Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial.

BACKGROUND: Neural stem cells (NSCs) are believed to have the most therapeutic potential for neurological disorders because they can differentiate into various neurons and glial cells. This research evaluated the safety and efficacy of intranasal administration of NSCs in children with cerebral palsy (CP). The functional brain network (FBN) analysis based on electroencephalogram (EEG) and voxel-based morphometry (VBM) analysis based on T1-weighted images were performed to evaluate functional and structural changes in the brain. METHODS: A total of 25 CP patients aged 3-12 years were randomly assigned to the treatment group (n = 15), which received an intranasal infusion of NSCs loaded with nasal patches and rehabilitation therapy, or the control group (n = 10) received rehabilitation therapy only. The primary endpoints were the safety (assessed by the incidence of adverse events (AEs), laboratory and imaging examinations) and the changes in the Gross Motor Function Measure-88 (GMFM-88), the Activities of Daily Living (ADL) scale, the Sleep Disturbance Scale for Children (SDSC), and some adapted scales. The secondary endpoints were the FBN and VBM analysis. RESULTS: There were only four AEs happened during the 24-month follow-up period. There was no significant difference in the laboratory examinations before and after treatment, and the magnetic resonance imaging showed no abnormal nasal and intracranial masses. Compared to the control group, patients in the treatment group showed apparent improvements in GMFM-88 and ADL 24 months after treatment. Compared with the baseline, the scale scores of the Fine Motor Function, Sociability, Life Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the treatment group 24 months after treatment, while the SDSC score decreased considerably. Compared with baseline, the FBN analysis showed a substantial decrease in brain network energy, and the VBM analysis showed a significant increase in gray matter volume in the treatment group after NSCs treatment. CONCLUSIONS: Our results showed that intranasal administration of NSCs was well-tolerated and potentially beneficial in children with CP. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NCT03005249, registered 29 December 2016, https://www. CLINICALTRIALS: gov/ct2/show/NCT03005249 ) and the Medical Research Registration Information System (CMR-20161129-1003).

Risk factors of arytenoid dislocation after endotracheal intubation: A propensity-matched analysis.

Objective: Arytenoid dislocation (AD) after general anesthesia with endotracheal intubation (EI) is an iatrogenic injury that impairs patient function and requires reduction. We aimed to investigate the risk factors of AD following EI. Methods: This retrospective case-control study involved surgical adults who received EI for general anesthesia at a single institution from June 2010 to June 2020. Cases included all the patients who had AD. We used a ratio of 1:5 to identify patients in the propensity-matched control group. Results: Multivariate analysis of 49 cases with AD and 245 controls without AD demonstrated that the use of a nasogastric (NG) tube (odds ratio [OR], 23.9; 95% confidence interval [CI], 6.8-84.1), undergoing abdominal surgery (OR, 3.7; 95% CI, 1.2-11.9), and an operative time longer than 3 h (OR, 5.2; 95% CI, 2.1-12.9) were risk factors for AD. We did not find significant independent associations between AD and 40 years or older age, gender, body mass index, whether a laryngeal mask airway was used, endotracheal tube size, and EI performers' experience. Conclusion: The use of an NG tube, abdominal surgery, and longer operative time were risk factors for AD. Among these, the NG tube application showed a strong association with AD. Preventive measures of informing the patients of the increased risk and providing high-level patient monitoring can reduce the incidence of AD. Level of Evidence: III.

[Effect of the diameter of tympanostomy with CO2 laser on secretory otitis media after radiotherapy].

Objective:To investigate the postoperative effect of different diameters of CO2 laser tympanostomy in the treatment of secretory otitis media caused by radiotherapy in patients with head and neck tumor, and to find out the best diameter range of tympanostomy according to the curative effect. Methods:The 40 ears after radiotherapy in the otorhinolaryngology department. The average 40 ears were divided into two groups: the diameter of perforation ≤3 mm and the diameter of perforation > 3 mm. Each group was 20 ears. Both groups were compared with tympanum and pure tone threshold after perforation, and then performed pure tone threshold measurement, tympanoplasty, and otoendoscopy 1,3,6 month after operation respectively. Meanwhile, patients were asked to assist in filling in the score scale of eustachian tube dysfunction（ETDQ-7）, to understand the difference in clinical symptoms and to count the complications after the operation. The changes of the size of the holes were compared with the corresponding attractors during the follow-up. Results:①After the operation, the mean value of pure tone hearing threshold air bone conduction difference in the diameter of perforation ≤3 mm group was significantly lower than that in the diameter of perforation >3 mm group （P<0.05）, indicating that the postoperative hearing recovery in the diameter of perforation ≤3 mm group was better than that in the diameter of perforation >3 mm group. ②Within six months after the operation, the tympanic membrane in the group a healed more than that in the diameter of perforation >3 mm group（P< 0.01）; in patients with an unclosed tympanic membrane in the diameter of perforation ≤3 mm group and the diameter of perforation >3 mm group, the number of smaller tympanic membrane diameter in the diameter of perforation ≤3 mm group was more than that in the diameter of perforation >3 mm group（P< 0.01）. ③The effective rates of the diameter of perforation≤3 mm group and the diameter of perforation>3 mm group were 75% and 35%, respectively. ④The incidence of postoperative complications such as middle ear infection and tympanic membrane nonunion in the diameter of perforation ≤3 mm group and the diameter of perforation>3 mm group were 25% and 45%, respectively, the incidence of postoperative complications in the diameter of perforation ≤3 mm group was significantly lower than that in the diameter of perforation>3 mm group（P<0.05）. ⑤The subjective feelings of patients in the diameter of perforation ≤3 mm group was significantly improved after the operation（P<0.01）. Compared with the postoperative questionnaire, the scores of Eustachian tube dysfunction score in the the diameter of perforation ≤3 mm groups after treatment were significantly better than the diameter of perforation>3 mm group（P<0.01）. Conclusion:According to this experimental study, in the range of 2-4 mm, 2.5 mm ≤ diameter ≤ 3.0 mm, the postoperative effect is better.

Decreased levels of superoxide dismutase in inner pillar cells contribute to ribbon synapse impairment in presbycusis.

OBJECTIVE: To determine if decreased Cu/Zn superoxide dismutase (SOD1) levels in inner pillar cells is associated and diminished inner hair cell ribbon synapse plasticity in presbycusis. METHODS: We evaluated the auditory brainstem responses (ABRs) of 2-, 5-, 6-, and 7-month-old C57BL/6J mice. ABRs were obtained using clicks and 4-, 12-, and 32-kHz tone bursts. Cochleae were collected immediately after audiometric assessment for Western blot analysis. The inner and outer hair cells and the inner hair cell ribbon synapses were separately counted. Frozen tissue sections were exposed to immunofluorescent staining for examine of SOD1 expression in the cochlea. RESULTS: ABR thresholds were elevated in the 6- and 7-month groups. The maximal elevation was detected at 32 kHz. Distortion product otoacoustic emission amplitudes decreased in the mice at 5 months. SOD1 levels in the cochlea decreased as the mice aged. A reduction of SOD1 in the inner pillar cells was detected. Hair cell counting showed an apparent decrease in OHCs from 6 months onwards. The mean number of ribbon synapses was 17.2 ± 1.4, 17.7 ± 2.74, 12.8 ± 0.95, and 9.7 ± 3.08 in the 2-, 5-, 6-, and 7-month groups, respectively. This number significantly decreased with increasing age (P < 0.05). CONCLUSION: Our study revealed that age-related hearing loss (ARHL) of C57BL/6J mice was caused by multi-site degeneration in the cochlea. Decreased expression of SOD1 in the cochlea is consistent with changes in the hearing threshold. Decreased SOD1 levels in the inner pillar cells may lead to diminished basilar membrane vibration and a reduction in the number of ribbon synapses, which plays an essential role in age-related hearing loss (ARHL).

Long­term treatment with salicylate enables NMDA receptors and impairs AMPA receptors in C57BL/6J mice inner hair cell ribbon synapse.

Salicylate is widely used to produce animal models of tinnitus in mice and/or rats. The side effects on auditory function, including hearing loss and tinnitus, are considered the results of the auditory nerve dysfunction. A recent study indicated that chronic treatment with salicylate for several weeks reduces compressed action potential amplitude, which is contradictory to the studies reporting excessive activation of N­methyl­D­aspartate receptors (NMDAR) in tinnitus­induced animals. The specific aims of the experiment were to detect the effect of salicylate on the inner hair cells (IHCs), ribbon synapse, as well as the association between the hearing threshold and the number of mismatched ribbon synapses. In the present study, mice were injected intraperitoneally with a low dose of salicylate (200 mg/kg) for 14 days. The auditory brainstem response and otoacoustic emission were measured to assess auditory function of the mice. The postsynaptic regions of IHC were identified with two types of immunostaining targets: Postsynaptic density protein 95 and Glu2/3. The number of spheres was counted and the synapses were reconstructed in 3­dimensional images. Increases in distortion product otoacoustic emissions amplitudes of the salicylate group were detected, however, an elevation in the hearing threshold was also observed. A mismatch between pre­and post­ribbon synapses was observed. In addition, the cochlear components, including the numbers of outer hair cells and IHCs, were unlikely to be affected by salicylate. IHC ribbon synapses were more susceptible to salicylate stimuli. Furthermore, mismatch of pre­ and post­ribbon synapses may indicate a competitive inhibition between NMDAR and α-amino­3­hydroxy-5-methyl-4-isoxa-zole-propionate receptors and dysfunction of ribbon synapses.

MicroRNA-1469, a p53-responsive microRNA promotes Genistein induced apoptosis by targeting Mcl1 in human laryngeal cancer cells.

Genistein, a plant isoflavone, is reported to have therapeutic potentials in multiple cancers, However, the molecular mechanism underlying promoting cell apoptosis in laryngeal cancer remains unclear. In this study, we report that miR-1469 was induced by genistein in laryngeal cancer. Elevated miR-1469 promoted cell apoptosis and inhibited Mcl1 expression. In addition, we also observed that tumor suppressor p53 was increased under genistein treatment. Elevation of p53 promoted miR-1469 expression, leading to miR-1469 increase and Mcl1 decrease. Therefore, our findings suggest that genistein can suppress laryngeal cancer cell survival through p53 -miR-1469-Mcl1pathway.

Effect evaluation of repeated debridement after endoscopic sinus surgery.

OBJECTIVE: To investigate the effect of early phase debridement by the different intervention frequencies on postoperative symptoms recovery and turnover of mucosa after functional endoscopic sinus surgery (FESS). METHODS: 67 patients undergone FESS were divided into intervention group and control group. Intranasal corticosteroids, macrolides antibiotics and postoperative saline douching were used in both groups. Debridement was performed on the 1(st), 4(th), 8(th) postoperative week on patients of invention group, while once per week on patients of control group. The primary outcome measure was visual analogue scale (VAS) and Lund-Kennedy Endoscopic Score (LKES) Results: On the 4(th) week, the control group presented more release on nasal block, the VAS of the two groups is 3.45 ± 1.16 and 4.83 ± 1.47 in the control group and intervention group respectively which was significantly different. The LKES on crust decreased more in the control group (1.12 ± 0.64 in the control group and 1.90 ± 0.47 in the intervention group). However, the control group complained more sever facial pain and uncomfortable; the VAS of two groups is 5.92 ± 0.91 and 2.74 ± 1.41 respectively. On the 8(th) week, there were no significant difference between the two groups on all domains of VAS and LKES except lower scar was shown in the control group. CONCLUSIONS: Benefit of frequent debridement during the early postoperative was not in positive correlation with patients recovering from ESS. Excessive debridement may induce more surgical trauma and cause more facial pain to patients. Therefore, in terms of subjective recovery and health care costs, appropriate extending postoperative management time and decreasing intervention frequencies will not affect the therapeutic effect of endoscopic surgery for chronic sinusitis.

[Dentinogenic ghost cell tumor presenting as a giant cyst: a case report].

A 55 year old man complained of a painless mass at the left maxillofacial region. The mass had continuously grown over 10 years. Upon physical examination a cystic mass with size of 5 cm in length with bulging smooth surface was seen on the left maxillofacial region. Computed tomography (CT) scan showed a giant cyst with bone destruction and invasion in the left maxilla, maxillary sinus and nasal cavity. Needle aspiration of the mass yielded 80 milliliter of brown fluid. The excisional biopsy was made which revealed ghost cells and dysplastic dentin that were features of dentinogenic ghost cell tumor. Finally, a dentinogenic ghost cell was diagnosed.

HMLH1 gene mutation in gastric cancer patients and their kindred.

AIM: To study the status of hMLH1 gene point mutations of gastric cancer kindreds and gastric cancer patients from northern China, and to find out gene mutation status in the population susceptible to gastric cancer. METHODS: Blood samples of 120 members from five gastric cancer families, 56 sporadic gastric cancer patients and control individuals were collected. After DNA extraction, the mutations of exon 8 and exon 12 of hMLH1 gene were investigated by PCR-SSCP-CE, followed by DNA sequencing. RESULTS: In the five kindreds, the mutation frequency was 25% (5/16) for the probands and 18% (19/104) for the non-cancerous members, which were significantly higher than the controls (P<0.01 chi2 = 7.71, P<0.01 chi2 = 8.65, respectively). In the sporadic gastric cancer, the mutation frequency was 7% (4/56), which was similar to that (5/100) in the healthy controls. The mutation point of exon 8 was at 219 codon of hMLH1 gene (A-G), resulting in a substitution of Ile-Val (ATC-GTC), whereas the mutation of exon 12 was at 384 codon of hMLH1 gene (T-A) resulting in a substitution of Asp-Val (GTT-GAT), which were the same as previously found in hereditary nonpolyposis colorectal carcinoma. CONCLUSION: The members of gastric cancer families from northern China may have similar genetic background of hMLH1 gene mutation as those of hereditary nonpolyposis colorectal carcinoma.