This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals ; Rats ; Male ; Fermentation ; Rats, Sprague-Dawley ; Rhizome/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Bile/chemistry* ; Antipyretics/chemistry* ; Fever/metabolism* ; Cattle ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; Ethanol/chemistry* ; Interleukin-6/blood* ; Interleukin-1beta/blood*

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

Ferroptosis is a unique regulated form of cell death that is distinct from apoptosis, necrosis, and other well-characterized regulated cell death types, and plays an important role in the occurrence and development of chronic metabolic diseases, including diabetes, hypertension, hyperlipidemia, and non-alcoholic steatohepatitis. Recently, increasing evidence has supported traditional Chinese medicine (TCM) as a new hot spot for the treatment of chronic metabolic diseases by mediating ferroptosis. Unfortunately, few systematic reviews have described the importance of TCM in treating chronic metabolic diseases through the ferroptosis pathway. In the current review, the mechanism of ferroptosis and the roles of ferroptosis in chronic metabolic diseases are summarized. Additionally, this review illustrates that the regulation of ferroptosis by TCM could be an effective approach for treating chronic metabolic diseases based on experimental evidence and clinical application. In summary, this work will improve the understanding of ferroptosis and the ability of TCM to regulate ferroptosis in chronic metabolic diseases, thereby promoting the development and application of natural TCM.

Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.

Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.

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. CONCLUSION Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Humans ; Neurofibromatosis 1/pathology* ; Neurofibromin 1/metabolism* ; GTPase-Activating Proteins ; Mutation ; Genetic Predisposition to Disease ; Genetic Therapy

Plexiform neurofibromas (pNF) is significant hallmark of type Ⅰ neurofibromatosis, posing substantial negative impacts on patients’ quality of life and daily functionality. Surgical intervention remains the primary modality of treatment. However, the surgery is fraught with challenges due to the rich vascularization, intricate neural involvement, and ill-defined borders of the tumors. The risk of recurrence and complications further complicates the surgical approach. Through extensive literature review and integrative analysis, this article summarizes the current surgical treatment options and adjunctive techniques available for pNF management. Preoperative radiological assessments, vascular embolization, intraoperative neural monitoring, and fluorescence navigation are among the ancillary techniques that can effectively mitigate surgical risks. The timing of surgery should be guided by specific indications and contraindications, while the surgical plan must be individualized based on the patient’s unique presentation, sometimes necessitating a multidisciplinary approach. Overall, a comprehensive assessment of the patient’s condition and the implementation of multifaceted adjunctive measures are imperative for maximizing tumor resection while minimizing the risks of recurrence and complications.

Plexiform neurofibromas (pNF) is significant hallmark of type Ⅰ neurofibromatosis, posing substantial negative impacts on patients’ quality of life and daily functionality. Surgical intervention remains the primary modality of treatment. However, the surgery is fraught with challenges due to the rich vascularization, intricate neural involvement, and ill-defined borders of the tumors. The risk of recurrence and complications further complicates the surgical approach. Through extensive literature review and integrative analysis, this article summarizes the current surgical treatment options and adjunctive techniques available for pNF management. Preoperative radiological assessments, vascular embolization, intraoperative neural monitoring, and fluorescence navigation are among the ancillary techniques that can effectively mitigate surgical risks. The timing of surgery should be guided by specific indications and contraindications, while the surgical plan must be individualized based on the patient’s unique presentation, sometimes necessitating a multidisciplinary approach. Overall, a comprehensive assessment of the patient’s condition and the implementation of multifaceted adjunctive measures are imperative for maximizing tumor resection while minimizing the risks of recurrence and complications.