Severe epistaxis after posterior nasal nerve ablation requiring surgical intervention: A multi-center case series.

KEY POINTS: Severe epistaxis occurs in 2% of PNN ablation cases, independent of method or device type. Major epistaxis requiring intervention after PNN ablation can occur on average 20 days post-procedure.

Transcatheter aortic valve replacement: Past, present, and future.

Transcatheter aortic valve replacement (TAVR) has emerged as a ground-breaking, minimally invasive alternative to traditional open-heart surgery, primarily designed for elderly patients initially considered unsuitable for surgical intervention due to severe aortic stenosis. As a result of successful large-scale trials, TAVR is now being routinely applied to a broader spectrum of patients. In deciding between TAVR and surgical aortic valve replacement, clinicians evaluate various factors, including patient suitability and anatomy through preprocedural imaging, which guides prosthetic valve sizing and access site selection. Patient surgical risk is a pivotal consideration, with a multidisciplinary team making the ultimate decision in the patient's best interest. Periprocedural imaging aids real-time visualization but is influenced by anaesthesia choices. A comprehensive postprocedural assessment is critical due to potential TAVR-related complications. Numerous trials have demonstrated that TAVR matches or surpasses surgery for patients with diverse surgical risk profiles, ranging from extreme to low risk. However, long-term follow-up data, particularly in low-risk cases, remains limited, and the applicability of published results to younger patients is uncertain. This review delves into key TAVR studies, pinpointing areas for potential improvement while delving into the future of this innovative procedure. Furthermore, it explores the expanding role of TAVR technology in addressing other heart valve replacement procedures.

De Garengeot's hernia: A masked abdominal perforation.

INTRODUCTION: de Garengeot's hernias occur when an inflamed appendix is encased within a femoral sac. This is a relatively rare type of femoral hernia. As a result, there are currently no guidelines for the management of these hernias. CASE: We present a 90-year-old woman with a de Garengeot's hernia complicated with strangulation and perforation. The diagnosis was made intraoperatively, and it was managed with hernia repair and an appendicectomy. There were no postoperative complications. DISCUSSION: The presentation of de Garengeot's hernias is non-specific. Enclosure of the bowel content within the hernia sac may mask systemic systems of disease. Rarely, septic signs or symptoms are identified on presentation. It is typically diagnosed intraoperatively, thus prompt emergency surgery should not be delayed by clinicians awaiting precise knowledge of the sac content via imaging. Prompt surgery with a single McEvedy incision enables treatment for both the appendicitis and abdominal wall defect, an appendectomy and hernia repair, respectively. In patients that present with an irreducible femoral hernia and biochemistry suggestive of an acute inflammatory process, there should be a high clinical suspicion for de Garengeot's hernia due to the risk of perforation being masked by an anatomical encasement around the perforated bowel content.

Intramedullary spinal cord metastasis treated with prophylactic laminoplasty prior to radiation to the spinal cord: a case report.

Background: A cervical laminoplasty is a surgical procedure used to treat moderate-to-severe cervical stenosis resulting in cervical myelopathy. It is performed to widen the spinal canal and reduce compression on the spinal cord and surrounding nerves. Though often performed electively on patients presenting with varying degrees of neurologic dysfunction including weakness and imbalance, it may also be used prophylactically when spinal cord inflammation or edema is anticipated. Radiotherapy in the spinal cord is known to produce radiation-induced damage leading to radiation myelopathy. Case Description: We present the case of a 62-year-old male diagnosed with both cervical stenosis and an intramedullary cervical spinal cord metastatic tumor. This patient presented with significant symptoms including limited mobility, numbness, lower back pain, paresthesia, and spasms in both legs as well as worsening sexual function. Given that the patient was to undergo radiotherapy, a cervical laminoplasty was performed to eliminate ongoing spinal cord compression as well to prevent future neurologic decline resulting from post-radiation inflammation and edema. Conclusions: This case highlights that cervical laminoplasty can be performed safely and effectively with significant improvement in patients with metastatic disease. By treating the underlying symptomatic stenosis, and protect the patient from the potential for spinal cord edema from radiation to a spinal cord lesion in an already narrow spinal canal.

Case report: A rare occurrence of triple malignancy of the stomach, rectum and liver in a single patient.

Malignant tumors of the digestive system are common worldwide; however, it is extremely rare for more than two malignancies to occur simultaneously. Here, we report a case with a triple malignancy of the digestive system, including gastric, rectal, and hepatic tumors. The patient underwent surgical resection of three tumors followed by chemotherapy. Negative image-based screenings and the absence of serum tumor biomarkers elevation were found at 2.5 years after the surgery, indicating the absence of recurrence and metastasis of cancers.

Amyloid-Tau-Neurodegeneration Profiles and Longitudinal Cognition in Sporadic Young-Onset Dementia.

We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A- N+, and A- N- profiles via cerebrospinal fluid amyloid-ß1-42 (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration- N), and confluent white matter hyperintensities cerebrovascular disease (CVD). A, T, and CVD effects on longitudinal Mini-Mental State Examination (MMSE) were evaluated. A+N+ patients demonstrated steeper MMSE decline than A- N+ (ß = 1.53; p = 0.036; CI 0.15:2.92) and A- N- (ß = 4.68; p = 0.001; CI 1.98:7.38) over a mean follow-up of 1.24 years. Within A- N+, T- CVD+ patients showed greater MMSE decline compared to T+CVD- patients (ß = - 2.37; p = 0.030; CI - 4.41:- 0.39). A+ results in significant cognitive decline, while CVD influences longitudinal cognition in the A- sub-group.

Activation of GLP-1 receptor signalling by sacubitril/valsartan: Implications for patients with poor glycaemic control.

Sacubitril/valsartan is a first-in-class Angiotensin Receptor-Neprilysin inhibitor (ARNi) to be approved for the treatment of heart failure with reduced ejection fraction (HFrEF). The combination tablet has become a mainstay of treatment in the management of heart failure (HF) due to its composite inhibition of the neurohumoral system. There is growing support to show that sacubitril/valsartan may enhance glycaemic control through the augmentation of neprilysin substrates - in particular, glucagon-like peptide 1 (GLP-1). Given that HF and Diabetes Mellitus (DM) frequently coexist, with 44% of patients hospitalised with heart failure also having diabetes as a co-morbidity, it is plausible that sacubitril/valsartan may represent a novel way to address glucose intolerance in HF. However, the role of neprilysin in the degradation of GLP-1 raises important clinical considerations such as the risk of hypoglycaemia and potential drug-drug interactions in patients with and without concurrent DM. We review the current body of research addressing the effect of neprilysin inhibition on GLP-1 receptor signalling and discuss the implications for treatment of HF and DM.

Improved Electrophile Design for Exquisite Covalent Molecule Selectivity.

Covalent inhibitors are viable therapeutics. However, off-target reactivity challenges the field. Chemists have attempted to solve this issue by varying the reactivity attributes of electrophilic warheads. Here, we report the development of an approach to increase the selectivity of covalent molecules that is independent of warhead reactivity features and can be used in concert with existing methods. Using the scaffold of the Bruton's tyrosine kinase (BTK) inhibitor Ibrutinib for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but retain rates of cysteine reactivity comparable to that of an acrylamide. Using chemical proteomic techniques, we demonstrate that elaboration of the electrophile to a tert-butyl (t-Bu) fumarate ester decreases time-dependent off-target reactivity and abolishes time-independent off-target reactivity. While an alkyne-bearing probe analogue of Ibrutinib has 247 protein targets, our t-Bu fumarate probe analogue has only 7. Of these 7 targets, BTK is the only time-independent target. The t-Bu inhibitor itself is also more selective for BTK, reducing off-targets by 70%. We investigated the consequences of treatment with Ibrutinib and our t-Bu analogue and discovered that only 8 proteins are downregulated in response to treatment with the t-Bu analogue compared to 107 with Ibrutinib. Of these 8 proteins, 7 are also downregulated by Ibrutinib and a majority of these targets are associated with BTK biology. Taken together, these findings reveal an opportunity to increase cysteine-reactive covalent inhibitor selectivity through electrophilic structure optimization.

Mechanisms underlying the therapeutic potential of mesenchymal stem cells in atherosclerosis.

Atherosclerosis is a chronic inflammatory condition resulting in the formation of fibrofatty plaques within the intimal layer of arterial walls. The identification of resident stem cells in the vascular wall has led to significant investigation into their contributions to health and disease, as well as their therapeutic potential. Of these, mesenchymal stem cells (MSCs) are the most widely studied in human clinical trials, which have demonstrated a modulatory role in vascular physiology and disease. This review highlights the most recent knowledge surrounding the cell biology of MSCs, including their origin, identification markers and differentiation potential. The limitations concerning the implementation of MSC therapy are considered and novel solutions to overcome these are proposed.

Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging.

Aging is a fundamental biological process accompanied by a general decline in tissue function. Indeed, as the lifespan increases, age-related dysfunction, such as cognitive impairment or dementia, will become a growing public health issue. Aging is also a great risk factor for many age-related diseases. Nowadays, people want not only to live longer but also healthier. Therefore, there is a critical need in understanding the underlying cellular and molecular mechanisms regulating aging that will allow us to modify the aging process for healthy aging and alleviate age-related disease. Here, we reviewed the recent breakthroughs in the mechanistic understanding of biological aging, focusing on the adenosine monophosphate-activated kinase (AMPK), Sirtuin 1 (SIRT1) and mammalian target of rapamycin (mTOR) pathways, which are currently considered critical for aging. We also discussed how these proteins and pathways may potentially interact with each other to regulate aging. We further described how the knowledge of these pathways may lead to new interventions for antiaging and against age-related disease.

Long QT syndrome type 2: mechanism-based therapies.

Long QT syndrome type 2 is a life-threatening disorder of cardiac electrophysiology. It can lead to sudden cardiac death as a result of QT prolongation and can remain undetected until it presents clinically in the form of life-threatening cardiac arrythmias. Current treatment relies on symptom management largely through the use of ß-adrenergic blockade and presently no mechanism-based therapies exist to treat the dysfunction in the hERG channels responsible for the rapid delayed rectifier K+ current which is the pathological source of long QT syndrome type 2. We review the pathophysiology, diagnosis and current management of this life-threatening condition and also analyze some promising potential mechanism-based therapies.

Lay abstract Long QT syndrome is a condition which is characterized by an abnormally lengthened time period of electrical activity in the heart. This abnormality can result in the initiation of heart rhythms which can cause the patient to lose consciousness or cause the patient to enter a heart rhythm which is not conducive to life resulting in sudden cardiac death. In this article we look more closely at a subtype of this disease known as long QT syndrome type 2. We look at how this disease can cause sudden cardiac death, how it is currently managed and how future treatments may be able to work at a genetic and cellular level to reverse the disease-causing mechanisms behind this life-threatening syndrome.

Swallowing dysfunction following radiation to the rat mylohyoid muscle is associated with sensory neuron injury.

Radiation-based treatments for oropharyngeal and hypopharyngeal cancers result in impairments in swallowing mobility, but the mechanisms behind the dysfunction are not clear. The purpose of this study was to determine if we could establish an animal model of radiation-induced dysphagia in which mechanisms could be examined. We hypothesized that 1) radiation focused at the depth of the mylohyoid muscle would alter normal bolus transport and bolus size and 2) radiation to the mylohyoid muscle will induce an injury/stress-like response in trigeminal sensory neurons whose input might modulate swallow. Rats were exposed to 48 or 64 Gy of radiation to the mylohyoid given 8 Gy in 6 or 8 fractions. Swallowing function was evaluated by videofluoroscopy 2 and 4 wk following treatment. Neuronal injury/stress was analyzed in trigeminal ganglion by assessing activating transcription factor (ATF)3 and GAP-43 mRNAs at 2, 4, and 8 wk post treatment. Irradiated rats exhibited decreases in bolus movement through the pharynx and alterations in bolus clearance. In addition, ATF3 and GAP-43 mRNAs were upregulated in trigeminal ganglion in irradiated rats, suggesting that radiation to mylohyoid muscle induced an injury/stress response in neurons with cell bodies that are remote from the irradiated tissue. These results suggest that radiation-induced dysphagia can be assessed in the rat and radiation induces injury/stress-like responses in sensory neurons.NEW & NOTEWORTHY Radiation-based treatments for head and neck cancer can cause significant impairments in swallowing mobility. This study provides new evidence supporting the possibility of a neural contribution to the mechanisms of swallowing dysfunction in postradiation dysphagia. Our data demonstrated that radiation to the mylohyoid muscle, which induces functional deficits in swallowing, also provokes an injury/stress-like response in the ganglion, innervating the irradiated muscle.

Cytokine and Growth Factor Response in a Rat Model of Radiation Induced Injury to the Submental Muscles.

Submental muscles (i.e., mylohyoid and geniohyoid) play a vital role during swallowing, protecting the airway from ingested material. To design therapies to reduce the functional deficits associated with radiation treatment relies in part on our understanding of the changes in the cytokine and growth factor response that can impact muscle function. The purpose of this study is to quantify changes in the inflammatory, pro-fibrotic, and pro-angiogenic factors following 48 Gy of fractionated radiation to the mylohyoid muscle. We hypothesized that (1) irradiation will provoke increases in TGF-1ß and MMP-2 mRNA in the mylohyoid muscle; and (2) muscles surrounding the target location (i.e., geniohyoid and digastric muscles) will exhibit similar alterations in their gene expression profiles. Rats were exposed to 6 fractions of 8 Gy using a 6 MeV electron beam on a clinical linear accelerator. The highest dose curve was focused at the mylohyoid muscle. After 2- and 4-weeks post-radiation, the mylohyoid, geniohyoid, and digastric muscles were harvested. Expression of TNF-α, IFNγ, IL-1ß, IL-6, TGF-1ß, VEGF, MMP-2, and MMP-9 mRNA was analyzed via PCR and/or RT-PCR. TGF-1ß, MMP-2, and IL-6 expression was upregulated in the irradiated mylohyoid compared to non-irradiated controls. No notable changes in TNF-α, IFNγ, and IL-1ß mRNA expression were observed in irradiated muscles. Differing expression profiles were found in the surrounding muscles post-radiation. Results demonstrated that irradiation provokes molecular signals involved in the regulation of wound healing, which could lead to fibrosis or atrophy in the swallowing muscle after radiation.

Combined effect of interventions with pure or enriched mixtures of (poly)phenols and anti-diabetic medication in type 2 diabetes management: a meta-analysis of randomized controlled human trials.

PURPOSE: (Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of (poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes. METHODS: A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol. RESULTS: Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (- 3.32 mg/dL; 95% CI - 5.86, - 0.77; P = 0.011). Hb1Ac was only slightly reduced (- 0.24%; 95% CI - 0.43, - 0.044; P = 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (- 5.86 mg/dL, 95% CI - 11.34, - 0.39; P = 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (- 10.17 mg/dL, 95% CI - 16.59, - 3.75; P = 0.002). CONCLUSIONS: Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.

Assessing the Variability and Quality of Lung Stereotactic Radiation Therapy Treatment Plans Using a Web-Based Crowdsourcing Platform.

PURPOSE: The quality of stereotactic body radiation therapy (SBRT) treatment plans for early stage lung cancer are unknown outside of peer-reviewed publications. Thus, a study was conducted to crowdsource and analyze a variety of lung SBRT treatment plans from around the world. METHODS AND MATERIALS: This study had 2 parts, planning and contouring, and each was facilitated by a web-based technology platform. For planning, lung SBRT planners were invited to design, score, and submit their treatment plans (prescription of 11 Gy × 5) for a centralized stage I lung cancer case using standardized images and predefined contours. Each plan was scored with 20 weighted metrics adapted from currently recruiting phase 3 lung SBRT trials. For contouring, a separate image set was used to evaluate organ-at-risk contour accuracy using Dice coefficients and a StructSure score. RESULTS: For planning 227 plans were submitted in total with 7 different treatment planning systems and 7 different delivery methods represented. Variability was primarily user driven and not associated with the treatment planning system, delivery modality, total monitor units, or estimated beam-on time. Many of the highest-quality plans required the shortest amount of time to deliver, independent of the delivery technique. For contouring, organ-at-risk contours were frequently over- or undercontoured and often included only the luminal air of the trachea, proximal bronchial tree, and esophagus, even when the mucosal linings were within a few centimeters of the target tumor. CONCLUSIONS: These findings demonstrate the importance of quality assurance to help improve planning and contouring and the value of peer review and comparison. More readily accessible quality evaluation software solutions, such as the one used herein, may help meet this growing need.

Comparison of surface guidance and target matching for image-guided accelerated partial breast irradiation (APBI).

PURPOSE: We investigate the feasibility of surface guided radiation therapy (SGRT) for accelerated partial breast irradiation (APBI) by comparing it with in-room, fan beam kV computed tomography on rails (CTOR) imaging of the targeted region. The uniqueness of our study is that all patients have multiple daily CTOR scans to compare corresponding SGRT AlignRT (VisionRT, United Kingdom) images to. METHODS/MATERIALS: Twelve patients receiving APBI were enrolled in this study. Before each treatment fraction, after patients were setup on tattoos, SGRT was performed using AlignRT, and then target matching was performance using CTOR. The average and maximum difference in shifts between SGRT and CTOR were calculated and analyzed for each patient, so as the correlation between surgical cavity size and shift difference. RESULTS: Our study showed that SGRT agreed well with CTOR for patients with small surgical cavity volume changes (<10%). There were nine patients who had a ≥5 mm maximum shift difference between SGRT and CTOR along any direction, and in two patients the difference was more than 10 mm (one patient with surgical cavity change 44.3% and one patient with 27 cc cavity volume decrease). All patients, except one, had a mean shift difference < 5 mm along any direction. CONCLUSION: For the patients studied here, SGRT appears to be a reasonable and potentially valuable image guidance approach for APBI for patients who experience small changes in surgical cavity volume (<10%) between CT simulation and treatment. However, there is potential for larger alignment errors (up to 11 mm) when using SGRT for patients who experience larger surgical cavity changes.

Calculation of delivered composite dose from Calypso tracking data for prostate cancer: And subsequent evaluation of reasonable treatment interruption tolerance limits.

PURPOSE: In this study we calculate composite dose delivered to the prostate by using the Calypso tracking -data- stream acquired during patient treatment in our clinic. We evaluate the composite distributions under multiple simulated Calypso tolerance level schemes and then recommend a tolerance level. MATERIALS AND METHODS: Seven Calypso-localized prostate cancer patients treated in our clinic were selected for retrospective analysis. Two different IMRT treatment plans, with prostate PTV margins of 5 and 3 mm respectively, were computed for each patient. A delivered composite dose distribution was computed from Calypso tracking data for each plan. Additionally, we explored the dosimetric implications for "worst case" scenarios by assuming that the prostate position was located at one of the eight extreme corners of a 3 or 5 mm "box." To characterize plan quality under each of the studied scenarios, we recorded the maximum, mean, and minimum doses and volumetric coverage for prostate, PTV, bladder, and rectum. RESULTS AND DISCUSSIONS: Calculated composite dose distributions were very similar to the original plan for all patients. The difference in maximum, mean, and minimum doses as well as volumetric coverage for the prostate, PTV, bladder, and rectum were all < 4.0% of prescription dose. Even for worst scenario cases, the results show acceptable isodose distribution, with the exception for the combination of a 3 mm PTV margin with a 5 mm position tolerance scheme. CONCLUSIONS: Calculated composite dose distributions show that the vast majority of dosimetric metrics agreed well with the planned dose (within 2%). With significant/detrimental deviations from the planned dose only occurring with the combination of a 3 mm PTV margin and 5 mm position tolerance, the 3 mm position tolerance strategy appears reasonable, confirming that further reducing prostate PTV margins to 3 mm is possible when using Calypso with a position tolerance of 3 mm.

Towards real-time respiratory motion prediction based on long short-term memory neural networks.

Radiation therapy of thoracic and abdominal tumors requires incorporating the respiratory motion into treatments. To precisely account for the patient's respiratory motions and predict the respiratory signals, a generalized model for predictions of different types of patients' respiratory motions is desired. The aim of this study is to explore the feasibility of developing a long short-term memory (LSTM)-based generalized model for the respiratory signal prediction. To achieve that, 1703 sets of real-time position management (RPM) data were collected from retrospective studies across three clinical institutions. These datasets were separated as the training, internal validity and external validity groups. Among all the datasets, 1187 datasets were used for model development and the remaining 516 datasets were used to test the model's generality power. Furthermore, an exhaustive grid search was implemented to find the optimal hyper-parameters of the LSTM model. The hyper-parameters are the number of LSTM layers, the number of hidden units, the optimizer, the learning rate, the number of epochs, and the length of time lags. The obtained model achieved superior accuracy over conventional artificial neural network (ANN) models: with the prediction window equaling to 500 ms, the LSTM model achieved an average relative mean absolute error (MAE) of 0.037, an average root mean square error (RMSE) of 0.048, and a maximum error (ME) of 1.687 in the internal validity data, and an average relative MAE of 0.112, an average RMSE of 0.139 and an ME of 1.811 in the external validity data. Compared to the LSTM model trained with default hyper-parameters, the MAE of the optimized model results decreased by 20%, indicating the importance of tuning the hyper-parameters of LSTM models to obtain superior accuracies. This study demonstrates the potential of deep LSTM models for the respiratory signal prediction and illustrates the impacts of major hyper-parameters in LSTM models.

Calpain inhibitor MDL28170 improves the transplantation-mediated therapeutic effect of bone marrow-derived mesenchymal stem cells following traumatic brain injury.

BACKGROUND: Studies have shown that transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) protects against brain damage. However, the low survival number of transplanted BMSCs remains a pertinent challenge and can be attributed to the unfavorable microenvironment of the injured brain. It is well known that calpain activation plays a critical role in traumatic brain injury (TBI)-mediated inflammation and cell death; previous studies showed that inhibiting calpain activation is neuroprotective after TBI. Thus, we investigated whether preconditioning with the calpain inhibitor, MDL28170, could enhance the survival of BMSCs transplanted at 24 h post TBI to improve neurological function. METHODS: TBI rat model was induced by the weight-drop method, using the gravitational forces of a free falling weight to produce a focal brain injury. MDL28170 was injected intracranially at the lesion site at 30 min post TBI, and the secretion levels of neuroinflammatory factors were assessed 24 h later. BMSCs labeled with green fluorescent protein (GFP) were locally administrated into the lesion site of TBI rat brains at 24 h post TBI. Immunofluorescence and histopathology were performed to evaluate the BMSC survival and the TBI lesion volume. Modified neurological severity scores were chosen to evaluate the functional recovery. The potential mechanisms by which MDL28170 is involved in the regulation of inflammation signaling pathway and cell apoptosis were determined by western blot and immunofluorescence staining. RESULTS: Overall, we found that a single dose of MDL28170 at acute phase of TBI improved the microenvironment by inhibiting the inflammation, facilitated the survival of grafted GFP-BMSCs, and reduced the grafted cell apoptosis, leading to the reduction of lesion cavity. Furthermore, a significant neurological function improvement was observed when BMSCs were transplanted into a MDL28170-preconditioned TBI brains compared with the one without MDL28170-precondition group. CONCLUSIONS: Taken together, our data suggest that MDL28170 improves BMSC transplantation microenvironment and enhances the neurological function restoration after TBI via increased survival rate of BMSCs. We suggest that the calpain inhibitor, MDL28170, could be pursued as a new combination therapeutic strategy to advance the effects of transplanted BMSCs in cell-based regenerative medicine.