A 43-year-old male patient presented with recurrent edema in different anatomical sites for over 10 years, with facial edema worsening 1 day prior to admission. He had been repeatedly admitted to dermatology, general surgery, and emergency departments of external hospitals due to " acute abdomen" and " laryngeal edema, " resistant to antihistamines and glucocorticoid therapy. Physical examination revealed non-pitting swelling of the right upper eyelid, bilateral cheeks, and lips asymmetrically. On the night of admission, he developed acute laryngeal edema with dyspnea, which was promptly treated, leading to clinical stabilization. Laboratory screening during the attack revealed decreased serum complement C4 levels, along with reduced functional activity and concentration of C1 esterase inhibitor, confirming a diagnosis of type 1 hereditary angioedema. The patient received lanadelumab for prophylaxis and achieved satisfactory clinical outcomes. He remains under long-term follow-up.

OBJECTIVE: To construct a predictive model for the reduction in methadone maintenance treatment (MMT) and evaluate the effects of different interventions and other clinical factors on methadone reduction using Shapley additive explanations (SHAP). METHODS: Two clinical trials of acupuncture for methadone reduction in MMT patients were analyzed, and the baseline data, MMT related information, intervention measures, the data related to dose-reduction outcomes were collected. The predictive model was constructed by means of 6 machine learning algorithms including support vector machine (SVM), K-nearest neighbors (KNN), logistic regression (LR), Naive Bayes (NB), random forest (RF) and categorical-boosting (CatBoost), and 2 integration methods, blending-ensemble method (Blending) and Stacking-ensemble method (Stacking). SHAP was employed for the interpretability analysis of the optimal model. RESULTS: A total of 251 MMT patients were included, 128 cases in the acupuncture group and 123 cases in the non-acupuncture group. CatBoost and Stacking performed optimally in the test set. CatBoost obtained an accuracy of 0.780 0±0.060 8, a precision of 0.500 0±0.120 0, a recall of 0.818 2±0.140 2, F1 score of 0.620 7±0.114 0, and receiver operating characteristic-area under curve (ROC-AUC) of 0.857 8±0.140 2 for the subjects. In MMT patients with acupuncture as an adjunctive therapy, the top 5 important features for methadone reduction, included intervention measures, body mass index (BMI), the duration of MMT, the history of opioid use and occupation; and SHAP values were 1.25, 0.36, 0.21, 0.19 and 0.12, respectively. The SHAP feature dependence plot showed that BMI, MMT duration and the history of opioid use presented a nonlinear negative correlation with the reduction effect. CONCLUSION In acupuncture as adjunctive therapy for methadone reduction, the clinical factors should be considered comprehensively; and the interpretable predictive model provides a scientific basis for it, which is conducive to the improvement of clinical strategy of acupuncture for methadone reduction and the development of personalized reduction scheme.
Humans ; Methadone/therapeutic use* ; Acupuncture Therapy ; Adult ; Female ; Male ; Machine Learning ; Middle Aged ; Opiate Substitution Treatment ; Young Adult

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Parkinson's disease (PD) is a common neurodegenerative disorder mainly related to mitochondrial dysfunction of dopaminergic neurons in the midbrain substantia nigra. This study aimed to investigate the effects of exercise preconditioning on motor deficits and mitochondrial function in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sedentary + saline (SS), sedentary + MPTP (SM), exercise + saline (ES), and exercise + MPTP (EM) groups. Mice in the ES and EM groups received 4 weeks of treadmill training, and then SM and EM groups were treated with MPTP for 5 days. Motor function was assessed by behavioral tests, and morphological and functional changes in dopaminergic neurons and mitochondria in the substantia nigra of the midbrain were evaluated using immunohistochemistry, Western blot, and transmission electron microscopy technology. The results showed that, compared with the SM group, the EM group exhibited significantly improved motor ability, up-regulated protein expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the midbrain, and down-regulated protein expression of α-synuclein (α-Syn) in the mitochondria of substantia nigra. Compared with the SM group, the EM group showed up-regulated protein expression levels of mitochondrial fusion proteins, including optical atrophy protein 1 (OPA1) and mitofusin 2 (MFN2), and biogenesis-related proteins, including peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM), while the protein expression levels of dynamin-related protein 1 (DRP1) and mitochondrial fission protein 1 (FIS1) were significantly down-regulated. Compared with the SM group, the EM group showed significantly reduced damage to substantia nigra mitochondria, restored mitochondrial membrane potential and ATP production, and decreased levels of reactive oxygen species (ROS). These results suggest that 4-week treadmill pre-training can alleviate MPTP-induced motor impairments in PD mice by improving mitochondrial function, providing a theoretical basis for early exercise-based prevention of PD.
Animals ; Male ; Physical Conditioning, Animal/physiology* ; Mice ; Mice, Inbred C57BL ; Mitochondria/physiology* ; Dopaminergic Neurons ; MPTP Poisoning/physiopathology* ; Substantia Nigra ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals ; Mice ; Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Light ; Cytokines/genetics* ; Humans

In recent years, the reform of the registration, evaluation, and approval system for traditional Chinese medicine(TCM) has been promoted at the national level, with establishment of an evaluation evidence system for TCM registration that combines TCM theory, human use experience, and clinical trials(known as the "three-combined" evaluation evidence system). This system, which aligns with the characteristics of TCM clinical practice and the laws of TCM research and development, recognizes the unique value of human use experience in medicine and returns to the essence of medicine as an applied science, thus receiving widespread recognition from both academia and industry. However, it meanwhile poses new and higher challenges. This article delves into the value and challenges faced by the "three-combined" evaluation evidence system from three perspectives: registration management, medical institutions, and the TCM industry. Furthermore, it discusses how the China Association of Chinese Medicine, leveraging its academic platform advantages and leading roles, has made exploratory and practical efforts to facilitate the research and development of new TCM drugs and the implementation of the "three-combined" evaluation evidence system.
Drugs, Chinese Herbal/standards* ; Humans ; Medicine, Chinese Traditional/standards* ; China ; Drug Development

OBJECTIVE: To explore clinical efficacy of membrane-induced technique combined with gastrocnemius muscle flap transposition in treating traumatic osteomyelitis of the upper tibia. METHODS: A retrospective analysis was conducted on 7 patients with traumatic osteomyelitis of the upper tibia who were treated with membrane-induced technique combined with gastrocnemius muscle flap transposition from January 2022 to December 2023. Among them, there were 4 males and 3 females; aged from 29 to 57 years old; 4 patients were treated after open fracture, 2 patients were treated after closed fracture, and 1 patient was treated after scalding; the courses of disease ranges from 2 weeks to 8 years; sinus tracts were present in all patients, and the lesion range of the tibia ranged from 5 to 9 cm. The results of deep tissue bacterial culture showed that 2 patients were negative, 3 patients were staphylococcus aureus, 1 patient was methicillin-resistant staphylococcus aureus, and 1 patient was pseudomonas aeruginosa and 1 patient was klebsiella pneumoniae. After debridement, the range of bone defect ranged from 8 to 12 cm, and the cortical defect accounted for approximately 30% of the circumference. The area of soft tissue defect ranged from 8.0 cm×2.0 cm to 10.0 cm×6.0 cm. At the first stage, vancomycin-loaded/meropenem/gentamicin-loaded bone cement was implanted. The gastrocnemius muscle flap was repositioned to cover the wound surface and free skin grafting was performed. After an interval of 7 to 10 weeks, the stageⅡsurgery was performed to remove bone cement. Autologous iliac bone mixed with vancomycin/gentamicin and calcium sulfate artificial bone was transplanted, and the wound was sutured. One patient retained the original internal plants, one patient removed the internal plants and replaced them with steel plate external fixation, one patient replaced the internal plants and added steel plate external fixation, and three patients were simply fixed with steel plate external fixation. One year after operation, the recovery of knee joint and ankle joint functions was evaluated by using Hospital for Special Surgery (HSS) knee joint score and Kofoed ankle joint function score respectively. RESULTS: All patients had their wounds closed simultaneously with bone cement implantation and healed well. All patients were followed up for 12 to 17 months after operation, and satisfactory bone healing was achieved at 6 months after stageⅡsurgery. Twelve months after operation, all patients had good bone healing without obvious limping was observed when walking. At 12 months after operation HSS knee joint score ranged from 93 to 100 points, and Kofoed ankle function score ranged from 96 to 100 points. CONCLUSION For traumatic osteomyelitis of the upper tibia, a staged treatment plan combining membrane-induced technique and gastrocnemius flap transposition on the basis of thorough debridement could safely cover the wound surface, effectively control bone infection and achieve satisfactory bone healing, without adverse effects on limb function.
Humans ; Male ; Female ; Middle Aged ; Osteomyelitis/surgery* ; Adult ; Surgical Flaps ; Retrospective Studies ; Tibia/injuries* ; Muscle, Skeletal/surgery*

Asthma is a chronic inflammatory disease of the airway involving various cellular players. Among the different phenotypes of asthma, neutrophilic asthma is often associated with severe airway inflammation and a notable resistance to corticosteroid treatment. Macrophages, as innate immune cells, play a crucial role in the pathogenesis of neutrophilic asthma. They regulate neutrophil recruitment and activation to promote the progression of airway inflammation. During this process, macrophages also undergo changes in aspects such as efferocytosis. We reviewed the recent research progresses regarding the role of macrophages in the pathogenesis of neutrophilic asthma, aiming to provide valuable insights for future studies in this area.
Humans ; Asthma/pathology* ; Neutrophils/pathology* ; Macrophages/immunology* ; Animals ; Phagocytosis

Neurofibromas are benign peripheral nerve sheath tumors. It is more common in neurofibromatosis type Ⅰ. However, isolated vagal nerve neurofibroma（VNN） of the neck is extremely rare, and only a few case reports have been reported. Its etiology and pathogenesis are not clear. The diagnosis is mainly based on pathological examination and immunohistochemistry, and surgical resection is the main treatment. This study reports a rare case of giant solitary vagus neurofibroma in the neck. The patient was a 29-year-old female who was found to have a mass on the right side of the neck by physical examination, which was considered to be a vagus nerve tumor by neck ultrasound and imaging examination. The tumor was completely removed during the operation, with the size of about 10.0 cm×2.5 cm, and the patient had no special discomfort. Postoperative pathology and immunohistochemistry confirmed neurofibroma. After surgery, the patient had right vocal cord paralysis, hoarseness, choking and paroxysmal cough. After swallowing function training and voice rehabilitation treatment in the department, the patient recovered satisfactorily. There was no complication and recurrence during the follow-up of 1 year. This article reviews the literature to improve the diagnosis and treatment of solitary vagus neurofibroma in the neck by combining its medical history, imaging features, pathology and immunohistochemistry, and surgical treatment.
Humans ; Female ; Adult ; Neurofibroma ; Vagus Nerve/pathology* ; Neck ; Cranial Nerve Neoplasms

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].