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Background: Idiopathic pulmonary fibrosis (IPF) is a deadly chronic interstitial lung disease with no effective treatment options other than lung transplantation. Allogeneic adipose-derived mesenchymal stem cells (ADSCs) are considered ideal as seed cells for stem cell-based therapy, and some studies illustrated the therapeutic effect of ADSCs on IPF, but the underlying mechanisms remain unclear.Methods: A single intratracheal dose of bleomycin (BLM) was administered to induce pulmonary injury/fibrosis in C57BL/6 mice, after GFP-labeled mouse ADSCs (mADSCs) were implanted intratracheally to explore their potential therapeutic effects in the inflamed/fibrotic lung microenvironment. The mADSCs were then retrieved through fluorescence-activated cell sorting and subjected to single-cell RNA sequencing (scRNA-seq).Results: Our data indicate that the single-dose intratracheal administration of mADSCs could significantly increase the life span of IPF mice by remodeling the extracellular matrix and promoting the polarization of macrophages to an anti-inflammatory phenotype. Conclusions: A single intratracheal injection of mADSCs alleviated BLM-induced pulmonary fibrosis by readjustment of the mouse lung microenvironment, which was reflected in changes of the lung C1QB+, APOE+ and TREM2+ macrophages in the mouse model.

Objective To investigate the effects of autologous and allogeneic adipose derived mesenchymal stem cells (ADMSCs) transplantation on rat model of acute myocardial infarction (AMI) and possible mechanisms. Methods The AMI models were established with 45 male Lewis rats by ligation of left anterior descending coronary artery, and then randomly divided into 3 groups (15 each) including AMI group, allogeneic ADMSC transplantation group (Allo-ADMSC group) and autologous ADMSC transplantation group (Auto-ADMSC group). After successfully modeling, CM-Dil-labeled third-generation ADMSCs (2×106) were implanted into the myocardium of rats within 1 hour, and rats in AMI group were injected with equal amount of PBS. The cardiac function, immunofluorescence and Masson were identified 4 weeks after transplantation. Results Four weeks after transplantation, compared with AMI group, the left ventricular ejection fraction in Allo-ADMSC group and Auto-ADMSC group increased significantly, the left ventricular end-systolic and end-diastolic diameter decreased, the collagen deposition fraction decreased significantly (P

OBJECT 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.

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, 3×10(5) 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.

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.

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).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.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.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.

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.

To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children.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.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 (P0.05).These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.

To study the clinical efficacy of transplantation of human neural progenitor cells (hNPCs) in the treatment of severe cerebral palsy (CP) in children.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.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.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.

To analyze the therapeutic effect of human neural precursor cells transplantation in treatment of neonates with severe brain injury.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.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.hNPCs transplantation is safe and effective in treatment of severe neonatal brain injury. More clinical trials and further observation are needed.

To explore feasibility and surgical highlight of cochlear implantation in infants under 12 months of age.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.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, P0.05). 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, P0.05). 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].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.

To investigate the impact of S518 phosphorylation in Merlin on the interaction with CD44 in vestibular schwannoma and the tumor growth.Thirty-five samples of vestibular schwannoma were identified by pathology. Immunohistopathology and western blot were employed to analyze the expression and localization of S518 phosphorylated Merlin in the tumor tissues. Nerve tissues that were collected during other surgical operation were used as control. The expression level of S518 phosphorylated Merlin was compared with clinical stages, tumor size, clinical course and cystic degeneration. Immunoprecipitation was used to evaluate the impact of S518 phosphorylation in Merlin on the interaction with CD44.In vestibular schwannoma, Merlin was phosphorylated at S518 and demonstrated perinuclear localization. The S518 phosphorylation level was much lower in the normal control nerve tissues than that in vestibular schwannoma tissues. There was no correlation between the phosphorylation level on Merlin and clinical stages, tumor size, clinical course and cystic degeneration. The S518 phosphorylated Merlin bound CD44 was higher than wild-type Merlin bound CD44 in vestibular schwannoma tissues.The affinity of Merlin to CD44 was increased after phosphorylation at S518. Different cellular biological results might be triggered through binding to wild type Merlin and S518 phosphorylated Merlin.

To analysis the effectiveness of preoperative digital subtraction angiography (DSA) on glomus jugularis tumors.A retrospective study of 14 cases of glomus jugularis tumors which received preoperative DSA was carried out. Among them, 10 cases were accepted balloon occlusion test and selective embolization of supplied vessels.Hypervascular changes was found in all 14 cases and compression of internal carotid artery was found in 5 cases. Ascending pharyngeal artery was the main supplied vessel. Balloon occlusion test was applied in 10 cases, 2 were intolerable and 8 were passed occlusion test. Ten cases were accepted embolizations and tumor blood supply was conspicuous decreased. Neurovascular complications did not occurred after DSA but postoperatively in 2 cases. Intraoperative bleeding was less in embolization patients than that of without embolization.Preoperative DSA association with balloon occlusion test and embolizations might be a safe option on surgery of glomus jugularis tumors.

To discuss the early diagnosis and the treatment of chordoma in the jugular foramen area.Three cases of chordoma in the jugular foramen area were diagnosis and reviewed retrospectively. The initial symptom was facial paralysis. Surgical removal was performed through the infratemporal fossa approach in 1 case, through petro-occipital approach in 2 cases. For repairing facial nerve defect, great auricular nerve was used in 1 case and facial-hypoglossal anastomosis was used in another 2 cases.The tumor were totally removed in all 3 cases. The patients were follow-up for 6 months to 1 year and no recurrence was found. The function of facial nerve was II grade (House-Brackmann) in one patient and IV grade in another 2 patients. No complications occurred in 3 cases.Although chordoma originating from the jugular foramen area were extremely rare, it was possible to make early diagnosis through finding clinical feature and imaging methods. The final diagnosis depended on pathology. Generally, the different surgical approaches were used according to the size and position of the tumor. The classic infratemporal fossa approach for tumor removal and facial nerve reconstruction should be considered in the patients with chordoma around jugular foramen.

To study the effect of hyperbaric oxygenation (HBO) on the differentiation of the implanted human neural stem cells (hNSCs) into neurons in neonatal rats following hypoxic-ischemic brain damage (HIBD).HIBD model was prepared by ligation of the left common carotid artery, followed by 8% hypoxia exposure in 7-day-old Sprague-Dawley rat pups. Three days later, the rats received implantation of hNSCs into the left cerebral ventricles. Then the survived rats were randomly divided into two groups: transplantation alone and transplantation+HBO (n=8 each). HBO treatment was administered (1.8 ATA, 1 hr once daily for 10 days) in the transplantation+HBO group 1 hr after hNSCs transplantation. Brains were removed 10 days after transplantation. Frozen coronal sections were prepared for immunofluorescence analysis to detect the neural differentiation of the transplanted cells in the cerebral cortex and hippocampus.Differentiated neurons of implanted cells distributed mainly in the cortex and the hippocampus of the injured side. There was no difference in the number of neurons in the cortex between the two groups, while the number of neurons in the hippocampus significantly increased in the transplantation+HBO group compared with that in the transplantation alone group (231.4+15.1 vs 162.6+5.6; P0.05).HBO treatment may promote the differentiation of implanted hNSCs into neurons in the hippocampus of neonatal rats following HIBD.

To investigate the diagnosis and surgical treatment of lower cranial schwannomas of jugular foramen.Retrospective review of 11 cranial schwannomas of jugular foramen which received surgical removal from November 2001 to June 2005. According to classification, 5 cases were as intracranial type, 3 as jugular foramen type, 1 as neck extension type and the other 2 as combination type. Surgical procedures composed of 3 translabyrinthine, 2 retrosigmoid and 6 subtemporal fossa approach.One-stage total tumor removal was accomplished in all the cases without any severe complications. Residue hearing was preserved in two cases received retrosigmoid approach. Anatomic completion of facial nerve was maintained in all the cases. Lower cranial neuropathy was found in 9 cases before surgery and occurred in all the cases after surgery. During in-hospital period complete compensation of swallowing ability was gained in 7 cases, near total, partial compensation and total decompensation was found in 1, 2 and 1 cases, respectively. Followed-up for 6 months, 10 cases caught normal swallowing function while the other one with partial compensation. Hoarseness was occurred in all the cases immediately after surgery and improved during follow-up. CSF leakage was occurred in 2 cases, no intracranial infection was found in all the cases.Surgical treatment was the optimal management to cranial schwannoma of jugular foramen. Surgical approach selections depends on tumor classification on magnetic resonance imaging features. Nerve protection in surgery and postoperative rehabilitation were the key to better prognosis.

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.

To evaluate the various surgical approaches in removing the jugular foramen region tumors in order to obtain the maximal functional preservation.Between March 1993 and May 2005, 32 patients with jugular foramen region tumors were operated. The mastoid and neck approach, the infratemporal fossa approach with and without rerouting the facial nerve, the combined transcochlear and infratemporal fossa approach were respectively used according to the tumor type, size, auditory, facial and lower cranial nerve functions. The cranial nerve monitoring was used and a postoperative CT or MRI scanning was taken in all cases.In this series of 32 patients, 13 were paragangliomas, 10 schwannomas,2 meningiomas, 2 giant cell tumors, 1 chondrosarcoma, 1 mucochondrosarcoma, 1 adenoid cystic carcinoma, 1 rhabdomyosarcoma and 1 case cholesterol Granuloma. The follow-up period was 3-60 months. Total removals were achieved in 26 cases, near-total removal in 5 cases, and subtotal removal in one case. One patient died after surgery because of intracranial hemorrhage. Another patient died two year after operation because of recurrence. Postoperative cerebrospinal fluid leakage was occurred in 5 cases and meningitis in two cases. They were all treated conservatively. The facial function one week after operation was grade 1-2 in 13 cases, grade 3-4 in 12 cases and grade 5-6 in 7 cases. It changed into grade 1-2 in 23 cases, grade 3-4 in 7 cases and grade 5-6 in 2 cases. The postoperative hearing was improved in 4 cases, stable in 10 cases, deteriorated in 11 cases and totally lost in 7 cases. The lower cranial nerve function was normal in 9 cases, transient palsy in 11 cases, permanent paralysis with compensation in 10 cases and without compensation in 2 cases.The jugular foramen region tumor could be removed with maximal function preservation by using various surgical approaches. The postoperative life quality was acceptable in most cases. Surgical techniques and postoperative complications management were fundamental in achieving a good result.