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.

Puerariae Lobatae Radix and Puerariae Thomsonii Radix are the dried roots of Pueraria lobata and Pueraria thomsonii of the Leguminosae family， respectively. Since their separate inclusion in the 2005 edition of Pharmacopoeia of the People's Republic of China， the two herbs have been individually recorded. Although they share the same functions and indications， the required content of puerarin differs by a factor of up to eightfold between them. The current quality standard relies solely on a single indicator， puerarin， which fails to reflect the correlation between chemical constituents and core therapeutic effects. This has resulted in prominent issues of mixed use in clinical practice and production， thereby constraining the high-quality development of the industry. Modern research has demonstrated that Puerariae Lobatae Radix contains a comprehensive range and higher content of isoflavonoid constituents， while Puerariae Thomsonii Radix is rich in starch and polysaccharides. Puerariae Lobatae Radix exhibits stronger effects in antipyresis， cardiovascular and cerebrovascular protection， and central analgesia， while Puerariae Thomsonii Radix demonstrates greater advantages in anti-inflammation， hypoglycemia， and peripheral analgesia. Based on this， the chemical material bases of Puerariae Lobatae Radix and Puerariae Thomsonii Radix at both the macromolecule and micromolecule levels were systematically reviewed and compared. The pharmacodynamic material bases and mechanisms of action underlying their three core therapeutic effects， namely "relieving exterior syndrome and clearing heat"， "promoting fluid production to quench thirst"， and "dredging channels and activating collaterals"， were summarized. The most highly correlated common metabolic pathway shared by both herbs for these three therapeutic effects is the arachidonic acid metabolic pathway， and their common core target is prostaglandin-endoperoxide synthase 2 （PTGS2）. This review provided clinical application recommendations based on the therapeutic differences between the two herbs， elucidated the scientific connotation of their "same origin but different effects"， and， grounded in the quality marker （Q-Marker）， proposed the concept of efficacy-related Q-Marker based on "substance-efficacy-syndrome" association， as well as a novel strategy for efficacy-oriented quality evaluation. Preliminary screening of quality markers associated with different therapeutic effects was also conducted. This study aims to provide critical scientific evidence for the precise clinical application of Puerariae Lobatae Radix and Puerariae Thomsonii Radix， the improvement of quality standards， and the high-quality development of the industry.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Demyelination and remyelination play key roles in spinal cord injury (SCI), affecting the recovery of motor and sensory functions. Research in rodent models is extensive, but the study of these processes in non-human primates is limited. Therefore, our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis. In a previous study, we created an SCI model in M. fascicularis by controlling the contusion displacement. We used Eriochrome Cyanine staining, immunohistochemical analysis, and toluidine blue staining to evaluate demyelination and remyelination. The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally, the former mainly impacting sensory pathways, while the latter primarily affected motor pathways. Toluidine blue staining showed myelin loss and axonal distension at the injury site. Schwann cell-derived myelin sheaths were only found at the center, while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas. Our study showed that long-lasting demyelination occurs in the spinal cord of M. fascicularis after SCI, with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
Animals ; Spinal Cord Injuries/physiopathology* ; Demyelinating Diseases/etiology* ; Remyelination/physiology* ; Macaca fascicularis ; Disease Models, Animal ; Myelin Sheath/pathology* ; Oligodendroglia/pathology* ; Schwann Cells/pathology* ; Female ; Spinal Cord/pathology* ; Axons/pathology*

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Traditional Chinese medicine(TCM) processing is a unique and highly distinctive pharmaceutical technology in China. Utilizing modern scientific methods to elucidate the connotations of traditional processing theory and its effects is expected to facilitate the inheritance, development, innovation, and enhancement of TCM processing, and lead to more original research outcomes in the field of TCM. The breakthrough in TCM processing lies in the study of its underlying principles, and analyzing these principles involves researching the transformation mechanisms of chemical components and the biological effect mechanisms of the transformed components. This paper proposed the concept of "TCM processing chemical biology"(TCMPCB) for the first time. Under the guidance of TCM theory, the active components transformed during TCM processing were used as chemical tools to study their targets and molecular regulatory mechanisms, aiming to clarify the scientific principles by which TCM processing affected biological effects in the organism. The research findings also provided new directions for discovering novel active components, new lead compounds, creating new decoction pieces, and developing new TCM drugs. This paper provided a detailed introduction to the background, definition, research content, research ideas, research methods, and prospects of TCMPCB, with the aim of offering new research perspectives for analyzing the principles of TCM processing and providing new pathways for achieving the "four new and eight transformations" in TCM processing.
Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Humans ; Animals

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

Panax ginseng as a perennial herb of Araliaceae, exhibits pharmacological effects such as central nervous system stimulation, anti-tumor properties, and cardiovascular and cerebrovascular protection. The B3 gene family plays a crucial role in growth and development, antioxidant activity, stress resistance, and secondary metabolism regulation of plants and has been extensively studied in various plants. However, the identification and analysis of the B3 gene family in P. ginseng have not been reported. In this study, a total of 145 B3 genes(PgB3s) with complete open reading frames(ORF) were identified from P. ginseng and classified into five subfamilies based on domain types. Through correlation analysis with ginsenoside content, SNP/InDels analysis, and interaction analysis with key enzyme genes, 15 PgB3 transcripts were found to be significantly correlated with ginsenoside content and exhibited a close interaction network with key enzyme genes involved in ginsenoside biosynthesis, which indicated that these genes may participate in the regulation of ginsenoside biosynthesis. Additionally, this study found that PgB3 genes exhibited induced expression in response to methyl jasmonate(MeJA) stress, which aligned with the presence of abundant stress response elements in their promoters, confirming the important role of the B3 gene family in P. ginseng in stress resistance. The results of this study revealed the potential functions of PgB3 genes in ginsenoside biosynthesis and stress response, providing a significant theoretical basis for further research on the functions of PgB3 genes and their regulatory mechanisms.
Panax/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Ginsenosides/biosynthesis* ; Multigene Family ; Phylogeny

Microbial detection and control of traditional Chinese medicine(TCM) decoction pieces are crucial for the quality control of TCM preparations. It is also a key area of research in the measurement technology and equipment development for TCM manufacturing. Guided by TCM manufacturing measurement methodologies, this study presented a design of a novel portable microbial detection device, using Atractylodis Macrocephalae Rhizoma decoction pieces as a demonstration. Immunomagnetic separation technology was employed for specific isolation and labeling of target microorganisms. Enzymatic signal amplification was utilized to convert weak biological signals into colorimetric signals, constructing an optical biosensor. A self-developed smartphone APP was further applied to analyze the colorimetric signals and quantify target concentrations. A portable and automated detection system based on Arduino microcontroller was developed to automatically perform target microbial separation/extraction, as well as mimetic enzyme labeling and catalytic reactions. The developed equipment specifically focuses on the rapid and quantitative microbial analysis of TCM active pharmaceutical ingredients, intermediates in TCM manufacturing, and final TCM products. Experimental results demonstrate that the equipment could detect Salmonella in samples within 2 h, with a detection limit as low as 5.1 × 10~3 CFU·mL~(-1). The equipment enables the rapid detection of microorganisms in TCM decoction pieces, providing a potential technical solution for on-site rapid screening of microbial contamination indicators in TCM. It has broad application prospects in measurement technology for TCM manufacturing and offers strong technical support for the modernization, industrialization, and intelligent development of TCM.
Drugs, Chinese Herbal/analysis* ; Atractylodes/microbiology* ; Rhizome/microbiology* ; Biosensing Techniques/methods* ; Medicine, Chinese Traditional ; Colorimetry/instrumentation* ; Quality Control