ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

General anesthesia is widely used in clinical practice,whereas the exact mechanism behind the general anesthetic-induced reversible loss of consciousness remains unclear.Recent studies have revealed a close relationship between the dopaminergic system and general anesthetic-induced loss of consciousness.This system,encompassing dopamine neurons,dopamine receptors,and related neural pathways,regulates functions such as movement,memory,arousal,and cognition.The dopaminergic neurons in the ventral periaqueductal gray and ventral tegmental area,along with D1 receptors,have been shown to facilitate emergence from anesthesia.However,the role of D2 receptors remains controversial.This review summarizes recent advancements in the role of the dopaminergic system in general anesthesia and the underlying mechanism,with the aim of clarifying the mechanism of general anesthesia and providing a theoretical basis for preventing delayed emergence from anesthesia.
Humans ; Anesthesia, General ; Brain/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine/physiology* ; Animals

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

OBJECTIVE: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E₂) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF. METHODS: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E₂ levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E₂ threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E₂ levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E₂ levels. RESULTS: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E₂ levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E₂ levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E₂ levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E₂ levels ⩽ 10092 pmol/L (P<0.05). CONCLUSIONS WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E₂ levels. It may be more suitable for high-risk OHSS patients with E₂ levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Humans ; Ovarian Hyperstimulation Syndrome/blood* ; Female ; Adult ; Prospective Studies ; Drugs, Chinese Herbal/pharmacology* ; Estradiol/blood* ; Ovulation Induction ; Chorionic Gonadotropin

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

Objective:To evaluate the efficacy of the flipped classroom combined with 3D body anatomy software in the teaching of ultrasound-guided transversus thoracic muscle plane block.Methods:In this randomized controlled trial, 100 second-year resident physicians from the Department of Anesthesiology and Perioperative Medicine at our hospital, male or female, aged 22-26 yr, who rotated during January 2023 to January 2025, were selected and divided into 2 groups ( n=50 each) using a table of random numbers: experimental group and control group. Experimental group employed the teaching model of flipped classroom combined with 3D body anatomy software, while control group used the traditional teaching model. The scores of theoretical assessment, accuracy rate of ultrasound image identification, scores of procedural skills, success rates of clinical procedure, teaching satisfaction, and success rates of clinical translation after 1 month follow-up were compared between two groups. Results:Compared with control group, the scores of theoretical assessment, accuracy rate of ultrasound image identification, scores of procedural skills, success rates of clinical procedure, teaching satisfaction, and success rates of clinical translation after 1 month follow-up were significantly increased in experimental group ( P<0.05). Conclusions:The combination of flipped classroom and 3D body anatomy software is more effective than the traditional teaching methods when used for teaching of ultrasound-guided transversus thoracic muscle plane block.

The triterpenoid saponins of Centella asiatica, including asiaticoside, madecassoside, asiatic acid, and madecassic acid, are pivotal bioactive compounds of the plant. These constituents exhibit a spectrum of pharmacological activities, such as antioxidant, antitumor, and antidepressant effects, promotion of wound healing, and enhancement of microcirculation. Owing to these therapeutic properties, C. asiatica is widely employed in pharmaceutical and cosmetic industries. However, the escalating global demand for its extracts has led to potential supply shortages, prompting researchers to use multiple strategies such as multi-omics, molecular biology, and synthetic biology to conduct extensive studies. These studies encompass the elucidation of the biosynthetic pathways of triterpenoid saponins in C. asiatica, metabolic regulation, the hormonal induction of secondary metabolite synthesis, and the application of biotechnological strategies for natural product production to increase the yield of secondary metabolites in C. asiatica, or to produce active components via microbial chassis, thus satisfying market demands and promoting the sustainable exploitation of wild C. asiatica resources. This article first introduced the triterpenoid saponins of C. asiatica and their biological activities, then summarized the latest research advancements in their biosynthetic pathways, metabolic regulation, and heterologous biosynthesis, and provided an outlook on future development directions, with the aim of providing reference for comprehensive resource development and biotechnological synthesis of active components from C. asiatica.
Centella/genetics* ; Triterpenes/chemistry* ; Biosynthetic Pathways ; Humans ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts