OBJECTIVE:To investigate the expression of matrix metallopro teinase-2(MMP-2),tissue inhibitor of metalloproteinase-2(TIMP-2) and collagen Ⅳ(Ⅳ-C) in kidney of diabetic rats and the intervention effect of irbesartan.METHODS:30 male SD rats were randomly divided into three groups:normal control group(NC group),diabetes mellitus group(DM group) and diabetes mellitus+50 mg?kg-1 irbesartan group(DI group).DM and DI group were injected with streptozocin intraperitoneally to reduce diabetic model.After 8 weeks the expression of MMP-2,TIMP-2 and Ⅳ-C in kidney tissure were determined by immunohistochemistry method(SP) and RT-PCR.RESULTS:Compared with NC group,DM group showed the expression of protein and mRNA of MMP-2 significantly reduced while that of TIMP-2 and Ⅳ-C increased(P

objective To investigate the protective effect and possible mechanisms of extract of Gingko biloba(EGB)on early diabetic nephropathy(DN).Methods Fifty-one patients with early DN were randomly divided into control group(n=25)treated by irbesartan alone and treated group(n=26)treated by EGB combined with irbesartan.Serum high sensitive C-reactive protein(hs-CRP)and monocyte chemoattractant protein-1(MCP-1)were determined with ELISA before and after treatment,and urinary albumin excretion rate(UAER),fasting blood glucose (FBG),serum creatinine(SCr),blood urea nitrogen(BUN)and lipid profiles were examined as well.Results Compared with pretreatment,at the end of 6 months'treatment,the values of hs-CRP decreased from(194.37±34.02)and(191.51±27.15)mg/L to(164.13±32.86)and(134.65±20.47)mg/L in control group and treatment group,respectively.MCP-1 was downregulated from(304.23±38.56)and(299.66±44.07)ng/L to (235.43±28.66)and(165.53±21.96)ng/L in control group and treated group(all P＜0.05).After treatment,the decrement of hs-CRP and MCP-1 level in the treated group was more significant than that in control group(P＜0.05).Conclusion EGB could retard the development of early DN,through down-regulating the expresssion of seram MCP-1,decreasing serum hs-CRP concentration and inhibiting inflammatory reaction.

Objective To explore the clinical application of the multi-network anatomical lavage on the treatment of chronic osteomyelitis after fracture surgery. Methods A retrospective analysis of 40 patients (41 sites) with chronic osteomyelitis after fracture surgery was performed from June 2006 to December 2008. There were 35 males and 5 females with an average of 42.7 years (range, 16-68). All 40 cases were treated with debridement, closing the cavity, and placing the multi-tube drainage network anatomical catheter lavage system. At the same time, sensitive antibiotics were used for 3 to 4 weeks. Rechecks were scheduled every 3 months after operation, including wound healing, X-ray presentation, ESR and C-reactive protein.Cure criteria depends on the conditions of the inflammation when the lavage treatment was over, and whether it relapsed six months after operation, including wound healing, systemic symptoms, ESR and C-reactive protein. Results Judged by the clinical outcomes when the lavage treatment was over and six months after operation, the effects were categorized into 3 levels, including excellent in 37 cases with primary wound healing, and without relapse six months later;, good in 2 with poor wound healing, the wound healed after a period of treatment without recurrence; poor in one with recurrent sinus infection and a prolonged unhealed wound, after another operation he was healed. 36 cases were treated with bone graft and internal fixation operation, and the fractures were healed after surgery, the fractures were healed directly in 4 cases without bone graft. The patients were followed up for an average of 43.2 months (range, 30-50) after operation, and none relapsed. Conclusion The multi-tube drainage network anatomical method is feasible and effective on the treatment of chronic osteomyelitis after fracture surgery with a high cure rate.

Objective To investigate the effects of Notch1 siRNA on VEGF and angiogenesis of myeloma cell line RPMI-8226 in vitro and in vivo.Methods In vitro,Notch siRNA was transfected into RPMI-8226 cells,and then cell supernatant VEGF secretion was detected using ELISA method.Expression levels of Notch1 and VEGF proteins were assayed by Western blotting.RPMI-8226 cells were subcutaneously transplanted in NOD/SCID mice,and then the tumor mice were divided into three groups randomly:NS group (Notch1 siRNA-transfected group),CS group (Control siRNA-transfected group) and UN group (Untransfected group),and the changes of tumor volume were observed.Immunohistochemical staining was used to detect the changes in expression levels of Notch1,VEGF and CD34.Results Notch1 and VEGF proteins expressions of RPMI-8226 cells were significantly decreased by Notch1 siRNA.At 48 h and 72 h,VEGF secretion level in NS group was significantly different with CS group [(120 ± 25) ng/L ∶ (175 ± 15) ng/L,t =3.27,P ＜ 0.05;(145 ± 24)ng/L ∶ (295 ± 17)ng/L,t =8.83,P＜0.01].At 13 d,17 d and 21 d,tumor volume in NS group was significantly reduced,that was significantly different with CS group [(1 548 ± 218) mm3 ∶ (1 820 ± 64) mm3,t =2.68,P ＜0.05;(1 200 ±75)mm3 ∶ (2 180 ±84)mm3,t =19.46,P＜0.01;(1 150 ±88)mm3 ∶ (2 250 ± 145)mm3,t =14.50,P ＜0.01].The expression levels of Notch1 and VEGF protein were decreased by Notch1 siRNA.The expression levels of Notchl and VEGF in NS group were different with CS group [(16.33 ±2.52)％∶ (75.33 ±2.52)％,t=28.71,P＜0.01;(5.00±1.00)％∶29.67±2.08 ％,t=18.50,P ＜ 0.01].Notch1 siRNA reduced the number of transplanted tumor neovascularization in NS group.Microvascular density in NS group was significantly less than that in CS group [(14.67 ± 2.52) ∶ (30.00 ± 5.00),t =4.74,P ＜ 0.01].Conclusion In vitro,Notch siRNA reduces human myeloma cell RPMI-8226 cell supernatant VEGF secretion.In vivo,Notch siRNA can reduce tumor volume and the number of new blood vessels in transplanted-multiple myeloma mice.Thus,Notchl is an effective molecular target for anti-angiogenesis in myeloma.

Objective Based on the theory of"lung governs the skin and hair"in"Yellow Emperor's Inner Classic",this paper analyzes the medication rules of whitening and freckle-removing.The aim of this study is to provide reference for the clinical practice of traditional Chinese medicine(TCM)theory and the medication in TCM cosmetics.Methods"Chinese Medical Classics"was used to search the records of whitening and freckle-related drugs.The frequency,nature,flavor,meridian tropism and compatibility laws of TCM for whitening and freckle-removal were analyzed by statistics and association rules.The network pharmacology research was used to analyze the whitening and freckle-removing effects and mechanisms of high-frequency drugs.Then,the potential active ingredients were analyzed.The whitening and anti-freckle effect was verified through cytotoxicity experiments and melanin content detection.Results A total of 171 external prescriptions were selected in eligible articles,including 261 Chinese medicinals,most of which were pungent and belong to the lung meridian.The most frequently used Chinese medicinals was"Erbai Yixin"(EBYX,Angelicae Dahuricae Radix,Typhonii Rhizoma,Asari Radix et Rhizoma).Network pharmacological analysis showed that the core targets of EBYX for whitening and removing freckles are TP53,EGFR,ALB,etc.,which are mainly involved in oxygen perception and response,skin immune regulation,skin cell growth,differentiation,stress,inflammatory response,and other biological processes.Based on the results of molecular docking,biological analysis proved that the active ingredients of EBYX are chrysophanol,gallic acid and caffeic acid,which have inhibitory effects on the proliferation of melanoma cells and melanin production.Conclusion Most of the ancient prescriptions for whitening and removing freckles are pungent and belong to the lung meridian,which embodies the theory of"lung governs the skin and hair".The high-frequency drug EBYX may play a role by regulating skin redox,immunity and inflammation.The active ingredients of EBYX have an inhibitory effect on melanin formation.This study enriches the scientific connotation of TCM whitening and freckle-removing prescriptions based on the theory of"lung governs the skin and hair",realizes interdisciplinary integration and provides support for the modernization of TCM.

Objective To explore the analysis of the relationship of the serum levels of focal adhe-sion kinase(FAK)and fatty acid-binding protein 4(FABP4)with myocardial injury and cardiac function in elderly patients with acute myocardial infarction(AMI).Methods A total of 211 AMI patients admitted to our hospital from January 2020 to April 2023 were enrolled and assigned into the AMI group,while another 60 healthy volunteers who took routine physical examinations in our hospital during the same period served as the control group.The serum FAK and FABP4 lev-els were compared between the two groups.Multivariate logistic regression analysis was employed to identify influencing factors associated with AMI,and ROC curve was plotted to assess the pre-dictive efficacy of the serum FAK and FABP4 levels for AMI in the elderly population.Pearson correlation analysis was conducted to explore the relationship between serum FAK and FABP4 levels and myocardial injury as well as cardiac function.Results The AMI group exhibited signifi-cantly elevated serum FAK,FABP4,CK-MB,cTnⅠ and CK levels,and larger LVESD and LVEDD,but lower LVEF when compared with the control group(P＜0.05,P＜0.01).For the AMI patients,the serum FAK and FABP4 levels were positively correlated with CK-MB,cTnⅠ and CK levels,as well as LVESD and LVEDD,and negatively with LVEF(P＜0.05).Multivariate logistic regression analysis revealed that both serum levels of FAK(OR=2.872,95％CI:2.230-3.698,P=0.000)and FABP4(OR=2.667,95％CI:1.713-4.154,P=0.000)were influencing factors for AMI.ROC analysis indicated that the cut-off value of FAK level for diagnosing AMI was 25.60 pg/L,with an AUC value of 0.801(95％CI:0.750-0.852).Similarly,the cut-off value of FABP4 in the diagnosis was 23.22 pg/L,with an AUC value of 0.760(95％CI:0.707-0.812).Combined FAK and FABP4 levels yielded,with an AUC value of 0.899(95％CI:0.839-0.918).Conclusion Serum FAK and FABP4 levels are abnormally high in the elderly patients with AMI,which is closely related to myocardial injury and cardiac function.The two indicators alone or in combination can effectively predict the occurrence of AMI.

Objective:To investigate the impact of intraoperative multimodal neurophysiological monitoring combined with blood pressure precise control on incidence of acute cerebral infarction after carotid endarterectomy.Methods:A retrospective study was peformed; 305 patients with atherosclerotic stenosis of the carotid artery admitted to and accepted carotid endarterectomy in Department of Vascular Neurosurgery, Dong'e County People's Hospital from January 2020 to September 2023 were selected. Intraoperative multimodal neurophysiological monitoring combined with traditional empirical modalities for blood pressure control was applied to 153 patients admitted to our hospital from January 2020 to December 2021 (control group), and intraoperative multimodal neurophysiological monitoring combined with blood pressure precise control (based on monitored sensory or motor wave amplitude changes) was applied to 152 patients admitted to our hospital from January 2022 to September 2023 (experimental group). Difference in postoperative acute cerebral infarction incidence between the 2 groups was compared.Results:The experimental group had significantly lower postoperative acute cerebral infarction incidence compared with the control group (4.6% vs. 13.0%, P<0.05). The experimental group had significantly lower postoperative asymptomatic acute cerebral infarction incidence compared with the control group (3.3% vs. 9.8%, P<0.05), while no significant difference was noted in postoperative symptomatic acute cerebral infarction incidence between the 2 groups ( P>0.05). Conclusion:Intraoperative multimodal neurophysiological monitoring combined with blood pressure precise control can reduce the postoperative acute cerebral infarction incidence in patients accepted carotid endarterectomy, especacailly postoperative asymptomatic acute cerebral infarction incidence, thereby enhancing surgical safety.

Objective:To compare the clinical efficacy between modified open wedge high tibial osteotomy (MOWHTO) versus traditional open wedge high tibial osteotomy (TOWHTO) for varus knee osteoarthritis (KOA).Methods:A retrospective study was conducted to analyze the 50 patients (60 knees) with varus KOA who had received high tibial osteotomy at Department of Sports Medicine, The Affiliated Hospital of Qingdao University between September 2019 and December 2020. The patients were divided into 2 groups according to different ways of osteotomy: a traditional group and a modified group. In the traditional group subjected to TOWHTO, there were 25 cases (30 knees); in the modified group subjected to MOWHTO, there were 25 cases (30 knees). In MOWHTO, the bone block attached to the medial collateral ligament (MCL) of the knee was first chiseled at the MCL insertion before osteotomy to reduce excessive stripping of the MCL in the osteotomy area, and then the bone fragment attached to the MCL was filled into the osteotomy area to increase bone filling and bone coverage after the alignment of the lower limb was corrected. The hip-knee-ankle angle (HKAA), medioproximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured preoperatively and at 18 months postoperatively in both groups to evaluate correction of the alignment of the lower limb. Fracture healing time, bone loss in the osteotomy area, Hospital for Special Surgery (HSS) knee score and visual analogue scale (VAS) were recorded to evaluate the postoperative efficacy.Results:There was no statistically significant difference between the TOWHTO and MOWHTO groups in the general clinical data before operation, showing comparability ( P>0.05). At 18 months after operation, HKAA was (179.1° ± 1.1°) in the TOWHTO group and (179.3° ± 0.7°) in the MOWHTO group while MPTA was (91.9° ± 0.4°) in the TOWHTO group and (91.9° ± 0.4°) in the MOWHTO group, showing no statistically significant difference between the 2 groups ( P>0.05) but a significant difference between preoperation and postoperation in each group ( P<0.05). At 18 months after operation, JLCA was (1.8° ± 0.4°) in the TOWHTO group, significantly larger than that in the MOWHTO group (1.5° ± 0.4°), HSS score was 81.5 (79.5, 83.0) points in the TOWHTO group, significantly lower than that in the MOWHTO group [85.0 (82.5, 87.5) points], and VAS was 1.8 (1.6, 2.0) points in the TOWHTO group, significantly higher than that in the MOWHTO group [1.5 (1.5, 2.0) points] (all P<0.05). At 18 months after operation, the preoperative JLCA was significantly improved in both groups ( P<0.05). The time required for a fracture healing score higher than 4 points was (3.3 ± 0.6) months in the TOWHTO group and (4.5 ± 0.9) months in the MOWHTO group, and the rate of bone loss in the osteotomy area was 20% in the TOWHTO group (6/30) and 0 (0/30) in the MOWHTO group, both showing a significant difference between the 2 groups ( P<0.05). Conclusions:Both TOWHTO and MOWHTO can effectively treat varus KOA. MOWHTO is more effective in promoting bone healing in the osteotomy area, reducing bone defects in the osteotomy area and improving knee function.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.