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Cranial nerve injury by a laryngeal mask airway is rare but a serious complication. The nerve injuries must be prevented during the intubation using a laryngeal mask airway. We report a female patient who complained of tongue numbness, slurred speech, and slight difficulty in swallowing solid food after a hand surgery. She was then diagnosed with unilateral lingual nerve and hypoglossal nerve injuries. Extreme head rotation, relatively small oral cavity, and wide rigid composition at the lower part of the novel laryngeal mask probably resulted in cranial nerve injury.

Purpose: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA–arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. Experimental Design: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). Results: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. Conclusions: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.

Hyperselective neurectomy is used to treat spastic arm paralysis. The aim of the study was to analyze the nerve branching patterns of elbow and wrist flexors/pronator to inform hyperselective neurectomy approached.Eighteen upper extremities of fresh cadaver specimen were dissected. The number of motor branches from the musculocutaneous nerve to biceps brachii and brachialis, median nerve to pronator teres, flexor carpi radialis and ulnar nerve to flexor carpi ulnaris were counted. The origin site of each primary motor branch was documented.Either biceps or brachialis was innervated by one or two primary motor branches. Pronator teres was innervated by one to three motor trunks and the pattern for flexor carpi radialis was a common trunk with other branches. The origin of the biceps and brachialis nerve trunk was located approximately 30% to 60% of the length of the arm. The median nerve branched to pronator teres and flexor carpi radialis at the region about 34mm (SD 18.8mm) above and 50mm (SD 14.9mm) below the medial epicondyle. Flexor carpi ulnaris was innervated by one to three motor trunks and the mean distance from the medial epicondyle to the origin of flexor carpi ulnaris nerve on ulnar nerve was 18.7 mm (SD 6.5mm).Primary motor branches to elbow flexors, wrist flexors and pronators were various, while the regions of their origins were relatively settled. It was recommended the incisions be designed according to the location of the primary motor trunks.

Oxidative stress induces the formation of oxidized low‑density lipoprotein (ox‑LDL), which accelerates the development of atherosclerosis and the rupture of atherosclerotic plaques by promoting lipid accumulation and inhibiting autophagy in vascular cells. Lipophagy is known to be involved in maintaining the balance of neutral lipid metabolism; however, the phenomenon of lipophagy deficiency in ox‑LDL‑treated endothelial cells (ECs) remains to be elucidated. It has been demonstrated that lipid accumulation caused by ox‑LDL inhibits autophagy, which promotes apoptosis in ECs. The aim of the present study was to investigate the association between decreased autophagy and lipid accumulation in ECs treated with ox‑LDL. Electron microscopy demonstrated that the formation of autolipophagosomes was decreased in ox‑LDL‑treated human umbilical vein ECs compared with that in the LDL‑treated group and was accompanied by a decrease in the autophagy‑associated proteins via western blotting analysis. Using laser focal colocalization detection, decreased lipid processing was observed in the lysosomes of ox‑LDL‑treated ECs, which indicated that lipophagy may be attenuated and subsequently result in lipid accumulation in ox‑LDL‑treated ECs.

Background Cushing’s syndrome has been described as a complex endocrine disorder characterized with high cortisol concentration. Correct and early diagnosis of Cushing’s syndrome is challenging. According to the latest guideline, bilateral inferior petrosal sinus sampling (BIPSS) is considered to be the gold standard for the differential diagnosis. However, in some unusual cases, this method may be false positive. Here, we presented a rare case of orbital neuroendocrine tumor secreting adrenocorticotrophic hormone with false positive inferior petrosal sinus sampling. Case presentation A 48-year-old woman was admitted to West China Hospital of Sichuan University, presenting with fatigue, whole body edema for 1 year, alopecia and skin pigmentation for 5 months. Hormonal profiles including plasma cortisol and adrenocorticotrophic hormone (ACTH) measurements and low-dose dexamethasone inhibition test suggested that the patient had Cushing’s syndrome. However, during tumor location phase, the results of high-dose dexamethasone inhibition test (HDDST) contradicted desmopressin (DDAVP) stimulation test. Thus, BIPSS was employed, and its results indicated a pituitary origin. Interestingly, MRI of sellar region showed an innocent pituitary but caught a serendipitous lesion in the lateral rectus muscle of left eye, which was later proved to be an orbital neuroendocrine tumor secreting ACTH by pathological and immunohistochemical results. ACTH level of the patients was Conclusion We reported a rare case of endogenous Cushing’s syndrome due to ectopic ACTH secreting from an orbital neuroendocrine tumor. This unique case of orbital EAS suggests that orbital venous blood backflow, owning to abnormal anatomic structures, may possibly lead to false positive BIPSS results.

Amyloid beta (Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease (AD). ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke by interrupting the interaction of neuronal nitric oxide synthase and postsynaptic density protein 95. However, few studies are reported on the role of ZL006 in AD. To investigate whether ZL006 exerted neuroprotective effects in AD, we used Aβ1–42 to treat primary cortical neurons and N2a neuroblastoma cells as an in vitro model of AD. Cortical neurons were incubated with ZL006 or dimethyl sulfoxide for 2 hours and treated with Aβ1–42 or NH3•H2O for another 24 hours. The results of cell counting Kit-8 (CCK-8) assay and calcein-acetoxymethylester/propidium iodide staining showed that ZL006 pretreatment rescued the neuronal death induced by Aβ1–42. Fluorescence and western blot assay were used to detect oxidative stress and apoptosis-related proteins in each group of cells. Results showed that ZL006 pretreatment decreased neuronal apoptosis and oxidative stress induced by Aβ1–42. The results of CCK8 assay showed that inhibition of Akt or NF-E2-related factor 2 (Nrf2) in cortical neurons abolished the protective effects of ZL006. Moreover, similar results were also observed in N2a neuroblastoma cells. ZL006 inhibited N2a cell death and oxidative stress induced by Aβ1–42, while inhibition of Akt or Nrf2 abolished the protective effect of ZL006. These results demonstrated that ZL006 reduced Aβ1–42-induced neuronal damage and oxidative stress, and the mechanisms might be associated with the activation of Akt/Nrf2/heme oxygenase-1 signaling pathways.

The present study was aimed at investigating the hepatoprotective effect of pyrroloquinoline quinone (PQQ) against acute alcoholic liver injury in mice. Acute alcoholic liver injury model was established in mice, and they were administrated with PQQ to investigate its hepatoprotective effect. Our results shows that PQQ can significantly ameliorate acute alcoholic liver injury by decreasing the hepatic marker enzymes, including serum alanine transaminase (ALT) and aspartate transaminase (AST), and increasing the levels of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver. And PQQ can also significantly reduce the content of hepatic triglyceride (TG) and malondialdehyde (MDA). Moreover, PQQ attenuated alcohol-induced oxidative damage by activating NF-E2-related factor 2 (Nrf2)-mediated signaling pathway, and inhibiting Toll-like receptor 4 (TLR4)-mediated nuclear factor-kappa B (NF-κB) signaling pathway. Our findings have elucidated the liver protection mechanism of PQQ, which would encourage the further exploitation of PQQ as a hepatoprotective functional food.

Corticospinal neurons (CSNs) undertake direct cortical outputs to the spinal cord and innervate the upper limb through the brachial plexus. Our previous study has shown that the contralateral middle trunk transfer to the paralyzed upper extremity due to cerebral injury can reconstruct the functional cerebral cortex and improve the function of the paralyzed upper extremity. To interpret the cortical reconstruction and the motor improvement after the middle trunk transfer, we explored the distribution of CSNs connecting to the middle, upper, and lower trunk of the brachial plexus by retrograde trans-neuronal tracing using pseudorabies virus (PRV-EGFP or PRV-mRFP). We show that, rather than an individual specific area, these CSNs labelled by each trunk of the brachial plexus were widespread and mainly assembled within the primary motor cortex (M1), secondary motor cortex (M2), primary somatosensory cortex (S1), and slightly within the secondary somatosensory cortex (S2). The three trunk-labelled CSNs were intermingled in these cortices, and mostly connected to more than two trunks, especially the middle trunk-labelled CSNs with higher proportion of co-labelled neurons. Our findings revealed the distribution features of CSNs connecting to the adjacent spinal nerves that innervate the upper limb, which can improve our understanding of the corticospinal circuits associated with motor improvement and the functional cortical reconstruction after the middle trunk transfer.

Our previous investigation suggested that faster seventh cervical nerve (C7) regeneration occurs in patients with cerebral injury undergoing contralateral C7 transfer. This finding needed further verification, and the mechanism remained largely unknown. Here, Tinel's test revealed faster C7 regeneration in patients with cerebral injury, which was further confirmed in mice by electrophysiological recordings and histological analysis. Furthermore, we identified an altered systemic inflammatory response that led to the transformation of macrophage polarization as a mechanism underlying the increased nerve regeneration in patients with cerebral injury. In mice, we showed that, as a contributing factor, serum amyloid protein A1 (SAA1) promoted C7 regeneration and interfered with macrophage polarization in vivo. Our results indicate that altered inflammation promotes the regenerative capacity of the C7 nerve by altering macrophage behavior. SAA1 may be a therapeutic target to improve the recovery of injured peripheral nerves.

Docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) has attracted increasing attention because of its unique health benefits. In this study, DHA-PS was biosynthesized from DHA-enriched phosphatidylcholine (DHA-PC), which was extracted from herring roe, Clupea harengus. The ameliorating effect of DHA-PS on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) was investigated using a mouse model. The DHA-PS treatment ameliorated NAFLD and effectively decreased the serum total cholesterol, triglyceride, non-esterified fatty acid, and low-density lipoprotein cholesterol levels and considerably increased the serum high-density lipoprotein cholesterol levels. Moreover, the DHA-PS treatment reduced the levels of liver-function enzymes and pro-inflammatory cytokines and also the oxidative stress indices. Furthermore, DHA-PS increased the diversity and richness of the beneficial intestinal microorganisms, suggesting its potential as a dietary supplement and functional food to combat HFD-induced NAFLD.

Objective. To explore the effect of applying binocular visual training after slanted lateral rectus recession on orthophoric rate and binocular visual function recovery on patients with convergence insufficiency-type intermittent exotropia (CI-IXT). Methods. A total of 76 CI-IXT child patients treated at the Strabismus and Pediatric Ophthalmology Department of our hospital from June 2019 to June 2020 were selected as the research objects, and those who met the inclusion criteria were equally divided into group A (63 eyes) and group B (61 eyes) according to the sealed envelope randomization. All child patients accepted the slanted lateral rectus recession, and after that, those in group A accepted the binocular visual training and those in group B accepted the conventional visual function rehabilitation training, so as to compare their position of eye, the best corrected visual acuity, etc., after training for statistical analysis. Results. Compared with group B after one month of surgery, group A had significantly less patients with grade I binocular vision function ( P P P P P P P

IntroductionThe pathology of Alzheimer’s disease (AD) includes -amyloid (A) (plaques) and neurofibrillary tangles (NFTs). This study aimed to explore the efficacy of Huatuo Zaizao pill (HTZP) in an AD mouse model induced by injecting A1-42, and the neuroprotective mechanism of HTZP in AD.Material and methodsC57BL/6 (B6) mice were randomly divided into 4 groups (n = 10, per group): control group, AD model group, and 2 different doses of HTZP treated groups. The Morris water maze test was carried out on AD mice to assess the learning ability after treatment with HTZP for 15 day. The levels of inflammatory factors and the nuclear factor-B (NF-B) pathway were examined by western blot and real-time polymerase chain reaction (PCR). The content of microglia was investigated by immunofluorescence.ResultsThis study revealed that a cognitive disorder could be mitigated when the AD mice were treated with HTZP, which might be associated with the decreased level of pro-inflammatory factors, and the inhibitory activities of microglia. Additionally, phosphorylation of IB and NF-B p65 could be reduced by prohibiting the neuroinflammation of NF-B activation in the hippocampus of AD mice.ConclusionsThese results showed that HTZP could mitigate a cognitive disorder, diminish the activation of microglia, and inhibit the content of inflammatory factors through the NF-B pathway in A1-42-induced AD mice. HTZP may be an appropriate agent for AD treatment in the future.

Aims Cyclophosphamide (CTX) is an effective anti-tumor and immunosuppressive agent, but it induces nephrotoxicity in clinical applications. The present study aimed to evaluate the protective effect of pyrroloquinoline quinone (PQQ) on CTX-induced nephrotoxicity. Main methods We injected male ICR mice with CTX (80 mg/kg/day), and determined nephrotoxicity indices, MDA and antioxidant defenses, inflammatory cytokines, and the levels of main proteins in the Nrf2-HO-1 and NLRP3 signaling pathways. Key findings PQQ has significantly decreased the serum levels of creatinine and urea compared to Model group. When treated with PQQ, MDA, IL-1β, IL-6, and TNF-α levels have decreased, and SOD, GSH-Px, and CAT activity have increased in the kidney tissues of CTX-induced mice. PQQ activated the Nrf2-mediated signaling pathway, as indicated by the increased expression of Nrf2, HO-1, GCLM, and NQO1. Moreover, PQQ inhibited the NLRP3 inflammatory pathway, as indicated by the reduced expression of NLRP3, ASC, and Caspase-1. Significance Our results suggest that PQQ protects against CTX-induced nephrotoxicity, probably by activating the Nrf2-mediated antioxidant pathway and inhibiting the NLRP3 inflammatory pathway.

Background: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. Results: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor-a, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-kB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. Conclusions: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

BACKGROUND Spinal cord injury (SCI) is an injury-triggered event that is associated with permanent neurologic deficit. The deficit instigated by SCI leads to medical co-morbidity, not only affecting sensory and motor capabilities, but also having an impact on the physiological and economic condition of the patient. Against this backdrop, the present study was carried out to investigate the effect of lycopsamine, a plant-derived alkaloid in SCI rats. MATERIAL AND METHODS The traumatic SCI injury in rats was created using a force-calibrated weight-drop device. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to investigate the functional consequences of SCI. DAPI (4',6-diamidino-2-phenylindole) and Tunnel staining were used to detect apoptosis. Western blot and qRT-PCR was used to examine the protein and gene expressions, respectively. RESULTS The results revealed that lycopsamine significantly (p

Background: Endometrial cancer (EC) occurs most commonly after menopause. A proportion of patients present with advanced age and comorbidities, and become ineligible for surgery. The optimal treatment strategy of these patients remains a clinical challenge. Aromatase inhibitor (AI) combined with Gonadotropin-releasing hormone agonist (GnRH-a) possesses profound effect in suppressing the estrogen level, has become a valid treatment in the breast cancer. However, the combined use of an AI and a GnRH-a in EC has rarely been studied. Case presentation: Herein, we report the combination of an AI and a GnRH-a in the treatment of three patients with advanced age or comorbidities who were ineligible for surgery. The disease remained stable for two years in patients who received the combination treatment as an initial approach without any adverse effects. Moreover, an AI combined with a GnRH-a also effective as salvage treatment of recurrent patients. Further, we provide a brief review of the literature. Conclusion: The combination of an AI and a GnRH-a presents satisfactory therapeutic effect and provides an optimal option for inoperable EC patients.

Background: Polycythemia vera (PV) is the most common type of Philadelphia-negative myeloproliferative neoplasms (MPNs). PV is a long-term debilitating and life-threatening cancer that is associated with the risk of thrombosis, hemorrhage, and a long-term risk of developing myelofibrosis and acute myeloid leukemia. Early intervention with a disease-modifying treatment that can eradicate the mutated clones is needed to prevent disease progression and transformation. To date, therapeutic options for PV are limited and they only address the signs and symptoms. Most low-risk patients with PV are treated with phlebotomy and low-dose aspirin to manage increased blood viscosity and reduce the risk of vascular events, whereas high-risk and certain low-risk patients are treated with cytoreductive agents. Several cytoreductive agents are available such as hydroxyurea (HU) which is commonly used as a first-line therapy. Ruxolitinib, a JAK2 inhibitor, is also used. While interferon alfa agents have been used off label in clinical practice for more than three decades, their use has been limited due to the tolerability concerns. Ropeginterferon alfa-2b (P1101), a long-acting, mono-pegylated proline interferon, was developed for the treatment of MPNs, including PV. The novel formulation of P1101 improves its pharmacokinetic properties allowing treatment every 2 weeks with improved tolerability and convenience. P1101 was evaluated for the treatment of PV in the phase 3 PROUD-PV trial and its extension study CONTINUATION-PV. In the PROUD-PV study, due to the slow P1101 titration schedule, the maximum P1101 dose was not reached until week 28 and the primary analysis was done at 52 weeks. In CONTINUATION-PV, when patients were on their effective doses, a significantly higher proportion of patients treated with P1101 achieved a complete hematologic response (CHR) with improved disease burden compared to HU-treated patients. At 48 months there was a significant reduction in allelic burden from a baseline of 37.3% to 9.8% with 13.8% of patients achieving a complete molecular response (CMR). The molecular response rates (complete + partial) at 60 months was 69.1%. P1101 was approved by the European Medicines Agency in 2019 and the Taiwan Food and Drug Administration in 2020 as monotherapy in adults for the treatment of PV without symptomatic splenomegaly. Here, we describe a phase 2 study of P1101 in Chinese patients with PV utilizing an accelerated P1101 dose titration schedule. Study Design and Methods: This phase 2, multicenter, single-arm study is designed to evaluate safety and efficacy of P1101 in Chinese patients with PV utilizing a 250-350-500 ug P1101 dose titration schedule. The primary analysis will be conducted at 24 weeks. The study will recruit approximately 49 subjects in 15-20 sites in China. Key eligibility criteria include diagnosis of PV according to the 2016 WHO criteria, and resistance or intolerance to prior HU according to 2020 guidelines of CSCO. Patients who previously received interferon therapy have to be anti-P1101 binding antibody negative during the screening visit to be eligible. The study excludes patients with symptomatic splenomegaly. Eligible patients receive subcutaneous administration of P1101. Patients will receive an initial dose of 250 µg at Week 0, 350 µg at Week 2, and then 500 µg at Week 4. The dose is maintained at the highest dose that can be tolerated and delivers the best disease response. The maximum recommended dose is 500 μg every 2 weeks. Low-dose aspirin is administered during the 52 weeks of study treatment, unless contraindicated. The primary efficacy endpoint is the phlebotomy-free CHR rate at Week 24. Secondary endpoints include changes in hematocrit, white blood cell count, platelet count; time requiring no phlebotomy; time to first response; and duration of response. All patients will continue receiving treatment until week 52 to provide long-term follow-up information (blood parameters, molecular and cytogenetic data, safety parameters, and optional bone marrow data). This study has been granted IND approval by China CDE on Apr2021. Recruitment is expected to begin in early September 2021 with trial results expected in Q3 2022. Figure ： Study Design Figure 1 Figure 1. Disclosures Zagrijtschuk: PharmaEssentia U.S.A. Corp.: Current Employment. Urbanski: PharmaEssentia Corporation: Current Employment. Qin: PharmaEssentia Corp.: Current Employment.

Carpal tunnel syndrome (CTS) is a most common peripheral nerve entrapment neuropathy characterized by sensorimotor deficits in median nerve innervated digits. Block-design task-related functional magnetic resonance imaging (fMRI) studies have been used to investigate CTS-related neuroplasticity in the primary somatosensory cortices. However, considering the persistence of digital paresthesia syndrome caused by median nerve entrapment, spontaneous neuronal activity might provide a better understanding of CTS-related neuroplasticity, which remains unexplored. The present study aimed to investigate both local and extensive spontaneous neuronal activities with resting-state fMRI. A total of 28 bilateral CTS patients and 24 normal controls were recruited, and metrics, including amplitude of low-frequency fluctuation (ALFF) and voxel-wise functional connectivity (FC), were used to explore synaptic activity at different spatial scales. Correlations with clinical measures were further investigated by linear regression. Decreased amplitudes of low-frequency fluctuation were observed in the bilateral primary sensory cortex (SI) and secondary sensory cortex (SII) in CTS patients (AlphaSim corrected P < .05). This was found to be negatively related to the sensory thresholds of corresponding median nerve innervated fingers. In the voxel-wise FC analysis, with predefined seed regions of interest in the bilateral SI and primary motor cortex, we observed decreased interhemispheric and increased intrahemispheric FC. Additionally, both interhemispheric and intrahemispheric FC were found to be significantly correlated with the mean ALFF.

The present study aimed to evaluate the efficacy and safety of acetyl-L-carnitine (ALC) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). The study was carried out as a prospective, randomized, double-blind, placebo-controlled and paralleled clinical study. A total of 239 patients with CIPN were selected as the study subjects. Of the 239 subjects, 118 subjects received 3 g/day ALC orally for 8 weeks and 121 received a placebo. The primary endpoint was improvement of peripheral neuropathy by at least one grade. Patient status was assessed at week 4, 8 and 12 after enrollment into the study. In both the full analysis set (FAS) and the per-protocol set (PPS), peripheral sensory neuropathy was significantly ameliorated in the ALC group with 50.5 and 51.6% patients meeting the primary endpoint at week 8, compared with 24.1 and 23.1% of patients in the placebo group (P

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation–seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.

Peripheral artery disease (PAD) is caused by the building up of plaques in the arteries that carry blood to the lower limbs. The present study aimed to assess the predictive value of the plasma levels of P-selectin (Ps) or endothelin-1 (ET-1) regarding the occurrence of vascular restenosis after endovascular therapy for PAD. Patients with or without vascular restenosis confirmed by computed tomography angiography after endovascular therapy between March and December 2015 (n=20 per group) were enrolled. The serum levels of Ps and ET-1 prior to the operation and at 1 h, as well as 1, 2 and 3 weeks after the operation were compared between the two groups. At 1 h after the operation, the serum levels of Ps and ET-1 were significantly increased as compared with the pre-operative levels (P0.05). The diagnostic sensitivity and specificity of the serum ET-1 levels at 1 h after the operation for predicting post-operative restenosis in PAD patients with a cut-off of 0.1089 pg/ml were 85 and 85%, respectively. In conclusion, the serum levels of Ps and ET-1 have a high predictive value for post-operative vascular restenosis after endovascular therapy for PAD patients.

The objective of the study was to investigate the feasibility of CUBE-SITR MRI and high-frequency ultrasound for the structural imaging of the brachial plexus to exclude neoplastic brachial plexopathy or structural variation and measure the lengths of anterior and posterior divisions of the C7 nerve, providing guidelines for surgeons before contralateral cervical 7 nerve transfer.A total of 30 patients with CNS and 20 with brachial plexus injury were enrolled in this retrospective study. All patients underwent brachial plexus CUBE-STIR MRI and high-frequency ultrasound, and the lengths of the anterior and posterior divisions of C7 nerve were measured before surgery. Precise length of anterior and posterior divisions of contralateral C7 nerve was measured during surgery.MRI-measured lengths of anterior and posterior divisions of C7 nerves were positively correlated with that measured during surgery (anterior division, r = 0.94, p .01; posterior division, r = 0.92, p .01). High agreement was found between MRI-measured and intra-surgery measured length of anterior and posterior divisions of C7 nerve by BLAD-ALTMAN analysis. Ultrasonography could feasibly image supraclavicular C7 nerve and recognize small variant branches derived from middle trunk of C7 nerve root, which could be dissected intra-operatively and confirmed by electromyography during the procedure of contralateral C7 nerve transfer.CUBE-STIR MRI had advantages for the imaging of the brachial plexus and measurement of the length of root-trunk-anterior/posterior divisions of C7 nerve. The clinical role of ultrasonography may be a simple way of evaluating general condition of C7 nerve and provide guidelines for contralateral C7 nerve transfer surgery.

IntroductionEarly adolescence is a developmental period in which peer victimization, bullying, relational aggression, and social exclusion are particularly prominent. As these behaviors have long-term implications for children, in this study, we investigated early variations of prosocial behaviors as one of the critical precedents that shape youth's subsequent peer relational outcomes. Specifically, we identified different profiles of prosocial behaviors in middle childhood (Grade 4) and related these profiles to peer relationships in early adolescence (Grade 6).MethodUsing longitudinal data from the NICHD Study of Early Child Care and Youth Development (N=914; 52% girls), a three-step latent profile analysis was conducted on Grade 4 prosocial behaviors, which were then related to Grade 6 teacher- and student-rated peer relationships (e.g., relational aggression).ResultsFour patterns of prosocial behaviors emerged: low prosocial (18%), high prosocial (67%), primarily friendly (8%), and primarily kind (7%). These four patterns of prosocial behaviors were differentially related to later problematic peer relationships: Low prosocial youth demonstrated the most problematic peer relationships (Mdiff=0.36-0.93, all p&nbsp

FosB, a Mg2+ dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.

Objective: Contralateral C7 nerve root transfer surgery has been successfully applied to rescue motor function of a hemiplegic upper extremity in patients with central neurological injury. This surgical technique is challenging, and limited anatomical space makes it difficult to manipulate tissues and may lead to higher complication rates. The authors hypothesis a new surgical route in which cervical nerve roots of both donor and recipient sides are exposed from a posterior intradural approach and neurorrhaphy is performed easily and clearly. The feasibility of this operation is tested in a cadaver model. Methods: A fresh cadaver was placed prone. After a standard midline incision and extensive cervical laminectomy, the dura and arachnoid were widely opened, and the spinal nerve roots of C6, C7, and C8 were exposed bilaterally. Nerve grafting was attempted between pairs of donor and recipient nerve roots on contralateral sides of the spinal cord. After completion of neurorrhaphy, the dura was closed. Results: Precise neurorrhaphy could be performed intradurally between posterior and anterior nerve roots of C7 on both sides. Multiple anastomoses of C7 to various nerve roots on the contralateral side could also be performed within the same surgical field with an interposition nerve graft. Conclusion: The posterior intradural repair idea affords many advantages, the pathway is shorter and more straightforward, which provides more access to multiple nerve roots repair in one surgical field, and is more familiar to many neurosurgeons and spine surgeons. It may potentially be adapted for clinical use.

Spastic arm paralysis after central neurological injury has a long-term effect on the patient's quality of life. Effective neurosurgical treatment for this dysfunction has been described in our previous studies. It is of great significance to determine a set of unified and concise clinical standards for motor function grading in the neurosurgical treatment and management.We first conducted a retrospective study that included 51 hemiplegic patients from the Neurosurgery and Microsurgery outpatient database of Huashan Hospital. The neurosurgeons cooperated with rehabilitation experts to design and administer the new rating system (Hua-Shan Grading of Upper Extremity, H-S grading) after analyzing the scale scores and video records of these patients. We then randomly enrolled 64 patients with unilateral spastic arm paralysis after stroke or brain trauma. The Fugl-Meyer Assessment, the Ashworth scale and the new grading system were applied and analyzed to evaluate the participants' motor function.Based on rehabilitation medicine scales and long-term follow-up, a feasible and concise grading system was applied that was based on the patients' characteristics and the examination experiences of neurosurgeons and rehabilitation experts in clinical practice. This method could effectively grade upper extremity motor function, usually in 3-5 minutes. A significant correlation was found between H-S grading and the Fugl-Meyer score by the Spearman test (r = .937, P.01). The mean difference between any two levels of the new grading system was significant (P.05). And good test-retest reliability, the Cronbach's alpha coefficient and the validity indices were presented. In addition, it was more sensitive to motor function compared with the Ashworth scale.As a supplement to the classic scales, H-S grading was developed in the area of spastic hemiplegia treatment. It is standardized and simplified for patients in the chronic stage after central neurological injury.

Patients with cerebral palsy and spastic hemiplegia may have extremely poor upper extremity function. Unfortunately, many current therapies and treatments for patients with spastic hemiplegia offer very limited improvements. One innovative technique for treating these patients is the use a contralateral C7 nerve root transfer to neurotize the C7 nerve root in the affected limb. This may result not only in less spasticity in the affected limb, but also improved control and motor function vis-a-vis the new connection to the normal cerebral hemisphere. However, contralateral C7 transfers can require large incisions and long nerve grafts. The aim of this study was to test the feasibility of a contralateral C7 nerve root transfer procedure with the use of a prevertebral minimally invasive robot-assisted technique. In a cadaver, both sides of the C7 root were dissected. The right recipient C7 root was resected as proximally as possible, while the left donor C7 root was resected as distally as possible. With the use of the da Vinci (®) SI surgical robot (Intuitive Surgical ™, Sunnyvale, CA, USA), we were able to eliminate the large incision and use a much shorter nerve graft when performing contralateral C7 nerve transfer.

Chronic heart failure (CHF) may be associated with an energy deficit in cardiac muscle. As levo-carnitine (LC) is involved in the production of myocardial energy, it is hypothesized that LC supplementation may ameliorate CHF symptoms. This multicentre, randomized, double-blind, and placebo-controlled study included 265 patients with CHF. Patients were randomized to receive either LC or placebo, twice a day. Endpoints were measured after 7 days of treatment. Primary endpoint was a reduction of at least one NYHA class. Secondary endpoints were changes in 6-min walk distance (6-MWD) compared with baseline, either alone or in combination with NYHA class decrease, left ventricular ejection fraction, and NT-proBNP level, together with adverse events. The primary endpoint was reached in 60.9% of patients treated with LC, compared with only 44.7% of the placebo group ( P = 0.012). Among the secondary endpoints, 6-MWD, alone or in combination with NYHA class, improved significantly in the LC group compared with placebo ( P = 0.0497 and P = 0.003, respectively). l-Carnitine was well tolerated. The lowest baseline values of plasma-free carnitine were observed in patients with NYHA classes III and IV where the effect of LC supplementation was greatest ( P = 0.002). Treatment with LC significantly improved CHF symptoms in Chinese patients, probably by correcting a status of carnitine insufficiency.

Human health is threatened by obesity which causes the increasing incidence of various diseases, especially stroke. Ischemic stroke (IS) is mostly caused by the rupture of arterial plaque, whose instability is positively associated with matrix metalloproteinases (MMPs) that degrades extracellular matrix components. Studies have shown that matrix metalloproteinase-12 (MMP-12) may be involved in the pathogenesis of IS. Because of the higher incidence of stroke in obese patients than that in normal weight people, it is urgent for obesity to forecast stroke early. Considering high levels MMP-12 in obesity, we put forward that MMP-12 may be a potential biomarker for IS in obese patients.

We previously demonstrated that for long-term spastic limb paralysis, transferring the seventh cervical nerve (C7) from the nonparalyzed side to the paralyzed side results in increase of 17.7 in Fugl-Meyer score. One strategy for further improvement in voluntary arm movement is selective activation of five target muscles innervated by C7 during recovery process. In this study, we develop an implantable multisite optogenetic stimulation device (MOSD) based on shape-memory polymer. Two-site stimulation of sciatic nerve bundles by MOSD induces precise extension or flexion movements of the ankle joint, while eight-site stimulation of C7 nerve bundles induce selective limb movement. Long-term implant of MOSD to mice with severed and anastomosed C7 nerve is proven to be both safe and effective. Our work opens up the possibility for multisite nerve bundle stimulation to induce highly-selective activations of limb muscles, which could inspire further applications in neurosurgery and neuroscience research., Optogenetic stimulation of damaged peripheral nerves has advantages over electrical stimulation but it’s limited to single-site stimulation. Here the authors develop a spiral-shaped LED implant for precise optogenetic stimulation of peripheral nerve bundles at multiple sites and use it to induce distinct limb movements in mice.

Background Spasticity and muscle weakness are common severe neurologic sequelae after stroke. Contralateral peripheral neurotization has been applied successfully to promote motor function of the hemiplegic upper extremity in patients with central neurological injury. To our knowledge, we present the first report of contralateral lumbar to sacral nerve transfer for the lower extremities in hemiplegic patients after stroke. Case Description Two patients were enrolled in the study. The first patient is a 57-year-old man who experienced permanent muscle weakness in his left leg after a right cerebral infarction. The second patient is a 42-year-old man who had spasticity and hemiplegia in both upper and lower limbs on the right side 32 months after a left cerebral hemorrhage. Both patients underwent contralateral lumbar–to–sacral nerve rerouting to improve lower-limb motor function. Twenty months after surgery, both patients experienced significant improvement in ambulatory status. Conclusions Although long-term follow-up and a randomized controlled trial are required, this study demonstrates the safety and possible benefits of contralateral lumbar–to–sacral nerve transfer for hemiplegic patients after stroke. This novel surgical approach could provide a new means for lower-limb motor functional recovery.

Electrical stimulation could enhance nerve regeneration and functional recovery. The objective of this study was to evaluate the regenerative effects of implanted electrodes with different contacts in resected sciatic nerve. Sciatic nerve resection and microsurgical repair models were established and randomly divided into four groups (point contact, 1/4 circle contact; whole-circle contact; no electrodes as control). Electrical stimulation was performed and electrophysiological, morphological and histological exams (of the sciatic nerve and muscle) were conducted at 4 and 10 weeks post-implantation. Point and 1/4 circle contact groups showed significantly higher scores in the sciatic functional index (SFI), increased amplitude of compound muscle action potential (AMP) and motor nerve conduction velocity (MNCV) compared to the control group at both 4 and 10 weeks post-implantation. Point and 1/4 circle contact morphologically promoted sciatic nerve regeneration and reduced muscular atrophy with less mechanical injury to the nerve trunk observed compared with the whole-circle contact group at both 4 and 10 weeks post-implantation. Electrodes with point and 1/4 circle contacts represented an alternatively portable and effective method of electrical stimulation to facilitate injured sciatic nerve regeneration and reduce subsequent muscular atrophy, which might offer a promising approach for treating peripheral nerve injuries.

OBJECTIVEContralateral C7 (CC7) nerve root has been used as a donor nerve for targeted neurotization in the treatment of total brachial plexus palsy (TBPP). The authors aimed to study the contribution of C7 to the innervation of specific upper-limb muscles and to explore the utility of C7 nerve root as a recipient nerve in the management of TBPP.METHODSThis was a 2-part investigation. 1) Anatomical study: the C7 nerve root was dissected and its individual branches were traced to the muscles in 5 embalmed adult cadavers bilaterally. 2) Clinical series: 6 patients with TBPP underwent CC7 nerve transfer to the middle trunk of the injured side. Outcomes were evaluated with the modified Medical Research Council scale and electromyography studies.RESULTSIn the anatomical study there were consistent and predominantly C7-derived nerve fibers in the lateral pectoral, thoracodorsal, and radial nerves. There was a minor contribution from C7 to the long thoracic nerve. The average distance from the C7 nerve root to the lateral pectoral nerve entry point of the pectoralis major was the shortest, at 10.3 ± 1.4 cm. In the clinical series the patients had been followed for a mean time of 30.8 ± 5.3 months postoperatively. At the latest follow-up, 5 of 6 patients regained M3 or higher power for shoulder adduction and elbow extension. Two patients regained M3 wrist extension. All regained some wrist and finger extension, but muscle strength was poor. Compound muscle action potentials were recorded from the pectoralis major at a mean follow-up of 6.7 ± 0.8 months; from the latissimus dorsi at 9.3 ± 1.4 months; from the triceps at 11.5 ± 1.4 months; from the wrist extensors at 17.2 ± 1.5 months; from the flexor carpi radialis at 17.0 ± 1.1 months; and from the digital extensors at 22.8 ± 2.0 months. The average sensory recovery of the index finger was S2. Transient paresthesia in the hand on the donor side, which resolved within 6 months postoperatively, was reported by all patients.CONCLUSIONSThe C7 nerve root contributes consistently to the lateral pectoral nerve, the thoracodorsal nerve, and long head of the triceps branch of the radial nerve. CC7 to C7 nerve transfer is a reconstructive option in the overall management plan for TBPP. It was safe and effective in restoring shoulder adduction and elbow extension in this patient series. However, recoveries of wrist and finger extensions are poor.

BACKGROUND Central neurological injury (CNI) is a major contributor to physical disability that affects both adults and children all over the world. The main sequelae of chronic stage CNI are spasticity, paresis of specific muscles, and poor selective motor control. Here, we apply the concept of contralateral peripheral neurotization in spasticity releasing and motor function restoration of the affected upper extremity. OBJECTIVE A clinical investigation was performed to verify the clinical efficacy of contralateral C7 neurotization for rescuing the affected upper extremity after CNI. METHODS In the present study, 6 adult hemiplegia patients received the nerve transfer surgery of contralateral C7 to C7 of the affected side. Another 6 patients with matched pathological and demographic status were assigned to the control group that received rehabilitation only. During the 2-year follow-up, muscle strength of bilateral upper extremities was assessed. The Modified Ashworth Scale and Fugl-Meyer Assessment Scale were used for evaluating spasticity and functional use of the affected upper extremity, respectively. RESULTS Both flexor spasticity release and motor functional improvements were observed in the affected upper extremity in all 6 patients who had surgery. The muscle strength of the extensor muscles and the motor control of the affected upper extremity improved significantly. There was no permanent loss of sensorimotor function of the unaffected upper extremity. CONCLUSION This contralateral C7 neurotization approach may open a door to promote functional recovery of upper extremity paralysis after CNI.

Background It is well known that Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and synaptic dysfunction play important roles in the pathophysiology of Alzheimer’s disease (AD). The Huatuo Zaizao pill (HT) is a Traditional Chinese Medicine (TCM) that has been used clinically for many years in China, mainly for post-stroke rehabilitation and cognitive decline; however, the mechanism of cognitive function is not clear. In this study, we investigated the effect of HT on hippocampal synaptic function, Amyloid-β (Aβ) deposition in APP/PS1 AD transgenic mice. Method Six-month-old APP/PS1 transgenic (Tg) mice were randomly divided into control, HT-treated, and memantine (MEM)-treated groups. Then, these groups were orally administered vehicle (for the control), HT (0.25 g/kg) and MEM (5 mg/kg) respectively for 4 weeks. The Morris water maze, Novel Object Recognition, and Open field tests were used to assess cognitive behavioral changes. We evaluated the effects of HT on neuronal excitability, membrane ion channel activity, and synaptic plasticity in acute hippocampal slices by combining electrophysiological extracellular tests. Synaptic morphology in the hippocampus was investigated by electron microscopy. Western blotting was used to assess synaptic-associated protein and Aβ production and degrading levels. Immunofluorescence staining was used to determine the relative integrated density. Results HT can ameliorate hippocampus-dependent memory deficits and improve synaptic dysfunction by reversing LTP impairment in APP/PS1 transgenic mice. Moreover, HT reduces amyloid plaque deposition by regulating α-secretase and γ-secretase levels. Conclusion HT can improve the learning and memory function of APP/PS1 transgenic mice by improving synaptic function and reducing amyloid plaque deposition. Electronic supplementary material The online version of this article (10.1186/s12906-018-2237-2) contains supplementary material, which is available to authorized users.

Vestibular evoked myogenic potential (VEMP) in response to a loud air conducted sound (ACS) recorded from extraocular muscles, the so-called ocular VEMP (oVEMP), has been confirmed to be able to evaluate utricular function. This study aimed to evaluate the effect of sleep deprivation (SD) on oVEMP parameters. oVEMPs were recorded in 20 male healthy subjects once after an ordinary sleep and once after 26–29 h of SD. The latencies of peak N1 and P1, N1-P1 amplitude, N1-P1 interval, and asymmetry ratio (AR) of oVEMP recorded from both eyes under normal sleep and SD conditions were 10.04 ± 0.59 ms versus 10.56 ± 0.69 ms (left eye), 14.95 ± 0.92 ms versus 15.64 ± 1.05 ms (left eye), and 7.44 ± 2.86 µV versus 5.26 ± 2.15 µV (left eye); 10.08 ± 0.66 ms versus 10.64 ± 0.73 ms (right eye), 14.88 ± 0.89 ms versus 15.59 ± 1.02 ms (right eye), and 7.16 ± 2.88 µV versus 5.04 ± 2.05 µV(right eye); 10.40 ± 5.81% versus 11.43 ± 6.37%, respectively. After SD, the latencies of oVEMP were delayed and N1-P1 amplitude was lower, whereas N1-P1 interval and AR remained unchanged. The present study showed that oVEMP test could be used to evaluate the fatigue induced by SD.

Craniopharyngioma (CP), a rare benign and slow-growing epithelial tumor, is mainly located within the sellar/parasellar region. Primary CP involving the nasal cavity and the sellar region with extensive erosion of the skull base and ossification simultaneity has not been described previously. The authors report a 23-year-old man who presented to our institute with complaints of repeated nasal cavity bloodshed, liquid flow, and progressive visual loss. A neuroimaging examination showed a giant cranionasal and cystic-solid CP extending from the suprasellar region to the nasopharynx with inhomogeneous enhancement, which is associated with extensive erosion of the skull base and ossification. The patient underwent a transsphenoidal surgery to resect the nasopharyngeal component of CP and a subfrontal craniotomy with a total removal of intracranial component by grinding 3 months later. A histopathologic examination revealed characteristic features of adamantinomatous CP associated with ossification. The current study demonstrates that CP can exhibit cranionasal growth pattern and arise from residue of craniopharyngeal duct. Extensive erosion of the skull base, calcification, and ossification can present in tumor simultaneity. A 2-stage stratagem is important for its total removal because of the peculiar hardness. Postsurgical course is unevenly and should be dealt with carefully.

Spatial disorientation in airplane pilots is a leading factor in many fatal flying accidents. Spatial orientation is the product of integrative inputs from the proprioceptive, vestibular, and visual systems. One condition that can lead to sudden pilot incapacitation in fight is vestibular neuritis. Vestibular neuritis is commonly diagnosed by a finding of unilateral vestibular failure, such as a loss of caloric response. However, because caloric response testing reflects the function of only the superior part of the vestibular nerve, it cannot detect cases of neuritis in only the inferior part of the nerve. We describe the case of a Chinese naval command fighter pilot who exhibited symptoms suggestive of vestibular neuritis but whose caloric response test results were normal. Further testing showed a unilateral loss of vestibular evoked myogenic potentials (VEMPs). We believe that this pilot had pure inferior nerve vestibular neuritis. VEMP testing plays a major role in the diagnosis of inferior nerve vestibular neuritis in pilots. We also discuss this issue in terms of aeromedical concerns.

The present study was performed in China to compare the efficacy and safety of an advanced wound dressing made of crystalline cellulose (Veloderm) to a conventional treatment of three Vaseline gauzes in the management of skin donor sites of burns or reconstructive plastic surgery. In this prospective, multicenter, open-labeled, randomized clinical trial performed in three Chinese burn centers in China, 96 patients who required autologous split skin graft were randomized into either the test (Veloderm) group or the control (Vaseline gauze) group. Average healing times in the test group and in the control group were 8.40±2.90 and 8.92±2.58 days, respectively, with median values of 7.00 and 8.00 days, respectively: the difference between two groups was statistically significant (P=.045). Scores for exudates, pain intensity, and peripheral erythema showed no difference between the groups; however, composite scores of three variables on day 10 postoperatively was significantly lower in the test group (0.00±0.00 vs. 0.13±0.49; P = .043). The need for a dressing change was also significantly lower in the test group (12.5 vs. 31.25%; P = .036). Veloderm is a safe and effective dressing that may offer some advantages over the traditional application of Vaseline gauze in the management of donor sites in burn or reconstructive plastic surgery patients.

Objective There is little information available regarding Chinese patients with Hodgkin lymphoma (HL). We analyzed the clinical features, outcome, and prognostic factors of Chinese patients with HL, aiming to establish a new risk model for better risk-adapted therapeutic strategy. Patients and Methods Patients with newly diagnosed HL at 4 medical centers from January 2000 to August 2014 were recruited. Results A total of 150 patients were reviewed. The median age was 30 years (range, 15-91 years). At completion of initial therapy, 73.65% of patients achieved complete remission. The 5-year event-free survival (EFS) of the entire cohort was 61.1%, the overall survival was 84.7%, and the disease-free survival was 78.8%. B symptoms, extranodal involvement, and International Prognostic Score ≥ 3 remained as independent prognostic factors of EFS. Patients who failed to reach complete remission on interim positron emission tomography/computed tomography or computed tomography had a significantly worse outcome than those who did. A new risk model incorporating traditional risk factors and interim response stratified patients into 3 classes, with a 5-year EFS of 100%, 83.1%, and 33.1%, respectively ( P Conclusions General clinical features were comparable with those of Western patients, whereas therapeutic outcomes were slightly inferior. The novel risk assessment model showed potential as a more powerful prognostic tool by identifying 3 subsets of patients with significantly distinct outcomes, which warrants further validations.

We introduce a more flexible optogenetics-based mapping system attached on a stereo microscope, which offers automatic light stimulation to individual regions of interest in the cortex that expresses light-activated channelrhodopsin-2 in vivo. Combining simultaneous recording of electromyography from specific forelimb muscles, we demonstrate that this system offers much better efficiency and precision in mapping distinct domains for controlling limb muscles in the mouse motor cortex. Furthermore, the compact and modular design of the system also yields a simple and flexible implementation to different commercial stereo microscopes, and thus could be widely used among laboratories.

This study evaluated the ability of human osteoprotegerin gene-modified autologous periodontal ligament cells (PDLCs) in combination with cell transplantation to promote periodontal regeneration in beagle dogs. Adenovirus Ad5-hOPG-EGFP-transfected PDLCs and BME-10X collagen membranes were fabricated and used for periodontal repair. Buccal periodontal defects (mesiodistal width × depth: 5 × 5 mm) were created on the second, third, and fourth mandibular premolars in six normal beagle dogs, and the defects were histologically and histomorphometrically assessed for periodontal regeneration in the following four groups: (1) hOPG-PDLCs + BME-10X, (2) mock-PDLCs + BME-10X, (3) PDLCs + BME-10X, and (4) BME-10X. The radiographic and histological results suggested that hOPG-PDLCs significantly promoted periodontal defect repair. This study demonstrates the potential of hOPG-modified PDLCs for periodontal tissue regeneration.

To evaluate the safety and effectiveness of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions, an open, multicenter, controlled, phase Ⅳ clinical trial was conducted in the drug clinical trial centers of 16 domestic hospitals. 2 123 patients from June 10, 2011 to November 29, 2012 were enrolled in the trial. Drug clinical trial was approved by Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital Ethics Committee before implementation. Before the start of trial, subjects were selected according to the research scheme and inclusion criteria, then they would step into the 14 d study after signing Informed Consent Form. All subjects were treated according to the research scheme, evaluated the conditions and filled in CFR sheet, to provide the evaluation data and information on safety and efficacy of Shenbei Guchang capsules. Shenbei Guchang capsules were used to treat diarrhea type irritable bowel syndrome in widely used conditions (2 123 cases), and 2 029 cases of them entered FAS set, cure+markedly effective in 1 921 cases, with a comprehensive curative effect rate of 94.68%; 2 010 cases of them entered PPS set, cure+markedly effective in 1 906 cases, with a comprehensive curative effect rate of 94.83%. The primary symptoms of IBS were abdominal pain and diarrhea. After treatment, both abdominal pain and diarrhea were improved, with significant differences (P

There have been controversies on the contribution of contralesional hemispheric compensation to functional recovery of the upper extremity after a unilateral brain lesion. Some studies have demonstrated that contralesional hemispheric compensation may be an important recovery mechanism. However, in many cases where the hemispheric lesion is large, this form of compensation is relatively limited, potentially due to insufficient connections from the contralesional hemisphere to the paralyzed side. Here, we used a new procedure to increase the effect of contralesional hemispheric compensation by surgically crossing a peripheral nerve at the neck in rats, which may provide a substantial increase in connections between the contralesional hemisphere and the paralyzed limb. This surgical procedure, named cross-neck C7-C7 nerve transfer, involves cutting the C7 nerve on the healthy side and transferring it to the C7 nerve on the paretic side. Intracortical microstimulation, Micro-PET and histological analysis were employed to explore the cortical changes in contralesional hemisphere and to reveal its correlation with behavioral recovery. These results showed that the contralesional hemispheric compensation was markedly strengthened and significantly related to behavioral improvements. The findings also revealed a feasible and effective way to maximize the potential of one hemisphere in controlling both limbs.

The morbidity of hepatocellular carcinoma (HCC), which has become a significant killer to human life, is getting higher over the years. Not only the shape and structure of liver cells are abnormal in pathological images, but also liver cell cords show some unusual phenomena, such as incrassation and disorder. So our paper proposes a novel method of HCC pathological images recognition based on morphological distribution of liver cell cords, to assist pathologist to diagnose hepatic pathology. In the method, we firstly apply binarization and morphological operation to hepatic pathological images, and screen connected regions with their area and circularity. Adopted regions are considered as candidate centers of liver cell cords (vein center). Secondly we define different features (irregularity feature), according to the number of candidate centers in a pathological image, to recognize how structured liver cell cords are. Finally, we utilize the feature and classifier to identify HCC pathological images. The experiments indicate that the proposed method shows high accuracy of all HCC pathological images in well, moderately, poorly differentiated and normal forms.

AIMS The use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical observational and experimental studies but has remained inadequately explored. This study was designed to examine whether statins can reduce the risk of AF.

Leukemic transformation (LT) of myeloproliferative neoplasms (MPNs) is associated with a poor prognosis and resistance to therapy. Although previous candidate genetic studies have identified mutations in MPN patients who develop acute leukemia, the complement of genetic abnormalities in MPN patients who undergo LT is not known nor have specific molecular abnormalities been shown to have clinical relevance in this setting. We performed high-throughput resequencing of 22 genes in 53 patients with LT after MPN to characterize the frequency of known myeloid mutations in this entity. In addition to JAK2 and TET2 mutations, which occur commonly in LT after MPN, we identified recurrent mutations in the serine/arginine-rich splicing factor 2 (SRSF2) gene (18.9%) in acute myeloid leukemia (AML) transformed from MPNs. SRSF2 mutations are more common in AML derived from MPNs compared with LT after myelodysplasia (4.8%) or de novo AML (5.6%), respectively (P = .05). Importantly, SRSF2 mutations are associated with worsened overall survival in MPN patients who undergo LT in univariate (P = .03; HR, 2.77; 95% CI, 1.10-7.00) and multivariate analysis (P < .05; HR, 2.11; 95% CI, 1.01-4.42). These data suggest that SRSF2 mutations contribute to the pathogenesis of LT and may guide novel therapeutic approaches for MPN patients who undergo LT.