Volume 101 ·  Issue 02 ·  2021

Cochlear implantation is currently the most effective treatment for patients with severe-to-profound sensorineural hearing loss. How to achieve minimally invasive treatment, preserve the residual hearing, and further improve curative effect and reduce surgical complications is the goal of cochlear implantation practice. This article introduces the minimally invasive cochlear implantation technique in terms of the idea of minimally invasive operation, the advantages of electric acoustic stimulation, the key points of electrode implantation technique, the design of surgical incision, and the precise processing of perioperative period. This technique not only has the merits of less operative damage and better hearing and speech rehabilitation after surgery, but also reserves favorable structures and function for the future application of gene therapy and hair cell regeneration technique. Therefore, it is strongly recommended for further promotion in clinical practice.

Auditory brainstem implantation is a hearing restoration technique on the central auditory pathway, which directly stimulates neural tissues of cochlear nucleus by electrode array to produce hearing, so it will not be restricted by abnormalities of the cochlea and cochlear nerve. In the past 30 years since the birth of multi-channel ABI, its indications have expanded from patients with neurofibromatosis type 2 (NF2) to congenital deafness patients with severe inner ear and/or cochlear nerve malformations, and the age of recipients decreases from adults to young children. This article summarizes the principle, indications, surgical techniques, complications and auditory outcomes of ABI.

Genetic screening is an important measure to achieve disease group prevention, early diagnosis and early intervention. Genetic screening of hereditary deafness has been carried out in China for more than 10 years, and it has played an important role in preventing birth defects of deafness and reducing hearing and speech disabilities. With the deepening of the research on hereditary deafness, the development of screening technology, the update of screening tools, the improvement of laboratory conditions and the support of government policies, more doctors with genetic counseling qualifications have been formed, and the number of areas of genetic screening for hereditary deafness has gradually increased. At present, it has covered major cities in most provinces in China, and the examined population has changed from the initial deaf patients or family members at high risk of deafness to large-scale population screening covering newborns, pre-marriage, pre-pregnancy and prenatal, and the technical methods have gradually diversified. This article focuses on the principles, procedures, technical methods, report interpretation, genetic counseling and other aspects of deafness gene screening, aiming at providing guiding opinions for professionals engaged in this work, standardizing the deafness gene screening and the work flow after screening in China, and making deafness gene screening more effectively serve the early diagnosis, treatment and prevention of deafness.

To explore the application value of high-throughput gene detection method of copy number variations (CNV) in the diagnosis of enlarged vestibular aqueduct (EVA).

A total of 46 nonsyndromic hearing loss patients with EVA were recruited between May 2014 and December 2016 from Department of Otolaryngology of Xiangya Hospital, Central South University. A high-throughput multiplex analysis method based on double ligation and multiple fluorescent PCR was designed and performed to detect CNV in the three EVA-related genes (SLC26A4, FOXI1 and KCNJ10). The data were analyzed by GeneMapper v4.1. Healthy volunteers (n=100) were selected as normal controls.

A total of 46 EVA patients were detected (32 males, 14 females, aged 1 to 26 years). In 4 EVA patients, deletions of exons 1-3 of SLC26A4 gene (4/46, 8.7%) were detected, which were not reported in the database of genomic variants (DGV), and were absent in 100 normal controls. There was no CNV detected in FOXI1 and KCNJ10 in the study.

In the current study, three known EVA-related genes were designed as the target area for CNV detection by high-throughput ligation-dependent probe amplification (HLPA) analysis. This method can be used as a supplementary analysis of point mutation detection of hearing loss, which helps achieve the accurate genetic diagnosis of EVA.

To perform a comprehensive comparison on the therapeutic effects of unilateral 31.5 mm and 28 mm cochlear implantation (CI) on the post-operative hearing rehabilitation outcomes, including hearing threshold, speech recognition and quality of life, in patients with bilateral sensorineural hearing loss.

A total of 26 patients [12 males, 14 females, aged 19-71 (43±16) years] diagnosed with bilateral severe-to-profound sensorineural hearing loss at Peking Union Medical College Hospital from April 2018 to August 2019 were included. Patients underwent temporal bone high resolution CT (HRCT), based on which the electrode lengths were calculated using OTOPLAN. Eleven and fifteen ears were implanted with MED-EL Flex 31.5 mm and Flex 28 mm electrode arrays respectively, via round window approach under minimally invasive surgery. The patients were followed up regularly for up to 2 years. At each follow-up, aided hearing threshold, speech recognition in quiet and noise, and Nijmegen Cochlear Implantation Questionnaire (NICQ) scores were evaluated and compared.

Post-operative hearing thresholds were (46.5±3.4) dB and (48.5±2.2) dB in patients implanted with MED-EL Flex 31.5 mm and Flex 28 mm electrode arrays, respectively, with no statistically significant difference (P=0.074). Both hearing thresholds and speech recognition demonstrated significant post-operative improvement compared with pre-operative results. Hearing thresholds after 1-year post-operation were (32.1±1.2) dB and (32.5±0.9) dB, respectively (P=0.355). Patients implanted with Flex 31.5 mm electrode scored significantly higher at speech recognition under 65 dB sound pressure level (SPL) at most of the follow-ups (All P<0.05). Speech recognition in noise (S/N=10 dB) was also improved in patients implanted with Flex 31.5 mm electrode. All sub-divisions of the NICQ demonstrated significant post-operative improvement, and no significant difference between the 2 groups was observed apart from the"self-confidence"sub-division.

Selection of MED-EL Flex 31.5 mm and 28 mm implantation based on pre-operative OTOPLAN evaluation can both bring significant improvements to patients′ hearing and quality of life. Flex 31.5 mm electrode can potentially provide better speech recognition within a certain period after surgery.

To perform the phenotype and genetic analysis on two families with moderate sensorineural hearing impairment and determine the cause of deafness.

The phenotype and genetic analysis was performed on the two hearing impairment pedigrees coming to Chinese PLA General Hospital from January 2014 to August 2020. DNA samples of the proband from family 1 and the parents from family 2 were collected and tested through next generation sequencing on all deafness genes, and Sanger sequencing was performed to verify the mutation sites. The reported pathogenic variants of the otogelin-like (OTOGL) gene, the autosomal recessive inherited deafness genes that cause moderate sensorineural hearing loss and the clinical manifestations of the deafness genes that have the similar expression location as the OTOGL gene were summarized and analyzed.

The pathogenic variants in the families were compound heterozygous variants in the OTOGL gene c.2773C>T/c.2826C>G (p.Arg925*/p.Tyr942*) and c.4455G>A/c.875C>G (Trp1485*/p.Ser292*), respectively. c.2773C>T was an already reported pathogenic variant causing hearing impairment in the literature, while c.2826C>G, c.4455G>A and c.875C>G were novel reported variant sites. The above four variants were classified as pathogenic variants according to the variant interpretation standards and guideline of the Amercian College of Medical Genetics and Genomics.

Pathogenic variants in OTOGL gene is an important genetic factor leading to moderate sensorineural hearing loss. The newly discovered variant sites c.2826C>G, c.4455G>A and c.875C>G enrich the variant spectrum of OTOGL gene. The results of the current study provide a basis for genetic counseling of the related families and a new target for the treatment of hereditary hearing loss in the future.

To analyze the clinical characteristics and identify the causative gene of a case with congenital deafness.

Detailed medical history and clinical examination of a 4-year-old male child with congenital deafness were conducted in the First Affiliated Hospital of Army Military Medical University in June 2016. He was diagnosed with sensorineural deafness. The venous blood of the child and his parents was drawn, and genomic DNA was extracted. Proband's DNA was performed with targeted capture of high-throughput sequencing, then Sanger sequencing was used to verify the suspected mutation and segregation in this pedigree. According to the genetic diagnosis of the proband's deafness, ophthalmic examinations were performed. Genetic prenatal diagnosis was performed when the proband's mother was pregnant again.

The patient was detected with p.Trp1466Ter/p.Tyr2042Ter compound heterozygous mutations of MYO7A gene with targeted high-throughput sequencing. The mutation of p.Trp1466Ter was a reported mutation, while p.Tyr2042Ter has not been reported. In addition to congenital deafness, retinitis pigmentosa was also found by ophthalmologic examination, and the patient was clinically diagnosed with Usher syndrome type 1. Amniocentesis and fetal DNA sequencing were performed on the repregnancy fetus of this family at 18 weeks of gestation. The heterozygous mutation of MYO7A gene p.Tyr2042Ter was found, and the other allele was the wild type, indicating that the child will not exhibit clinical manifestations of Usher syndrome type 1. Indeed, the second child passed neonatal hearing screening.

The clinical features and genetic variants were delineated in this family with Usher syndrome type 1. The results of the current study have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

To analyze the prevalence and the related factors of dyslipidemia in 21-hydroxylase deficiency (21-OHD) patients.

A total of 205 patients with 21-OHD were recruited in Peking Union Medical College Hospital from January 2016 to January 2018. The basic information, glucocorticoid replacement therapy, and laboratory examination results of patients were obtained from medical records. The genotypes of CYP21A2 were identified by Sanger sequencing and multiplex ligation dependent probe amplification. The prevalence of dyslipidemia among 21-OHD patients, basic information and related hormone levels of 21-OHD patients with different status of blood lipid were described. Logistic regression model was used to analyze the related factors of dyslipidemia in 21-OHD patients.

The age of subjects was 17.0 (8.3, 25.0) years old, including 51 males (24.9%). According to CYP21A2 genotypes, there were 16 cases in Null group, 26 cases in Group A, 105 cases in group B, 27 cases in group C, and 31 cases in group D. The incidence of dyslipidemia was 29.3% (60/205), among which 37.3% (19/51) in male and 26.6% (41/154) in female patients, respectively. The M (Q₁, Q₃) of total cortisol level (nmol/L) and body mass index (kg/m²) of male 21-OHD patients with dyslipidemia were 0.17 (0.06, 0.35) and 25.76 (17.01, 30.45), respectively, which were higher than those with ortholiposis [0.04 (0.02, 0.21) and 18.83 (16.53, 23.88)] (all P<0.05). TheM (Q₁, Q₃) of progesterone level (nmol/L), body mass index (kg/m²) and age (years) of female 21-OHD patients with dyslipidemia were 74.40 (50.97, 98.52), 23.09 (21.78, 27.78) and 23.00 (16.50, 28.00), respectively, which were higher than those with ortholiposis [52.81 (33.41, 68.85), 21.55 (18.63, 25.71) and 18.00 (9.50, 25.00)] (all P<0.05). The risk of dyslipidemia increased by 5.0% [OR (95%CI): 1.05 (1.01, 1.09)] for every 1 nmol/L increase of progesterone.

The incidence of dyslipidemia is high in 21-OHD patients, and progesterone level is positively correlated with dyslipidemia.

To analyze the correlations among different common scales for evaluating the severity of the first-visit Charcot-Marie-Tooth disease (CMT), and explore the cross-sectional characteristics of neurological dysfunction in patients with four common genotypes (CMT1A, CMT1X, CMT2A and MPZ-related CMT) at their first visits.

A total of 117 genetically confirmed CMT patients (aged ≥10 years) from the Department of Neurology of the Third Xiangya Hospital from 2009 to 2019 were included in the study, which consisted of 45 CMT1A, 41 CMT1X, 19 CMT2A, and 12 MPZ-related CMT patients. Clinical data of these patients at first visits were collected and neurological deficits were evaluated by Charcot-Marie-Tooth Neuropathy Score (CMTNS), Charcot-Marie-Tooth Examination Score (CMTES), Overall Neuropathy Limitation Scale (ONLS) and Functional Disability Scale (FDS). Spearman′s correlation was performed to analyze the relationship between CMTNS, CMTES, ONLS and FDS. The age of onset, duration of disease, scores of CMTNS, CMTES, ONLS and FDS were compared among four genotypes.

In the 117 CMT patients, the male to female ratio was 1.79/1, and the age of onset was (19±13) years. The duration of disease was 10(3, 15) years, and the scores of CMTNS, CMTES, ONLS and FDS were 11.4±6.2, 8.8±5.7, 2.7±1.4 and 2.6±1.3, respectively. There was a significant correlation between CMTES, ONLS, FDS and CMTNS in the overall CMT patients and four subtypes respectively (r≥0.40, P<0.05). CMTNS, CMTES and ONLS scores of four subtypes showed positive correlations with duration of disease (P<0.05), but FDS scores of CMT1A, CMT1X and MPZ-related CMT patients exhibited no correlation with duration of disease (P>0.05) at their first visits. The age of onset in CMT2A patients was younger than that of the patients with the other three genotypes (P<0.05), furthermore, the scores of four scales in early-onset CMT2A patients were higher than those of adult-onset type CMT2A patients (CMTNS:P=0.031, CMTES: P=0.048, ONLS: P=0.042, FDS: P=0.047). In CMT1X patients, the males had higher scores than those of females for all four scales (CMTNS: P=0.028, CMTES: P=0.014, ONLS: P=0.023, FDS: P=0.002).

CMTNS, CMTES and ONLS could be used in natural history studies and clinical trials according to the different clinical situations. In the four genotypes, CMT2A patients have younger age of onset, and the earlier the age of onset, the severer the dysfunction. Moreover, male CMT1X patients relatively have severer neurological dysfunction than female patients.

To compare the clinical effect of different total prostate volume (TPV) and different transitional zone volume (TZV) on benign prostatic hyperplasia (BPH) treated with transurethral resection of prostate(TURP).

Clinical data of 210 patients with BPH admitted to Guizhou provincial people′s hospital from June 2016 to August 2018 were retrospectively collected and analyzed. All patients underwent transrectal ultrasonography, and they were divided into three groups according to TPV: 70 patients in group A:TPV<40mL, 98 patients in group B: 40 ml≤TPV<80 ml, and 42 patients in group C:TPV≥80 ml. Meanwhile, three groups were divided according to TZV: 88 patients in group a: TZV<20ml, 67 patients in group b: 20 ml≤TZV<40 ml, and 55 patients in group c:TZV≥40 ml. All of the patients with TURP were followed up for 6 months after surgery, and the data of international prostate symptom score (IPSS), storage symptoms IPSS (IPSS-S), voiding symptoms IPSS (IPSS-V), Quality of Life (QoL) index, and maximum urinary flow rate (Qmax) were collected before and after surgery. Finally, the effect of TPV and TZV on TURP was analyzed respectively by analysis of variance.

There were no statistically significant differences in preoperative IPSS, IPSS-V, IPSS-S, QoL and Qmax among the three groups of patients grouped by TPV (P>0.05), but the age of patients in group C(73.5±6.5) was significantly higher than that in group A (69.3±7.6) and group B (70.9±7.3) (P=0.015). Postoperative IPSS, IPSS-V, IPSS-S, QoL and Qmax of patients in groups A, B and C also showed no significant difference (P>0.05). There were no statistically significant differences in preoperative IPSS, IPSS-V, IPSS-S, QoL, and Qmax among the three groups of patients grouped according to TZV (P>0.05), while the age of patients in group a (69.2±7.6) was significantly lower than that of patients in group b (72.1±7.2) and group c (72.5±6.7) (P=0.017). There were statistically significant differences in IPSS (P=0.010), IPSS-V (P=0.037), IPSS-S (P=0.022), QoL (P=0.038) and Qmax (P=0.037) among the groups a, b, and c after surgery. Moreover, IPSS, IPSS-V, IPSS-S and QoL were negatively correlated with TZV, while Qmax was positively correlated with TZV. Postoperative IPSS, IPSS-V, IPSS-S, QoL and Qmax were significantly different from those before surgery in groups A, B, C and groups a, b, c (P<0.001).

TPV and TZV may not be significantly correlated with BPH symptoms, but may be correlated with age. TURP is an effective treatment for patients with different TPV and TZV. There is no significant statistical difference in the surgical efficacy among patients with different TPV, but patients with larger TZV tended to have better outcome. TZV may be better than TPV in predicting the postoperative efficacy.

To explore the clinical value of ambulatory urodynamics monitoring (AUM) in the diagnosis and treatment of children with refractory monosymptomatic nocturnal enuresis (RMNE) by comparing the urodynamic parameters of AUM with those of conventional urodynamics (CUD).

A total of 40 children (22 males and 18 females) diagnosed with RMNE in the First Affiliated Hospital of Zhengzhou University from May 2017 to September 2019 were collected. They were aged 9-16 years, and their frequency of nocturnal bed-wetting was≥2 times per week. CUD and one sleep cycle AUM were performed, respectively. Then, the urodynamic parameters were recorded and analyzed.

Five of the 40 children dropped out of the study because of the poor compliance. The age of children with RMNE was(12.6±2.1)years old, the ratio of male to female was 19∶16, and the severity of enuresis (enuresis frequency) was(4.2±1.7) times per week. Compared to the CUD group, the bladder compliance (BC) [(28.4±7.7) ml/cmH₂O vs (23.6±6.1) ml/cmH₂O(1 cmH₂O=0.098 kPa)] and maximum detrusor pressure (Pmax.det) [(44.6±9.1) cmH₂O vs (36.8±8.3) cmH₂O] in the AUM group were significantly higher (P<0.05). The maximum flow rate (Qmax) [(19.6±7.2) ml/s vs (20.9±5.4) ml/s] and post void residual (PVR) [(9.5±5.7) ml vs (10.9±5.3) ml] between the two groups showed no statistically significant differences (P>0.05). Detrusor overactivity (DO) was detected in 27 cases (77.1%) during AUM and in 16 cases (45.7%) during CUD; the difference was statistically significant (P<0.05). Among them, 15 cases (42.9%) with DO were detected both in CUD and AUM, while 12 (34.3%) with DO were not detected in CUD. For the 15 cases with DO detected by both CUD and AUM, the frequency [(3.1±1.0) times/h vs (2.4±0.8) times/h] and maximum value of DO [(22.9±4.5) cmH₂O vs (19.2±4.0) cmH₂O] in the AUM group were both higher than those in the CUD group (P<0.05).

Bladder dysfunction can be diagnosed in children with RMNE using AUM. Furthermore, AUM is more accurate than CUD in evaluating BC, Pmax.det, DO, and other parameters. For children with RMNE and with unsatisfactory CUD results, further AUM examination is recommended to clarify the etiology.

To investigate the expression of SQSTM1 in thyroid papillary carcinoma and its influence on the invasion and migration of thyroid papillary carcinoma cells TPC-1.

From April to June 2019, cancer tissues and adjacent tissues of 21 cases with thyroid papillary carcinoma in the First Affiliated Hospital of Zhengzhou University were collected, and the expression of SQSTM1 was detected by RT-qPCR. SQSTM1 knockdown cell line SQSTM1-KD-TPC-1 was constructed in TPC-1 cells by lentivirus transfection. RT-qPCR was used to detect SQSTM1 expression in TPC-1 cells and SQSTM1-KD-TPC-1 cells. The changes of invasion and migration before and after SQSTM1 knockdown in TPC-1 cells were detected by transwell test. The proliferation of TPC-1 and SQSTM1-KD-TPC-1 cells were detected by MTT and clone formation test. RT-qPCR was used to detect the gene expression of proliferation related proteins.

The expression of SQSTM1 in papillary thyroid carcinoma tissues was significantly higher than that in normal adjacent tissues, and 76.2%(16/21) of the petients showed high mRNA expression. Knock down SQSTM1 significantly inhibited the ability of tumor proliferation, invasion and migration, and the expression of proliferation-related proteins were significantly decreased (P<0.01), indicating that SQSTM1 was involved in the regulation of proliferation related pathway mechanism.

SQSTM1 significantly promotes invasion, migration and proliferation in thyroid papillary cancer cells TPC-1 and may be a potential gene therapy target.

To discuss the value and technique of clip remodeling in microsurgical treatment of intracranial aneurysms via keyhole approaches.

The clinical data of patients with intracranial aneurysms, who were treated by microsurgical clipping via keyhole approaches from January 2017 to December 2019, were retrospectively analyzed. The clips were remodeled based on the aneurysmal characteristics during the procedure in 27 cases. Angiography was obtained within one week after surgery in order to evaluate the position of clips and the security of lesions. All patients were followed up at the outpatient clinic to assess the clinical outcomes.

A total of 27 patients harbored 30 intracranial aneurysms, including 23 ruptured lesions and 7 unruptured ones. There were 9 middle cerebral artery aneurysms, 11 anterior communicating artery aneurysms, 9 posterior communicating artery aneurysms and 1 anterior cerebral artery aneurysm, respectively. Nine patients were operated via supraorbital keyhole approach, as well as 17 via pterional keyhole approach and one via hemispheric keyhole approach. Postoperative angiography revealed complete obliteration of lesions without residual filling in all cases. Twenty-five patients recovered well at discharge and two presented with mild disability. After 3-36 months of follow-up, no rebleeding and new-onset neurological deficits were noted.

Clip remodeling technique is a simple and effective option, which can alleviate the limitation of manipulative freedom under keyhole approaches and improve the microsurgical effect of intracranial aneurysms.

This article reports an elderly male patient who was admitted to hospital for 1 month due to persistent abdominal distension with vomiting. Physical examination revealed abnormal abdominal bulge, abdominal CT revealed giant pancreatic pseudocyst, sudden gastrointestinal bleeding and hemorrhagic shock during hospital stay. After interventional embolization of the left gastric artery, the vital signs of the patient tended to be stable, and then recovered after supportive treatment.

Chronic obstructive pulmonary disease (COPD) is one of the important chronic diseases of respiratory system. Its early recognition and intervention is a hot topic at home and abroad. This article reviews the domestic and international controversies on the definition of early COPD, laboratory evaluation and early screening of early COPD, and whether drug intervention is needed, so as to further understand the identification, prevention and control of early COPD.

From November 21 to 22, 2020, the National Clinical Forum on the Diagnosis and Treatment of Helicobacter Pylori and Digestive Diseases and the 4th National Summit Forum on the Integration of Traditional Chinese and Western Medicine of Helicobacter Pylori and Gastrointestinal Microecology were successfully held in Beijing. This conference is a combination of offline and online, sponsored by Beijing Medical Association and China Helicobacter Pylori Information Center, co-sponsored by Peking University First Hospital, Chinese Medical Journal of Chinese Medical Association, Chinese Medical Promotion Association Integrated Traditional Chinese and Western Medicine Digestive Diseases Branch, and co-organized by China Health Promotion Foundation, Beijing Health Education Association, Beijing Medical Association Intestinal Microecology and Helicobacter Pylori Branch.