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Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.
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Objective To assess the efficacy and safety of nalbuphine in preventing the side effect of pruritus induced by intrathecal morphine after cesarean section. Methods Sixty patients aged 18- 35 years with ASAⅠ~Ⅱand undergoing cesarean section with combined spinal-epidural anesthesia were randomly and double blindly divided into two groups. Patients in Group N (30 patients) received nalbuphine 4 mg (2 ml) by intravenous route after clamping of the umbilical cord; Patients in Group P (30 patients) received 0.9% NaCl (2 ml) by intravenous route after clamping of the umbilical cord. The protocol of postoperative analgesia was intrathecal morphine 0.2 mg. The patients were followed up for 4 h , and the vital signs were detected at the time of returning to patient s room (T0), 1 h (T1), 2 h(T2), 3 h(T3) and 4 h(T4) after operation. The VAS scores, pruritus severity scores, time of pruritus onset, Ramsay sedation scores and and other adverse effects were recorded. Results The levels of MAP, SpO2, HR in two groups at T0, T1, T2, T3, T4 had no significant differences (P>0.05). The rate of pruritus severity score 0-1 score in group N was significantly higher than that in group P (χ2=17.4, P=0.00). The VAS scores and the rate of drowsiness, nausea, vomiting, shivering and dizziness in two groups had no significant difference (P>0.05). Conclusions Nalbuphine provides a significant reduction of morphine induced pruritus for patients who received intrathecal morphine analgesia after cesarean section.
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OBJECTIVE:To compare clinical efficacy,ADR and cost of moxifloxacin alone vs. piperacillin/tazobactam com-bined with azithromycin in the treatment of elderly community acquired pneumonia(CAP). METHODS:In retrospective study, 60 elderly CAP patients were selected from respiratory department of a third grade Class A hospital during Oct. 2015-Apr. 2016, and then divided into group A,B with 30 cases in each group according to the medication regimen. Group A was given Moxifloxa-cin hydrochloride and sodium chloride injection 250 mL,ivgtt,qd;group B was given Azithromycin latobionate for injection 0.50 g,ivgtt,qd+Piperacillin sodium and tazobactam sodium for injection 3.375 g,ivgtt,q8 h. Both groups were treated for 10 d. Clini-cal efficacy,bacteriological efficacy and the occurrence of ADR were compared between 2 groups. The economics of 2 therapy plans were evaluated. RESULTS:Total response rates of group A and B were 90.00% and 93.33%;bacterial clearance rates were 85.00% and 86.36%;the incidence of ADR were 3.33% and 6.67%,without statistical significance(P>0.05). Minimum cost analysis was adopted for economic evaluation;treatment cost of group A was 16646.51 yuan,and that of group B was 19605.74 yuan;the cost of group A was lower than group B. The results of minimum cost analysis were supported by sensitivity analysis. CONCLUSIONS:For empiric treatment of antibiotics in elderly CAP patients,moxifloxacin alone should be the first choice. The therapy plan is effective,low-cost and safe.
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Objective · To establish human cervical cancer xenografts in nude mice and investigate the antitumor therapeutic effects and safety of EGF modified cisplatin-alginate conjugate liposomes. Methods · Cervical cancer-bearing mouse model was established by subcutaneously injecting Hela cells in nude mice. Generalstate and xenograft growth of the mice were observed. Tumor volumes, tumor weights, and the body weights of mice during the treatment were recorded and analyzed. The expression levels of EGFR in xenografts were detected by immunohistochemistry. Results · ① EGFR was highly expressed in the xenografts. ② CS-EGF-Lip inhibited the tumor growth effectively (P=0.000). ③ The inhibition rates of tumor volume and tumor weight of CS-EGF-Lip were 80.22% and 58.60% respectively, which were betterthan those of cisplatin (P=0.000). ④ CS-EGF-Lip had minimal influence on body weight in mice (P=0.000). Conclusion · CS-EGF-Lip has more effective antitumoreffects than cisplatin in cervical cancer-bearing mice, which can inhibit tumor growth of solid tumors with enhanced efficacy and safety.
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OBJECTIVE:To study the effect of peiminine on increasing the chemosensitivity of 5 kinds of cancer cells. METH-ODS:Using human esophageal cancer Eca-109 cell,human breast cancer MCF-7 cell,human small cell lung cancer A549 cell,hu-man hepatoma HepG2 cell and human cervical cancer HeLa cell as objects,MTT colorimetric method was used to detect the growth inhibition rate of above-mentioned 5 kinds of cancer cells after treated by peiminine with maximal non-toxic mass concentra-tion(20 μg/mL)and adriamycin with different gradient mass concentrations(0.026-2.1,0.026-2.1,0.125-2.0,0.125-2.0,0.0625-0.10μg/mL)for 72 h. The half inhibitory concentration(IC50)was calculated. Crystal violet staining method was adopted to observe the proliferation of above-mentioned cancer cells after treated by peiminine with maximal non-toxic mass concentration and adriamycin with low mass concentrations(0.02,0.005,0.04,0.02,0.01 μg/mL)for 7 d. Solvent control,single use of peiminine and adriam-ycin control were conducted. RESULTS:Compared with single use of adriamycin,the combination use of peiminine and adriamy-cin can improve the growth inhibition rate of 5 kinds of cancer cells to certain degree,most of the differences were statistically sig-nificant (P<0.05 or P<0.01);and IC50 was obviously decreased,with statistical significances (P<0.05 or P<0.01). Compared with solvent control,single use of peiminine or adriamycin had no obvious effects on the proliferation of above-mentioned cancer cells in 7 d,and the combination use of peiminine and adriamycin can obviously inhibit the proliferation of above-mentioned cancer cells in 7 d. CONCLUSIONS:Peiminine can enhance the sensitivity of above-mentioned-mentioned 5 kinds of cancer cells to cer-tain degree,showing certain chemosensitivity increasing effect.
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Objective:To investigate the application of photoplethysmogram in analyzing the fingertip pulse amplitude volume (PAV)to evaluate the endothelial function in diagnosing coronary heart disease,and to clarify its relationship with the risk factors of cardiovascular diseases.Methods:Total 409 patients with chest pain accepted coronary angiography (CAG)were selected and diveded into positive group (CAG+)(n=288)and negative group (CAG-) (n = 121)according to angiographic results.Fingertip photoplethysmogram was used to analyze the fingertip PAV by the way of applying endothelial function diagnostic after reactive ischemia,and the relationship between the PAV value and the risk factors of coronary heart diseases was analyzed,and the critical reference value of prediction index of coronary heart disease was determined.The risk factors such as age,gender,serum total cholesterol (TC ), low density lipoprotein (LDL ), high density lipoprotein (HDL ), non-HDL, serum triglyceride (TG),hypertension,diabetes,smoking,family history of coronary heart disease,body mass index (BMI)of the subjects in various groups were analyzed,and the relationship between the risk factors of coronary heart disease and PAV was analyzed by Logistic regression analysis.Results:The PAV of patients in CAG+group was significantly lower than that in CAG-group (P <0.01).The peak point of PAV was<1.37,if PAV<1.37 was used to predict the coronary heart disease,the predictive sensitivity,the specificity,the positive prediction and the negative prediction were 74.65%,44.63%, 76.24%, and 42.52%.The Logistic regression analysis showed that PAV was negatively associated with hypertension,smoking history,TG (OR= 1.476,OR=2.002, OR = 1.844;P < 0.01 ). Conclusion: PAV is associated with coronary heart disease and its risk factors (hypertension,smoking history,TG),and PAV=1.37 can be used as the peak point to predict the coronary heart disease.
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BACKGROUND:Bipolar femoral head prosthesis has achieved the desired repair effect in patients with femoral neck fracture, but there is stil much controversy on the biomechanical properties of bipolar artificial femoral head prosthesis. OBJECTIVE:To compare biomechanical properties of the bipolar femoral head prosthesis replacement and internal fixation in the repair of femoral neck fracture in the elderly. METHODS:Twenty-three (46 sides) senile femoral neck fracture specimens were analyzed and randomized into internal fixation group(n=23)and bipolar femoral head prosthesis replacement group (n=23). Specimens in the internal fixation group underwent conventional metal implant fixation. Specimens in the bipolar femoral head prosthesis replacement group underwent bipolar femoral head prosthesis replacement. Mechanical properties of femoral prosthesis stem were tested on universal testing machine. Biomechanical properties after bipolar femoral head prosthesis replacement and internal fixation were compared. RESULTS AND CONCLUSION:(1) The maximum loadwassignificantly higher in the bipolar femoral head prosthesis replacement group than in the internal fixation group (P< 0.05). The maximum load trend images showed that the maximum load was significantly higher in the bipolar femoral head prosthesis replacement group than in the internal fixation group (P< 0.05). (2) The displacement in axial pul test was significantly shorter in the bipolar femoral head prosthesis replacement group than in theinternal fixation group (P< 0.05). The displacement trend images exhibited that the displacement in axial pul test was significantly shorter in the bipolar femoral head prosthesis replacement group than in the internal fixation group (P< 0.05). (3) These findings suggest that compared with the implant, bipolar femoral head prosthesis replacement in the repair of femoral neck fracture in the elderly is more stable, has better repair effects, can elevate hip function and obtain good initial stability.
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<p><b>BACKGROUND</b>How the transcriptional factors regulated the innate and adaptive immune system in pregnancy and pre-eclampsia are less understood. Nevertheless, what the plasma work in the development of this disease was not sure. The present study was design to evaluate what the transcriptional factors change in innate and adaptive immune system and what the plasma do in this filed.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMC) from non-pregnant women (n = 18), women with clinically normal pregnancies (n = 23) and women with pre-eclampsia (n = 20) were separated from peripheral blood to isolate monocytes and T cells. The purity of monocytes and T cells were analysed by flow cytometry. Monocytes and T cells were stimulated in either lipopolysaccharides (LPS) or phorbol-myristate-acetate (PMA), respectively. Transcription Factor Arrays were used to screen the transcription factors of interest in comparing of different groups. PBMC were isolated from another 8 non-pregnant samples were co-incubated with different groups of plasma. Polymerase chain reaction (PCR) was performed using whole cell extractions of the samples.</p><p><b>RESULTS</b>Nuclear factor of activated T-cells-1 (NFAT-1), signal transducers and activators of transcription-1 (STAT-1) and activator protein-1 (AP-1) are up-regulated in monocytes in pregnancy and more so in pre-eclampsia. On the the contrary, NFAT-1, STAT-1 and AP-1 are down-regulated in T cells in pregnancy and more so in pre-eclampsia. A reduction was observed in interferon (IFN)-γ, interleukin (IL)-12 and IL-4 expression in T cells incubated with pre-eclamptic plasma. An elevation was observed in tumor necrosis factor (TNF)-α, IL-1 and IL-12 expression in monocytes incubated with pre-eclamptic plasma.</p><p><b>CONCLUSIONS</b>Innate immunity is over activated and adaptive immunity is over suppressed in the development of pre-eclampsia. NFAT-1, STAT-1 and AP-1 might be the central transcription factors in the pathogenesis of pre-eclampsia. They induced some changes in plasma and "educate" the monocytes and T cells for relevant cytokine production. Successful completion of this study will enhance our understanding of pre-eclampsia and will discover new knowledge beyond pregnancy. The work will inform future therapies for the treatment of a wide range of condition such as transplantation immunology and a wide range of immune and inflammatory conditions.</p>
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Adult , Female , Humans , Male , Pregnancy , Young Adult , Immunity, Innate , Physiology , Interferon-gamma , Metabolism , Interleukin-12 , Metabolism , Interleukin-4 , Metabolism , Leukocytes, Mononuclear , Metabolism , NFATC Transcription Factors , Genetics , Metabolism , Pre-Eclampsia , Allergy and Immunology , Metabolism , STAT1 Transcription Factor , Genetics , Metabolism , Transcription Factor AP-1 , Genetics , Metabolism , Transcription Factors , Genetics , MetabolismABSTRACT
Chronic ulcer of the lower extremities amounts for a grave and serious problem for public health. Western medicine focuses on controlling infection, improving blood circulation, surgical debridement, skin grafting, etc, but there are bottlenecks in the treatment. Traditional Chinese medicine (TCM) has a long history and a legacy of sound clinical efficacy in this area. TCM has developed a unique, effective external theory, and a large number of topical prescriptions and external technology. Through this research, a safe and effective treatment protocol of TCM for chronic ulcer of the lower extremities can be formed. To this end, during China's "Eleventh Five-Year" Plan, special research committees and projects on TCM external treatments and external technologies were established. This study on ulcer of the lower extremities constitutes one of the major research topics.
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To investigate the effects of Chinese herbs for replenishing qi (Yiqi) and dissolving stasis (Huayu) on substance P expression in granulation tissue of skin ulcers in rats with diabetes mellitus.
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Objective To develop a method of loop-mediated isothermal amplification(LAMP) to Staphyloccocus aureus rapidly, specifically, sensitively and simply suited for the primary health agency. Methods According to conserved nucleotide of Staphyloccocus aureus and principle of LAMP, we designed a set of LAMP primers and set up an LAMP reaction system. We evaluated the specificity, sensitivity and re-peatability of the method. In addition,we evaluated the linearity between initial template copies 1g value and reaction time (the time when the fluorescent value is 1×10~4). Results The optimal assay showed that it was no cross-reaction with other closely related members of pathogens, and was 10 times more sensitive than PCR. The coefficient of variance between tests was less than 5% ,and the kinetics curves showed a good line-arity between initial template copies lg value and reaction time(r~2=0. 9501). The detection activity could be finished within 1 h with the sensitivity of LAMP was 100% and the specificity was 94.4%, and the accuracy was 96.6%. Conclusion These findings demonstrated that the LAMP had the potential clinical application for detection and differentiation of Staphyloccocus aureus in the public health agency for its sensitive, specific and simple feature.
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OBJECTIVE: To evaluate the effects of the therapy mainly for strengthening healthy energy to promote blood circulation in treating diabetic patients with gangrene. METHODS: A series of 112 diabetic patients with gangrene were investigated before and after treatment in the changes of wounds, clinical symptoms and quality of life. RESULTS: Fifty-eight cases were cured, 12 cases showed response, 36 cases improved, and 6 cases failure of treatment. The total obvious effect rate was 62.5% (70/112) and the amputation rate was 8.9% (10/112). The 104 diabetic cases of three-stage gangrene were classified into grade I, II and III. The total effect rates of the diabetic cases of grade I, II and III were 83.3% (30/36), 55.6% (35/63) and 20% (1/5), and the amputation rates were 0%, 12.7% (8/63), and 40% (2/5) respectively. After the treatment, the clinical symptoms, gangrene number, gangrene area and gangrene depth were obviously improved (P<0.05), and the quality of life was obviously improved (P<0.01), especially in physical condition, emotional well-being and therapeutic effects on patients (P<0.05). CONCLUSION: Strengthening healthy energy to promote blood circulation is effective in treating diabetic patients with gangrene.
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Collateral disease theory has been applied to investigate the pathogenesis of chronic dermal ulcer in traditional Chinese medicine. It is suggested that deficiency of vital qi is the pathological basis of chronic dermal ulcer with collaterals stagnation as the major pathological factor, and collaterals impairment by toxin evil is the main pathological change. The important principle in treatment of chronic dermal ulcer is established as strengthening the body resistance, dredging collaterals and removing toxins, and this enriched the theory of wound healing in traditional Chinese medicine, and has practical value.
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The thread-dragging therapy, as a new external treatment of traditional Chinese medicine, could eliminate pathogenic factors and restore the vital qi by promoting qi and activating blood circulation to advance tissue repair in treating refractory sinus tracts or fistulae. This article reviewed its origin and development, and introduced its use in treating refractory sinus tracts or fistulae.
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OBJECTIVE: To explore the effects of Chinese herbs for replenishing qi and resolving stagnation on hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in granulation tissue of skin ulcers in rats with syndrome of blood stasis and qi deficiency. METHODS: Diabetic rats with back full-thickness skin lesion and syndrome of blood stasis and qi deficiency were divided in to five groups: untreated group, basic fibroblast growth factor (bFGF)-treated group, Yiqi Huayu Recipe (a recipe for replenishing qi and resolving stagnation)-treated group, Yiqi Recipe (a recipe for replenishing qi)-treated group and Huayu Recipe (a recipe for resolving stagnation)-treated group, and another eight normal rats served as normal control group. Immunohistochemical method and image analysis were used to test the expressions of HIF-1alpha and VEGF in granulation tissue of skin ulcers in rats with diabetes. RESULTS: In the untreated group, the expression of HIF-1alpha was significantly increased and the expression of VEGF was significantly decreased as compared with those in the normal control group (P<0.01). The expression of HIF-1alpha was obviously lower (P<0.01) and the expression of VEGF was significantly higher in the four drug treated groups as compared with those in the untreated group. In the Yiqi Huayu Recipe-treated group, the expression of HIF-1alpha was obviously lower than those in the bFGF-treated, Yiqi Recipe-treated and Huayu Recipe-treated groups (P<0.05 or P<0.01), and the expression of VEGF was significantly higher than that in the bFGF-treated group (P<0.01). CONCLUSION: Chinese herbs for replenishing qi and resolving stagnation can promote the wound healing in rats through reducing the expression of HIF-1alpha, accelerating the expression of VEGF in granulation tissue of skin ulcers in rats with diabetes and ameliorating the status of ischemia and hypoxia.
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OBJECTIVE: To explore the effects of Yiqi Huayu Recipe, a compound traditional Chinese herbal medicine for replenishing qi and resolving stagnation, on transforming growth factor-beta1(TGF-beta1) of skin ulcers in rats with diabetes. METHODS: Sixty rats were randomly divided into six groups, Yiqi Huayu Recipe-treated group, Yiqi (replenishing qi) Recipe-treated group, Huayu (resolving stagnation) Recipe-treated group, basic fibroblast growth factor (bFGF) treated group, untreated group and normal control group. Diabetes was induced by peritoneal injection of streptozotocin and skin ulcers were made by surgery method in rats except for the normal control group. Then the rats were administered with different drugs respectively, and the expression of TGF-beta1 in granulation tissue of the skin ulcers was detected with the methods of Western blotting, image analysis and immunohistochemistry. RESULTS: The level of TGF-beta1 expression in the untreated group was lower than that in the normal control group (P<0.01); and the level of TGF-beta1 expression in the drug-treated groups was higher than that in the untreated group (P<0.01); and the TGF-beta1 expression in the Yiqi Huayu Recipe-treated group was higher than that in the Yiqi Recipe-treated group, Huayu Recipe-treated group and bFGF-treated group (P<0.05). CONCLUSION: The replenishing qi and resolving stagnation therapy can control the secretion of TGF-beta1 of the wound in the process of wound healing in the levels of gene and molecule.