Multilineage-differentiating stress-enduring cells: a powerful tool for tissue damage repair.

Multilineage-differentiating stress-enduring (Muse) cells are a type of pluripotent cell with unique characteristics such as non-tumorigenic and pluripotent differentiation ability. After homing, Muse cells spontaneously differentiate into tissue component cells and supplement damaged/lost cells to participate in tissue repair. Importantly, Muse cells can survive in injured tissue for an extended period, stabilizing and promoting tissue repair. In addition, it has been confirmed that injection of exogenous Muse cells exerts anti-inflammatory, anti-apoptosis, anti-fibrosis, immunomodulatory, and paracrine protective effects in vivo. The discovery of Muse cells is an important breakthrough in the field of regenerative medicine. The article provides a comprehensive review of the characteristics, sources, and potential mechanisms of Muse cells for tissue repair and regeneration. This review serves as a foundation for the further utilization of Muse cells as a key clinical tool in regenerative medicine.

Agreements between the Global Leadership Initiative on Malnutrition using left calf circumference as criterion for reduced muscle mass and the Patient-Generated Subjective Global Assessment, and the Global Leadership Initiative on Malnutrition using the a.

Introduction: Objective: this study aimed to explore the agreements between the Global Leadership Initiative on Malnutrition (GLIM) using left calf circumference (CC) as criterion for reduced muscle mass and the Patient-Generated Subjective Global Assessment (PG-SGA), or GLIM using appendicular skeletal muscle index (ASMI) for the diagnosis of malnutrition in gastric cancer patients. Methods: the Nutritional Risk Screening 2002 (NRS 2002) was used as nutritional risk screening. PG-SGA and GLIM were applied for malnutrition diagnosis. Agreements were evaluated by Kappa, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC). Results: a total of 405 gastric cancer patients were included. The values of Kappa, sensitivity, specificity, PPV, NPV, accuracy and AUC were 0.463, 67.9 %, 87.3 %, 92.9 %, 52.8 %, 73.6 % and 0.776, and 0.496, 76.7 %, 78.0 %, 89.4 %, 57.9 %, 77.0 % and 0.773, respectively, between GLIM using CC with or without NRS 2002 and PG-SGA. All values of agreement were higher than 0.800 or 80.0 % between GLIM using left CC and GLIM using ASMI. Conclusion: the agreements were both acceptable between GLIM using left CC and PG-SGA, and GLIM using ASMI. Left calf circumference can be one of the credible references indicating a reduced muscle mass in patients with gastric cancer.

Introducción: Objetivo: este estudio tenía como objetivo explorar los acuerdos entre la Iniciativa Global de Liderazgo en Malnutrición (GLIM) utilizando la circunferencia de la pantorrilla izquierda (CC) como criterio de masa muscular reducida y la Evaluación Global Subjetiva Generada por el Paciente (PG-SGA), o la GLIM utilizando el índice de músculo esquelético apendicular (ASMI) para el diagnóstico de malnutrición en pacientes con cáncer gástrico. Métodos: se utilizó el Cribado de Riesgo Nutricional 2002 (NRS 2002) como cribado de riesgo nutricional. PG-SGA y GLIM se utilizaron para el diagnóstico de desnutrición. Los acuerdos se evaluaron mediante Kappa, sensibilidad, especificidad, valor predictivo positivo (VPP), valor predictivo negativo (VPN), exactitud y área bajo la curva (AUC). Resultados: se incluyó un total de 405 pacientes con cáncer gástrico. Los valores de Kappa, sensibilidad, especificidad, VPP, VPN, exactitud y AUC fueron de 0,463, 67,9 %, 87,3 %, 92,9 %, 52,8 %, 73,6 % y 0,776, y de 0,496, 76,7 %, 78,0 %, 89,4 %, 57,9 %, 77,0 % y 0,773, respectivamente, entre la GLIM utilizando CC con o sin NRS 2002 y PG-SGA. Todos los valores de concordancia fueron superiores a 0,800 u 80,0 % entre la GLIM utilizando la CC izquierda y la GLIM utilizando el ASMI. Conclusión: los acuerdos fueron aceptables entre la GLIM utilizando la CC izquierda y la PG-SGA, y la GLIM utilizando el ASMI. La circunferencia de la pantorrilla izquierda puede ser una de las referencias creíbles que indiquen reducción de la masa muscular en los pacientes con cáncer gástrico.

Computed tomography-guided microwave ablation for right middle lobe pulmonary nodules: a retrospective, single-center, case-control study.

PURPOSE: This retrospective, single-center, case-control study evaluated the safety and efficacy of Computed tomography (CT)-guided microwave ablation (MWA) for pulmonary nodules located in the right middle lobe (RML), a challenging location associated with a high frequency of complications. METHODS: Between May 2020 and April 2022, 71 patients with 71 RML pulmonary nodules underwent 71 MWA sessions. To comparison, 142 patients with 142 pulmonary nodules in non-RML were selected using propensity score matching. The technical success, technique efficacy, complications, and associated factors were analyzed. The duration of the procedure and post-ablation hospital stay were also recorded. RESULTS: Technical success was achieved in 100% of all patients. There were no significant differences in technique efficacy rates between the RML and non-RML groups (97.2% vs. 95.1%, p = 0.721). However, both major (47.9% vs. 19.7%, p < 0.001) and minor (26.8% vs. 11.3%, p = 0.004) pneumothorax were more common in the RML group than non-RML group. MWA for RML pulmonary nodules was identified as an independent risk factor for pneumothorax (p < 0.001). The duration of procedures (51.7 min vs. 35.3 min, p < 0.001) and post-ablation hospital stays (4.7 days vs. 2.8 days, p < 0.001) were longer in the RML group than non-RML group. CONCLUSIONS: CT-guided MWA for RML pulmonary nodules showed comparable efficacy compared with other lobes, but posed a higher risk of pneumothorax complications, necessitating longer MWA procedure times and extended hospital stays.

Changes in the pulmonary function of CT-guided microwave ablation for patients with malignant lung tumors.

PURPOSE: To investigate the changes in pulmonary function after computed tomography (CT)-guided microwave ablation (MWA) in patients with a malignant lung tumor. MATERIALS AND METHODS: From June 2020 to January 2022, 133 patients with a malignant lung tumor who underwent CT-guided percutaneous MWA were included in the study. Pulmonary function tests (PFTs) were performed before (the baseline) and 1 month after the MWA. Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1%, maximum mid-expiratory flow (MMEF), and diffusion capacity of the lung for carbon monoxide (DLCO-SB) at 1 month post MWA were compared with that at the baseline. The time of procedure and post-procedure length of hospital stay were also recorded. RESULTS: The mean VC, FVC, FEV1, FEV1%, MMEF, and DLCO-SB at the baseline and 1 month post MWA were 3.23 ± 0.75 and 3.22 ± 0.77 (P = 0.926), 3.20 ± 0.75 and 3.21 ± 0.77 (P = 0.702), 2.35 ± 0.70 and 2.35 ± 0.71 (P = 0.992), 91.97 ± 23.14 and 91.87 ± 23.16 (P = 0.837), 1.83 ± 0.93 and 1.81 ± 0.95 (P = 0.476), and 6.38 ± 1.67 and 6.32 ± 1.62 (P = 0.389), respectively. There was no significant difference in the PFT results before and 1 month post MWA. The mean time of procedure and post-MWA length of hospital stay were 33 min and 2.5 days, respectively. CONCLUSIONS: MWA is a lung parenchyma-sparing local treatment, and pulmonary function at 1 month post MWA was not statistically different from the baseline, indicating that MWA may not affect pulmonary function.

Lung microwave ablation: Post-procedure imaging features and evolution of pulmonary ground-glass nodule-like lung cancer.

PURPOSE: To retrospectively examine the imaging characteristics of chest-computed tomography (CT) following percutaneous microwave ablation (MWA) of the ground-glass nodule (GGN)-like lung cancer and its dynamic evolution over time. MATERIALS AND METHODS: From June 2020 to May 2021, 147 patients with 152 GGNs (51 pure GGNs and 101 mixed GGNs, mean size 15.0 ± 6.3 mm) were enrolled in this study. One hundred and forty-seven patients underwent MWA procedures. The imaging characteristics were evaluated at predetermined time intervals: immediately after the procedure, 24-48 h, 1, 3, 6, 12, and ≥18 months (47 GGNs). RESULTS: This study population included 147 patients with 152 GGNs, as indicated by the results: 43.5% (66/152) adenocarcinoma in situ, 41.4% (63/152) minimally invasive adenocarcinoma, and 15.1% (23/152) invasive adenocarcinoma. Immediate post-procedure tumor-level analysis revealed that the most common CT features were ground-glass opacities (93.4%, 142/152), hyperdensity within the nodule (90.7%, 138/152), and fried egg sign or reversed halo sign (46.7%, 71/152). Subsequently, 24-48 h post-procedure, ground-glass attenuations, hyperdensity, and the fried egg sign remained the most frequent CT findings, with incidence rates of 75.0% (114/152), 71.0% (108/152), and 54.0% (82/152), respectively. Cavitation, pleural thickening, and consolidation were less frequent findings. At 1 month after the procedure, consolidation of the ablation region was the most common imaging feature. From 3 to 12 months after the procedure, the most common imaging characteristics were consolidation, involutional parenchymal bands and pleural thickening. At ≥18 months after the procedure, imaging features of the ablation zone revealed three changes: involuting fibrosis (80.8%, 38/47), consolidation nodules (12.8%, 6/47), and disappearance (6.4%, 3/47). CONCLUSIONS: This study outlined the anticipated CT imaging characteristics of GGN-like lung cancer following MWA. Diagnostic and interventional radiologists should be familiar with the expected imaging characteristics and dynamic evolution post-MWA in order to interpret imaging changes with a reference image.

Early enlarging cavitation after percutaneous microwave ablation of primary lung cancer.

PURPOSE: This retrospective study assessed the incidence rate, risk factors, and clinical course of early enlarging cavitation after percutaneous microwave ablation (MWA) of primary lung cancer (PLC). METHODS: This study included 557 lesions of 514 patients with PLC who underwent CT-guided percutaneous MWA between 1 January 2018 and 31 December 2021. Of these patients, 29 developed early enlarging cavitation and were enrolled in the cavity group, and 173 were randomly enrolled in the control group. Early enlarging cavitation of the lung was defined as the development of a cavity ≥30 mm within 7 days after MWA. RESULTS: Overall, 31 (5.57%, 31/557 tumors) early enlarging cavitations occurred at an average of 5.83 ± 1.55 d after MWA. The risk factors were lesion contact with a large vessel (diameter ≥3 mm), lesion contact with the bronchus (diameter ≥2 mm), and a large ablated parenchymal volume. The cavity group had a higher incidence rate of delayed hydropneumothorax (12.9%) and bronchopleural fistula (9.68%) than the control group, resulting in a longer hospitalization (9.09 ± 5.26 days). Until Dec 31, 2022, 27 cavities disappeared after a mean of 217.88 ± 78.57 d (range, 111-510 d), two persisted, and two were lost to follow-up. CONCLUSIONS: Early enlarging cavitation occurred in 5.57% PLC cases that underwent MWA, causing serve complications and longer hospitalization. The risk factors were ablated lesion contact with large vessels and bronchi, as well as a larger ablated parenchymal volume.

The safety and feasibility of three-dimensional visualization planning system for CT-guided microwave ablation of stage I NSCLC (diameter ≤2.5 cm): A pilot study.

Background: Microwave ablation (MWA) of lung tumors is a technique that is dependent on the ablationist's level of expertise. The selection of the optimum puncture path and determination of appropriate ablative parameters is the key to the success and safe of the procedure. The objective of this study was to describe the clinical use of a novel three-dimensional visualization ablation planning system (3D-VAPS) for aided MWA of stage I non-small cell lung cancer (NSCLC). Methods: This was a single-arm, single-center, retrospective study. From May 2020 to July 2022, 113 consented patients with stage I NSCLC received MWA treatment in 120 MWA sessions. The 3D-VAPS was used to determine that: (1) the overlap between the gross tumor region and simulated ablation; (2) the proper posture and appropriate puncture site on the surface of the body; (3) the puncture path; and (4) presetting preliminarily ablative parameters. Patients were monitored with contrast-enhanced CT scans at 1, 3, and 6 months, as well as every 6 months following that. The primary endpoints were technical success and a complete ablation rate. Local progression-free survival (LPFS), overall survival (OS), and comorbidities were secondary study objectives. Results: The mean diameter of tumors was 1.9 ± 0.4 cm (range 0.9-2.5 cm). The mean duration was 5.34 ± 1.28 min (range 3.0-10.0 min). The mean power output was 42.58 ± 4.23 (range 30.0-50.0W). The median follow-up time was 19.0 months (6.0-26.0 months). The technical success rate was 100%. Three-month after the procedure, the complete ablation rate was 97.35%. 6, 9, 12, and 24 months LPFS rates were 100%, 98.23%, 98.23%, and 96.46%, respectively. One-year and 2-year OS rates were 100% and 100%. There were no patients who died both during the procedure and after the MWA of 30 days. The complications after MWA included pneumothorax (38.33%), pleural effusion (26.67%), intrapulmonary hemorrhage (31.67%), and pulmonary infection (2.50%). Conclusions: This research describes and confirms that 3D-VAPS is a feasibility and safe method for MWA of stage I NSCLC treatment. 3D-VAPS may be helpful to optimize the puncture path, assess reasonable ablative parameters, and minimize complications.

Synchronous computed tomography-guided percutaneous biopsy and microwave ablation for highly suspicious malignant lung ground-glass opacities adjacent to mediastinum.

BACKGROUND: This retrospective study aimed to assess the safety and efficacy of synchronous biopsy and microwave ablation (MWA) for highly suspected malignant lung ground-glass opacities (GGOs) adjacent to the mediastinum (distance ≤10 mm). MATERIALS AND METHODS: Ninety patients with 98 GGOs (diameter range, 6-30 mm), located within 10 mm of the mediastinum, underwent synchronous biopsy and MWA at a single institution from 1 May 2020, to 31 October 2021 and were enrolled in this study. Synchronous biopsy and MWA involving the completion of the biopsy and MWA in a single procedure was performed. Safety, technical success rate, and local progression-free survival (LPFS) were evaluated. The risk factors for local progression were calculated using the Mann-Whitney U test. RESULTS: The technical success rate was 97.96% (96/98 patients). The LPFS rates at 3, 6, and 12 months were 95.0%, 90.0%, and 82.0%, respectively. The diagnostic rate of biopsy-proven malignancy was 72.45% (n = 71/98). Invasion of lesions into the mediastinum was a risk factor for local progression (p = 0.0077). The 30-day mortality rate was 0. The major complications were pneumothorax (13.27%), ventricular arrhythmias (3.06%), pleural effusion (1.02%), hemoptysis (1.02%), and infection (1.02%). Minor complications included pneumothorax (30.61%), pleural effusion (24.49%), hemoptysis (18.37%), ventricular arrhythmias (11.22%), structural changes in adjacent organs (3.06%), and infection (3.06%). CONCLUSIONS: Synchronous biopsy and MWA was effective for treating GGOs adjacent to the mediastinum without severe complications (Society of Interventional Radiology classification E or F). Invasion of lesions into the mediastinum was identified as a risk factor for local progression.

HPF Modulates the Differentiation of BMSCs into HLCs and Promotes the Recovery of Acute Liver Injury in Mice.

Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to alleviate acute liver injury (ALI). Herpetfluorenone (HPF), as an active ingredient in the dried, mature seeds Herpetospermum caudigerum Wall, used in Tibetan medicine, has been proven to effectively alleviate ALI. Therefore, the purpose of this study was to determine whether HPF can promote the differentiation of BMSCs into HLCs and promote ALI recovery. Mouse BMSCs were isolated, and the BMSCs' differentiation into HLCs was induced by HPF and hepatocyte growth factor (HGF). Under the induction of HPF and HGF, the expression of hepatocellular specific markers and the accumulation of glycogen and lipids in the BMSCs increased, indicating that BMSCs successfully differentiated into HLCs. Then, the ALI mouse model was established, using carbon tetrachloride, followed by an intravenous injection of BMSCs. Then, only HPF was injected intraperitoneally, in order to verify the effect of HPF in vivo. In vivo imaging was used to detect the homing ability of HPF-BMSCs, and it was detected that HPF-BMSCs significantly increased the levels of serum AST, ALT and ALP in the liver of ALI mice, and alleviated liver cell necrosis, oxidative stress and liver pathology. In conclusion, HPF can promote the differentiation of BMSCs into HLCs and promote the recovery of ALI in mice.

Microwave ablation plus camrelizumab monotherapy or combination therapy in non-small cell lung cancer.

Purpose: Immunotherapy has become widely applied in non-small cell lung cancer (NSCLC) patients. However, the relatively low response rate of immunotherapy monotherapy restricts its application. Combination therapy improves the response rate and prolongs patient survival; however, adverse events (AEs) associated with immunotherapies increase with combination therapy. Therefore, exploring combination regimens with equal efficacy and fewer AEs is urgently required. The aim of this study was to evaluate the efficacy and safety of microwave ablation (MWA) plus camrelizumab monotherapy or combination therapy in NSCLC. Materials and methods: Patients with pathologically confirmed, epidermal growth factor receptor/anaplastic lymphoma kinase-wild-type NSCLC were retrospectively enrolled in this study. Patients underwent MWA to the pulmonary lesions first, followed by camrelizumab monotherapy or combination therapy 5-7 days later. Camrelizumab was administered with the dose of 200 mg every 2 to 3 weeks. Treatment was continued until disease progression or intolerable toxicities. The technical success and technique efficacy of ablation, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), complications of ablation, and AEs were recorded. Results: From January 1, 2019 to December 31, 2021, a total of 77 patients underwent MWA and camrelizumab monotherapy or combination therapy. Technical success was achieved in all patients (100%), and the technique efficacy was 97.4%. The ORR was 29.9%. The PFS and OS were 11.8 months (95% confidence interval, 9.5-14.1) and not reached, respectively. Smoking history and response to camrelizumab were correlated with PFS, and response to camrelizumab was correlated with OS in both the univariate and multivariate analyses. No periprocedural deaths due to ablation were observed. Complications were observed in 33 patients (42.9%). Major complications included pneumothorax (18.2%), pleural effusion (11.7%), pneumonia (5.2%), bronchopleural fistula (2.6%), and hemoptysis (1.3%). Grade 3 or higher AEs of camrelizumab, including reactive capillary endothelial proliferation, fatigue, pneumonia, edema, and fever, were observed in 10.4%, 6.5%, 5.2%, 2.6%, and 2.6% of patients, respectively. Conclusion: MWA combined with camrelizumab monotherapy or combination therapy is effective and safe for the treatment of NSCLC.

Safety and efficacy of microwave ablation for lung cancer adjacent to the interlobar fissure.

BACKGROUND: This retrospective study aimed to assess the safety and efficacy of microwave ablation for lung tumors adjacent to the interlobar fissures. METHODS: From May 2020 to April 2021, 59 patients with 66 lung tumors (mean diameter, 16.9 ± 7.7 mm; range, 6-30 mm) adjacent to the interlobar fissures who underwent microwave ablation at our institution were identified and included in this study. Based on the relationship between the tumor and the interlobar fissure, tumors can be categorized into close to the fissure, causing the fissure, and involving the fissure. The complete ablation rate, local progression-free survival, complications, and associated factors were analyzed. RESULTS: All 66 histologically proven tumors were treated using computed tomography-guided microwave ablation. The complete ablation rate was 95.5%. Local progression-free survival at 3, 6, 9, and 12 months were 89.4%, 83.3%, 74.2%, and 63.6%, respectively. The complications included pneumothorax (34.8%), pleural effusion (24.2%), cavity (18.2%), and pulmonary infection (7.6%). There were statistical differences in the incidence of pneumothorax, cavity, and delayed complications between the groups with and without antenna punctures through the fissure. CONCLUSIONS: Microwave ablation is a safe and effective treatment for lung tumor adjacent to the interlobar fissure. Antenna puncturing though the interlobar fissure may be a potential risk factor for pneumothorax, cavity, and delayed complications.

IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome.

Interleukin- (IL-) 38 is an emerging cytokine with multiple functions involved in infection and immunity. However, the potential role of IL-38 in the host immune response during sepsis remains elusive. Herein, we investigated if macrophages in septic mice express IL-38, the molecular mechanisms behind its expression, and the downstream effects of its expression. In mouse peritoneal macrophages, lipopolysaccharide (LPS) upregulated IL-38 and its receptor IL-36R, and the resulting IL-38 shifted macrophages from a M1 to M2 phenotype. Moreover, exposure to IL-38 alone was sufficient to inhibit macrophage apoptosis and LPS-driven activation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome. These effects were partly abrogated by IL-38 downregulation. In septic mice, IL-38 markedly lowered serum concentrations of proinflammatory cytokines and greatly improved survival. Conversely, IL-38 blockade aggravated their mortality. Collectively, these findings present IL-38 as a potent immune modulator that restrains the inflammatory response by suppressing macrophage apoptosis and activation of the NLRP3 inflammasome. IL-38 may help protect organs from sepsis-related injury.

Ultra-brilliant GeV betatronlike radiation from energetic electrons oscillating in frequency-downshifted laser pulses.

Electrons can be accelerated to GeV energies with high collimation via laser wakefield acceleration in the bubble regime and emit bright betatron radiation in a table-top size. However, the radiation brightness is usually limited to the third-generation synchrotron radiation facilities operating at similar photon energies. Using a two-stage plasma configuration, we propose a novel scheme for generating betatronlike radiation with an extremely high brilliance. In this scheme, the relativistic electrons inside the bubble injected from the first stage can catch up with the frequency-downshifted laser pulse formed in the second stage. The laser red shift originates from the phase modulation, together with the group velocity dispersion, which enables more energy to be transfered from the laser pulse to γ-photons, giving rise to ultra-brilliant betatronlike radiation. Multi-dimensional particle-in-cell simulations indicate that the radiated γ-photons have the cut-off energy of GeV and a peak brilliance of 1026 photons s-1 mm-2 mrad-2 per 0.1%BW at 1 MeV, which may have diverse applications in various fields.

Atorvastatin attenuates surgery-induced BBB disruption and cognitive impairment partly by suppressing NF-κB pathway and NLRP3 inflammasome activation in aged mice.

In clinic, perioperative neurocognitive disorder is becoming a common complication of surgery in old patients. Neuroinflammation and blood-brain barrier (BBB) disruption are important contributors for cognitive impairment. Atorvastatin, as a strong HMG-CoA reductase inhibitor, has been widely used in clinic. However, it remains unclear whether atorvastatin could prevent anesthesia and surgery-induced BBB disruption and cognitive injury by its anti-inflammatory property. In this study, aged C57BL/6J mice were used to address this question. Initially, the mice were subject to atorvastatin treatment for 7 days (10 mg/kg). After a simple laparotomy under 1.5% isoflurane anesthesia, Morris water maze was performed to assess spatial learning and memory. Western blot analysis, immunohistochemistry, and enzyme-linked immunosorbent assay were used to examine the inflammatory response, BBB integrity, and cell apoptosis. Terminal-deoxynucleotidyl transferase mediated nick end labeling assay was used to assess cell apoptosis. The fluorescein sodium and transmission electron microscopy were used to detect the permeability and structure of BBB. The results showed that anesthesia and surgery significantly injured hippocampal-dependent learning and memory, which was ameliorated by atorvastatin. Atorvastatin could also reverse the surgery-induced increase of systemic and hippocampal cytokines, including IL-1ß, TNF-α, and IL-6, accompanied by inhibiting the nuclear factor kappa-B (NF-κB) pathway and Nucleotide-Binding Oligomerization Domain, or Leucine Rich Repeat and Pyrin Domain Containing 3 (NLRP3) inflammasome activation, as well as hippocampal neuronal apoptosis. In addition, surgery triggered an increase of BBB permeability, paralleled by a decrease of the ZO-1, occludin, and Claudin 5 proteins in the hippocampus. However, atorvastatin treatment could protect the BBB integrity from the impact of surgery, by up-regulating the expressions of ZO-1, occludin, and Claudin 5. These findings suggest that atorvastatin exhibits neuroprotective effects on cognition in aged mice undergoing surgery.

Risk factors for nephrotoxicity associated with polymyxin B therapy in Chinese patients.

Background The widespread application of Polymyxin B, an active agent against multidrug resistance and extensive drug resistance Gram-negative bacteria, is majorly impeded by nephrotoxicity. Studies on the safety of polymyxin B in Chinese patients have not been widely reported. Objective This study aimed to explore the risk factors for polymyxin B-associated nephrotoxicity and guide its optimal place in therapy. Setting A tertiary care hospital located in eastern China. Methods This being a retrospective cohort study, we evaluated adult patients who received ≥ 72 h of polymyxin B therapy from January 2018 to December 2019. However, patients who received polymyxin B therapy for less than 3 days or received renal replacement therapy at baseline were excluded. Pertinent information was retrieved from medical records. All statistical analysis was performed in SPSS version 22.0. Main outcome measure(s) The main outcome measures included the proportion of patients who developed nephrotoxicity when subjected to polymyxin B treatment and the independent risk factors for nephrotoxicity. Results A total of 119 patients received polymyxin and met the overall inclusion criterion. Of the 119, 46 patients (38.7%) developed nephrotoxicity. Through multiple logistic regression analysis, we found three variables as independent risk factors for nephrotoxicity, including co-morbidities of malignancy (OR 4.55; 95% CI 1.44-14.41; P = 0.010), co-infection with other microorganisms (OR 4.15; 95% CI 1.48-11.63; P = 0.007), and polymyxin B daily dose (OR 1.02; 95% CI 1.00-1.03; P = 0.026). Conclusion This retrospective cohort study identified three risk factors for polymyxin B-associated nephrotoxicity therapy in Chinese patients. These include malignancy, co-infection with other microorganisms, and polymyxin B daily dose.

Homochiral Nickel Nitrite ABX3 (X = NO2-) Perovskite Ferroelectrics.

Chiral organic-inorganic perovskites (COIPs) have recently attracted increasing interest due to their unique inherent chirality and potential applications in next-generation optoelectronic and spintronic devices. However, COIP ferroelectrics are very sparse. In this work, for the first time, we present the nickel-nitrite ABX3 COIP ferroelectrics, [(R and S)-N-fluoromethyl-3-quinuclidinol]Ni(NO2)3 ([(R and S)-FMQ]Ni(NO2)3), where the X-site is the rarely seen NO2- bridging ligand. [(R and S)-FMQ]Ni(NO2)3 display mirror-relationship in the crystal structure and vibrational circular dichroism signal. It is emphasized that [(R and S)-FMQ]Ni(NO2)3 show splendid ferroelectricity with both an extremely high phase-transition point of 405 K and a spontaneous polarization of 12 µC/cm2. To our knowledge, [(R and S)-FMQ]Ni(NO2)3 are the first examples of nickel-nitrite based COIP ferroelectrics. This finding expands the COIP family and throws light on exploration of high-performance COIP ferroelectrics.

Endometrial polyp-like perivascular epithelioid cell neoplasm associated with TFE3 translocation: report of one case.

This article reports the pathologic features and malignant biological behavior of a perivascular epithelioid cell neoplasm (PEComa) with the clinical manifestation being endometrial polyps. The case was cured with curettage in a local hospital one year ago. The postoperative diagnosis was "endometrial polyps". This time, due to "irregular bleeding", we carried out another curettage in our hospital. After the operation, 3 pieces of polyps were inspected with diameters of 0.3 cm, 0.5 cm and 0.6 cm, respectively. The tumor consisted of epithelioid cells with alveolar and nesting pattern and showed a diffuse strong expression of HMB45, Melan-A and TFE3. The patient then underwent a hysterectomy and the "polyps" were sent for pathological examination. The result showed that tumor cells infiltrated the deep muscle layer, close to the outer membrane, suggesting a malignant biologic behavior. TFE3-related PEComa is different from general PEComa. This neoplasm and Melanotic Xp11 renal carcinoma have similar clinicopathologic features, histology, immunity and molecular phenotypes, belonging to the same type of tumor. It has been suggested in the literature naming this neoplasm as 'Xp11 neoplasm with melanocytic differentiation' or 'melanotic Xp11 neoplasm'. Our case has expanded our understanding of PEComa characteristics and increased data for TFE3 translocation-related PEComa, reminding us to avoid misdiagnosis when PEComa manifests as small polyps.

Malignant ascites-derived exosomes promote peritoneal tumor cell dissemination and reveal a distinct miRNA signature in advanced gastric cancer.

Peritoneal dissemination (PD) is the most frequent metastasis with poor prognosis in patients with advanced gastric cancer (GC). However, the molecular mechanisms of PD remain poorly defined. Exosomes play a pivotal role in cancer progression. Thus, this study aims to investigate the effects of malignant ascites (MA)-derived exosomes from GC patients on tumor cells and to elucidate the underlying mechanism. In vitro and in vivo analysis showed that compared to exosome-depleted supernatants, exosomes from MA of GC patients promoted invasion of AGS cells by up-regulation of Epithelial-mesenchymal transition (EMT) signaling. In a mouse abdominal xenograft model, the median survival was shorter after MA-derived exosomes treatment than the control group (35.5 days versus 67 days, p = 0.0005). Moreover, 29 exosomal miRNAs from ascites were identified by high throughput sequencing among 8 paired GC patients before and after peritoneal chemotherapy and 3 individuals with non-malignant disease. In summary, MA-derived exosomes from patients with GC promote EMT signaling in GC cells and in mouse peritoneal tumor model. Differential exosomal miRNAs might be targeted therapeutically for inhibiting peritoneal metastasis, which provides new insights for the molecular mechanisms of PD in GC.

Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment. Although tremendous advances have been made in the investigation of HCC, the specific mechanisms of the progression of this disease are still only partially established. Hence, more research is needed to elucidate the underlying potential mechanisms to develop effective strategies for HCC. AIM: To determine the role of developing brain homeobox 2 (Dbx2) gene in promoting the development of HCC. METHODS: Dbx2 expression in clinical specimens and HCC cell lines was detected by Western blot (WB) and immunohistochemistry. Gain and loss of Dbx2 function assays were performed in vitro and in vivo. Cell viability assays were used to investigate cell growth, flow cytometry was employed to assess cell cycle and apoptosis, and trans-well assays were conducted to evaluate cell migration, invasion, and metastasis. The expression of key molecules in the sonic hedgehog (Shh) signaling was determined by WB. RESULTS: Compared to matched adjacent non-tumorous tissues, Dbx2 was overexpressed in 5 HCC cell lines and 76 surgically resected HCC tissues. Dbx2 overexpression was correlated with large tumor size. Both gain and loss of function assays indicated that Dbx2 promoted HCC cell proliferation by facilitating the transition from G1 to S phase, attenuating apoptosis and promoted HCC proliferation, migration, and invasion in vitro and in vivo. Mechanistically, Dbx2 modulated Shh signaling by enhancing FTCH1 and GLi1 expression in HCC cells that overexpressed Dbx2, which was reversed in HCC cells with Dbx2 knockdown. CONCLUSION: Our results indicate that Dbx2 is significantly upregulated in HCC tissues and plays significant roles in proliferation and metastasis of HCC cells by activating the Shh pathway.

The sap flow-based assessment of atmospheric trace gas uptake by three forest types in subtropical China on different timescales.

Assessing the uptake of trace gases by forests contributes to understanding the mechanisms of gas exchange between vegetation and the atmosphere and to evaluating the potential risk of these pollutant gases to forests. In this study, the multi-timescale characteristics of the stomatal uptake of NO, NO2, SO2 and O3 by Schima superba, Eucalyptus citriodora and Acacia auriculiformis were investigated by continuous sap flow measurements for a 3-year period. The peak canopy stomatal conductance (GC) for these three species appeared between 9:00 and 12:00, which was jointly regulated by the vapour pressure deficit (VPD) and photosynthetically active radiation (PAR). Additionally, annual and seasonal variations in the stomatal uptake of trace gases for these three tree species suggested that there was a combination effect between canopy stomatal conductance and ambient concentration on the uptake of trace gases. Furthermore, the result demonstrated that the trace gas absorption capacities among these three forest types followed the order of S. superba > E. citriodora > A. auriculiformis. The findings of this study have theoretical significance and application value in assessing air purification and the risk of harm to forests in Southern China.