OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

Atherosclerosis （AS） is a chronic inflammatory pathological process in which lipid and/or fibrous substances are deposited in the intima of arteries， and it is one of the pathological bases of many cardiovascular and cerebrovascular diseases. Endoplasmic reticulum stress （ERS） is a protective mechanism of cell adaptation. Moderate ERS can reduce abnormal protein aggregation and increase the degradation of misfolded proteins to repair and stabilize the internal environment， while excessive ERS can cause unfolded protein reaction， activate inflammation， oxidative stress， apoptosis， autophagy， and other downstream pathways， and lead to cell damage， or even apoptosis. A large number of studies have shown that ERS mediates a variety of pathological processes related to AS， affects endothelial cells， smooth muscle cells， macrophages， endothelial progenitor cells， and other cell components closely related to its occurrence and development， influences the progress of AS by regulating cell function， and promotes the formation of AS plaque， the transformation of stable plaque to unstable plaque， and the rupture of unstable plaque. Regulation of ERS may be a key target for the prevention and treatment of AS， and it is a research hotspot at present. Traditional Chinese medicine （TCM） believes that the origin of AS is the imbalance of Yin and Yang， the disharmony of Zangfu organs， and the abnormal operation of Qi， blood， and body fluid， which leads to the accumulation of phlegm， blood stasis， and other pathological products in the pulse channels， making the blood flow blocked or misfunction and causing the disease， which belongs to the syndrome of deficiency in origin and excess in superficiality. As the pathogenesis of AS is complex， and the symptoms are diverse， TCM has significant advantages in treating AS because of its multiple targets， multiple pathways， stable efficacy， strong individualization， and high safety. This paper systematically elaborated on the role of ERS in the occurrence and development of AS and summarized the mechanism research on the regulation and control of ERS by Chinese herbal monomer， Chinese herbal extract， Chinese herbal compound， and proprietary medicine， so as to provide a theoretical basis for clinical research and drug development in the prevention and treatment of AS.

Diabetic nephropathy （DN） is one of the serious and common microvascular complications of diabetes mellitus （DM） and the main cause of end-stage renal disease （ESRD）. Endoplasmic reticulum stress （ERS） is a common stress defense mechanism in eukaryotic cells. In the ERS state， cells activate the unfolded protein response （UPR） to enhance the folding of unfolded proteins and the degradation of misfolded proteins， so as to restore the normal physiological function of the endoplasmic reticulum and avoid cell damage. However， excessive or chronic persistent ERS can induce apoptosis， inflammation， oxidative stress and other pathways to eventually cause cell damage. In recent years， a large number of studies have confirmed that ERS is closely associated with the occurrence and development of DN. In the case of DN， ERS is involved in the damage or protection of podocytes， glomerular mesangial cells， renal tubular epithelial cells， and glomerular endothelial cells. The regulation of ERS has become one of the hotspots in the prevention and treatment of DN and has received extensive attention in the field of traditional Chinese medicine. This paper systematically expounds the role of ERS in the occurrence and development of DN and summarizes the ERS-targeted regulation of DN by traditional Chinese medicine， with a view to providing certain research ideas for the prevention and control of DN with traditional Chinese medicine.

The basic pathological change of diabetic macroangiopathy is atherosclerosis （AS）， which is mainly associated with vascular endothelial cells （VECs） injury， oxidative stress， glucose and lipid metabolism disorders， hemorheological abnormalities， and endoplasmic reticulum stress. The injury and dysfunction of VECs are the initiating factors of diabetic macroangiopathy. Autophagy is a subcellular self-protection mechanism that regulates basic intracellular metabolism through lysosome-mediated degradation of proteins and damaged organelles to maintain homeostasis. Insufficient autophagy of VECs leads to enhanced inflammation， apoptosis， and oxidative stress of VECs， which promotes AS. According to the theory of traditional Chinese medicine （TCM）， diabetic macroangiopathy corresponds to the syndrome of internal deficiency and pathogen invasion， with Qi deficiency and stagnation as the key pathogenesis. Qi deficiency is the root cause， and Qi stagnation is the manifestation. The disease occurs with the initial cause of nutrient-defense disharmony and instability of vessels， the main cause of the deficiency of kidney Qi and the lack of source for generation and transformation， the internal cause of Qi and blood loss in the viscera and the stagnation of Qi， blood， and fluid， and the superficial cause of the stagnation of pathological products and the damage of vessels. Autophagy is a microscopic manifestation of Qi， which has the function of dispelling pathogens and maintaining homeostasis. Insufficient autophagy of VECs leads to Qi deficiency and stagnation， and the gradual deficiency and heavy stagnation of Qi lead to insufficient autophagy， which form a vicious cycle. Modern research has demonstrated that regulating the autophagy of VECs is the main way to prevent and treat AS， and TCM can exert the therapeutic effect in a multi-target and multi-pathway manner. Therefore， based on the theory of Qi deficiency and stagnation， the method of tonifying deficiency of and removing stagnation can be adopted to select prescriptions for regulating the autophagy of VECs and treating AS， which can slow down the procession of diabetic macroangiopathy.

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H₂O₂-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H₂O₂, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H₂O₂ levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE^‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H₂O₂-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

The basic pathological change of diabetic macroangiopathy is atherosclerosis， and the metabolism legacy effect of hyperglycemia will cause continuous damage to the large vessels. Oxidative stress is a common mechanism for diabetes and its chronic complications and it is also the basis of the metabolism legacy effect which keeps damaging the large vessels. Anti-oxidant therapy can delay the course of diabetic macroangiopathy. According to the theory of traditional Chinese medicine （TCM）， the pathogenicity of hidden pathogen is concealing， lingering， and refractory. On the basis of the syndrome and treatment of collateral diseases， vessel-collateral theory， and hidden pathogen theory of TCM， the pathological changes of diabetic macroangiopathy are summarized as pathogen concealment-accumulation of sugar and lipids leading to phlegm and blood stasis-accumulation of toxins-damage to vessels and collaterals-hardening vessels. The core pathogenesis is the hidden pathogen damaging the collaterals， and the basic pathological change is vessel hardening. The toxins of sugar， lipid， phlegm， and stasis are the pathological products and the key to be treated. According to this theory， the medicinal materials with the functions of activating blood to dredging collaterals， resolving phlegm to clearing collaterals， Promoting qi to unblocking collaterals and removing toxins to shunting collaterals can be selected for prescription. These medicinal materials can inhibit the generation of reactive oxygen species， affect the oxidase activity， and enhance the antioxidant capacity， thereby regulating the oxidative stress response， protecting the vascular endothelial function， reducing the damage of the large blood vessels， and slowing down the progression of the disease. Such therapy is of great significance in clinical practice and research， providing a new idea for the prevention and treatment of diabetic macroangiopathy.

Objective:To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy.Methods:Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary micro-bubble SonoVue by biotin-avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time intensity curve was used to analyse rat kidney perfusion characteristics in different groups. Results:Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased(P<0.05); the peak intensity of medulla increased (P<0.05), and the total area under the curve of medulla increased (P<0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P<0.05). The peak intensity of the curve increased (P<0.05), and the total area under the curve increased (P<0.05). Compared with the ordinary angiography group, the peak of GK rat medullacurve in targeted angiography group intensity increased (P<0.05), and the total area under the curve increased (P<0.05).Conclusions:Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Objective To investigate the characteristic of MRS in patients suffered diffuse axonal injury (DAI)in acute and suba-cute stage,and the correlation between MRS changes and the severity of disease.Methods We reported MRI and proton magnetic resonance spectroscopy studies of 3 6 head-inj ured patients in acute and subacute stage.Proton magnetic resonance spectra were ac-quired from the white matter and gray matter of bibateral frontal lobe that on conventional MRI appeared normal by using 2D MRSI at 3.0T MRI .30 volunteers as contronl were studied at the same time.Results In patient group,N-acetylaspartate/creatine ratios were (2.14±0.15)and (1.71±0.08)choline/creatine ratios were(1.35±0.13)and (1.03±0.08)for the white matter and the gray matter,respectivily.The brain N-acetylaspartate/creatine ratio was reduced and the choline/creatine ratio was increased in pa-tient group compared with the controls.The increase in the choline/creatine ratio was significant even in the moderate and severe in-j ured groups.Furthermore,there was a significantly correlation between the severity of head inj ury and the N-acetylaspartate/cho-line ratio,and changes in patients with metabolite ratios of the GCS score had a strong correlation.Conclusion We conclude that DAI patients with normal conventional imaging manifestations of the frontal lobe appear metabolite ratio change,suggesting the existence of local cerebral inj ury,and it has a strong correlation between the prognosis and MRS changes.MRS may provide an useful method that can tell us the severity of the brain inj ury in patients with DAI .

Objective To investigate the protective effect of the myocaidial ischemic postconditioning on ischemic-reperfused myocardium of rat and its signaling mechanism.Methods Healthy SD rats weighing 250 to 300 g were divided into blank control(N) group,ischemiareperfusion(IR) group and postconditioning(Post) group.We measured heart coronary perfusion flow and myocardial infarct size of the rats in each group.The expression of phosphorylated protein kinase B(P-Akt) was detected by Western blot.The morphological changes of myocardial fibers and mitochondrial were observed under the transmission electron microscopy.Results More coronary flow and less myocardial infarction were found in Post group than those in IR group.The expression level of P-Akt was higher in Post group.The integrity of myocardial fibers and mitochondrial was better in Post group than IR group.Conclusion Postconditioning had a protective effect for the ischemic isolated rat heart.Akt activation might play an important role in its mechinism.

Objective This study describes the protective effect of myocardial isehemic post- conditioning on ischemic-reperfused myocardium (I/ R) of diabetic rat and its Signaling mechanism. Methods Healthy SD rats weighing 25O-30Og were divided into 6 groups; (1) Blank control; (2) Ischemia-reperfusion; (3) Post conditioning; (4) Diabetic postconditioning ; (5) Diabetic ischemia-reperfusion; ( 6) Diabetic blank control group. Ten rats in each group were randomly selected. Introduction of diabetic rat model: 65 mg/kg STZ was injected into the intraperitoneal cavity, until 2 consecutive blood glucose measurements≥ 16.65 mmol/L were reached after48h. The diabetic model was successful when rats had following symptoms, such as more drinking, more eating, polyuria, weight loss and epilation. Langendorff isolated rat heart perfusion was used for the experiment. Following parameters were measured and compared: Coronary perfusion flow, myocardial infarct size, western blot for measurement of P-Akt, changes in myocardium and mitochondrian observed by Electron microscopy. Results Blood glucose concentration in diabetic group was (23. 15±2. 16) mmol/L and (4. 16±0. 31) mmol/L in non-diabetic group. There was a significant difference (P <0. 01) between the two groups. There were more coronary flow in post-conditioning groups (Post group and Dpost group) than ischemia-reperfusion groups (IR group and DIR group) (6.5±1.2、5.6±1.0 vs. 3.4±1.0、2.0±1.3). The myocardial infarction size was smaller in post-conditioning groups than in ischemia-reperfusion groups (25.2±2.1、34.2±3.6 vs. 47.5±3.5 、65.2±4.5). There was more expression of P-Akt and the myocardial fibers and mitochondrian in post-conditioning groups were better preserved. Conclusion Postconditioning has protective effects in diabetic rat hearts. The mechanism may be associated with Akt activation.