Spinal cord injuries (SCIs) are sustained by an increasing number of patients each year worldwide. The treatment of SCIs has long been a hard nut to crack for doctors around the world. Mesenchymal stem cells (MSCs) have shown benefits for the repair of SCI and recovery of function. Our present study aims to investigate the effects of intravenously infused human umbilical cord blood-derived MSCs (hUCB-MSCs) on functional recovery after subacute spinal cord compression injury of two noncontinuous segments. In addition, we compared the effects of single infusion and repeated intravenous (i.v.) injections on the recovery of spinal cord function. A total of 43 adult rabbits were randomly divided into four groups: control, single injection (SI), repeated injection at a 3-day (3RI) or repeated injection at a 7-day interval (7RI) groups. Non-immunosuppressed rabbits in the transplantation groups were infused with either a single complete dose or three divided doses of 2 × 106 hUCB-MSCs (3-day or 7-day intervals) on the first day post decompression. Behavioural scores and somatosensory evoked potentials (SEPs) were used to evaluate hindlimb functional recovery. The survival and differentiation of the transplanted human cells and the activation of the host glial and inflammatory reaction in the injured spinal cord were studied by immunohistochemical staining. Our results showed that hUCB-MSCs survived, proliferated, and primarily differentiated into oligodendrocytes in the injured area. Treatment with hUCB-MSCs reduced the extent of astrocytic activation, increased axonal preservation, potentially promoted axonal regeneration, decreased the number of Iba-1+ and TUNEL+ cells, increased the amplitude and decreased the onset latency of SEPs and significantly promoted functional improvement. However, these effects were more pronounced in the 3RI group compared with the SI and 7RI groups. Our results suggest that treatment with i.v. injected hUCB-MSCs after subacute spinal cord compression injury of two noncontinuous segments can promote functional recovery through the differentiation of hUCB-MSCs into specific cell types and the enhancement of anti-inflammatory, anti-astrogliosis, anti-apoptotic and axonal preservation effects. Furthermore, the recovery was more pronounced in the rabbits repeatedly injected with cells at 3-day intervals. The results of this study may provide a novel and useful treatment strategy for the transplantation treatment of SCI.

Objective: Microvascular invasion (MVI) is a significant adverse prognostic indicator of intrahepatic cholangiocarcinoma (ICC) and affects the selection of individualized treatment regimens. This study sought to establish a radiomics nomogram based on the optimal VOI of multi-sequence MRI for predicting MVI in ICC tumors. Methods: 160 single ICC lesions with MRI scanning confirmed by postoperative pathology were randomly separated into training and validation cohorts (TC and VC). Multivariate analysis identified independent clinical and imaging MVI predictors. Radiomics features were obtained from images of 6 MRI sequences at 4 different VOIs. The least absolute shrinkage and selection operator algorithm was performed to enable the derivation of robust and effective radiomics features. Then, the best three sequences and the optimal VOI were obtained through comparison. The MVI prediction nomogram combined the independent predictors and optimal radiomics features, and its performance was evaluated via the receiver operating characteristics, calibration, and decision curves. Results: Tumor size and intrahepatic ductal dilatation are independent MVI predictors. Radiomics features extracted from the best three sequences (T1WI-D, T1WI, DWI) with VOI_10mm (including tumor and 10 mm peritumoral region) showed the best predictive performance, with AUC_TC = 0.987 and AUC_VC = 0.859. The MVI prediction nomogram obtained excellent prediction efficacy in both TC (AUC = 0.995, 95%CI 0.987–1.000) and VC (AUC = 0.867, 95%CI 0.798–0.921) and its clinical significance was further confirmed by the decision curves. Conclusion: A nomogram combining tumor size, intrahepatic ductal dilatation, and the radiomics model of MRI multi-sequence fusion at VOI_10mm may be a predictor of preoperative MVI status in ICC patients.

Purpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs). Methods: HCECs were cultured in 70– 120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-1β and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed. Results: HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-1β, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-1β and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs. Conclusion: The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.

XNW4107 is a novel β-lactamase inhibitor that possesses broad activity against serine-β-lactamases. XNW4107 in combination with imipenem exhibited potent in vitro activity against carbapenem-resistant bacteria and particularly against carbapenem-resistant Acinetobacter baumannii. This study aimed to evaluate the in vitro and in vivo antibacterial activities of imipenem/XNW4107. The minimum inhibitory concentrations, minimum bactericidal concentrations, time-kill curves, post-antibiotic effects, and spontaneous frequency of resistance were used to investigate the imipenem/XNW4107 in vitro activity. A mouse systemic infection model was used to evaluate the imipenem/XNW4107 in vivo efficacy. MIC₉₀ of imipenem/XNW4107 against imipenem-nonsusceptible A. baumannii (n = 106) was 8 mg/L, which was 16-fold lower than the MIC₉₀ of imipenem; the resistance rate decreased from 90% to 20% applying the CLSI imipenem breakpoint. MIC₉₀ of imipenem/XNW4107 against imipenem-resistant Klebsiella pneumoniae (n = 54) was 2 mg/L, which was 128-fold lower than the MIC₉₀ of imipenem; 80% imipenem-nonsusceptible Pseudomonas aeruginosa (n = 101) exhibited MICs of imipenem/XNW4107 from 2 to 8 mg/L, which were 4- to 8-fold lower than the MICs of imipenem. Imipenem/XNW4107 was bactericidal against A. baumannii, K. pneumoniae, and Escherichia coli. The time-kill curves showed that increasing concentrations did not result in progressively increased killing at concentrations >4 × MIC. Imipenem/XNW4107 has a low potential for resistance development in tested strains except for K. pneumoniae. Imipenem/XNW4107 provided good protection against imipenem-resistant A. baumannii and K. pneumoniae in vivo. The broad-spectrum profile and potent in vitro and in vivo antibacterial activities support imipenem/XNW4107 as a promising investigational candidate.

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