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.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Irritable bowel syndrome （IBS） is a functional gastrointestinal disease， but it often causes extreme gastrointestinal discomfort and prolonged illness， which seriously affects the quality of life of patients. The global incidence rate is increasing year by year. Clinically， western medicine mainly uses oral antispasmodics， secretagogues， and antidepressants， but there are many disadvantages such as adverse reactions and poor long-term efficacy. Therefore， finding an efficient and safe treatment method is an urgent problem to be solved. A large number of studies have shown that traditional Chinese medicine has definite curative and long-lasting effects on the treatment of IBS， which has become a hot research direction in recent years. By searching Chinese and foreign literature， it is found that electroacupuncture， moxibustion， Chinese medicine monomers， and compound decoctions are the main methods in the mechanism research of traditional Chinese medicine in the treatment of IBS-related pathways， and their signaling pathways involve nuclear transcription factor kappa B （NF-κB）， transient receptor potential vanillin subfamily 1 （TRPV1）， 5-hydroxytryptamine （5-HT）， mitogen-activated protein kinase （MAPK）， and so on. Traditional Chinese medicine can repair intestinal inflammation， reduce visceral sensitivity， enhance intestinal mucosal barrier， and regulate intestinal motility by regulating this series of signaling pathways， thereby playing an important role in the treatment of IBS with multi-level， multi-link and multi-target characteristics. Based on the cell signaling pathways， this paper reviewed the research progress on the mechanism of traditional Chinese medicine in the treatment of IBS， hoping to provide theoretical support and diagnosis and treatment ideas for the clinical treatment of IBS with traditional Chinese medicine.

Humans ; Cranial Sinuses/surgery* ; Intracranial Hypertension/etiology*

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.

Objective: To investigate clinical efficacy of Duhuo Xuduan Tang in treatment of lumbar disc herniation with different syndrome types and its effect on serum pain factors, bone morphogenetic protein-7 (BMP-7) and Aggrecan. Method: A total of 121 patients with non-emergency lumbar disc herniation admitted to the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2017 to June 2018 were randomly divided into observation group (62 cases) and control group (59 cases). The two groups of patients were treated by repositioning maneuver before absolute bed rest. observation group was given Duhuo Xuduan Tang, 150 mL·time^-1, 3 times·d^-1 orally, while control group was orally given ibuprofen, 300 mg·time^-1, vitamin B₁, 10 mg·time^-1, 2 times·d^-1, drugs were taken for 5 days a week, and then stopped for 2 days. Both groups were treated continuously for 4 weeks. changes in visual analogue score (VAS), modified Oswestry dysfunction index (MODI), serum substance P (SP), dopamine (DA), serotonin (5-HT), BMP-7 and Aggrecan were observed before and after treatment with enzyme-linked immunosandwich assay (ELISA). Result: Compared with before treatment, VAS and modified Oswestry dysfunction index scores were lower in both groups (P<0.05), BMP-7 and Aggrecan contents were higher, while SP, DA and 5-HT contents were lower (P<0.05). Compared with control group, VAS and modified Oswestry dysfunction index scores of observation group were lower (P<0.05), clinical efficacy was improved (P<0.05), levels of BMP-7 and Aggrecan in serum were higher, whereas contents of SP, DA and 5-HT were lower (P<0.05). Conclusion: Duhuo Xuduan Tang has a certain efficacy on different types of lumbar disc herniation, with best efficacy for patients with liver and kidney yin deficiency.

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.

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.

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.

Objective: To assess the incidence and independent risk factors for clinical anastomotic leakage (AL) in patients undergoing anterior resection (AR) or low anterior resection, (LAR) for rectal cancer. Methods: This was a retrospective case-control study of 550 patients with rectal cancer who underwent AR or LAR from April 2007 to March 2017 in Beijing Friendship Hospital, Capital Medical University. The relationship between the incidence of AL and clinicopathological manifestations was analyzed by Chi-squared test and Fisher exact test, and the independent risk factors of AL were analyzed using logistic regression analysis. AL is defined as a defect (including necrosis or abscess formation) of the intestinal wall at the anastomotic site, leading to a communication between the intra- and extra-luminal compartments. AL can be divided into three grades. Grade A anastomotic leakage results in no change in the management of patients, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy. Results: AL was noted in 32 (5.8%) of 550 patients with rectal cancer who underwent AR or LAR, including 15 (46.9%) , 4 (12.5%) , and 13 patients (40.6%) with Grades A, B, and C, respectively. Five patients (0.9%, 5/550) died peri-operatively. AL- and non-AL-related deaths occurred in 3 (9.4%, 3/32, all cases were Grade C) and 2 patients (0.4%, 2/518) , respectively, with the two mortality rates being significant difference (P = 0.002) . Chi-squared test or Fisher exact test showed that the incidence of AL was associated with neoadjuvant chemoradiotherapy (P = 0.011) , intraoperative bleeding (≥100 ml) (χ² = 11.980, P = 0.001) , and tension-reducing suture of anastomosis (P = 0.015) . The results of logistic regression analysis showed that the independent risk factors of AL were neoadjuvant chemoradiotherapy (OR = 2.402, 95%CI: 1.004 - 5.749, P = 0.049) , intraoperative bleeding (≥100 ml) (OR = 2.971, 95%CI: 1.269 - 6.957, P = 0.012) and tension-reducing suture of anastomosis (OR = 2.304, 95%CI: 1.008 - 5.263, P = 0.048) . Conclusion The incidence of AL in patients undergoing AR for rectal cancer is 5.8%. The high-risk factors for AL are neoadjuvant chemoradiotherapy, intraoperative bleeding (≥100 ml) , and tension-reducing suture of anastomosis. Patients with these three risk factors have a high risk of AL rate, and a defunctioning stoma should be performed.