OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

ObjectiveTo investigate the mechanism of Huangqin Tang （HQT） in regulating metabolic reprogramming during the inflammation-cancer transformation in colitis-associated colorectal cancer （CAC）. MethodsCAC mouse model was established using the carcinogen azoxymethane （AOM） combined with the inflammatory agent dextran sulfate sodium （DSS）. HQT treatment was adopted. Serum metabolomics analysis was performed at three stages （inflammation， proliferation， and tumor formation） using liquid chromatography-tandem mass spectrometry （LC-MS/MS） untargeted metabolomics coupled with multivariate statistical analysis to explore the mechanism of HQT intervention in metabolism in CAC. ResultsThe results revealed that HQT significantly reversed the disturbance of key metabolites in CAC mice. A total of 52， 67， and 45 differential metabolites were identified in the model group， compared to the normal group， during inflammation， proliferation， and tumor stages， respectively. Lactate， linoleic acid， oleic acid， elaidic acid， and betaine were characteristic metabolites persistently enriched throughout colitis-cancer transformation. Pathway enrichment analysis of differential metabolites showed that linoleic acid metabolism and arachidonic acid metabolism were the most significantly disturbed in CAC pathogenesis. The proliferation stage featured expanded amino acid metabolic networks， while the tumor stage uniquely exhibited two new pathways of nicotinate and nicotinamide metabolism and phosphoinositide metabolism. HQT exerted stage-specific regulatory effects： targeting arachidonic acid metabolism in the inflammation stage， correcting the dysregulation of choline-carnitine metabolism in the proliferation stage， and rescuing nicotinamide and tryptophan metabolic collapse in the tumor stage. ConclusionHQT exerts regulatory effects on metabolic disorders at various stages of the colitis-cancer transformation process， thereby effectively slowing the progression from colitis to cancer. The study also reveals the dynamic metabolic characteristics of colorectal "inflammation-cancer transformation，"providing new insights for research on the targeted mechanisms of traditional Chinese medicine in anti-tumor therapy based on metabolic reprogramming.

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

Quality control is a key link in the modernization process of traditional Chinese medicine(TCM). Studies have shown that the effects of active components in TCM depend on not only their chemical composition but also their suitable physical forms and states. The physical phase structures, such as micelles, vesicles, gels, and nanoparticles, can improve the solubility, delivery efficiency, and targeting precision of active components. These structures significantly enhance the pharmacological activity while reducing the toxicity and side effects, demonstrating functional activity surpassing that of active components and highlighting the key effects of "structures" on "functions" of active components. Taking the physical phase structure as a breakthrough point, this paper outlines the common types of TCM physical phase structures. Furthermore, this paper explores how to realize the quality upgrading of TCM through the precise regulation of physical phase structures based on the current applications and potential of TCM physical phase structures in processing to increase the efficacy and reduce the toxicity, compounding and decocting processes, drug delivery systems, and quality control, aiming to provide novel insights for the future quality control of TCM.
Quality Control ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional/standards* ; Humans ; Drug Delivery Systems

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Inflammation represents a critical immune response triggered by cellular activities and inflammatory mediators following tissue damage. It plays a central role in the pathological progression of diverse diseases, including psychiatric disorders, cancer, and immunological conditions, rendering it an essential target for therapeutic intervention. Periodontitis, a prevalent oral inflammatory disease, is a leading cause of tooth loss and poses significant health challenges globally. Traditionally, inflammatory diseases such as periodontitis have been treated with systemic administration of synthetic chemicals. However, recent years have witnessed challenges, including drug resistance and microbial dysbiosis associated with these treatments. In contrast, natural products derived from Chinese medicine offer numerous benefits, such as high safety profiles, minimal side effects, innovative pharmacological mechanisms, ease of extraction, and multiple targets, rendering them viable alternatives to conventional antibiotics for treating inflammatory conditions. Numerous effective anti-inflammatory natural products have been identified in traditional Chinese medicine (TCM), including alkaloids, flavonoids, terpenoids, lignans, and other natural products that exhibit inhibitory effects on inflammation and are potential therapeutic agents. Several studies have confirmed the substantial anti-inflammatory and immunomodulatory properties of these compounds. This comprehensive review examines the literature on the anti-inflammatory effects of TCM-derived natural products from databases such as PubMed, Web of Science, and CNKI, focusing on terms like "inflammation", "periodontitis", "pharmacology", and "traditional Chinese medicine". The analysis systematically summarizes the molecular pharmacology, chemical composition, and biological activities of these compounds in inflammatory responses, alongside their mechanisms of action. This research seeks to deepen understanding of the mechanisms and biological activities of herbal extracts in managing inflammatory diseases, potentially leading to the development of promising new anti-inflammatory drug candidates. Future applications could extend to the treatment of various inflammatory conditions, including periodontitis.
Humans ; Periodontitis/immunology* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional ; Animals ; Anti-Inflammatory Agents/chemistry*

Objective:To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism.Methods:Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice.Results:Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p ( r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 ( r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p ( r=-0.394, P＜0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G 0/G 1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G 2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased ( P＜0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm 3 vs (857±114) mm 3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, P＜0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion:Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.

Adipose-derived mesenchymal stem cell (ADSC) has become a research hotspot in the field of regenerative medicine and stem cells in recent years because of its rich stock, easy access and low immunogenicity. ADSC can regulate immune system not only directly by interacting with immune cells, such as T cells, macrophages and B cells, but also indirectly via secreting soluble cytokines, such as interleukin (IL), growth factors and extracellular vesicles. Meanwhile, the immunomodulatory effects of ADSC have been demonstrated in vitro and in vivo experiments and applied to treat various of immune-related diseases with good results, such as systemic scleroderma, systemic lupus erythematosus and atopic dermatitis, etc. In this article, the direct and indirect immunomodulatory mechanisms and clinical applications of ADSC are described, its research direction and application prospect are also prospected.