Diabetic kidney disease （DKD） is one of the most common and harmful microvascular complications of diabetes， and there is currently a lack of effective treatment methods to delay its progression. Traditional Chinese medicine has a long history of treating DKD and offers unique advantages. As a traditional Chinese medicine， Rehmannia glutinosa has shown potential in the treatment of DKD in clinical and modern pharmacological research. After integrating relevant research on the pharmacological mechanism of R. glutinosa in treating DKD， it has been found that the main active components of R. glutinosa， such as catalpol， rehmannioside D， aucubin， verbascoside， salidroside， echinacoside and R. glutinosa polysaccharides， along with its extracts and compounds （such as Liuwei dihuang pills， Shenqi dihuang decoction， and Shenqi pills）， can exert multiple effects by intervening in various signaling pathways， including advanced glycation end product （AGE）/receptor for AGE， nuclear factor kappa-B （NF- κB）， and transforming growth factor-β1 （TGF-β1）/Smads. These effects include ameliorating metabolic disorders and oxidative stress in DKD， inhibiting the processes of renal inflammation and fibrosis， regulating cell death modalities including apoptosis and ferroptosis， as well as autophagy， and reshaping the gut microbiota. Consequently， it can improve physical and chemical indices and renal tissue pathological damage， thus delaying the progression of DKD.

Objective To explore the effect of scutellarin(SCU)through regulation of nuclear transcription factor kappa B(NF-κB)p65 signaling pathway on the proliferation and migration of gastric cancer cells line MGC803.Methods To select SCUs with concentrations of 100,250,and 500 nmol/L for subsequent experiments;MGC803 gastric cancer cells were separated into a control group,SCU-L group(100 nmol/L),SCU-M group(250 nmol/L),SCU-H group(500 nmol/L),SCU-H+PMA group(NF-κB activator,200 nmol/L PMA).Cell plate cloning experiments were applied to detect cell proliferation.Scratch healing experiment was used to detect the migration of MGC803 cells;Tran swell assay was used to detect the invasive ability of MGC803 cells;Enzyme linked immuno-sorbent assay(ELISA)was used to detect the level of IFN-γ,IL-4,and IL-10 in the supernatant of MGC803 cells;Western blot detection of NF-κB p65 pathway related protein expression.Results SCU inhibited proliferation of MGC803 in a concentration dependent manner.SCU concentrations of 100,250,and 500 nmol/L were selected for subsequent experiments.Compared with the control group,the number of cell clones formed,scratch healing rate,number of invasive cells,IL-10 level and p-p65/p65 ratio all decreased in SCU-L group,SCU-M group,and SCU-H group,while IFN-γ and IL-4 increased(P＜0.05).Compared with the SCU-H group,the number of cell clones,scratch healing rate,number of in-vasive cells,IL-10 level,and p-p65/p65 ratio obviously increased in the SCU-H+PMA group,while IFN-γ and IL-4 level significantly reduced(P＜0.05).Conclusions SCU may inhibit the proliferation and migration of gastric cancer cell line MGC803.

Objective:To assess the prognostic value of cerebrospinal fluid (CSF) neuron specific enolase (NSE) combined with protein content in predicting poor prognosis in patients with intraventricular hemorrhage after external ventricular drainage (EVD).Methods:The clinical data of 73 intraventricular hemorrhage patients underwent EVD in the Second Affiliated Hospital of Wenzhou Medical University from February 2019 to January 2022 were retrospectively analyzed. After 90 d of surgery, 37 patients (good prognosis group) had a modified Rankin score of 0 to 2, while 36 cases (poor prognosis group) had a score of 3 to 5. The baseline characteristics including gender, age, hypertension, diabetes and Glasgow coma score (GCS) upon admission were recorded. The peripheral blood samples were collected within 24 h of admission to measure C-reactive protein, white blood cell and blood potassium. The CSF samples were obtained within 24 h after EVD to measure NSE, protein content, white blood cell and red blood cell. Binary Logistic regression analysis was used to analyze the independent risk factors of poor prognosis in patients with intraventricular hemorrhage after EVD. The efficacy of CSF NSE combined with protein content in predicting the poor prognosis in patients with intraventricular hemorrhage after EVD was evaluated by the receiver operating characteristics (ROC) curve.Results:There were no statistical differences in gender distribution, age, hypertension, diabetes, blood C-reactive protein, white blood cell and blood potassium between two groups ( P>0.05); the GCS upon admission in poor prognosis group was significantly lower than that in good prognosis group: (5.83 ± 0.20) scores vs. (9.54 ± 0.43) scores, the CSF NSE, protein content, white blood cell and red blood cell were significantly higher than those in good prognosis group: (377.94 ± 21.91) μg/L vs. (86.43 ± 11.96) μg/L, (16.70 ± 2.07) g/L vs. (2.92 ± 0.74) g/L, (731.61 ± 141.36) × 10 6/L vs. (302.16 ± 90.99) × 10 6/L and (410 332 ± 88 584) × 10 6/L vs. (156 075 ± 61 387) × 10 6/L, and there were statistical differences ( P<0.01 or <0.05). Binary Logistic regression analysis result showed that elevated CFS NSE and higher CSF protein content were independent risk factors of poor prognosis in patients with intraventricular hemorrhage after EVD ( OR = 1.053 and 1.270, 95% CI 1.005 to 1.103 and 1.020 to 1.581, P<0.05). ROC curve analysis result showed that the area under the curve of CFS NSE combined with protein content detection to predict the poor prognosis in patients with intraventricular hemorrhage after EVD was larger than that of CFS NSE and protein content alone detection (0.982 vs. 0.971 and 0.903), and the optimal cutoff values of CSF NSE and protein content were 233.090 μg/L and 1.425 g/L, respectively. Conclusions:CSF NSE and protein content are significantly elevated in patients with intraventricular hemorrhage after EVD. The combined detection of CSF NSE and protein content provides valuable prognostic information for prognosis in patients with intraventricular hemorrhage after EVD, and it can provide important basis for prognosis evaluation.

Objective:To analyze the incidence trend and epidemiological characteristics of typhoid fever in Fujian Province from 2011 to 2022, and understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures.Methods:The surveillance data of typhoid fever during 2011-2022 in Fujian Province were obtained from the National Disease Reporting Information System and analyzed with SAS 9.4. The spatial autocorrelation analysis of typhoid fever incidence at county/district levels was performed with ArcGlS 10.8.Results:A total of 5 126 cases of typhoid fever were reported in Fujian Province from 2011 to 2022, with an average annual incidence rate of 1.10/100 000. The average annual incidence rate was 0.96/100 000 from 2011 to 2015, 1.49/100 000 from 2016 to 2019, and 0.81/100 000 from 2020 to 2022. The disease occurred all the year round, with high epidemic season from May to September. A total of 23.59% (1 209/5 126) of the cases occurred at the age of 0-4, and 9.62% (493/5 126) at the age of 5-9. The male to female ratio of the cases was 0.97∶1 (2 524∶2 602) for the whole population, 1.19∶1 (925∶777) for people under 10 years old, 0.75∶1 (1 060∶1 404) for people between 10 and 54 years old, and 1.28∶1 (539∶421) for people over 55 years old. Cases in Ningde City accounted for 30.65% (1 571/5 126) of the total cases. Most hotspots were occurred in Ningde City. Recurrent and clustered cases were found in family members.Conclusions:Typhoid fever was prevalent at a low level in Fujian Province during 2011-2022, indicating that strengthening the prevention and control measures should target key areas and populations. The incidence of typhoid fever in Fujian Province showed spatial aggregation phenomenon, and most cases gathered in Ningde City. Intensive study for the influencing factors of spatial clustering should be conducted.

Objective To observe the therapeutic effect of laparoscopic sleeve gastrectomy (LSG) in treating patients with obesity and polycystic ovary syndrome (PCOS). Methods In this retrospective analysis, clinical materials of 60 patients with obesity and PCOS by LSG were analyzed, and postoperative improvements of PCOS symptoms were observed. Results A total of 60 patients had a preoperative mean body mass index (BMI) of (39.4±5.4) kg/m² and an average age of (26.3±6.1) years old, and all of them successfully completed LSG. After follow-up of 12 to 18 months, 50 cases (83.3%) had normalized menstrual cycles, with an average recovery time of (4.5 ±2.2) months after surgery, and 7 cases had natural pregnancy after surgery. Before surgery, ultrasound results in 35 patients indicated polycystic ovarian morphology (PCOM), and 29 cases (82.9%) regained normal ovarian status with an average recovery duration of (6.3±2.8) months. Complicated hyperandrogenemia was observed in 31 patients, and 29 cases (93.5%) exhibited normalization of testosterone levels within 18 months after surgery. At 18 months after surgery, the BMI was (26.47±4.70) kg/m², the average weight loss was (32.4±7.4) %. Conclusion LSG is a safe and effective treatment for obese PCOS.

Abstract OBJECTIVE To explore the material basis and mechanism of Crataegi Fructus in improving metabolic hypertension(MH) by using network pharmacology and molecular docking technique.METHODS The components of Crataegi Fructus were collected by HERB, ETCM database and literature survey; screening all ingredients of Crataegi Fructus to improve MH targets through databases such as SwissTargetPrediction and GeneCards; build "active ingredient-target-disease" network of Crataegi Fructus with Cytoscape software; DAVID was used to analyze GO enrichment and KEGG pathway. The core components and core targets were verified by molecular docking with Autodock software. RESULTS The total of 89 active components were screened from Crataegi Fructus and acted on 84 targets. Among them, the core active components of Crataegi Fructus to improve MH were maslinic acid, fomefficinic acid B, linolenic acid, linoleic acid, methyl-n-nonylketone, apigenin, ursolic acid, etc. The core targets were CYP19A1, PPARA, ESR1, PTGS2, PPARG, NR3C1, MMP9, TNF, etc. The mechanism of action mainly involved multiple signaling pathways such as inflammation, glycolipid metabolism, and vascular endothelial function. Molecular docking showed that the core active ingredients of Crataegi Fructus had high affinity with core targets. CONCLUSION Crataegi Fructus may regulate multiple signaling pathways such as TNF, IL-17, AGE-RAGE, HIF-1, cGMP-PKG through multi-component regulation, thereby inhibiting inflammatory response, improving glucose and lipid metabolism abnormalities, and improving vascular endothelial function, so as to comprehensively exert the role of improving MH in various aspects.

Objective    To investigate the effect of simvastatin and mechanical pretreatment on intimal hyperplasia of venous graft and its mechanism. Methods    Twelve New Zealand rabbits were selected and randomly divided into 4 groups: a blank control group, a simvastatin topical treatment group, a mechanical precondition group and a combined group (n=3 in each group). Ultrasound was used to evaluate the changes of graft wall and blood flow velocity in the graft, and pathological section was used to evaluate the intimal hyperplasia. Human umbilical cord endodermal cells were cultured in vitro. A simvastatin group and a solvent control group were set to detect YAP phosphorylation, downstream target gene expression and cell proliferation. Results    Vascular ultrasound showed that except the simvastatin topical treatment group, the flow velocity in vein grafts in the other three groups significantly increased 21 days after surgery compared with 7 days after surgery (P<0.01). Pathological sections showed that the thickness of new intima in the simvastatin topical treatment group, mechanical precondition group, combined group and blank control group were 45.56±4.11 μm, 201.28±16.71 μm, 143.57±7.82 μm, 249.45±13.33 μm, respectively, and there were statistical differences compared with the blank control group (P<0.05). In vitro results showed that compared with the solvent control group, cell death was observed in high concentration simvastatin (5 mmol/L) group, cell proliferation was inhibited in low concentration simvastatin (2.5 mmol/L) group (P<0.05), the expression of YAP protein in the simvastatin group was unchanged, but the expression of phosphorylated YAP protein significantly increased (P<0.05), and the expression of downstream target gene ccn1 was down-regulated (P<0.001). Conclusion    Intravascular local application of simvastatin and mechanical preconditioning alone or in combination can inhibit intimal hyperplasia of venous graft. High concentration of simvastatin has cytotoxicity, while low concentration of simvastatin has inhibitory effect on cell proliferation. Simvastatin can inhibit the formation of new intima by inhibiting the entry of YAP into the nucleus and reducing the transcription of cell proliferation-related target gene ccn1.

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects.This study aimed to explore its radio-sensitizing effects and the underlying mechanisms.Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis.Bioinformatic molecular docking prediction and following validation by surface plasmon resonance(SPR)technology,cellular thermal shift assay(CETSA),and isothermal titration calorimetry(ITC)were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha(HSP90α).The effects of ginsenoside Rg5 on HSP90-cell division cycle 37(CDC37)interaction,the client protein stability,and the downstream regulations were further explored.Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis.It could bind to HSP90α with a high affinity,but the affinity was drastically decreased by HSP90α Y61A mutation.Co-immunoprecipitation(Co-IP)and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner.It reduced irradiation-induced upre-gulation of the HSP90-CDC37 client proteins,including SRC,CDK4,RAF1,and ULK1 in A549 cell-derived xenograft(CDX)tumors.Ginsenoside Rg5 or MRT67307(an IKKe/TBK1 inhibitor)pretreatment suppressed irradiation-induced elevation of the LC3-Ⅱ/β ratio and restored irradiation-induced downregulation of p62 expression.In A549 CDX tumors,ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage.In conclusion,ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma.It interacts with HSP90α and reduces the binding between HSP90 and CDC37,thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

Objective:To investigate clinical characteristics for in-stent reocclusion lesions after coronary stent implantations in aged patients.Methods:229 patients diagnosed with chronic total reocclusions were recruited from Jan 2005 to Dec 2019 in this retrospective study.According to age, patients were divided into a 40-49 year-old group(n=60), a 50-59 year-old group(n=58), a 60-69 year-old group(n=55), and a 70-80 year-old group(n=56)to examine different lesion characteristics after coronary stent implantations.Results:In the 40-49 year-old group, the 50-59 year-old group, the 60-69 year-old group and the 70-80 year-old group, the rates of multi-vessel reocclusions were 11.6%, 15.5%, 21.8% and 25.0%, respectively( χ2=10.03, P=0.01). For each group, lesions with concurrent proximal and middle coronary reocclusions accounted for 8.3%, 12.0%, 30.9% and 35.7%, respectively( χ2=11.83, P=0.005); Reocclusions with severe coronary calcification accounted for 6.6%, 15.5%, 36.3% and 37.5%, respectively( χ2=11.56, P=0.006); Long coronary reocclusion lesions(36-47 mm)accounted for 15.0%, 17.2%, 21.8% and 25.0%, respectively( χ2=11.56, P=0.007); Coronary reocclusions with diffuse long calcified lesions accounted for 8.3%, 13.7%, 32.7% and 35.7%, respectively( χ2=10.80, P=0.01). Conclusions:The clinical characteristics of in-stent reocclusion lesions after coronary stent implantations include multiple chronic total coronary reocclusions, concurrent proximal and middle coronary reocclusions, heavily calcified coronary reocclusions, long coronary reocclusions and diffuse long calcified coronary reocclusions in aged patients.

Objective: To detect the hemodynamic mechanism of the novel endovascular stent on complicated abdominal aortic aneurysms by Computational Fluid Dynamics(CFD) firstly, and then compare the effect of the novel endovascular stent and the streamliner multilayer flow modulator(SMFM) stent. Methods: All medical images were obtained by computed tomography. A semiautomatic segmentation protocol within Mimics(v17.0; Materialise, Leuven, Belgium) was used to extract the threedimensional aortic aneurysms. The stents was generated numerically and fitted along the aortic aneurysms. The lumen volume represented the fluid domain that was discretised in smaller volumes, which defined a mesh within the ICEM software(Ansys ICEM CFD v15.0). Hemodynamic analysis was performed with software Fluent 16.0. Results: Both kinds of stents can change the pattern of flow distribution. Compared with SMFM, the novel endovascular stent can significantly reduce the flow velocity in aneurysms, the shear force and the pressure on the aneurysms wall.What’s more, the flow velocity of the branch artery was accelerated by the novel endovascular stent. Conclusion The novel endovascular stent can significantly reduce the flow velocity in aneurysms, the shear force and the pressure on the aneurysms wall, and acceleratethe the flow velocity of the branch artery.