Accidental ingestion of multiple magnetic beads by children and their impact on the gastrointestinal tract: a single-center study.

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.

Inhibition of endogenous hydrogen sulfide production suppresses the growth of nasopharyngeal carcinoma cells.

Hydrogen sulfide (H2 S) has been widely recognized as one of gasotransmitters. Endogenous H2 S plays a crucial role in the progression of cancer. However, the effect of endogenous H2 S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine-ß-synthase), dl-propargylglycine (PAG, an inhibitor of cystathionine-γ-lyase), and l-aspartic acid (l-Asp, an inhibitor of 3-mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2 S in NPC growth. The results indicated that the combine (PAG + AOAA + l-Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l-Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)-extracellular signal-regulated protein kinase but higher expressions of p-p38 and p-c-Jun N-terminal kinase than those in the AOAA, PAG, and l-Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2 S generation could dramatically inhibit NPC growth via the ROS/mitogen-activated protein kinase pathway. Endogenous H2 S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2 S-producing enzymes could be designed and developed for NPC treatment.

Actinomycin D: a novel Pseudomonas aeruginosa quorum sensing inhibitor from the endophyte Streptomyces cyaneochromogenes RC1.

The infections caused by Pseudomonas aeruginosa are difficult to treat due to its multidrug resistance. A promising strategy for controlling P. aeruginosa infection is targeting the quorum sensing (QS) system. Actinomycin D isolated from the metabolite of endophyte Streptomyces cyaneochromogenes RC1 exhibited good anti-QS activity against P. aeruginosa PAO1. Actinomycin D (50, 100, and 200 µg/mL) significantly inhibited the motility as well as reduced the production of multiple virulence factors including pyocyanin, protease, rhamnolipid, and siderophores. The images of confocal laser scanning microscopy and scanning electron microscopy revealed that the treatment of actinomycin D resulted in a looser and flatter biofilm structure. Real-time quantitative PCR analysis showed that the expression of QS-related genes lasI, rhlI, rhlR, pqsR, pslA, and pilA were downregulated dramatically. The production of QS signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone and N-butanoyl-L-homoserine lactone were also decreased by actinomycin D. These findings suggest that actinomycin D, a potent in vitro anti-virulence agent, is a promising candidate to treat P. aeruginosa infection by interfering with the QS systems.

PCNP is a novel regulator of proliferation, migration, and invasion in human thyroid cancer.

Thyroid cancer (TC) has increased globally, with a prominent increase in small, papillary thyroid cancers. PEST-containing nuclear protein (PCNP), a nuclear protein, has been found to be associated with human cancers in recent years. However, the role and molecular mechanism of PCNP in thyroid cancer remain underexplored. In the present study, the results showed that the expression levels of PCNP in human thyroid tissues were higher than those in adjacent non-tumor tissues. Overexpression of PCNP reduced the proliferation, migration, and invasion of human thyroid cancer cells and down-regulation of PCNP showed reverse effects. In addition, PCNP regulated cell cycle arrest through modifications in the expression of cell cycle regulating genes and PCNP affected apoptosis via activation of ERK/JNK/p38 pathway in thyroid cancer cells. Moreover, PCNP overexpression promoted autophagy by reducing the expression levels of Wnt/ß-catenin pathway in TC cells, however, PCNP knockdown had opposite effects. Furthermore, PCNP overexpression reduced the growth of xenografted human thyroid cancer, whereas PCNP knockdown showed opposite trends. In conclusion, in vitro and in vivo data demonstrate that PCNP as a tumor suppressor gene may serve as a novel prognostic and potential therapeutic marker in human thyroid cancer.

Genetic Susceptibility Study of Chinese Sudden Sensorineural Hearing Loss Patients with Vertigo.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: SSNHL has some relationship with hereditary in Chinese population, but its complex genetic pathogenic mechanisms need further study.

ER stress mediated­autophagy contributes to neurological dysfunction in traumatic brain injury via the ATF6 UPR signaling pathway.

A major public health problem, traumatic brain injury (TBI) can cause severe neurological impairment. Although autophagy is closely associated with the pathogenesis of TBI, the role of autophagy in neurological deficits is unclear. The purpose of the present study was to investigate the molecular mechanisms of endoplasmic reticulum (ER) stress­induced autophagy and its detrimental effects on neurological outcomes following TBI. A rat model of TBI was established by controlled cortical impact. ER stress activation, autophagy induction and autophagic flux dysfunction were examined in the damaged hippocampus post­TBI. Pharmacological inhibition of ER stress significantly blocked post­traumatic autophagy activation, as evidenced by decreased conversion of microtubule­associated protein 1 light chain 3 (LC3)­I to LC3­II and Beclin­1 expression levels in the hippocampus region. Short hairpin RNA­mediated activating transcription factor 6 knockdown significantly prevented ER stress­mediated autophagy stimulation via targeting essential autophagic genes, including autophagy related (ATG)3, ATG9 and ATG12. Furthermore, neurological scores, foot fault test and Morris water maze were used to evaluate the neurological functions of TBI rats. The results revealed that the blockage of ER stress or autophagy attenuated TBI­induced traumatic damage and functional outcomes. In conclusion, these findings provided new insights into the molecular mechanisms of ER stress­induced autophagy and demonstrated its potential role in neurological deficiency following TBI.

Overexpression of miR-329-3p sensitizes osteosarcoma cells to cisplatin through suppression of glucose metabolism by targeting LDHA.

Osteosarcoma (OS) is one of the most frequent malignant bone tumor types. Traditional treatments of OS involve standard chemotherapy or combination with radiation before and after surgery. Cisplatin is one of the most effective chemotherapeutic drugs used for treating osteosarcoma. However, patients with advanced tumor stages develop cisplatin resistance, leading to a major clinical challenge. In this study, we investigated the roles of miR-329-3p in cisplatin sensitivity of osteosarcoma cells. We found miR-329-3p was significantly downregulated in osteosarcoma tissues compared with normal bone tissues. Overexpression of miR-329-3p suppressed osteosarcoma cell proliferation. Moreover, we observed low-toxic cisplatin treatments suppressed miR-329-3p but higher concentrations of cisplatin-induced miR-329-3p expression. In addition, miR-329-3p was significantly downregulated in cisplatin-resistant Saos-2 cells which displayed elevated glucose metabolism. Overexpression of miR-329-3p significantly impaired glucose metabolism of Saos-2 cells. Bioinformatics analysis and luciferase assay consistently demonstrated the glycolysis enzyme, lactate dehydrogenase-A (LDHA) was a direct target of miR-329-3p in osteosarcoma cells. Rescue experiments revealed restoration of LDHA in miR-329-3p-overexpressed cisplatin-resistant cells effectively recovered glucose metabolism, resulting in increased cisplatin resistance. This study demonstrates a miR-329-3p-LDHA-glucose metabolism-cisplatin resistance axis in osteosarcoma cells, providing a miRNA-based therapeutic strategy against chemoresistant osteosarcoma.

The effects of m 6A modification in central nervous system function and disease.

N 6-methyladenosine (m 6A) is an important RNA modification, which is highly active in brain tissues, participates in global intracellular mRNA metabolism, and regulates gene expression and a variety of biological processes. Stable m 6A modification contributes to the normal embryonic brain development and memory formation and plays an important role in maintaining the functions of the central nervous system. However, changes in the level of m 6A modification and the expression of its related proteins cause abnormal nervous system functions, including brain tissue development retardation, axon regeneration disorders, memory changes, and stem cell renewal and differentiation disorders. Recent studies have also found that m 6A modification and its related proteins play key roles in the development of various nervous system diseases, such as Alzheimer's disease, Parkinson's disease, fragile X-chromosome syndrome, depression and glioblastoma. In this review, we summarize the research progresses of m 6A modification regulation mechanism in the central nervous system in recent years, and discusses the effects of gene expression regulation mediated by m 6A modification on the biological functions of the central nervous system and related diseases, thereby providing some insights on the new research targets and treatment directions for the central nervous system diseases.

Serum Bilirubin Level as a Potential Marker for the Hearing Outcome in Severe-Profound Bilateral Sudden Deafness.

OBJECTIVE: To investigate the association of serum bilirubin level with hearing outcomes in bilateral sudden sensorineural hearing loss (BSSHL) patients. PARTICIPANTS: One hundred thirteen in-patient BSSHL patients were consecutively enrolled between July 2008 and December 2015 in a tertiary center. MAIN OUTCOME MEASURES: Multivariable linear regression, generalized estimating equations (GEE), and stratified analyses were applied to examine the association between serum bilirubin level and hearing outcome measures such as final hearing threshold and absolute and relative hearing gains in BSSHL. RESULTS: After full adjustment for potential confounders, total bilirubin levels (TBIL) were observed to be positively and independently associated with hearing outcomes as measured by final hearing (ß [95% confidence interval {CI}]: -1.5 [-2.7, -0.2] dB HL per 1 µmol/L increase in TBIL) and absolute and relative hearing gains (ß [95% CI]: 1.4 [0.2, 2.7] dB and 1.6 [0.2, 3.1] dB, respectively) in the severe to profound hearing loss subpopulation. CONCLUSIONS: Higher TBIL levels, within the normal or mildly elevated ranges, were independently and significantly associated with better hearing outcome in BSSHL patients with severe to profound hearing loss. Given bilirubin elevation treatments exist, our finding suggests a novel pharmacological strategy for this specific subpopulation.

PEST-containing nuclear protein regulates cell proliferation, migration, and invasion in lung adenocarcinoma.

Lung cancer is the leading cause of cancer-related mortality worldwide. PEST-containing nuclear protein (PCNP) has been found in the nucleus of cancer cells. Whether PCNP plays a role in the growth of lung adenocarcinoma is still unknown. In the present study, the results indicated that the level of PCNP in lung adenocarcinoma tissue was significantly higher than that in corresponding adjacent non-tumor tissue. Over-expression of PCNP promoted the proliferation, migration, and invasion of lung adenocarcinoma cells, while down-regulation of PCNP exhibited opposite effects. PCNP over-expression decreased apoptosis through up-regulating the expression levels of phospho (p)-signal transducers and activators of transcription (STAT) 3 and p-STAT5 in lung adenocarcinoma cells, whereas PCNP knockdown showed opposite trends. PCNP overexpression enhanced autophagy by increasing the expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) in lung adenocarcinoma cells, however an opposite trend was observed in the sh-PCNP group. In addition, overexpression of PCNP showed the tumor-promoting effect on xenografted lung adenocarcinoma, while PCNP knockdown reduced the growth of lung adenocarcinoma via regulating angiogenesis. Our study elucidates that PCNP can regulate the procession of human lung adenocarcinoma cells via STAT3/5 and PI3K/Akt/mTOR signaling pathways. PCNP may be considered as a promising biomarker for the diagnosis and prognosis in patients with lung adenocarcinoma. Furthermore, PCNP can be a novel therapeutic target and potent PCNP inhibitors can be designed and developed in the treatment of lung adenocarcinoma.

Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease.

Hydrogen sulfide (H2S), a colorless gas smelling of rotten egg, has long been recognized as a toxic gas and environment pollutant. However, increasing evidence suggests that H2S acts as a novel gasotransmitter and plays important roles in a variety of physiological and pathological processes in mammals. H2S is involved in many hepatic functions, including the regulation of oxidative stress, glucose and lipid metabolism, vasculature, mitochondrial function, differentiation, and circadian rhythm. In addition, H2S contributes to the pathogenesis and treatment of a number of liver diseases, such as hepatic fibrosis, liver cirrhosis, liver cancer, hepatic ischemia/reperfusion injury, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, hepatotoxicity, and acute liver failure. In this review, the biosynthesis and metabolism of H2S in the liver are summarized and the role and mechanism of H2S in liver health and disease are further discussed.

Tumour necrosis factor-α-induced protein 8-like 2 is a novel regulator of proliferation, migration, and invasion in human rectal adenocarcinoma cells.

Tumour necrosis factor-α-induced protein 8-like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non-tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down-regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down-regulating the expression levels of Wnt3a, phospho (p)-ß-Catenin, and p-glycogen synthase kinase-3ß in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p-Smad2, p-Smad3, and transforming growth factor-beta (TGF-ß) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/ß-Catenin and TGF-ß/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma.

Hydrogen Sulfide Alleviates Lipopolysaccharide-Induced Diaphragm Dysfunction in Rats by Reducing Apoptosis and Inflammation through ROS/MAPK and TLR4/NF-κB Signaling Pathways.

Diaphragm dysfunction is an important clinical problem worldwide. Hydrogen sulfide (H2S) is involved in many physiological and pathological processes in mammals. However, the effect and mechanism of H2S in diaphragm dysfunction have not been fully elucidated. In this study, we detected that the level of H2S was decreased in lipopolysaccharide- (LPS-) treated L6 cells. Treatment with H2S increased the proliferation and viability of LPS-treated L6 cells. We found that H2S decreased reactive oxygen species- (ROS-) induced apoptosis through the mitogen-activated protein kinase (MAPK) signaling pathway in LPS-treated L6 cells. Administration of H2S alleviated LPS-induced inflammation by mediating the toll-like receptor-4 (TLR-4)/nuclear factor-kappa B (NF-κB) signaling pathway in L6 cells. Furthermore, H2S improved diaphragmatic function and structure through the reduction of inflammation and apoptosis in the diaphragm of septic rats. In conclusion, these findings indicate that H2S ameliorates LPS-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF-κB signaling pathways. Novel slow-releasing H2S donors can be designed and applied for the treatment of diaphragm dysfunction.

PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways.

BACKGROUND: PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. METHODS: ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo. RESULTS: PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis. CONCLUSIONS: PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma.

Comparison between Bilateral and Unilateral Sudden Sensorineural Hearing Loss.

BACKGROUND: Bilateral sudden sensorineural hearing loss (BSSHL) is rare and assumed to be a different clinical entity compared to unilateral SSHL (USSHL). This study examined the differences between the idiopathic BSSHL and USSHL. METHODS: Forty-six sequential BSSHL patients (Se-BSSHL) and 68 simultaneous BSSHL (Si-BSSHL) were consecutively admitted between June 2008 and December 2015. Two sets of patients served as control groups: (1) USSHL patients with healthy contralateral ear and (2) USSHL patients with contralateral preexisting hearing loss (USSHLwCHL). We retrospectively analyzed differences among four cohorts using analysis of variance, Kruskal-Wallis test, Welch's t-test, and Chi-square test as appropriate before and after propensity score matching (PSM) based on age, gender, and body mass index (BMI). RESULTS: The prevalence of idiopathic BSSHL was 8.6% (114/1329) among the total SSHL patients. In the total cohort, USSHL patients tended to be younger, female, and tended to have lower BMI, renal parameters, and total cholesterol in addition to higher high-density lipoprotein compared to the other three groups. Most routine blood indicators, some coagulation markers, and immunoglobulin M (H = 13.4, P = 0.004) were significantly different among the study groups. After PSM, the major significant differences were found in audiometric characteristics. Si-BSSHL and Se-BSSHL patients demonstrated similar hearing thresholds as USSHL but were significantly better than the USSHLwCHL patients across most frequencies before and after treatment (H = 30.0, P < 0.001 for initial hearing and H = 12.0, P = 0.007 for final hearing). Moreover, the BSSHL patients showed different hearing loss distribution patterns (more descending type, χ2 = 33.8, P = 0.001) with less hearing gain (H = 17.5, P < 0.001) compared to the USSHL patients. CONCLUSIONS: Idiopathic BSSHL is a relatively rare subtype of SSHL with a higher rate of descending audiogram type and inferior hearing outcome rather than being classified as a completely different disease entity compared to USSHL.

Clinical Auditory Phenotypes Associated with GATA3 Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome.

BACKGROUND: Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases. METHODS: Three affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided. RESULTS: In Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations. CONCLUSIONS: This study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.

A POU3F4 Mutation Causes Nonsyndromic Hearing Loss in a Chinese X-linked Recessive Family.

BACKGROUND: The molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family. METHODS: A series of clinical evaluations including medical history, otologic examinations, family history, audiologic testing, and a high-resolution computed tomography scan were performed for each patient. Bidirectional sequencing was carried out for all polymerase chain reaction products of the samples. Moreover, 834 controls with normal hearing were also tested. RESULTS: The pedigree showed X-linkage recessive inheritance pattern, and pathogenic mutation (c.499C>T) was identified in the proband and his family member, which led to a premature termination prior to the entire POU domains. This mutation co-segregated with hearing loss in this family. No mutation of POU3F4 gene was found in 834 controls. CONCLUSIONS: A nonsense mutation is identified in a family displaying the pedigree consistent with X-linked recessive pattern in POU3F4 gene. In addition, we may provide molecular diagnosis and genetic counseling for this family.

Clinical Study on 136 Children with Sudden Sensorineural Hearing Loss.

BACKGROUND: The prevalence of sudden sensorineural hearing loss in children (CSSNHL) is consistently increasing. However, the pathology and prognosis of CSSNHL are still poorly understood. This retrospective study evaluated clinical characteristics and possible associated factors of CSSNHL. METHODS: One hundred and thirty-six CSSNHL patients treated in Department of Otolaryngology-Head and Neck Surgery and Institute of Otolaryngology at Chinese PLA General Hospital between July 2008 and August 2015 were included in this study. These patients were analyzed for clinical characteristics, audiological characteristics, laboratory examinations, and prognostic factors. RESULTS: Among the 136 patients (151 ears), 121 patients (121 ears, 80.1%) were diagnosed with unilaterally CSSNHL, and 15 patients (30 ears, 19.9%) with bilateral CSSNHL. The complete recovery rate of CSSNHL was 9.3%, and the overall recovery rate was 37.7%. We found that initial degree of hearing loss, onset of treatment, tinnitus, the ascending type audiogram, gender, side of hearing loss, the recorded auditory brainstem response (ABR), and distortion product otoacoustic emissions (DPOAEs) had prognostic significance. Age, ear fullness, and vertigo had no significant correlation with recovery. Furthermore, the relevant blood tests showed 30.8% of the children had abnormal white blood cell (WBC) counts, 22.1% had elevated homocysteine levels, 65.8% had high alkaline phosphatase (ALP), 33.8% had high IgE antibody levels, and 86.1% had positive cytomegalovirus (CMV) IgG antibodies. CONCLUSIONS: CSSNHL commonly occurs unilaterally and results in severe hearing loss. Initial severe hearing loss and bilateral hearing loss are negative prognostic factors for hearing recovery, while positive prognostic factors include tinnitus, gender, the ascending type audiogram, early treatment, identifiable ABR waves, and DPOAEs. Age, vertigo, and ear fullness are not correlated with the recovery. Some serologic indicators, including the level of WBC, platelet, homocysteine, ALP, positive CMV IgG antibody, fibrinogen, and some immunologic indicators, are closely related to CSSNHL.

[The application of CRISPR/Cas9 genome editing technology in cancer research].

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease) genome editing technology has become more and more popular in gene editing because of its simple design and easy operation. Using the CRISPR/Cas9 system, researchers can perform site-directed genome modification at the base level. Moreover, it has been widely used in genome editing in multiple species and related cancer research. In this review, we summarize the application of the CRISPR/Cas9 system in cancer research based on the latest research progresses as well as our understanding of cancer research and genome editing techniques.