To examine the effect of multisensory exercise on balance disorders.
PubMed, Scopus and Web of Science were searched to identify eligible studies published before January 1, 2020. Eligible studies included randomized control trials (RCTs), non-randomized studies, case-control studies, and cohort studies. The methodological quality of the included studies was evaluated using JBI Critical Appraisal Checklists for RCTs and for Quasi-Experimental Studies by two researchers independently. A narrative synthesis of intervention characteristics and health-related outcomes was performed.
A total of 11 non-randomized studies and 9 RCTs were eligible, including 667 participants. The results supported our assumption that multisensory exercise improved balance in people with balance disorders. All of the 20 studies were believed to be of high or moderate quality.
Our study confirmed that multisensory exercise was effective in improving balance in people with balance disorders. Multisensory exercises could lower the risk of fall and enhance confidence level to improve the quality of life. Further research is needed to investigate the optimal strategy of multisensory exercises and explore the underlying neural and molecular mechanisms of balance improvement brought by multisensory exercises.
Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.
To study the value of the subjective visual vertical (SVV) in the diagnosis of vestibular migraine (VM).
This study recruited 128 VM patients and 64 age-matched normal subjects. We detected the SVV during the interval between attacks in both groups, in sitting upright, and the head tilted at 45° to the left or right. We then examined the correlation between the SVV results with the vestibular evoked myogenic potential (VEMP) and canal paresis (CP).
It was found there was a significant difference in SVV at the upright position between VM patients and normal controls (P=0.006) and no significant difference was found at the tilts of 45° to the left or right between the two groups. The SVV results at the upright position were significantly correlated with cervical VEMP (P=0.042) whereas not significantly correlated with CP and VEMP. There existed no significant difference in the conformity to the Müller effect (M effect) between the two groups. ROC analysis exhibited that the sensitivity, specificity of SVVs at the upright were 67.200% and 62.500% respectively. The diagnostic value of SVV at the upright position was significantly higher than that at tilts of 45° to the left and right (P=0.006). Nonetheless the diagnostic accuracy was relatively low.
Abnormality in SVV possibly stems from the lasting functional disorder of cerebellar or high-level cortical centers in VM patients or is linked to the vestibular compensation. The SVV is of low diagnostic value for VM and the value of SVV in VM warrants further study.
Vestibular schwannomas (VS) are benign tumors of the vestibular nerve. The common first symptoms are hearing loss and tinnitus, followed by imbalance, vertigo, and facial nerve involvement. The subjective symptoms of VS patients are not consistent with the severity of vestibular lesions and the results of vestibular tests, which often interfere with clinicians’ diagnoses. Thus, the main screening and diagnostic methods for VS are audiometry and magnetic resonance imaging (MRI), ignoring the evaluation of vestibular function at the source of pathological lesions. With the development and improvement of vestibular evaluation technology and its wide application in the clinic, modern vestibular examination technology can reflect the severity and frequency of vestibular lesions and compensation from multiple perspectives, providing an objective basis for the diagnosis and treatment of vestibular diseases. In this report, we review the results and characteristics of vestibular tests in VS patients and further clarify the clinical value of vestibular function assessment in the diagnosis and treatment of VS.
Previous study suggested that estradiol (E2) plays an important role in otolith shedding by regulating the expression of otoconin 90 (OC90). The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith.
The rats receiving bilateral ovariectomy (OVX) were used as animal models. Co-immunoprecipitation was used to observe the relationship between estrogen receptor (ER) and estrogen-related receptor α (ERRα). The morphology of otolith was observed under the scanning electron microscopy. Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRα in regulating OC90 expression.
The looser otoliths were observed in rats receiving bilateral OVX, which could be reversed by supplementation with E2. The level of ERRα was decreased in bilateral OVX rats. ER and ERRα interacted with each other on the regulation of the expression of OC90.
Our results suggest ER and ERRα are both important downstream receptors involved in regulating OC90 expression in utricles of rats, and ERRα probably functions by interacting with ER. This provides evidence for the mechanism of otolith shedding. And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.
To investigate the genetic causes of sudden sensorineural hearing loss (SSNHL) patients in China. This study focused on analyzing variations of coding sequence of common genes related to deafness, revealing the molecular pathogenesis of sudden deafness from a genomics perspective, discovering molecular markers associated with the onset of deafness, and then supplying prevention to high-risk populations, classifying disease according to accurate etiology, and choosing a much more precision therapy.
We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital. In this study, mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo.
We identified 51 cases of unilateral sudden deafness, including 2 cases of low-mid frequency hearing impairment, 18 cases of mid-high frequency hearing loss, 11 cases of flat-type hearing loss, and 20 cases of all frequency hearing loss. Among the 51 cases, 8 (15.69%) cases of GJB2 heterozygous variations, 1 (1.96%) case of GJB3 heterozygous variations, 5 (9.8%) cases of SLC26A4 heterozygous variations, 2 (3.92%) cases of COCH heterozygous variations, 14 (27.45%) cases of CDH23 heterozygous variations, 14 (27.45%) cases of OTOF heterozygous variations, 1 (1.96%) case of SLC17A8 heterozygous variations and 2 (3.92%) cases of KCNE1 heterozygous variations. No mtDNA gene variations were identified.
SSNHL has some relationship with hereditary in Chinese population, but its complex genetic pathogenic mechanisms need further study.
Age-related hearing loss (AHL), characterized by degeneration of cochlea structures, is the most common sensory disorder among the elderly worldwide. The calcium channel is considered to contribute to normal hearing. However, the role of the T-type voltage-activated calcium channel, Cav3.1, remains unclear in AHL. Here, we investigate the age-related change of Cav3.1 expression in the cochlea and D-gal-induced senescent HEI-OC1 cells.
Cochleae from C57BL/6 mice at 2 months and 12 months of age were assessed. Senescence in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells was induced by D-gal treatment. The immunofluorescence technique was employed to investigate the distribution of Cav3.1 in vivo and in vitro. Quantitative assessment was achieved by Western blotting and real-time PCR.
In comparison with 2-month-old animals, 12-month old C57BL/6 mice exhibited great loss of hair cells and elevated auditory brainstem threshold. The Cav3.1 was located in hair cells, spiral ganglion cells, lateral walls, and the expression of Cav3.1 protein and mRNA decreased in the aged cochleae. D-gal-induced senescence assay confirmed the down-regulation of Cav3.1 expression in senescent HEI-OC1 cells.
Our results show that age-related down-regulated expression of Cav3.1 in the cochleae is associated with AHL and may contribute to the pathogenesis of AHL.
Patients suffered a lot from decompensated vestibular vertigo. Pharmacotherapy and vestibular rehabilitation training have been proven to be effective in prompting vestibular compensation. Routine rehabilitation training is faced with the challenges of patients’ compliance, completion, the average recuperation time and so on. This study is aimed to investigate advantages of short-term personalized vestibular rehabihitation at home guided by professional therapist.
A short-term personalized vestibular rehabilitation program (ST-PVR) was designed for patients with decompensated vestibular vertigo in this study.
Patients experiencing the ST-PVR program showed significant improvement of Self-Rating Anxiety Scale (SAS), Dizziness Handicap Inventory (DHI), Activities-Specific Balance Confidence Scale (ABC) scores by the second follow-up (at 2nd week after treatment, P<0.05). However-improvement in the medication group occurred slightly later, DHI for 1 month and SAS for 2 months after treatment (P<0.05). Also, the improvement in the onset time of unilateral weakness (UW) at 2nd week after treatment in the personalized vestibular rehabilitation (PVR) group was faster than that in the medication group.
In general, the short-term PVR program showed great advantages by prompting vestibular compensation quickly and putting forward future direction for clinical treatment on decompensated vestibular vertigo.
Auditory neuropathy (AN) is a unique pattern of hearing loss with preservation of hair cell function. The condition is characterized by the presence of otoacoustic emissions (OAE) or cochlear microphonic (CM) responses with severe abnormalities of the auditory brainstem response (ABR). The vestibular branches of the VIII cranial nerve and the structures innervated by it can also be affected. However, the precise lesion sites in the vestibular system are not well characterized in patients with AN.
The air-conducted sound (ACS) vestibular-evoked myogenic potentials (VEMPs) and galvanic vestibular stimuli (GVS)-VEMPs were examined in 14 patients with AN.
On examination of VEMPs (n=14, 28 ears), the absent rates of ACS-cervical VEMP (cVEMP), ACS-ocular VEMP (oVEMP), GVS-cVEMP, GVS-oVEMP and caloric test were 92.9% (26/28), 85.7% (24/28), 67.9% (19/28), 53.6% (15/28), and 61.5% (8/13), respectively. Impaired functions of the saccule, inferior vestibular nerve, utricle, superior vestibular nerve, and horizontal semicircular canal were found in 25.0% (7/28), 67.9% (19/28), 32.1% (9/28), 53.6% (15/28) and 61.5% (8/13) patients, respectively. On comparing the elicited VEMPs parameters of AN patients with those of normal controls, both ACS-VEMPs and GVS-VEMPs showed abnormal results in AN patients (such as, lower presence rates, elevated thresholds, prolonged latencies, and decreased amplitudes).
The study suggested that patients with AN often have concomitant vestibular disorders. Retro-labyrinthine lesions were more frequently observed in this study. GVS-VEMPs combined with ACS-VEMPs may help identify the lesion sites and facilitate detection of areas of vestibular dysfunction in these patients.
To compare the performances among three different systems for video head impulse test (vHIT), and to identify an optimal target angle for precisely evaluating the function of vertical semicircular canals in vHIT.
A two-center prospective study was done. Participants were sit 1.2 m away from the wall in a noise-proved room that dedicated for vHIT experiments. During the comparison experiments, similar settings were ensured in both hospitals, with the same distance to wall and angle of staring. For each equipment, the procedures followed the developers’ recommendations. The same examiner performed the comparison between two systems in one location. For the eye-position projects, targets were placed on the wall sequentially at the pre-marked lines for different angles. For the comparison projects, 9 and 13 participants were recruited, respectively. Any participant with otologic or vestibular disorders was excluded. A total of 26 healthy participants were recruited in the eye-position experiments, 16 of which were further involved in inter-examiner tests.
Our evaluations of three different systems showed that a new vHIT system, VertiGoggles® ZT-VNG-I (VG) performed as good as the long-tested Otometrics® ICS impulse (Oto) and EyeSeeCam® (ESC). During the comparison, we validated 25-degree, instead of right ahead at 0 degree, is a better place to set the targets when torsion was applied at vertical semicircular canal planes.
The new VG system is good for clinical practices. Furthermore, we proposed a new protocol to set the targets 25 degrees from right ahead after tilting head 45 degrees to evaluate vertical canals during vHIT.
Atherosclerosis (AS), a chronic inflammatory disease, is the basis of cardiovascular disease (CVD). Although the treatment has been greatly improved, AS still imposes a large burden on human health and the medical system, and we still need to further study its pathogenesis. As a novel biomolecule, transfer RNA-derived fragments (tRFs) play a key role in the progression of various disease. However, whether tRFs contribute to atherosclerosis pathogenesis remains unexplored.
With deep sequencing technology, the change of tRFs expression profiles in patients with AS compared to healthy control group was identified. The accuracy of the sequencing data was validated using RT qPCR. Subsequently, we predicted the potential target genes of tRFs by online miRNA target prediction algorithms. The potential functions of tRFs were evaluated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
There were 13 tRFs differentially expressed between patients with AS and healthy controls, of which 2 were up-regulated and 11 were down-regulated. Validation by RT-qPCR analysis confirmed the sequencing results, and tRF-Gly-GCC-009 was highly up-regulated in the AS group based on the results of sequencing which was confirmed by RT-qPCR analysis. Furthermore, GO enrichment and KEGG pathway analyses indicated that 10 signaling pathways were related to tRF-Gly-GCC-009. These pathways might be physiopathological fundamentals of AS, mainly involving in Apelin signaling, Notch signaling and calcium signaling.
The results of our study provide important novel insight into the underlying pathogenesis and demonstrate that tRFs might be potential biomarkers and therapeutic targets for AS in the future.
To observe effects of medication use on small airway function, airway inflammation and acute exacerbations in patients with clinically controlled asthma.
Forced expiratory flow over the middle half of the forced expiratory curve (FEF25%–75%), percentage of eosinophil, concentrations of eosinophil cationic protein (ECP) and interleukin (IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone. Subsequently, acute exacerbations were compared between two groups during the 24-week follow-up period.
FEF25%–75% in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone. Meanwhile, the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone. Additionally, the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.
Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations, presumably secondary to reduction in airway inflammation.
Several clinical obstructive sleep apnea syndrome (OSAS) phenotypes associated with heterogeneous cardiovascular risk profiles have been recently identified. The purpose of this study was to identify clusters amongst these profiles that allow for the differentiation of patients.
This retrospective study included all moderate-to-severe OSAS patients referred to the sleep unit over a 5-year period. Demographic, symptom, comorbidity, polysomnographic, and continuous positive airway pressure (CPAP) adherence data were collected. Statistical analyses were performed to identify clusters of patients.
A total of 567 patients were included (67% men, 54±13 years, body mass index: 32±7 kg/m2, 65% Caucasian, 32% European African). Five clusters were identified: less severe OSAS (n=172); healthier severe OSAS (n=160); poorly sleeping OSAS patients with cardiometabolic comorbidities (n=87); younger obese men with sleepiness at the wheel (n=94); sleepy obese men with very severe desaturating OSAS and cardiometabolic comorbidities (n=54). Patients in clusters 3 and 5 were older than those in clusters 2 and 4 (P=0.034). Patients in clusters 4 and 5 were significantly more obese than those in the other clusters (P=0.04). No significant differences were detected in terms of symptoms and comorbidities. Polysomnographic profiles were very discriminating between clusters. CPAP adherence was similar in all clusters but, among adherent patients, daily usage was more important in cluster 1 (less severe patients) than in cluster 5.
This study highlights that the typical sleepy obese middle-aged men with desaturating events represent only a minority of patients in our multi-ethnic moderate-to-severe OSAS cohort of 33% females.
To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiation therapy (IMRT).
The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy.
The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10–106 months) for the entire cohort. The 5-year overall survival rate was 79.7%. The 5-year local relapse-free survival rate, regional relapse-free survival rate, distant metastasis-free survival rate and progression-free survival rate were 92.4%, 93.3%, 79.2% and 74.3%, respectively. A total of 153 patients had experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories. Stage T4 and N3 were closely associated with distant metastasis, with the metastatic rate of 29.3% and 45.5%, respectively.
IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. Both T stage and N stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.
The use of an antibiotic with immunomodulatory properties could be fascinating in treating multifactorial inflammatory conditions such as ulcerative colitis (UC). We report our investigations into the immunomodulatory properties of levornidazole, the S-enantiomer of ornidazole, which displayed a tremendous therapeutic potential in UC induced by dextran sodium sulfate (DSS). Levornidazole administration to DSS-colitic mice attenuated the intestinal inflammatory process, with an efficacy better than that shown by 5-amino salicylic acid. This was evidenced by decreased disease activity index, ameliorated macroscopic and microscopic colon damages, and reduced expression of inflammatory cytokines. Additionally, levornidazole displayed anti-inflammatory activity through Caveolin-1-dependent reducing IL-1β and IL-18 secretion by macrophages contributing to its improvement of the intestinal inflammation, as confirmed in vitro and in vivo. In conclusion, these results pointed out that the immunomodulatory effects of levornidazole played a vital role in ameliorating the intestinal inflammatory process, which would be crucial for the translation of its use into clinical settings.
The aim of this study was to identify the effects of melatonin on acute gouty inflammation and to investigate the underlying mechanisms. We found significantly lower serum melatonin levels in gout patients in the acute phase than in those in the remission phase or in normal individuals. The mRNA expression of melatonin receptor 2 (MT2) was also lower in gout patients than in normal individuals. To verify the in-vivo role of melatonin, a gouty arthritis model was established by intraarticular injection of monosodium urate (MSU, 1 mg) crystals into the paws of C57BL/6 mice. Joint inflammation in the mouse model was evaluated by measuring the thickness of the right paw/left paw, and the inflammation index was determined by examining infiltrating neutrophils with haematoxylin and eosin (H&E) staining. Melatonin was found to reduce both paw thickness and the inflammation index in the mouse model, and melatonin also reduced the mRNA levels of interleukin-1 beta (IL-1β), IL-6 and NLR family pyrin domain containing 3 (NLRP3) inflammasome. To mimic gouty inflammation in vitro, mouse peritoneal macrophages were stimulated with lipopolysaccharides (LPS) plus MSU. Melatonin was revealed to reduce IL-1β secretion by stimulated macrophages. The mRNA expression levels of IL-1β and IL-6 were also inhibited by melatonin. Western blot analysis showed that the expression of NLRP3, caspase-1 and pro-IL-1β was also inhibited by melatonin. In conclusion, our study demonstrated that melatonin alleviated gouty inflammation in vivo and in vitro, and the underlying mechanism may involve inhibiting the assembly of the NLRP3 inflammasome.
The expression levels of histone deacetylase 2 (HDAC2), eukaryotic initiation factor 5 (eIF5), and eukaryotic initiation factor 6 (eIF6), and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were investigated, in order to charify the relationship between HDAC2 and the prognosis of lung cancer patients and its influence on the expression of eIF5 and eIF6.
The expression of HDAC2, eIF5, and eIF6 in lung cancer tissues was detected by quantitative reverse transcription polymerase chain reaction. The expression correlation between HDAC2 and eIF5 or eIF6 was tested using a t test. The correlation between HDAC2 and eIF5 or eIF6 was analyzed using the TCGA database. The identified cells were constructed with small interfering siRNA and HDAC2 overexpression plasmid. The proliferation and migration ability of the identified cells was investigated by CCK8 and Transwell assays, respectively.
HDAC2, eIF5, and eIF6 were overexpressed in lung cancer tissues, and HDAC2 expression level was negatively correlated with the prognosis of lung cancer patients. HDAC2 expression level was positively correlated with eIF5 and eIF6 expression levels. HDAC2 could regulate the expression of eIF5 and eIF6. The regulation of proliferation and invasion of lung cancer cells by HDAC2 depended on eIF5 and eIF6.
HDAC2, eIF5, and eIF6 were closely related with lung cancer tumorigenesis, which might be potential biological markers and therapeutic targets for lung cancer.
Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.
From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed.
Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18–129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33–55) showed no recurrence of new CRKP infection in the 7 surviving recipients.
It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.
Supracondylar humerus fractures are the most frequent fractures of the paediatric elbow. The present study introduced a modified surgical procedure for treatment of supracondylar humerus fractures in children.
From February 2015 to August 2019, 73 patients with Gartland’s type II and III supracondylar fractures were treated with this modified method. Totally, 68 of all patients were followed up for 3–12 months (mean 8.25 months). The evaluation results included fracture nonunion, ulnar nerve injury, pin track infection, carrying angle and elbow joint Flynn score.
The results showed that bone union was observed in all children, one case had an iatrogenic ulnar nerve injury, and the symptoms were completely relieved in 4 months after removing of the medial-side pin. All children had no cubitus varus deformity and no pin track infection, and the rate of satisfactory results according to Flynn’s criteria score was 100%.
The modified closed reduction and Kirschner wires internal fixation could effectively reduce the rate of open reduction, the risk of iatrogenic ulnar nerve injury, and the incidence of cubitus varus deformity in treatment of supracondylar humerus fractures in children.
Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years. However, reports on one-session hybrid surgery for arteriovenous malformations (AVMs) are relatively rare. The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room (OR) at one stage.
We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018. The data for resection rate, microcatheter adhesion, surgical position and postoperative outcomes were analyzed. Total resection or near-total resection was achieved in all cases.
A total of 13 patients were under combined endovascular and surgical procedures, and 7 experienced surgery with intraoperative digital subtraction angiography. Sitting position was applied in 3 of them; 2 niduses in cerebellum, and 1 in parietal lobe. Compared with admission modified Rankin Scale (mRS) in all patients, postoperative 12-month mRS showed a significant decline. Besides, 3 patients experienced microcatheter adhesion after endovascular embolization, thereafter underwent surgical adhesion removal while nidus resection was done.
Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs. The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position. It also reduces the risk of microcatheter adhesion, which enables interventional radiologists to perform aggressively.
Antipsychotics, in particular olanzapine, are first-line medications for schizophrenia. The prefrontal cortex (PFC) is an important region for antipsychotics’ therapeutic effects. The PFC inflammatory and immune pathways are associated with schizophrenia pathogenesis. However, the effect of antipsychotics on the inflammatory and immune pathways in the PFC remains unclear. We aimed to examined the time-dependent effect of olanzapine on inflammatory and immune markers in the PFC of rats. Since the inflammatory and immune pathways are related to endoplasmic reticulum (ER) stress, we further investigated whether or not olanzapine-induced inflammation and immune responses were related to ER stress.
Expression of pro-inflammatory markers including IkappaB kinase β (IKKβ), nuclear factor kappa B (NFκB), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and IL-1β, and immune-related proteins including inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2) and cluster of differentiation 14 (CD14) were examined by Western blotting.
Olanzapine treatments for 1, 8 and 36 days significantly activated the inflammatory IKKβ/NFκB signaling, and increased the expression of TNF-α, IL-6, IL-1β and immune-related proteins such as iNOS, TLR4 and CD14. Olanzapine treatment for 1 day, 8 and 36 days also induced ER stress in the PFC. Co-treatment with an ER stress inhibitor, 4-phenylbutyrate, inhibited olanzapine-induced inflammation and the immune response in the PFC.
These results suggested olanzapine exposure could be a factor that induces central inflammation and immunological abnormities in schizophrenia subjects. Olanzapine induces PFC inflammation and immune response, possibly via activating ER stress signaling.
Autophagy was prominently activated by cerebral ischaemia. This study was to investigate the exact role of autophagy in ischaemic stroke.
Two rat models of transient middle cerebral artery occlusion (tMCAO) and permanent MCAO (pMCAO) were prepared. The brain tissues in the penumbra were obtained to observe the dynamic variations of autophagy activity with Beclin1 and LC3 antibodies by Western blotting. At the characteristic time points, when autophagy activity was markedly elevated or reduced, the autophagy activation signaling was intervened with rapamycin and 3-methyladenine, respectively. Thereafter, key proteins in the autopahgic/lysosomal pathway were detected with the antibodies of LC3, p62, ubiquitin, LAMP-1 and cathepsin B. Meanwhile, TTC staining, neurological score and immunofluorescence were performed to evaluate brain infarct volume, neurological deficit and neuron survival, respectively.
Both Beclin1 and LC3 expression levels were remarkably altered at 6 h, 12 h, 2 days and 7 days after tMCAO. Interestingly, the dynamic changes of autophagy activity following pMCAO were identical to those after tMCAO. Neither autophagy induction nor autophagy inhibition was able to ameliorate the pMCAO-induced neurological injury due to lysosomal dysfunction, as indicated by low levels of LAMP-1 and cathepsin B, accompanied with the accumulation of LC3-II, ubiquitin and insoluble p62. Comparatively, autophagy induction elicited overt neuroprotection at 2 and 7 days after tMCAO, and this neuroprotection might be elicited by the enhancement of autophagy flux.
Our study suggests that autophagy confers neuroprotection at the subacute phase of tMCAO but has few effects on neurological outcomes after pMCAO.
Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases.
A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children’s Medical Center.
All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge.
This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.
To investigate the feasibility of subtraction coronary computed tomographic (CT) angiography (SubCCTA) to decline calcium artifacts and improve diagnostic accuracy in the presence of coronary calcification and analyze the factors that influence SubCCTA.
A total of 294 patients suspected of having coronary artery diseases underwent coronary computed tomographic angiography (CCTA) and SubCCTA. Coronary stenoses were blindly evaluated by two experienced radiologists, which were compared with invasive coronary angiography (ICA). Multiple statistical indexes were adopted to analyze the value of SubCCTA for the diagnosis of calcium stenoses.
The diagnosable rate of SubCCTA was 67.2% (n=197), and the non-diagnosable rate was 32.8% (n=97). Using SubCCTA, the false positive rate decreased from 56.5% to 17.4%, and the corresponding diagnostic accuracy was increased from 83.6% to 92.9%. Univariate logistic regression analysis showed that height (OR=1.029, 95% CI=1.001–1.058), weight (OR=1.025, 95% CI=1.004–1.046), left ventricular size (OR=1.018, 95% CI=1.007–1.030), cardiothoracic ratio (OR=39.917, 95% CI=1.244–1281.098), the average heart rate (OR=0.866, 95% CI=0.836–0.896) and heart rate range (OR=0.882, 95% CI=0.853–0.912) might be the factors influencing SubCCTA.
This study suggested that SubCCTA could help improve diagnostic accuracy in the presence of calcium plaques. Moreover, several factors were discovered for the first time to possibly influence SubCCTA, which will be helpful in improving the subtracted image quality.
The characteristics of oxaliplatin-induced hypersensitivity reactions (HSRs) in Chinese patients were investigated to provide a reference for patients treated with oxaliplatin.
The study reviewed the records of patients who developed oxaliplatin-induced HSRs in 17 hospitals from May 2016 to May 2017. We collected and analyzed the basic information, history of oxaliplatin administration and premedication treatments, chemotherapy cycles, HSR symptoms, and the management and outcomes of these patients.
Oxaliplatin-induced HSRs were recorded in 137 patients who had been treated with oxaliplatin-containing regimens. Five different chemotherapy regimens were applied. The median infusion cycle when oxaliplatin-induced HSRs occurred was 7, and HSRs occurred during or shortly after oxaliplatin infusion. Most of the patients experienced grade 1 or grade 2 HSRs with mild symptoms of pruritis (49.64%), flushing (46.72%), chest discomfort (26.28%), and urticaria (25.55%). The majority of the patients completely recovered from HSRs following treatment with antihistamines and dexamethasone. Seven patients completed chemotherapy with oxaliplatin after the symptoms resolved with proper management.
The results indicate that oxaliplatin-induced HSRs remain an important issue in safely and successfully fulfilling oxaliplatin-containing chemotherapy. Further studies are needed to analyze the risk factors and establish prophylaxis for such reactions.
Bacillus strains are well known for their natural bioactive products that have antimicrobial and/or anti-cancer activities. Many of Bacillus’ structurally unique metabolites can combat human diseases, including cancers. However, because Bacillus’ metabolites are so abundant, few have been studied extensively enough to fully characterize their chemical constitutions and biological functions.
In this study, we focused on the isolation and purification of a new Bacillus strain, and determined the effects of its metabolites on bacteria and cancer cells. Our study focused on a new strain of Bacillus isolated from deer dung. Based on BLAST results, this isolate belongs to Bacillus subtilis, and therefore we named the strain Bacillus subtilis NC16. Congo red assay was used to test the cellulase activity. The inhibition zone was measured to test the antimicrobial activity. CCK-8, wound healing and flow cytometry were used to test the anti-cancer activity.
Metabolites from Bacillus subtilis NC16 have both antimicrobial and anti-cancer activities. They can both suppress the growth of Trichoderma vride and Staphylococcus aureus, and inhibit the proliferation and promote the apoptosis of non-small cell lung cancer cell lines.
Our results suggest that Bacillus subtilis NC16 can not only degrade cellulose, but its metabolites may be sources of antibiotics and anti-cancer drugs.