ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg^-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg^-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

Moyamoya disease (MMD) is a cerebrovascular disorder characterized by a steno-occlusive internal carotid artery and compensatory vascular network formation. Although the precise pathogenic mechanism remains elusive, genetic association studies have identified RNF213 as the principal susceptibility gene for MMD, with the single nucleotide polymorphism p.R4810K recognized as the founder variant predominantly in the Asian populations. Distinct genotype-phenotype correlations are observable in RNF213-related MMD. The clinical manifestations linked to p.R4810K bear commonalities within Asian cohort, including familial predisposition, earlier age of onset, ischemic episodes, and involvement of the posterior cerebral artery (PCA). However, despite these shared phenotypic characteristics, there is significant heterogeneity in RNF213-related MMD presentations. This diversity manifests as variations across ethnic groups, inconsistent clinical symptoms and prognosis, and occurrence of other vasculopathies involving RNF213. This heterogeneity, in conjunction with the observed low disease penetrance of RNF213 mutations, suggests that the presence of these mutations may not be sufficient to cause MMD, underscoring the potential influence of other genetic or environmental factors. Although the current research might not have fully identified these additional contributors, experimental evidence points toward the involvement of RNF213 in angiogenesis, lipid metabolism, and the immune response. Future research is required to unveil the molecular mechanisms and identify the factors that synergize with RNF213 in the pathogenesis of MMD.

Phlegm-dampness syndrome is a common syndrome type of rheumatoid arthritis (RA), which is closely related to spleen dysfunction. Combined with the understanding of modern medicine on the pathogenesis of phlegm dampness and spleen dysfunction, it is believed that the important factors to promote the development of RA include inflammation related to lipid metabolism disorders, abnormal glucose regulation, and intestinal flora imbalance. Improper diet or external factors lead to glucose and lipid metabolism disorders and affect the imbalance of intestinal microbiota, causing damage to the intestinal mucosal barrier. The metabolites produced promote endogenous glucose and lipid metabolism imbalance and inflammatory response, thus forming the biological basis of RA with phlegm dampness syndrome. The method of invigorating spleen, removing dampness and resolving phlegm can correct the disorder of glucose and lipid metabolism in the body. It can also adjust endogenous glucose and lipid metabolism and inhibit RA inflammation by improving the composition of intestinal flora in RA patients, thus playing a therapeutic role.

Post-stroke cognitive impairment (PSCI), one of the important complications of stroke, seriously affects the quality of life of these patients. PSCI is an important cause of disease burden of stroke. In recent years, more and more evidences show that blood biomarkers are of great significance in PSCI diagnosis, and the detection of blood biomarkers is relatively simple and more suitable for clinical application. Therefore, this paper sorts out the values of 5 blood biomarkers, nerve injury marker, metabolic biomarker, inflammatory biomarker, oxidative stress marker and other biomarker, in diagnosing PSCI, to provide references for early diagnosis and intervention of PSCI.

Objective:To evaluate the complications of complex intracranial aneurysms after intervention with flow-diverter (FD) devices.Methods:Sixty patients with complex intracranial aneurysms accepted FD devices in Department of Cerebrovascular Diseases, Second Affiliated Hospital of Guilin Medical University from July 2018 to June 2021 were chosen. Clinical and imaging data of these patients were retrospectively analyzed, and complications were recorded: procedure-related adverse events, early postprocedural complications, complications during follow-up, and covered branch occlusion.Results:A total of 61 FD devices (47 Pipeline Flex, 10 Tubridge, 4 Surpass Streamline) were implanted in 60 patients. Incidence of procedure-related adverse events was 8.3% (5/60), including 3 with incomplete stent apposition, 1 with intraoperative bleeding, 1 with aneurysm neck not covered by stent; incidence of early postprocedural complications was 6.7% (4/60), including 3 with hemorrhagic complication and 1 with ischemic complication. DSA follow-up ([22.7±16.8] months) was completed in 54 patients; aneurysm healed rate was 83.3% (45/54). First DSA follow-up 6 months after surgery showed that in-stent restenosis was 7.4% (4/54), of which 2 deteriorated to parent vessel occlusion at 2- and 3-year after procedure, respectively. A total of 78 branch arteries were covered by FD devices, and only 1 (1.3%, 1/78) demonstrated branch artery occlusion at last follow-up, without clinical symptoms.Conclusion:The complications of complex intracranial aneurysms after intervention with FD devices should be recognized; incomplete stent apposition is the main procedure-related adverse event, and hemorrhagic complication mainly appear in the early postprocedural period; in-stent restenosis should be vigilant during follow-up.

RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers. However, efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging. Recently, more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating. Due to the flexibility and deformability of nucleic acids, the nanoassemblies could be fabricated with different shapes and structures. With hybridization, nucleic acid nanoassemblies, including DNA and RNA nanostructures, can be applied to enhance RNA therapeutics and diagnosis. This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.

OBJECTIVE To establish a method for simultaneous determination of atorvastatin （ATV） and its active metabolites 2-hydroxy atorvastatin acid （2-HAT）， 4-hydroxy atorvastatin acid （4-HAT） and toxic metabolite atorvastatin lactone （ALT） in rat plasma and apply it for pharmacokinetic study. METHODS LC-MS/MS method was adopted for analysis. The one-step precipitation method was used for processing plasma samples （plasma samples were pretreated by acidification to adjust pH value so as to prevent inversion of configuration）， gradient elution was used to analyze the samples， and the analysis time was 5 min. Electrospray positive ionization was adopted， and positive ion scanning was performed in multi-reaction monitoring. The m/z of quantified ion pairs of ATV and its metabolites such as 2-HAT， 4-HAT and ATL， and internal standard pitavastatin were 559.3→ 440.2， 575.2→440.3， 575.0→440.2， 540.9→448.2 and 422.2→290.0， respectively. After conducting a comprehensive methodological investigation of the analytical method， the concentrations of ATV and its metabolites 2-HAT， 4-HAT，and ATL were determined， and the pharmacokinetic parameters of ATV and its metabolites were calculated using the non- compartment model of WinNonlin 6.1. RESULTS The results of methodological validation showed that endogenous substances in blank plasma did not interfere with the determination of the components to be tested， and the standard curve had a good linear relationship； the lower limits of quantification for ATV， 2-HAT， 4-HAT and ATL were 0.5， 0.5， 0.25 and 0.063 nmol/L， respectively. The precision， accuracy， recovery， matrix effect and stability investigation were all in line with the requirements of biological analysis. Pharmacokinetic analysis showed that after intragastric administration in rats， ATV calcium metabolized rapidly， and was mainly exposed to blood circulation in the form of ATV and 2-HAT， with the lowest concentration of lactone-type metabolites. CONCLUSIONS The established method is precise， rapid and accurate for plasma concentration analysis of ATV and its active/toxic metabolites. The application of the method could help to fully elucidate the pharmacokinetic characteristics of atorvastatin calcium in rats.

Objective:To observe the effect of Ginsenoside Re on the proliferation and protein secretion of primary cardiac fibroblasts (CFs) cultured in high glucose by vitro, and the regulation of Wnt/β-catenin signaling pathway.Methods:The myocardial fibroblast proliferation model induced by high glucose in vitro was used. Cell proliferation was detected by MTT method, cell cycle was measured by flow cytometry, concentration of type Ⅰ,Ⅲ collagens and TGF-β 1 protein were tested by ELISA assay. Protein expression of β-catenin, GSK-3β and p-GSK-3β were determined by Western blot. Results:Compared with the model group, the cell proliferation in Ginsenoside Re high, medium, low group were significantly decreased ( P<0.01), the percentage of cells in G 0 + G 1 phase was increased ( P<0.01), and the percentage of cells in S + G 2 + M phase was decreased ( P<0.01), the content of TGF-β 1 was significantly decreased( P<0.01). The content of type Ⅲ collagen [(6.566±1.620)ng/ml,(7.170±0.470)ng/ml vs. (11.241±2.234)ng/ml] in Ginsenoside Re high, medium group were significantly decreased ( P<0.01). The expression of β-catenin (0.281±0.016, 0.301±0.021 vs. 0.409±0.037) was significantly decreased and the expression of p-GSK-3β (0.369±0.049 vs. 0.268±0.048) in Ginsenoside Re high, medium group were significantly increased ( P<0.01). Conclusion:Ginsenoside Re plays an important role in inhibiting CFs proliferation and reducting the synthesis of collagen and TGF-β 1 by regulating abnormal expression of Wnt/β-catenin signaling pathway. It has the potential to delay the myocardial fibrosis of diabetes mellitus.

Objective:To compare the effects of dexmedetomidine combined with propofol on anesthesia and thromboelastography in patients undergoing radical gastrectomy.Methods:From September 2017 to December 2019, 120 patients undergoing radical gastrectomy in Chaoyang Central Hospital were prospectively selected and divided into control group and observation group according to random number table method, with 60 cases in each group.The two groups used the same drugs before induction and the same way of anesthesia induction. During the maintenance of anesthesia, remifentanil and propofol were injected intravenously in the control group, and dexmedetomidine was injected in the observation group on the basis of the control group. The indexes of thromboelastography, preoperative and postoperative cellular immune function, postoperative analgesic effect [Visual Analogue Scale (VAS)], Ramsay sedation score, and postoperative adverse reactions were compared between the two groups at different times.Results:The reaction time of coagulation factor (R) and fibrinogen (K) in the two groups decreased 3 hours after operation, and those in the observation group were lower than those in the control group (all P<0.05); The maximum thrombus amplitude (MA) of the two groups increased 3 hours after operation, and MA in the observation group was higher than that in the control group (all P<0.05). Compared with that before operation, the VAS scores and Ramsay sedation scores in the control group and the observation group at 24 h and 48 h after operation were significantly lower (all P<0.05), and the VAS scores and Ramsay sedation scores in the observation group at 24 h and 48 h after operation were significantly lower than those in the control group (all P<0.05). Compared with that before operation, the CD4 +, CD8 +, CD4 + /CD8 + in the control group and the observation group were improved at 6 h and 48 h after operation (all P<0.05), and the improvement in the observation group was significantly better than that in the control group at 6 h and 48 h after operation (all P<0.05). The incidence of adverse reactions in the control group was 6.67%(4/60), which was slightly higher than that in the observation group of 5.00%(3/60), but the difference was not statistically significant ( P>0.05). Conclusions:Compared with propofol and remifentanil alone, combined application of dexmedetomidine can help patients undergoing radical gastrectomy for gastric cancer to achieve better analgesic effect, improve the blood coagulation state of patients, and play a better regulatory role on cellular immune function, which is worthy of further promotion in clinic.

ObjectiveTo investigate the effects and underlying mechanism of Yinxing Mihuan oral solution （YM） on neovascularization and vascular remodeling in chemical photothrombosis-induced focal cerebral ischemia model in mice. MethodFifty SPF C57BL/6J mice were randomly divided into sham group， model group， ginaton group （12.5 mg·kg^-1）， and low- （YM-L， 412 mg·kg^-1） and high-dose （YM-H， 824 mg·kg^-1） YM groups， with 10 mice in each group. The focal cerebral ischemia model was established by chemical photothrombosis method. Drugs in each group were administered by gavage for 14 consecutive days after operation. The modified neurological severity score （mNSS） and measurement of forelimb grasping were used to evaluate the neurologic impairment of mice. The vascular density of infarct border-zone （IBZ） was measured by fluorescein labelled dextran （FITC-dextran） method. The morphology of IBZ was evaluated and observed by hematoxylin-eosin （HE） staining. The expression of proteins related to neovascularization and vascular remodeling in brain tissues， including vascular endothelial growth factor （VEGF）， platelet and endothelial cell adhesion molecule 1 （CD31）， hypoxia-inducible factor-1α （HIF-1α）， von Willebrand factor （vWF）， and angiogenin （ANG）， was detected by Western blot. ResultCompared with the sham group， the model group showed manifest neurological deficits （P<0.01）， weakened forelimb grasping （P<0.01）， increased vascular density of IBZ （P<0.01）， and obvious pathological changes， such as neuronal necrosis and gliocyte proliferation. After treatment for 14 days， compared with the model group， the YM-H group showed improved neurological deficits （P<0.01）， and the YM-L group and the YM-H group showed strengthened forelimb grasping （P<0.01）. Moreover， the YM-L group displayed increased vascular density of IBZ （P<0.05）， reduced pathological damage， and up-regulated protein expression of CD31， ANG， HIF-1α， and vWF （P<0.05， P<0.01）. ConclusionYM could improve motor function and pathological morphological impairment in chemical photothrombosis-induced focal cerebral ischemia mouse model， and the underlying mechanism might be related to the promotion of neovascularization and vascular remodeling in IBZ.