Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2＞0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.

Objective Evaluation of the effect and mechanism research of Qi-Shen-Yi-Zhi formula on improving learning and memory ability in mice injected with Aβ1-42 in hippocampus.Methods Alzheimer's disease model mice were constructed by injecting β amyloid peptide 1-42 into hippocampus and treated with water extracts of Qi-Shen-Yi-Zhi formula.The cognitive abilities of mice were assessed using Morris water maze and Y maze tests,which measure learning and memory capabilities.HE staining was used to observe the damage and TUNEL method was used to determine apoptosis of hippocampus.Detection of the expression of oxidative factors,inflammatory factors,and related antioxidant proteins and apoptotic proteins in the hippocampal tissue of a mouse model of dementia.Results Both high-dose and low-dose groups of Qi-Shen-Yi-Zhi formula significantly improved cognitive dysfunction in mice injected with Aβ1-42 in hippocampus,and attenuated the damage and apoptosis of the hippocampus.It also inhibited oxidative stress and downregulated the expressions of inflammatory factors IL-6,IL-1β and TNF-a,increased the expression of antioxidant proteins Nrf2 and HO-1,and regulated the expressions of apoptotic proteins Caspase-9,Caspase-3,Bax and Bcl-2.Conclusion Qi-Shen-Yi-Zhi formula improves the learning and memory abilities of mice injected with Aβ1-42 in hippocampus,which might be related to the attenuation of oxidative stress and neuronal inflammation of hippocampus.

Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

Objective:To assess the impact of health insurance packaged payment in medical communities on the economicburden of patients,income and satisfaction of medical staff in counties.Methods:Using sample data from 2018-2022 from the national monitoring counties of medical communities,taking 2020 as the year of implementation of packaged payment,a double difference model was constructed with county population density and county per capita GDP as the control variables to assess the impact of packaged payment on the economic burden of patients,medical staff income and satisfaction in the county.Results:The packaged payment policy reduced the economic burden of patients to a certain extent and had a statistically significant positive effect on medical staff income in 2021,but it did not significantly increase the satisfaction of both supply and demand.Conclusion:The implementation of health insurance packaged payment of the MEC will not increase the economic burden of patients.It has a good pro-poor effect,and the income of medical staff has been improved to some extent,but there is still room for optimisation and improvement of the policy.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To compare the clinical outcomes of all-arthroscopic suture bridge fixation and posteromedial approach open reduction and internal fixation with screws for avulsion fractures of the posterior cruciate ligament (PCL) attachment in the knee joint. Methods A retrospective analysis was conducted on the clinical data of 45 patients with avulsion fractures of the PCL attachment in the knee who were admitted to the Orthopedics and Traumatology Joint Ward of Zhangjiagang Traditional Chinese Medicine Hospital of Jiangsu Province between April 2021 and July 2023. The patients were divided into arthroscopic group (undergoing all-arthroscopic suture bridge fixation) and open internal fixation group (undergoing posteromedial approach open reduction and internal fixation with screws) based on varied surgical approach they received. The operative time and length of hospital stay for both groups were recorded, and the Visual Analogue Scale (VAS) scores before surgery, at 1 month and 6 months after surgery were assessed. The International Knee Documentation Committee (IKDC) subjective score, Lysholm knee function score, and Hospital for Special Surgery (HSS) knee function score were used to evaluate knee function before surgery and at 6 months after surgery. At 6 months after surgery, the range of motion of the affected knee joint was recorded, and the posterior drawer test was performed to assess the degree of PCL injury. Results None of 45 patients experienced vascular or nerve injury intraoperatively, and there were no postoperative wound infections. X-ray examinations conducted 3 days after surgery showed good reduction of the fractures. All patients were followed up for 6 months. There were statistically significant differences in operative time, length of hospital stay and VAS scores at 1 month after surgery between the two groups (P < 0.05). However, there were no statistically significant differences in preoperative IKDC scores, Lysholm function scores, HSS knee function scores, range of motion at 6 months after surgery, and HSS scores between the two groups (P>0.05). There were statistically significant differences in IKDC scores and Lysholm function scores between the two groups at 6 months after surgery (P < 0.05). At 6 months after surgery, there were 16 cases with grade I injury and 6 cases of grade II injury in the arthroscopic group, and 15 cases of grade I injury and 8 cases of grade II injury in the open internal fixation group. There was no statistically significant difference in the degree of PCL injury between the two groups (Z=-0.538, P=0.591). Conclusion Both all-arthroscopic suture bridge fixation and posteromedial approach open reduction and internal fixation with screws can achieve satisfactory clinical outcomes in the treatment of avulsion fractures of the PCL attachment. However, arthroscopic surgery has shorter incision and hospital stays, and can relieve early postoperative knee pain, with more pronounced advantages in knee function recovery.

OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg-1·d-1)and Qishen Yizhi formula water extracts in low(1.33 g·kg-1·d-1)and high dose group(2.67 g·kg-1·d-1).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory fac-tors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula signifi-cantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi for-mula can improve the learning and memory ability of subacute aging model mice injected with D-galactose,which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.

OBJECTIVE To investigate the effect of Lycii Fructus-Chrysanthemi Flos herbal pair on the occurrence and progres-sion of light source-induced myopia in guinea pigs.METHODS The three-band fluorescent lamp was used to irradiate guinea pigs to establish a model of light source-induced myopia.Lycii Fructus-Chrysanthemi Flos herbal pair extract was added in the feed to raise guinea pigs.Ophthalmic A-type ultrasonic measuring instrument was used to detect the eye axis.HE staining was used to observe pathological damage to the retina of the guinea pigs.Enzyme-linked immunosorbent assay(ELISA)was used to detect dopamine(DA)and melatonin(MT)levels in guinea pig retinas,and transcriptomic analysis and other methods were used to explore the effects of Lycii Fructus-Chrysanthemi Flos on light-induced myopia in guinea pigs.RESULTS After 6 weeks,compared with the normal group,the eye axis of model group guinea pigs increased significantly(P<0.01),thus,the myopia model was successfully established.Lycii Fruc-tus-Chrysanthemi Flos herbal pair extract could effectively slow down the thickening of the lens and the deepening of the vitreous cavi-ty,thereby delaying the overgrowth of the eye axis in model guinea pigs.The retinal tissue of guinea pigs in the model group became thinner,the thickness and number of cells in the inner and outer nuclear layer of the retina were significantly reduced,the ganglion nu-clei were sparse,the vacuolization of the ganglion cell layer was obvious.Lycii Fructus-Chrysanthemi Flos extract could protect retinal cells.The thickness and cell number of the retinal inner nuclear layer and outer nuclear layer were increased,and ganglion cell nuclei were increased.ELISA assay showed that the concentrations of DA and MT in the retina of model group guinea pigs were significantly reduced(P<0.05),and the medium and high doses of Lycii Fructus-Chrysanthemi Flos herbal pair extract could effectively increase the concentration of dopamine in the retina and serum of guinea pigs in the model group(P<0.01,P<0.001).The differential genes screened by eye transcriptomics analysis were mainly enriched in PPAR signals pathway,collagen-containing extracellular matrix and other related pathways.ELISA results showed that the high dose of Lycii Fructus-Chrysanthemi Flos extract could significantly increase the content of PPARγ and COL1A1(P<0.01)and reduce the content of SMA(P<0.05).CONCLUSION The Lycii Fructus-Chry-santhemi Flos herbal pair extract has effects on delaying the occurrence and progression of light source-induced myopia in guinea pigs,protecting retinal cells,improving DA secretion disorders caused by artificial light environment,and regulating the level of PPAR,which has positive significance for the prevention and control of light source-induced myopia and provides a scientific basis for the ra-tional use of drugs in clinical practice and the creation of eye health products.

Evaluate the interventional effect of Lycium barbarum leaves extract on cataract rats and its effects on plasma and liver tissue metabolites. The ultimate goal is to explore the scientific connotation of Lycium barbarum leaves extract on vision improvement. All experiments were approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (202306A067). D-Galactose (D-gal) induced cataract model in rats was established. The lens opacity, lens and liver tissue pathology, level of oxidative stress and polyol metabolism regulation in the lens, level of oxidative stress in serum and liver tissue, and the content of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue were analysed to evaluate the effect of Lycium barbarum leaves extract on cataract. The metabolite profiles of plasma and liver tissue of rats were analyzed by UPLC-QTOF-MS/MS. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to compare and analyze the metabolic data in control group and cataract group, and screen potential biomarkers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that lens and liver pathology of cataract rats were improved after being intervened by the leaves extract of Lycium barbarum. The contents of AR and Ca²⁺ were significantly decreased in lens, and the contents of SDH and GSH and the ability of CAT were significantly increased; the content of GSH and the ability of SOD were significantly improved in serum and liver tissue, the content of MDA, the abilities of ALT and AST and the level of inflammatory factors were significantly reduced. The metabolomics results showed that there were 15 different metabolites in plasma and liver tissue of cataract rats, and 9 different biomarkers including retinyl ester, stearic acid, and palmitic acid, were returned by Lycium barbarum leaves extract. As revealed by pathway enrichment in plasma and liver tissue, it was found that the retinol metabolic pathway was mainly regulated by Lycium barbarum leaves extract. In summary, Lycium barbarum leaves can effectively alleviate the pathological changes of cataract, inhibit inflammation and improve antioxidant capacity, which may relate to the retinol metabolic pathway. It provides scientific basis and support for revealing the scientific connotation of the effect of Lycium barbarum leaves on vision improvement.