ALM patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2004–2015. The 1686 cases were divided into the training and internal validation cohorts at a ratio of 7:3. The Cox regression analyses were performed to select risk factors for the nomogram. The performances of the nomogram were evaluated using the concordance index (C-index), area under receiver operating characteristic curve (AUC), and calibration plots, and validated in an external multicenter cohort. Results: Age, gender, race, and stage were significantly associated with overall survival (OS), with a C-index of 0.727 and 0.722 in the training and internal validation groups, respectively. The AUC of 2-,4-, and 6 years were higher than or equal to 0.75. Age, gender, race, site, and stage were related to ALM patients' CSS which have better C-index of 0.791 and 0.774 in the training and internal validation set. The AUC of 2-,4-, and 6- were higher than or equal to 0.80. Both survival calibration curves of 2-,4, and 6-year OS and CSS brought out a good consistency. The external multicenter cohort authenticated the value of the nomogram of OS, with a C-index of 0.657 and an AUC of 0.67, 0.72, and 0.65 at 2, 4, and 6 years. Good consistency was also observed. Conclusion: A prognostic nomogram was established and validated to help predict the survival of ALM patients and guide individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR)-T cell therapy revolutionized treatment for various hematologic malignances. However, limited studies were reported to compare the efficacy and safety of CAR-T and donor lymphocyte infusion (DLI) for patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after hematopoietic stem cell transplantation (HSCT) comprehensively. We conducted a single-center, retrospective comparative study that consisted of 12 patients who were treated with DLI (control group) and 12 patients treated with donor-derived CD19 CAR-T cells (experimental group, 6 patients also received CD22 or CD123 CAR-T cells sequentially) with 3 overlaps. The event-free survival (EFS) of patients in experimental group was superior to that of the control group: 516 days versus 98 days (p = 0.0415). Compared with 7 of 12 patients treated with DLI suffered grades III–IV acute graft versus host disease (aGVHD), one grade III aGVHD developed in patients treated with CAR-T therapy. No significant difference in the incidence of infection was identified between these two groups. Most patients in the experimental group had only mild cytokine release syndrome and none developed neurotoxicity. The univariate analysis of patients in the experiment group revealed that earlier CAR-T therapy for post-transplantation relapse was associated with better EFS. There was no significant difference in EFS between patients treated with dual-target CAR-T with those with single CD19 CAR-T. In this study, our data supported that donor-derived CAR-T therapy is a safe and potentially effective treatment for relapsed B-ALL after HSCT and may be superior to DLI. [ABSTRACT FROM AUTHOR]

Over the past decade, heavy metal (HMs) contamination in soil environments has become severe worldwide. However, their resulting ecological and health risks remained elusive across a variety of soil ecosystems due to the complicated distributions and sources. This study investigated the HMs (Cr, As, Cu, Pb, Zn, Ni, Cd, and Hg) in areas with multi-mineral resources and intensive agricultural activities to study their distribution and source apportionment using a positive matrix factorization (PMF) model coupled with self-organizing map (SOM). The potential ecological and health risks were assessed in terms of distinct sources of HMs. The results disclosed that the spatial distribution of HM contaminations in the topsoil was region-dependent, primarily located in areas with high population intensity. The geo‑accumulation index (Igeo) and enrichment factor (EF) values collectively displayed that the topsoils were severely contaminated by Hg, Cu, and Pb, particularly in residential farmland areas. The comprehensive analysis combined with PMF and SOM identified both geogenic and anthropogenic sources of HMs including natural, agricultural, mining, and mixed sources (caused by multi-anthropogenic factors), accounting for 24.9%, 22.6%, 45.9%, and 6.6% contribution rates, respectively. The potential ecological risk was predominantly due to the enrichment of Hg, followed by Cd. The non-carcinogenic risks were mostly below the acceptable risk level, while the potential carcinogenic health risks caused by As and Cr should be paid prime attention to, particularly for children. In addition to the 40% geogenic sources, agricultural activities contributed to 30% of the non-carcinogenic risk, whereas mining activities contributed to nearly half of the carcinogenic health risks. [ABSTRACT FROM AUTHOR]

This article offers a novel understanding of China's changing engagement in global climate governance over the past decade. This article argues that China has embedded the construction of its international identity, which has been transforming towards what this article conceptualizes to be a 'Yinling leading power', in promoting and leading global climate governance. China's transforming identity construction has contributed to changing its construction of climate justice and led China to proactively undertake more responsibilities, provide international public goods and promote international climate cooperation. Global climate governance has become one of China's prototypical discursive frames in constructing its new international identity, an important platform where China seeks to share leadership with other major powers and the climate leadership in turn constitutes China's new identity. However, China's inadequate response to international expectations and lack of self-reflection in its climate policy have influenced international recognition on its climate leadership and new identity. In general, China's transforming identity construction and its reconstruction of climate justice have far-reaching implications for China and Europe to cooperate and coordinate in strengthening global climate justice and promoting global climate governance. [ABSTRACT FROM AUTHOR]

Studies about microwave absorption properties of Li1.3Al0.3Ti1.7(PO4)3 (LATP) ceramics are rare, so this work attempted to develop them as high-temperature, light weight microwave absorbing material. Li1.34Al0.26M0.04Ti1.7(PO4)3 (M=Co, Mg, Ni) and Li1.3+xAl0.3−xMgxTi1.7(PO4)3 (x = 0, 0.04, 0.08, 0.12) ceramics were prepared and analyzed for their microstructure, phase, conductivity, dielectric properties and microwave absorption properties. Results showed that both the doping ion and doping content had significant effects on the conductivity of LATP ceramics. Li1.34Al0.26Co0.04Ti1.7(PO4)3 ceramics had the highest conductivity of 1.18 × 10−3S·cm−1. The dielectric properties and microwave absorption properties among Li1.34Al0.26M0.04Ti1.7(PO4)3 (M=Co, Mg, Ni) ceramics are similar. Their bandwidth covered the entire X-band in 2.2 mm and the minimum reflection loss (RLmin) reached − 20.2 dB. The complex permittivity decreased and the microwave absorption property became worse as the doping content of Li1.3+xAl0.3−xMgxTi1.7(PO4)3 ceramics increased from 0.04 mol to 0.12 mol. [ABSTRACT FROM AUTHOR]

Melanoma is an extremely rare tumor in Asia. This retrospective study aimed to identify the clinical characteristics and prognostic factors of metastatic melanoma patients at Tianjin Medical University Cancer Hospital over the last 30 years. Survival analysis was performed with Kaplan-Meier, log-rank test, and multivariate Cox regression method using SPSS 19.0 software. The 1-, 2-, and 5-year survival rates of metastatic melanoma patients were 52, 32, and 16 %, respectively. Median overall survival (OS) was 13.5 months, median progression-free survival (PFS) 9.0 months, and median disease-free survival 20.3 months. Furthermore, patients with a single metastatic site achieved better OS and PFS than those with two or more metastatic lesions (OS 21.6 vs. 8.9 months, P < 0.001; PFS 11.3 vs. 7.1 months, P < 0.001). Survival times of patients with visceral metastases were the shortest (OS 8.5 months; PFS 7.5 months). Specifically, patients with primary mucosal lesions had a worse OS (9.7 months) and PFS (6.8 months) than those with acral (19.2 and 15.6 months, respectively) or non-acral primary lesions (11.8 and 11.1 months, respectively). The treatment of advanced melanoma was unitary, and prognoses of patients with metastatic melanoma in China were poor. Visceral metastasis, multiple metastatic sites, and primary mucosal lesions were significant predictors of survival of patients with metastatic melanoma. Those with primary mucosal lesions had significantly worse survivals than those with primary cutaneous lesions. More active involvement in clinical studies and more feedback on various treatment options are required. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a highly aggressive bone disease with a tendency to metastasize to the lung. The 5-year survival of patients with metastatic osteosarcoma is only 20 %. Many studies have demonstrated SDF-1/CXCR4 and MMP9 play important roles in the metastasis of malignant tumors, including osteosarcoma. The aim of this study was to investigate the association of CXCR4 and MMP9 expression with clinicopathological features and pulmonary metastasis in osteosarcoma. Using tumor tissue microarrays, we analyzed the expression of CXCR4 and MMP9 among 34 primary osteosarcomas with pulmonary metastasis and 62 primary osteosarcomas without metastasis. A median time of 57.5 months (range: 6 to 171 months) follow-up was performed to evaluate tumor metastasis and the patient survival. The prognostic values were determined by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics (ROC) curves (AUC). The expression of CXCR4 and MMP9 was significantly correlated in tumor tissues ( P = 0.026). Both CXCR4 and MMP9 were independent predictors for overall survival and metastasis-free survival by Cox multivariate analysis, and high expression for both CXCR4 and MMP9 were even more significant and better biomarkers for osteosarcoma metastasis and survival. The combination of CXCR4 and MMP9 high expression is very likely to be a valuable independent predictor of lung metastasis and survival in osteosarcoma patients. [ABSTRACT FROM AUTHOR]

The gain of E-cadherin and loss of Vimentin known as 'Cadherin switching' resulting in epithelial differentiation play an important role in tumor cell invasion and metastasis. In soft tissue leiomyosarcoma (LMS), aberrant expression of E-cadherin and down-regulation of Vimentin-related Mesenchymal to Epithelial Reverting Transition was defined, but the role of these proteins in various subtypes of LMS have not been well demonstrated yet. The aim of this study was to evaluate the prognostic role of E-cadherin and Vimentin expression in 45 soft tissue leiomyosarcoma samples by Immunohistochemistry analysis. E-cadherin was positive in a small proportion of LMS, accounting for 15.6 % (7/45). All LMS samples expressed Vimentin, concluding 20 patients as strong positive group (44.4 %), 25 patients as week positive group (55.6 %). Although the aberrant expression of E-cadherin had no differences among various subtypes of LMS, it was significantly associated with early clinical stages. The patients with strong positive expression of Vimentin suffered significant high risk of recurrence and metastasis and also had significant worse overall survival. These data suggest that the epithelial differentiation of LMS evaluated by E-cadherin expression does not belong to certain subtypes in LMS. The patients with the gain of E-cadherin and loss of Vimentin expression represent favorable trend of survival. They might serve as good biomarkers of the LMS clinical outcome after further investigations. [ABSTRACT FROM AUTHOR]

Extraskeletal osteosarcoma (ESOS) is an extremely rare malignancy with poor prognosis, accounting for 2-4% of all osteogenic sarcomas. The purpose of this study was to examine the oncological outcomes of this disease related to surgical treatment and/or combined adjuvant therapies and to analyze the associated prognostic factors in ESOS. From January 1990 to June 2016, 22 patients with primary ESOS were analyzed in this retrospective study. Overall survival (OS) and progression-free survival (PFS) rates were calculated by Kaplan-Meier methods and compared with log-rank test. 22 patients were diagnosed with ESOS, 19 showed localized diseases and 3 presented with metastatic lesions. The median age at diagnosis was 55.5 years. Surgery resection was performed for all patients, 18 of whom received adjuvant chemotherapy. The median follow-up time was 48.5 months. There were 10 cases of recurrence and 9 patients developed new metastases. The 5-year OS rate for all patients was 58%. For localized cohort, the 5-year OS rate was 62%, and the 3-year PFS rate was 31% with a median PFS of 16 months. Univariate analysis of related prognosis factors showed that larger size of tumor (>5.5 cm) and higher histologic grade emerged as significant factors associated with worse OS. The addition of combination chemotherapy has no effect found on OS or PFS in this study. In summary, for patients who presented with ESOS, larger tumor size and higher histologic grade indicate a lower OS rate. The combination chemotherapy does not improve the OS or PFS. [ABSTRACT FROM AUTHOR]

This study demonstrates characteristics and mechanisms of deformation of an aquifer system in response to seasonal fluctuations of groundwater level when groundwater pumping has been strictly regulated after experiencing longtime land subsidence. Two boreholes with depth of 1226 m (G2 site) and 905 m (G3 site) were drilled at the Tianjin coastal region where severe land subsidence had occurred since the 1950s. Extensometer/piezometer groups installed at the G2 site illustrate synchronized variations of compaction and groundwater level since 2010 in the aquifer system between depth of 100-400 m which contributes most groundwater pumpage. Monitored land subsidence demonstrates that the shallow aquifer has become the main contributor to the land subsidence, and inelastic compaction still occurred in the aquifers where groundwater level has recovered. Pre-consolidation stresses show that clayey soils in depth < 100 m are under-consolidated, and deep clayey soils show the state of normal- to over-consolidation. The effects of the cyclic groundwater level oscillation on deformation were investigated using repeated loading and unloading tests. Void ratio changes in loading/unloading cycles illustrate that inelastic deformation rate decreases gradually and elastic deformation rate remains almost unchanged with increases of cyclic numbers. The deformation of soil samples from 100 to 400 m is mostly elastic for loading stress in the over-consolidation stress range. These findings suggest that groundwater dewatering in the shallow (depth < 100 m) aquifer will be the primary target to control land subsidence. Groundwater level fluctuations higher than pre-consolidation value in 100-400 m only lead to elastic and recoverable deformation even small residual permanent deformation may continue for a long time. The results improve the understanding of deformation in complex urban aquifers affected by groundwater level fluctuations and highlight the importance of city planning management for controlling land subsidence in coastal cities. [ABSTRACT FROM AUTHOR]