3D SHINKEI MR neurography in evaluation of traumatic brachial plexus.

3D SHINKEI neurography is a new sequence for imaging the peripheral nerves. The study aims at assessing traumatic brachial plexus injury using this sequence. Fifty-eight patients with suspected trauma induced brachial plexus injury underwent MR neurography (MRN) imaging in 3D SHINKEI sequence at 3 T. Surgery and intraoperative somatosensory evoked potentials or clinical follow-up results were used as the reference standard. MRN, surgery and electromyography (EMG) findings were recorded at four levels of the brachial plexus-roots, trunks, cords and branches. Fifty-eight patients had pre- or postganglionic injury. The C5-C6 nerve postganglionic segment was the most common (average 42%) among the postganglionic injuries detected by 3D SHINKEI MRN. The diagnostic accuracy (83.75%) and the specificity (90.30%) of MRN higher than that of EMG (p < 0.001). There was no significant difference in the diagnostic sensitivity of MRN compared with EMG (p > 0.05). Eighteen patients with brachial plexus injury underwent surgical exploration after MRN examination and the correlation between MRN and surgery was 66.7%. Due to the high diagnostic accuracy and specificity, 3D SHINKEI MRN can comprehensively display the traumatic brachial plexus injury. This sequence has great potential in the accurate diagnosis of traumatic brachial plexus injury.

Effect of Quality of Life on Radiation Adherence for Patients With Cervical Cancer in an Urban Safety Net Health System.

PURPOSE: Outcomes for patients undergoing chemoradiation for cervical cancer are dependent on adherence to radiation therapy (RT). In other diseases, quality of life (QoL) is associated with treatment adherence, but the association between QoL and RT adherence for patients with cervical cancer remains unclear. METHODS AND MATERIALS: This prospective study included patients undergoing RT for cervical cancer from 2017 to 2021 at an urban safety net hospital. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 was used to assess QoL based on 5 subscales (physical, functional, social and emotional, and cervical-cancer specific). The survey was administered at radiation consult, then weekly during RT and at follow-up. Patient information was abstracted from the medical record. Radiation nonadherence was defined as missing ≥2 days of external beam RT. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 total and subscale scores were compared between adherent and nonadherent patients. Multivariable logistic regression was performed to control for confounding variables. RESULTS: Ninety-three patients were enrolled, completing 522 surveys. Median age at diagnosis was 46 years (interquartile range, 40-51); 76% of patients were Hispanic, and 12% were Black. Only 30% of patients were nonadherent with RT. A psychiatric comorbidity (P = .012) and symptomatic presentation (P = .027) were associated with decreased adherence. Baseline total QoL was higher in treatment-adherent than in nonadherent patients (median, 124.86; range, 48-160; 108.9, 46-150; P = .01). Higher baseline functional and physical subscale scores were associated with adherence (P < .05). Change from baseline to lowest score during treatment in the emotional subscale was also associated with patient adherence (P < .05). In multivariable analysis, higher baseline physical score, baseline total score, and change in emotional subscale score were associated with adherence (P < .05). CONCLUSIONS: Poor QoL during chemoradiation for cervical cancer is associated with missed treatments. Physician assessment of a patient's well-being while they are undergoing RT is of utmost importance to improve adherence to treatment.

Red fluorescent AIEgens based multifunctional nonviral gene vectors for the efficient combination of gene therapy and photodynamic therapy in anti-cancer.

Precise molecular engineering of AIEgens-based cationic delivery systems for high transfection efficiency (TE) and effective photodynamic therapy (PDT) holds a huge potential for cancer treatment. Herein, three amphiphiles (DT-C6/8/12-M) consisting of di(triazole-[12]aneN3) (M) and 1,1-dicyano-2-phenyl-2-(4-diphenylamino)phenyl-ethylene (DT) units have been developed to achieve luminescent tracking, efficient TE, and effective PDT in vitro and in vivo. These compounds exhibited strong aggregated induced emission (AIE) at 630 nm and mega Stokes shifts of up to 160 nm. They were able to bind DNA into nanoparticles with suitable sizes, positive surface potential, and good biocompatibility in the presence of DOPE. Among them, vector DT-C12-M/DOPE with n-dodecyl linker achieved a transfection efficiency as high as 42.3 folds that of Lipo2000 in PC-3 cell lines. DT-C12-M/DOPE exhibited the capability of successful endo/lysosomal escape and rapid nuclear delivery of pDNA, and the gene delivery process was clearly monitored via confocal laser scanning microscopy. Moreover, efficient reactive oxygen species (ROS) generation by DT-C12-M upon light irradiation led to effective PDT in vitro . We further show that combination of p53 gene therapy and PDT dramatically enhanced cancer therapeutic outcome in vivo. This "three birds, one stone" strategy offers a novel and promising approach for real-time tracking of gene delivery and better cancer treatment.

Heavy Metal Pollution and Health Risk Assessment of Vegetable-Soil Systems of Facilities Irrigated with Wastewater in Northern China.

Soil pollution by heavy metals is a major concern in China and has received much attention in recent years. Aiming to investigate the status of heavy metal pollution and the safety of vegetables in the soil of wastewater-irrigated facilities, this study investigated the distribution and migration characteristics of heavy metals in vegetable−soil systems of facilities in a typical sewage irrigation area of the Xi River, Shenyang City, northern China. Health risks due to the fact of exposure to heavy metals in the vegetable soil of facilities and ingrown vegetables through different exposure pathways were evaluated. Spatial interpolation and a potential ecological risk assessment were applied to evaluate the soil quality. Bioaccumulation factors (BCFs) were used to analyze the absorption and transportation capacity of Cd, Cu, Pb, and Zn by different parts of different vegetables. The results showed that the average concentration of Cd exceeded the standard values by 1.82 times and accumulated by 11 times, suggesting that Cd poses the most severe pollution among the four metals in the soil of facilities in the Xi River sewage irrigation area. In the city, a significant accumulation of Cd in the soil was identified with different spatial distributions. Cd also contributed the most in terms of the estimated potential ecological risk index, while the impacts of the other three metals were relatively small. The concentrations of heavy metals were mostly lower than the limit set by the corresponding Chinese standards. Various BCFs were observed for the four metals in the order Cd > Zn > Cu > Pb. Vegetables also demonstrated different BCFs in the order of leaf vegetables > Rhizome vegetable > Solanaceae vegetable. The magnitude of the noncarcinogenic risk for all four heavy metals was less than one for all three exposure routes and did not cause significant noncarcinogenic health effects in humans. However, the carcinogenic risk of Cd from some vegetables via dietary intake was considered higher. Protection measures should be taken to implement better pollution control and land use planning.

Sp1 induced gene TIMP1 is related to immune cell infiltration in glioblastoma.

Tumor immune microenvironment exerts a profound effect on the population of infiltrating immune cells. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is frequently overexpressed in a variety of cells, particularly during inflammation and tissue injury. However, its function in cancer and immunity remains enigmatic. In this study, we find that TIMP1 is substantially up-regulated during tumorigenesis through analyzing cancer bioinformatics databases, which is further confirmed by IHC tissue microarrays of clinical samples. The TIMP1 level is significantly increased in lymphocytes infiltrating the tumors and correlated with cancer progression, particularly in GBM. Notably, we find that the transcriptional factor Sp1 binds to the promoter of TIMP1 and triggers its expression in GBM. Together, our findings suggest that the Sp1-TIMP1 axis can be a potent biomarker for evaluating immune cell infiltration at the tumor sites and therefore, the malignant progression of GBM.

Fast Ripples as a Biomarker of Epileptogenic Tuber in Tuberous Sclerosis Complex Patients Using Stereo-Electroencephalograph.

Objectives: To evaluate the value of fast ripples (FRs) (200-500 Hz) recorded with stereo-electroencephalograph (SEEG) in the localization of epileptogenic tubers in patients with tuberous sclerosis complex (TSC). Methods: Seventeen TSC patients who underwent preoperative SEEG examination and resective epilepsy surgery were retrospectively enrolled. They were divided into two groups according to the seizure control at 1-year postoperative follow-up. The occurrence frequencies of FRs were automatically counted, and the FR rate was calculated. The high FR rate was defined as FR rate ≧0.5. According to different positions, the contacts' locations were divided into three groups: inner of the tubers, the junction region of the tubers, and out of the tubers. The influence factors of postoperative seizure freedom were also analyzed. Results: Twelve patients reached postoperative seizure freedom at 1-year follow-up. In total, FRs were found in 24.2% of the contacts and 67.1% of the tubers in all assessed patients. There were 47 high FR rate contacts localized in the junction region of the tubers, which was 62.7% of the 75 high FR rate contacts in total and was 8.4% of the total 561 contacts localized in the junction region of the tubers. Total removal of epileptogenic tubers and total resection of the high FR rate tubers/contacts were associated with postoperative seizure freedom (P < 0.05). Conclusion: FRs could be extensively detected in TSC patients using SEEG, and high FR rate contacts were mostly localized in the junction region of the epileptogenic tuber, which could aid in the localization of epileptogenic tubers.

Deep brain stimulation of the anterior nucleus of the thalamus in a patient with super-refractory convulsive status epilepticus.

We report the first patient to die from refractory convulsive status epilepticus (SE) after the removal of a stimulator. The removal occurred after a two-year period of successful control of super-refractory convulsive SE with deep brain stimulation of the bilateral anterior nucleus of the thalamus (ANT-DBS). The female patient, born in 1990, suffered from high fever and seizures, and was diagnosed with viral encephalitis in 2005. After four weeks of medical treatment, she recovered with no neurological disabilities, but suffered from monthly seizures. Ten years later, the patient presented with convulsive SE, while four months pregnant in February of 2015. Her SE remained super-refractory to drugs despite the termination of pregnancy. Therefore, ANT-DBS was performed in March of 2015. The patient became SE-free following activation of an ANT-DBS stimulator. However, the stimulation treatment was terminated according to the family's request when a tremor developed two years after the treatment had begun. Subsequently, four SE episodes occurred and the tremor did not improve. The stimulator and electrodes were removed in August of 2017. The patient died of an uncontrolled SE two months later. This case demonstrates the effectiveness of ANT-DBS for emergency super-refractory convulsive SE with both positive and negative outcomes.

Small molecule inhibitor agerafenib effectively suppresses neuroblastoma tumor growth in mouse models via inhibiting ERK MAPK signaling.

Neuroblastoma (NB) is the most common extracranial solid tumor in early childhood. Despite intensive multimodal therapy, nearly half of children with high-risk disease will relapse with therapy-resistant tumors. Dysregulation of MAPK pathway has been implicated in the pathogenesis of relapsed and refractory NB patients, which underscores the possibility of targeting MAPK signaling cascade as a novel therapeutic strategy. In this study, we found that high expressions of RAF family kinases correlated with advanced tumor stage, high-risk disease, tumor progression, and poor overall survival. Targeted inhibition of RAF family kinases with the novel small molecule inhibitor agerafenib abrogated the activation of ERK MAPK pathway in NB cells. Agerafenib significantly inhibited the cell proliferation and colony formation ability of NB cells in vitro, and its combination with traditional chemotherapy showed a synergistic pro-apoptotic effect. More importantly, agerafenib exhibited a favorable toxicity profile, potently suppressed tumor growth, and prolonged survival in NB mouse models. In conclusion, our preclinical data suggest that agerafenib might be an effective therapeutic agent for NB treatment, both as a single-agent and in combination with chemotherapy.

Lnc-UCID Promotes G1/S Transition and Hepatoma Growth by Preventing DHX9-Mediated CDK6 Down-regulation.

Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been functionally characterized. Here, we identified an oncogenic lncRNA, named lnc-UCID (lncRNA up-regulating CDK6 by interacting with DHX9). Lnc-UCID was up-regulated in hepatocellular carcinoma (HCC), and a higher lnc-UCID level was correlated with shorter recurrence-free survival of HCC patients. Both gain-of-function and loss-of function studies revealed that lnc-UCID enhanced cyclin-dependent kinase 6 (CDK6) expression and thereby promoted G1/S transition and cell proliferation. Studies from mouse xenograft models revealed that tumors derived from lnc-UCID-silenced HCC cells had a much smaller size than those from control cells, and intratumoral injection of lnc-UCID small interfering RNA suppressed xenograft growth. Mechanistically, the 850-1030-nt domain of lnc-UCID interacted physically with DEAH (Asp-Glu-Ala-His) box helicase 9 (DHX9), an RNA helicase. On the other hand, DHX9 post-transcriptionally suppressed CDK6 expression by binding to the 3'-untranslated region (3'UTR) of CDK6 mRNA. Further investigation disclosed that lnc-UCID enhanced CDK6 expression by competitively binding to DHX9 and sequestering DHX9 from CDK6-3'UTR. In an attempt to explore the mechanisms responsible for lnc-UCID up-regulation in HCC, we found that the lnc-UCID gene was frequently amplified in HCC. Furthermore, miR-148a, whose down-regulation was associated with an increase of lnc-UCID in HCC, could bind lnc-UCID and inhibit its expression. Conclusion: Up-regulation of lnc-UCID, which may result from amplification of its gene locus and down-regulation of miR-148a, can promote HCC growth by preventing the interaction of DHX9 with CDK6 and subsequently enhancing CDK6 expression. These findings provide insights into the biological functions of lncRNAs, the regulatory network of cell cycle control, and the mechanisms of HCC development, which may be exploited for anticancer therapy.

First five generations Chinese family of tuberous scleroses complex due to a new mutation of the TSC1 gene.

Tuberous scleroses complex (TSC) is a rare neurocutaneous syndrome and has autosomal dominant inheritance. However, larger family with TSC is very rare. Here, we report the first five generations family with TSC from China, and localize the pathogenic gene. A boy with TSC and epilepsy underwent preoperative evaluation and epileptic surgery. His TSC family history was gotten, and the clinical data of a Chinese family with TSC were collected in 2016. Complete exons sequencing was performed in the proband and his parents, and whole exons sequence of TSC was performed in the other family members. The family showed autosomal dominant inheritance, and it was the largest reported family with TSC. In this pedigree, there were 14 patients in 5 generations, but only 1 case with epilepsy in them. All of examined patients had TSC 1 gene exon 15 c.1846delG p.A616Pfs*13 mutation. In conclusion, TSC patients with TSC 1 deletion presented mild neurological symptom and rendered larger family.

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury.

The optimal treatment for chronic intermittent hypoxia (CIH)-induced cardiovascular injuries has yet to be determined. The aim of the current study was to explore the potential protective effect and mechanism of a C1 inhibitor in CIH in the myocardium. The present study used a rat model of CIH in which complement regulatory protein, known as C1 inhibitor (C1INH), was administered to the rats in the intervention groups. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The expression of proteins associated with the apoptotic pathway, such as B-cell lymphoma 2 (Bcl-2), Bax and caspase-3 were detected by western blot analysis. The expression of complement C3 protein and RNA were also analyzed. C1INH was observed to improve the cardiac function in rats with CIH. Myocardial myeloperoxidase activity, a marker of neutrophil infiltration, was significantly decreased in the C1INH intervention group compared with the CIH control group, and cardiomyocyte apoptosis was significantly attenuated (P<0.05). Western blotting and reverse transcription-polymerase chain reaction analysis indicated that the protein expression levels of Bcl-2 were decreased and those of Bax were increased in the CIH group compared with the normal control group, but the protein expression levels of Bcl-2 were increased and those of Bax were decreased in the C1INH intervention group, as compared with the CIH group. Furthermore, the CIH-induced expression and synthesis of complement C3 in the myocardium were also reduced in the C1INH intervention group. C1INH, in addition to inhibiting complement activation and inflammation, preserved cardiac function in CIH-mediated myocardial cell injury through an anti-apoptotic mechanism.

Resective surgery combined with corpus callosotomy for children with non-focal lesional Lennox-Gastaut syndrome.

BACKGROUND: The first prospective trial for resective surgery combined with corpus callosotomy (CCT) was performed to investigate the outcomes of the combined surgery in children with Lennox-Gastaut syndrome (LGS) without focal lesion on brain MRI. METHODS: This study enrolled 68 children with LGS and without focal lesion on brain MRI, of which 25 received medicine (medicine group) and 43 underwent surgery (surgery group), including 20 with exclusively resective surgery (exclusively resection subgroup) and 23 with resective surgery combined with CCT (combined CCT subgroup). All patients were followed for 3-5 years. RESULTS: Significant differences in seizure control were observed between the medicine group and the exclusively resection subgroup and combined CCT subgroup at the 1-year, 3-year, and 5-year follow-ups. There was a trend that the children with resection combined with CCT had better seizure control than those with exclusively resection at the three follow-ups, but this could not be verified by the statistical method used. Furthermore, significant differences were not observed in seizure control between children with different MRI findings, age at surgery, or pathology in the surgery group. The percentage of long-term seizure-free did not remain as high as the percentage of early stage seizure-free at 1-year follow-up. However, the children with combined CCT surgery demonstrated more postoperative improvement than the children with resective surgery alone based on the mean QOL score (10.78 vs. 5.75, p = 0.0152) and full-scale IQ (7.91 vs. 4.55, p = 0.0446). CONCLUSIONS: Resective surgery combined with CCT can provide favorable seizure control and obvious improvements in QOL and IQ in children with LGS. This combined approach can be performed in carefully selected LGS children without focal lesions and can localize the epileptogenic zone following a comprehensive preoperative evaluation.

Neuroprotective Effect of Electric Conduction Treatment on Hippocampus Cell Apoptosis in KA Induced Acute Temporal Lobe Epileptic Rats.

BACKGROUND: Electronic conduction, a new treatment approach for epilepsy, has been confirmed to reduce epileptiform discharge on EEG and convulsive behaviors, particularly epileptic discharge propagation and serious behavioral seizures, in rats with kainic acid (KA)-induced acute temporal lobe epilepsy (TLE). OBJECTIVE: Hippocampal cell apoptosis was examined to confirm the neuroprotective effect of electronic conduction therapy in rats with KA-induced acute TLE. METHODS: Rats were divided into four groups: control group (right CA3 injection of saline), KA group (right CA3 injection of KA), sham conduction group (KA rats with sham conduction), and conduction group (KA rats with electric conduction). Apoptotic cells were evaluated by flow cytometry, TUNEL staining, and mRNA expression levels of caspase-3, tumor necrosis factor-alpha, and glial fibrillary acidic protein measured by real-time quantitative PCR (qRT-PCR). RESULTS: The frequency of convulsive behaviors in the conduction group decreased significantly compared with the KA group and the sham conduction group. Significantly fewer apoptotic cells were detected in rats with conduction based on flow cytometry and TUNEL staining results. The qRT-PCR results indicated that KA-induced up-regulation of hippocampal caspase-3 mRNA expression was reduced 24 hours after KA injection in rats that received conduction treatment. CONCLUSION: Electronic conduction treatment can reduce seizure frequency and hippocampal cell apoptosis in rats with KA-induced acute TLE.

[Research on the method of interference correction for nondispersive infrared multi-component gas analysis].

A method of interference correction for nondispersive infrared multi-component gas analysis was described. According to the successive integral gas absorption models and methods, the influence of temperature and air pressure on the integral line strengths and linetype was considered, and based on Lorentz detuning linetypes, the absorption cross sections and response coefficients of H2O, CO2, CO, and NO on each filter channel were obtained. The four dimension linear regression equations for interference correction were established by response coefficients, the absorption cross interference was corrected by solving the multi-dimensional linear regression equations, and after interference correction, the pure absorbance signal on each filter channel was only controlled by the corresponding target gas concentration. When the sample cell was filled with gas mixture with a certain concentration proportion of CO, NO and CO2, the pure absorbance after interference correction was used for concentration inversion, the inversion concentration error for CO2 is 2.0%, the inversion concentration error for CO is 1.6%, and the inversion concentration error for NO is 1.7%. Both the theory and experiment prove that the interference correction method proposed for NDIR multi-component gas analysis is feasible.

Long-term follow up of very low-dose LINAC based stereotactic radiotherapy in temporal lobe epilepsy.

OBJECTIVE: Several prospective multicenter studies have demonstrated high safety efficacy for mesial temporal lobe epilepsy (TLE) with Gamma Knife radiosurgery using 24 Gy at the margin. In this paper we reported the long-term outcome of 7 patients with TLE treated with very low-dose linear accelerator (LINAC) based fractionated stereotactic radiotherapy (FSRT). We also discussed the feasibility of LINAC for TLE. METHODS: To record the treatment process, outcomes and side effects for 7 patients with TLE treated with low-dose LINAC, whose marginal dose of all cases was 12 Gy at the 85% isodose line, and post-FSRT seizure frequencies were compared with those of patients pre-FSRT. One special case (case 6) was reported in detail. RESULTS: Reduction of seizure frequency post-FSRT was 50% in 2 cases, 30% in 1 case, and 0% in 2 cases, and seizure frequency increased more than 100% in 2 cases. No patient was seizure free at the last follow up. 2 cases presented transitory complications and 2 cases showed an obvious drop in IQ, memory decline and permanent neurologic complications, including partial aphasia and mild hemiplegia in 1 case, progressive ataxia and cognition decline in another case. CONCLUSION: Outcome of TLE treated by very low-dose LINAC based FSRT was poor because of mild reduction in seizure attack frequency and serious complications.