Non-invasive prediction of the chronic degree of lupus nephropathy based on ultrasound radiomics.

OBJECTIVE: Through machine learning (ML) analysis of the radiomics features of ultrasound extracted from patients with lupus nephritis (LN), this attempt was made to non-invasively predict the chronicity index (CI)of LN. METHODS: A retrospective collection of 136 patients with LN who had renal biopsy was retrospectively collected, and the patients were randomly divided into training set and validation set according to 7:3. Radiomics features are extracted from ultrasound images, independent factors are obtained by using LASSO dimensionality reduction, and then seven ML models were used to establish predictive models. At the same time, a clinical model and an US model were established. The diagnostic efficacy of the model is evaluated by analysis of the receiver operating characteristics (ROC) curve, accuracy, specificity, and sensitivity. The performance of the seven machine learning models was compared with each other and with clinical and US models. RESULTS: A total of 1314 radiomics features are extracted from ultrasound images, and 5 features are finally screened out by LASSO for model construction, and the average ROC of the seven ML is 0.683, among which the Xgboost model performed the best, and the AUC in the test set is 0.826 (95% CI: 0.681-0.936). For the same test set, the AUC of clinical model constructed based on eGFR is 0.560 (95% CI: 0.357-0.761), and the AUC of US model constructed based on Ultrasound parameters is 0.679 (95% CI: 0.489-0.853). The Xgboost model is significantly more efficient than the clinical and US models. CONCLUSION: ML model based on ultrasound radiomics features can accurately predict the chronic degree of LN, which can provide a valuable reference for clinicians in the treatment strategy of LN patients.

Longitudinal association between the dynamic nature of depression with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH).

BACKGROUND: Depression is associated with an increased risk of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Whether the dynamic nature of depression affects the incidence of LUTS/BPH remains unknown. A four-year cohort study based on the China Health and Retirement Longitudinal Study (CHARLS) was conducted to assess their association. METHODS: This study included 3433 Chinese men from the CHARLS 2011, representative of > 95 million individuals. All eligible individuals underwent three assessments of LUTS/BPH and depression in 2011, 2013 and 2015. The dynamic nature of depression was classified as acute depression with remission, acute depression with recurrence, or chronic major depression. Weighted, generalized additive analyses with three binomial models were used to investigate the relationship between LUTS/BPH and the dynamic nature of depression. RESULTS: During the four-year follow-up, 11.5% (95% confidence interval [95% CI] = 9.5-13.3%) of Chinese men were diagnosed with newly incident LUTS/BPH. Meanwhile, there were 60.6% (95% CI = 58.5-62.7%) of the individuals without depression and 8.9% (95% CI = 7.9-10%) of the individuals with chronic major depression. A total of 25.1% (95% CI = 23.4-26.9%) and 5.4% (95% CI = 4.6-6.3%) of the individuals were categorized as acute depression with remission and recurrence. After weighted, adjusted all included confounding risk factors, chronic major depression (RR = 1.63, 95% CI = 1.14-2.33, P < 0.01) but not acute depression with remission (RR = 1.2, 95% CI = 0.92-1.56, P = 0.18) and recurrence (RR = 1.32, 95% CI = 0.82-2.10, P = 0.26) significantly increased the incidence of LUTS/BPH compared with no depression. The subgroup analysis showed that the above relationships appeared to be evident among Chinese men < 60 years. CONCLUSIONS: Our results suggest that the dynamic nature of depression has a different effect on the incidence of LUTS/BPH. The monitoring and treatment of depression are important in preventing LUTS/BPH.

Dynamic space-time dark level correction approach for lunar radiometric calibration of the Lunar Observation Imaging Spectrometer.

Lunar radiometric calibration is used to solve the problem of consistent radiometric calibration for multiple satellite platforms and remote sensors. However, the dark level fluctuates when observing the Moon with a short-wave infrared spectrometer, which seriously affects the accuracy of lunar radiation data. In this work, we propose a dynamic space-time dark level correction approach to address the fluctuation of the dark level. This method employs cold space signals in space and time dimensions to estimate the dark level for each frame individually and to reduce errors due to environmental variations. Experiments on lunar observations at multiple phase angles were conducted, and the dark level correction results demonstrate that our proposed method is effective even in the short-wave infrared, and is also superior to currently existing techniques. For a single-band (1700 nm) image of the full Moon, the mean background proportion of the proposed method is 1.00%, which is better than that of the static dark correction method (2.25%) and linear dark correction method (5.93%).

The promoting effects of pyriproxyfen on autophagy and apoptosis in silk glands of non-target insect silkworm, Bombyx mori.

Pyriproxyfen is a juvenile hormone analogue. The physiological effects of its low-concentration drift during the process of controlling agricultural and forestry pests on non-target organisms in the ecological environment are unpredictable, especially the effects on organs that play a key role in biological function are worthy of attention. The silk gland is an important organ for silk-secreting insects. Herein, we studied the effects of trace pyriproxyfen on autophagy and apoptosis of the silk gland in the lepidopteran model insect, Bombyx mori (silkworm). After treating fifth instar silkworm larvae with pyriproxyfen for 24 h, we found significant shrinkage, vacuolization, and fragmentation in the posterior silk gland (PSG). In addition, the results of autophagy-related genes of ATG8 and TUNEL assay also demonstrated that autophagy and apoptosis in the PSG of the silkworm was induced by pyriproxyfen. RNA-Seq results showed that pyriproxyfen treatment resulted in the activation of juvenile hormone signaling pathway genes and inhibition of 20-hydroxyecdysone (20E) signaling pathway genes. Among the 1808 significantly differentially expressed genes, 796 were upregulated and 1012 were downregulated. Among them, 30 genes were identified for autophagy-related signaling pathways, such as NOD-like receptor signaling pathway and mTOR signaling pathway, and 30 genes were identified for apoptosis-related signaling pathways, such as P53 signaling pathway and TNF signaling pathway. Further qRT-PCR and in vitro gland culture studies showed that the autophagy-related genes Atg5, Atg6, Atg12, Atg16 and the apoptosis-related genes Aif, Dronc, Dredd, and Caspase1 were responsive to the treatment of pyriproxyfen, with transcription levels up-regulated from 24 to 72 h. In addition, ATG5, ATG6, and Dronc genes had a more direct response to pyriproxyfen treatment. These results suggested that pyriproxyfen treatment could disrupt the hormone regulation in silkworms, promoting autophagy and apoptosis in the PSG. This study provides more evidence for the research on the damage of juvenile hormone analogues to non-target organisms or organs in the environment, and provides reference information for the scientific and rational use of juvenile hormone pesticides.

Direct Detection of Reactive Gallium-Hydride Species on the Ga2O3 Surface via Solid-State NMR Spectroscopy.

Surface metal hydrides (M-H) are ubiquitous in heterogeneous catalytic reactions, while the detailed characterizations are frequently hindered by their high reactivity/low concentration, and the complicated surface structures of the host solids, especially in terms of practical solid catalysts. Herein, combining instant quenching capture and advanced solid-state NMR methodology, we report the first direct and unambiguous NMR evidence on the highly reactive surface gallium hydrides (Ga-H) over a practical Ga2O3 catalyst during direct H2 activation. The spectroscopic effects of 69Ga and 71Ga isotopes on the 1H NMR signal are clearly differentiated and clarified, allowing a concrete discrimination of the Ga-H signal from the hydroxyl crowd. Accompanied with quantitative and two-dimensional NMR spectroscopical methods, as well as density functional theory calculations, information on the site specification, structural configuration, and formation mechanism of the Ga-H species has been revealed, along with the H2 dissociation mechanism. More importantly, the successful spectroscopic identification and isolation of the surface Ga-H allow us to clearly reveal the critical but ubiquitous intermediate role of this species in catalytic reactions, such as propane dehydrogenation and CO2 hydrogenation reactions. The analytic approach presented in this work can be extended to other M-H analysis, and the insights will benefit the design of more efficient Ga-based catalysts.

Value of contrast-enhanced ultrasonography in radiofrequency ablation of secondary hyperparathyroidism.

OBJECTIVES: The purpose of the current study was to determine the performance of contrast-enhanced ultrasound (CEUS) in the assessment of radiofrequency ablation (RFA) of hyperplastic parathyroid glands due to secondary hyperparathyroidism (SHPT). METHODS: Thirty-two patients, each with ≥4 hyperplastic parathyroid glands due to SHPT, underwent RFA via hydro-dissection. CEUS was performed in each patient before and during RFA. The patients in whom the intact parathyroid hormone (iPTH) level did not decrease to 300 pg/ml were examined by CEUS. The iPTH, serum calcium, and serum phosphorus levels before and after RFA were compared. RESULTS: Ablation was achieved in all patients (131 ablated glands). The volume of the glands was 479.88 ± 549.3mm3. The pre-operative and day 1 post-operative iPTH levels were 2355 ± 1062 and 292.7 ± 306.8 pg/ml, respectively. Three nodules in three patients showed little enhancement on CEUS on post-operative day 1. The iPTH level was <300 pg/mL on post-operative day 1 in 23 patients, which indicated complete ablation; follow-up evaluations were therefore performed. The pre- and post-operative iPTH levels in the 23 patients were 2113 ± 787.2 and 106.2 ± 84.62 pg/ml, respectively (p < 0.05), and the 6- and 12-month post-operative iPTH levels were 111.1 ± 56.57 and 117.6 ± 97.08 pg/ml, respectively (p > 0.05). CONCLUSIONS: CEUS-guided RFA is effective and feasible for the treatment of ≥4 hyperplastic parathyroid glands. CEUS was shown to assist the surgeon before, during, and after RFA. CEUS on post-operative day 2, but not immediately post-operatively, was shown to accurately reflect gland perfusion.

Diagnosis efficacy of CEUS for hepatic inflammatory lesions.

PURPOSE: In this study, the efficacy of US/CEUS and clinicopathologic parameters in differential diagnosis of hepatic inflammatory lesions were evaluated. METHODS: This was a retrospective study in which CEUS imaging was performed on 182 patients. Among these patients, 44 patients had hepatic inflammatory lesions and 138 patients had malignant lesions. The ultrasound (US), CEUS, and clinicopathologic parameters with respect to differential diagnosis of hepatic inflammatory lesions were analyzed. RESULTS: Irregular lesion shape and unclear margin were commonly seen in hepatic inflammatory lesions by US/CEUS examination. Hypoenhancement in arterial phase (AP) and portal venous phase (PVP), and isoenhancement in delayed phase (DP) were more commonly found in inflammatory lesions rather than malignant lesions [9% (4/44), 68% (30/44), and 16% (7/44) vs 2% (3/138), 11% (15/138), 1% (1/138), respectively; P < .05]. The enhancement coverage was also a significant indicator for the differentiation of inflammatory lesions and malignant lesions (P < .05). History of hepatitis or cirrhosis, and higher serum alpha-fetoprotein (AFP) level were indicators for malignant lesions, while liver parasites and higher body temperature were indicators for inflammatory lesions. When the US/CEUS findings were combined with clinicopathologic parameters, the diagnostic accuracy of inflammatory lesions could reach 93.3%, with sensitivity, specificity, positive predictive value, and negative predictive value of 63.64%, 96.03%, 84.85%, and 88.32%, respectively. CONCLUSION: The US/CEUS findings combined with clinical characteristics can accurately differentiate hepatic inflammatory lesions and malignant lesions. The results of study will improve the diagnostic confidence for hepatic inflammatory lesions.

Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy.

BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) and bone marrow mononuclear cells (BMMNCs) are both used to treat spastic cerebral palsy. However, the differences in therapeutic effect remain unknown. METHODS: A total of 105 patients with spastic cerebral palsy were enrolled and randomly assigned to three groups: the BMMSC group, the BMMNC group and the control group. Patients in both transplantation groups received four intrathecal cell injections. Patients in the control group received Bobath therapy. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were used to evaluate the therapeutic efficacy before transplantation and 3, 6, and 12 months after transplantation. RESULTS: Three months after cell transplantation, scores in the A dimension of GMFM and the A and C dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). Six months after cell transplantation, scores in the A, B dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are higher than those of the BMMNC and the control groups (P < 0.05). Twelve months after cell transplantation, scores in the A, B, and C dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). No obvious adverse effects were investigated during follow-up. CONCLUSIONS: BMMSC transplantation for the treatment of cerebral palsy is safe and feasible, and can improve gross motor and fine motor function significantly. In addition, compared with BMMNC, the motor function of children improved significantly in terms of gross motor and fine motor functions.

Comparative Study of Data Compression Methods for Large Aperture Static Imaging Spectrometer.

Facing the problem of choosing different data source as compressing object results in different compression effect, several techniques are investigated to explore a better data source which can reduce the loss of image and spectral information while getting higher compression ratio in the compression work of the large aperture static imaging spectrometer. In this paper the optical path difference dimension data source of LASIS was proposed after analyzing the characteristic of LASIS and then compared with the LASIS and LAMIS data source in detail. The SWIR data collected with the principle prototype of LASIS were used in our experiment. Firstly, three forms of data sources were extracted after detailedly introducing their data characteristic and extracting methods. Secondly, the mature algorithms in engineering JPEG and JPEG2000 were employed to compress and reconstruct the three forms of data sources respectively. Finally, the compression effect was evaluated in the aspect of image content, interference dimension, spectral dimension and compression ratio respectively, and the original spectral curves of three materials choosing from the field of view and those after reconstruction were extracted next, then the loss of spectral information of these three materials were measured by using the SA (Spectral Angle) and RQE (Relative Quadratic Error) values of the spectral curves to evaluate the compression effect. It is demonstrated that using the optical path difference dimension data as compressing object shows obvious advantages compared with LASIS and LAMIS, which achieves a combination of higher compression ratio, lower mean square error, lower peak signal noise ratio and less information loss that is competitive with the best results from the literature. The results show that the proposed optical path difference dimension data source has good performance in preserving the spatial and spectral information during the compression of LASIS than the other two common forms data sources of LASIS.

Drug targets in the cytokine universe for autoimmune disease.

In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders.

[Experiment Research and Analysis of Spectral Prediction on Soil Leaking Oil Content].

The spectral analysis method was applied experimentally to extract the spectral indices, measure and analyze the spectral characteristics and their difference of the mixture which are composed in soil in Central Shaanxi Plain and the diesel and motor oil respectively, aiming to provide solutions to practical difficulties in detecting, analyzing the spectral characteristics and difference between the soil leaking with equal content diesel and motor oil and predicting the leaking content of diesel in the soil. The spectral response curves of the soil leaking with different oil respectively and the soil leaking with diesel with different content were collected. Then the spectral prediction model for the leaking content of diesel in the soil was built based on the reflectance characteristics. The coefficient of the detection (R2) was introduced to evaluate the stability of the built model，and the parameter root mean squared error (RMSE) was introduced to estimate the precision and the predictability of the model built in this work. It is demonstrated that : (1) The reflectance of soil leaking with diesel is less than that of the equal content motor oil. And there is a double absorption trough of the reflectance curve of both soil leaking with diesel and motor oil at 1 740 and 2 328 nm. The spectral absorption indices and absorption depth of the soil leaking with diesel keep less than the equal content motor oil. (2) The built spectral prediction model for the leaking content of diesel in the soil demonstrates good stability with the coefficient of determination at R2=0.854, and performs favorable predictability (Root-Mean-Square Error, RMSE=0.016), which can benefit the effective prediction and quick estimation methods of the leaking content of diesel in the soil, enrich and progress the experimental method and theoretical research work of spectral prediction on soil leaking oil content and promote the application of remote sensing in safety production and environmental protection.

Effect of umbilical cord mesenchymal stromal cells on motor functions of identical twins with cerebral palsy: pilot study on the correlation of efficacy and hereditary factors.

BACKGROUND AIMS: The objective of this study was to compare the impact of umbilical cord-derived mesenchymal stromal cell (UCMSC) transplantation on the motor functions of identical twins with cerebral palsy (CP) and to analyze the correlation between the efficacy and hereditary factors. METHODS: Eight pairs (16 individuals) of identical twins with CP were recruited and received allogenic UCMSC transplantation by means of subarachnoid injection. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were performed before and 1 and 6 months after the treatment to analyze the results of individuals before and after the therapy, between two individuals of an identical twin and among twin pairs. Repeated-measured data variance was used to analyze the GMFM and FMFM scores of patients before and 1 and 6 months after the therapy. RESULTS: Eight pairs (16 individuals) of children with CP had significant improvement in the GMFM at the end of the 1st and 6th months after the therapy compared with that before the therapy, whereas the amelioration of the FMFM was not statistically significant. The improvements in motor functions between two individuals of an identical twin but not among twin pairs were correlated. CONCLUSIONS: UCMSC transplantation significantly improves GMFM in children with CP; motor function improvements in the GMFM between two individuals of an identical twin were closely correlated, but improvements among twin pairs were not correlated. We hypothesize that hereditary factors contribute to the mechanisms of UCMSC transplantation in motor function improvement in children with CP.

Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury.

BACKGROUND: Umbilical cord mesenchymal stem cells (UCMSCs) have a considerable advantage and potential in treating for central nervous system diseases and have become a novel alternative treatment for spinal cord injury. This study aims to compare the neurological function outcome of stem cell transplantation, rehabilitation therapy, and self-healing for sequelae of spinal cord injury. METHODS: Thirty-four cases of thoracolumbar spinal cord injury were randomly divided into three groups: the stem cell transplantation group was given CT-guided UCMSC transplantation twice; the rehabilitation group received rehabilitation therapy; and the blank control group did not receive any specific treatment. AIS grading, ASIA scoring, the manual muscle strength and muscle tension scale, and the Barthel index were used to evaluate the clinical outcome. Urodynamic examination was also performed for patients in the UCMSC group and the rehabilitation therapy group. RESULTS: Seven of the ten patients in the UCMSC group had significant and stable improvement in movement, self-care ability, and muscular tension; five of the forteen patients (36%) in the rehabilitation group also had certain improvement in these aspects. Urodynamic examination demonstrated that patients in the UCMSC group exhibited an increase in maximum urinary flow rate and maximum bladder capacity, as well as a decrease in residue urine volume and maximum detrusor pressure. The rehabilitation group exhibited decreased maximum bladder capacity, but no perceptible change in maximum urinary flow rate, residue urine volume or maximum detrusor pressure. CONCLUSIONS: UCMSC transplantation can effectively improve neurological functional recovery after spinal cord injury, and its efficacy is superior to that of rehabilitation therapy and self-healing. TRIAL REGISTRATION: The present clinical study was registered at chictr.org (registration number: NCT01393977).

TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1.

T-helper type 17 cells (T(H)17) are implicated in rodent models of immune-mediated diseases. Here we report their involvement in human uveitis and scleritis, and validate our findings in experimental autoimmune uveoretinitis (EAU), a model of uveitis. T(H)17 cells were present in human peripheral blood mononuclear cells (PBMC), and were expanded by interleukin (IL)-2 and inhibited by interferon (IFN)-gamma. Their numbers increased during active uveitis and scleritis and decreased following treatment. IL-17 was elevated in EAU and upregulated tumor necrosis factor (TNF)-alpha in retinal cells, suggesting a mechanism by which T(H)17 may contribute to ocular pathology. Furthermore, IL-27 was constitutively expressed in retinal ganglion and photoreceptor cells, was upregulated by IFN-gamma and inhibited proliferation of T(H)17. These findings suggest that T(H)1 cells may mitigate uveitis by antagonizing the T(H)17 phenotype through the IFN-gamma-mediated induction of IL-27 in target tissue. The finding that IL-2 promotes T(H)17 expansion provides explanations for the efficacy of IL-2R antibody therapy in uveitis, and suggests that antagonism of T(H)17 by IFN-gamma and/or IL-27 could be used for the treatment of chronic inflammation.

What exercise strategies are best for people with cognitive impairment and dementia? A systematic review and meta-analysis.

OBJECTIVE: Explore the types of exercise that are appropriate for people with dementia, as well as the intensity and frequency of exercise training that is appropriate for older patients to carry out. METHODS: Cochrane Library, PubMed, Embase, Web of Science, Scopus databases were searched by computer to collect RCT studies that met the inclusion criteria of this article. The search time limit was until January 2024. Two reviewers independently screened literature, extracted data, and assessed the quality and risk of bias of the included studies. Then, meta-analysis was performed using RevMan 5.4 and Stata 15.1 software. RESULTS: The results of our study showed that physical exercise improved patients' cognitive ability and walking ability, with aerobic and multicomponent training showing the best improvement, and that the number of training sessions should not be too high, with the experimental group showing the best results when the total number of interventions was less than 30. CONCLUSION: We recommend long-term exercise training for middle-aged and elderly patients with dementia or those who are predisposed to dementia. The type of training we recommend is multi-component training and aerobic training, and we recommend 2-3 sessions of exercise per week for about 60 min each.

The effect of moderate and vigorous aerobic exercise training on the cognitive and walking ability among stroke patients during different periods: A systematic review and meta-analysis.

OBJECTIVE: The study examined whether rehabilitation using aerobic exercise is more appropriate for patients less than 3 months post-stroke or more appropriate for patients more than 3 months post-stroke. METHOD: PubMed, Embase, Web of Science, Scopus and CNKI databases were searched from inception to September 2023. All studies included must be written in English and grey literature was excluded. The quality of the study was evaluated using the PEDro scale. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated. The primary outcomes are cognitive ability and walking ability. The intervention of the experimental group must be or include high-intensity aerobic training or moderate-intensity aerobic training. In addition, we required low intensity routine exercises in control group. RESULT: Only 15 studies were included in this meta-analysis. The results showed that aerobic exercise has a positive rehabilitation effect on cognitive and walking ability of stroke patients. Global Cognitive Function (SMD = 0.81 95%CI 0.49-1.12), Walking Capacity (SMD = 1.19, 95%CI 0.75-1.62), VO2peak (SMD = 0.97, 95%CI 0.66-1.28), and brain-derived neurotrophic factor (SMD = 2.73, 95%CI 2.03-3.43). We further observed that patients who suffered a stroke within the past three months exhibited superior rehabilitation outcomes compared to patients who suffered a stroke more than three months ago, specifically in terms of cognitive ability, walking tests, and cardiopulmonary function. CONCLUSIONS: It is recommended to carry out treatment for patients in the initial stage of stroke, and it is required to pay attention to exercise intensity in the process of treatment to ensure patient safety.

Prospects of focal adhesion kinase inhibitors as a cancer therapy in preclinical and early phase study.

INTRODUCTION: FAK, a nonreceptor cytoplasmic tyrosine kinase, plays a crucial role in tumor metastasis, drug resistance, tumor stem cell maintenance, and regulation of the tumor microenvironment. FAK has emerged as a promising target for tumor therapy based on both preclinical and clinical data. AREAS COVERED: This paper aims to summarize the molecular mechanisms underlying FAK's involvement in tumorigenesis and progression. Encouraging results have emerged from ongoing clinical trials of FAK inhibitors. Additionally, we present an overview of clinical trials for FAK inhibitors, examining their potential as promising treatments. The pertinent studies gathered from databases including PubMed, ClinicalTrials.gov. EXPERT OPINION: Since the first finding in 1990s, targeting FAK has became the focus of interests in many pharmaceutical companies. Through 30 years' discovery, the industry and academy gradually realized the features of FAK target which may not be a driver gene but a solid defense system for the cancer initiation and development. Currently, the ongoing clinical regimens involving FAK inhibition are all the combination strategies in which FAK inhibitors can further strengthen the cancer cell killing effects of other testing agents. The emerging positive signal in clinical trials foresee targeting FAK as class will be an effective mean to fight against cancers.

Comparative analysis of curative effect of CT-guided stem cell transplantation and open surgical transplantation for sequelae of spinal cord injury.

BACKGROUND: This study compared the clinical efficacies, advantages and disadvantages of two transplantation approaches for treating spinal cord injury: open surgical exploration combined with local stem cell transplantation (referred to as open surgical transplantation) and local stem cell transplantation by CT-guided puncture (referred to as CT-guided transplantation). METHODS: The patients were divided into the following three groups to perform a retrospective controlled study: Group A included nine patients who underwent open surgical transplantation, Group B included nine patients who underwent CT-guided transplantation, and Group C included nine patients who did not receive stem cell transplantation. The Abbreviated Injury Scale (AIS), the American Spinal Injury Association (ASIA) score and the motor evoked potentials (MEP) examination were utilized to compare the differences in the clinical efficacies. The advantages and disadvantages of the two transplantation approaches were also compared, including the surgical risks, the possibility of repeating the operation, the interval between surgery and rehabilitation exercises and the scope of conditions suitable for the operation. RESULTS: Whether evaluated by the AIS grading scale, the ASIA score or the MEP results, there were significant differences in the clinical efficacy among the three patient groups. Group B exhibited the best clinical outcome, followed by Group A, and Group C fared the worst. The CT-guided transplantation had the advantages of lower surgical risk, the potential to repeat the operations within a short time-frame and a short interval between surgery and rehabilitation exercise compared with the open surgical transplantation. The conditions that are suitable for CT-guided transplantation versus the conditions suitable for open surgical transplantation are not identical. The application scopes for the two approaches had their respective strengths. CONCLUSIONS: CT-guided stem cell transplantation was confirmed as a safe and effective approach to treat sequelae of spinal cord injury with the advantages of simpler operation, minimal invasion, less adverse reaction and quicker recovery. CLINICAL TRIALS REGISTRATION NUMBER: ChiCTR-TNRC-12002477.

Protective effect of human umbilical cord mesenchymal stem cell derived conditioned medium in a mutant TDP-43 induced motoneuron-like cellular model of ALS.

Amyotrophic lateral sclerosis (ALS) is a multi-factor neurodegenerative disease, characterized by the loss of motor neurons. TAR DNA-binding protein 43 (TDP-43) mutation, accumulation and aggregation, as well as oxidative stress are recognized as major pathological denominators and biochemical markers for ALS. Recently, human umbilical cord mesenchymal stem cell-derived conditioned medium (UC-CM) has been introduced to treat ALS patients. However, there is no research for the protective effect of UC-CM on the TDP-43 model of ALS. In this study, we evaluated the potential neuroprotective effect of UC-CM on a cellular ALS model expressing TDP-43mutant M337V, as well as its underlying mechanism. We found that 24 h UC-CM treatment could protect M337V expressing motor neurons by increasing cell viability and reducing LDH leakage. Furthermore, the aggregation of M337V, generation of ROS, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), protein carbonyl and 8-OHdG were also reduced by UC-CM, indicating that UC-CM protected cells by reducing oxidative damage. Moreover, UC-CM significantly increased the expression of nuclear Nrf2 and its downstream enzyme HO1. The Nrf2 translocation inhibitor ML385 could inhibit the effect of UC-CM on the cell viability and aggregate of M337V. Our results suggest that UC-CM protect cells against M337V expression by its strong antioxidative effect via Nrf-2/HO-1 axis activation.

Umbilical cord mesenchymal stem cell-conditioned medium inhibits microglial activation to ameliorate neuroinflammation in amyotrophic lateral sclerosis mice and cell models.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease for which few effective therapeutic strategies are available. Increasing evidence indicates that neuroinflammation plays a significant role in ALS pathogenesis. Mesenchymal stem cell (MSC)-based therapy has been proposed for the treatment of neurodegenerative diseases, including ALS. In this study, we first demonstrated that systemic administration of conditioned medium derived from umbilical cord MSCs (UCMSC-CM) extends the lifespan of transgenic SOD1-G93A mice, a well-characterized model of familial ALS. Moreover, UCMSC-CM inhibits microglial activation and astrogliosis and alleviates the inflammatory milieu by reducing the release of proinflammatory cytokines and the expression of iNOS in the spinal cord. Using BV-2 cells overexpressing the SOD1-G93A mutant as an ALS cellular model, we uncovered that UCMSC-CM also suppresses the lipopolysaccharide (LPS)-induced inflammatory response, including reduced expression of proinflammatory cytokines and iNOS. Importantly, by culturing astrocytes alone in microglia-conditioned medium (MCM) or together with microglia in a transwell coculture system, we found that UCMSC-CM modulates the secretome of microglia exposed to inflammatory stimuli, thereby preventing the conversion of astrocytes to the A1 neurotoxic phenotype. This study revealed the anti-inflammatory properties of UCMSC-CM and its regulatory effect on glial activation in the treatment of neuroinflammation in ALS, providing strong evidence for the clinical application of UCMSC-CM.