Objective To investigate the clinical features, treatment methods, and prognostic influence factors of patients with malignant peripheral nerve sheath tumor (MPNST). MethodsA retrospective analysis was conducted on 96 MPNST patients treated between January 1, 2015 and December 31, 2021. There were 46 males and 50 females, aged between 15 and 87 years (mean, 48.2 years). The tumors were located in the trunk in 50 cases, extremities in 39 cases, and head and neck in 7 cases. The maximum tumor diameter was <5 cm in 49 cases, ≥5 cm in 32 cases, with 15 cases missing data. Tumor depth was deep in 77 cases and superficial in 19 cases. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histological grading was G1 in 9 cases, G2 in 12 cases, and G3 in 34 cases, with 41 cases missing data. There were 37 recurrent MPNST cases, 32 cases with neurofibromatosis type 1 (NF1), and 26 cases in stage Ⅳ. Postoperative adjuvant radiotherapy was administered to 25 patients, perioperative chemotherapy to 45 patients, and anlotinib-targeted therapy to 30 patients. R0 resection was achieved in 73 cases. Patients were divided into groups based on the presence or absence of NF1, and baseline data between the two groups were compared. Kaplan-Meier curves were generated to assess disease-free survival (DFS) and overall survival (OS) based on various factors (age, gender, presence of NF1, recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R0 resection, tumor location, tumor size, tumor depth, perioperative chemotherapy, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy), and differences between survival curves were analyzed using the Log-Rank test. Multivariate COX proportional hazards regression was used to identify independent prognostic factors for MPNST. Results Patients with NF1 had a significantly higher proportion of superficial tumors and lower FNCLCC grade compared to those without NF1 (P<0.05); no significant difference was found for other variables (P<0.05). Kaplan-Meier analysis showed that recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R0 resection, perioperative chemotherapy, and anlotinib-targeted therapy were factors influencing 1-year DFS (P<0.05), while stage Ⅳ MPNST, FNCLCC grade, and perioperative chemotherapy were factors affecting 3-year OS (P<0.05). Multivariate COX proportional hazards regression analysis revealed that recurrent MPNST and high-grade FNCLCC (G3) were independent prognostic factors for 1-year DFS (P<0.05), while stage Ⅳ MPNST, superficial tumor depth, age over 60 years, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy were independent prognostic factors for 3-year OS (P<0.05). Conclusion MPNST patients with NF1 tend to have more superficial tumors and lower FNCLCC grades. FNCLCC grade, R0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease caused by mutations in the NF1 gene. The disease is characterized by neurofibromatosis, which simultaneously affects multiple systems such as nerves, skin, and bone, and has complex clinical manifestations. Since the National Institutes of Health (NIH) established diagnostic criteria in 1988, the diagnosis and treatment of NF1 have progressed significantly. However, due to the complexity of the disease and the lack of effective treatments, the diagnosis and treatment of NF1 still face many challenges. Strengthening multidisciplinary collaboration, improving and popularizing disease diagnosis and treatment strategies, and developing more effective drugs and treatment methods are the keys to further improve the treatment level of NF1 diseases.
摘要:目的:探讨Ⅰ型肾小管酸中毒( RTA) 患者的临床特征及误诊分析。方法: 回顾性分析我院51例Ⅰ型RTA患者的临床资料, 包括临床表现、实验室检查、诊断及误诊情况、并发症及治疗转归等。结果:Ⅰ型RTA 临床表现多样,复杂,无特异性,外院误( 漏)诊率高达64.7%,易并发或伴发多种疾病。 结论: 临床上应提高对Ⅰ型RTA的认识, 做出早期诊断和治疗。Abstract: Objective: To investigate the clinical features and misdiagnosis of distal renal tubular acidosis(RTA), or type 1 RTA. Methods: Data of 51 cases with type 1 RTA were analyzed retrospectively,including clinical features, laboratory examinations,diagnostic errors, complications and therapeutics. Results: The clinical features of type 1 RTA were complicated and were easy to be misdiagnoed.The misdiagnosis rate were as high as 64.7% in other hospitals.Conclusion: Type 1 RTA should be further recognized in clinic in order to make earlier diagnose and treatment.
To investigate the inhibitory effect of Col I A1 antisense ol igodeoxyneucleotide (ASODN) transfection mediated by cationic l iposome on Col I A1 expression in human hypertrophic scar fibroblasts. Methods Scar tissue was obtained from volunteer donor. Human hypertrophic scar fibroblasts were cultured by tissue block method. The cells at passage 4 were seeded in a 6 well cell culture plate at 32.25 × 104 cells/well, and then divided into 4 groups: group A, l iposomeand Col I A1 ASODN; group B, Col I A1 ASODN; group C, l iposome; group D, blank control. At 8 hours, 1, 2, 3 and 4 days after transfection, total RNA of the cells were extracted, the expression level of Col I A1 mRNA was detected by RT-PCR, the Col I A1 protein in ECM was extracted by pepsin-digestion method, its concentration was detected by ELISA method. Results Agarose gel electrophoresis detection of ampl ified products showed clear bands without occurrence of indistinct band, obvious primer dimmer and tailing phenomenon. Relative expression level of Col I A1 mRNA: at 8 hours after transfection, group A was less than groups B, C and D (P lt; 0.05), and groups B and C were less than group D (P lt; 0.05), and no significant difference was evident between group B and group C (Pgt; 0.05); at 1 day after transfection, groups A and B were less than groups C and D (P lt; 0.05), and there was no significant difference between group A and group B, and between group C and group D (P gt; 0.05 ); at 2 days after transfection, there were significant differences among four groups (P lt; 0.05); at 3 and 4 days after transfection, group A was less than groups B, C and D (P lt; 0.05), group B was less than groups C and D (P lt; 0.05), and no significant difference was evident between group C and group D (P gt; 0.05). Concentration of Col I protein: at 8 hours after transfection, group A was less than groups B, C and D (P lt; 0.05), groups B and C were less than group D (P lt; 0.05), and no significant difference was evident between group B and group C (P gt; 0.05); at 1 day after transfection, significant differences were evident among four groups (P lt; 0.05); at 2, 3 and 4 days after tranfection, groups A and B were less than groups C and D (P lt; 0.05), and no significant difference was evident between group A and group B (P gt; 0.05). Conclusion Col I A1 ASODN can inhibit mRNA and protein expression level of Col I A1. Cationic l iposome, as the carrier, can enhance the inhibition by facil itating the entry of ASODN into cells and introducing ASODN into cell nucleus.
Objective To review the emergency management and perioperative strategies for ruptured neurofibromatosis type 1 (NF1)-related giant plexiform neurofibroma (PNF), providing a systematic treatment protocol to improve the therapeutic outcomes and quality of life for patients with giant PNF. Methods The literature on the management of giant PNF rupture and hemorrhage was reviewed, and the diagnosis, treatment, and perioperative management were summarized based on clinical experiences. Results By implementing an integrated diagnostic and treatment strategy that includes early diagnosis, imaging evaluation, emergency ultra-selective arterial embolization combined with surgical excision, acute hemorrhage can be effectively controlled while also reducing the risk of major intraoperative bleeding and minimizing postoperative complications. As a result, this approach significantly improves treatment success rates and patient quality of life. Conclusion For ruptured NF1-related giant PNF, employing emergency ultra-selective arterial embolization combined with surgical excision, under the collaboration of a multidisciplinary team, can effectively improve treatment success rates, rapidly control bleeding, reduce tumor size, and lower mortality. Future research should focus on assessing the long-term quality of life of patients treated for ruptured and hemorrhaging giant PNF and on further optimizing treatment protocols.
The purpose of this study was to investigate the effect of biaxial tensile strain on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. The rBMSCs were isolated from tibia and femur of 4 weeks-old Sprague-Dawley (SD) rats. The rBMSCs were cultured in DMEM-LG complete culture medium and grew to subconfluence in the cell culture device for loading tensile strain. The biaxial tensile strain was applied to the rBMSCs for periods of 2, 4 and 6 hours every day, respectively, lasting 3 days. The amplitude of biaxial tensile strain applied to the rBMSCs were 1%, 2% and 5% respectively, at a frequency of 1 Hz. Unstrained rBMSCs were used as blank control (control group). The rBMSCs cultured with DMEM-LG complete culture medium containing 100 nmol/L β-Estradiol (E2) were used as positive control. The mRNA expression of alkaline phosphatase (ALP), collagen typeⅠ (ColⅠ), Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) was examined with real-time quantitative PCR and the protein expression of ALP, ColⅠ, Runx2 and OCN was detected with Western blot method. The results showed as follws: (1) The mRNA and protein expression of the ALP, ColⅠ, Runx2, OCN were significantly higher in rBMSCs of the E2 group than those in the control group (P＜0.05). (2) The mRNA and protein expression level of the ALP, Runx2 were higher markedly in the 1% tensile strain groups than those in the control group (P＜0.05), but lower than those in the E2 group (P＜0.05). (3) The mRNA and protein expression level of the ALP, ColⅠ, Runx2, OCN were significantly higher in the 2% tensile strain groups than those in the control group (P＜0.05), and the mRNA and protein expression level of ColⅠ and Runx2 in the group applied with 2% amplitude of tensile strain for 4 h/d was significantly higher than those in E2 group (P＜0.05). (4) The mRNA and protein expression level of the ALP, ColⅠ, Runx2 were significantly higher in the groups applied with 5% amplitude of tensile strain for 2 h/d or for 4 h/d than those in the control group (P＜0.05). In our study, E2 and mechanical stimulation played an important role in the regulation of differentiation of rBMSCs into osteoblasts, and the manner applied with the 2% amplitude of tensile strain for 4 h/d, lasting 3 days was an optimal stimulus for up-regulating the mRNA and protein expression of ALP, ColⅠ, Runx2, OCN of rBMSCs.
ObjectiveTo explore the plastic surgical treatment and the way to reduce hemorrhage for scalp and facial plexiform neurofibromas. MethodsBetween July 2004 and July 2013, 20 patients with scalp and facial plexiform neurofibromas (17 cases of neurofibromatosis type Ⅰ and 3 cases of plexiform neurofibroma) were treated, and the clinical data were retrospectively analyzed. There were 9 males and 11 females with an average age of 37 years (range, 18-56 years). The disease duration ranged from 8 to 56 years (mean, 19 years). The scalp was involved in 6 cases, the face in 7 cases, and both the scalp and face in 7 cases. The extent of involvement ranged from 4 cm×3 cm to 15 cm×13 cm. Obvious pigmentation was seen in 2 cases. Endovascular embolization was performed before surgical intervention in 4 cases. Preliminary sutures around the lesion were carried out in 18 cases having an involved range over 5 cm×5 cm. One-stage excision was performed in 17 cases, and two-stage excision in 3 cases. Wound repair and facial orthopedic treatment were performed after tumor excision. ResultsThe intraoperative blood loss was 100-500 mL (mean, 300 mL) for patients undergoing single operation. For 3 patients undergoing two-stage excision, the blood loss of the first operation was 500, 600, and 800 mL respectively, and the blood loss of the second operation was all 50 mL. Autologous blood transfusion of 200, 400, and 400 mL was performed in 3 cases respectively. The preliminary sutures were removed at 3-7 days (mean, 5 days) after operation. All the incisions healed primarily without secondary hemorrhage and hematoma, and the flap and skin graft survived totally. Fifteen patients were followed up 1 year to 7 years (mean, 2.5 years). All patients showed significant improvement in appearance. No significant progression, expanding, and sagging were observed. ConclusionEndovascular embolization and preliminary sutures around the lesion can be used to reduce hemorrhage in resection of plexiform neurofibroma in the scalp and face. Personalized surgical plan of benign neurofibromatosis should be made to reduce the tumor mass, to improve function and appearance.
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 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 investigate the effects of heat injured keratinocytes (KC) supernatant on the expressions of collagen type I, collagen type III, and matrix metalloproteinase 1 (MMP-1) of dermal fibroblasts (Fb). Methods KC and Fb were isolated and cultured. Then the models of heat injured KC and Fb were reproduced in vitro, respectively. The heat injured and normal culture supernatant were collected respectively at 12 hours, and formulated as a 50% concentration of cell-conditioned medium. According to the culture medium, Fb at passage 3-5 was divided into 3 groups. Normal Fb was cultured with the conditioned medium containing 50% heat injured KC culture supernatant (group A), the conditioned medium containing 50% normal KC culture supernatant (group B), and DMEM (group C), respectively. The cells in 3 groups were collected at 24 hours. In addition， the cells in group A were collected at 0, 1, 2, 6, 12, 24, and 48 hours， respectively. Normal Fb was cultured with the conditioned medium containing 50% heat injured Fb culture supernatant. Then, the cells were collected at 0, 1, 2, 6, 12, 24, and 48 hours, respectively. The mRNA levels of the collagen type I, collagen type III, and MMP-1 of Fb were measured by real-time fluorescent quantitative PCR techniques. Results At 24 hours after cultured with supernatant of heat injured KC，mRNA relative expression levels of collagen type I, collagen type III, and MMP-1 in group A were significantly higher than those in groups B and C (P lt; 0.05). The mRNA relative expression levels of collagen type I, collagen type III, and MMP-1 in group A gradually increased with time going, showing significant differences between 0 hour and 2, 6, 12, 24, and 48 hours (P lt; 0.05); significant differences were found between different time points after 2 hours (P lt; 0.05). After Fb was treated with supernatant of heat injured Fb, the mRNA relative expression levels of MMP-1 gradually decreased with time going, showing significant differences between 0 hour and 1, 2, 6, 12, 24, and 24 hours (P lt; 0.05); after 2 hours of culture, significant differences were found among different time points (P lt; 0.05). Conclusion Heat injured KC supernatant may regulate the mRNA expressions of collagen type I, collagen type III, and MMP-1 of Fb.