Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice / 临床耳鼻咽喉头颈外科杂志

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Preparation and in-vitro drug release of Baizhu Huanglian pellets containing colon-targeting capsules / 药学实践杂志

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.

Temporal bone anatomy via transcanal endoscopy / 中华耳鼻咽喉头颈外科杂志

Based on anatomy and clinical operation, this article discussed the anatomical structure of temporal bone and its contiguous relationship under oto-endoscope, through two approaches: the natural external auditory canal and the enlarged external auditory canal. To give an account of the anatomical characteristics of temporal bone under oto-endoscope.

Progress in middle ear dysventilation research / 中华耳鼻咽喉头颈外科杂志

Disfunction of Eustachian tube will cause negative pressure of middle ear, which may result in tympanic membrane retraction pocket. Severe pocket can consequently cause cholesteatoma. In clinical practice it is not uncommon to find a cholesteatoma limited to epitympanum, with an otherwise normal pars tensa and mesotympanum. This review explains the theory of "selective epitympanic dysventilation syndrome" developed by endoscopic technique. In the majority of the patients, the only ventilation pathway to the epitympanum is through the tympanic isthmus. Even if Eustachian tube function has recovered, an isthmus blockage with selective epitympanic dysventilation may lead to common attic cholesteatoma.

Evaluation of the safety and effect of the endoscopic stapes surgery: a multi-center study / 中华耳鼻咽喉头颈外科杂志

Objective@#To analyze the safety of endoscopic stapes surgery, and to compare the results with stapes surgery under microscopic approach.@*Methods@#This was a retrospective study. One hundred and thirty seven patients from Eye Ear Nose and Throat Hospital of Fudan University and other seven hospitals were enrolled in this study. Eighty eight patients, in whom 29 were male, and 59 were female, aged from 29 to 66 years old, with an average of 40.1±10.7, underwent endoscopic stapedotomy and 49 patients, in whom 17 were male, and 33 were female, aged from 32 to 64 yeas old, with an arerage of 38.7±9.2, underwent microscopic stapedotomy for otosclerosis. Interventions included endoscopic and microscopic stapes surgeries. Main outcome measures consisted of operating time, preoperative and postoperative hearing, intraoperative findings, and postoperative complications. SPSS 16.0 software was used to analyzed the date (t test and χ2 test) .@*Results@#Patients in the group who underwent endoscopic stapes surgery showed a mean operative time of (74.1±26.0) min. Patients in the group treated by microscopic approach had a mean operative time (66.5±15.9) min. Statistical difference was evident (t=1.279, P<0.05) . The average operative time of endoscopic surgery became shorter as the cases increased. The average duration of the last 10 cases was shorter than that of the first 10 cases in both groups. The differences were significant (t value was 3.028, 3.610, both P<0.05). No statistical difference was found in air conduction threshold improvement (t=1.074, P=0.289) , air-bone gap closure (t=-0.135, P=0.893) and bone conduction improvement (t=1.222, P=0.228) between the two groups. No difference regarding the incidence of the postoperative complications (chorda tympanum damage: 6 cases vs 2 cases, χ2=0.08,P>0.05; vertigo:18 cases vs 9 cases,χ2=0.09, P>0.05; facial paralysis: 0 case vs 0 case) between the two groups was found.@*Conclusion@#Audiological outcomes achieved by endoscopic surgery are similar to the results obtained through a microscopic approach. Endoscopic stapes surgery is safe.

Frequency of Th22 cells and expression of their related cytokines in peripheral blood of patients with alopecia areata and their significance / 中华皮肤科杂志

Objective To determine the frequency of Th22 cells and expression of their related cytokines in peripheral blood of patients with alopecia areata(AA), to investigate their significance, and to explore the role of T lymphocytes in the occurrence of AA. Methods A total of 38 patients with AA were enrolled from Central Hospital of Minhang District in Shanghai between January 2015 and May 2016, and served as the case group. At the same time, 38 healthy people served as the control group. Peripheral blood samples were obtained from these patients and controls. Flow cytometry was performed to determine the percentage of Th22 cells, and enzyme?linked immunosorbent assay(ELISA)to measure serum levels of interleukin?22(IL?22)and IL?17. Results Compared with the control group, the case group showed significantly increased percentages of Th22 cells, Th17 cells, IL?17+IL?22+CD4+T cells and IFN?γ+IL?22+CD4+ T cells(all P < 0.01), as well as serum levels of IL?22 and IL?17(both P < 0.05). A significant increase was observed in percentages of Th22 cells, Th17 cells, IL?17+IL?22+CD4+T cells and IFN?γ+IL?22+CD4+T cells, as well as serum levels of IL?22 and IL?17, in patients with severe AA compared with those with mild AA, and in patients with active AA compared with those with stable AA (all P < 0.05). Conclusion Th22 cells and their related cytokines may participate in the occurrence, development and prognosis of AA.

Clinic significance of CT scan in diagnosis and management unsudden unilateral sensorineural hearing loss / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the clinic significance of the temporal bone high-resolution CT in discovering unilateral sensorineural hearing loss of adolescents, and to provide the basis for the rational using of medical resources.@*METHOD@#A retrospective study was conducted on 28 outpatients with unilateral sensorineural hearing loss at unsure time. Their medical history and CT examine were reevaluated,combined with associated articles in this report.@*RESULT@#All of the 28 patients with unilateral sensorineural hearing loss had the normal external ear and middle ear and received CT scan. Nine out of twenty-eight cases had inner ear malformation. Among the nine cases, 1 cases was Mondini malformation and 1 cases was common cavity, 5 cases were single stenosis of IAC, and 2 cases were semicircular canal and vestibular malformation. 19 cases were not found abnormal by CT, and 4 cases had had suffered from mumps.@*CONCLUSION@#CT scan was available in diagnosis of unsudden unilateral sensorineural hearing loss, which would help us to use medical resource more rationally.

Vestibular schwannoma: a case report of misdiagnosis / 临床耳鼻咽喉头颈外科杂志

Vestibular schwannoma is a rare tumor, which is easily misdiagnosed. The authors presented a case of vestibular schwannoma in a 36-year-old woman. The clinical manifestations were recurrent vertigo, hearing loss of the left ear, and tinnitus. The pure tone audiometry threshold of the left ear was 45dBHL with air conduction, and 33 dBHL with bone conduction. A CT scan of the temporal bone region didn't show any abnormal finding. A MRI scan of the head showed nodule abnormal signal in the internal of left vestibular and the narrow of perilymphaticum gap in T2W1 + T2Flair. The initial diagnosis was Meniere's disease. And the post-operation pathologic diagnosis was vestibular schwannoma.

Efficacy of Xiaoyin decoction combined with calcipotriol ointment in patients with vulgaris psoriasis of blood heat type and their effects on related cytokines / 中华皮肤科杂志

Objective To estimate the efficacy of Xiaoyin decoction combined with calcipotriol ointment in patients with mild to moderate vulgaris psoriasis of blood heat type as well as their effects on the expression of interleukin (IL)-17,-22 and tumor necrosis factor (TNF) α.Methods Sixty patients with mild to moderate vulgaris psoriasis of blood heat type were enrolled in this study,and equally divided into 2 groups to be treated with Xiaoyin decoction and placebo respectively for 12 weeks.Calcipotriol ointment was applied in both groups of patients.Thirty healthy volunteers served as the controls.Bicolor flow cytometry was conducted to determine the proportion of peripheral blood Th17 cells,and enzyme linked immunosorbent assay (ELISA) to measure the serum levels of IL-17,IL-22 and TNF-α,in the controls and patients before and after treatment.Clinical efficacy was evaluated by psoriasis area and severity index (PASI) score.Results Increased proportion of Th17 cells and serum levels of IL-17,IL-22 and TNF-α were observed in the patients with psoriasis before treatment compared with the controls (all P ＜ 0.05).After treatment,a significant decrease was noted in the proportion of Th17 cells ((8.32 ± 1.28)％ vs.(14.24 ± 1.97)％,P ＜ 0.05) and serum levels of IL-17,IL-22 and TNF-α in the Xiaoyin decoction group (all P ＜ 0.05 ),but not in the placebo group.The PASI score was significantly different between the Xiaoyin decoction and placebo group after treatment (1.83 ± 1.28 vs.2.91 ± 1.42,P ＜ 0.05).The total response rate was 93.33％ in the Xiaoyin decoction group,significantly higher than that in the placebo group (73.33％,P ＜ 0.05).Conclusions There is an abnormality in the proportion of Th17 cells and serum levels of IL-17,IL-22 and TNF-α,which may be ameliorated by the combined treatment with Xiaoyin decoction and calcipotriol ointment.

Study on the expression and clinical significance of MMP9 and MVD in the external auditory canal and middle ear squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression and clinical significance of MMP9 and MVD in the carcinogenesis of squamous cell carcinoma of external auditory canal and middle ear.@*METHOD@#Immunohistochemical SP method was used to detect the expression of MMP9 and MVD proteins in 26 squamous cell carcinoma tissues of external auditory canal and middle ear and 20 normal external ear canal skin tissues.@*RESULT@#The positive rate of MMP9 in squamous cell carcinoma tissues of external auditory canal and middle ear was 73.1% (19/26) lower than that in the normal external ear canal skin tissues 25.0% (5/20). The positive rates of CD34 were 33.58 +/- 3.04 and 22.50 +/- 5.22, respectively. The positive rates of MMP9 and CD34 were correlated with the histological grade and tumor grade, but had no relationship with age and sex. The positive rates between MMP9 and CD34 were related (r=0.42, P<0.05).@*CONCLUSION@#MMP9 may be involved in the carcinogenesis of squamous cell carcinoma of external auditory canal and middle ear, and may play an important role in the invasion and metastasis of squamous cell carcinoma of external auditory canal and middle ear. MMP9 and CD34 play a cooperative role in the process of squamous cell carcinoma of external auditory canal and middle ear.

Effects of rhPTH (1-34) on the proliferation and cell cycle of human keratinocyte HaCaT cells induced by tumor necrosis factor-α / 中华皮肤科杂志

Objective To investigate the influence of recombinant human parathyroid hormone [rhPTH (1-34)]on the proliferation of HaCaT cells induced by tumor necrosis factor-α (TNF-α) in vitro.Methods Cultured HaCaT cells were treated with various concentrations of rhPTH (1-34) for different durations after incubation with recombinant human TNF-α of 10 g/L for 24 hours.MTT assay and flow cytometry were performed to detect the proliferation and cell cycle of HaCaT cells,respectively.Results As contrast phase microscopy showed,the growth of HaCaT cells was inhibited by rhPTH (1-34) along with a decrease in the growth speed.MTT assay showed a suppressed proliferation of HaCaT cells after being treated with rhPTH (1-34) of 0.05,0.2,0.8,3.2 and 12.8 pmol/L for 36 and 48 hours (P＜ 0.01 or 0.05).The percentage of cells at G1 phase in HaCaT cells markedly increased (all P ＜ 0.01 ),while that at S phase declined (all P ＜ 0.01 )after 48-hour treatment with rhPTH(1-34) of 0.2,0.8,3.2 and 12.8 μ mol/L.Conclusions rhPTH(1-34) has an obvious inhibitive effect on the proliferation of HaCaT cells induced by TNF-α in vitro,and the effect is in a dose-dependent manner.

Diagnosis and management of pulsatile tinnitus of venous origin / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To discuss the diagnosis and management of pulsatile tinnitus of venous origin.@*METHOD@#A retrospective study was conducted on 12 patients who were diagnosed with pulsatile tinnitus of venous origin and treated with ligation of internal jugular veins. We reevaluated the evidences of identifying pulsatile tinnitus of venous origin and reviewed the short-term and long-term postoperative effects and complications. We also reviewed associated articles in this report.@*RESULT@#Seven patients got relief of tinnitus in less than one week after the surgery, while the other 5 patients had no relief. Seven patients were inquired in this study and the other five lost to follow-up. According to the long review (from one to five years postoperatively), two patients who acquired immediate effect got relief of tinnitus, four including complained of no relief and the seventh aggravated into roaring. Three patients who got no immediate relief got no improvement at all. No one in our review complained of any complications.@*CONCLUSION@#It's assumed that a history of pulsatile tinnitus, alleviation of tinnitus when pressing jugular veins, tinnitus changing with head position or posture and no occupying lesion in temporal CT scan or cranial MRI are inadequate in diagnosing pulsatile tinnitus of venous origin. Vascular imaging is also necessary to exclude other pathological changes like dura arteriovenous fistula, sigmoid diverticulum and so on. CT arteriography and venography are recommended preferentially. Ligation of internal jugular veins is controversial in patients who have no absence of transverse and sigmoid sinus and identified as pulsatile tinnitus of venous origin.

The Functions of the Middle Ears of Children with Adenoid Hypertrophy / 听力学及言语疾病杂志

Objective To explore the influence of adenoid hypertrophy on the state of the middle ear in children.Methods Two hundred and seventy two adenoid hypertrophy patients,aged from 2 to 12 years old,were examined with otoscopy,tympanometry and temporal bone computered tomography before adenoidectomy.The average age of the patients was 6.3 years old.These patients were divided into two groups:Group A contained 94 normal hearing patients(188 ears),Group B 178 patients(356 ears) containing of hearing loss.Results Out of the temporal bone computed tomography (CT) revealed that 209 patients(396 ears) had middle ear effusions in(72.79%,396/544ears),and 37 patients(65/188 ears,34.57%) hydrotympanum in Group A and 172 patients(331/356 ears,92.98%) in Group B.All the 396 ears effusion were confirmed by operation.Three hundred seventy three ears effusion were confirmed by the CT and operation in the two groups,377 ears with B type tympanogram(373/377,98.94%),93.85%(61/65 ears) in Group A,100%(312/312 ears) in Group B,respectively.The positive predictive value for middle ear effusion of the B-type tympanogram was higher in Group B than in Group A(P＜0.01).Fourteen ears with peak pressure ＜-200 daPa revealed hydrotyrnpanum and 23 ears with normal acoustic stapedius reflex revealed no fluid by CT and operation in 73 ears with C-type tympanogram.CT also revealed two patients suffered from large vestibular aqueduct syndrome and one with cochlear malformation in Group B.Conclusion Type B tracing tympanogram has a high positive predictive value for middle ear effusion in adenoid hypertrophy children.Type C tympanogram could not exclude effusion when the peak pressure is＜-200 daPa.CT is the best tool for identifying hydrotympanum.