ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

OBJECTIVES: To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification. METHODS: C57BL/6J mice were randomized into blank control group, catalpol group, triptolide group and triptolide+catalpol group. After 13 days of treatment with the agents by gavage, the mice were examined for liver tissue pathology, liver function, hepatocyte subcellular structure, lipid peroxidation, ferrous ion deposition and expressions of ferroptosis-related proteins in the liver. In a liver cell line HL7702, the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions, Fe²⁺ concentration, lipid peroxidation, ROS level and the ferroptosis-related proteins. RESULTS: In C57BL/6J mice, catalpol significantly alleviated triptolide-induced hepatic injury, lowered the levels of ALT, AST and LDH, and reversed the elevation of Fe²⁺ concentration and MDA level and the reduction of GP_X level. In HL7702 cells, inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT, AST and LDH levels. Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11, FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells. CONCLUSIONS The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
Animals ; Phenanthrenes/toxicity* ; Ferroptosis/drug effects* ; Diterpenes/toxicity* ; Epoxy Compounds/toxicity* ; Mice, Inbred C57BL ; Hepatocytes/metabolism* ; Mice ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Iridoid Glucosides/pharmacology* ; Liver/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Male ; Amino Acid Transport System y+/metabolism*

Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

Objective: To investigate the efficacy and incidence of adverse reactions of therapeutic erythrocytapheresis in high altitude polycythemia (HAPC) population. Methods: A retrospective study was conducted on 243 HAPC patients who were either native residents or long-term workers in Xizang and underwent therapeutic erythrocytapheresis in the Chengdu Office Hospital of the People's Government of Xizang Autonomous Region from 2021 to 2023. A comparative study was carried out on the changes in blood routine, vital signs, skin color, serum iron metabolism data, and the incidence of adverse reactions before and after the procedure. Results: After erythrocytapheresis, significant decreases were observed in red blood cell (RBC) count (7.06±0.89×10 vs 6.08±0.93×10 /L, P<0.001], hemoglobin (HGB, 211.59±17.99 vs 182.76±19.83 g/L, P<0.001), hematocrit (Hct) [(65.30±6.45)% vs (55.56±8.12)%, P<0.001], serum iron (14.46±4.38 vs 11.77±3.78 μmol/L, P=0.003), total iron-binding capacity (126.62±4.47 vs 123.73±3.77 μmol/L, P=0.002), transferrin (1.88±0.41 vs 1.77±0.12 g/L, P=0.023), transferrin saturation [(11.32±3.11)% vs (9.43±2.78)%, P=0.004], serum ferritin (832.4±295.6 vs 665.3±249.2 ng/mL, P<0.001), systolic blood pressure (123.86±14.43 vs 118.51±13.68 mmHg, P<0.001) and diastolic blood pressure (81.68±9.54 vs 74.28±7.61 mmHg, P<0.001). In contrast, platelet count (Plt, 137.21±46.21 ×10 vs 147.94±50.66 ×10 /L, P<0.001) and oxygen saturation [(93.97±3.29)% vs (95.84±2.27)%, P<0.001] increased. No significant differences were found in white blood cell (WBC) count [5.35 (4.59, 6.44)×10 /L vs 5.43 (4.54, 6.53) ×10 /L, P=0.690], unsaturated iron-binding capacity (112.15±0.50 vs 111.96±0.25 μmol/L, P=0.074) and pulse rate (73.42±11.28 vs 73.19±7.18 beats/min, P=0.750). Furthermore, skin color of the face (conjunctiva, lips) and palms mitigated after therapeutic erythrocytapheresis, changing from purplish-red to red. The total incidence of adverse reactions during erythrocytapheresis was 13.98% (34/243), including citrate toxicity 12.75% (31/243), puncture site hematoma 0.82% (2/243) and blood volume imbalance 0.41% (1/243). Conclusion: Therapeutic erythrocytapheresis could rapidly decrease HCT, Hb, serum iron, transferrin and transferrin saturation levels in HAPC patients, with a low incidence of adverse reactions. Therefore, therapeutic erythrocytapheresis has broad clinical application prospects in Xizang Autonomous Region.