BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

OBJECTIVE To investigate the improvement effect and mechanism of processed Oxytropis falcata on renal fibrosis （RF） in rats. METHODS RF model was induced by adenine. After modeling， the rats were divided into the model group， positive control group （colchicine， 0.45 mg/kg）， and processed O. falcata low-， medium- and high-dose groups （0.5， 1， 2 g/kg）， respectively. Additionally， a blank group without modeling was set up， with 8 rats in each group. The positive control group and the various dosage groups of processed O. falcata were given the corresponding medicinal solutions intragastrically， while the blank group and model group were given equal volume of normal saline intragastrically， once daily for 28 consecutive days. The appearance and histopathological morphology of the rats’ kidneys were observed. Serum levels of renal function indexes [bl ood urea nitrogen （BUN）， creatinine （Cr） ] and inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） ] in rats were detected. Protein expressions of fibronectin （FN）， α -smooth muscle actin （ α -SMA） and collagen type Ⅰ （Col-Ⅰ） in renal tissue of rats were determined. mRNA expressions of transforming growth factor-β 1 （TGF-β 1 ）， Smad3 and extracellular signal-regulated kinase 1/2 （ERK1/2） in renal tissues were measured. Protein expression of TGF-β 1 and phosphorylation levels of Smad3 and ERK1/2 in renal tissues were detected. RESULTS Compared with the blank group， the rats in the model group exhibited enlarged kidneys with pale color， rough and uneven surface. There was a significant infiltration of inflammatory cells and vacuolated cells in the renal tubules， along with marked proliferation of collagen fibers. Serum levels of BUN， Cr， IL-6 and TNF-α， protein expressions of α -SMA， Col-Ⅰ and FN in renal tissues， mRNA expressions of TGF-β 1 ， Smad3， ERK1 and ERK2 and protein expression of TGF-β 1 as well as phosphorylation levels of Smad3 and ERK1/2 in renal tissues were increased significantly （ P ＜0.05）. Compared with the model group， renal pathological changes of rats were alleviated in processed O. falcata groups， with reduced infiltration of inflammatory cells and proliferation of collagen fibers. The levels of the aforementioned quantitative indicators were all significantly reversed （ P ＜0.05）. CONCLUSIONS Processed O. falcata can improve renal function in RF rats， alleviate inflammatory responses， and reduce abnormal collagen fiber deposition. Its mechanism of action may be related to the inhibition of the activity of the TGF-β 1 /Smad signaling pathway.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

Objective To explore the correlation between kinesiophobia and disease uncertainty, personal mastery, cardiac discomfort symptoms in patients with acute myocardial infarction (AMI) during recovery period. Methods A total of 320 patients with AMI admitted to the hospital were enrolled between January 2020 and January 2024. According to the results of Tampa Scale for Kinesiophobia Heart (TSK-H), they were divided into AMI kinesiophobia group (n=166) and simple AMI group (n=154). The disease uncertainty was evaluated by Mishel Uncertainty in Illness Scale for Adults (MUIS-A), personal mastery was evaluated by Personal Mastery Scale (PMS), and cardiac discomfort symptoms were evaluated by cardiac discomfort symptom scale. The correlation between kinesiophobia and disease uncertainty, personal mastery, cardiac discomfort symptoms in AMI patients was analyzed by Pearson correlation analysis. Results The scores of MUIS-A and cardiac discomfort symptoms in AMI kinesiophobia group were higher than those in simple AMI group (P<0.05), and PMS scores were lower than those in simple AMI group (P<0.05). The score of kinesiophobia was significantly positively correlated with scores of disease uncertainty and cardiac discomfort symptoms (r=0.628, 0.689, P<0.05), while significantly negatively correlated with the score of personal mastery (r=-0.526, P<0.05). Conclusion Kinesiophobia is related to disease uncertainty, personal mastery and cardiac discomfort symptoms in AMI patients during recovery period. Clinical medical staffs should focus on patients with the above characteristics. The targeted intervention measures can improve kinesiophobia and promote recovery of patients.

OBJECTIVE To evaluate the efficacy， safety， and cost-effectiveness of posaconazole for the prevention of invasive fungal infections （IFIs）. METHODS PubMed， Embase， CNKI， Wanfang data and other Chinese and English databases were searched， as well as the official websites of related health technology assessment （HTA）. Systematic review （SR）/meta-analysis， pharmacoeconomic studies， and HTA reports of posaconazole for the prevention of IFIs were collected. The retrieval time limit was from the establishment of the database to November 1， 2025. After screening the literature， extracting the data， and evaluating the quality of the literature， the results of the included studies were descriptively analyzed. RESULTS A total of 45 studies were included， involving 17 SR/meta-analyses， 26 pharmacoeconomic studies， 1 SR/meta-analysis combined with a pharmacoeconomic study， and 1 HTA report. In terms of effectiveness， posaconazole was significantly superior to other antifungal drugs （eg.， fluconazole， itraconazole） in reducing the incidence of IFIs， the incidence of invasive aspergillosis， all-cause mortality， and IFI-related mortality （ P ＜0.05）. In terms of safety， posaconazole was significantly superior to other antifungal drugs in the incidence of total adverse reactions （ P ＜0.05）， but there was no significant difference in the incidence of serious adverse reactions， the incidence of gastrointestinal advers e reactions， drug-induced liver injury， and the withdrawal rate due to adverse drug reactions （ P ＞0.05）. In terms of cost-effectiveness， most studies have shown that posaconazole possesses more cost-effectiveness advantages. CONCLUSIONS Posaconazole demonstrates favorable efficacy， safety， and cost-effectiveness in preventing IFIs.

ObjectiveTo meet the requirements of Good Laboratory Practice (GLP), Sichuan Institute for Drug Control (Sichuan Testing Center of Medical Devices, Sichuan Institute of Musk Deer Breeding) Safety Evaluation Center (hereinafter referred to as the center) conducts a targeted validation study to address the lack of supporting data for the specified validity periods of disinfectants, feed, and bedding during their use in laboratory animal facilities. The study summarizes practical experience in material management and provides a scientific basis for the standardized management of materials in the facility. MethodsUnder the routine operating conditions of the laboratory animal facility at the center, the disinfection efficacy of four commonly used disinfectants was confirmed using the quantitative suspension kill test, with the disinfectants tested on day 0, day 7, and at 1, 2, and 3 months after preparation and after opening; for laboratory animal feed, nutritional components, chemical contaminants, and microbial indicators were tested 7 days after opening; microbial indicators of laboratory animal corncob bedding were tested after storage for 7 days following opening and sterilization. ResultsUnder the GLP management system of our center, the disinfection efficacy log reduction values of prepared 0.04% sodium hypochlorite solution, 0.1% didecyldimethylammonium bromide solution, and 0.2% benzalkonium bromide solution were all ≥5 on days 0 and 7. The log reduction values of opened 75% ethanol were ≥5 on days 0 and 7 and at 1, 2, and 3 months after opening. All disinfectants were therefore qualified and effective. Compared with the factory inspection data, the nutritional components, chemical contaminants, and microbial indicators of SPF-grade rat and mouse maintenance feed, SPF-grade guinea pig growth and reproduction feed, conventional-grade guinea pig growth and reproduction feed, rabbit maintenance feed, and dog maintenance feed showed a slight overall downward trend but no significant differences 7 days after opening. The microbial indicators of specialized corncob bedding for SPF-grade laboratory animals stored for 7 days after opening and conventional-grade corncob bedding stored for 7 days after sterilization showed no significant fluctuations. All indicators still met the relevant requirements of GB/T 14924.2—2001 Laboratory Animals—Hygienic Standard for Formula Feeds and GB 14924.3—2010 Laboratory Animals—Nutrients for Formula Feeds. ConclusionBased on practical experience in managing the center's GLP laboratory animal facility and validation of core quality indicators, the specified validity periods of disinfectants, feed, and bedding meet the quality requirements, providing a practical reference for the standardized management of laboratory animal facilities.

By systematically combing ancient and modern literature， this paper examined Tribuli Fructus and Astragali Complanati Semen（ACS） used in the famous classical formulas from the aspects of name， origin， production area， harvesting and processing， clinical efficacy， so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology， and there were nicknames such as Baijili， Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas， and there were nicknames such as Baijili， Shayuan Jili and Tongjili. Because both of them had the name of Baijili， confusion began to appear in the Song dynasty. In ancient and modern times， the main origin of Tribuli Fructus were Tribulus terrestris， and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu， but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part， harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times， and the plump， firm texture， grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing， while modern commonly used is purified， fried and salt-processed. The ancient records of Tribuli Fructus were spicy， bitter， and warm in nature， with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders， improving vision， promoting muscle growth， and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today， the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed， traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter， followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior， while modern standards prioritize plump， uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying， while modern practice commonly employs purification methods. In terms of medicinal properties， the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus， its effects were thus regarded as equivalent to those of Tribuli Fructus， serving as the medicine for treating wind disorders， additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang， solidify sperm and reduce urine， nourish the liver and brighten the eye， etc. Based on the textual research results， it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials， we should pay attention to the specific reference object of Baijili， T. terrestris and A. complanatus should be identified and selected， and the processing method should be in accordance with the requirements of the formulas.

ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group， a model group， and a Danshen Tongluo formula （28 mg·kg^-1·d^-1） group. The efficacy was evaluated by examining the cardiac ultrasound， determination of the plasma level of N-terminal pro-brain natriuretic peptide， and pathological staining. After single-cell sequencing， SingleR package， public datasets， and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis， and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide （ NT-proBNP ） level （P<0.05）， ameliorated myocardial cell damage and fibrosis， and increase left ventricular ejection fractions （LVEF） in the rat model of heart failure after myocardial infarction（P<0.05）. Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells， venous endothelial cells， and capillary-arterial endothelial cells， while reducing the proportion of capillary-venous endothelial cells. In addition， this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells， while downregulating Mif-（CD74⁺CXCR44） signaling in endothelium-M1 macrophages and Mif-（CD74⁺CD44） signaling in endothelium-M2 macrophages. It reduced the citric acid cycle， oxidative phosphorylation， and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells， venous endothelial cells， and venous capillary endothelial cells can all regulate oxidative phosphorylation， cell adhesion molecules， and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.

Esophageal cancer cases in China account for more than 50% of the world, among which approximately 90% are histological subtypes of esophageal squamous cell carcinoma. Over 50% of esophageal cancer patients are initially diagnosed at locally advanced or advanced stages. The R0 resection rate with surgical treatment alone is relatively low, and local recurrence and distant metastasis are prone to occur, resulting in a low 5-year survival rate. Recent research has focused on neoadjuvant therapy for esophageal cancer, but the most effective form of such therapy remains undetermined. Immunotherapy is currently the most active research field in tumor treatment. Further exploration of the treatment model combing immunotherapy with neoadjuvant chemotherapy or chemoradiotherapy is expected to improve the therapeutic effect and survival benefit in patients with locally advanced resectable esophageal squamous cell carcinoma.

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high global incidence rate, accounting for about 10.54% of all new cancer cases and posing a serious threat to human health. Due to significant individual variations in the efficacy of immunotherapy among NSCLC patients, it is necessary to identify accurate detection indicators to screen appropriate populations, monitor treatment efficacy, and assist in prognosis assessment. Programmed death-ligand 1 (PD-L1), as an immunosuppressive molecule expressed on the surface of tumor cells and various immune cell membranes, can serve as a "companion diagnostic" or "supplementary diagnostic" tool to guide clinical treatment decisions for metastatic NSCLC patients. Given that tumor tissue PD-L1 testing is an invasive procedure and its reliability is still under debate, the assessment of PD-L1 expression via liquid biopsies, such as circulating tumor cells, will play a significant role in predicting treatment response and prognosis in NSCLC patients.