A randomized trial of Bacteroides fragilis 839 on preventing chemotherapy-induced myelosuppression and gastrointestinal adverse effects in breast cancer patients.

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.

Inhibitory activity of linarin on osteoclastogenesis through receptor activator of nuclear factor κB ligand-induced NF-κB pathway.

Linarin, a natural flavonoid glycoside widely found in plants, has been reported to possess anti-inflammation, neuroprotection and osteogenic properties. However, its impact on osteoclast remains unclear. In the present study, the effects of linarin on osteoclastogenesis and its underlying molecular mechanisms of action were investigated. Using the culture systems of osteoclasts derived from bone marrow macrophages (BMMs), we found that linarin dose-dependently inhibited osteoclasts formation and bone resorptive activity. The Cell Counting Kit-8 test displayed that the viability of cells was not influenced by linarin at doses up to 10 µg/mL. In addition, linarin downregulated osteoclast-related genes expression, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR) and c-Fos, as shown by quantitative real time polymerase chain reaction (RT-qPCR). Western blot analysis further showed that linarin inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced nuclear factor kappa B (NF-κB) p65 and NFATc1 activity. The present findings show that linarin exerted a potent inhibitory effect on osteoclastogenesis through RANKL-induced NF-κB signaling pathway. In conclusion, the results suggest that linarin has anti-osteoclastic effects and may serve as potential modulatory agents for the prevention and treatment of bone loss-associated diseases.

Age- and Parkinson's disease-related evaluation of gait by General Tau Theory.

The degeneration of postural control in the elderly and patients with Parkinson's disease (PD) can be debilitating and may lead to increased fall risk. This study evaluated the changes in postural control during gait affected by PD and aging using a new method based on the General Tau Theory. Fifteen patients with PD, 11 healthy old adults (HOs), and 15 healthy young adults (HYs) were recruited. Foot trajectories of each participant were monitored during walking by a three-camera Optotrak Certus(®) motion capture system. The anteroposterior direction of foot movement during stepping was analyzed by tau-G and tau-J guidance strategies. Two linear regression analyses suggested that the tau of the step-gap was strongly coupled onto the tau-J guidance during walking. The regression slope K could estimate the coupling ratio in the tau-coupling equation which reflects the performance of postural control during gait. The mean K value for the PD group, which was highest among the three groups, was approximately 0.5. Therefore, participants in the PD group walked with the poorest postural control and exhibited a relatively hard contact with the endpoint during stepping when compared with those in the HO and HY groups. The HY and HO groups obtained mean K values significantly lower than 0.5, which indicated that the gait was well controlled and ended at low speed with low deceleration. However, the HO group showed a decreased tendency for postural control, in which the mean K value was significantly higher than that of the HY group. The K value was moderately positively correlated with the double support time and negatively correlated with the stride length and walking speed. The tau-J coupling ratio can provide additional insight into gait disturbances and may serve as a reliable, objective, and quantitative tool to evaluate dynamic postural control during walking.

Novel κ-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation.

AIM: To characterize the pharmacological profiles of a novel κ-opioid receptor agonist MB-1C-OH. METHODS: [(3)H]diprenorphine binding and [(35)S]GTPγS binding assays were performed to determine the agonistic properties of MB-1C-OH. Hot plate, tail flick, acetic acid-induced writhing, and formalin tests were conducted in mice to evaluate the antinociceptive actions. Forced swimming and rotarod tests of mice were used to assess the sedation and depression actions. RESULTS: In [(3)H]diprenorphine binding assay, MB-1C-OH did not bind to µ- and δ-opioid receptors at the concentration of 100 µmol/L, but showed a high affinity for κ-opioid receptor (Ki=35 nmol/L). In [(35)S]GTPγS binding assay, the compound had an Emax of 98% and an EC50 of 16.7 nmol/L for κ-opioid receptor. Subcutaneous injection of MB-1C-OH had no effects in both hot plate and tail flick tests, but produced potent antinociception in the acetic acid-induced writhing test (ED50=0.39 mg/kg), which was antagonized by pretreatment with a selective κ-opioid receptor antagonist Nor-BNI. In the formalin test, subcutaneous injection of MB-1C-OH did not affect the flinching behavior in the first phase, but significantly inhibited that in the second phase (ED50=0.87 mg/kg). In addition, the sedation or depression actions of MB-1C-OH were about 3-fold weaker than those of the classical κ agonist (-)U50,488H. CONCLUSION: MB-1C-OH is a novel κ-opioid receptor agonist that produces potent antinociception causing less sedation and depression.

Chronic high-frequency stimulation therapy in hemiparkinsonian rhesus monkeys using an implanted human DBS system.

Deep brain stimulation (DBS) is routinely used in the treatment of Parkinson's disease, tremor disease, dystonia, and epilepsy. This study aims to establish a hemiparkinsonian monkey model and to investigate the effect of implanted human DBS system for the chronic alleviation of parkinsonian symptoms. Hemiparkinsonism was induced in four rhesus monkeys by unilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. DBS leads were implanted stereotaxically in the right subthalamic (STN) of the monkeys. Subcutaneous extension wires were used to connect the leads to the internal pulse generators (IPG) for stimulation in two of the monkeys (human DBS test group). Post-operative imaging studies confirmed optimal locations of lead contacts. One week later, the IPG was turned on to determine the optimal stimulating parameters, using apomorphine (APO)-induced rotation as a behavioral readout. Animal behavior was scored on a scale of 0-10 over a 12-month period using the modified disability rating scale of hemiparkinsonian monkeys (DRSH). Parkinsonian symptoms in the group of monkeys with DBS improved dramatically (DRSH 3-4) compared to controls (DRSH 7-8). DBS leads were within the STN without intracranial hemorrhage, infection, or other serious complications. Histological examination showed cell necrosis and lymphocytic infiltration of the tissues around the lead and STN gliosis surrounding the lead contact. This study demonstrates that therapeutically effective human DBS systems can be established in relevant disease models in monkeys. Such combination of human DBS systems in hemiparkinsonian monkeys should be valuable in studying the mechanism of action and chronic consequences of DBS therapy in humans.

Preparation of fish collagen and vancomycin microspheres based on microfluidic technology and its application in osteomyelitis.

At present, the clinical treatment of osteomyelitis and osteomyelitis-induced bone defects is challenging, easy to recur, drug toxic side effects, secondary or multiple surgeries, etc. The design of biodegradable composite biomaterials to improve antibiotics in the local precise anti-infection at the same time to complete the repair of bone defects is the current research hot spot. Herein, a composite hydrogel with a double bond at the end (FA-MA) was prepared by affinity addition reaction between fish collagen (FA) and methacrylic anhydride (MA) under photoinitiator initiation conditions, then, FA-MA was amino-activated by EDC/NHC, and vancomycin was attached to FA-MA via amide bonding to prepare FA-MA-Van hydrogels, and finally, the composite hydrogel microspheres were prepared by microfluidic technology. The structure of the hydrogel was confirmed by SEM (elemental analysis), optical microscopy, FTIR, and XPS to confirm the successful preparation. The composite hydrogel microspheres showed the better antimicrobial effect of hydrogel microspheres by bacterial coated plate experiments and SEM morphology results, with the antimicrobial class reaching 99.8%. The results of immunofluorescence staining and X-ray experiments showed that the hydrogel microspheres had a better effect on promoting bone repair. This engineered design of hydrogel microspheres provides clinical significance for treating osteomyelitis at a later stage.

Social Media Support and Funding Assistance for Psychological Injuries in Social Work.

Introduction: Psychological injuries in social work are on the rise in complex modern society. Some individuals are incurring both physical and psychological injuries. Often, psychological injuries are more miserable than physical injuries. To combat the psychological injury suffered by individuals involved in social work, authorities should mobilize support via social media and raise funds by this and other feasible means to cover the cost of care for these individuals. This study focuses on social media support and funding assistance that could play useful roles in helping to treat psychological injuries among social workers and their clients in China. Methods: A scoping review of academic and gray literature was undertaken to identify the different injuries involved in social work. Semi-structured interviews were carried out with 7 experts, including social workers, social media professionals, and social fund directors. Empirical studies on psychological injuries in social work provided examples in support of the policy advocacy reported in this paper. Results: The scoping review found diverse literature on the subject of psychological injury in social work over the past decade in China. Semi-structured interviews with experts indicate that social media support can alleviate psychological suffering and that funding assistance has a positive influence on assisting individuals coping with psychological injuries. The empirical cases support the plan to encourage more support from social media and funding sources. Conclusion: Psychological injury is greatly influenced by social bias and discrimination. According to cases and actions are taken to mitigate the harm done, supportive social media strategies could greatly diminish the psychological injuries to social workers and their clients and help them avoid much suffering. This study finds that funding organizations could provide a new treatment mechanism-social media marketing strategies and functional activities-to help a large number of individuals with psychological injuries out of the disease trap in China.

Lipophilic Modified Hierarchical Multiporous rGO Aerogel-Based Organic Phase Change Materials for Effective Thermal Energy Storage.

In the field of thermal energy storage, organic phase change materials (PCMs) are widely used as functional materials to boost thermal applications. However, there is often a tradeoff between constructing shape-stable composite PCMs with high enthalpy value and those with low leakage rates. Here, we proposed a promising scheme to address this issue. A novel hydrogel consisting of reduced graphene oxide (rGO) and covalent organic framework (COF) was prepared via hydrothermal methods, and the rGO-COF ultralight aerogel with a hierarchical porous structure was formed after freeze-drying. The rGO-COF aerogel shows excellent absorption ability and affinity for organic solvents. It can sufficiently adsorb the molten organic PCMs, such as polyethylene glycol (PEG), and synthesize shape-stable composite PCMs with excellent leak resistance. The COF grown on the surface of rGO has a superior affinity for PEG, so rGO-COF aerogel shows an outstanding PEG loading rate of up to 96.1 wt %, which is 1.7 wt % higher than that of rGO aerogel. In addition, the COF effectively reduces the subcooling of PEG/rGO-COF with 20.3%, compared to PEG/rGO. Meanwhile, the prepared PEG/rGO-COF exhibits extremely high enthalpy and relative enthalpy efficiency (164.6 J/g, 97.4%). This demonstrates that a promising direction was highlighte for the preparation of high-enthalpy shape-stable composite organic PCMs in this work.

Optimal Contact Position of Subthalamic Nucleus Deep Brain Stimulation for Reducing Restless Legs Syndrome in Parkinson's Disease Patients: One-Year Follow-Up with 33 Patients.

Objectives: To determine the short- and medium-term therapeutic effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on restless legs syndrome (RLS) in patients with Parkinson's disease (PD) and to study the optimal position of activated contacts for RLS symptoms. Methods: We preoperatively and postoperatively assessed PD Patients with RLS undergoing STN-DBS. Additionally, we recorded the stimulation parameters that induced RLS or relieved RLS symptoms during a follow-up. Finally, we reconstructed the activated contacts' position that reduced or induced RLS symptoms. Results: 363 PD patients were enrolled. At the 1-year follow-up, we found that the IRLS sum significantly decreased in the RLS group (preoperative 18.758 ± 7.706, postoperative 8.121 ± 7.083, p < 0.05). The results of the CGI score, MOS sleep, and RLS QLQ all showed that the STN-DBS improved RLS symptoms after one year. Furthermore, the activated contacts that relieved RLS were mainly located in the central sensorimotor region of the STN. Activated contacts in the inferior sensorimotor part of the STN or in the substantia nigra might have induced RLS symptoms. Conclusions: STN-DBS improved RLS in patients with PD in one year, which reduced their sleep disorders and increased their quality of life. Furthermore, the central sensorimotor region part of the STN is the optimal stimulation site.

Highly efficient Cr(VI) removal from industrial electroplating wastewater over Bi2S3 nanostructures prepared by dual sulfur-precursors: Insights on the promotion effect of sulfate ions.

In this work, different Bi2S3 nanostructures were prepared from various single and dual sulfide precursors via a solvothermal method. It was found that Bi2S3 nanostructures prepared from dual sulfur precursors of L-cysteine and ammonium sulfide exhibited highest Cr(VI) removal ability with maximum Cr(VI) removal capacity of 148.95 mg/g in Cr(VI) solution (pH = 2). More importantly, the removal capacity strikingly increased to 223.33 and 240.25 mg/g in two kinds of actual industrial electroplating wastewater. By analyzing the components of actual electroplating wastewater and the results of control experiments in the absence and presence of different ions in Cr(VI) solution, it was found that SO42- played a critical role in the Cr(VI) removal over Bi2S3. The addition of SO42- could promote the conversion of Cr(VI) to Cr(III) on the surface of Bi2S3, thus leading to the enhanced Cr(VI) removal ability in actual electroplating wastewater. The Bi2S3 maintained its original Cr(VI) removal ability after four cycles in the electroplating wastewater, indicating the moderate reuse ability of the sample. This work not only demonstrated an highly efficient nanomaterials for the Cr(VI) removal in industrial electroplating wastewater, but also provided an insight on the influence of the components in wastewater on Cr(VI) removal.

A synonymous variant contributes to a rare Wiedemann-Rautenstrauch syndrome complicated with mild anemia via affecting pre-mRNA splicing.

Wiedemann-Rautenstrauch syndrome (WDRTS) is an extremely rare autosomal recessive neonatal disorder. Currently, over 50 cases with variable phenotypes of WDRTS have been reported. In our cohort of prenatal and postnatal growth retardation, a female proband was found to have general growth retardation, neurocutaneous syndrome, and anemia. Karyotype test and array-CGH detected no obvious chromosomal aberrations. Trio-based whole-exome sequencing (Trio-WES) identified bi-allelic compound mutations in the coding sequence (CDS) of POLR3A gene (c.3342C > T, p.Ser1114 = and c.3718G > A, p.Gly1240Ser). For the mild anemia phenotype, the underlying causal genetic factors could be attributed to the compound heterozygous mutations in FANCA gene (c.2832dup, p.Ala945CysfsTer6 and c.1902 T > G, p.Asp634Glu). Mini-gene reporter assays revealed that the synonymous variant of POLR3A and the missense variant of FANCA could affect pre-mRNA splicing of each gene. For POLR3A, the synonymous mutation (c.3342C > T, p.Ser1114=) generated three types of aberrant isoforms. Therefore, the female patient was finally diagnosed as WDRTS caused by POLR3A. For FANCA, the missense variant (c.1902 T > G, p.Asp634Glu) disrupted the normal splicing between exon 21 and 22, and produced two types of abnormal isoforms, one carrying the 1902G and the other spliced between exon 21 and 23 to exclude exon 22. Network analysis showed that POLR3A and FANCA could be STRINGed, indicating both proteins might collaborate for some unknown functions. Current investigation would broaden the knowledge for clinicians and genetic counselors and remind them to interpret those synonymous or predicted "benign" variants more carefully.

Reconstruction of chronic scalp erosion after deep brain stimulation surgery.

OBJECTIVE: To investigate the reconstructive effectiveness for chronic scalp erosion after deep brain stimulation (DBS). BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease. However, this surgery is not exempt from hard-ware related complications, especially scalp erosions on scalp. Scalp erosions usually accompanied with chronic infection and wound contamination. If not arrested, infections may spread through the entire equipment which would endanger the patient's life. Along with review of previous literatures, we summarized our experience in the management of scalp erosion and implemented a systemic treatment plan for reconstruction. METHODS: We retrospectively analyzed the clinical data of patients with chronic scalp erosion after DBS in the past 40 months. The treatment plan was composed of three sequential major steps, including wound care and conservative methods, debridement and local flap, and revaluation of the wound. In each of the cases, wound debridement and local scalp flap repair were conducted, and assisted by negative pressure wound therapy (NPWT) device and double cannula irrigation. RESULTS: The local scalp flap survived in all 6 patients. The chronic scalp erosions all healed without refractory. The DBS devices still functioned properly after the treatments in all patients. The average follow-up period was 13.33 months (range: 4 to 23 months), and no infection recurrence or re-erosion of the scalp flap was reported. CONCLUSION: A combination of wound debridement, local scalp flap repair, the use of NPWT device and double cannula irrigation provides effective treatment method for chronic erosion post DBS surgery.

A novel therapy for granulomatous lobular mastitis: Local heat therapy.

Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast condition that is characterized by granulomatous inflammation. GLM remains a refractory disease due to its failure to respond to routine anti-inflammatory therapies and its high recurrence rate. Thus, the present study aimed to investigate the application of local heat therapy in GLM as a potential therapeutic strategy. The results revealed that the application of local heat therapy was associated with a shortened remission time for GLM, while the remission and recurrence rates were similar to those of existing therapies. The median first remission time following local heat therapy was significantly decreased compared with that following corticosteroid therapy (5.30 months vs. 11.27 months; P<0.05). The remission rates were not significantly different between the local heat therapy (76.9%), extensive excision (90.4%) and the corticosteroid therapy (85.7%) groups (P>0.05). In addition, the recurrence rates were not statistically different between the groups (local heat therapy, 8.3%; extensive excision, 10%; and corticosteroid therapy, 10%; P>0.05). The local heat therapy showed mild adverse effects and shortened healing times compared to the other therapies; however, further confirmation is required.

Management of Parkinson's disease patients after DBS by remote programming: preliminary application of single center during quarantine of 2019-nCoV.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for patients with Parkinson's disease (PD). On time follow-up and timely programing of symptoms are important measures to maintain the effectiveness of DBS. Due to the highly contagious nature of 2019-nCoV, patients were quarantined. With the help of Internet technologies, we continued to provide motor and non-motor symptom assessment and remote programming services for postsurgical PD-DBS patients during this extraordinary period. METHODS: A retrospective analysis was performed on postsurgical PD-DBS patients who could not come to our hospital for programming due to the impact of the 2019-nCoV. The differences between the pre- and post-programming groups were analyzed. We designed a 5-level Likert rating scale to evaluate the effects and convenience of the remote programming and Internet self-evaluation procedures. RESULTS: Of the 36 patients engaged in the remote programming, 32 patients met the inclusion criteria. Four of the 32 patients set initiated stimulation parameters, and the other 28 patients had significant improvement in UPDRS-III. Nearly all the 28 patients were satisfied with the effect of the remote programming. Most of the patients were willing to use remote programming again. CONCLUSION: Remote programming based on the online evaluation of patient's symptoms can help improve motor symptoms of postsurgical DBS patients with PD during the quarantine period caused by 2019-nCoV.

Avoidance and management of surgical and hardware-related complications of deep brain stimulation.

OBJECTIVE: Although deep brain stimulation (DBS) is nonablative, it may give rise to many complications. In order to identify and reduce factors contributing to the complications, we performed a retrospective analysis of patients who received DBS in our institution over a 9-year period from March 2000 to December 2008. METHODS: Included in this study were 161 patients (85 male and 76 female). Data from these patients were collected and analyzed with respect to the complications and factors potentially related to these complications. RESULTS: A total of 25 surgical and hardware-related complications occurred in 24 patients, including confusion in 11 cases (6.83%), asymptomatic intracranial hemorrhage in 1 case (0.62%), electrode misplacement in 2 cases (1.24%), infection of the subcutaneous pocket receiving the pulse generator in 1 case (0.62%), skin erosion in 2 cases (1.24%), pulse generator seroma formation in 6 cases (3.72%), and device malfunction in 1 case (0.62%). There was no permanent neurological deficit. CONCLUSION: Confusion is the most common complication in simultaneous bilateral DBS targeting the subthalamic nucleus, especially in patients with severe Parkinson's disease. With increasing experience of surgeons, complete obedience to intraoperative surgical routines and reasonable application of the microelectrode recording technique, other complications could also be reduced.

Impact of intraoperative radiotherapy on the perioperative period of patients after breast-conserving surgery.

BACKGROUND: To investigate the effect of intraoperative radiotherapy (IORT) in the perioperative period of patients after breast-conserving surgery (BCS). METHODS: The clinical data of 100 patients with early breast cancer undergoing breast-conserving surgery (BCS) followed by treatment with IORT using the Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany) (BCS + IORT group, n=100) between June 2016 and December 2019 were analyzed and compared with the data of 60 matched patients who only underwent breast-conserving therapy over the same period (BCS group, n=60). The surgical settings and postoperative acute complications between the groups were assessed. RESULTS: There was no significant statistical difference between the groups in terms of age, tumor size, grading, lymph node status, hormone receptor status, and human epidermal growth factor receptor 2 (HER-2) status (P>0.05). The BCS + IORT group had a significantly longer surgery duration (P<0.05), but there was no significant statistical difference in terms of intraoperative blood loss, amount of bleeding, drainage tube removal time, postoperative length of hospitalization, incision suture removal time, or incidence of postoperative complications (P>0.05). CONCLUSIONS: IORT using the Intrabeam system safely delivers radiation therapy, is well-tolerated, has acceptable acute toxicity, and does not significant increase the risk of surgery or the incidence of perioperative complications.

Intracranial hemorrhage risk factors of deep brain stimulation for Parkinson's disease: a 2-year follow-up study.

OBJECTIVE: This study aimed to analyze the risk factors of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) for idiopathic Parkinson's disease (PD). METHODS: Patients who received DBS from March 2014 to December 2016 were retrospectively analyzed. The hemorrhage index was derived by combining the hemorrhagic volume and clinical manifestations of ICH. All patients with IHC were followed up for 2 years. RESULTS: Computed tomography showed 13 events of ICH in 11 patients (nine cases in the subthalamic nucleus), including eight cases with symptomatic hemorrhage (seven cases in the subthalamic nucleus). Hemorrhage was characterized by intracranial hematoma in the electrode puncture tract. Male sex and hypertension were significant risk factors for ICH. Hemorrhage in the preferred puncture side was significantly higher than that in the non-preferred puncture side. The mean hemorrhage index was 2.23 ± 0.83 in 11 patients, and no permanent neurological impairment was found during the 2-year follow-up. The effect of DBS on motor symptoms was similar in patients with and without ICH. CONCLUSION: Male sex and hypertension are risk factors of ICH after DBS in PD. The risk of hemorrhage on the first puncture site is significantly higher than that on the second puncture site.

Synergistic effect of electric stimulation and mesenchymal stem cells against Parkinson's disease.

Electroconvulsive therapy (ECT) has known beneficial effects on the core motor symptoms of Parkinson's disease (PD), likely through induction of dopamine release and sensitivity of dopamine receptors. Mesenchymal stem cells (MSCs) can salvage loss of dopamine in PD through their differentiation into dopaminergic neurons. However, it is not known if combined ECT and MSC transplantation may have a synergistic effect against PD. Here, we showed that ECT significantly increased the differentiation of the transplanted MSCs into dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. On the other hand, transplantation of MSCs significantly increased dopamine levels after ECT. Co-application of ECT and MSC transplantation generated a synergistic effect through increases in dopamine and decreases in pro-inflammatory cytokines, resulting in significantly attenuated defect in stepping test and rotational behavior in MPTP-mice. Together, our data suggest that combined ECT and MSC transplantation can be a valuable treatment of PD.

The Effect of High-Frequency Electrical Stimulation of Bilateral Nucleus Accumbens on the Behavior of Morphine-Induced Conditioned Place Preference Rats at Extinction and Reinstatement Phases.

OBJECTIVE: To explore the optimal time points for deep brain stimulation (DBS) on the treatment of morphine addiction and its possible mechanisms by investigating how high-frequency stimulation (HFS) in bilateral nucleus accumbens (NAc) at different time points influences the addictive behaviors of rats with drug addiction. METHODS: The rats were randomly divided into extinction stimulation group (n = 20) and postextinction stimulation group (n = 20). Ten rats in the extinction stimulation group were treated using 120 Hz HFS during extinction stage while another 10 rats with pseudostimulation were served as control group. The CPP scores were evaluated at the second day after intervention, with total 9 sections accomplished. The CPP scores were evaluated at the second day of the intervention. In the postextinction stimulation group, 120 Hz HFS was intervened during the postextinction stage in 10 experimental rats and pseudostimulation was performed in 10 control rats. Stimulation was performed for 7 days continuously, and a small dose of morphine was administrated to induce relapse after the postextinction period. RESULTS: During the extinction phase, CPP scores after HFS were significantly higher. During the postextinction phase, relapse CPP scores after HFS were dramatically lower. CONCLUSION: HFS of bilateral NAc inhibits the extinction of addictive behavior during the extinction phase, and HFS during the postextinction period suppresses relapse of drug seeking behavior.

Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3.

BACKGROUND: Src associated with mitosis of 68 kDa (Sam68), is often highly expressed in human cancers. Overexpression of Sam68 has been shown to be correlated with poor survival prognosis in some cancer patients. However, little is known whether Sam68 plays a role in promoting metastasis in breast cancer. MATERIALS AND METHODS: The expression of Sam68 protein in breast cancer tissue was detected by immunohistochemistry. Trans-well assay, wound-healing, real-time PCR and Western blotting analysis were used to detect the effect of Sam68 on promoting EMT or metastasis of breast cancer. Next-generation RNA sequencing was used to analyze genes that may be regulated by Sam68. RESULTS: Sam68 plays a positive role in promoting breast cancer metastasis. Sam68 was found to be overexpressed in breast cancer along with lymph node metastasis. MMP-9 was also found to be overexpressed in breast cancer tissue and was correlated to the expression of Sam68 (P<0.01). Xenograft in NOD/SCID mice and in vitro experiments confirmed that the invasion and metastatic ability of breast cancer cells were regulated by Sam68. And EPHA3 could be up-regulated by Sam68 in breast cancer. CONCLUSION: High expression of Sam68 participates in breast cancer metastasis by up-regulating the EPHA3 gene.