Genetically modified pigs: Emerging animal models for hereditary hearing loss.

Hereditary hearing loss (HHL), a genetic disorder that impairs auditory function, significantly affects quality of life and incurs substantial economic losses for society. To investigate the underlying causes of HHL and evaluate therapeutic outcomes, appropriate animal models are necessary. Pigs have been extensively used as valuable large animal models in biomedical research. In this review, we highlight the advantages of pig models in terms of ear anatomy, inner ear morphology, and electrophysiological characteristics, as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss. Additionally, we discuss the prospects, challenges, and recommendations regarding the use pig models in HHL research. Overall, this review provides insights and perspectives for future studies on HHL using porcine models.

The Role of Genetic Variants in the Susceptibility of Noise-Induced Hearing Loss.

Noised-induced hearing loss (NIHL) is an acquired, progressive neurological damage caused by exposure to intense noise in various environments including industrial, military and entertaining settings. The prevalence of NIHL is much higher than other occupational injuries in industrialized countries. Recent studies have revealed that genetic factors, together with environmental conditions, also contribute to NIHL. A group of genes which are linked to the susceptibility of NIHL had been uncovered, involving the progression of oxidative stress, potassium ion cycling, cilia structure, heat shock protein 70 (HSP70), DNA damage repair, apoptosis, and some other genes. In this review, we briefly summarized the studies primary in population and some animal researches concerning the susceptible genes of NIHL, intending to give insights into the further exploration of NIHL prevention and individual treatment.

Sox10 Gene Is Required for the Survival of Saccular and Utricular Hair Cells in a Porcine Model.

Pathological changes of the cochlea and hearing loss have been well addressed in Waardenburg syndrome (WS). However, the vestibular organ malformation in WS is still largely unknown. In this study, the differentiation and development of vestibular sensory epithelium and vestibular function caused by SOX10 mutation, a critical gene induces WS, have been studied in minature pig model. Degeneration of vestibular hair cells was found in this Sox10 mutation porcine model. Inner ear phenotype of the SOX10+/R109W miniature pigs showed cochlear abnormalities as well as saccular hypofunction. In the mutant pigs, no prominent dissimilarity was shown in the bone structure of the semicircular canals. However, the saccular membrane was collapsed, and the infusion of stereocilia of the hair cells was observed. There were no dark cells in the utricles in the mutant pigs. The density of the utricular hair cells was also significantly lower in the mutant pigs compared to the wild type. Our study demonstrated that the SOX10 gene and melanocytes play important roles in the vestibular organ development. Sox10 mutation disrupts the KIT-DCT signaling pathway, affects the development of melanocytes, and leads to vestibule morphogenesis.

Serum 25-hydroxyvitamin D is associated with stroke history in a reverse J-shape.

Background: 25-hydroxyvitamin D [25(OH)D], the major form of vitamin D in the body, has a non-linear association with stroke risk. However, the association is not fully understood. The specific shape of the association and the ideal value of 25(OH)D related to minimum risk of stroke remain unclear. Aim: We conducted the study to establish the correlation between circulating 25(OH)D and stroke history and determine the ideal value of 25(OH)D in relation to the lowest stroke prevalence. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were used for analyzes. We used multivariate logistic regression analysis with fitted smooth curves to explore the relationship between 25(OH)D and self-reported stroke history. Subsequently, 40,632 participants were enrolled in the study. Results: A reverse J-shaped association between 25(OH)D and stroke history was determined, where the lowest stroke prevalence for the 25(OH)D level was about 60 nmol/L. After adjusting for confounding factors, prevalence of stroke showed an increasing trend below and above the middle quintile (53.2-65.4 nmol/L) of 25(OH)D. Participants with 25(OH)D levels in the lowest quintile (≤ 39.3 nmol/L) had a 38% increased prevalence of stroke (OR 1.38, 95 %CI 1.12-1.70), while those in the higher level range of 25(OH)D (65.5-80.8 nmol/L) had a 27% higher stroke prevalence (OR 1.27, 95 %CI 1.03-1.57). Conclusion: Using data from a large, cross-sectional cohort program, we found that circulating 25(OH)D was related to stroke history in a reverse J-shaped manner. Given how the causal relationship between circulating 25(OH)D and history of stroke has not been established, more high-quality evidence based on the reverse J-shaped feature is needed to elucidate the link between vitamin D and stroke risk, and the effect of vitamin D supplements on stroke prevention.

Involvement of Cholesterol Metabolic Pathways in Recovery from Noise-Induced Hearing Loss.

The objective of this study was to explore the molecular mechanisms of acute noise-induced hearing loss and recovery of steady-state noise-induced hearing loss using miniature pigs. We used miniature pigs exposed to white noise at 120 dB (A) as a model. Auditory brainstem response (ABR) measurements were made before noise exposure, 1 day and 7 days after noise exposure. Proteomic Isobaric Tags for Relative and Absolute Quantification (iTRAQ) was used to observe changes in proteins of the miniature pig inner ear following noise exposure. Western blot and immunofluorescence were performed for further quantitative and qualitative analysis of proteomic changes. The average ABR-click threshold of miniature pigs before noise exposure, 1 day and 7 days after noise exposure, were 39.4 dB SPL, 67.1 dB SPL, and 50.8 dB SPL, respectively. In total, 2,158 proteins were identified using iTRAQ. Both gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses showed that immune and metabolic pathways were prominently involved during the impairment stage of acute hearing loss. During the recovery stage of acute hearing loss, most differentially expressed proteins were related to cholesterol metabolism. Western blot and immunofluorescence showed accumulation of reactive oxygen species and nuclear translocation of NF-κB (p65) in the hair cells of miniature pig inner ears during the acute hearing loss stage after noise exposure. Nuclear translocation of NF-κB (p65) may be associated with overexpression of downstream inflammatory factors. Apolipoprotein (Apo) A1 and Apo E were significantly upregulated during the recovery stage of hearing loss and may be related to activation of cholesterol metabolic pathways. This is the first study to use proteomics analysis to analyze the molecular mechanisms of acute noise-induced hearing loss and its recovery in a large animal model (miniature pigs). Our results showed that activation of metabolic, inflammatory, and innate immunity pathways may be involved in acute noise-induced hearing loss, while cholesterol metabolic pathways may play an important role in recovery of hearing ability following noise-induced hearing loss.

Degeneration of saccular hair cells caused by MITF gene mutation.

BACKGROUND: Waardenburg syndrome (WS) is the consequence of an inherited autosomal dominant mutation which causes the early degeneration of intermediate cells of cochlear stria vascularis (SV) and profound hearing loss. Patients with WS may also experience primary vestibular symptoms. Most of the current WS studies did not discuss the relationship between WS and abnormal vestibular function. Our study found that a spontaneous mutant pig showed profound hearing loss and depigmentation. MITF-M, a common gene mutation causes type WS which affect the development of the intermediate cell of SV, was then identified for animal modeling. RESULTS: In this study, the degeneration of vestibular hair cells was found in pigs with MITF-M. The morphology of hair cells in vestibular organs of pigs was examined using electron microscopy from embryonic day E70 to postnatal two weeks. Significant hair cell loss in the mutant saccule was found in this study through E95 to P14. Conversely, there was no hair cell loss in either utricle or semi-circular canals. CONCLUSIONS: Our study suggested that MITF-M gene mutation only affects hair cells of the saccule, but has no effect on other vestibular organs. The study also indicated that the survival of cochlear and saccular hair cells was dependent on the potassium release from the cochlear SV, but hair cells of the utricle and semi-circular canals were independent on SV.

The contrast of procedure for prolapse and hemorrhoids between the local anesthesia and the combined spinal epidural anesthesia / 中国医师进修杂志

Objective To explore the clinical effect of procedure for prolapse and hemorrhoids (PPH) treating for Ⅲand Ⅳ degree hemorrhoid under the local anesthesia.Methods One hundred and fifty patients with Ⅲ and Ⅳ degree hemorrhoid were divided into two groups randomly.One group was the local anesthesia group (LA group) which included 73 cases,the other one was the combined spinal epidural anesthesia group (CSE group) which included 77 cases.Compared the safety and efficacy of different procedure.Results The original symptom of the two groups were improved.There was a significant difference in the time of hospitalization time and the hospitalization expense between the two groups (P＜0.05).The LA group was(4.8±1.1)days with(3980±639)yuan,and the CSE group was(6.8±1.1) days with(5128±728)yuan.The rates of two groups of urine retention were 9.6% and 24.7% (P＜0.05) after the operation respectively,and there were no significant differences in recovery normal activity time,the pain index,copracrasia and pruritus,the bleed,the anal fistula,the prolapse of hemorrhoid,the skin tag (P ＞0.05).Conclusion PPH under the local anesthesia is safe,compare to the combined spinal epidural anesthesia,it excels in shortening the hospitalization time and reducing the hospitalization expense,also it can reduce significantly the rate of urine retention after operation.

Laparoscopic versus open appendectomy in patients with chronic appendicitis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the advantages and disadvantages of laparoscopic versus open appendectomy in patients with chronic appendicitis.</p><p><b>METHODS</b>Two hundred twenty- four patients were divided into laparoscopic group (n=98) and open appendectomy group (n=126) according to individual willing. Prospective non- randomized study was performed to compare the operative time, operative bleeding, hospitalization time, the discovery and management concerned in operation. Abdominal pain in these chronic appendicitis cases was followed up.</p><p><b>RESULTS</b>The operative time was (54.8+/-21.8) min in open group and (51.8+/-18.0) min in laparoscopic group (t=0.80,P > 0.05). The operative bleeding was (18.6+/-23.3) ml in open group and (9.8+/-4.7) ml in laparoscopic group (t=3.13, P < 0.05). The hospitalization time was (8.9+/-5.3) d in open group and (6.8+/-3.0) d in laparoscopic group (t=2.66,P < 0.05). Twenty- five cases had abdominal adhesion in laparoscopic group, including 9 cases of adhesion around appendix, 6 cases of adhesion between ileocecum and anterior or lateral abdominal wall, 4 cases of adhesion between epiploon and abdominal wall or intestines, 6 cases of adhesion around colon and others. All adhesion had been dissected. Fourteen cases adhesion around appendix had been discovered in 126 cases of open group and dissected (chi(2) =7.95,P < 0.05). In follow- up research, 24 cases still had chronic abdominal pain in 98 case of open group, and 9 cases had chronic abdominal pain in 87 of laparoscopic group, the difference was significant (chi(2)=6.29,P < 0.05).</p><p><b>CONCLUSION</b>The laparoscopic appendectomy possesses more advantages in treating chronic appendicitis and can decrease the incidence of chronic abdominal pain after operation.</p>

A Clinical Contrast Study on the Tension-free Hernioplasty with Three Operative Methods / 中国医师杂志

Objective To compare the clinical efficacy of tension-free hernioplasty with three operative methods, and analyze the reasons of complications. Methods All Chinese articles dealing with the tension-free hernioplasty included in CNKI from 1997 to 2004 were collected, and divided into three groups according to different operative methods, the clinical efficacy of which was compared. Results The frequecy of foreign matter feel in the Rutknow group was significantly higher than that in the other two groups (P