Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature.

AIM: To detect the pathogenic gene variant in a family with neurofibromatosis type 1 (NF1). METHODS: This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology. After detecting the suspicious pathogenic variant type, the pathogenic variant sites of the patient and the patient's family members were verified by multiple ligation dependent probe amplification and Sanger sequencing. Sift, polyphen-2, Mutation Taster and GERP++ software were used to predict the pathogenicity of the unknown loci. The clinical data, diagnosis and treatment process of the patients were reviewed. Using the keyword "NF1; frameshift pathogenic variant", relevant literature was gathered for analysis from Chinese and international databases, with articles dating from the establishment of each database to April 2022. RESULTS: A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient. The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497. Sanger sequencing validation and segregation analysis were performed, which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family. This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA (p.I1497Nfs*12). Relevant literature retrieval found 7 Chinese articles and 12 foreign articles. With NF1 gene mutation, mutation types are diverse, including point mutation, frameshift mutation, splice site mutation, exon mutation, chimeric mutation and de novo mutation. Foreign reports are based on autosomal dominant inheritance. CONCLUSION: This study's results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family, expanding the mutational spectrum of the NF1 gene.

[Effects of CO2 concentration and soil water content on short-term water-use efficiency at whole-plant level]. / CO2浓度和土壤含水量对植物个体尺度短期水分利用效率的影响.

Uncovering the variations of short-term water-use efficiency (WUEp) at whole-plant level in response to CO2 concentration (Ca) and soil water content (SWC) can improve the understanding of plant survival strategies under climate change. In this study, Platycladus orientalis saplings were cultured in simulated climate chambers.There were totally 15 treatments, including Ca of 400 (C400), 600 (C600) and 800 (C800) µmol·mol-1 and SWC of 35%-45% field water holding capacity (FC), 50%-60%FC, 60%-70%FC, 70%-80%FC and 95%-100%FC. The WUEp was measured by mini-lysimeters, weighting method, and static assimilation chamber. The results showed that both daytime (0.12-1.87 mol·h-1) and nighttime transpiration rates (0.01-0.16 mol·h-1) at whole-plant level reached the maximum at C400×70%-80%FC, while the whole-plant daytime net photosynthetic rate (2.12-22.10 mmol·h-1) reached the maximum at C800×70%-80%FC. In contrast, nighttime respiration rate (0.84-4.41 mmol·h-1) increased with increasing SWC, but decreased with increasing of Ca, reaching the maximum at C400×95%-100%FC. For WUEp (5.37-24.35 mmol·mol-1), it reached the maximum at C800×50%-60%FC, indicating that plants could use less water and fixed more carbon by adjusting adaptation strategies under high Ca and drought conditions. In addition, leaf instantaneous water-use efficiency was a good predictor of WUEP when the canopy structure was similar.

Single-Cell RNA Sequencing Reveals the Interaction of Injected ADSCs with Lung-Originated Cells in Mouse Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a severe chronic lung disease with little effective treatment options other than lung transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have been shown to exert therapeutic effects on PF, but the underlying mechanisms remain to be further elucidated. Here, we show the interaction of ADSCs and lung-originated cells at the single-cell level, using bleomycin- (BLM-) induced mice PF model and green fluorescent protein- (GFP-) labeled mouse ADSCs. The intratracheally injected ADSCs were successfully recollected with flow cytometry and, together with lung-originated cells, were subjected to single-cell RNA sequencing (scRNA-seq). The ADSC treatment drastically changed the transcriptomic profile and composition of lung cells, especially macrophages. We explored the signal pathway interactions between ADSCs and lung-originated cells, showing potentially regulative pathways including NGR, ANNEXIN, HGF, and PERIOSTIN. Our data indicate that the injected ADSCs increased the number of Trem2 + antiinflammatory lung macrophages and lowered further inflammation and fibrosis in the lung. Our work realized the direct analysis of injected ADSCs to explore its in vivo interaction with the lung environment under PF and may provide critical information for future engineering of ADSCs to achieve better therapeutic effects in PF.

Facial reanimation with interposition nerve graft or masseter nerve transfer: a comparative retrospective study.

Both interposition nerve grafts and masseter nerve transfers have been successfully used for facial reanimation after irreversible injuries to the cranial portion of the facial nerve. However, no comparative study of these two procedures has yet been reported. In this two-site, two-arm, retrospective case review study, 32 patients were included. Of these, 17 patients (eight men and nine women, mean age 42.1 years) underwent interposition nerve graft after tumor extirpation or trauma between 2003 and 2006 in the Ear Institute, School of Medicine, Shanghai Jiao Tong University, China, and 15 patients (six men and nine women, mean age 40.6 years) underwent masseter-to-facial nerve transfer after tumor extirpation or trauma between November 2010 and February 2016 in Shanghai Ninth People's Hospital, China. More patients achieved House-Brackmann III recovery after masseter nerve repair than interposition nerve graft repair (15/15 vs. 12/17). The mean oral commissure excursion ratio was also higher in patients who underwent masseter nerve transfer than in patients subjected to an interposition nerve graft. These findings suggest that masseter nerve transfer results in strong oral commissure excursion, avoiding obvious synkinesis, while an interposition nerve graft provides better resting symmetry. This study was approved by the Institutional Ethics Committee, Shanghai Ninth People's Hospital, China (approval No. SH9H-2019-T332-1) on December 12, 2019.

[Long-term effect of oligodendrocyte precursor cell transplantation on a rat model of white matter injury in the preterm infant].

OBJECTIVE: To investigate the long-term effect of oligodendrocyte precursor cell (OPC) transplantation on a rat model of white matter injury (WMI) in the preterm infant. METHODS: A total of 80 Sprague-Dawley rats aged 3 days were randomly divided into sham-operation group, model control group, 5-day ventricular/white matter transplantation group, 9-day ventricular/white matter transplantation group, 14-day ventricular/white matter transplantation group (n=10 each). All groups except the sham-operation group were treated with right common carotid artery ligation and hypoxia for 80 minutes to establish a rat model of WMI in the preterm infant. OPCs were prepared from the human fetal brain tissue (10-12 gestational weeks). At 5, 9, and 14 days after modeling, 3×105 OPCs were injected into the right lateral ventricle or white matter in each transplantation group, and myelin sheath and neurological function were evaluated under an electron microscope at ages of 60 and 90 days. RESULTS: Electron microscopy showed that at an age of 60 days, each transplantation group had a slight improvement in myelin sheath injury compared with the model control group; at an age of 90 days, each transplantation group had significantly thickened myelin sheath and reduced structural damage compared with the model control group, and the 14-day transplantation groups had the most significant changes. There were no significant differences in the degree of myelin sheath injury between the ventricular and white matter transplantation groups at different time points. At an age of 60 or 90 days, the transplantation groups had a significantly higher modified neurological severity score (mNSS) than the sham-operation group and a significantly lower mNSS than the model control group (P<0.05). CONCLUSIONS: OPC transplantation may have a long-term effect in the treatment of WMI in the preterm infant, and delayed transplantation may enhance its therapeutic effect.

Diagnosis and treatment of cavernous hemangioma of the internal auditory canal.

OBJECTIVE: Cavernous hemangioma of the internal auditory canal (IAC) is an extremely rare type of tumor, and only 50 cases have been reported in the literature prior to this study. The aim in this study was to describe the symptomatology, radiological features, and surgical outcomes for patients with cavernous hemangioma of the IAC and to discuss the diagnostic criteria and treatment strategy for the disease. METHODS: The study included 6 patients with cavernous hemangioma of the IAC. All patients presented with sensorineural hearing loss and tinnitus, and 2 also suffered from vertigo. Five patients reported a history of facial symptoms with hemispasm or palsy: 3 had progressive facial weakness, 1 had a hemispasm, and 1 had a history of recovery from sudden facial paresis. All patients underwent CT and MRI to rule out intracanalicular vestibular schwannomas and facial nerve neuromas. Five patients had their tumors surgically removed, while 1 patient, who did not have facial problems, was followed up with a wait-and-scan approach. RESULTS: All patients had a presurgical diagnosis of cavernous hemangioma of the IAC, which was confirmed pathologically in the 5 patients who underwent surgical removal of the tumor. The translabyrinthine approach was used to remove the tumor in 4 patients, while the middle cranial fossa approach was used in the 1 patient who still had functional hearing. Tumors adhered to cranial nerves VII and/or VIII and were difficult to dissect from nerve sheaths during surgeries. Complete hearing loss occurred in all 5 patients. In 3 patients, the facial nerve could not be separated from the tumor, and primary end-to-end anastomosis was performed. Intact facial nerve preservation was achieved in 2 patients. Patients were followed up for at least 1 year after treatment, and MRI showed no evidence of tumor regrowth. All patients experienced some level of recovery in facial nerve function. CONCLUSIONS: Cavernous hemangioma of the IAC can be diagnosed preoperatively through analysis of clinical features and neuroimaging. Early surgical intervention may preserve the functional integrity of the facial nerve and provide a better outcome after nerve reconstruction. However, preservation of functional hearing may not be achieved, even with the retrosigmoid or middle cranial fossa approaches. The translabyrinthine approach seems to be the most appropriate approach overall, as the facial nerve can be easily located and reconstructed.

Decision making in dissection range of temporal bone: refinements to enlarged translabyrinthine approach.

The aim of the study was to describe the refinements to the classic enlarged translabyrinthine approach (ETLA) by modifying the bony dissection range of temporal bone and to analyze the main outcomes achieved in a series of vestibular schwannoma (VS) cases submitted to microsurgery by ETLA. This was a retrospective study of 382 patients who underwent VS surgical removal via ETLA between January 2001 and December 2012. Among those cases, 332 were via classic ETLA, while 28 cases were via ETLA with blind sac technique and middle ear eradication and 22 via transotic approach. Total tumor removal was achieved in 368 cases, whereas near total removal in 11 patients and subtotal in 3 patients. In cases of large VS (>3 cm) via classic ETLA, good short-term and long-term facial nerve function (HB I-II) was gained in 27.8 % (32/115) and 42.6 % (49/115) cases, respectively, meanwhile in VS operated via blind sac technique, good short-term (p = 0.048) and long-term (p = 0.044) facial nerve function was reached in 44.0 % (22/50) and 60.0 % (30/50) cases, respectively. Postoperative facial nerve function was proved to be better in modified ETLA group. CSF leakage occurred in 16 (4.2 %) patients via classic ETLA. In 115 cases of large VS (>3 cm), postoperative CSF leakage occurred in 10 (8.7 %) patients. Whereas in 50 cases via blind sac technique, none developed CSF leakage (p = 0.03). The incidence of CSF leakage was lower in modified ETLA group. Our refinements to classic ETLA by changing the temporal bone resection range provide a wide surgical field, well prevention of CSF leakage and preservation of facial nerve function in large VS.

Effects of combined alendronate and alfacalcidol on prevention of fractures in osteoporosis patients: a network meta-analysis.

BACKGROUND: Published literatures report controversial results about the effect of combined treatment with alendronate and alfacalcidol for the prevention of fractures in osteoporosis patients. METHODS: Seven common databases were searched for related randomized controlled trials published up to April, 2015. Bayesian random effects network meta-analysis was used to assess the pairwise odds ratios (OR), 95% credible intervals (CI). RESULTS: Thirteen randomized controlled trials were identified (3710 patients). The network meta-analysis results indicated that combining treatment with alendronate and alfacalcidol was significantly better to prevent bone fractures in osteoporosis patients than alendronate (OR=0.53, 95% CI: 0.19-0.95) and alfacalcidol (OR=0.25, 95% CI: 0.08-0.49). In addition, there was no significant difference for adverse events among the three therapeutic regimen. CONCLUSIONS: Combined treatment with alendronate and alfacalcidol was more active than the monotherapies in preventing bone fractures in osteoporosis patients. Large-scale randomized, controlled trials are recommended to confirm the result.

The effect of obstructive sleep apnea syndrome on growth and development in nonobese children: a parallel study of twins.

OBJECTIVE: To explore the effects of obstructive sleep apnea syndrome (OSAS) on children's growth by the study of identical twins. STUDY DESIGN: Seventeen cases of nonobese children with OSAS were included in this study. The control group was their identical twin sibling, who had no signs of OSAS. Data including height, weight, and serum insulin-like growth factor 1 levels were analyzed before tonsillectomy and adenoidectomy (T&A) and at 3, 6, and 12 months after surgery. RESULTS: The mean apnea hyponea index was 3.9 times/hour in patients with OSAS and became normal after surgery. Minimum oxygen saturation gradually increased after T&A. The height and weight of the OSAS group before T&A was lower than the control group. During the follow-up period, height and weight increased but were lower than the control group. Serum insulin-like growth factor 1 levels in the OSAS group before T&A were lower than the control group. The level was significantly increased 3 months after T&A. CONCLUSION: OSAS impairs growth and development. Significant growth recovery occurs after T&A, and early surgical intervention is an important factor for improvement in growth.

P14ARF deficiency and its correlation with overexpression of p53/MDM2 in sporadic vestibular schwannomas.

Recent studies have shed considerable light into schwannomas. To date, only merlin has been identified as a hallmark or pathogenesis of both sporadic and NF2-related schwannomas. Here, we show, by immunoblot and immunohistochemical analyses of 58 sporadic vestibular schwannomas, that upregulation of p53 was observed in 90 % of tumors examined. No p53 mutations were found in 12 % tumors analyzed. Expression of p14ARF was negative in 95 % of tumors, while overexpression of MDM2 was found in all specimens. Aberrant DNA hypermethylation of the p14ARF promoter was observed in three of seven tumors examined (43 %), associated with remarkably decreased mRNA levels. The very high degree of concordance in the aberrations of the p14ARF/MDM2/p53 pathway in this tumor may be considered to be a new player in the pathogenesis of sporadic vestibular schwannomas. Moreover, expression of p21 (waf1) was negative in all tumors, suggesting that the aberration of this pathway is associated with greater attenuation of p21-mediated signals that are critical for growth inhibition. These data are in agreement with the model in RT-4 rat schwannoma cells: i.e., overexpression of ARF was associated with accumulation of p21 expression both at protein and mRNA levels. ShRNA knock-down of p53 expression attenuated p21-mediated increase in cellular arrest in the G1-phase, suggesting that p14ARF regulates p21 protein levels through a p53-dependent pathway. Thus, this study reveals a high degree of concordance in the aberrations of the p14ARF/MDM2/p53 pathway with the development of sporadic vestibular schwannomas.

[Clinical effect of stem cell transplantation via hepatic artery in the treatment of type II hyperammonemia: a report on 6 cases].

This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 µmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.

[Transplantation of human neural precursor cells in the treatment of children with pervasive developmental disorder].

OBJECTIVE: To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children. METHODS: Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later. RESULTS: No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05). CONCLUSIONS: These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.

Brain-derived neurotrophic factor stimulates proliferation and differentiation of neural stem cells, possibly by triggering the Wnt/ß-catenin signaling pathway.

Brain-derived neurotrophic factor (BDNF) has critical functions in promoting survival, expansion, and differentiation of neural stem cells (NSCs), but its downstream regulation mechanism is still not fully understood. The role of BDNF in proliferation and differentiation of NSCs through Wnt/ß-catenin signaling was studied via cell culture of cortical NSCs, Western blotting, immunocytochemistry, and TOPgal (Wnt reporter) analysis in mice. First, BDNF stimulated NSC proliferation dose dependently in cultured neurospheres that exhibited BrdU incorporation and neuronal and glial differentiation abilities. Second, BDNF effectively enhanced cell commitment to neuronal and oligodendrocytic fates, as indicated by increased differentiation marker Tuj-1 (neuronal marker), CNPase (oligodendrocyte marker), and neuronal process extension. Third, BDNF upregulated expression of Wnt/ß-catenin signaling (Wnt1 and free ß-catenin) molecules. Moreover, these promoting effects were significantly inhibited by application of IWR1, a Wnt signaling-specific blocker in culture. The TOPgal mouse experiment further confirmed BDNF-triggered Wnt signaling activation by ß-gal labeling. Finally, an MEK inhibition experiment showed a mediating role of the microtubule-associated protein kinase pathway in BDNF-triggered Wnt/ß-catenin signaling cascades. This study overall has revealed that BDNF might contribute to proliferation and neuronal and oligodendrocytic differentiation of NSCs in vitro, most possibly by triggering the Wnt/ß-catenin signaling pathway. Nevertheless, determining the exact cross-talk points at which BDNF might stimulate Wnt/ß-catenin signaling pathway in NSC activity requires further investigation.

[Facial nerve function and hearing preservation experience in middle fossa approach removal of small acoustic tumor surgery].

OBJECTIVE: The aim of this study was to investigate the hearing and facial nerve preservation in the middle fossa approach surgery for the removal of small acoustic tumor (vestibular schwannomas, VS). METHODS: A prospective database was established, and data were retrospectively reviewed. Between January 2004 and February 2013, 13 patients with acoustic tumor underwent surgery via middle fossa approach for hearing preservation. The patients consisted of six men and seven women with a mean age of 48 years. Tumor size ranged from 0.8 cm to 1.5 cm. Hearing loss was categorized as American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) class A, class B, class C and class D. Facial nerve function was evaluated according to House-Brackmann (HB) Grade I-VI. RESULTS: Gross-total resection was accomplished in 12 of 13 patients. Preoperative hearing as class A in ten, class B in two, and class C in one patient respectively. Postoperatively, hearing was graded as class A in eight patients, class B in 3, and class C in 2 patients. Facial nerve function was House-Brackmann (HB) grade I in twelve patients, grade II in one patient preoperatively. Postoperatively, facial nerve function was HB Grade I in twelve patients and Grade III in one patient. The overall hearing preservation rate was at least 80% (8/10) and HB Grade I facial nerve outcome of 100% (12/12) . All cases were followed up for 0.5 to 5 years, no complications were observed. CONCLUSIONS: The middle fossa approach for the resection of small VS with hearing preservation is a viable and relatively option. It should be considered among the various options available for the management of small and growing VS.

[Treatment of cerebral palsy with transplantation of human neural progenitor cells].

OBJECTIVE: To study the clinical efficacy of transplantation of human neural progenitor cells (hNPCs) in the treatment of severe cerebral palsy (CP) in children. METHODS: Forty-five children with CP were voluntarily accepted transplantation of hNPCs. The cells obtained from the forebrain of 10 to 12-week-fetus were cultured and amplified into hNPCs. Then the hNPCs were injected into the cerebral ventricle of the patients with the supersonic guidance. RESULTS: Dyssomnia, irritability and muscular tension were improved in one patient 3 days after transplantation. The clinical improvements were observed in the majority of the patients 1 month after transplantation. The therapeutic effects slowed down 3 to 6 months after transplantation. One year after transplantation the gross and fine motor skills and the congnition ability in the transplantation group were considerably surpassed to those in the control group. No delayed severe complications were observed after transplantation. No tumorigenesis was noted 5 years after transplantation. CONCLUSIONS: The transplantation of hNPCs as a novel therapy is effective and safe for severe CP. Many investigations are needed to evaluate the effect of the therapy.

[Treatment of newborns with severe injured brain with transplantation of human neural precursor cells].

OBJECTIVE: To analyze the therapeutic effect of human neural precursor cells transplantation in treatment of neonates with severe brain injury. METHOD: The transplantation was performed on 6 newborns, one of them was diagnosed as extremely severe carbon monoxide poisoning at 5(th) day after birth; one of them was diagnosed as severe hypoglycemia; the others had asphyxia at birth with Apgar scores from 1 to 3 and were diagnosed as severe neonatal asphyxia, severe hypoxic ischemic encephalopathy according to images, electroencephalogram, biochemical examination and clinical manifestation. With the approval of hospital ethics committee and informed consent of the family members, the newborns received human neural precursor cells transplantation at the 4(th) to 20(th) day after birth. With the agreement of a pregnant woman, forebrain cells were obtained from the forebrain of her 12-week old fetus after spontaneous abortion. The cells from the fetal brain were amplified into human neural precursor cells in vitro and were injected into the cerebral ventricle of the patients. RESULT: On the 2(nd) day after transplantation, sucking and swallowing reflexes gradually appeared in all the patients, muscular tension was also improved, and convulsion stopped. NBNA scoring in 3 of the patients reached normal level on the 28(th) day after birth. The 6 patients were followed up for 12 months. Four patients were normal in psychomotor development and scores of each scale reached normal level. Two patients have cerebral palsy. CONCLUSION: hNPCs transplantation is safe and effective in treatment of severe neonatal brain injury. More clinical trials and further observation are needed.

[Feasibility analysis and surgical highlight of cochlear implantation in infants under 12 months of age].

OBJECTIVE: To explore feasibility and surgical highlight of cochlear implantation in infants under 12 months of age. METHODS: A retrospective review was performed in 14 infants under 12 months of age and 63 cases from 13 to 24 months of age with bilateral profound sensorineural hearing loss, who underwent unilateral cochlear implantation surgery. The operative parameters, including operation duration, amount of intraoperative bleeding, length of hospital stay, surgical complications and auditory outcomes, including warble tone average aided in free field, category of auditory performance (CAP), language behavior development quotient, babbling onset or spurt were recorded. RESULTS: There was no significant difference between infants younger than 12 months and older in operation duration, amount of intraoperative bleeding, except for the length of hospital stay. Otherwise, less complication occurred in younger group (7.1% and 11.1%, respectively, χ(2) = 0.19, P > 0.05). The surgical highlights and experience, strictly restricted operation duration, intimate cooperation among the treatment team members and reduction of intraoperative bleeding are key points to ensure safety and success of the operation. The warble tone average aided in free field and language behavior developmental quotient of younger infants were both improved during follow-up and showed no significant difference compared with older group (t = 4.6 and 3.8, P > 0.05). 80% of infants who finished 24 months follow-up had a CAP score of 6 or 7. The babbling onset in younger group occurred at (14.1 ± 0.9) months of life, which was better than that in older group [(22.6 ± 3.0) months of life]. CONCLUSIONS: It is feasible to put cochlear implantation in infants under 12 months of age. And the earlier cochlear implantation could shorten auditory deprivation for children with bilateral congenital profound sensorineural hearing loss. Considering the high requirement of surgical highlights and experience, the suggest was that only experienced otologists challenge this domain cautiously.