Objective To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. Methods The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. Results NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. ConclusionGene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Objective To summarize application effect and clinical experience of multimodal intraoperative neurophysiological monitoring (IONM) technology in the surgery of neurofibromatosis type 1 (NF1) related peripheral nerve tumors. Methods A retrospective study was conducted on NF1 patients, who admitted between January 2019 and December 2023 and treated with peripheral nerve tumor resection surgery assisted by multimodal IONM technology. There were 49 males and 45 females. The age ranged from 5 to 78 years, with an average of 33.7 years. Tumor morphological classification included 71 cases of nodular type, 13 cases of diffuse type, and 10 cases of mixed type. Target tumors were distributed in craniofacial region (47 cases), neck (11 cases), trunk (12 cases), and limbs (24 cases). Preoperatively, 44 cases had no obvious neurological symptoms, while the remaining patients had neurological symptoms, including 15 cases of visual impairment, 5 cases of hearing impairment, 16 cases of somatic movement disorders, and 31 cases of somatic sensory disorders, of which 7 cases had more than one symptom. IONM plans were selected based on the relevant nerves and adjacent important structures of the target tumor, including visual evoked potential (17 cases), somatosensory evoked potential (44 cases), motor evoked potential (88 cases), and electromyogram (94 cases).Results All surgeries were successfully completed. Ninety-three patients underwent total/near total resection and 1 patient underwent palliative resection. Pathological examination showed 80 cases of neurofibroma and 14 cases of malignant peripheral nerve sheath tumors. Complications included 2 cases of hematoma and 3 cases of incision infection. All patients were followed up 3-61 months (median, 15 months). During follow-up, no significant changes in neurological symptoms or tumor recurrence were found. Among the patients with preoperative visual impairment, there were 14 cases with no improvement in symptoms and 1 with improvement after surgery. Among the patients with somatic movement disorders, there were 11 cases with no improvement in symptoms, 3 cases with improvement, 2 cases with aggravation, 4 newly onset cases, and 1 case with significant impact on daily life after surgery. Among the patients with somatic sensory disorders, there were 17 cases with no improvement in symptoms, 14 cases with improvement, and 13 newly onset cases. The patients with hearing impairment showed improvement after surgery. Conclusion The clinical manifestations of NF1 related peripheral nerve tumors are complex. Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.
Objective To explore the feasibility of combining high level Le Fort Ⅰ osteotomy with bone grafting in the same operation for correction of secondary midface deformities in cleft patients. Methods From January 2002 to January 2005, 10 patients suffering from secondary midface deformities were treated. There were 4 males and 6 females, aged from 16 to 32 years. The unilateral cleft was involved in 8 patients and the bilateral cleft in2 patients. All patients received combining high level Le Fort Ⅰ osteotomy with bone grafting in the same operation. The horizontal corticotomy of high level Le Fort Ⅰosteotomy on anterior wall of maxillary bone is higher than that of traditionalLe Fort Ⅰ osteotomy, it is only 5 mm close to infraorbital foramen. Results All 10 patients were satisfied with their appearances after operation. Dental articulation was improved greatly in 9 patients. With an X-ray re-examination, maxillary was returned to normal position in all patients. After a follow up from 6months to 2 years, dental arch had good appearance. The X-ray films showed no obvious bone absorption. The density of grafting bone was approximation to the normal bone.Conclusion High level Le Fort Ⅰ osteotomy can make notonly maxillary advance, but also regions of lateral and floor of nose and partial infraorbital region advance. Combining with bone grafting in the same operation can decrease the frequency of operation, save the treatment expense and obtain an ideal effect. So it is an effective method for correction of the secondary midface deformities in cleft patients.
Objective Col I A1 antisense oligodeoxyneucleotide (ASODN) has inhibitory effect on collagen synthesis in cultured human hypertrophic scar fibroblasts. To investigate the effects of intralesional injection of Col I A1 ASODN on collagen synthesis in human hypertrophic scar transplanted nude mouse model. Methods The animal model of humanhypertrophic scar transplantation was established in the 60 BALB/c-nunu nude mice (specific pathogen free grade, weighing about 20 g, and aged 6-8 weeks) by transplanting hypertrophic scar without epidermis donated by the patients into the interscapular subcutaneous region on the back, with 1 piece each mouse. Fifty-eight succeed models mice were randomly divided into 3 groups in accordance with the contents of injection. In group A (n=20): 5 μL Col I A1 ASODN (3 mmol/L), 3 μL l iposome, and 92 μL Opti-MEM I; in group B (n=20): 3 μL l iposome and 97 μL Opti-MEM I; in group C (n=18): only 100 μL Opti-MEM I. The injection was every day in the first 2 weeks and once every other day thereafter. The scar specimens were harvested at 2, 4, and 6 weeks after injection, respectively and the hardness of the scar tissue was measured. The collagens type I and III in the scar were observed under polarized l ight microscope after sirius red staining. The ultrastructures of the scar tissues were also observed under transmission electronic microscope (TEM). Additionally, the Col I A1 mRNAs expression was determined by RT-PCR and the concentrations of Col I A1 protein were measured with ELISA method. Results Seventeen mice died after intralesional injection. Totally 40 specimens out of 41 mice were suitable for nucleic acid and protein study, including 14 in group A, 13 in group B, and 14 in group C. The hardness of scars showed no significant difference (P gt; 0.05) among 3 groups at 2 weeks after injection, whereas the hardness of scars in group A was significantly lower than those in groups B and C at 4 and 6 weeks (P lt; 0.05), and there was no significant difference between groups B and C (P gt; 0.05). The collagen staining showed the increase of collagentype III in all groups, especially in group A with a regular arrangement of collagen type I fibers. TEM observation indicated that there was degeneration of fibroblasts and better organization of collagen fibers in group A, and the structures of collagen fibers in all groups became orderly with time. The relative expressions of Col I A1 mRNA and the concentrations of Col I A1 protein at 2 and 4 weeks after injection were significant difference among 3 groups (P lt; 0.05), and they were significantly lower in group A than in groups B and C (P lt; 0.05) at 6 weeks after injection, but no significant difference was found between groups B and C (P gt; 0.05). Conclusion Intralesional injection of Col I A1 ASODN in the nude mice model with human hypertrophic scars can inhibit the expression of Col I A1 mRNA and collagen type I, which enhances the mature and softening of the scar tissue. In this process, l iposome shows some assistant effect.
Objective To investigate short-term effectiveness of arthroscopic repair via modified subacromial viewing portal (hereinafter referred to as modified viewing portal) in treatment of LafosseⅠsubscapularis tendon tears. Methods A clinical data of 52 patients with LafosseⅠsubscapularis tendon tears, who underwent the arthroscopic repair via modified viewing portal between October 2020 and November 2022 and met the selective criteria, was retrospectively analyzed. There were 15 males and 37 females with an average age of 63.4 years (range, 41-76 years). Twelve patients had trauma history and the other 40 patients had no obvious inducement. The main clinical symptom was shoulder pain and the hug resistance tests were positive in all patients. The interval between symptom onset and admission ranged from 3 to 26 months (mean, 7.2 months). The shoulder pain and function were evaluated by visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, and University of California Los Angeles (UCLA) score before operation and at 12 months after operation. The shoulder range of motion (ROM) of forward flexion, abduction, and external rotation and the internal rotation strength were measured before operation and at 3 and 12 months after operation. MRI was performed at 3-6 months after operation to assess the tendon healing and the structural integrity and tension of reattached tendon. Patient’s satisfactions were calculated at last follow-up. Results All incisions healed by first intention, no complication such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.5 months). The VAS, UCLA, and ASES scores at 12 months after operation significantly improved when compared with those before operation (P<0.05). The ROMs of abduction and forward flexion and the internal rotation strength at 3 and 12 months significantly improved when compared with those before operation (P<0.05); and the ROMs at 12 months significantly improved compared to that at 3 months (P<0.05). However, there was no significant difference (P>0.05) in the ROM of external rotation at 3 months compared to that before operation; but the ROM at 12 months significantly improved compared to that before operation and at 3 months after operation (P<0.05). Thirty-one patients underwent MRI at 3-6 months, of which 28 patients possessed intact structural integrity, good tendon tension and tendon healing; 3 patients underwent tendon re-tear. At last follow-up, 41 patients (78.8%) were very satisfied with the effectiveness, 7 were satisfied (13.5%), and 4 were dissatisfied (7.7%). Conclusion Arthroscopic repair via modified viewing portal for Lafosse Ⅰsubscapularis tendon tears, which can achieve the satisfactory visualization and working space, can obtain good short-term effectiveness with low overall re-tear risk.
ObjectiveTo observe the predictive value of Volume OXygeneration (VOX) index for early non-invasive positive pressure ventilation (NIPPV) treatment in patients with type I Respiratory failure. MethodsRetrospective analysis was made on the patients with type I Respiratory failure admitted to the intensive care medicine from September 2019 to September 2022, who received early NIPPV treatment. After screening according to the discharge standard, they were grouped according to the NIPPV 2-hour VOX index. The observation group was VOX Youden index >20.95 (n=69), and the control group was VOX index ≤20.95 (n=64). Collect patient baseline data and NIPPV 2-hour, 12-hour, and 24-hour arterial blood gas values, and calculate NIPPV outcomes, intubation status, NIPPV usage time, hospital stay, and mortality rate. ResultsThere was a statistically significant difference in respiratory rate (RR) between the baseline data onto the two groups of patients, but others not. After early NIPPV treatment, the 2-hour oxygenation index (P/F) [(182.5 ± 66.14) vs. (144.1 ± 63.6) mm Hg, P<0.05] of the observation group showed a more significant increase. The failure rate of NIPPV intubation within 12 hours was lower (4.35% vs. 32.81%, P<0.05), the success rate of NIPPV withdrawal from 24 hours was higher (40.58% vs. 0%, P<0.05), and the failure rate of NIPPV intubation was lower (4.35% vs. 46.88%, P<0.05). The comparison of treatment outcomes showed that the intubation rates in the observation group (4.35% vs. 67.19%, P<0.05) was lower. The threshold of NIPPV 2-hour VOX index 20.95 was used as a predictor of Tracheal intubation, with sensitivity of 74.7% and specificity of 93.5%. ConclusionIn the early NIPPV treatment of patients with type I Respiratory failure, the NIPPV 2-hour VOX index>20.91 is taken as the evaluation index, which can better to predict the improvement in hypoxia and the risk of NIPPV failure Tracheal intubation, and has clinical significance.
ObjectiveTo summarize the treatment strategies and clinical experiences of 5 cases of giant plexiform neurofibromas (PNF) involving the head, face, and neck. MethodsBetween April 2021 and May 2023, 5 patients with giant PNFs involving the head, face, and neck were treated, including 1 male and 4 females, aged 6-54 years (mean, 22.4 years). All tumors showed progressive enlargement, involving multiple regions such as the maxillofacial area, ear, and neck, significantly impacting facial appearance. Among them, 3 cases involved tumor infiltration into deep tissues, affecting development, while 4 cases were accompanied by hearing loss. Imaging studies revealed that all 5 tumors predominantly exhibited an invasive growth pattern, in which 2 and 1 also presenting superficial and displacing pattern, respectively. The surgical procedure followed a step-by-step precision treatment strategy based on aesthetic units, rather than simply aiming for maximal tumor resection in a single operation. Routine preoperative embolization of the tumor-feeding vessels was performed to reduce bleeding risk, followed by tumor resection combined with reconstructive surgery. Results All 5 patients underwent 1-3 preoperative embolization procedures, with no intraoperative hemorrhagic complications reported. Four patients required intraoperative blood transfusion. A total of 10 surgical procedures were performed across the 5 patients. One patient experienced early postoperative flap margin necrosis due to ligation for hemostasis; however, the incisions in the remaining patients healed without complications. All patients were followed up for a period ranging from 6 to 36 months, with a mean follow-up duration of 21.6 months. No significant tumor recurrence was observed during the follow-up period. Conclusion For patients with giant PNF involving the head, face, and neck, precision treatment strategy can effectively control surgical risks and improve the standard of aesthetic reconstruction. This approach enhances overall treatment outcomes by minimizing complications and optimizing functional and cosmetic results.
Objective
To assess clinical value of thyroidectomy by meticulous capsular dissection technique through neck incision approach in treatment of 75 patients with type Ⅰ substernal goiter.
Methods
The clinical data of 75 patients with type Ⅰ substernal goiter in the Department of General Surgery of the Central Hospital of Xiaogan from April 2013 to April 2017 were retrospectively analyzed. These patients received the surgical resection by the meticulous capsular dissection technique with an ultrasonic scalpel and a bipolar coagulation forcep through neck incision approach.
Results
There were 12 Hashimoto thyroiditis, 10 thyroid adenoma, 41 nodular goiter, and 12 thyroid carcinoma in the 75 patients with type Ⅰ substernal goiter. Five cases underwent the unilateral total thyroidectomy. Fifty-eight cases underwent the bilateral total thyroidectomy. The bilateral total thyroidectomy plus central lymph node dissection were performed in the 9 patients with thyroid carcinoma, the bilateral total thyroidectomy plus central lymph node dissection plus affected ipsilateral neck lymph node dissection were performed in the 3 patients with thyroid carcinoma. The average operative time was 100 min, the average intraoperative blood loss was 50 mL, the average postoperative hospital stay was 5 d. The rate of parathyroid injury was 2.7% (2/75), the rate of hypocalcemia caused by parathyroid injury was 2.7% (2/75). There were 3 cases (4.0%) of unilateral recurrent laryngeal nerve injury, 1 case (1.3%) of the outer branch of the upper laryngeal nerve injury. There were 2 cases of tracheal partial softening in the 75 patients. None of postoperative bleeding and seroma happened. No death and the tumor recurrence and metastasis of patients happened during follow-up period.
Conclusions
Preliminary results in this study show that operation of meticulous capsular dissection technique with an ultrasonic scalpel and a bipolar coagulation forcep through neck incision approach in treatment of type Ⅰ substernal goiter is safe and feasible, it could effectively reduce postoperative complications of thyroidectomy, and protect parathyroid and it’s function, recurrent laryngeal nerve, and superior laryngeal nerve.
ObjectiveTo analyze the phasic changes of bone mass, bone turnover markers, and estrogen levels at different time points after glucocorticoid (GC) intervention in rat and their correlation.
MethodsThirty-four female 3-month-old Sprague Dawley rats were randomly divided into the following 3 groups:baseline group (n=6), dexamethasone (DXM) group (n=14), and control group (n=14). Rats were injected with DXM at the dose of 0.75 mg/kg, twice a week for 12 weeks in DXM group, with salt solution lavage in control group, and no treatment was given in baseline group. The body mass, adrenal weight, and uterus weight were measured. Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) of lumbar vertebral and femurs were detected by dual energy X-ray absorptiometry. Meanwhile, the serum levels of N-terminal propeptide of type I procollagen (PINP), C-terminal cross-linking telopeptide of type I collagen (β-CTX), and estrogen levels were determined by ELISA before experiment in baseline group and at 4, 8, and 12 weeks after experiment in control and DXM groups. At last, the correlation was analyzed among body weight, BMD, PINP, β-CTX, estrogen levels, and GC intervention duration of DXM group.
ResultsThe body mass, adrenal weight, and uterus weight in DXM group were significantly lower than those in baseline group and control group at all the time points (P<0.05). The levels of PINP and β-CTX elevated slowly in DXM group, significant difference was found at 12 weeks (P<0.05), but no significant difference at the 4 and 8 weeks (P>0.05) when compared with those in baseline group and control group. The estrogen level in DXM group was significantly lower than that in baseline group and control group at all the time points (P<0.05). BMD, BMC, and BA of lumbar vertebral and femurs in DXM group were significantly lower than those in control group at all the time points after GC intervention (P<0.05). Loss of bone mass of L2 and femoral trochanteric region in DXM group was the lowest of all ranges of interest (ROIs). BMC and BA of lumbar vertebrae and BA of femoral shaft in DXM group at 4 weeks were significantly lower than those in baseline group (P<0.05). But there was no significant difference in BMD, BMC, and BA of other lumbar vertebrae and femurs' ROIs between DXM group and baseline group at all the time points (P>0.05). After GC intervention, BMD of lumbar vertebrae and femurs had negative correlation with PINP and β-CTX (P<0.05) and positive correlation with estrogen level (P<0.05).
ConclusionThe bone mass decreases rapidly at the early stage after GC intervention and then maintains a low level with time, the levels of bone turnover markers show a progressive increase, and the estrogen levels show a decrease trend. In addition, body weight, the levels of bone turnover markers and estrogen are associated with the change of bone mass.
【摘要】 目的 探討微弧氧化（microarc oxidation，MAO）結合應用于純鈦種植體表面處理的可行性。 方法 根據對純鈦鈦片處理的不同將實驗分為對照組（A組，不作處理）、MAO組（B組，純鈦片上進行MAO處理）及MAO加Ⅰ型膠原組（C組，純鈦片上MAO處理后吸附Ⅰ型膠原）。將成骨細胞培養于各組鈦片上，通過掃描電鏡、MTT法檢測不同時間點各組鈦片表面的細胞生長及增殖情況，并檢測堿性磷酸酶（alkaline phosphatase，ALP）活性。 結果 掃描電鏡顯示成骨細胞在C組鈦片上細胞黏附情況優于A、B組；MTT法及ALP活性檢測示培養3、6 d，成骨細胞在C組鈦片上的增殖及ALP活性與A、B組比較差異均有統計學意義（Plt;0.05）。 結論 MAO結合Ⅰ型膠原處理的鈦片可更有效提高成骨細胞表面附著、增殖，且具有較高的ALP活性。【Abstract】 Objective To study the feasibility of applying microarc oxidation (MAO) with collagen Ⅰ in surface modification of pure titanium. Methods According to different processing methods, the pure titanium was divided into three groups: the control group (without surface modification, group A), MAO group (with microarc oxidation applied in pure titanium surface modification, group B), MAO+Ⅰ group (with microarc oxidation and collagen Ⅰ applied in pure titanium treatment, group C). Osteoblasts were cultured on the surface of titanium in each group, and the cell proliferation in each group was detected at different time points by scanning electron microscopy and MTT method. Moreover, the activity of alkaline phosphatase (ALP) was also detected. Results Scanning electron microscopy showed that adhesion of osteoblasts for group C was better than group A and group B. MTT method and ALP activity detection indicated that there was a significant difference between group C and group A, B in cell proliferation and ALP activity on the third and sixth day of cultivation (Plt;0.05). Conclusion MAO with collagen Ⅰ applied in surface modification of pure titanium may increase osteoblast attachment, and promote its proliferation and ALP activity.
