Adipose-derived stem cell modulate tolerogenic dendritic cell-induced T cell regulation is correlated with activation of Notch-NFκB signaling.

BACKGROUND: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs. METHODS: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs. RESULTS: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway). CONCLUSIONS: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application.

Turbocharging as a strategy to boost extended perforator flap vascularity in head and neck reconstruction-A report of two cases.

Perforator flap has been applied as the most common flap for soft tissue defect reconstruction. Here, we presented two cases using turbocharging procedure of perforator to perforator as a salvage strategy. The first case was a 54-year-old male with recurrent squamous cell carcinoma (SCC) in the left buccal area and mouth floor. A 6 × 22 cm posteromedial thigh (PMT) flap was designed for reconstruction. The two eccentric perforators of the PMT flap could not conjoin together during dissection nearby the main pedicle of profunda femoral artery (PFA) resulting in inadequate perfusion. Side branched stump before clipped the branch of distal perforator was preserved, then the proximal perforator was divided and end-to-end anastomosis of side branch of distal perforator was done successfully. The second case was a 52-year-old male underwent wide composite excision of right tongue SCC. After excision, anterolateral thigh (ALT) flap around 7 × 15 cm was harvested from left thigh and two perforators were included which one tiny perforator supplied by the descending branch (DB) and the other major perforator originated from oblique branch (OB) of lateral circumflex femoral artery (LCFA). However, the OB main perforator injury showed inadequate perfusion of flap. We trimmed the injury zone of OB perforator, and shift to re-anastomosis of OB perforators to side branch of DB of LCFA directly. The flap demonstrated excellent perfusion immediately after the operation, and it exhibited complete survival 2 weeks postoperatively. These results indicated that the turbocharging procedure, from perforator to perforator, could serve as a strategy for salvaging perfusion-compromised flaps, especially in cases of eccentric perforators or perforator injury resulting in inadequate perfusion.

Deep Learning Can Predict Bevacizumab Therapeutic Effect and Microsatellite Instability Directly from Histology in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) remains a significant cause of mortality among gynecologic cancers, with the majority of cases being diagnosed at an advanced stage. Before targeted therapies were available, EOC treatment relied largely on debulking surgery and platinum-based chemotherapy. Vascular endothelial growth factors have been identified as inducing tumor angiogenesis. According to several clinical trials, anti-vascular endothelial growth factor-targeted therapy with bevacizumab was effective in all phases of EOC treatment. However, there are currently no biomarkers accessible for regular therapeutic use despite the importance of patient selection. Microsatellite instability (MSI), caused by a deficiency of the DNA mismatch repair system, is a molecular abnormality observed in EOC associated with Lynch syndrome. Recent evidence suggests that angiogenesis and MSI are interconnected. Developing predictive biomarkers, which enable the selection of patients who might benefit from bevacizumab-targeted therapy or immunotherapy, is critical for realizing personalized precision medicine. In this study, we developed 2 improved deep learning methods that eliminate the need for laborious detailed image-wise annotations by pathologists and compared them with 3 state-of-the-art methods to not only predict the efficacy of bevacizumab in patients with EOC using mismatch repair protein immunostained tissue microarrays but also predict MSI status directly from histopathologic images. In prediction of therapeutic outcomes, the 2 proposed methods achieved excellent performance by obtaining the highest mean sensitivity and specificity score using MSH2 or MSH6 markers and outperformed 3 state-of-the-art deep learning methods. Moreover, both statistical analysis results, using Cox proportional hazards model analysis and Kaplan-Meier progression-free survival analysis, confirm that the 2 proposed methods successfully differentiate patients with positive therapeutic effects and lower cancer recurrence rates from patients experiencing disease progression after treatment (P < .01). In prediction of MSI status directly from histopathology images, our proposed method also achieved a decent performance in terms of mean sensitivity and specificity score even for imbalanced data sets for both internal validation using tissue microarrays from the local hospital and external validation using whole section slides from The Cancer Genome Atlas archive.

Long-term follow-up and comparison of programmable and non-programmable ventricular cerebrospinal fluid shunts among adult patients with different hydrocephalus etiologies: a retrospective cohort study.

BACKGROUND: Programmable valve (PV) has been shown as a solution to the high revision rate in pediatric hydrocephalus patients, but it remains controversial among adults. This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients with different hydrocephalus etiologies. METHOD: We reviewed the chart of all patients with hydrocephalus receiving index ventricular cerebrospinal fluid (CSF) shunt operations conducted at a single institution from January 2017 to December 2017. Patients included in the study were followed up for at least 5 years. Statistical tests including independent t-test, chi-square test, and Fisher's exact test were used for comparative analysis, and Kaplan-Meier curve using log-rank test was performed to compare the revision-free survival between the PV and NPV groups. RESULTS: A total of 325 patients were included in the study, of which 181 patients were receiving PVs and 144 patients receiving NPV. There were 23 patients (12.8%) with PV and 22 patients (15.3%) with NPV receiving initial revision. No significant statistical difference in the initial revision rate was observed between the two groups (p = 0.52). No survival difference was found between the PV and NPV groups. However, better revision-free survival was noted in the PV group among idiopathic normal pressure hydrocephalus (iNPH) (p = 0.0274) and post-traumatic hydrocephalus (p = 0.017). CONCLUSIONS: The combination of the different etiologies of hydrocephalus and the features of PV and NPV results in different outcomes-revision rate and revision-free survival. PV use might be superior to NPV in iNPH and post-traumatic hydrocephalus patients. Further studies are needed to clarify the indications of PV use in adult hydrocephalus patients.

Selective Myectomy and Myotomy In Situ for the Management of Refractory Blepharospasm in Meige Syndrome.

BACKGROUND: Meige syndrome is characterized by involuntary blepharospasm and varied subphenotypes of oromandibular tonic-clonic muscle contraction. Despite botulinum toxin (BTx) being the mainstay of treatment for Meige syndrome, a small subset of patients remain refractory to its effects because the disease is a form of functional blindness. An integrative surgical procedure combining selective myectomy and myotomy in situ of eyelid protractors, blepharoptosis correction, and tightening of the lower eyelid laxity was first applied to treat refractory blepharospasm in patients with Meige syndrome. MATERIALS AND METHODS: This study is a retrospective review conducted on 24 patients with refractory Meige syndrome between 2013 and 2020. Besides selective myectomy and myotomy in situ of eyelid protractors, levator plication and lateral tarsoplasty or canthopexy was performed for blepharoptosis correction and lower eyelid tightening, respectively. Patient demographics, associated diseases, medical treatment history, associated surgical procedures, final aesthetic outcomes, and therapeutic effects as reflected by changes in function disability score and Botox (BTx) treatment were thoroughly recorded and analyzed. RESULTS: The mean age of the patients was 65.2 ± 8.9 years. Twenty-one patients (87.5%) received blepharoptosis correction by levator plication with an average of 11.2 ± 2.9 mm in length. Lateral tarsoplasty was performed in 16 patients (66.7%) by pentagonal tarsal resection with an average of 3.9 ± 0.8 mm in width. Five patients (20.8%) received lateral canthopexy. Among the total of 96 operated eyelids, scar revision with fat graft was performed in 3 eyelids (3.1%). The average amount of BTx treatment decreased from 49.2 ± 12.8 U once every 2.7 ± 0.8 months before surgery to 35.4 ± 7.8 U once every 3.8 ± 0.7 months after surgery. Function disability score improved from 76.7 ± 17.5% preoperatively to 15.6 ± 9.9% postoperatively ( P < 0.001). Only 3 upper eyelids (3.1%) received scar revision and fat grafting due to minor postoperative contour depression. All patients expressed high satisfaction with both functional and aesthetic outcomes (Likert scale 4.5 ± 0.5). CONCLUSIONS: Selective myectomy and myotomy in situ of eyelid protractors combining blepharoplasty correction and lower eyelid tightening can produce long-lasting functional and aesthetic results with minimal complication in patients with refractory Meige syndrome.

Is decompressive craniectomy necessary in malignant posterior reversible encephalopathy syndrome with brain edema caused uncal herniation? A case report of reversible coma without surgical decompression.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is considered a benign entity and is usually reversible with only medical management, but persistent neurologic deficits and disability or death can occur without adequate treatment. Favorable outcomes have been associated with surgical decompression in malignant-type PRES in which hemorrhagic transformation or brain stem compression has developed. CASE DESCRIPTION: Here we report a case of malignant PRES in a 61-year-old female of Asian descent in which the disease rapidly progressed to coma and a near-fatal condition with uncal herniation caused by severe brain edema; however, this patient achieved a dramatic recovery without surgical decompression. CONCLUSION: After reviewing previous reports regarding malignant PRES, we propose that hemorrhagic transformation is a crucial indicator for surgical decompression and an important prognostic factor in malignant PRES.

Factors influencing loneliness among older people using homecare services during the COVID-19 pandemic.

BACKGROUND: Elderly homecare service users may reduce their level of social participation and interpersonal interactions due to physiological loss, which may lead to loneliness and depression over the years. However, there is a lack of research on loneliness among older people who use homecare services. The purpose of this study was to examine the factors influencing loneliness among older people using homecare services. METHODS: This is a longitudinal study conducted in communities in Central Taiwan, and data were collected using a structured questionnaire. The questionnaire was first administered as a pre-test to obtain baseline information about the participants, and the same questionnaire was administered as a post-test after 6 months to follow-up. The pre- and post-test questionnaires included five sections, that is, participant demographics, Brief Symptom Rating Scale, Interpersonal Interaction Scale (IIS), Frenchay Activities Index, and UCLA Loneliness Scale (UCLA). RESULTS: A total of 178 participants were recruited in this study. Results indicated that gender, whether participants eat alone or with others at dinner, social media use, perceived economic status, and IIS score were significantly correlated with the loneliness score on the UCLA. Furthermore, there was a significant increase in the loneliness score among male participants in the low loneliness group from baseline to 6 months follow-up. CONCLUSIONS: Gender, presence of others at dinner, social media use, perceived economic status, and interpersonal interaction skills are significant factors that influence loneliness among older people using homecare services. Men tend to experience higher levels of loneliness over time.

Double Fillet Flap for End-Stage Pelvic Pressure Injuries in a Paraplegic Patient.

ABSTRACT: Recurrent pelvic pressure injuries are common among paraplegic patients with spinal cord injury. Most of them experienced multiple surgical treatments because of recurrence. Based on the "spare part" concept, the double fillet flap is feasible when all other reconstructive procedures were exhausted. In this case report, we present the double fillet flap technique to manage recurrent extended pelvic pressure ulcers in a paraplegic spinal cord injury patient.

Lateral Tarsoplasty for Managing Ectropion and Laxity of the Lower Eyelid.

BACKGROUND: The most challenging complication associated with lower blepharoplasty is ectropion, and the traditional lateral canthopexy or canthoplasty procedure may carry the risk of eyelid malposition or subsequent chemosis. We propose lateral tarsoplasty with a detailed description of the techniques to treat and even prevent ectropion by not involving the medial or lateral canthal ligament so as to avoid complications. MATERIALS AND METHODS: Lower eyelid laxity was analyzed with the snap-back test and distraction test before surgery. Approximately 5 mm medial to the lateral canthus, lateral tarsoplasty is performed through a full-thickness pentagonal tarsal-conjunctival resection according to the "overlapping test" for an accurate measurement of the amount of the tarsus to be resected. Seventy-two eyelids that received either ectropion correction or prevention with lateral tarsoplasty over an 8-year period at a single institution were collected and analyzed for this retrospective review. RESULTS: Lateral tarsoplasty was performed in 39 patients with a mean age of 63.8 years. Thirteen patients with 20 eyelids presented for ectropion correction, in whom 5 to 10 mm of tarsus was resected, 6.0 mm in average. The other 26 patients with 52 eyelids presented for ectropion prevention, in whom 3 to 7 mm of tarsus was resected, 4.1 mm in average. Apart from temporary mild chemosis, all patients experienced highly satisfactory results without any ectropion or malposition of the involved lower eyelids after a follow-up of 8.1 months in average. CONCLUSIONS: For patients with moderate and severe laxity of lower eyelids, lateral tarsoplasty without involvement of the lateral canthal ligament proves to be an effective way to treat and prevent lower eyelid ectropion.

Microwave-Assisted Synthesis for Silver Nanoplates with a High Aspect Ratio.

In this work, a simple and rapid synthesis method was developed to prepare silver nanoplates (AgNPLs) with a high aspect ratio. A microwave heating process with a high heating rate and uniform heating was used to promote the silver reduction reaction. Silver nitrate (AgNO3) was used as the precursor of AgNPLs, and N,N-dimethylformamide (DMF) played the role of a solvent and reducing agent. Poly(vinylpyrrolidone) (PVP) with a molecular weight of 29,000 and a PVP/AgNO3 ratio of 10 were used to control the shape of synthesized AgNPLs. By adjusting the optimal microwave heating parameters, temperature ramping rate, reaction time, and reaction temperature, triangular AgNPLs with high aspect ratios could be produced. The synthesized AgNPLs had an edge length up to 700 nm and a thickness of 35 nm with aspect ratios up to 20. The AgNPLs were also used to produce conductive patterns via pen writing with a conductivity of 2 × 106 S/m to demonstrate the feasibility of applying the synthesized nanomaterials for electronic applications.

Palmitate Enhances the Efficacy of Cisplatin and Doxorubicin against Human Endometrial Carcinoma Cells.

Endometrial cancer is the most common gynecological cancer worldwide. At present there is no effective screening test for its early detection and no curative treatment for women with advanced-stage or recurrent disease. Overexpression of fatty acid synthase is a common molecular feature of a subgroup of sex steroid-related cancers associated with poor prognoses, including endometrial cancers. Disruption of this fatty acid synthesis leads to cell apoptosis, making it a potential therapeutic target. The saturated fatty acid palmitate reportedly induces lipotoxicity and cell death by inducing oxidative stress in many cell types. Here, we explored the effects of palmitate combined with doxorubicin or cisplatin in the HEC-1-A and RL95-2 human endometrial cancer cell lines. The results showed that physiological concentrations of exogenous palmitate significantly increased cell cycle arrest, DNA damage, autophagy, and apoptosis in both RL95-2 and HEC-1-A cells. It also increased the chemosensitivity of both cell types. Notably, we did not observe that palmitate lipotoxicity reflected increased levels of reactive oxygen species, suggesting palmitate acts via a different mechanism in endometrial cancer. This study thus provides a potential therapeutic strategy in which palmitate is used as an adjuvant in the treatment of endometrial cancer.

In-Silico Evaluation of Genetic Alterations in Ovarian Carcinoma and Therapeutic Efficacy of NSC777201, as a Novel Multi-Target Agent for TTK, NEK2, and CDK1.

Ovarian cancer is often detected at the advanced stages at the time of initial diagnosis. Early-stage diagnosis is difficult due to its asymptomatic nature, where less than 30% of 5-year survival has been noticed. The underlying molecular events associated with the disease's pathogenesis have yet to be fully elucidated. Thus, the identification of prognostic biomarkers as well as developing novel therapeutic agents for targeting these markers become relevant. Herein, we identified 264 differentially expressed genes (DEGs) common in four ovarian cancer datasets (GSE14407, GSE18520, GSE26712, GSE54388), respectively. We constructed a protein-protein interaction (PPI) interaction network with the overexpressed genes (72 genes) and performed gene enrichment analysis. In the PPI networks, three proteins; TTK Protein Kinase (TTK), NIMA Related Kinase 2 (NEK2), and cyclin-dependent kinase (CDK1) with higher node degrees were further evaluated as therapeutic targets for our novel multi-target small molecule NSC777201. We found that the upregulated DEGs were enriched in KEGG and gene ontologies associated with ovarian cancer progression, female gamete association, otic vesicle development, regulation of chromosome segregation, and therapeutic failure. In addition to the PPI network, ingenuity pathway analysis also implicate TTK, NEK2, and CDK1 in the elevated salvage pyrimidine and pyridoxal pathways in ovarian cancer. The TTK, NEK2, and CDK1 are over-expressed, demonstrating a high frequency of genetic alterations, and are associated with poor prognosis of ovarian cancer cohorts. Interestingly, NSC777201 demonstrated anti-proliferative and cytotoxic activities (GI50 = 1.6 µM~1.82 µM and TGI50 = 3.5 µM~3.63 µM) against the NCI panels of ovarian cancer cell lines and exhibited a robust interaction with stronger affinities for TTK, NEK2, and CDK1, than do the standard drug, paclitaxel. NSC777201 displayed desirable properties of a drug-like candidate and thus could be considered as a novel small molecule for treating ovarian carcinoma.

The Function-Preserving Frontalis Orbicularis Oculi Muscle Flap for the Correction of Severe Blepharoptosis With Poor Levator Function.

BACKGROUND: Severe blepharoptosis with poor levator function (LF) has traditionally been managed with exogenous frontalis suspension but complications such as lagophthalmos, infection, and rejection are often reported. OBJECTIVES: The aim of this study was to design a function-preserving frontalis orbicularis oculi muscle (FOOM) flap to correct severe blepharoptosis with poor LF. The long-term surgical outcome of the technique was assessed. METHODS: This retrospective study included only adult patients with severe blepharoptosis and poor LF, all of whom had their surgery performed by the senior surgeon over a 6-year period. Clinical assessment of LF, palpebral fissure height (PFH), marginal reflex distance 1 (MRD1), duration of follow-up, and postoperative complications were recorded. RESULTS: A total of 34 patients and 59 eyelids were recorded during a mean follow-up period of 17.7 months. Postoperative evaluation yielded mean [standard deviation] improvements of PFH gain of 5.62 [1.61] mm (P < 0.001), and MRD1 and PFH increases of 4.03 [0.82] mm (P < 0.001) and 8.94 [0.81] mm (P < 0.001), respectively. All patients demonstrated normalization of orbicularis function: no lagophthalmos was observed at the 8-month postoperative follow-up. Recurrence of ptosis was recorded in 4 eyelids (6.78%). Revisions were performed in 2 eyelids (3.39%). No infection or granuloma was noted. CONCLUSIONS: The function-preserving FOOM flap is a useful vector for frontalis suspension. Not only does it effectively address lagophthalmos as well as other complications, but it provides aesthetically pleasing outcomes in patients with severe blepharoptosis and poor LF.

TET1 reprograms the epithelial ovarian cancer epigenome and reveals casein kinase 2α as a therapeutic target.

Ten-eleven translocation methylcytosine dioxygenase-1, TET1, takes part in active DNA demethylation. However, our understanding of DNA demethylation in cancer biology and its clinical significance remain limited. This study showed that TET1 expression correlated with poor survival in advanced-stage epithelial ovarian carcinoma (EOC), and with cell migration, anchorage-independent growth, cancer stemness, and tumorigenicity. In particular, TET1 was highly expressed in serous tubal intraepithelial carcinoma (STIC), a currently accepted type II EOC precursor, and inversely correlated with TP53 mutations. Moreover, TET1 could demethylate the epigenome and activate multiple oncogenic pathways, including an immunomodulation network having casein kinase II subunit alpha (CK2α) as a hub. Patients with TET1high CK2αhigh EOCs had the worst outcomes, and TET1-expressing EOCs were more sensitive to a CK2 inhibitor, both in vitro and in vivo. Our findings uncover the oncogenic and poor prognostic roles of TET1 in EOC and suggest an unexplored role of epigenetic reprogramming in early ovarian carcinogenesis. Moreover, the immunomodulator CK2α represents a promising new therapeutic target, warranting clinical trials of the tolerable CK2 inhibitor, CX4945, for precision medicine against EOC. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Comparison of narcotic pain control between stereotactic electrocorticography and subdural grid implantation.

INTRODUCTION: The choice of subdural grid (SDG) or stereoelectroencephalography (sEEG) for patients with epilepsy can be complex and in some cases overlap. Comparing postoperative pain and narcotics consumption with SDG or sEEG can help develop an intracranial monitoring strategy. MATERIALS AND METHODS: A retrospective study was performed for adult patients undergoing SDG or sEEG monitoring. Numeric Rating Scale (NRS) was used for pain assessment. Types and dosage of the opioids were calculated by converting into milligram morphine equivalents (MME). Narcotic consumption was analyzed at the following three time periods: I. the first 24 h of implantation; II. from the second postimplantation day to the day of explantation; and III. the days following electrode removal to discharge. RESULTS: Forty-two patients who underwent SDG and 31 patients who underwent sEEG implantation were analyzed. After implantation, average NRS was 3.7 for SDG and 2.2 for sEEG (P < .001). After explantation, the NRS was 3.5 for SDG and 1.4 in sEEG (P < .001). Sixty percent of SDG patients and 13% of sEEG patients used more than one opioid in period III (P < .001). The SDG group had a significantly higher MME throughout the three periods compared with the sEEG group: period I: 448 (SDG) vs. 205 (sEEG) mg, P = .002; period II: 377 (SDG) vs. 102 (sEEG) mg, P < .001; and period III: 328 (SDG) vs. 75 (sEEG) mg; P = .002. Patients with the larger SDG implantation had the higher NRS (P = .03) and the higher MME at period I (P = .019). There was no correlation between the number of depth electrodes and pain control in patients with sEEG. CONCLUSIONS: Patients undergoing sEEG had significantly less pain and required fewer opiates compared with patients with SDG. These differences in perioperative pain may be a consideration when choosing between these two invasive monitoring options.

An Engineered Gene Nanovehicle Developed for Smart Gene Therapy to Selectively Inhibit Smooth Muscle Cells: An In Vitro Study.

In-stent restenosis is a serious concern for patients treated through the stenting procedure, although this can be solved using drug-eluting stents and/or drug-eluting balloon catheters. However, the chemical agents released from the drug-eluting layer for inhibiting smooth muscle cell (SMC) migration are inevitably associated with damage to vascular endothelial cell (ECs). The present in vitro study used a distinct strategy, in which a smart gene (phEGR1-PKCδ, an engineered plasmid consists of an SMC-specific promoter (human early growth response 1, hEGR1 promoter) ligated with a gene encoding apoptosis-inducing protein (protein kinase C-delta, PKCδ) was incorporated into a novel gene vehicle (Au cluster-incorporated polyethylenimine/carboxymethyl hexanoyl chitosan, PEI-Au/CHC) to form the PEI-Au/CHC/phEGR1-PKCδ complex, which was proposed for the selective inhibition of SMC proliferation. It was found that the cell viability of SMCs receiving the PEI-Au/CHC/phEGR1-PKCδ complex under simulated inflammation conditions was significantly lower than that of the ECs receiving the same treatment. In addition, the PEI-Au/CHC/phEGR1-PKCδ complex did not demonstrate an inhibitory effect on EC proliferation and migration under simulated inflammation conditions. Finally, the PEI-Au/CHC/phEGR1-PKCδ complexes coated onto a balloon catheter used in percutaneous transluminal coronary angioplasty (PTCA) could be transferred to both the ECs and the SMC layer of Sprague Dawley (SD) rat aortas ex vivo. These preliminary in vitro results suggest that the newly developed approach proposed in the present study might be a potential treatment for reducing the incidence rate of in-stent restenosis and late thrombosis in the future.

Awake craniotomies for epileptic gliomas: intraoperative and postoperative seizure control and prognostic factors.

PURPOSE: Awake craniotomy is well-established for tumors resected in eloquent brain areas. Whether awake craniotomy provides improved seizure control in patients with epileptic gliomas has not been well evaluated. This study analyzed the incidence, risk factors and outcome of seizures during and following awake craniotomies for patients presenting with epilepsy and glioma. METHODS: Forty-one patients undergoing awake craniotomies for epileptic gliomas were retrospectively analyzed. Postoperative seizure was defined as either early (postoperative day 7 + before) or late onset (after postoperative day 7). Neurologic function was assessed with modified Rankin Scales (mRS) and seizure outcome was assessed using International League Against Epilepsy (ILAE) classification. Multivariable logistic regression was used for clinical variables associated with postoperative seizures. RESULTS: Three patients (7.3%) had intraoperative seizures however did not fail the awake craniotomies. Mean mRS before and after the awake craniotomies were 2.4 and 2.1, respectively (P = 0.032). Fourteen (34.1%) patients had early seizures, which caused longer hospitalization than those without early seizures (P = 0.03). Surgical resection to isocitrate dehydrogenase 1 (IDH1) mutation tumors, comparing to IDH1 wild type tumors, caused better postoperative seizure control. 6-month late seizure freedom was achieved in 33 patients (80.5%). Early seizure recurrence (odds ratio = 30.75; P = 0.039) and postoperative mRS ≥ 3 (odds ratio = 7.00; P = 0.047) were independent risk factors for late seizures. CONCLUSIONS: Intraoperative seizures could be well-controlled during awake craniotomies. Early postoperative seizures extended hospitalization and strongly predicted late seizure recurrence. Awake craniotomies benefited long-term seizure control in patients with epileptic gliomas.

The suppression effect of dendritic cells maturation by adipose-derived stem cells through TGF-ß1 related pathway.

BACKGROUND: Our previous studies demonstrated that adipose-derived stem cells (ASCs) could modulate regulatory T cells (Treg) and prolong hind-limb allotransplant survival in vitro and in vivo. Dendritic cells (DCs) play a pivotal role in innate and adaptive immunity. The aim of this study is to investigate the underlying mechanism of ASCs in modulating DC maturation. MATERIALS AND METHODS: ASCs were isolated from rodent adipose tissue, DCs were derived from the bone marrow, and CD4+ T cells were purified from splenocytes. DCs were co-cultured with ASCs to evaluate the suppressive effects of ASCs. CD4+ T-cells were co-cultured with DCs pre-treated with or without ASCs. The cell surface markers of DCs were analyzed by flow cytometry. T-cell proliferation was analyzed by the BrdU proliferation test. Tolerogenic cytokines and indoleamine 2,3-dioxygenase (IDO) expressions after different treatments were detected by quantitative real-time PCR, Western blotting, and ELISA analysis. RESULT: ASCs suppressed DC maturation as evidenced by low expressions of CD80, CD86, and MHC-II. Also, ASC-treated mature DCs showed higher levels of TGF-ß1, IL-10, and IDO expressions, as compared to that in matured DCs (mDCs) alone. ASC-treated mDCs co-cultured with CD4+ T cells revealed a significant higher percentage of Treg than mDC without treatment. The IDO level in ASC-treated mDCs and Treg induction effects were blocked by the ASCs pre-treated with TGF-ß1 siRNAs, but not IL-10 siRNAs. CONCLUSION: ASC-modulated DC maturation correlated with TGF-ß1 secretion, IDO expression, and Treg induction. ASCs could be used as a potential immunomodulatory strategy for clinical application in allotransplantation.

Decreased fracture incidence with traditional Chinese medicine therapy in patients with osteoporosis: a nationwide population-based cohort study.

BACKGROUND: There are no published studies regarding the efficacy of traditional Chinese medicine (TCM) for the prevention of osteoporotic fracture. Therefore, we conducted this nationwide, population-based cohort study to investigate the probable effect of TCM to decrease the fracture rate. METHODS: We identified cases with osteoporosis and selected a comparison group that was frequency-matched according to sex, age (per 5 years), diagnosis year of osteoporosis, and index year. The difference between the two groups in the development of fracture was estimated using the Kaplan-Meier method and the log-rank test. RESULTS: After inserting age, gender, urbanization level, and comorbidities into the Cox's proportional hazard model, patients who used TCM had a lower hazard ratio (HR) of fracture (adjusted HR: 0.47, 95% CI: 0.37-0.59) compared to the non-TCM user group. The Kaplan-Meier curves showed that osteoporosis patients who used TCM had a lower incidence of fracture events than those who did not (p < 0.00001). Our study also demonstrated that the longer the TCM use, the lesser the fracture rate. CONCLUSION: Our study showed that TCM might have a positive impact on the prevention of osteoporotic fracture.

Epigenetic loss of heparan sulfate 3-O-sulfation sensitizes ovarian carcinoma to oncogenic signals and predicts prognosis.

Precision medicine requires markers for therapeutic guidance. The purpose of this study was to determine whether epithelial ovarian cancer (EOC) epigenetics can lead to the identification of biomarkers for precision medicine. Through integrative methylomics, we discovered and validated the epigenetic signature of NEFH and HS3ST2 as an independent prognostic factor for type II EOC in our dataset (n = 84), and two independent methylomics datasets (total n = 467). Integrated transcriptomics dataset (n = 1147) and tissue microarrays (n = 54) of HS3ST2 also related to high-methylation statuses and the EOC prognosis. Mechanistic explorations of HS3ST2 have assessed responses to oncogenic stimulations such as IL-6, EGF, and FGF2 in cancer cells. The combination of HS3ST2 and various oncogenic ligands also confers the worse outcome. 3-O-sulfation of heparan sulfate by HS3ST2 makes ovarian cancer cells intrinsically sensitive to oncogenic signals, which sheds new light on the application of HS3ST2 as a companion diagnostic for targeted therapy using kinase inhibitors or therapeutic antibodies.