Objective:To observe the clinically curative effects of Qingwen Baidu drink(清瘟败毒饮) on epidemic hemorrhagic fever (EHF).Methods:One hundred and eighty cases with EHF who were admitted to hospital within 5 days after onset were randomly divided into two groups.The control group (n=60) was treated with Ribavirin infused intravenously and liquid therapy,and treating complications simultaneously,meanwhile the treated group (n=120) based on the same therapy as control group treated with Qingwen Baidu drink number Ⅰ,Ⅱ or Ⅲtaken orally two times a day according to different course.Results:In treated group all the days of fever,polyuria,recovering platelet to normal,and transforming proteinuria to negative were significantly shorter than those in control group (both P<0.01),otherwise the overphase rates of oliguria and hypotension shock were higher than those in control group too (all P<0.01).The occurance rate of complications in treated group was lower than that in control group(P<0.05).Conclusions:The curative effects adding Qingwen Baidu drink on EHF are significant and worth spreading.

[Objective]To evaluate the operability and clinical efficacy of injectable calcium sulfate for grafting bone defects.[Method]From June 2004 to August 2005,22 cases with benign bone lesions were treated with curettage and grafting with injectable calcium sulfate bone graft substitute(minimally invasive injectable graft X3,MIIG X3).There were 13 male cases and 9 femal cases.Their average age was 34.6(ranged,4~55).All the 22 cases were followed-up from 23 months to 37 months,average 31.6 months.All cases took radiographic examination regularly after the operation to assess the absorption rate of MIIGX3 and the formation rate of new bone.[Result]This injectable calcium sulfate with vacuum mixing was easy to use,providing complete fill and bony strength instantly when grafting bone defects.According to the raeiographs,MIIGX3 was absorbed almost at the same rate as new bone ingrowth in 8 to 24 weeks.[Conclusion]MIIGX3 is convenient to graft bone defects with fewer complications,capable of absorbing almost at the same rate as replacement of new bone.It's one of the best bone graft substitutes for grafting bone defects induced by benign bone lesions.

BACKGROUND:To overcome the disadvantages of traditional mechanical analysis of specimens, and establish the finite element model of realistic foot, are the important basements for the finite element mechanical analysis on foot.
OBJECTIVE:To establish three-dimensional finite element model of foot and lay the foundation for the finite element analysis of normal foot and foot injury.
METHODS:A healthy female volunteer was involved in this study and was detected with spiral CT scanning on the feet. The resulting image was used to reconstruct the three-dimensional model by using Mimics software. Then entity model was generated in Geomagic software. Final y three-dimensional finite element model was established based on the digital main structure in Ansys. RESULTS AND CONCLUSION:The established finite element digital model of human foot included al bone, cartilage and ligament, skin and soft tissue. The three-dimensional finite element model of human foot was established based on CT data and using Mimics, Geomagic, Ansys softwares. The established model had similar size and shape with skeletal mode, and can rotate freely in any angle for a variety of measurement, the foot bones can be arbitrarily split or merge, which is suitable for biomechanical analysis.

OBJECTIVE: To explore the pathogenesis characteristics of variant angina pectoris (VAP) by extracting its syndrome elements and analyzing the combination and distribution regularity of the syndrome elements. METHODS: One hundred and seventy-five case files of VAP patients were collected. The extraction of syndrome elements and symptom contribution to syndrome was completed by the partition method of complex system based on entropy theory. Diagnostic threshold was established by receiver operator characteristic curve. According to the results diagnosed by diagnostic criteria for syndrome element with quantitation, the combination and distribution regularity of the syndrome elements in patients with VAP was analyzed. RESULTS: The basic syndrome elements in the patients with VAP were qi deficiency, qi stagnation, blood stasis, phlegm turbidity, phlegm-heat, stagnation-heat, yin deficiency and yang deficiency syndromes. It showed that the combination types of syndrome elements could be made up of one syndrome, two, three, four or more than four syndromes. Qi deficiency, yin deficiency, qi stagnation, blood stasis and phlegm turbidity syndromes had the higher frequency than other syndrome elements in the patients with VAP. CONCLUSION: The partition method of complex system based on entropy theory can be used in extracting the syndrome elements of the patients with VAP. It is found that VAP has complicated pathogenesis according to the combination and distribution regularity of syndrome elements. Qi deficiency, qi stagnation, blood stasis, phlegm turbidity and yin deficiency syndromes are the main syndrome elements.

In order to improve the poor solubility and low bioavailability of paeonol (Pae), paeonol-nanoemulsion (Pae-NE) was prepared, and its effect on uptake of human umbilical vein endothelial cells (HUVECs) was investigated.Pae-NE was prepared by phase inversion composition (PIC), the formulation of Pae-NE was optimized by single factor method and central composite design-response surface method (CCD), and the pharmaceutical properties were further characterized.Moreover, MTT was applied to evaluate the toxicity of Pae-NE on HUVECs, and the cellular uptake efficiency of Pae-NE was detected by fluorescence microscopy and flow cytometry.The results showed that the optimal formulation of Pae-NE was 20 mg of Pae, 55.1 mg of LCT, 144.9 mg of MCT, 600 mg of HS15, and 200 mg of 1,2 propylene glycol.The Pae-NE appearance was a light blue emulsion, and the average particle size is (25.69 ± 0.03) nm, with PDI of 0.182 ± 0.09, Zeta potential of -(4.01 ± 0.30) mV and good stability.The drug loading of Pae-NE was (1.967 ± 0.28) mg/mL and encapsulation rate of (99.36 ± 0.1)%.Pae-NE performed no significant effect on HUVECs growth in the Pae concentration range of 10-1-10-3 μg/mL.Moreover, NE as a drug delivery carrier significantly enhanced the uptake efficiency of Pae on HUVECs.In conclusion, Pae-NE preparation method was simple and stable, and promotes HUVECs uptake efficiency of Pae, suggesting that NE was a better dosage form reference for the lipid-soluble drug of Pae.

Objective We aimed to compared matrix metalloproteinase-13 (MMP-13) and transforming growth factor-β1 (TGF-β1) in synovial fluid,the phosphorylation level of Smad3 in articular cartilage (P-Smad3),and their correlation with traditional Chinese medicine (TCM) patterns in patients with knee osteoarthritis (KOA) of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis.Methods Using a cross-sectional field investigation method,KOA patients hospitalized in the Orthopedics Department of Dongzhimen Hospital,Beijing University of Chinese Medicine from September 2019 to February 2023 were collected. A total of 112 KOA patients were included,among which 63 cases were diagnosed with liver-kidney deficiency pattern,and 49 cases were diagnosed with pattern of intermingled phlegm and blood stasis. The intensity of knee pain,function,and X-ray imaging result were quantified using the Visual Analogue Scale (VAS),Lysholm Knee Scoring Scale,and Kellgren-Lawrence (K-L) Grading Scale,respectively. The TCM pattern was identified and quantified using a TCM Pattern Scoring Scale. Immunohistochemistry was used to determine the phosphorylation characteristics of Smad3 in articular cartilage,and ELISA was used to measure the contents of MMP-13 and TGF-β1 in synovial fluid. The level characteristics and their correlation with the degree of syndrome were analyzed.Results (i) There was no statistically significant difference in VAS scores,Lysholm scores,and K-L grades between KOA patients with different TCM patterns. (ii) Compared with KOA patients with pattern of intermingled phlegm and blood stasis,patients with pattern of liver-kidney deficiency had higher levels of MMP-13 in synovial fluid and lower levels of TGF-β1 in synovial fluid (P<0.05). (iii) In KOA patients with liver-kidney deficiency pattern,there was a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.292,P=0.020),while there was a negative correlation between the level of TGF-β1 in synovial fluid and the score of TCM pattern (r=-0.781,P<0.001). In KOA patients with pattern of intermingled phlegm and blood stasis,there was also a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.936,P<0.001). (iv) The mean optical density value of P-Smad3 in articular cartilage was lower in KOA patients with liver-kidney deficiency pattern than in pattern of intermingled phlegm and blood stasis (P<0.05).Conclusion KOA patients with liver-kidney deficiency pattern or pattern of intermingled phlegm and blood stasis have different levels of TGF-β1 and MMP-13 in synovial fluid,as well as varying degrees of Smad3 phosphorylation in articular cartilage,which is consistent with the analysis of etiology and pathogenesis under different patterns. The levels of TGF-β1 and MMP-13 in synovial fluid of patients with liver-kidney deficiency pattern can reflect the severity of the pattern to a certain extent,and the mechanism may be related to the inhibition of the activation level of the TGF-β/Smad signaling pathway. This study enriches the research content of the material basis of TCM patterns.

OBJECTIVE:To study the effects of salvianolic acid B(Sal B)on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac fibro-blast proliferation,secretion of type Ⅲ collagen,protein expressions of matrix metalloproteinase 9 (MMP-9),Smad2/3,Smad7, and explore its mechanism of anti-myocardial fibrosis. METHODS:Cells were divided into blank control group(culture medium) Ang Ⅱ model group,Sal B low-dose,medium-dose,high-dose groups (12.5,25,50 μmol/L). After cultured 1 h by blank or drug-containing culture,except for blank control group,cells in other groups were added 1 μmol/L Ang Ⅱ to induce proliferation. for 24 h. MTT method and hematoxylin-eosin staining method were adopted investigate the effect of Sal B on proliferation. Western blot method was adopted to detect the effects of Sal B on protein expressions of type Ⅲ collagen,MMP-9,Smad2/3,Smad7. RE-SULTS:Compared with blank control group,cells in Ang Ⅱ model group were significantly proliferated,protein expressions of type Ⅲ collagen,MMP-9,Smad2/3 were obviously enhanced,protein expression of Smad7 was obviously weakened,with statisti-cal significances(P<0.05). Compared with Ang Ⅱ model group,the cell proliferation in Sal B groups were inhibited,protein ex-pressions of typeⅢcollagen,MMP-9,Smad2/3 were weakened,while protein expression of Smad7 was enhanced. Except the pro-tein expression of type Ⅲ collagen in Sal B low-dose and medium-dose groups,the protein expression of Smad2/3 in Sal B high-dose group did not change significantly,other indexes had statistical significances(P<0.05). CONCLUSIONS:The anti-myo-cardial fibrosis effect of Sal B may be associated with inhibiting the proliferation of cardiac fibroblasts,down-regulating protein ex-pressions of typeⅢcollagen,MMP-9,Smad2/3 and up-regulating protein expression of Smad7.

Objective To investigate the effects of zalcitabine(ddC),a mitochondrial DNA polymerase γ(POLG)inhibitor,on the migration,invasion,and to preliminarily explore mitochondrial biogenesis of human tri-ple-negative breast cancer MDA-MB-231 cells.Methods The effect of ddC on cell viability was detected using the MTT assay.The migration and invasion abilities of the cells were evaluated using the cell scratch and Transwell in-vasion assays.Cell apoptosis was determined using flow cytometry and a V-FITC/PI cell apoptosis detection kit.The protein expression of POLG,NADH dehydrogenase subunit Ⅰ(NADH1),NADH dehydrogenase subunit Ⅱ(NADH2),ATP synthase subunit 6(ATPase6),cytochrome c oxidase subunit Ⅰ(COX-1)and cytochrome c ox-idase subunit Ⅲ(COX-3)were determined using Western blot.The POLG mRNA level and mtDNA copy number were determined using qPCR.The mitochondrial content and ATP levels were determined using MitoTracker Green fluorescent probe staining and an ATP determination kit.MDA-MB-231 cells were transfected with pcDNA3.1-EG-FP-POLG plasmids to overexpress POLG.The inhibitory effects of ddC on cell migration and invasion were detected in POLG-overexpressed MDA-MB-231 cells.Results POLG expression was higher in MDA-MB-231 cells than in normal mammary epithelial cells(MCF-10A)(P＜0.01).ddC inhibited cell viability in a dose-dependent man-ner.ddC inhibited the migration(P＜0.01)and invasion(P＜0.01)of MDA-MB-231 cells;however,it dis-played no significant inhibitory effects on cell viability in normal mammary epithelial cells(MCF-10A)at the same concentration.ddC downregulated the protein(P＜0.01)and mRNA(P＜0.01)levels of POLG,reduced mtD-NA copy number(P＜0.01)and downregulated mtDNA-coded NADH1,NADH2,ATPase6,COX-1 and COX-3 protein expression(P＜0.01)in MDA-MB-231 cells.Furthermore ddC inhibited mitochondrial content(P＜0.01)and ATP(P＜0.01)levels in MDA-MB-231 cells.POLG overexpression increased the migration(P＜0.05)and invasion(P＜0.05)abilities of MDA-MB-231 cells,while ddC did not significantly inhibit the migra-tion and invasion abilities of MDA-MB-231 cells overexpressing POLG.Conclusion ddC downregulates POLG ex-pression in MDA-MB-231 cells and inhibits mitochondrial biogenesis and ATP levels,thereby inhibiting the migra-tion and invasion of MDA-MB-231 cells.

Objective: To explore the effect of hypoxia inducible factor 1α(HIF-1α)on tamoxifen resistance in breast cancer MCF-7,and to established a human breast cancer cell line(MCF-7/TR)with 4-hydroxy tamoxifen(4-OHT)resistance. Methods: 4-OHT was an active form of tamoxifenin vivo, resistant breast cancer cells MCF-7/TR were establishedin vitrousing 4-OHT. MTT assay was used to detect the effect of 4-OHT on the MCF-7 and MCF-7/TR cells, and the drug resistance multiple was detected. Western blot was used to detect the expression level of HIF-1α protein in MCF-7 and MCF-7/TR cells. The effects of HIF-1α inhibitor(LW6) or siRNA HIF-1α on MCF-7/TR cells and 4-OHT on MCF-7 cells treated with HIF-1α stabilizer(FG-4592) were detected by MTT and flow cytometry AV/PI staining. Results: The results showed that the MCF-7/TR was successfully constructed, and the drug resistance ratio was(5.56±0.80). Compared with MCF-7 cells, MCF-7/TR cells had higher expression of HIF-1α protein and it was up-regulated after tamoxifen treatment. After giving LW6 or silencing the expression of HIF-1α,the down-regulation of HIF-1α expression enhanced the inhibitory effect of 4-OHT on MCF-7/TR cells. After treatment of FG-4592, the expression level of HIF-1α in breast cancer cells MCF-7 was up-regulated, and hindered the inhibition effect of tamoxifen on MCF-7 cells. Conclusion The above results indicate that HIF-1α plays an important role in 4-OHT resistant breast cancer, and targeting HIF-1α may be an effective way to increase the sensitivity of MCF7/TR cells to tamoxifen.

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.