OBJECTIVE To prepare the β -cyclodextrin （ β -CD） inclusion complex with volatile oil from Qianghuo qushi qingwen granules， and to characterize and quantitatively analyze the inclusion complex. METHODS The comprehensive scores calculated by inclusion rate and inclusion compound yield were used as indicators for screening the inclusion method. The single-factor experiments and Box-Behnken response surface experiments were used to op timize the inclusion conditions， with the above comprehensive score as response value， and taking the ratio of β -CD to volatile oil， inclusion temperature and inclusion time as indexes. The volatile oil inclusion complex of Qianghuo qushi qingwen granules was prepared according to the determined optimal process， followed by validation. Ultraviolet （UV）-visible spectroscopy， thin-layer chromatography （TLC）， and microscopic imaging were also performed. Ultra-high performance liquid chromatography was used to determine the contents of perillaldehyde， pogostone and atractylodin. RESULTS The saturation aqueous solution method was adopted. The optimal inclusion process conditions were as follows： the ratio of β -CD to volatile oil was 7.5∶1， the inclusion temperature was 40 ℃， and the inclusion time was 2.2 h. In three verification experiments， the average inclusion rate was 72.32%， the average yield of inclusion compound was 74.45%， the average comprehensive score was 72.96 points， and the relative error with the predicted value （74.15 points） of the model was 1.61%. UV-visible spectroscopy， TLC and microscopic imaging showed that β -CD and volatile oil successfully formed a new inclusion complex. The average contents of perillaldehyde， pogostone and atractylodin were 4.498 2， 0.814 9， 0.905 7 mg/g， respectively， with RSDs of 0.31%， 0.56% and 0.63% （ n ＝3）. CONCLUSIONS A stable and feasible preparation process of the volatile oil inclusion complex of Qianghuo qushi qingwen granules is successfully established.

OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

Rare neurological diseases account for over one-third of the diseases included in the first and second batches of China′s Rare Disease Catalogue. They are generally characterized by high disability rates, heavy care burdens, and prominent unmet clinical treatment needs. In recent years, China has been continuously improving medication accessibility for patients with rare neurological diseases by optimizing the review and approval pathways for rare disease drugs, implementing dynamic medical insurance access, and providing policy support for scientific research. However, challenges remain, including weak independent research and development (R&D) capacity and insufficient translation of high-quality research achievements into clinical practice. Based on the supply gap of clinical treatment resources for rare neurological diseases in China and the overall landscape of global R&D pipelines, this paper summarizes and discusses the current status, characteristics, and future directions of drug development for rare neurological diseases in China.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoen-cephalopathy (CADASIL) is caused by NOTCH3 gene variants and is predominantly characterized by cerebral small vessel disease. Previous studies have suggested that CADASIL may also involve the macrovascular system. This study aimed to explore the association between rare NOTCH3 variants and macrovascular lesions.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective To explore the characteristics and temporal trends of renal cancer burden among Chinese adolescents and young adults(AYA), and predict its future epidemic situation, so as to provide evidence for formulating public health policies and reducing the disease burden.Methods Epidemiological data of renal cancer in Chinese AYA(15-39 years)from 1990 to 2021 were obtained from the Global Burden of Disease(GBD)2021 database. The current status and trends of renal cancer in this population were analyzed. The incidence and mortality trends of renal cancer in AYA over the next 15 years was predicted with ARIMA model. The impacts of smoking and body mass index(BMI)on the disease burden were evaluated. Results In 2021, the incidence(1.12/100000), prevalence(8.61/100000), mortality(0.19/100000), and disability-adjusted life years(DALYs)(11.37/100000 person-years)of renal cancer in Chinese AYA were significantly higher than those in 1990 and above the global average. All burden indicators and their increases were higher in males than in females, and the burden accelerated after 30 years of age. The incidence rose steadily from 2003 to 2021(APC=3.95), while the mortality increased significantly from 2013 to 2021(APC=2.40). The burden attributed to high BMI continued to rise, and the smoking-attributable fraction in males first increased then decreased. ARIMA predicted that the incidence of renal cancer in Chinese AYA males would accelerate, while the mortality in both genders would stabilize. Conclusion The burden of renal cancer in Chinese AYA shows a significant upward trend. Males and people over 30 years old are key targets for prevention and control. Strengthening the management of risk factors(smoking, high BMI)and promoting early diagnosis and treatment are essential to reduce the disease burden.

Objective To screen the aging-related genes associated with prognosis in clear cell renal cell carcinoma (ccRCC), construct a prognostic model to optimize risk stratification, explore the underlying mechanisms, and provide reference for individualized diagnosis and treatment of this disease.Methods RNA sequencing data, clinical data, and aging-related genes of ccRCC were obtained from databases.After differentially expressed genes were screened, a prognostic model was constructed using Cox regression.The performance of the model was evaluated with Kaplan-Meier curves and receiver operating characteristic (ROC) curves, and validated with clinical features.Key genes were verified with immunohistochemistry.Results A total of 70 differentially expressed genes were identified, including IFI16, PECAM1, and ABCB1 as key genes, and a model formula was constructed.Internal and external validations showed that the survival rate of the high-risk group was significantly lower, with the area under the ROC curve (AUC)＞0.6.The risk score was correlated with clinical features.IFI16 was highly expressed in cancer tissues and associated with poor prognosis.Conclusion The prognostic model constructed in this study has good performance.Integrating clinical features, it can improve the accuracy of prognosis assessment of ccRCC.

After the production of the gradient coil of the magnetic resonance imaging system, electromagnetic field testing is required to verify whether the assembly accuracy meets the electromagnetic field requirements. Since the passive magnetic field B _z satisfies the Laplace ^,s equation and is a harmonic function, and according to the extreme value principle of harmonic function, the maximum or minimum values of B _z can only appear on the boundaries, so the observation points of the magnetic field are generally selected on the surface of the spherical imaging area. For superconducting magnets used for human body magnetic resonance imaging, a spherical area with a center diameter of 40~50 cm is generally selected as the shimming target area. Only the field value of the target area needs to be measured, and the spherical harmonic coefficients obtained after data processing are used to determine the magnetic field performance of the gradient coil. There are many testing principles and methods for electromagnetic fields, so there is no unified way and method in the field of commercial applications. This article is based on the Gauss-Legendre numerical integration, measures and analyzes the magnetic field performance of gradient coils by building a data acquisition system, and this article applies numerical analysis methods to calculate the spherical harmonic coefficients of the magnetic field using discrete test data, providing a feasible method for the production and testing of gradient coils.
Magnetic Resonance Imaging/methods* ; Magnetic Fields ; Electromagnetic Fields ; Equipment Design

The casting and curing of gradient coils in the production process is a relatively complex process. The chemical process similar to the black box model requires confirmation of the impact of each step of input on the output results, while the curing temperature and molding method affect the roundness and deformation of the gradient coils. The analysis of the curing temperature and demolding method of gradient coils has important practical significance for the formation and micro deformation of gradient coils. This article uses ANSYS finite element simulation software to analyze the thermal structural coupling and the specific performance of actual products. It has been found that the product quality is more stable under the heat conduction mode, and the roundness of the mold is better when placed vertically and waiting for temperature cooling before being demolding than when placed horizontally.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.