The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

Objective To retrospectively analyze the efficacy and safety of combined hetrombopag in the treatment of cancer therapy induced thrombocytopenia(CTIT)after chemotherapy for germ cell tumors.Methods The data of patients with CTIT ≥ grade Ⅲcombined with chemotherapy for intracranial germ cell tumors admitted from January 2021 to March 2024 were collected and analyzed,and 33 patients met the enrollment criteria.The patients in the study group were treated with oral hetrombopag combined with subcutaneous injections of recombinant human thrombopoietin(rhTPO)or interleukin-11(IL-11),and those in the control group were treated with subcutaneous injections of rhTPO or IL-11.The differences of the two groups of patients in platelet counts,platelet-raising response rate,mean onset of action time,and prolongation of the next cycle of treatment before and after the treatment were compared to each other,and the adverse reactions of the two groups were also counted.Results The platelet counts of patients in both groups were improved post-treatment,with no statistical significance between the two groups for platelet count elevation on days d1,d2,and d3 of the medication(P＞0.05).The platelet elevation counts of the study group were significantly elevated on day d(7±3)after the medication compared with the control group,with a statistically significant difference(P＜0.05),and the rate of platelet elevation response increased with time prolongation.The mean time to onset of drug administration was 3(3,5)in the study group and 4(3,7)in the control group,with no statistically significant difference(P＞0.05).The incidence of prolongation of the time to the next cycle of treatment was 54.5％in the study group and 81.8％in the control group,and the difference between the two groups was not statistically significant(P＞0.05).Two patients in the study group developed mild reversible liver function abnormalities.Conclusion The efficacy of hetrombopag combined with subcutaneous injection of t rhTPO or IL-11 in the treatment of thrombocytopenia after chemotherapy for intracranial germ cell tumors is reliable,and it can significantly elevate platelet counts with tolerable adverse effects.

Perimenopausal women are more susceptible to fire pathogen disturbances,often resulting in the restlessness of the mind owing to the deficiency and decline of the thoroughfare and conception vessels,as well as the insufficiency of the essence and blood of the viscera.CHENG Zhongling's theory of thief and child fire in Medical Insights proposes that thief fire primarily arises from exogenous pathogen invasion and improper diet,leading to syndromes such as food retention in the stomach or phlegm-fire stagnation.In contrast,child fire is generated endogenously,often owing to liver and kidney deficiency,resulting in an imbalance of water and fire and liver dysfunction,leading to excessive fire transformation.This theory provides a novel perspective for understanding the pathogenesis of perimenopausal insomnia.An in-depth exploration of the role of thief fire and child fire in perimenopausal insomnia is presented,along with a detailed discussion of corresponding treatment strategies.For the invasion of thief fire,therapeutic approaches include ascending and dispersing stagnant fire,clearing and moistening to remove interior heat,purging the heat accumulation to unblock the bowels,and subduing the fire and nourishing yin to eliminate depression.When child fire disturbs the spirit,treatment methods involve smoothing and relieving the liver qi to clear the stagnant heat,nourishing the true yin to restrain the yang,warming and nurturing the primordial qi and harmonizing the nutrient and defensive qi,and guiding and reducing the deficient heat to remove the floating fire.Clinical practice necessitates precise identification of thief and child fire,thorough investigation of exogenous pathogens and internal damage,and careful differentiation between deficiency and excess,as well as the superficial and internal aspects.Strict adherence to the treatment principle of"nourishing the child fire can drive out the thief fire,but driving out the thief fire should not harm the child fire"ensures a balanced approach.By harmonizing the yin and yang of the viscera and allowing the mind to be at ease,this strategy effectively alleviates perimenopausal insomnia.The application of these principles provides a practical and feasible theoretical foundation and practical guidance for the treatment of perimenopausal insomnia using traditional Chinese medicine.

Objective:To investigate a novel coating technology for artificial blood vessel pipelines, conducting preliminary tests on the mechanical stability, hemocompatibility, and biocompatibility of the coating.Methods:The polyester braided artificial blood vessels produced by Terumo Corporation were subjected to three different experimental treatments and divided into three groups. Model group: The uncoated artificial blood vessels were thoroughly cleaned and freeze-dried. Experimental group: The artificial blood vessels were first immersed in a dopamine solution to form a polydopamine(PDA) coating on their surface, and then further immersed in an earthworm active protein/gelatin(EWAP/GT) solution to create PDA/GT/EWAP-modified artificial blood vessels. Collagen group: The untreated polyester woven artificial blood vessels served as the control. The study detailed the characterization, porosity, water permeability, degradation rate, blood compatibility, and cytotoxicity of the PDA/GT/EWAP-coated artificial blood vessels. Additionally, a 2-week in vivo study was conducted to evaluate the biocompatibility of the PDA/GT/EWAP-coated artificial blood vessels implanted subcutaneously in SD rats.Results:The PDA/GT/EWAP-coated artificial vascular grafts were successfully fabricated. The artificial blood vessels in the PDA/GT/EWAP group exhibited a porosityof(50.53±1.10)%, with water permeability showing a gradual decreasing trend over time. The overall in vitro degradation rate at 4 weeks was(1.83±0.08)%, and the PDA/GT/EWAP group demonstrated favorable mechanical stability. The activated partial thromboplastin time(APTT) of the PDA/GT/EWAP group was(26.30±0.46)s, the thrombin time(TT) was(18.83±0.49)s, the hemolysis rate was(2.15±0.09)%, and the plasma recalcification time(PRT) was(191.00±10.54)s, indicating excellent blood compatibility and anticoagulant properties. MTT assay evaluation of the PDA/GT/EWAP group revealed no significant cytotoxicity. After subcutaneous implantation of vascular samples in rats for 2 weeks, analysis of blood immune parameters and hematoxylin-eosin(HE) staining of the artificial vascular samples showed that the immune response in the PDA/GT/EWAP group exhibited no significant difference compared to the collagen group and was superior to the model group. Conclusion.Conclusion:The PDA/GT/EWAP composite-coated artificial blood vessel demonstrates excellent mechanical properties, good hemocompatibility, biocompatibility, and low cytotoxicity. It also shows remarkable stability. This research offers a new approach for domestic technological breakthroughs in related fields.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

The unique characteristics of the deep space environment, microgravity, cosmic radiation, and extreme temperature fluctuations, are emerging as major driving forces for pharmaceutical innovation. These factors provide new avenues for optimizing drug formulations, improving crystal structure quality, and accelerating the discovery of therapeutic targets. Advances in deep space research not only help overcome critical bottlenecks in terrestrial drug development but also promote progress in structure-based drug design and deepen understanding of cellular stress-response mechanisms. Current progress in space-based pharmaceutical research primarily includes the study of disease mechanisms under microgravity, protein crystallization in microgravity, and drug development utilizing deep space radiation and resources. However, the operational complexity, high costs, and limited data reproducibility of space experiments remain key challenges hindering widespread application. Looking ahead, with the integration of automation, artificial intelligence analysis, and on-orbit manufacturing, deep space drug development is expected to achieve greater scalability and precision, opening a new frontier in biopharmaceutical science.
Drug Design ; Drug Development/methods* ; Humans ; Weightlessness ; Space Flight ; Artificial Intelligence ; Extraterrestrial Environment

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Perimenopausal anxiety and depression state fall under the categories of"visceral agitation"and"perimenopausal syndrome"in traditional Chinese medicine(TCM).Grounded in the theory of"Yang transforms qi,yin shapes form",this study posits that the pathogenesis of this condition is complex,often presenting with concurrent deficiency and excess syndromes,and is closely associated with yang deficiency-induced stagnation and qi stagnation leading to mental decline.The pathological mechanism is summarized as yang deficiency being the root and qi stagnation the manifestation.This article proposes a"yang-oriented treatment"approach for perimenopausal anxiety-depression disorders,employing a stepwise integrated acupuncture protocol termed"One Needling,Two Moxibustion,Three Consolidation":"One Needling"prioritizes regulating qi flow via acupuncture to soothe the liver and harmonize the spirit;"Two Moxibustion"utilizes refined moxibustion to warm yang,resolve stagnation,and activate yang circulation;"Three Consolidation"combines bloodletting therapy to remove stasis and regenerate tissues with intradermal needle embedding to stimulate yang and regulate visceral functions.This synergistic protocol aims to nourish the heart-mind,awaken the orifices of consciousness,alleviate perimenopausal anxiety and depressive symptoms,and consolidate therapeutic efficacy.

Objective: To identify ferroptosis-related genes associated with gastric cancer prognosis and investigate their potential molecular functions. Methods: Gene expression profiles and clinical information of gastric cancer tissues and adjacent normal tissues were obtained from TCGA database. Differential expression analysis of ferroptosis-related genes was performed using the "DESeq2" package in R software. Key genes were identified and a prognostic model for gastric cancer was constructed through Cox regression analysis based on the LASSO algorithm. Patients were stratified into high-risk and low-risk groups according to the median risk score. The accuracy of the model was evaluated using Kaplan-Meier survival analysis and ROC curve analysis. Immune cell infiltration in gastric cancer patients was assessed with the "CIBERSORT" package. The mRNA expression of differentially expressed genes(DEGs) with prognostic significance was examined in both gastric cancer and adjacent normal tissue samples. In vitro experiments were conducted to validate the impact of hydroxycarboxylic acid receptor 1(HCAR1) on the malignant biological behavior of gastric cancer. Results: Based on ferroptosis-related genes from the TCGA database, a novel prognostic model was constructed. It demonstrated robust predictive power for survival in both training and validation cohorts. RT-qPCR analysis of 8 pairs of gastric cancer and normal tissues revealed that the expression patterns of 6 prognostic DEGs in cancer tissues were consistent with those predicted by the model. In vitro experiments confirmed that downregulation of the key gene HCAR1 could inhibit the proliferation, invasion, and metastasis of gastric cancer cells. Conclusion The ferroptosis-related gene based prognostic model exhibits robust predictive capability, allowing for accurate determination of prognosis and survival in individuals with gastric cancer.