Which factors are associated with adverse prognosis in multiple myeloma patients after surgery? - preliminary establishment and validation of the nomogram.

BACKGROUND: To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram. METHODS: Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated. RESULTS: Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%. CONCLUSION: This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.

A clinically feasible circulating tumor cell sorting system for monitoring the progression of advanced hepatocellular carcinoma.

BACKGROUND: Hematogenous metastasis is essential for the progression of advanced hepatocellular carcinoma (HCC) and can occur even after patients receive multidisciplinary therapies, including immunotherapy and hepatectomy; circulating tumor cells (CTCs) are one of the dominant components of the metastatic cascade. However, the CTC capture efficiency for HCC is low due to the low sensitivity of the detection method. In this study, epithelial cell adhesion molecule (EpCAM)/vimentin/Glypican-3 (GPC3) antibody-modified lipid magnetic spheres (LMS) were used to capture tumor cells with epithelial phenotype, mesenchymal phenotype and GPC3 phenotype, respectively, in order to capture more CTCs with a more comprehensive phenotype for monitoring tumor metastasis. RESULTS: The novel CTC detection system of Ep-LMS/Vi-LMS/GPC3-LMS was characterized by low toxicity, strong specificity (96.94%), high sensitivity (98.12%) and high capture efficiency (98.64%) in vitro. A sudden increase in CTC counts accompanied by the occurrence of lung metastasis was found in vivo, which was further validated by a clinical study. During follow-up, the rapid increase in CTCs predicted tumor progression in HCC patients. Additionally, genetic testing results showed common genetic alterations in primary tumors, CTCs and metastatic tissues. The proportion of patients predicted to benefit from immunotherapy with the CTC detection method was higher than that for the tissue detection method (76.47% vs. 41.18%, P = 0.037), guiding the application of clinical individualized therapy. CONCLUSIONS: The Ep-LMS/Vi-LMS/GPC3-LMS sequential CTC capture system is convenient and feasible for the clinical prediction of HCC progression. CTCs captured by this system could be used as a suitable alternative to HCC tissue detection in guiding immunotherapy, supporting the clinical application of CTC liquid biopsy.

Exosomal proteomics identifies RAB13 as a potential regulator of metastasis for HCC.

BACKGROUND: Exosomal proteins from cancer cells are becoming new biomarkers for cancer monitoring and efficacy evaluation. However, their biological function and molecular mechanism underlying tumor metastasis are largely unknown. METHODS: Bioinformatic methods such as bulk gene expression analysis, single-cell RNA sequencing data analysis, and gene set enrichment analysis were employed to identify metastasis-associated proteins. The in vitro and in vivo experiments were used to investigate the function of RAB13 in HCC metastasis. RESULTS: We identified RAB13 as one of the critical regulators of metastasis in HCC-derived exosomes for the first time. In vitro, the invasiveness of HCC cell lines could be attenuated by RAB13 silence. In vivo, tumor size and proportion of high-grade lung metastatic nodule could be reduced in the mice with orthotopic transplantation of tumors and intravenously injected with exosomes derived from MHCC97H cell with RAB13 silence (si-RAB13-Exo), as compared with those without RAB13 silence (si-NC-Exo). Moreover, in si-RAB13-Exo group, circulating tumor cell counts were decreased at the third, fourth, and fifth weeks after orthotopic transplantation of tumors, and MMP2 (matrix metalloproteinase 2)/TIMP2 (tissue inhibitor of metalloproteinases 2) ratio was also significantly decreased. In addition, RAB13 expression was also associated with VEGF levels, microvessel density, and tube formation of vascular endothelial cells by both in vitro and in vivo models, indicating that RAB13 was associated with angiogenesis in HCC. CONCLUSIONS: We have demonstrated exosomal RAB13 as a potential regulator of metastasis for HCC by in silico, in vitro, and in vivo methods, which greatly improve our understanding of the functional impact of exosomal proteins on HCC metastasis.

Significance of preoperative peripheral blood neutrophil-lymphocyte ratio in predicting postoperative survival in patients with multiple myeloma bone disease.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is often used to predict a poor prognosis in patients with tumors. This study investigated the preoperative peripheral blood NLR in predicting postoperative survival (POS) in patients with multiple myeloma bone disease (MMBD). AIM: To evaluate whether NLR can be used to predict the prognosis of MMBD patients after surgery. METHODS: The clinical data of 82 MMBD patients who underwent surgical treatments in Beijing Chao-yang Hospital were collected. The NLR was obtained from the absolute number of neutrophils and lymphocytes, calculated by the number of neutrophils and divided by the number of lymphocytes. The peripheral blood lymphocyte percentage was used as the major marker to analyze the change in characteristics of the immune statuses of multiple myeloma patients. RESULTS: The NLR cut-off values of NLR ≥ 3 patients and NLR ≥ 4 patients were significantly correlated with POS. The 3- and 5-year cumulative survival rates of the high NLR group (NLR ≥ 3 patients) were 19.1% and 0.0%, respectively, which were lower than those of the low NLR group (NLR < 3 patients) (67.2% and 48.3%) (P = 0.000). In the high NLR group, POS (14.86 ± 14.28) was significantly shorter than that in the low NLR group (32.68 ± 21.76). Univariate analysis showed that the lymphocyte percentage 1 wk after the operation (19.33 ± 9.08) was significantly lower than that before the operation (25.72 ± 11.02). Survival analysis showed that postoperative chemotherapy, preoperative performance status and preoperative peripheral blood NLR ≥ 3 were independent risk factors for POS. CONCLUSION: The preoperative peripheral blood NLR can predict POS in MMBD patients. MMBD patients with a high preoperative NLR (NLR ≥ 3) showed poor prognosis.

Research on the Construction of Bispecific-Targeted Sustained-Release Drug-Delivery Microspheres and Their Function in Treatment of Hepatocellular Carcinoma.

Lenvatinib (LEN) is approved as one of the commonly used drugs in the treatment of hepatocellular carcinoma (HCC). It is recognized to be a novel therapeutic choice for the direct and targeted delivery of effective drugs to HCC tumor sites. The key to the proposed method lies in the requirement for efficient targeted drug delivery carriers with targeting performance to deliver effective drugs directly and safely to tumor lesions. Methods: Here, magnetic liposomes (MLs) were modified by phosphatidylinositol proteoglycan 3 (GPC3) and epithelial cell adhesion molecules (EpCAMs). Subsequently, bispecific-targeted sustained-release drug-loaded microspheres containing LEN (GPC3/EpCAM-LEN-MLs) were constructed. In addition, both cytotoxicity and magnetic resonance imaging (MRI) analyses were performed to establish a mouse model and further perform corresponding performance assessments. Results: The corresponding results showed that GPC3/EpCAM-LEN-MLs were spherical-shaped and evenly dispersed. The encapsulation and drug-loading efficiencies were 91.08% ± 1.83% and 8.22% ± 1.24%, respectively. Meanwhile, GPC3/EpCAM-LEN-MLs showed a high inhibition rate on the proliferation of HCC cells and significantly increased their apoptosis. Furthermore, MRI revealed that the system possessed the function of tracking and localizing tumor cells, and animal experiments verified that it could exert the function of disease diagnosis. Conclusions: Our experiments successfully constructed a safe and efficient bispecific-targeted sustained-release drug delivery system for HCC tumor cells. It provides a useful diagnostic and therapeutic scheme for the clinical diagnosis and targeted therapy of HCC. Moreover, it can be used as a potential tumor-specific MRI contrast agent for the localization and diagnosis of malignant tumors.

Preliminary establishment of a spinal stability scoring system for multiple myeloma.

BACKGROUND: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, and the Spinal Instability Neoplastic Score scoring system may not be fully applicable to multiple myeloma (MM) patients. AIM: To evaluate the spinal stability of patients with MM spinal involvement to guide their clinical treatment. METHODS: By using the Delphi method, we collected and extracted information through a series of questionnaires and improved it via feedback. We also preliminarily established a spinal stability scoring system for multiple myeloma. RESULTS: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The MM spinal stability scoring system was created by calculating the scores of the six separate components: location, pain, number of segments, physiological curvature, comorbidities, and neurological function. The minimum value was "0", and the maximum value was "24". A score of "0-10" indicated "spine stability", a score of "11-17" indicated "potential instability", and a score of "18-24" indicated "spine instability". Patients with a score of "11-24" need an intervention such as surgery. CONCLUSION: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM.

Two 3D triazolate-tricarboxylate-bridged Cu(II/I) frameworks by one-pot hydrothermal synthesis exhibiting spin-canted antiferromagnetism and strong antiferromagnetic couplings.

Two 3D coordination polymers with the same components but different structures, [Cu(II)(2)Cu(I)(trz)(3)(Hbtc)](n) (1) and [Cu(4)(Htrz)(2)(mu(3)-OH)(2)(btc)(2)](n) (2), were obtained together by a one-pot hydrothermal reaction of Cu(OAc)(2).H(2)O, 1,2,4-triazole (Htrz), and 1,3,5-benzenetricarboxylic acid (H(3)btc). Complex 1 is a mixed-valence Cu(I/II) honeycomb built from wavy Cu(II)-trz-carboxylate layers and Cu(I) nodes with doubly deprotonated Hbtc(2-) ligands covalently filled in the channels. In contrast, 2 is a tetranuclear [Cu(4)(Htrz)(2)(mu(3)-OH)(2)](6+) cluster-based framework extended by a fully deprotonated btc(3-) ligand, displaying a 3,6-connected topological network. More interestingly, spin-canted antiferromagnetism and overall strong antiferromagnetic couplings up to -147.1 cm(-1) are respectively observed for 1 and 2, which are significantly due to the antisymmetric magnetic exchange in the wavy Cu(II)-trz-carboxylate sublayer of 1 and the cooperative 4-fold heterobridges within the tetranuclear cluster of 2.

2-Amino-6-methyl-1,3-benzothia-zole-deca-nedioic acid (2/1).

Co-crystallization of 2-amino-6-methyl-1,3--benzothia-zole with deca-nedioic acid under hydro-thermal conditions afforded the title 2:1 co-crystal, 2C(8)H(8)N(2)S·C(10)H(18)O(4). The deca-nedioic acid mol-ecule is located on an inversion centre. In the crystal, inter-molecular N-H⋯O and O-H⋯O hydrogen bonds connect the components into a two-dimensional wave-like layer structure extending parallel to (100).

[Clinical discussion on the pathological diagnosis of high-grade intraepithelial neoplasia in gastric biopsy].

OBJECTIVE: To evaluate the value and inadequacy in clinical practice of the concept of gastric high-grade intraepithelial neoplasia (HIN). METHODS: Forty-five cases with gastric HIN diagnosed by the esophagogastroduodenoscopy (EGD) biopsy were treated from 2003 to 2009. The clinical and histopathological data were analyzed retrospectively. RESULTS: Radical surgeries were successfully performed on all the patients, among whom 33 underwent distal subtotal gastrectomy, 3 proximal partial gastrectomy, 7 total gastrectomy, and 2 endoscopic mucosal resection. In postoperative pathological examination, only 15 cases (33.3%) were HIN, while 14 cases (31.1%) were found to be early gastric cancers, and 16 (35.6%) were advanced cancers. Twelve(40.0%) out of 30 cancers had regional lymph nodes metastasis. When the maximum diameter of the HIN lesion was greater than 3.0 cm, or when ulcer or the features of poorly-differentiated carcinoma or signet-ring cell carcinoma were present in preoperative biopsy, the likelihood of cancer in postoperative pathological examination was higher (P<0.05), and when malignancy was confirmed, the presence of the features above was associated with lymph nodes metastasis and advanced cancer. CONCLUSIONS: Carcinoma is identified in a large proportion of patients with gastric HIN by the EGD biopsy. Lymph nodes metastasis or advanced cancer may be detected in these cases. Cautions must be taken when the new concept of HIN is widely used for diagnosing gastric lesion. Radical resection should be considered when the maximum diameter of the HIN lesion is greater than 3.0 cm, or when ulcer, or the feature of poorly-differentiated carcinoma or signet-ring cell carcinoma are present in the EGD biopsy.