Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

HDAC1 is Involved in Neuroinflammation and Blood-Brain Barrier Damage in Stroke Pathogenesis.

Background: Stroke is a common cause of disability and mortality worldwide; however, effective therapy remains limited. In stroke pathogenesis, ischemia/reperfusion injury triggers gliosis and neuroinflammation that further activates matrix metalloproteinases (MMPs), thereby damaging the blood-brain barrier (BBB). Increased BBB permeability promotes macrophage infiltration and brain edema, thereby worsening behavioral outcomes and prognosis. Histone deacetylase 1 (HDAC1) is a repressor of epigenomic gene transcription and participates in DNA damage and cell cycle regulation. Although HDAC1 is deregulated after stroke and is involved in neuronal loss and DNA repair, its role in neuroinflammation and BBB damage remains unknown. Methods: The rats with cerebral ischemia were evaluated in behavioral outcomes, levels of inflammation in gliosis and cytokines, and BBB damage by using an endothelin-1-induced rat model with cerebral ischemia/reperfusion injury. Results: The results revealed that HDAC1 dysfunction could promote BBB damage through the destruction of tight junction proteins, such as ZO-1 and occludin, after stroke in rats. HDAC1 inhibition also increased the levels of astrocyte and microglial gliosis, tumor necrosis factor-alpha, interleukin-1 beta, lactate dehydrogenase, and reactive oxygen species, further triggering MMP-2 and MMP-9 activity. Moreover, modified neurological severity scores for the cylinder test revealed that HDAC1 inhibition deteriorated behavioral outcomes in rats with cerebral ischemia. Discussion: HDAC1 plays a crucial role in ischemia/reperfusion-induced neuroinflammation and BBB damage, thus indicating its potential as a therapeutic target.

Slow skeletal muscle troponin T acts as a potential prognostic biomarker and therapeutic target for hepatocellular carcinoma.

Slow skeletal muscle troponin T (TNNT1) as a poor prognostic indicator is upregulated in colon and breast cancers. However, the role of TNNT1 in the disease prognosis and biological functions of hepatocellular carcinoma (HCC) is still unclear. The Cancer Genome Atlas (TCGA), real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to evaluate the TNNT1 expression of human HCC. The impact of TNNT1 levels on disease progression and survival outcome was studied using TCGA analysis. Moreover, the bioinformatics analysis and HCC cell culture were used to investigate the biological functions of TNNT1. Besides, the immunoblot analysis and enzyme-linked immunosorbent assay (ELISA) were used to detect the extracellular TNNT1 of HCC cells and circulating TNNT1 of HCC patients, respectively. The effect of TNNT1 neutralization on oncogenic behaviors and signaling was further validated in the cultured hepatoma cells. In this study, tumoral and blood TNNT1 was upregulated in HCC patients based on the analyses using bioinformatics, fresh tissues, paraffin sections, and serum. From the multiple bioinformatics tools, the TNNT1 overexpression was associated with advanced stage, high grade, metastasis, vascular invasion, recurrence, and poor survival outcome in HCC patients. By the cell culture and TCGA analyses, TNNT1 expression and release were positively correlated with epithelial-mesenchymal transition (EMT) processes in HCC tissues and cells. Moreover, TNNT1 neutralization suppressed oncogenic behaviors and EMT in hepatoma cells. In conclusion, TNNT1 may serve as a non-invasive biomarker and drug target for HCC management. This research finding may provide a new insight for HCC diagnosis and treatment.

Risk factors for pressure ulcer recurrence following surgical reconstruction: A cross-sectional retrospective analysis.

Many studies on the recurrence of pressure ulcers after surgical reconstruction have focused on surgical techniques and socioeconomic factors. Herein, we aimed to identify the risk factors of the associated comorbidities for pressure ulcer recurrence. We enrolled 147 patients who underwent pressure ulcer reconstruction and were followed up for more than three years. The recurrence of pressure ulcers was defined as recurrent pressure ulcers with stage 3/4 pressure ulcers. We reviewed and analyzed systematic records of medical histories, including sex, age, associated comorbidities such as spinal cord injury (SCI), diabetes mellitus (DM), coronary artery disease, cerebral vascular accident, end-stage renal disease, scoliosis, dementia, Parkinson's disease, psychosis, autoimmune diseases, hip surgery, and locations of the primary pressure ulcer. Patients with recurrent pressure ulcers were younger than those without. Patients with SCI and scoliosis had higher odds, while those with Parkinson's disease had lower odds of recurrence of pressure ulcers than those without these comorbidities. Moreover, the decision tree algorithm identified that SCI, DM, and age < 34 years could be risk factor classifiers for predicting recurrent pressure ulcers. This study demonstrated that age and SCI are the two most important risk factors associated with recurrent pressure ulcers following surgical reconstruction.

Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations.

Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.

Approaching patients with panfacial fractures by using an anatomical reference: A novel concept and preliminary study.

Panfacial fractures are challenging for craniofacial surgeons. Aside from involving multiple subunits, they also lack the reliability of a useful landmark of the facial skeleton. Properly, reducing and fixing palatal fracture to re-establish the premorbid maxillary dental arch is important. This was a retrospective study conducted from 2015 to 2020. All patients underwent computed tomography (CT) scan for surgical planning of orthognathic surgery due to either esthetic or occlusion concerns. The classification of occlusion was recorded as class I, II, and III. The parameters measured on CT were the distance between the midpoint of the supra-orbital foramen/notch (IS), mesio-buccal cusp tips (IB), central fossa (IC), palatal cusp tips (IP), and the midpoint of the palatal marginal gingiva (IM) of the bilateral maxillary first molars. The IS was compared with the IB, IC, IP, and IM. The results were analyzed by using one-way repeated measurement analysis of variance. Eighty-seven patients (36 men and 51 women) were included in the study. There were 13 patients of class I malocclusion, 8 of class II malocclusion, and 66 of class III malocclusion. The IS was comparable to the IC in all three groups. The IS can predict the IC, regardless of the patient's occlusion, and can be subsequently used to decide the width of maxillary dental arch in panfacial fracture management. Further studies are necessary to obtain more definite results.

Purse-string suture combined with subcision and dermal graft for the treatment of wide depressed scars and boxcars.

BACKGROUND: Dermal layer injuries can result in depressed or indented scars even when there is no subcutaneous injury. These scars can result from acne, chickenpox, trauma, or skin infection. Several procedures, including primary closure, subcision, microneedling, and dermal grafting, have been reported to be used to treat depressed scars, boxcars, or acne cosmetics. These procedures have not, however, been shown to be very effective when applied to the treatment of deep depressed scars, boxcars, or acne cosmetics. In this retrospective study, we assessed scar improvement in patients with deep depressed facial scars and boxcars treated with our novel combination of techniques. METHODS: This study included all patients treated for deep depressed scars and boxcars at our clinic from 2018 to 2021. To be included, patients had to present in our clinic for the treatment of deep depressed scars or boxcars, have no prominent subcutaneous layer injury, and have full set of clear pre-and post-procedure photographs. All patients initially received technique combination including scar subcision, inner purse-string suturing, and dermal grafting for the first stage surgery treatment. In cases of residual uneven superficial scars, laser dermabrasion resurfacing was used as second-staged treatment. Preoperative and six-month postoperative scar appearance photographs were assessed for improvement by our three nonmedical staff members and divided into four improvement groups, as minimal, moderate, good, and excellent. RESULTS: This study included a total of 24 patients (20 females and four males) with facial scarring. Two patients (8.3%) had moderate, 13 (54.2%) good and nine (37.5%) excellent improvement post-treatment. There were no instances of minimal improvement. Four patients received second stage laser dermabrasion resurfacing for residual uneven superficial scars. CONCLUSION: We concluded deep depressed scars and boxcars can be easily, safely, and effectively treated using our novel combined scar subcision, inner purse-string suturing, and dermal grafting treatment with possible second-staged laser dermabrasion, and without major complications.

The Predictability of the Surgical Outcomes of Class III Patients in the Transverse Dimension-A Study of Three-Dimensional Assessment.

This study aimed to assess the outcomes of planned maxillary surgical movements in the transverse direction in patients possessing a Class III skeletal pattern. The available consecutive patients' records were retrospectively reviewed. Only those possessing a Class III skeletal pattern, and for whom the same virtual planning system was used, were enrolled. The waferless technique was used to guide the jawbone repositioning. A representative triangle in the virtual maxilla of each stage was used to validate the planned surgical movements (PSMs) and the outcome discrepancy (OD). The linear and angular measurements were retrieved for the assessments of the correlation between PSM and OD. In total, 44 adult patients who met the inclusion criteria were studied. The average linear OD of the A-point in the transverse direction was 0.66 ± 0.54 mm, and the yaw correction showed 1.02 ± 0.84 degrees in difference. There was no specific correlation between the linear PSMs and ODs; however, the angular ones were positively correlated. With the help of the waferless technique to transfer the virtual planning results, the practitioners could confidently predict the postsurgical maxillary position in the transverse direction in the orthognathic surgery of Class III patients. However, the yaw correction should be carefully planned to avoid postsurgical instabilities.

Repairing Facial Fractures with Interrupted Maxillary-mandibular Arches by Computer-assisted Reverse Planning Model Surgery.

BACKGROUND: Management of comminuted facial fractures with maxillary-mandibular arch interruption is difficult, resulting in inadequate bone reduction and malocclusion. Traditionally, a good quality dental splint is helpful, but difficult to obtain in acute trauma. We apply a computer-assisted design and three-dimensional printing technology to improve splint fabrication and utilization, thus facilitating restoration of dental occlusion and facial fracture. METHODS: We retrospectively reviewed patients who suffered from facial fractures with interruption of the maxillary-mandibular arches. We developed the "computer-assisted reverse planning and three-dimensional printing model surgery" algorithm and applied it in selected patients. An occlusal splint was created as a surgical guide to enhance the maxilla-mandibular unit repair by taking care of the bone reduction and occlusion. All included patients were followed up to assess the functional outcome and patients suitable for this method. RESULTS: From Jan 2015 to Aug 2020, 10 patients (eight men and two women) with comminuted facial fractures were included. The average time of surgery was 9.2 days. The average follow-up time was 8.6 months. There was no patient who needed major revision to correct malocclusion or facial asymmetry. CONCLUSIONS: A computer-assisted design splint decreases intraoperative inaccuracies and difficulty in comminuted maxillo-mandibular fractures. It is a useful and reliable alternative. Collaboration with an experienced engineer and patient selection are indispensable in delivering successful outcomes. Patients who have more than three bone fragments in a single dental arch or more than four bone fragments in the entire maxillary-mandibular unit appear to be excellent candidates for this method.

Smoking Status and Functional Outcomes in Young Stroke.

Objective: Stroke in young adults is uncommon, and the etiologies and risk factors of stroke in young adults differ from those in older populations. Smoker's paradox is an unexpected favorable outcome, and age difference is used to explain the association between smoking and the favorable functional outcome. This study aimed to investigate the existence of this phenomenon in young stroke patients. Methods: We analyzed a total of 9,087 young stroke cases registered in the nationwide stroke registry system of Taiwan between 2006 and 2016. Smoking criteria included having a current history of smoking more than one cigarette per day for more than 6 months. After matching for sex and age, a Cox model was used to compare mortality and function outcomes between smokers and non-smokers. Results: Compared with the non-smoker group, smoking was associated with older age, higher comorbidities, and higher alcohol consumption. Patients who report smoking with National Institutes of Health Stroke Scale scores of 11-15 had a worse functional outcome (adjusted odds ratio, 0.81; 95% confidence interval, 0.76 - 0.87). Conclusion: Smokers had a higher risk of unfavorable functional outcomes at 3 months after stroke, and therefore, we continue to strongly advocate the importance of smoking cessation.

Three-Dimensional Outcome Assessments of Surgical Correction in Cleft and Noncleft Patients with Class III Skeletal Relation: A Case-Control Study.

BACKGROUND: The orthognathic strategies to treat patients with a concave profile but different tissue conditions remain controversial. The aim of this case-control study was to investigate the outcome predictability of orthognathic surgery in cleft lip and palate (CLP) patients and matched controls. METHODS: Fifty consecutive CLP and 45 matched non-CLP patients who received whole-piece Le Fort I and bilateral sagittal split osteotomy to correct class III skeletal relations were enrolled. The outcome discrepancies (ODs) from simulations among all groups were evaluated with consideration of the possible influences from planned surgical movements (PSM). Receiver operating characteristic curves were used to determine threshold values of PSMs that yielded clinically relevant OD. RESULTS: Unilateral CLP (UCLP) patients had comparable postsurgical OD to non-CLP patients in both jaws, whereas bilateral CLP (BCLP) patients had greater deviations from predicted results. Vertical movement of the A - point > 1.33 mm and yaw correction > 1.65° in the BCLP patients was associated with clinically relevant maxillary OD. CONCLUSIONS: The OGS outcomes of BCLP patients were less predictable than those of the UCLP and noncleft patients. Vertical movements of the A - point > 1.33 mm and yaw correction > 1.65° in BCLP patients increased OD to a clinically relevant extent.

Silicone Breast Implant Injector: A Retooled Breast Augmentation Device.

Silicone breast implants are used worldwide for breast augmentation. After an axillary, periareolar or inframmary incision has been made to create an adequately sized pocket; the surgeon usually uses his or her fingers to insert the implant. The use of fingers makes the insertion process time-consuming, a few minutes or more. There are some complications, including need to ensure that the incision is long enough for the implant to be inserted, scar hypertrophy caused by implant insertion friction damage to the edge of incision, and the occasional need to ask the surgical assistant to lend more fingers to facilitate satisfactory insertion and placement. In addition, the use of gloved fingers to repeatedly push on the implant can increase the risk of contamination, postoperative silicone microleakage, and capsular contracture. To resolve these problems, we developed an improved silicone breast implant injector (reusable stainless steel 2007; single use polypropylene 2018) that can be used more easily than fingers and other "no touch" devices. From 2013 to 2017, the first author, a plastic surgeon at our clinic, used the 2007 reusable stainless steel injector to perform breast augmentations in 53 patients (Ave. age 23.8 years; range 19-67 years), 5 (8.8%) receiving 250-ml implants, 41 (77.4%) 251-300-ml implants, and 7 (13.8%) 301-400-ml implants. Overall, results were satisfactory except for two patients (3.7%) in whom capsular contracture occurred. There were no ruptures. Use of the injector made it possible to shorten the length of the incisions from the traditional 4-7 to 3-4 cm and expedited insertion time from a few minutes to a few seconds. This "no touch" insertion technique reduced implant damage caused by finger pushing, leading to a decrease in silicone microleakage and capsular contracture rate. It was performed with no friction trauma to the incision edge or harm to the surgeon's fingers. It was found to be an effective alternative operative tool for the insertion of silicone breast implants.Level of evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Velar Closing Ratio As a Predictor for the Verlopharyngeal Function After Double Opposing Z-Plasty for Postpalatoplasty Velopharyngeal Insufficiency in Patients With Cleft Palate.

BACKGROUND: This study was designed to identify the potential predictors of postoperative velopharyngeal function after double opposing Z-plasty (DOZP) for the treatment of velopharyngeal insufficiency (VPI) in patients who had prior palatoplasty for cleft palate. METHODS: This retrospective study reviewed the medical records of consecutive patients who received DOZP for VPI after receiving a prior palatoplasty treating cleft palate between 2004 and 2017. The speech outcome of patient was measured using the Pittsburgh Weighted Speech Scale (PWSS) at 6 months following surgery and determined the outcome suggests velopharyngeal competence (PWSS ≤2) or incompetence (PWSS >2). Stepwise logistic regression was used to identify the variables for the prediction of competent surgical outcome. The specific receiver operating characteristic curves with an area under the curve (AUC) was used to evaluate the predictor related to the surgical outcome as competence. RESULTS: The study included 93 patients. Age, relative velar length, velar lengthening, and closure pattern were not significantly associated with postoperative competence status of the patient. The only variable that predicted a successful surgical outcome was preoperative velar closing ratio. However, the accuracy of velar closing ratio in predicting a competent surgical outcome is only moderate (AUC = 70.37). CONCLUSION: The results of this study showed that preoperative velar closing ratio may predict, with moderate accuracy, a successful surgical outcome in patients with postpalatoplasty VPI who undergo DOZP. Therefore, in patients with a low preoperative velar closing ratio, some alternative surgical methods other than DOZP may be considered to avoid unsatisfactory surgical outcome.

Synthetic α5ß1 integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke.

Ischemic stroke is the leading cause of disability and death worldwide. An effective therapeutic approach is urgently needed. Stroke-induced angiogenesis and neurogenesis are essential mechanisms in the long-term repair. Extracellular matrix proteins are also involved in tissue self-repair. Recently, a PHSRN (Pro-His-Ser-Arg-Asn) peptide from the fibronectin synergistic motif that can promote wound healing in epithelia and induce endothelial proliferation and cancer cell migration was identified. The therapeutic potential of this peptide in stroke is unknown. Here, we examined the potential of PHSRN in stroke therapy using an ischemic rat model of middle cerebral artery occlusion (MCAO). PHSRN reduced the infarct volume in MCAO rats, improved neurological function, and alleviated motor function impairment. PHSRN targeted the damaged brain region and distributed to endothelial cells after intraperitoneal injection. PHSRN significantly promoted angiogenesis and vascular endothelial growth factor secretion through activation of integrin α5ß1 and its downstream intracellular signals, e.g., focal adhesion kinase, Ras, cRaf, and extracellular-signal-regulated kinase. PHSRN treatment also stimulated neurogenesis in MCAO rats, and maintained neuronal survival and neuronal morphologic complexity via induction of VEGF secretion. Together, these results provide insights into the role of integrin α5ß1 following ischemia and support the feasibility of using PHSRN peptide in stroke therapy.

Repair of the Nasal Floor by the Cleft Margin Flap in Bilateral Complete Cleft Lip.

Bilateral complete cleft lip deformity has been the most challenging to plastic surgeons, and lots of methods of repair have been described in the literature. The basic principles are to achieve continuity of the orbicularis oris muscle, a balanced Cupid's bow with nasal ala, and a complete reconstruction of the nasal floor. The last one is, however, easily neglected. A well-reconstructed nasal floor serves as a good support of the nasal cartilage, which minimizes secondary deformity. In addition, a nasal floor with sufficient soft tissue and minimal contracture makes bone grafting easier in the future. The cleft margin flap was first introduced by Tajima in 1983 and used for the nasal floor repair in the unilateral complete cleft lip. The authors have used this technique in bilateral complete cleft lip repair, and from our practice, tension-free repairs of the nasal floors could easily be achieved by the cleft margin flaps. The results were satisfying and no significant scar contracture or deformity of the nasal floor was observed during follow-up. The authors conclude that the cleft margin flaps are viable and alternative choices for the repair of the nasal floors in bilateral complete cleft lip without major complications.

Frontal Hyperostosis in the Patients of Craniosynostosis After Cranial Distraction Osteogenesis.

BACKGROUND: Conventional fronto-orbital advancement and distraction osteogenesis (DOG) have been used to treat craniosynostosis, both of which are considered effective. During the authors' practice, a phenomenon of frontal hyperostosis has been observed in the patients of craniosynostosis after DOG, which has yet to be reported in the literature. The purpose of this study is trying to identify the factors related to the phenomenon. MATERIALS AND METHODS: From 1997 to 2010, all patients of craniosynostosis undergoing DOG were reviewed. The patient's age at operation, consolidation period, numbers of distractor, distance of distraction, and duration from removal of the distractors to identification of the phenomenon on computed tomography were recorded. The phenomenon was considered positive when the hyperostosis appeared on the frontal bone, where it was neither the osteotomy site nor the previous position of distractor. RESULTS: A total of 61 patients were included in this study, including 26 syndromic and 35 nonsyndromic patients. Two syndromic and 6 nonsyndromic patients had the phenomenon. There was no statistical difference between the patients with and without the phenomenon in comparison with the age, number of the distractor, consolidation period, and the distance of distraction. CONCLUSION: Frontal hyperostosis happened in some patients of craniosynostosis after DOG. Although no significant difference was demonstrated, the incidence of hyperostosis was higher in nonsyndromic patients and the patients of hyperostosis had shorter distance of distraction in both syndromic and nonsyndromic groups. Although the definite cause was unknown, we should pay attention to the phenomenon after distraction.

Ankylosis of temporomandibular joints after mandibular distraction osteogenesis in patients with Nager syndrome: Report of two cases and literature review.

Nager syndrome, also known as Nager acrofacial dysostosis, was first described by Nager and de Reynier in 1948. The patients commonly present with micrognathia, and a preventive tracheostomy is necessary when there are symptoms of upper airway obstruction. Mandibular distraction osteogenesis is considered as an effective procedure, which not only improves micrognathia but also minimizes the chances of tracheostomy. However, mandibular distraction osteogenesis has some complications such as relapse, teeth injury, infection, and injury of the temporomandibular joints (TMJs). In this study, the author reported two patients with Nager syndrome who suffered from ankylosis of TMJs after mandibular distraction osteogenesis. In addition, a comprehensive literature review of post-distraction ankylosis of TMJs in patients with Nager syndrome was performed. Few studies demonstrated the condition of TMJs after mandibular distraction osteogenesis, and three studies were identified from the review. One study reported ankylosis of bilateral coronoid processes, in which coronoidectomies were necessary. Another study reported the use of prostheses to replace the ankylosed joints in a patient who had undergone many surgeries of the joints, such as gap arthroplasties, reconstructions with costochondral grafts, etc. One other study raised the concept of unloading the condyles during the mandibular distraction to prevent subsequent ankylosis. It seems that multiple factors are related to the ankylosis of TMJs after mandibular distraction osteogenesis in patients with Nager syndrome. Prevention of post-distraction ankylosis of the joints is important because the treatment is difficult and not always effective. We should conduct more studies about protection of the joints during mandibular distraction in the future.

G-CSF-mobilized Bone Marrow Mesenchymal Stem Cells Replenish Neural Lineages in Alzheimer's Disease Mice via CXCR4/SDF-1 Chemotaxis.

Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment can improve the cognitive function of Alzheimer's disease (AD) mice, and the mobilized hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown. Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic effects, which was involved in the recruitment of repair-competent cells. Furthermore, we found both mobilized HSCs and BM-MSCs were able to infiltrate into the brain, but only BM-MSCs replenished the neural lineage cells and contributed to neurogenesis in the brains of AD mice. Together, our data show that mobilized BM-MSCs are involved in the replenishment of neural lineages following G-CSF treatment via CXCR4/SDF-1 chemotaxis and further support the potential use of BM-MSCs for further autogenically therapeutic applications.

Gain of BDNF Function in Engrafted Neural Stem Cells Promotes the Therapeutic Potential for Alzheimer's Disease.

Stem cell-based therapy is a potential treatment for neurodegenerative diseases, but its application to Alzheimer's disease (AD) remains limited. Brain-derived neurotrophic factor (BDNF) is critical in the pathogenesis and treatment of AD. Here, we present a novel therapeutic approach for AD treatment using BDNF-overexpressing neural stem cells (BDNF-NSCs). In vitro, BDNF overexpression was neuroprotective to beta-amyloid-treated NSCs. In vivo, engrafted BDNF-NSCs-derived neurons not only displayed the Ca(2+)-response fluctuations, exhibited electrophysiological properties of mature neurons and integrated into local brain circuits, but recovered the cognitive deficits. Furthermore, BDNF overexpression improved the engrafted cells' viability, neuronal fate, neurite complexity, maturation of electrical property and the synaptic density. In contrast, knockdown of the BDNF in BDNF-NSCs diminished stem cell-based therapeutic efficacy. Together, our findings indicate BDNF overexpression improves the therapeutic potential of engrafted NSCs for AD via neurogenic effects and neuronal replacement, and further support the feasibility of NSC-based ex vivo gene therapy for AD.

Autoclaved metal-on-cement spacer versus static spacer in two-stage revision in periprosthetic knee infection.

BACKGROUND: Periprosthetic knee infection is troublesome for Orthopedic surgeons and a catastrophy for patients. Reported rates of periprosthetic joint infection following primary total knee arthroplasty (TKA) are 0.39-2%. Two stage revision arthroplasty, which has success rates exceeding 90%, has been the gold standard for treating subacute and chronic periprosthetic infection following TKA. Antibiotic spacers, a well established means of delivering local antibiotic therapy, maintain soft tissue tension during two stage revision arthroplasty. However, controversy remains around whether static or mobile antibiotic impregnated spacers are superior for treating infection following TKA. Various mobile spacers are available, including cement-on-cement, cement-on-polyethylene and metal-on-polyethylene. In this study, the efficacy of the modified metal-on-cement spacer, consisting of reinsertion of the autoclaved femoral component and implantation of antibiotic-loaded cement in the proximal tibia, is assessed. MATERIALS AND METHODS: Records of 19 patients diagnosed as periprosthetic knee infection were reviewed in this retrospective study. Among these patients, 10 patients received first stage debridement with the autoclaved metal-on-cement spacer and 8 patients with the static spacer, who eventually underwent two-stage re-implantation, were listed in the final comparison. Patient demographics, infection eradication rates, average range of motion (ROM), surgical time and blood loss during the second-stage of the surgery, and Knee Society (KS) knee scores at last followup after revision total knee replacement were clinically evaluated. RESULTS: At a minimum of 2-year followup after re-implantation, infection eradication rates, surgical times, blood loss during the second-stage of the surgery, and KS knee score after re-implantation were similar for the two groups. Patients receiving autoclaved metal-on-cement spacers had superior ROM after re-implantation compared to that of patients with static spacers. CONCLUSIONS: The autoclaved metal-on-cement spacer is an effective and simple method for two-stage re-implantation of a periprosthetic knee infection. Through this spacer, the good interim ROM can be achieved without the additional cost of prefabricated molds or new polyethylene tibial inserts. In addition, ROM after re-implantation is better than that with static spacers.